EFFECTS OF ENVIRONMENTAL POLLUTANTS ON HUMAN HEALTH WITH
SPECIAL REFERENCE TO LEAD
By
JAMAL ALI FAOUR B.S. (Environmental Health Sciences, American University of Beirut, Lebanon)
P.G.DIP.E.S & T. (Environmental Science and Technology, International Institute for Hydraulics and Environmental Engineering, Delft, The Netherlands)
M.Sc. (Environmental Pollution Control, University of Leeds, England)
A Thesis Submitted for the degree of fa ste r of Philosophy of the University of London and the Diploma of Imperial College.
Imperial College of Science Technology and Medicine Department of Mathematics (Environmental Technology Research)
London, February 1989 ABSTRACT
Exposure to lead and its possible effects on health has long been a topic of public and
scientific concern. Much of the concern about lead exposure of the general population comes
from non-medical scientists and journalists who consider lead from petrol the chief source. The overgrowth of medical and scientific journals has reached such proportions as to become a sort of literary pollution. Undoubtedly the issue which has generated the most widespread interest is whether lead in the environment affects the intelligence or behaviour of young
children.
Challenged by the lack of a common point of view as to whether or not this phenomenon
exists, I have scrutinized most of the scientific information available with respect to
methodological, design and interpretation aspects of the studies by exercising critical faculty in assessing these publications and attempting to identify the most serious contributor.
It is concluded with great certainty that the blood-lead level is governed to a large extent by
a multiplicity of factors, which are independent of inhaled lead. Blood-lead level depends significantly on nutritional intake and high blood-lead levels do not necessarily reflect lead absorption, but also signal slow excretion mechanisms due to the overriding importance of
dietary and physiological factors.
It is postulated that diet is the main determinant of population differences in blood-lead
levels. As the world food supply dwindles, much attention is to be focussed on elevating the
level of nutritional thinking among the public.
Brain function depends on the correct balance of nutrients reaching it, and the claimed effect
of lead on IQ is found illusory. The notion that lowering lead levels in petrol confers benefits
on inner city school children denies the association of social, cultural and economic
disadvantages with depressed levels of intellect and its profound effect on elevated rates of school failure. CONTENTS
Page
A B ST R A C T 1
TABLE OF CONTENTS 2
LIST OF TABLES 5
LIST OF FIGURES 6
ABBREVIATIONS 7
REFERENCES
ACKNOWLEDGEMENTS
CHAPTER 1: Environmental Pollution and Assessment of Health Risks 12
CHAPTER 2: Lead in the Environment 28
CHAPTER 3: Blood-Lead Level : A biomonitoring Index of Exposure 31
CHAPTER 4: Human Exposure and Blood-Lead Level Trends 40
4.1: Lead in Petrol as a Potential Pathway of Exposure 40
4.2: Lead in Air as a Potential Pathway of Exposure 54
4.3: Lead in Paint as a Potential Pathway of Exposure 62
4.4: Lead in Water as a .Potential Pathway of Exposure 69
4.5: Lead in Food as a Potential Pathway of Exposure 80
4.6: Urban-Rural Blood-Lead Levels Comparison 83
CHAPTER 5: Blood-Lead Levels Decline 85
5.1: Changes in Blood-Lead Levels 85
5.2: Epidemiological Observations 87
5.3: U.K. Blood-Lead Levels Monitoring Programme 90 (Discussion of Results)
5.4: Conclusion 101
2 Page
CHAPTER 6: Diet, Excretion and Body-Lead Content 103
6.1: Intestinal Uptake of Lead 103
6.2: Classification of Lead: An Essential Metal 107 or Contaminant Metal?
6.3: NutritionalFdCtorSand Susceptibility to 115 Lead Toxicity
6.4: The Intake and Excretion of Lead by the 121 Elderly
6.5: Dietary Intake of Lead 123
6.6: The Kinetics and Pathways of Lead Excretion 130
6.7: Sweat as a Significant Pathway of Lead 137 Excretion
6.8: Populations with Low Blood-Lead Levels 141
6.9: Interactions between Lead and Selenium 149
6.10: The Effects of Vitamin B Complex on 152 Lead Toxicity
6.11: Blood-Lead Levels of Greenlanders 155
6.12: Biliary Excretion of Lead and the Protective 160 Effects of Glutathione
6.13: High Blood-Lead Levels Signal Slow 165 Excretion Mechanism
6.14: The Influence of Iron Deficiency on 170 Lead Absorption
6.15: Enhancement of Lead Absorption by 177 Low Dietary Calcium
6.16: Effects of Malnutrition on Susceptibility 181 to Lead Poisoning
6.17: Conclusion 189
3 Page
CHAPTER 7: Low Level Lead Exposure and the Evaluation 191 of Mental Skills in Children
7.1: What is IQ and What Do IQ Tests Measure? 193
7.2: Verbal or Performance Effects of Lead 204
7.3: Confirmation of a Lead-IQ Hypothesis 212
7.4: Social Factopsand Lead 222
7.5: Undernutrition and the Intellectual Impairment 225
7.6: Lead in Teeth as an Index of Body Burden 230
7.7: Recent Findings on Lead Exposure and 237 Children’s Intelligence
CHAPTER 8: Concluding Comments 242
FIGURES 248
REFERENCES 257
ACKNOWLEDGEMENTS 308
4 LIST OF TABLES
Blood-lead levels Categories of Absorption 38
Pb-B levels in Japan 1965 46
Pb-B levels in Japan 1983 47
Blood Lead Concentrations in Adults and Pre-school children 56 in Birmingham
Blood Lead and Water Lead in 24 British towns 70
Trend of Dietary Intakes of Lead 124
Relation between Intake and Output of Lead in Man 137
Comparison of Food Consumption in Japan and Other 144 Industrial Countries
6-ALA-D Activities in Different Populations 146
Average Daily Contents of Nutritional Intake among the Nepalese 148 IQ Scores Classification 195 Occupational Classification by IQ Scores 196 IQ Scores of Ethnic Minorities in UK — Child Health 247 and Education Study, 1980.
5 LIST OF FIGURES
Page
1. Emission Trends of hydrocarbons, carbon monoxide, 24$ nitrogen oxides and lead in U.K.
2. Fate of Lead Added to Petrol in the U.K. 24*)
3. Variation of Airborne Lead Concentrations with Voo Distance from Motorway
4. Principal Pathways of Lead from the Environment 251. to Human Comsumption
5. Location of Surveys in U.K. Blood-Lead Monitoring 252. Programme 1984-1987
6. A Schematic Diagram of the Pathway of Bioynthesis 253 of Haemoglobin
7. A Schematic Diagram of the Pathway of Glucose 25^- Metabolism in the Red Cell
8. The Principal Tissues of Human Tooth. 25S
6 ABBREVIATIONS, SYMBOLS AND UNITS
ALA-D = (6-ALA-D), amino laevulinic acid dehydratase enzyme
ALA-S = (<5-ALA-S), am ino laevulinic acid synthetase enzyme n
AM = Arithmetic mean = -—^—
As = Arsenic
ASD = Arithmetic standard deviation
BAD = British Ability Scales
BBB = Blood Brain Barrier
BUN = Blood Urea nitrogen
Ca = Calcium
CaBP = Calcium binding protein
CaCOg = Calcium carbonate
C a(O H ) 2 = Calcium hydroxide, lime
C aN a 2 EDTA = Calcium disodium ethylene diamine tetraacetic acid (Chelating agent)
Cd = Cadmium
CDTA = Cyclohexylene diaminetetraacetic acid (Chelating agent)
CLEAR = Campaign for lead-free air
CO M A RE = Committee on Medical Aspects of Radiation in the Environment
Cu = Copper
Cysteine = Sulphur-containing amino acid: COOH
h 2n - C - H
c h 2s h
7 Cystine = Dipeptide formed when two molecules of cysteine are oxidized by very gentle means
| -SH HS-| — |-S - S-|
DDC = Diethyldithiocarbamate (Chelating agent)
DHSS = Department of Health and Social Security — UK
DTPA = Diethylenetriaminepentaacetic acid (chelating agent)
ECD = European Community Directive
EDTA = Ethylene diamine tetraacetic acid (Chelating agent)
EEC = European Economic Community
EPA = Environmental Protection Agency = U.S.E.P.A.
FAO = Food and Agriculture Organization
Fe = Iron
Ft = foot = 0.3 metres
gallon(U.S) = 3.8 litres
g/i = Grams of lead per litre of petrol (Maximum permissible level of lead additives in petrol = 0.15 g/£ — end of 1985)
GLC = Greater London Council
GM = Geometric mean = n^Jxi X 2 x^ ... xn
G.-6 -P.D. = Glucose- 6 -phosphate dehydrogenase enzyme
GSD = Geometric standard deviation
GSH = Reduced glutathione, a tripeptide: 7 -L-glutamyl-L-cysteinyl glycine
GSSH = Oxidized glutathione
GSH-Px = Glutathione peroxidase, a selenium-containing enzyme
Hb = Haemoglobin concentration, expressed in g/lOOml
ICRF = Imperial Cancer Research Fund, a lipophylic chelating agent derived from EDTA
ILE = Isotopic Lead Experiment
ILO = International Labour Organization
8 IQ = Intelligence Quotient
IU = International unit; vitamin D requirement is expressed in International units
Km = Kilometre
LET = Linear Energy Transfer Radiation m = m etre
MAFF = Ministry of Agriculture, Fisheries and Food
MCV = Mean Corpuscular volume = fl(femto litre = 10 litres)
Mg = Magnesium
MRC = Medical Research Council mSv = Millisievert, unit of expressing radiation dose
fi = micron = 1 0 metres fig = microgram
fig/dt = micrograms per decilitre = ^g/1 0 0 m£ = //g1 / 0 0 g = fig% = ppm x 100 = 0.048/z mol/£ fig/g = micrograms of lead per gram = mg/Kg = ppm (it is the unit used for expressing the concentration of lead in food) Current recommended maximum safe level = 1 fig/g = lp p m fig/d = micrograms per litre (It is the unit used for expressing the concentration of lead in water) Current recommended maximum safe level = 50 fig/1
o /ig/m° = micrograms of lead per cubic metres of air (It is the unit of expressing the concentration of lead in air) Current recommended maximum safe level for community exposure
= 2 fig/rc?
/ig/100ml = micrograms of lead per 100 millilitres of whole blood (It is the most commonly used unit of expressing the concentration of lead in blood) fimo\/d = micromoles of lead per litre of whole blood (It is the unit of expressing the concentration of lead in blood in SI units lfimo\/t = 20.72 //g/100ml) fiSv = microsievert, unit of expressing radiation dose
9 Ni = Nickel
NRPB = National Radiological Protection Board
O 3 = Ozone
Pb = Lead (plumbum), atomic weight = 207.2; atomic number 82; valence 2,4; specific gravity = 11.34; melting point = 327.43; a grey soft malleable metal; used in the preparation of many alloys because of its softness and low melting point
Pb-B = Lead in whole blood
PBB = Polybrominated biphenyls
Pb-F = Lead in faeces
PBG = Porphobilinogen
PbS = Lead sulphide, galena (major lead mineral)
Pb-T = Lead in teeth
Pb-U = Lead in urine
PCB = Polychlorinated biphenyls
PCV =Packed cell volume (haematocrit), a reliable index
of the red cell mass red cell volume total blood volume
ppm = Parts per million (It is the unit used for expressing the concentration of: lead in teeth, lead in paint, lead in soil and lead in dust) Paint lead is sometimes expressed as per cent w/w; recommended
GLC m axim um safe level is 1 %. No standard limits are set for soil-lead and dust-lead. r.b.c. = Red blood cells
RCEP = Royal Commission on Environmental Pollution
Se = Selenium
Si = Silicon
Sn = Tin
TCDD = 2,3,7, 8 — tetrachlorodibenzo p-dioxin
TEL = Tetraethyl lead, antiknock petrol additive
TEM = Tetramethyl lead, antiknock petrol additive
U.S.E.P.A = United Stated Environmental Protection Agency
10 vit = Vitamin
WAIS = Wechsler Adult Intelligence Scale
WHO = World Health Organization
WISC = Wechsler Intelligence Scale for Children
WISC-R = Wechsler Intelligence Scale for Children — Revised Version wk = week
Zn = zinc
> = Greater than
< = Less than or equal to
% = Per cent a = Blood-lead air-lead relationship is denoted by the a factor
11 CHAPTER 1
ENVIRONMENTAL POLLUTION AND ASSESSMENT OF HEALTH RISKS
Environmental Pollution, a blanket term, is one of the most overworked and loosely used
terms in today’s popular and scientific literature. It is used in a variety of texts and to mean
a variety of things. “Pollution” refers to an activity which causes damage either to man or to his environment. The word “pollution”most frequently is neither precise in its interpretation nor free from emotive undertones, but in the accepted sense it means the deliberate or accidental
discharge into the environment of waste products of human activities resulting in harmful
consequences.
However, one might consider certain additives which the manufacturers believe will result in
improvement, such as fluoridation of water, Constitutes environmental pollution, and affects
the purity of our body fluids. It is preferable for most purposes to regard pollution as
“anything we dislike”.
“Environmental pollution” probably shares with a spiral staircase ease of recognition but
impossibility of definition.
In the last decade, fear of adverse health risks from environmental pollution has considerably increased.
Consequently, the public demands a health surveillance study in the case of more or less insidious normal emissions from static or mobile sources or incidental/accidental release from e.g. chemical waste dumps. Activities which have been accepted as an asset in our post-
12 industrial age, are increasingly regarded as a liability.
The most important question put to local authorities and industries is : “Does this exposure carry specified health risks?” Another question is: “Are specified diseases caused by
ct exposure?” Moreover both questions may also be asked by individuals: Do I run a health risk? Is my disease caused by pollution?” What is an adverse health effect?
Adverse effects may be obvious or subtle. Severe effects such as death, serious illness or disability present little difficulty to define and would be generally agreed upon. Minor changes in symptoms and signs, physiological, biochemical and other parameters are more debatable. Tests of respiratory function (airways resistance (AWR), compliance of the lung, forced expiratory volume) may show a modest change which is hard to evaluate. Is a 30% increase in airways resistance for example adverse? Such a change may be transient, even in the presence of continuing exposure. It may be produced by many common exposures such as breathing cold air, taking a deep breath, coughing and so on. It may, in short, be a physiological response which may become exaggerated in some people as a result of exposure for other reasons.
When does physiological response become a pathological response? It is often not known whether acute change which causes no immediate effect on well being is likely to have such an effect in the future. Essentially, the question becomes one of comparing the risks of future events. Is it a certain biological change attributable to a specific exposure, and if so what is the relationship between exposure and effect? Do those persons with greater exposure experience a higher risk than those without it now, and in the absence of further relevant exposure, do they experience such an increase in risk in the future?
13 Excepting only cancer and certain inexorable forms of heart disease, most illnesses can reverse Some cencers are reversible. themselves. In schizophrenia and rheumatoid arthritis, for example, it is estimated that 35% of cases will recover no matter what is done (Thomas, L., 1977). A great many patients with hypertension can have a normal life-span. Also, the remarkable potency of placebos in providing transient relief of symptoms in many illnesses has become an important complication for clinical and epidemiological research.
One of the goals of environmental epidemiology is to ascertain and quantify the relationships that exist between long term, low-level human exposures to pollutants and the impairment of bodily functions or the development of chronic diseases. Eventually, such information might be used as a basis to regulate such pollutants or to modify existing regulations. Long-term, low-level doses, however, are hard to quantify, and any attempt to do so must take into account “a mess of complicating factors”.
Epidemiologists are still hammering away at this problem. One example of environmental risk in humans is that from radiation. We should realize that assessment of health risks not \ only has to do with establishment of increased health risks, but also and even may be more frequently, with establishment of non-risks.
The concept of risk and the notion of uncertainty are closely related. We may say that the lifetime risk of cancer is 25%, meaning that approximately 25% of all people develop cancer in their lifetimes. Once an individual develops cancer, we can no longer talk about the risk of cancer, for it is a certainty.
If two people are both heavy smokers, one may die of cancer and the other not; we cannot tell in advance. However, there is a systematic difference in this respect between being, for instance, a heavy smoker and a gluttonous eater of peanut butter, which contains aflatoxin.
14 Although aflatoxin is known to cause cancer, and quite likely even in humans (Searle, C.E.,
1986), the risk of cancer from eating peanut butter is much lower than that of smoking cigarettes. Exactly how much lower is uncertain, but it is possible to make estimates of how much lower and also to make estimates of how uncertain we are about the difference. Some estimates of uncertainties are subjective, with differences of opinion arising because there is a disagreement among those assessing the risks.
An example of risks that are similarly calculated is the comparison of risks of various chlorinated hydrocarbons in drinking water. The risks to humans are estimated from carcinogen bioassays in rodents (rats and mice). Chloroform, which is produced by interaction of chlorine with organic matter during the chlorination of surface waters to kill
bacteria, produces cancer in animals 2 0 times as readily as does trichloroethylene, an industrial solvent that is occasionally found in well waters as a result of accidental pollution.
(Wilson, R. and Crouch, E.A.C., 1987).
Cigarette smoke contains over 1000 chemical substances, some of which are recognized as potent carcinogens. Nitrosamines are one group of chemicals present in cigarette smoke, which have proved to be powerful, organ-specific carcinogens in animals (Stock, S., 1980).
He has estimated that even a non-smoker in a smoky atmosphere can inhale in 1 hour nitrosamines equivalent to inhaling the mainstream smoke from over 30 filter-tipped cigarettes. One would expect the incidence of lung cancer to hit non-smokers just the same as smokers, and this is in total conflict with observed facts.
The mean concentration of respirable particulate matter of a non-smoking sample exposed
O passively to tobacco smoke was 2 0 /ig/m , while the mean of the exposed group of smokers was 40/xg/m3 (WHO, 1982).
15 Perhaps the most powerful argument put forward against smoking as a cause in itself, is that a subject with a particular physical or genetic constitution may be prone to develop both a taste for the smoking habit and also a tendency towards the particular physical condition
(still not understood) which causes lung cancer (Peace, L.R., 1985). Under such a hypothesis, any association between smoking and lung cancer would be indirect rather than direct.
In 1983, Yorkshire television broadcast a programme entitled “Windscale — The Nuclear
Laundry” which suggested that an unusually high incidence of leukaemia had occurred in young people in the village of Seascale in West Cumbria. As Seascale is only 3 km from the
Sellafield nuclear establishment, which has the highest authorised radioactive discharges in
UK, it was suggested that there might be an association between the leukaemia incidence in
Seascale and the radioactivity from Sellafield discharges and that this should be investigated.
In response to these reports, the Minister for Health commissioned an independent advisory group chaired by Sir Douglas Black to investigate these findings. The Black report (1984) confirmed that there was a “higher incidence of leukaemia in young people resident in the area”. However, they also stated that the estimated radiation dose received by the local population from the Sellafield discharges and from other sources could not account for the observed leukaemia incidence on the basis of current knowledge. However, the uncertainties involved in the calculations and conclusions led the advisory group to make a number of recommendations for further investigations. Since there were few data on body levels of radionuclides in local people, it was recommended that more human monitoring data should be obtained, both locally in the area around the Sellafield site, and nationally and especially on children. Another recommendation was that there should be a coordinating body that has the responsibility of assessing all of the information available and deciding on the overall implication of the discharges with regard to the health of the community.
16 The Black report group has considered the likely dose of possible effects from both low Linear
Energy Transfer (LET) radiation (i.e. gamma radiation and beta radiation) and high LET
radiation (alpha radiation) to the red bone marrow of children in Seascale. The red bone
marrow dose, in particular, was considered because this is the target organ for induction of
leukaemia by radiation. High LET radiation is more biologically effective at low doses as
compared with low LET radiation, probably because the cell is less able to repair damage due
to high LET radiation and there are more uncertainties about its biological effects.
About 99.8% of the absorbed dose to red bone marrow is derived from low LET radiation and
0.2% from high LET radiation. X-rays and gamma rays become less biologically effective at
low doses, and alpha rays may be between 20-50 times more biologically effective than
gamma rays per unit dose; repair of DNA can occur to a greater extent at low dose rates
(Black report, 1984).
Natural radiation pervades the whole environment. In fact many sources of radiation are
inescapable. Cosmic rays from the sun and outer space bombard the earth and produce
f 3;.c|ioactive material as they pass through the atmosphere; the ground contains naturally
occurringMliioactive materials (Potassium-40, Uranium-238 and Thorium-232 Series), so to a
small extent, do building materials. As they penetrate the atmosphere, the rays are
gradually absorbed by it with the result that dose decreases as altitude decreases. Passengers
of airliners at an altitude of 1 0 km experience about 1 0 0 fold increase in exposure, but these
levels are still very low; the numbers of rays entering the atmosphere are affected by the
earth’s magnetic field, more entering near the poles than the equator (Squirrell, M., 1985).
In the U.K., the annual effective dose equivalent ranges from approximately 320 microsieverts
(^Sv) in the North of Scotland to 290 fiSv in the South of England; each person in the UK millisievertsper annum receives, on average, a dose of 2.2 . . . vmSv) (Squirrell, M., 1985).
17 The investigations made of leukaemia after gamma radiation from accidental, military, or medical exposure have been analyzed over many years to give estimates of risks which are used in recommending limits of radiation dose to radiation workers and to the public. If all the assumptions made by the Black report group are correct, their calculations have
demonstrated that at most less than 0 . 1 deaths from leukaemia would be expected from the discharges (accidental and planned) from Sellafield to the under 20 years-old population of
Seascale born between 1945-1975, giving a maximum risk of death from leukaemia of about 4 in one million young people per annum.
It is particularly important to assess whether the allegedly exposed population is in actual contact with the toxic agent.
This includes in the first place measurement of the concentrations of pollutants in all relevant sources of intake. Man does not respond to a concentration, but to an amount (intake).
For example, in estimating risks of air pollution, one usually assumes a respiratory volume
o of 24 m /24 hrs. However, in fact the respiratory volume may be considerably lower, and subjects are never exposed continuously to ambient air pollution.
Studies are often carried out in an emotionally disturbed situation; pressure groups and the media often tend to exaggerate health risks and may even present misleading information.
Such studies can never lead to a conclusive answer on exposure-effect relationships in such circumstances. Extensive training in matters of environmental/occupational epidemiology and toxicology is needed for assessment of exposure.
The choice of groups at risk differ according to the type of exposure: in exposure to carbon monoxide, adults over 40 years (decreased cardiovascular capacity); in
18 exposure to persistent halogenated hydrocarbons (e.g. PCB’s, PBB’s), pregnant and lactating women. Minimum size of the exposed and control groups and their locations haifeto be dealt with properly.
To detect the effects of a few millisieverts, would require a population of one or more hundred million people (Pochin, E. E., 1985) The National Radiological Protection Board (NRPB),
(1988) examined the main uncertainties in the analysis of radiation doses and risks of leukaemia to children and young persons living in the vicinity of nuclear establishments, and the result obtained from the Board’s study of radiation doses and risks in Seascale have been used as an example. The conclusion was that the doses and risks calculated from the
Sellafield discharges were lower, by a factor of about 300, than those needed to account for the 5 cases of fatal leukaemia observed in the population between 1950 and 1980. It was difficult to explain the observed incidence of leukaemia on the basis of environmental activity arising from nuclear sites. One explanation was that there could be a few children in the population who received doses from the Sellafield discharges that were substantially higher than those received by children with average habits; inhalation has been a less important pathway of exposure to releases from the Sellafield plant than ingestion.
The main areas where further information is needed for improving estimates of doses to the population from intakes of radionuclides include: the uptake and distribution of radionuclides in foetal tissues following intakes by the mother. Medical irradiation includes doses from diagnostic X-rays and radioisotopes and radiotherapy with X - or gamma rays. For the average individual, the largest artificial exposure is derived from these sources, and within this, diagnostic X-ray examinations are responsible for the major part of medical exposure.
Certain individuals may receive several times the average dose from this source.
19 According to Knox, E.G. et al (1987), there was no evidence of any reduction in the frequency of pregnancy X-rays between 1950 and 1979. They estimated that during this period of
time, about 7% of all childhood cancers, and 8 % of those with onset between the ages of 4 and 7 years, were caused by X-ray examinations. The dose-response relationship was one death per 990 obstetric X-ray examinations.
The incidence of leukaemia in children of Japanese survivors conceived after the atom bombs were dropped has not demonstrated an excess risk of leukaemia according to the NRPB figures.
MacMahon, B. (1962) reported that prenatal exposure to diagnostic X-ray increased the frequenciejbf childhood leukaemia, cancer of the nervous system and other cancers.
Radiation is a known cause of leukaemia, yet no clinical distinction can be made between cancers induced by radiation and those occurring from other causes. At present there is no convincing evidence that establishes a mechanism for cancer induction in man. All estimates can be criticized on the grounds that they are based on acute exposure rather than chronic exposure to radiation, and on dose values concerning which there is at least some uncertainty.
Other agents implicated in inducing cancer are : genetic factors, drugs, chemicals and toxic materials. Infectious agents, particularly viruses, have long been suspected as a cause of human leukaemia and have been demonstrated to be a leukaemogenic agent in experimental animals (NRPB, 1988). One important study which I would like to draw attention to is that of Fedrick, J. and Alberman, E.D. (1972). A longitudinal study of 1,959 infants born in the first week of March 1958 to mothers who were reported to have had influenza during pregnancy revealed an incidence of cancer of 4.1 per 1000 compared with only 0.8 per 1000 among the 14,791 infants of mothers who had not had influenza. This increase was caused
20 by cases of leukaemia and other neoplasms of lymphatic and haematopoietic tissue.
Socioeconomic status also influences the incidence of leukaemia, higher social classes having
an elevated incidence of leukaemia (NRPB, 1988). The color of the skin, seems to be one
predisposing factor to skin cancer, whites being more suscep ■tible than blacks (Peto, R.,
1985).
It seems that the incidence of cancer is inversely related to the frequency of G.- 6 .-P.D. (see
abbreviations) enzyme deficiency in Negroes (Naik, S.N. and Anderson, D.E., 1970).
Sardinia (Italy) has a lower cancer prevalence than both northern Italy as a whole and the
rest of Europe; G.- 6 .-P.D. deficiency affects 25-35% of the population in Sardinia (Sulis, E.,
1972). An explanation for these findings might be found in the block of the metabolic
pathway of glucose degradation known as the “pentose shunt”, of which G.- 6 .-P.D . is the key
enzyme (see fig. 7). This would cause slower formation of ribose and hence of nucleic acids,
with a subsequent obstacle to neoplastic proliferation. Carriers (of this enzymopathy) would
be spared from the neoplastic event, probably becasue of slow proliferation of the various
tissues. This would allow organic defence systems to act as an obstacle to, and destroy
tumour invasion, especially in its early stages.
We cannot directly observe time between exposure and diagnosis of a cancer caused by that exposure, because we cannot distinguish between radiation-induced cancers and others.
Obviously, something caused the sudden surge in mortality from lung cancer from the steady figure of 12 per million population in the 1911-1915 period, to a figure in excess of 700 per million by 1980. (Peace, L.R., 1985). Adverse publicity about smoking and health started in the 1950’s and 1960’s. Sales of cigarettes by weight have stabilized since the 1950’s and have recently started to fall significantly. Peak volume sales of cigarettes came in 1961, and began to fall in the early 1970’s.
21 The Committee on Medical Aspects of Radiation in the Environment (COMARE)( 1988)
recently addressed the question whether the incidence of leukaemia in young people near
Dounreay nuclear establishment, Caithness, Scotland is increased to an extent which is
unlikely to be due to chance.
Sellafield and Dounreay have certain features in common namely, nuclear fuel reprocessing.
They noted that they were unable to ascribe the observed incidence of leukaemia near
Dounreay to specific causes and that further information is required i.e. : Place of birth of
the child, as well as place of residence at time of diagnosis and parental occupation. It was
recommended that epidemiological studies should be set up to consider any possible effects on
the health of the offspring of parents occupationally exposed to radiation. Investigations on
whether there are hitherto unrecognized routes of exposure should continue; that dose
estimations should be based whenever possible on the results of environmental monitoring
rather than on discharge data; that scientific research should be conducted on the absorption
and metabolism of radionuclides expecially in the foetus and young child and children’s
habits in relation to potential pathways of exposure. From epidemiological studies, we know
that part of the increases may be due to more discriminating haematological diagnosis and to
more complete registration of cases.
In spite of the extensive scientific evidence that some nitroso compounds are powerful carcinogens in many organisms, clear association between exposure to these chemicals and cancer in man has not been established (Craddock, V.M., 1983). Theoretically, nitroso compounds can form when a secondary amine and nitrite combine under favourable conditions. Nitrite is, of course, found as an artificial preservative in human food and also in animal feed. Nitrates enter the environment because they are used as fertilizers in agriculture and are also used as preservatives in food processing.
22 They are not carcinogenic themselves, but they are reduced to nitrite by bacteria in the
mouth and — under pathological conditions — in the stomach and bladder, and nitrites can
react in vivo with a variety of protein substrates to form N-nitroso compounds, many of
which are carcinogenic to animals (Doll, R., 1987). First the disease is usually preceded by
atrophic gastritis, a condition which reduces gastric acidity (achlorhydria) and permits the
bacterial colonization of the stomach, thus allowing N-nitrosation.
The feature of diet that is most consistently associated with the disease is a deficiency of fresh
fruit and vegetables and hence presumably of vitamin C, which is an effective inhibitor of N-
nitrosation in physiological amounts (Mirvish, S.S. et al, 1972).
Meat treated with nitrate as a preservative and curing agent contains, therefore, the
precursors for the in vivo formation of nitrosamines; small amounts have indeed been
detected in samples of beef and pork (Low, H., 1974). Many food plants, green vegetables
like spinach and celery, as well as tobacco leaves, vary in their nitrates content depending
largely on soil conditions (Low, H., 1974). The high salt, micronutrients deficiency factor
seems to be a predisposing factor in stomach cancer. The commonest cancer causing death
in man is lung cancer, accounting for 36% of all cancer deaths, while the commonest cancer
causing death in women is still breast cancer (Searle, C.E., 1986). However, stomach cancer
is currently in the lead. Poor people who consistently rely on canned food (such as canned
meat etc.) are at a disadvantage as to the purchase of fresh vegetables and fruits. Zinc deficiency can increase the incidence of methyl-benzyl-nitrosamine-induced oesophageal cancer
from 15% to 80% (Craddock, V.M. 1983). The role of food in the aetiology of cancer (such
as high fat intake and breast cancer) has been discussed in detail by Thomas, J.S. (1986).
The fact that many nitrofurans are potent carcinogens has greatly restricted their use as antibacterial drugs. One nitrofuran (furylfuramide) is an extremely efficient antibacterial compound extensively used as a food preservative in Japan from 1966 until its carcinogenicity
23 was proven in 1974 (Searle, C.E., 1986). It has been thought inactive on the basis of tests
that were later realized to have been inadequate.
Benzene has a toxic action on the blood-forming cells of the bone marrow, one consequence of
which can be the development of leukaemia. Asbestos and chromium are associated with
lung cancer. Correlations between gastric cancer incidence and nitrates in drinking water
have not been consistent.
In my opinion, chemical carcinogens are the challenge of the future. It can be estimated that
about 1 % of all cancers may be caused by radiation, and mainly by the natural sources
(Pochin, E.E., 1985).
Gold, J. (1984) reported on the third conference on “Epidemiology in Occupational Health”
that was held in Singapore in September 1983.
Emeritus Professor Sir Richard Doll, an eminent cancer epidemiologist stressed that it was
not satisfactory for industry, after it is found that hundreds of thousands of unsuspecting
workers have had long exposures to cancer-causing agents, to plead ignorance by saying that
chemical toxins were “thought to be safe” when introduced.
It must be noted that, while governments allocate huge resources to preventive research in cardiovascular disease (a major cause of death among managers), relatively negligible
res-'Qurces are allocated to research into the problems of work-related disease in those involved in the production in industries.
Another programme on Yorkshire television (“Inside Britain’s Bomb”; Dec. 3, 1985) drew attention to leukaemia and lymphatic cancer in young people in areas very close to the
24 Berkshire nuclear weapons installations (Urquhart, J. et al, 1986). Findings revealed that,
by and large, knowledge of the public is not increased by mass media coverage of an accident
but that emotional reactions are significantly affected (Brown, J.M. and White, H.M., 1987).
Certainly there seems to be little gain in trying to teach the public probability theory, nuclear
physics or reactor engineering. The Chernobyl disaster had attained the high profile of
media coverage during 1986. The style and language of presentation of TV programmes are
so skilfully carried out rendering the conclusions unquestionable. Correspondents
concentrating on “failure of scientific teams to agree on conclusions”, “Controversy” (such
as lead controversy), “uncertainty”, “at least in the current state of knowledge”, all point to
the “low status of science”, can only create lack of confidence and mistrust in scientists.
Results of various opinion polls in the U.K. post-Chernobyl, show a decline in support for
nuclear power (Brown, J.M. and White, H.M., 1987) and at a time when there is
international concern about radiation effects and nuclear war.
Not much thought is given by the public as to where water, gas or electricity comes from provided it appears when its turned on.
I doubt it if many people understand, or wish to understand how a turbine or generator works, provided it does.
Governments play down their nuclear power programmes, and their reticence is taken as secrecy which in turn fuels suspicion and adversity. The exception to this is France, where the massive nuclear programme is proudly and openly acknowledged and thus more generally accepted by the public.
Dioxin is ranked alongside radiation as a word that evokes disturbing images in the public mind because it is seen as a dangerous chemical that causes irreversible toxic effects and even
25 death. People have been led to believe that 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) is one of the most deadly chemicals ever manufactured. Yet, no study has shown that TCDD causes severe chronic effects and no one has died from exposure to it. The only disease that
TCDD appears to cause is chloracne - an unpleasant but non-fatal skin condition (Page,
R.A., 1987). Why is it that the public perception of a risk usually far exceeds the actual risk incurred?
It is the nature of the risk and the difficulty in defining it that features prominantly in people’s minds.
Everyday we take risks and everyone accepts risks to a greater or lesser extent. It is reported that in 1986, 4832 people died in motor vehicle traffic accidents; of these only 523 were within Greater London - London can hardly claim to be a stress-free environment - (Ryan,
R., 1988). The Kings Cross escalator fire disaster, the Bradford football playground fire and the recent train crash close to Clapham junction are examples of accidents that could happen anytime and anywhere. The assumption of zero risk, can arise because people and government agencies have a propensity to ignore anything that is potentially hazardous.
This attitude is inconsistent with the objective of improving public health and may also lead to economic inefficiencies, and often leads to unnecessary contention between experts who disagree strongly.
The anti-nuclear lobby has for some years been demanding the closure of all nuclear-powered stations maintaining that with a policy of conservation and energy from renewables, demand and production could be equated. Nuclear power, like state Airlines is to be perceived as a symbol of national pride. There are two kinds of environmentalists in our modern world, namely the suitably qualified devotees of the science of the environment and its relationship to living organisms, particularly man, and hence is largely a biomedical science i.e.
26 Environmental health, and what may be called the “popular ecologists” stemming from an activist movement that started on some American campuses in the 1960’s whose objective is to save the world and do not seem to know where they are going. The spheres of interest and influence of both categories of environmentalists should not be collectively termed
“environmentalism”.
One thing is quite clear; in the absence of clearly ascertainable facts, the discussion becomes passionate, giving the lay observer very little opportunity to reach a sensible conclusion.
As Dunster, H.J. (1985) puts it : Human beings seem to have a need to attribute natural adversity to an identified cause, some form of universal culprit. If we cannot positively identify the cause, we look for any plausible candidate. Once it was the evil eye, now it is radiation.
27 CHAPTER 2
LEAD IN THE ENVIRONMENT
Metallic lead was one of the earliest metals used by man. Water pipes and primitive tools were made of lead; vessels used for cooking, eating, and wine storage contained the metal.
Lead was one of the seven metals of antiquity. Its discovery dates back to at least 3500
B.C. and lead artefacts have been discovered widespread throughout the ancient world
(Waldron, H.A., 1973). In the predynastic Egypt, galena (the major lead mineral, PbS) Is found in the tombs from this period.
Gradually lead became one of the most useful and abundant metals known to man. Of the non-ferrous metals, lead is the most widely used in industry and everyday life. Two decades ago, 113 different occupations were thought to entail an exposure to lead (Gafafer, W.M.,
1964). With its long history of industrial use, lead occupies a special position in our evaluation of environmental contaminants. Certain of the toxic effects of lead were familiar to Greek, Roman and Arabian physicians before the Christian era (Hunter, D., 1975). With the steady implementation of more stringent regulations designed to protect the industrially exposed, the hazards associated with the industrial handling of lead have been greatly reduced.
Man has always been exposed to lead simply by virtue of its being present in the earth’s crust and natural levels of lead have been estimated for all components of the environment (in rivers, lakes, seas and in the air, following the burning of wood and coal, and in plants both edible and inedible).
28 The presence of lead in the earth’s crust results in the natural mobilization of the metal into the environment. Lead in soil ranges from 2 to 200 ppm and averages 16 ppm (Stubbs, R.L.
1973). As with all elements, there are some areas with much higher concentrations including the lead ore deposits scattered throughout the world. Acid soils generally have a lower lead content than alkaline soil. Some organic matter in soil is rich in chelating agents, and it binds lead either promoting its movement out of soil, or fixing the metal depending on the solubility properties of the complex. As a consequence of its presence in soil and water, lead enters the food chain and becomes incorporated into plant and animal tissue (WHO, 1977).
The work done by Kehoe, R.A. (1961) demonstrated that lead is present in body tissue because the metal is well distributed on the surface of the earth.
Interest in measurements of the concentration of air pollutants in a city street was observed in the work of Waller, R.E. et al (1965). Airbdne lead, its uptake by inhalation, and possible health effects were discussed in a conference held at the Zoological Society of London by the Institute of Petroleum in association with the Chemical Society and the British
Occupational Hygiene Society (Hepple, P., 1972). Since the early seventies, the subject of contribution of lead in air to body lead burden has been a major topic in environmental pollution.
There is no doubt that many people today are very concern®!about the presence of toxic chemicals in the environment, especially in the atmosphere. One of the reasons why this public concern has increased in recent years is the often repeated assertion, that “the only safe concentration is zero”. In pollution control, decisions have to be made among the medical profession about the amounts of toxic substances that can be released from any source and the way in which those substances are discharged into the receptor environment. Water is essential for survival, however, drinking 20 to 30 litres of water in a short time would
29 probably kill most of us and such cases are occasionally reported where this has happened
(Gorsuch, T.T. 1987).
It is only the dose that distinguishes poison from remedy. Although nothing is absolutely safe, phasing lead out of petrol has been called for by environmentalists, and enlightened decision making takes time. Scientists take pride in seeing all sides of the argument, journalists want to communicate simple conclusions and politicians have to take policy decisions.
The imagination and emotion of the public was fired. Lead, especially in petrol, was incriminated of doing untold damage to children. When expert COmmittees.did not produce simple recommendations in line with public opinion, charges of bias and cover-up abounded.
Governments had to act and they did so in line with public opinion. The general principle of
“no toxic concentrations of substances” did not apply.
The evaluation of the health effects of lead relies on judgement and common sense as well as on objective, quantifiable data, but this makes it difficult to count the cost to health and to justify the expenditure required to eliminate or control sources (Ratcliffe, J. M., 1981)
Seemingly endless of information on lead continue to appear in the literature, in spite of the fact-&3i lead has been studied so intensively for so long. Interest in lead has not abated, and important new literature continues to appear. Its not surprising that one human brain cannot contain all the information dealing with lead.
It is hoped that this thesis will achieve its objective in disclosing some unrevealed facts, and in throwing more light on the nature of associations between environmental pollutants and adverse health effects.
30 CHAPTER 3
BLOOD LEAD LEVEL: A BIOMONITORY INDEX OF EXPOSURE
The concentration of lead in the blood may be regarded as the best means of estimating, indirectly and relatively, the “active” body burden of lead, when the latter is interpreted as the integrated result of the daily intake of lead and the duration of exposure (Zielhuis, R.L.,
1971).
It is important to distinguish between intake and uptake of lead: by intake is meant the amount of lead inhaled from the air or ingested in food and drink, while uptake refers to the amount subsequently absorbed into the bloodstream (Royal Commission on Environmental
Pollution, April 1983). Blood lead determination is believed to give the best estimates of the lead dose and is a good indicator of exposure, but it must be remembered that it is an indicator of the total exposure (i.e. it relates to intake from food and drink as well as air)
(WHO, 1982). The blood lead concentration is considered to be the most reliable indicator of recent exposure, and to be particularly useful for epidemiological studies (Araki, S. and Ushio,
K, 1982). The concentration of lead in whole blood is thought to be one of the best indicators of the effects on population groups of exposure to normal levels of environmental lead (Delves, H.T. et al, 1984).
All humans have a certain amount of lead in their bodies as a result of exposure to natural and man made sources (Putnam, R.D. 1986). There are two routes by which lead enters the body: by inhalation into the respiratory system and by ingestion into the alimentary system.
(Absorption through the skin is significant only with some organic compounds of lead and hence intake by this route is usually negligible) (RCEP, 1983).
31 Accordingly, the concentration of lead in blood reflects the absorption of lead but not its
effect (Haeger-Aronsen, B, 1971).
Lead absorption is not to be confused with lead intoxication, and it is thought appropriate to
define the two terms.
Lead absorption This refers to the uptake of lead by the subject from his environment by
any route. Absorption may or may not, be sufficient to give rise to lead intoxication
(Waldron, H.A., 1971).
Lead intoxication This may be either pharmacological or clinical. Pharmacological
intoxication may be said to be present when there is evidence that absorbed lead is interfering
with some metabolic process in the body, interference with haem synthesis) and there are
no clinical signs at this stage (Waldron, H.A., 1971). Increased absorption of lead, encountered in occupational exposure, with elevation of the lead content of the blood, may progress to lead intoxication (Kehoe, R.A., 1961) where the patient becomes aware of symptoms and the clinician can detect objective signs of toxicity.
On entry into the blood stream, lead is rapidly distributed throughout the body. Lead diffuses from the plasma into the extravascular space and then enters the cells. Lead will accumulate in the body with age (Schroeder, H. and Tipton, I., 1968). Studies have shown that over 90 per cent of the total body burden of lead in adults was in bone, of which 70 per cent was in dense bone (Barry, P.S.I., 1975; RCEP, 1983); while the deposition level for lead in the bones of children was 70 per cent (RCEP, 1983). The knowledge on the kinetics of this large pool is scanty, and the turnover rate is generally assumed to be low, although the evidence for this is circumstantial (Christoffersson, J. O. et al, 1986). The removal of lead from bone is extremely slow and the half-life of lead in bone in humans is of the order of 20-
32 50 years (Australian Academy of Sciences, 1981). Thus, it appears that the skeleton is a
repository for lead that reflects the long term cumulative human exposure, whereas the body
fluids and soft tissues (i.e. liver, kidney, spleen, muscle and lung-including blood-) equilibrate
reasonably fast and therefore reflect current and recent exposure (WHO, 1977).
The half-life of lead in the blood-stream was reported as 30 days by some authors (Harrison,
R.M. and Laxen, D.P.H., 1981). Delves, H.T. et al (1984) have reported the rate of decrease
in blood lead with time over the initial period of their study of 21 healthy adults exposed
only to environmental lead over periods from 7 to 11 months as 26-30 weeks after moderately
increased lead exposure. Thomas, H.F. et al (1979) studied the decline in blood lead levels
of villagers in Wales after the replacement of lead plumbing with copper and reported a similar figure of 22-36 weeks.
Schlegel, H. and Kufner, D., (1979) monitored changes in blood lead levels of two volunteer subjects who consumed 5 mg of lead daily. After cessation of exposure, the subsequent half-
life was 34 weeks which is also similar to the previous findings. The knowledge on the kinetics of lead in blood is incomplete, as it is regarding the metabolism of lead in the other tissues of the body, which is a phenomenon that lead in blood may mirror (Schiitz, A. et al,
1987). Since lead in blood may reflect other bone lead pools, its elimination from blood should reflect the lead turnover rate of the whole skeleton.
The portion of the ingested lead that is not absorbed passes through the gastrointestinal tract and is eliminated in the faeces. Lead that enters the blood stream, but is not retained, is excreted through the renal system and gastrointestinal tract. Human metabolic studies have shown that short term lead excretion in adult-humans amounts to 50-60 per cent of the absorbed fraction (Rabinowitz , M.B. et al., 1976).
33 The remaining amount moves primarily to the bone where a portion of it will be excreted
over time. Prerovska, I and Teisinger, J. (1970) have shown that after long intervals of
termination of exposure of a group of 27 occupational workers, lead was excreted for a
considerable period from the mineral part of bones.
It is now clear from what has been stated above that the level of lead in blood is influenced
by environmental factors as well as physiological factors.
Bone Cortex D
F G
The blood lead concentration will be a function of the amount of lead absorbed from the
environment less that deposited in the bone cortex and the soft tissues and that excreted in
the urine and faeces. This statement may be represented in the form of an equation :
A = B - (F+G) + (C+D+E) (Waldron, H.A., 1971) 6
We can also add perspiration as another route of lead excretion along with the rest of waste matters expelled from the system (Kehoe, R.A., 1961). Lead in whole blood is normally expressed in /ig/100ml, while the S.I. unit (fimo\/t) is less often used.
In non-occupationally exposed adults, the individual blood lead levels (Pb-B in /ig/100ml)
34 usually do not exceed 25-30 /ig/100ml, and are normally 15-25 /zg/100ml. Increased
occupational exposure increases the Pb-B level (ILO, 1983). The DHSS working party (1980)
concluded that while there was no convincing evidence of adverse health effects at Pb-B levels
below 35 /ig/100ml, there was uncertainty about possible effects in the range 35-80 ^g/100ml.
Accordingly, the Pb-B levels given should not be regarded as an absolute yardstick, since the
Pb-B level as such does not indicate the health status, but it predicts the health risk i.e. the
probability that certain effects will exist or will occur in the future if exposure goes on (ILO,
1983). The sequence over time (increase, decrease, stable) is more important than a single
value. Although Pb-B level is too responsive to evanescent environmental changes, serial Pb-
B levels measured over a 3-month period, taking normal excretion into account, appear to be
reasonably stable (David, 0. et al, 1982).
After 3-6 months the Pb-B levels can be used as an indicator of total exposure over the last
2-3 months (ILO, 1983). Pb-B level is the only measure of a tissue lead burden that can
botlst a reasonably consistent level of accuracy and reliability compared to other measures
(teeth, bone, hair, nails, urine) (David, 0. et al, 1982). Thus, in the last decade, it has
become the indicator of choice to assess exposure and health risk to the community at large,
as well as a laboratory test in the control of the industrial lead hazard for monitoring lead-
exposed workers. Delves, H.T. et al (1984) has cited that in the absence of substantial
changes in lead exposure, Pb-B levels in adults are remarkably stable and that for their
environmental monitoring a single Pb-B concentration is an excellent biological indicator.
The European Community Directive (EEC, 1977) requires that if the following reference
levels are exceeded, the commission must be told and measures taken to trace and reduce the source of exposure. The reference levels are:
35 — Maximum of 20 /ig/100ml for 50 per cent of any group
— Maximum of 30 /ig/100ml for 90 per cent of any group
— Maximum of 35 //g/100ml for 98 per cent of any group
Unfortunately, the Directive does not define the population which would constitute a group.
In addition, a Joint Circular from the Department of the Environment in U.K.(DOE, 1982a) advises that where one person - particularly a child - is confirmed as having a Pb-B level over
25 /zg/100ml, his or her environment should be investigated for sources of lead and steps taken to reduce exposure, thus conforming to the DHSS advice, 1980.
The European Community blood-lead survey (Quinn, M., 1985) has shown that levels over 35
^ig/100ml are uncommon in UK, while that of the UK blood-lead levels monitoring programme 1984-1987 has shown that levels over 25 /xg/100ml are rather rare (DOE, 1987).
A code of practice introduced by the Health and Safety Commission (HSE, 1980) which controls lead in work places states that a worker should be suspended from work if his Pb-B level exceeds 80 /ig/100ml but the relevant figure for women of reproduction age is 40
/jg/100m l.
A World Health Organization Study Group has recommended limits of 40 fig/ 100ml and 30
^g/100ml for men and women of reproductive age respectively (HSE, 1980).
This code of practice with respect to the provisions of the Control of Lead at Work
Regulations 1980 has been amended later on in 1985 as Approved Code of Practice (Revised
June 1985).
This legislation stated that any worker whose blood lead concentration is equal to or greater
36 than 70 ^g/100ml will have the test repeated, and if the result of the repeat test is equal to or greater than 70 /jg/100ml will be certified by the employment medical advisor/appointed doctor as unfit for work which exposes him to lead. The employment medical advisor/appointed doctor may certify as unfit for work which exposes him to lead a person whose blood lead concentration is less than 70 /ig/100ml if the results of other biological tests and/or clinical assessment indicate a need for suspension (Health and Safety Commission,
1985).
Where there is evidence that the blood lead level is greater than 40 ^g/100ml, the workers concerned will normally be under medical surveillance (Health and Safety Comm., 1985).
Acceptable levels of Pb-B have been revised downward over the past 15 years (Center for
Disease Control in 1985 recommended 25 /ig/100ml as the upper limit for children); yet many clinicians still use older values. Most of these clinicians who work in the field still consider adult values above 40 /ig/100 ml to be the upper limit of acceptability (Graef, J.W.,
1987).
Clearly, the definition of “upper limit of normality” for Pb-B has changed over the years, where it was taken at one time as 100 /ig/100ml (Tompsett, S.L. and Anderson, A.B., 1939).
Diagnosis of lead poisoning was based on clinical findings, Pb-B level and supported by biochemical evidence of excessive lead absorption and if possible by evidence of unusual exposure. The four arbitrary categories regarding lead absorption were:
37 TABLE 1: BLOOD-LEAD LEVELS CATEGORIES OF ABSORPTION
ABC D
Category Normal Acceptable Excessive Dangerous
Pb-B <40/ig/100ml 40-80/ig/100ml 80-120/xg/100ml >120 /ig/100m l
(Lane, R.E. et al, 1968; List of 15 internationally recognized lead experts)
In considering Pb-B levels of persons, it is a fundamental tenet that each individual is a different biological system because of individual variability in human anatomical structure, physiological function and biochemical performance, and that each system reacts in a slightly different manner from any other system (Grunder, F.I. and Moffitt, A.E., 1982). In this context, studies of children with very high levels of lead indicate the enormous variation among individuals.
Some suffer irreversible brain damage or even death at levels of around 100 ^g/100ml, whereas others appear to show no effect at levels double this. The variation may be due to individual differences in susceptibility, changes in levels over time, increased tolerance for gradually accumulating burdens or interacting factors such as nutritional state (Lansdown,
R., 1986).
Ong, C.N. and Lee, W.R. (1980a) showed that in whole blood at Pb-B of 50 //g/100ml, about
94 per cent of lead had been incorporated by the erythrocytes and 6 per cent remained in plasma. Though earlier work had suggested that lead was principally carried in membrane$^Ong, C.N. and Lee, W.R. (1980b) have found that 85 per cent of lead in erythrocytes was associated with cytoplasmic components, the rest being bound to the stromal membrane.
38 This leads us to the earlier suggestion (Lloyd Davies, T.A. and Rainsford, S.G., 1967) that a
correction factor for the amount of Pb in 100ml whole blood should be introduced so that the
level of lead in blood would be expressed as the actual amount of Pb attached to the
erythrocytes; and this has been used in publications to a limited extent. Direct assay of the
the red blood cells has been proposed as a more valid index of biotoxicity than whole blood
lead by the authors.
The influence of physiological and biochemical factors on the Pb-B level regardless of the
degree of exposure is exemplified by glucose-6-phosphate dehydrogenase enzyme deficient
individuals who exhibit increased lead retention (discussed under Section 6.13). Little is
known about the mechanism of transport of lead across human red blood cells and the
internal environment factors affecting lead uptake (Simons, T.J.B., 1986a).
Several authors have suggested that the distribution of Pb-B levels for any relatively
■jcOlflojehe'Cnis population closely follows a lognormal distribution (Snee, R.D., 1982; Azar A. et
al., 1975; Yankel, A.J. et al., 1977). A relatively homogeneous population is defined as one
with minimal effects from any factors that contribute to differences in blood lead levels
(U.S.E.P.A., 1986).
39 CHAPTER 4
HUMAN EXPOSURE AND BLOOD-LEAD LEVEL TRENDS
4.1 Lead in Petrol as a Potential Pathway of Exposure
In the interest of the status and validity of concepts of “normal values” of Pb in the blood and urine of different populations, a study was begun in 1961 with the cooperation of the
World Health Organization and the support of the Division of Occupational Health of the US
Public Health Service (Goldwater, L.J. and Hoover, A.W., 1967). Blood and urine samples were obtained from “normal” subjects (the term normal being defined as persons who have had no evident occupational, medicinal, or other unusual sources of exposure) of both sexes in rural and urban areas from 16 different countries. The sample size ranged from 20 to 98 subjects, many of whom were hospital employees or clinic patients because of easy availability. Specimens of blood (and urine) were obtained from each of no more than 30 subjects per year from each of the collaborating laboratories, and shipped by air mail or air express to a single central laboratory at Columbia University, Division of Occupational
Medicine for analysis by the standard dithizone method.
The “normal” values of lead in the blood ranged from 15 fig to 40 ^g/100ml. Of the total population, more than 98 per cent had levels less than 50 /zg/100ml. In general, Pb-B levels of urban subjects were found to be slightly higher than those from rural subjects and there was no significant difference between the sexes. However, the Pb-B levels reported in New
Guinea aborigines showed levels higher in range than urban and rural Californians in the
United States. Their mean figure of 22 ^ig/lOOml of blood was higher than that of samples from 13 other localities including California, Ohio and New York cities. This is of particular interest in that these natives, living in the hills of New Guinea away from industrialization and motorization, where the environment is completely free of even minimal amounts of petrol fumes, have shown average Pb-B levels comparable with those of industrialized
40 countries. There has been much conjecture but little experimental data that petrol lead is an important determinant of the Pb-B level, and a major contributor to the human body burden of Pb (Schroeder, H.A. and Tipton, I. H., 1968; Caprio, R. J. et al, 1974; Facchetti, S. and
Geiss, F., 1982; Jones, R.R., 1983; Tera, 0. et al 1985). These observations serve to illustrate the difficulties in assuming a simple relationship between petrol lead and Pb-B.
Goldwater, L.J. and Hoover, A.W. (1967) compared data on “normal” Pb-B levels (compiled by Stopps, G.J., 1965) from 1925 to 1965 with their own data, and found that there has been no significant change in the “normal” Pb-B levels over the past 3 or 4 decades. The apparent reason was that the increase in petrol consumption has been balanced by a decrease in the use of Pb in industry as well as from insecticides, lead pipes and paint.
Lead tetraalkyl compounds are blended into the petrol as antiknocking agents in automobile fuel. Lead tetraethyl, (TEL), was the first antiknock agent introduced into petrol in 1923, and it is still the most frequently used. Other lead alkyl compounds are, however, also effective and since 1960 tetramethyl lead (TML), and the mixed methyl-ethyl compounds of lead have been used (Australian Academy of Sciences, 1981). Tetramethyl lead, (TML), could replace TEL in petrol with a consequent reduction in lead emissions by about half, if a modern octane number were developed (Porter, F.D., 1974). TML is superior to TEL in high aromatic fuel and has proven to be more effective at low speed, and since 1960 it has gained a greater share of the market as a lead additive to petrol (Laveskog, A., 1984).
This important ingredient of petrol enables the engine to operate at higher compression ratios and under greater loads before knocking occurs, thereby achieving fuel economy and smooth operation (Assoc. Octel, 1983a). Antiknock compounds are a unique and effective means of producing high octane fuel and they make substantial savings in the energy which both the refinery and the motor vehicle consume. As yet, no viable alternative has been found either because of cost or because of technological difficulties (Assoc. Octel, 1983a). The increase in
41 lead alkyl usage for the years 1925 to 1964 reflects the increase in the application of the car as
a means of transport.
The maximum amount of lead in petrol permitted in the UK was reduced from 0.84 grams
per litre(g/£) in 1972 to 0.40 g/i in January 1981, and was further reduced to 0.15g/£ in
December 1985. Following a UK initiative, an EEC Directive was adopted in March 1985
which required unleaded petrol to be made available throughout the community from 1
October 1989 (DOE, 1986).
In 1975 in the United States, 15 per cent of the petrol used was lead free; in 1980, the unleaded contribution was 50 per cent; and by 1990, it is expected that 80 per cent of the petrol used will be unleaded (Kleinman, M.T. et al, 1980). In Japan, in February 1975, the addition of leadalkyl compounds to regular petrol was totally banned (Ohi, H. et al, 1981). In
Sweden, the maximum allowable concentration of lead in petrol in 1981 was reduced from 0.4 to 0.15 g/t (Elinder, C.G. et al, 1983). In Germany, in January 1976, the permissible lead content of petrol was decreased from 0.40 to 0.15 g fi (Sinn, W., 1980). Unleaded petrol was recently available in Canada and Mexico, where it was introduced to increase tourism from US residents (Laveskog, A., 1984). However, only in Japan is lead almost out of petrol.
However, other countries did not follow the examples set by the UK, US, Japan, Germany and Sweden. The lead content of petrol used in Egypt in 1984 was 0.85g/£, and was raised in 1985 to 0.97g/£ (Esmat, A.A. et al, 1986).
The production of lead-free petrol would require an increase in the aromatic content of about
60 per cent in order to boost its octane level. Many aromatics are poisonous and carcinogenic (Porter, F.D., 1974). Widespread use of high-aromatic-content petrol may increase ambient levels of harmful non-lead substances (Edwards, H., 1979).
42 In Canada, the United States and the Federal Republic of Germany, 70 to 75 per cent of total
benzene emissions have been calculated to originate from motor cars, mostly from exhaust
emissions (Laveskog, A., 1984). Additionally, increased production of carcinogenic
polynuclear hydrocarbons is linked to increased petrol aromaticity (Edwards, H., 1979).
The introduction of a new petrol with tetraethyl lead concentration of 0.64ml/gallon (~
0.13g/£) in Mexico city coincided with an increase in non-methane hydrocarbons and nitrogen
oxides (Humberto Bravo, A. et al, 1988). Hydrocarbons and nitrogen oxides are the
precursors of ozone formation (with atmospheric oxygen and ultra violet light), and since
September 1986, the ozone situation has worsened there although it has been noticed there a
long time ago and is now Mexico City’s number one air pollutant.
Not only removal of lead reduces the octane rating and consequently the engine efficiency, but
also the quality and composition of petrol markedly affect the combustion products emitted.
If the octane rating is low, efficiency drops, fuel consumption rises, and an increase of the
emission of nitrogen oxides and hydrocarbons takes place. We have observed a sharp decrease in the quantity of nitrogen oxides emitted in UK during the period 1983-1984. At present we are observing sharp increases in nitrogen oxides in 1985, as well as continuous increases in hydrocarbons (fig. 1). Yet, emissions of lead fell by about 12% between 1975 and
1985 (DOE, 1986). There is a clear evidence from the Mexico case that lead reduction in petrol resulted in a great increase in photochemical air pollution. There is the need to weigh the side effects of removing lead in petrol in order to avoid serious air pollution problems.
Ozone is a powerful gaseous oxidant, (sometimes used in disinfecting water), it causes material damage such as rubber to become brittle and so car tyres are damaged. It spoils many leafy vegetables such as spinach and beans, stunts the growth of other plants such as tomatoes and pine trees and is associated in people’s minds with the smarting of the eyes
(Scorer, R.S. 1974).
43 Phytopathological damage due to ozone (Og) is already being observed in the woods and vegetation of the southern zone of Mexico city (Humberto Bravo, A. et al, 1988). Further effects are to be expected not only on vegetation but also on the health of Mexico city’s inhabitants as the ozone levels are now several times those in previous years. Among common air pollutants, Og appears most likely to produce significant respiratory effects at ambient concentrations, on the basis of epidemiological and controlled human exposure studies. Epidemiological data suggest an association between aggravation of asthma, reduced athletic performance (decreased pulmonary function) and elevation of Og (oxidant); and controlled human exposure studies suggested that the symptoms of airway irritation observed in exercising students during the photochemical air pollution in Japan resulted mainly from exposure to Og(Kagawa, J., 1984). It was noted, however, that Og concentrations in the Los Angeles Area (USA) are much higher than those in Japan.
It is noteworthy that the average airborne lead level in Cincinnnati, Ohio fell by about 30 per cent between 1946 and 1966 despite a 200 per cent increase in traffic and at a time when the lead content of the petrol used had also increased (Mills, A.L., 1971).
An international study conducted under the auspices of the United Nations Environment
Programme and the World Health Organization provided the first analytical comparable Pb-
B data set available to infer the current similarities and differences in lead absorption from country to country (Friberg, L. and Vahter, M., 1983).
Two hundred school teachers from one urban area in each country constituted the target group, and both sexes were represented. School teachers were chosen because they would constitute a rather homogeneous group (teachers represent some form of middle class), would be fairly easy to select from lists in the chosen cities and areas and the samples could probably be collected at the working places without any particular risk of contamination. The analytical quality control (QC) involved analysis of both internal quality control samples
(IQC, concentrations of Pb known to the laboratories) and external quality control samples
(EQC, concentrations not known to the laboratories). No laboratory started the monitoring before achieving satisfactory results of quality control analysis.
The geometric mean (GM) values of Pb-B levels for the total number of teachers ranged from about 6 /zg/d£ in China (Beijing) and Japan (Tokyo) to 22.5 /zg/d i in Mexico (Mexico city).
The values were below 10 /zg/d t in USA (Baltimore), Israel (Jerusalem), Peru (Lima),
Sweden (Stockholm) and Yugoslavia (Zagreb), and between 10 and 20 /zg/d£ in Belgium
(Brussels) and the Indian cities. The United Kingdom did not participate in this study,
although 1 0 countries have participated.
Friberg, L. and Vahter, M., (1983) pointed out that “provided that the data from the 1967 study (i.e. Goldwater, L. J. and Hoover, A. W., 1967) are correct”, there is a general trend for decreasing blood lead levels. Jones, R.R., (1983), compared the Findings of the two studies and inferred that Pb-B levels in Japan (Tokyo) have fallen by 70 per cent due to the use of lead-free petrol.
This makes sense neither to the environmental epidemiologist nor to the environmental toxicologist. It is now necessary to examine the overall picture in more detail. Few points in my opinion are worth noting:
1. The first survey was based on 40 “normal” subjects (males and females) from urban and rural areas, many of whom were hospital employees and clinic patients “because of easy availability”.
The second survey was based on 200 school teachers constituting males and females as well; however, it was selected from one urban area in each country (i.e. the Capital) “since in some countries it would be difficult to find a limited group of persons representing the general
45 population, even for a limited area, and it would be fairly easy to select from lists in the chosen cities and areas”.
A research study can be based on a haphazard selection of readily available subjects where one could ask a number of readily available subjects such as patients, employees, friends and colleagues to submit to measurements of Pb-B levels (Collaborating laboratories made their arrangements for obtaining samples in the first study). However, results from this kind of study cannot be extrapolated beyond the subjects studied, because the mixture of patients, employees and whatever in a “grab” sample will depend crucially on one’s own personal bias in the selection of members of the group (Elwood, P.C., 1983a). The results of a study based on a particular group of subjects can be extrapolated with confidence to a larger group of subjects only if the group studied can be representative of the larger group e.g. the Japanese
population(Elwood, P.C., 1983a).
2. Table 2: Pb-B levels in Japan (urban and rural, 1967)
Sample Size Arithmetic Mean (AM) Median Range SD* (grab sample) (males and females)
40 20 /ig/100ml 20 ^g/100ml 5-60 /zg/100ml 8 /ig/100m l
* SD=standard deviation (Goldwater, L.J. and Hoover, A.W., 1967)
46 Table 3: Pb-B levels in Japan (Tokyo-urban, 1983)
Males Females Males and Females (teachers)
N f p b C f N F C (N + F + C)
Sample Size 17 19 64 77 8 15 2 0 0 ( 1 0 0 males and 1 0 0 females)
Geometric Mean 6.5 6 . 2 6.9 5.2 5.0 6.4 6 . 0 ^ g /1 0 0 ml (GM)/ig/100ml
Geometric standard D eviation 1.3 1 . 2 1.3 1.3 1 . 2 1.5 1.4 (GSD)jxg/100ml
(Friberg, L. and Vahter, M., 1983)
a N = nonsm oker b F = Former smoker c C = Current smoker
Elwood, P.C. (1983b) commented that it seems remarkable that anyone should judge that
these data-from two surveys sixteen years apart, neither of which attempted to study a
representative sample of the population in Tokyo-lead to the “obvious conclusion that petrol
is the main source of lead in human beings”.
Elwood, P.C. (1983b) calculated the fall in Pb-B levels to be 30% and not 70%. My first
comment is that the GM is always < AM.
The second comment is that since Pb-B levels are lognormally distributed in populations, we
can convert the GM of the 1983 survey into AM using the conversion formula: i 2 £nG M + |(G S D ) 2 AM = e ’ ‘sv 7 ( — a = — Aitchison, J. and Brown, J.A.C., 1957). The
AM turns out to be = 15.96 /jg/100ml. The percentage change in Pb-B levels among the
Japenese population turns out to be 20.2%, assuming that the two surveys were
epidemiologically perfect. The third comment is that misuse of statistics is unethical in
medical research (Altman, D.G., 1980).
Tetraalkyl lead which is added to petrol is burnt in the engine and most of it is exhausted as
suspended particulate emissions. The particulate matter emitted from cars is a complex
mixture of lead salts, iron as rust, base metals, soot, carbonaceous materials and tars (Habibi,
K., 1973). Measurement and characterization of these particles require elaborate sampling
procedures and sophisticated analytical methods. Many factors, in particular the mode of
vehicle operation, the age and mileage of the car and type of fuel, can affect the composition
and the total particulate emission rate.
Exhausted lead, depending on the condition of the exhaust system, ranges between 7 and 30%
of the lead consumed by the engine (Ter Haar, G.L., et al, 1972). Results by Habibi, K.,
(1973) indicated that for the average car, 57% of the exhausted lead is associated with
particles > 9 fi equivalent diameter. Size of the lead particles emitted from the vehicle
increase with mileage (Habibi, K., 1973; Ter Haar, G.L. et al, 1972). Very large particles >
200 n diameter contain approximately 60 — 65% lead salts, 30-35% Fe 2 and 2-3% soot and
carbonaceous material (Habibi, K., 1973).
About 18% of the lead burned is emitted as fine particles and 11% as coarse particles; these
represent emission rates of 0.051 and 0.028 grams/mile respectively. Over the life time of
the car, it was estimated that about 35% of the lead burned is emitted as fine particles and
40% as coarse (Ter Haar, G.L. et al, 1972).
4 8 Hirschler, D.A. and Gilbert, L.F. (1964) estimated that on average 70-75% of the lead in
petrol is discharged into the atmosphere.
Emissions of lead from petrol driven vehicles depend upon several factors in addition to the
lead concentrations, including traffic density, traffic patterns, fuel efficiency and fuel density
(DOE, 1987).
The lead compounds emitted from petrol engines are commonly present in complex
aggregates together with carbonaceous material and in this form they may be less available to
man than if they were present in simpler form (DHSS, 1980). The fact that a particle is
present in ambient air does not mean that it will be inhaled and if inhaled retained.
Evidence indicates th a t a heterOQeneOUS aerosol, such as is encountered in the am bient air,
clears the functional areas of the lung with constant kinetics (Gibb, F.R. and Morrow, P.E.,
1962). Because of its wide dispersion, only a minute proportion of the total lead emitted is
liable to find its way directly into human beings (DHSS, 1980).
The figure for the contribution of petrol lead to body lead burdens on which the British
Government is currently operating is 10 per cent (Jones, R.R. and Rutter, M., 1983).
The average reduction in airborne lead concentrations derived from 17 monitoring stations by
Warren Spring Laboratory in UK was 49%, this suggested that nearly 80% of airborne lead
was dependent on emissions from vehicles prior to 1986 (Mclnnes, G., 1986). This estimate of 80% contribution from lead in petrol is the first revision of the estimate of about 90%
made in the mid 70’s as stated by the author.
In the UK, it has been estimated that 50% of petrol lead emitted is transported in the air and deposited in the UK, and half is deposited elsewhere; this is shown diagramatically in figure
2 (RCEP, 1983). It follows that some of the lead in air in UK is derived elsewhere.
The isotopic lead experiments (ILE) have illustrated how air lead levels may be indicative of
49 human exposure only in a general sense.
The ILE (Facchetti, S. and Geiss, F., 1982) was a large-scale community study in which the
geologic source of lead for antiknock compounds in gasoline was manipulated to change the
isotopic composition of the atmosphere. Preliminary investigation of the environment of
Northwest Italy, and the blood of residents there, indicated that the ratio of 2 0 6 Pb/207Pb in
blood was a constant, about 1.16, and the ratio in gasoline was about 1.18. This preliminary
study also suggested that it would be possible to substitute for the currently used geologic
sources of lead for antiknock production a geologically distinct source of lead from Australia
that had an isotopic 2 0 6 Pb/207Pb ratio of 1.04. It was hypothesized that the resulting
change in 2 0 6 Pb/207Pb (from 1.16 to a lower value) would indicate the fraction of lead in
blood of exposed human populations attributed to lead in the air contributed by petrol
consumption. In August 1975, the Australian lead-labelled petrol was partially introduced
(50 per cent substitution), and by May 1977 the substitution was practically complete. By
the end of 1979, a partial return to the use of the original sources of lead began. The period
of the experiment was 18 months. The areas studied were: the city of Turin where the traffic
is very heavy and has the smallest inhabitant/car ratio in Europe, the nearby countryside
<25 Kms and the remote countryside >25 Kms. Because of geographic and climatic
conditions, there is little air movement in the city and air levels tend to be higher than that
of other cities in Europe. The mean lead in air level in Turin during the course of the
O experiment was 2/zg/m , and the lead content of petrol sold in Italy was 0.6 g ji and
approximately 90 per cent of the petrol sold was premium (Assoc. Octel, 1983b). Typical
3 mean air lead levels in London are 0.5 — 1 /xg/m (DHSS, 1980) and the lead content of petrol o in U.K. was 0.40g/£. Air lead level in the nearby communities was 0.56 /xg/m (<25 Q Kms), and 0.30 /xg/m in more distant communities (>25 Kms). The estimated contribution of petrol lead to blood lead was 24 to 27 per cent of total blood independently of
the blood lead concentration. Mean Pb-B level, of people living in Turin was 22.5/xg/ 100ml,
50 while that of people living in the outlying villages was 29.6 /ig/100mls.
Pb-B levels were higher in the rural areas than in the city. It is obvious that air has
contributed only very slightly to the exposure.
Elwood P.C. (1983d) has remarked that the sample studied in the test area consisted of 200
industrial workers, 699 voluntary blood donars, 10 volunteers from the staff of one of the
collaborating institutes, 48 Turin traffic wardens, an “extra group of 12 individuals, many
children (not described), and 8 “mother-infant situations”. These add up to 3971; whereas
blood results seem to have been presented for only 339 (i.e. 17 per cent). Data from the ILE
probably cannot be extrapolated to yield an estimate of the contribution petrol makes to the
blood lead of a whole population (Elwood, P.C., 1983d).
Lead in petrol is widely assumed to be an important source of environmental contamination.
It is interesting to see that the Pb-B level of rural communities in the ILE (29.6 /ig/100ml) in
Northwest Italy is remarkably similar to the Pb-B level of London Taxi Drivers (28.7
^/g/lOOml) reported during a survey in 1972 (Jones, R.D. et al, 1972).
Jones, R.D. et al (1972) reported that there was no difference of statistical significance in the
blood-lead levels of night-shift and day-shift drivers, although these two groups constituted distinctly different exposures.
Road traffic patterns, determined by air pollution emissions from vehicles show weekly and daily cycles (WHO, 1982). It was reasonable to infer that little of the lead found in the blood of the taxi drivers is attributable to the lead they inhaled whilst driving in London streets. The findings support the view that: In the general population, the major source of lead intake is from food (MAFF, 1982). Putnam, R.D. (1986) in his review of the toxicology of inorganic lead has stated that for non-occupationally exposed individuals, ingestion from
51 food and water contributes to the majority of the body burden of lead. Snedden, J.M. (1986) has indicated in his article on trace metals in food that metals from the environment mainly enter the body by gastrointestinal absorption and may originate from many different sources.
He pointed out that concentrations of heavy metals in air are too low to contribute to the total body burden (drinking water may constitute a significant proportion of dietary lead intake as in the case of babies) and that the accumulation in the body presumably results from the diet. Studies relating to population from northern Italy have consistently revealed somewhat higher mean values, ranging from 24 to 35 /zg/100ml (WHO, 1977).
Urinary lead excretion among Italians was found to be higher than other Europeans, and hence are expected to have higher body lead burdens. Unexposed Italian workers had an excretion level of 29 /zg/24 hrs as compared by Staessen, J. et al (1984) with their own figure for unexposed Belgian workers of 14 fj,g lead/g creati
The ILE results might be accounted for by higher consumption of wines and water among
Italians. Lead concentrations in Piedmont-made wines (the countryside surveyed) averaged
155 ± 67 /ig/£. Daily wine consumption for rural drinkers ranged from 0.5 to l£/day.
Lead concentration: in tap water in Turin was 4 /ig/£, while it ranged from 12 to 20 //g fi in the country-Maximum permitted level in water is 50 /ig/£-(U.S.E.P.A, 1986).
Concentrations of lead in wine in Sweden range from less than 10 to 500 pg fi with an average of 63 The sample selected in the Turin experiment was overwhelmingly male* Thus, the importance of wine consumption becomes evident. Elinder, C.G. et al (1983) have estimated that a daily consumption of 0.5 litres of wine could easily increase the daily intake of lead by 52 a factor of 2. Spirits can contain high concentrations of lead, especially if they illegally produced. (Elinder, C.G. et al, 1983). » 53 4.2 Lead in Air as a Potential Pathway of Exposure The concentration of airborne lead decreases rapidly with distance away from roads; a graphvalues illustrating this (fig. 3) suggests that concentrations fall to about 20% of their kerbside'fat a distance of 50 metres (DHSS, 1980). At greater distances the merging of the contributions O from all traffic produces a typical urban background value of about 0.5 /ig/m (DHSS, 1980). The phenomena of vertical and horizontal gradients of atmospheric lead at the roadside appear to be of special significance to children. In one roadside study in Brattleboro, Vermont (USA) twice as much ambient lead was found below 4 ft (1.20m) as above that height (Hunter, J.M., 1977), thus comparison of adult and child respiration zones above ground level (i.e. lower and upper floors of buildings) points to the importance of correct interpretations of human exposure to airborne lead. The horizontal fallout gradient of ambient lead indicates that children playing within 5-10ft (1.5—3m) are more vulnerable to lead exposure . Population-at-risk studies assume that each person spends 24 hours at his or her residence and that indoor pollution concentrations are correctly indicated by the nearest ambient air monitoring station. Elwood, P.C. (1983c) addressed this question by pointing out that there is no simple relationship between measurements made indoors and outdoors. The ratio is very much lower if made in a room at the rear of the dwelling rather than at the front. This is highly relevant because subjects who live in dwellings on a main road are likely to make their living rooms one of the back rooms in order to limit noise and dust and this will, pari passu, lead to a lowering of air lead levels. (Elwoods, P.C., 1983c). An investigation in England (Warwick) indicated average values of atmospheric lead to the rear of buildings facing a busy street to be only one-third of the average for the street itself (Bullock, J. and Lewis, W.M., 1968). 54 Laxen, D. P. H. et al (1985) studied the importance of lead-in-air as an exposure pathway for children 6 to 9 years old in Edinburgh over the period April 1983 - May 1984. Exposure levels were significantly lower than that of 1 /jg/m normally used to represent the exposure of urban populations (Royal Comm, on Env. Poll’n, 1983). The geometric mean Pb-B level for the 212 Edinburgh children surveyed in 1983/1984 was 11.6 /zg/100ml. The results of their measurement programme indicated that average lead-in-air exposure levels for Q Edinburgh children lie in the range 0.16 to 0.31 /ig/m . The authors have pointed out that the concentrations of lead in air are unlikely to have changed greatly over the last 6 to 9 years, and if anything they might have declined slightly, as lead emissions from vehicles have fallen in the UK by about 10 per cent since 1975 (DOE, 1983). This aSSSS^jnent.approach indicated that lead in air makes only a small contribution to total exposure from all Sources; the estimate being in the range of 1 to 20 per cent. The geometric mean Pb-B level of Edinburgh children (sample: 212, age: 6-9 years) of 11.6 /ig/100ml was less than that of 15.6 //g/100 ml (AM) reported for 187 pre-school children surveyed in Birmingham aged < 6 years (2.5 to 5 years - is the pre-school age) (Harvey, P.G. et al, 1984). That blood samples taken from pre-school children in Birmingham aged between 1 and 4 years of age showed blood lead concentrations most similar to those of adults (Waldron, H.A., 1979) is noteworthy. 55 Table 4: Blood Lead Concentrations in Adults and Pre-school Children in Birmingham (Waldron, H.A., 1979) A dults Pre-school children males females males females Pb-B (mean, fimol/£) 1.07 0.71 1 . 0 1 0.92 Pb-B(/zg/100ml) 2 2 . 1 14.7 20.9 19 Female pre-school children seem in fact to have higher Pb-B levels than those of adult females. Ingestion of lead from soil or dust is common among children of such age (< 6 years), but minimal among the adult population, and this might have contributed to such a result. Sherlock, J.C. et al (1985) have observed that if only a fraction of the lead from a child’s hands was transferred to the mouth either directly or via food, it could make a substantial contribution to lead intake. They found that children who washed their hands before eating had significantly lower Pb-B concentrations than those who did not. The point which I would like to draw the attention to here is the fact that the indoor concentrations of suspended particulate matter average ground 70 per cent of those outdoors (WHO, 1982). Pre-school children will normally spend greater time indoors, while school children will spend relatively more time outdoors even for short periods, for instance as they walk to school; yet still the pre-school children have shown higher Pb-B level. This certainly demonstrates the relative minor importance of air as an exposure source compared to other sources like dilapidated housing, peeling lead paint and old plumbing system. The Pb-B level of 15 fig/ 1 0 0 ml has been quoted in the literature as the background lead concentration in human blood for urban dwellers (Ramakrishna, R.S. and Ponnampalam, M., 1982), however, it does not compare with the average Pb-B levels recently reported for 1000 children 6 to 7 years old 56 to be representative as national mean levels. The levels reported were 10 /zg/100 ml in 1984, and 9 /zg/100 ml in 1985 (DOE, 1987). There is still uncertainty and argument about the relationship of lead in air and its contribution to lead in blood. To give one example, Chamberlain, A.C. et al (1975, 1978) using isotopically labelled lead alkyl in petrol which could then be traced when inhaled by o volunteer subjects, showed that for 1 /jg/m of lead in air breathed, there was an increment in blood lead of approximately 2 /zg/100 ml. Brunekreef, B. (1984) concluded from his review of community studies that a wide range of a values (blood-lead air-lead relationship is denoted by the symbol ‘a ’) can be estimated from the data in the different studies. He suggested a range of 3-5 rather than 1-2 which is usually reported for adults. Snee, R.D. 3 (1981) considers on the basis of his review that an exposure to an additional 1/ig Pb/m of air can result in an increase of approximately 1 /zg/ 1 0 0 ml of blood. He has clearly figured out that the accuracy of the a value is less clear for children than adults due to the small data base. Many studies of the contribution of airborne lead to blood lead in children have been carried out on populations living in the vicinity of smelters. Brunekreef, B. et al (1981) studied the uptake of 1 to 3 years old children living in the vicinity of a secondary lead smelter in Arnhem, The Netherlands, in which Pb-B levels were determined. He concluded that “because of the fact that significant relations exist between ( blood-lead) and (environmental-lead)”, this suggests that in several inner city areas with heavy traffic, lead uptake by small children leads to the same or even higher blood lead levels found in Arnhem. This is one fallacy to be guarded against. I am very much convinced of the line of reasoning that Snee, R.D. (1981) has followed, and my further discussion below will elucidate this. Snee, R.D. (1981) has seriously questioned the representativeness of the data of the air lead exposure of children living in urban and surburban communities. Chamberlain, A.C. (1983) reported that the sensitivity of Pb-B to air is higher at lower Pb-B 57 levels. Gallacher, J.E.J. et al (1984a), however, have expressed their reservations towards both field and experimental studies on the blood lead-air lead relationship since these involve exposure to very high air lead levels (Chamberlain, A.C., 1983) and the results are therefore of doubtful relevance to the levels to which most people are exposed, such as those for inside dwellings. Studies on the time budgets of people in the United States and Europe have indicated that on average, individuals may spend up to 90 per cent of their day indoors in residences, offices, schools, shops etc. . Exposure has been defined as the amount of a particular physical or chemical agent that reaches the target. Thus, the estimation of human exposure is usually based on measurements in which the human being is treated as the target (WHO, 1982). Because of its wide dispersion (either close to motorways where the more open situation and rapid movement aids dispersion), only a minute proportion of the total lead emitted is liable to find its way directly into human beings, and few people are likely to be exposed to long term average concentrations greater than 1 /zg/m (DHSS, 1980). Exposure to a given pollutant is a measure of the contact between the pollutant and the outer or inner surface of the human body. Thus, air pollution exposure estimation is the determination of the concentration of air pollutants in the inhaled air as a function of time and space coordinates, in which the space coordinates define the position of the exposed individual in particular his nose and mouth. Dose, on the other hand is the amount of air pollutant that crosses one of the body boundaries, e.g., the epithelium in the nose or lungs. Integrated exposure therefore incorporates the durations of the exposure by integrating the concentration with the duration of exposure; for example, ^g/m -hours (WHO, 1982). Unlike occupational exposure which refers to the 8 -hour work period, total exposure refers to 24-hours exposure. Because of these uncertainties, the results from population-at-risk studies are at present reported as potential exposures (WHO, 1982). 58 The ability to retain inhaled lead particles varies between healthy individuals by a factor of three or more as found by some human exposure studies (Hursh, J.B. et al, 1969). Efficiency of removal by the mucous membranes of the nasopharynx, biological adaptation to toxicological interactions among various pollutants in the air, nutritional differences and other personal and environmental factors (such as smoking) all have direct effects. It is important to recognize that the determination of the level of lead in blood was originally set for the purpose of monitoring lead-exposed workers (Tompsett, S.L. and Anderson, A.B., 1939; Lane, R. E. et al, 1968); and later on found applications in community health surveys in order to assess populations exposure. The half-life of lead in blood is estimated to be 2 to 3 months. If the exposure levels do not undergo major changes, blood lead levels may be used also for the evaluation of long term risks (Friberg, L. and Vahter, M., 1983). However, investigators do hotseem to understand the concept of potential exposure. Delves, H.T. et al (1984) during their investigations of the stability of Pb-B levels in which 2 1 healthy adults exposed only to environmental lead were studied came out with an interesting observation. The 21 adults of both sexes were divided into 2 groups. Group A consisted of 11 adults (males and females) who came from London, while group B consisted of 9 adults (males or females) who came from a surburban/ rural environment in Berkshire. Pb-B levels observed ranges were 9.4 to 15.5 /ig/100ml and 8.6-15.8 /xg/100ml for groups A and B respectively. The Pb-B levels were very similar with no significant difference between the mean blood lead levels of males in groups A and B. This is not surprising since, although environmental lead levels are higher in central London than in Berkshire, most of the people working in London lived outside the city and therefore probably spent less than 25 per cent of their total time in London. 59 In the most recent UK Blood Lead Monitoring Programme 1984-1987 (DOE, 1986), Pb-B levels in Liverpool and Manchester were 20-30 per cent higher than in London for exposed adults, exposed adults being people living on major roads (Results for 1984). The EEC Blood Lead Surveys, 1979-1981 (Quinn, M.J., 1985) have also shown a marked difference between levels in northern cities and London. If lead emissions from motor vehicles were a major contributor to the body burden of lead, one would have expected that people living in London, with its high traffic density, would have higher blood lead concentrations than people living in other cities. However, the level of lead in air and the level of lead in blood doijhjofcseem to run parallel to each other. It is clearly stated in the UK Blood Lead Programme! Monitoring " 1984-1987 that surveys were not planned in areas where either it was known that water was plumbosolvent e.g. Scotland, or there were lead/zinc smelters or battery factories, in order to assess the effect of the reduction in the maximum permissible lead content of petrol from 0.4g/£ to 0.15g/£ which took place at the end of 1985. Manchester and Liverpool were among 9 areas surveyed for exposed adults in the general population living in houses directly or heavily trafficked urban roads. (Quinn, M.J. and Delves, H.T., 1987). Boudene, C. et al (1977) have studied the fate of inhaled lead in rats exposed for a short period of time to an “urban-like-aerosol” labelled with Pb. The following results were obtained: (i) 40 per cent was eliminated by the gastrointestinal tract (ii) 15 per cent was excreted by the kidney (iii) 40 per cent was fixed in the skeleton (iv) 1 per cent remained in the lungs (v) 4 per cent was distributed among blood, spleen, liver etc. It was noted that a rather large amount of inhaled lead was excreted following mucociliary action. The skeleton was the main site of fixation of the lead. Heard, M.J. and Chamberlain, A.C. (1984) studied the uptake of 203Pb by human skeleton following its administration by intravenous injection, and translocation to bone was measured by j counting the feet of 60 subjects. It was reported that 55 per cent of a systemic input of Pb would rapidly become skeletal. Deposition in bone has been regarded as a detoxifying mechanism, for lead in bone is virtually inert. Extrapolation to the whole skeleton indicated that 20% of the dose had been taken up within 20 days; uptake of 203Pb by bone was comparatively small. In one study, Pb-B levels were determined among adults before and after the opening of a motorway interchange with a high traffic density. Pb-B levels were found to be considerably higher among men and women living in the immediate vicinity of the interchange after it was opened than before (Waldron, H.A., 1975a). In the evaluation of the results of the study, allowance must be made for the fact that no control group was studied, the procedure of drawing samples was changed after opening the interchange, the sampling took place at different times of the year (seasonal variation) and no data was given pertaining to quality control validation of blood analysis. Elinder, C.G. et al (1983) in their study of exposed adults in Sweden (Stockholm) found that residency close to streets with heavy traffic had only a slight effect; their results have shown that sex, smoking habits and alcohol consumption are factors of much greater importance than residency close to streets with heavy traffic. It is noteworthy that the maximum permissible concentration of lead in petrol was lowered from 0.4 to 0.15 g /i in 1981 in Sweden, while the study was conducted in 1980 before the reduction of lead in petrol took place. 61 4.3______Lead in Paint as a Potential Pathway of Exposure Lead in paint is dangerous not only in the form of peeling chips in poor housing but also as dust and fumes produced during renovation of old housing or burning of painted wood for fuel, and as soil lead after old buildings are demolished (Lin Fu, J.S., 1982). High Pb-B levels were found in pre-school children in Birmingham (47 of the 319 children surveyed i.e. 14.7 per cent had Pb-B > 35 /zg/100ml)(DOE, 1982b). There was some evidence that the concentration of lead in internal dust samples was greater in the houses of children with raised blood lead concentrations than in the houses of children whose blood lead concentration V/Bjs low. In view of the large number of paint samples which contained high concentrations of lead, it seems likely that some of the lead in the dust came from paint. Over 90 per cent of m g all the paint samples which were examined contained more than 2500 ppm(-r-2) of lead; a Kg substantial proportion contained over 1 per cent of lead, and some contained more than 30 per cent of lead. Paint is therefore suspected as being an important contributor to lead in dust. Exterior paint is usually heavily leaded and thus an exterior door, door-frame, windows with painted wood and wire frames, porch, fences or walls will present a paediatric risk. Weathered paint residues accumulate in the soil around a house and present an associated risk for young children playing outdoors. Humidity and high environmental temperatures typical of coastal areas of South Carolina (USA) serve to accelerate the weathering and decomposition of paint on exterior surfaces (Hunter, J.M. 1977). The hazard which lead paint presents to young children had been pointed out in the report “Lead and Health” (DHSS, 1980) and it was recommended that surveys should be undertaken to discover the extent to which children are at risk from this source. The findings which have emerged from their studies seem to underline the necessity to approach this problem as a matter of urgency (DOE, 1982b). In the USA, ct 1979 survey indicated that almost one third of housing units (27 million) were 62 built before 1940, when lead paint was in common use. Over half (49 million) were built before 1960 and may have lead paint. In 1979, 9 per cent of rental units had peeling paint, and 7 per cent had peeling plaster (Lin Fu, J.S., 1982). It might be expected that the high Pb-B values found among blacks in the USA during 1976- 1980 national estimates of Pb-B levels program, would reflect differences in the degree of urbanization of their place of residence (Mahaffey, K. R. et al, 1982). Ormandy, D. (1987) states that there has been no housing hygiene policy, and certainly not since the 1950s at least, even if there has been one at all in the USA. Legislation by the American Public Health Association was to deal with insanitary measures which would have an effect on the health of the occupiers, but not if it W«?sin disrepair. Lead in paint acquires particular significance since young children are particularly vulnerable to lead exposure through hand-to-mouth activities, such as thumb sucking, nail biting, or eating with dirty hands; lead in house dust and garden soil readily enters their bodies. Children with pica are exposed to more lead because they eat such items as paint chips, broken plaster and dirt. Moreover, intestinal absorption is greater in children than in adults (Lin Fu, J.S., 1973). Although the use of lead based paint in factories has been controlled by the Lead Paint Regulations 1927 (now incorporated in the Health and Safety Work Act, 1974), the lead content and use of paint by the general public are not subject to statutory control except in the case of toys (Page, R.A., 1984). There is a voluntary agreement between the Paintmakers Association and the Government under which paints which give more than 1 per cent total lead in dry film carry a warning that they should not be used in surfaces accessible to children (Page, R.A., 1984). 63 To put lead in paint into perspective, 1 per cent of lead in paint as dry film is the same as 1 0 , 0 0 0 mg/kg (ppm) in paint as dust. Laxen, D. P. H. et al (1987) have recently estimated that a 1000 ng/g (ppm) increase in dust lead concentration would increase blood lead by 1.9/ig/100ml for a child with a median population blood lead of 1 0 . 1 ^ g /1 0 0 ml. They proposed a level of 1000 ptg/g as an appropriate dust lead standard; this suggested standard applies to household dust collected by vacuuming from the floor. The lead content some time- of paint on toys and pencils has been controlled for The toys Safety Regulations 1974 prescribed 0.25 per cent of the dry paint film as the maximum pe-mitted level, and the Pencils and Graphic Instruments Safety Regulations 1974 set 0.025 per cent as the maximum level of soluble lead in paint for pencils (Page, R.A. et al, 1984). Rabinowitz, M. B. et al (1985) have measured the Pb-B levels of 249 infants semi-annually from birth to two years of age. They sampled the home paint and recorded any recent home refinishing activity. Mean Pb-B levels did correlate significantly with the amount of lead in the indoor paint (p< 0 .0 1 ). Refinishing activity in homes with high lead paint was associated with elevations of Pb-B levels averaging 69 per cent. Because of parental anxiety over children in the Greenwich London Borough living on or near an inner London arterial highway carrying about 35,000 vehicles/day, blood lead levels of a small group of children were measured for an assessment of the situation (Millar, I.B. and Cooney P.A., 1982). The analytical results have shown that the mean Pb-B level for children attending the school (Deansfield Infants School) and not residing on the highly 6 k trafficked highway (Rochester Way) was 14.02 /ig/100ml, while the mean for children attending this school and living on the highly trafficked Rochester way was 12.15 /ig/100ml. The difference was significant (P<0.05). The total number of blood samples taken was 221 with no failures. The number of children examined was 65 infants and 81 juniors, and the response rate was high (82 per cent for infants and 84 per cent for juniors). Residence of the children on the highly trafficked highway did not have any effect. Lead in dust levels in the school playground were low, possibly as a result of constant sweeping operations. Lead in dust levels, however, showed a marked increase in levels at a distance of 48m. This site was situated within an open-fronted shelter where children could sit and eat sandwiches, or gain protection from severe weather conditions. While sampling, it was observed that paint on the ceiling had badly deteriorated and that the floor of the shelter was covered in several places with large flakes of paint.' The paint had a lead content greatly in excess of the “less than 1 per cent” standard set by the Greater London Council (GLC) for use in dwellings or in schools. The most significant feature of this study was that distribution of small particles of paint into playground dust was directly responsible for the elevated level of lead in dust, and was that it a far more important source of exposure than lead from vehicles (levels of 2 0 0 0 ppm being quite common in samples taken throughout the Borough). It was noticed that paint on the walls showed distinct signs of having been picked, and this constitutes a serious health hazard to children particularly those with pica. In another study, children with high Pb-B levels (40 to 70 /ig/100ml) were investigated as to their environmental exposure with respect to lead-base paint in their home environments and traffic density near their residences (Hammond, P.B. et al, 1980). The objective of this study was to determine whether inner city children with elevated Pb-B’s have elevated faecal lead excretion (Pb-F) and to determine how well faecal lead excretion (Pb-F) correlates with lead- base paint hazard and traffic density near the home environment. Collection of stools in the homes was under the supervision of a nurse, arrangements were made to conduct an 65 environmental assessment of the home using a portable X-ray fluorescence analyzer of painted surfaces, and data concerning traffic density were obtained from city records. The results clearly showed that both Pb-B and Pb-F were positively correlated with interior paint hazard. There was an association between Pb-F and exterior paint hazard of marginal statistical significance. Neither Pb-F nor Pb-B were correlated with traffic density. The findings of this study are in agreement with the Greenwich one (Millar, I.B. and Cooney, P.A., 1982), thus lending support to the idea the lead in petrol has no measurable effect. Sometimes paints were labelled as containifij“no lead pigment” when they in fact contained 7000 ppm (0.7 per cent) of lead as a drying agent which is above the 600 ppm (0.06 per cent) limit, which has been set in the US by the Center for Disease Control (Dietch, R., 1984). The public, however, have no idea what they are getting inside a can of paint, nor do most paint shops understand the dangers of lead. In the USA a signifiant hazard exists from lead-containing paints as seen from Rabinowitz, M. B. et al (1985) studies and other American studies, yet paint does not appear on the diagram of major pathways of lead to man from the environment, fig. 4 (U.S.E.P.A., 1986). Every toddler is observed to have hand-to-mouth activities, yet little attention was paid to the internal home environment. The largest determinant of average non-occupational exposure would be the indoor residential levels of pollutants (WHO, 1982). The indoor environment is partially shielded from outdoor conditions. 66 Diemel, J. A. L. et al (1981) have found that in general, indoor pollution levels of lead were lower than the corresponding outdoor levels. The DHSS (1980) report stated that concentrations of lead in air inside houses are generally similar to, or a little lower than, those immediately outside. This probably refers to a well-maintained house. Ter Haar, G. L. and Chadzynski, R.S., (1979) studied the effect of distance of residences of 1309 children from three major roadways in Detriot, USA. The traffic density for the three roads was 170,000 cars/day, 45,000 cars/day and 40,000 cars/days. The data were divided into those living > 200ft and < 200ft from the road. 20 per cent of those living at > 200ft had Pb-B > 40 //g /1 0 0 ml, while only 4 per cent of those living at < 200ft had Pb-B>40 /ig/ 1 0 0 ml. However, 60 per cent of the housing at > 200ft was rated as deteriorated or dilapidated, while only 14 per cent of the housing < 200ft was rated as deteriorating and none was rated as dilapidatjhcj.* The data showed that when an older, deteriorating or dilapedating house is present, Pb-B levels would be higher. It was concluded that the primary cause of the lead problem in children can be greatly diminished by improved housing. Ter Haar, G. L. and Aronow, R. (1974) analyzed dirt samples for lead content in old urban and rural areas. In the old urban area, dirt samples were taken around 18 painted-frame houses and 18 brick- constructed ones. In the rural area remote from traffic, dirt samples were taken around farmhouses. Lead concentrations were similar in city and rural yards at corresponding distances from the houses. It was clear that traffic was not contributing significantly to lead in the dirt in the yards of the old urban houses. The implication is that lead antiknock additives are therefore not a significant contributor to the lead content of dirt around houses where children usually play. Stark, A.D. , et al (1982) attempted the breakdown of environmental lead sources (paint, dust and soil) by dwelling unit ownership in New Haven, USA. Air and water met standard 67 levels. The environmental lead levels did not follow a direct trend in relation to socioeconomic status. However the protective nature of new housing was illustrated by a significantly less lead content both inside and outside than older houses. Although owner- occupied units had the highest lead levels, children living in them had Pb-B levels 4 to 10 per cent lower (with an overall lowering of 8 per cent) than children living in private or public rental unit. It was inferred that low level socioeconomic status contributes to the explanation of increased blood lead levels. 68 4.4 Lead in Water as a Potential Pathway of Exposure Pocock, S.J. et al (1983) in a survey of middle-aged men in 24 British towns have found pronounced geographical variation in blood lead concentrations, and concluded that “It seems reasonable that lead in water should be given priority in any national campaign to reduce lead exposure”. That individuals exposed to raised water lead concentrations in soft water areas have a pronounced increase in blood lead concentrations is clearly shown in table 5. The greatest effort by pressure groups has been brought to bear on the issue of lead in petrol. Porritt, N. (1931) long time ago drew attention to the importance of soft waters, especially those from peaty moorlands which dissolve the lead of the service pipes in causing lead poisoning symptoms. He referred particularly to Huddersfield, and cited Dewsbury, Halifax, Rochdale and the county of Breconshire in England as supplied with plumbosofijfelit water. An investigation of the lead content of soft domestic water (cold tap water) in 23 Glasgow households, Scotland, has found levels of lead up to 18 times the upper acceptable limit, then 100 ngft (Beattie, A.D. et al, 1972). The blood lead levels of 71 inhabitants of these houses showed a significant positive correlation with water lead content. Soft water has a greater avidity for lead than hard water, which may form a shield of calcium salts over the lead surface of the pipes. Acid moorland waters appear to have the most aggressive action on lead piping (Bacon, A.P.C. et al, 1967). 69 Table 5: Blood lead and water lead in 24 towns (Pocock, S.J. et al, 1983) Blood lead Tap water lead (/ig/C) No with Town No of Mean* Mean blood lead No of First Draw Sample Daytime Sample men (/imol/£) (/iS /d C ) > 1.7/imol/£ households 50 /miol/£ — 100- 3 0 0 - 5 0 - 100- 3 0 0 - Ayr 257 0.992 20.8 21 (8%) 40 1 7 7 1 8 4 Harrogate 273 0.990 20.8 7 40 5 7 0 5 0 0 Wigan 333 0.941 19.8 12 39 6 11 2 9 3 1 Burnley 274 0.890 18.8 7 40 6 0 0 2 0 0 Dewsbury 323 0.890 18.7 4 39 1 2 1 1 0 0 Merthyr Tydfil 208 0.808 18.2 6 40 3 1 1 0 2 0 Newcastle under Lyme 276 0.851 17.9 2 38 4 0 0 2 1 0 Southport 318 0.793 16.0 1 40 4 0 0 2 0 0 Lowestoft 317 0.774 10.2 2 41 6 3 0 3 1 0 Falkirk 277 0.768 16.1 2 39 0 0 0 0 0 0 Shrewsbury 307 0.765 16.1 2 39 0 0 0 0 0 0 Mansfield 318 0.748 15.7 0 39 1 0 0 0 0 0 Exeter 330 0.732 15.4 2 39 7 1 0 0 1 0 Guildford 315 0.702 14.7 , 0 40 2 0 0 0 0 0 Scunthorpe 328 0.677 14.2 0 40 2 3 1 2 2 0 Darlington 345 0.660 13.9 1 40 l 1 0 0 1 0 Carlisle 305 0.649 13.6 0 38 4 1 0 1 1 0 Gloucester 202 0.641 13.5 1 38 5 1 0 2 1 0 Dunfermline 321 0.025 13.1 0 40 4 1 0 3 1 0 Maidstone 309 0.006 12.7 1 38 1 0 0 0 0 0 Bedford 286 0.596 12.5 0 37 3 0 0 0 0 0 Hartlepool 311 0.556 11.7 0 38 3 0 0 0 1 0 Grimsby 309 0.550 11.7 2 39 0 0 0 1 0 0 Ipswich 350 0.553 11.0 1 40 1 2 0 3 0 0 All towns 7378 0.738 15.5 74 (1%) 941 70 41 12 37 23 5 * * For every town the standard error of mean blood lead was less than 0.03 /nnol/l For every town the standard error of mean blood lead was less than 0.03 pmol/L 70 In this study water supplied by the local authority in Britain was well within the limit of 100 figji recommended by WHO (1971) at source, but lead contamination seemed to have occurred within the houses from the lead tanks and pipes which carried the cold water. The first attempt to obtain a picture of the national situation was made by the Ministry of Housing and Local Government in 1967 in Britain. The study concluded that there was no need for widespread action in the country with the exception of a few specific local supplies where treatment to reduce plumbosolvency was indicated . The publication of the DOE (1974) report on “Lead in the environment and its significance to man” drew attention to the problems of lead in water at the tap in areas supplied with plumbosolvent water. The Department of the environment published in 1977 (DOE, 1977) the results of a national survey of lead in drinking water. It was designed to give an estimate of the number of households in Britain where the lead levels exceeded the limit of 100 figji (i.e. a snapshot in time) and it has shown that there was an appreciable percentage of samples taken at the tap where the WHO limit was exceeded. Work associated with the survey showed, that even for a given water supply, lead concentrations could vary significantly both within and between houses depending on the nature and configuration of the plumbing, the pattern of household water use and the length of time the water has stood in the pipe. The WHO 1971 limit of 100 fig/l was adopted by this report. The DOE (1982a) report announced changes to approve grants for the replacement of lead plumbing. The grant is discretionary, and is likely in areas where water treatment is unlikely to be the most appropriate solution, where the problem is so serious that it is inadvisable to await water treatment, or where a household is at particular risk. The assessment of the exposure of individuals to lead in drinking water is made difficult by the 71 large within-house variation in tap-water lead concentrations according to the Water Research Centre (Bailey, R.J. and Russell, P.F., 1981). The variation is due to many factors such as the increase in lead concentrations with increasing contact time in the pipes, the flow- rate at which water is drawn from the tap and the volume of water drawn in relation to the length of pipe. Gallacher, J. et al (1983) suggested that the hardening of soft water supplies could make a substantial contribution to the general reduction of blood lead since the highest blood lead levels seem to occur in soft water areas. A reduction in blood lead was shown to occur even where initial water lead levels were negligible simply by hardening of the water, at a time where no reduction was shown to occur in a nearby area where water was not hardened. Soft upland waters occur in parts of Scotland, Wales and Northern England. Lead levels could be significantly reduced, in most cases to acceptable levels, by the addition of an alkali such as lime, Ca(OH) 2» or caustic soda, (NaOH), to maintain the pH value of the water above 8.0. It is important that the pH value is controlled at a consistent level above 8.0 and that this level is maintained throughout the distributed system to the tap (Goodman, A.H., 1984). It seems that some encouraging results have been obtained in preliminary trials by the addition of orthophosphate (to give about 100 /zg/£ as phosphorous) as an adjunct to pH control by alkali addition for soft waters (Goodman, A.H., 1984). Widespread replacement of lead pipes may involve enormous expenditure, yet it may become obligatory where technical difficulties occur particularly with some hard plumbosolvent waters. Studies at the Water R esea t Centre indicated an optimum pH of 8.5 for minimum plUm to solvency. Moore, M.R. et al (1981) examined 236 mothers in the postnatal wards of Stobhill Hospital in Glasgow aged 17-37 with no history of industrial lead exposure in 1977. Later, they examined 475 mothers in the same hospital and in the same time of the year (autumn and winter) in 1980. The pH of Glasgow water supply was raised from 6.3 in 1977 72 to 9 in 1980, which maintained a pH of over 8 at the tap. 7.5% of mothers in 1977 had blood lead levels in excess of 1.5 /zmol/£(31 /xg/d£), but only 0.4% of the equivalent group had blood lead levels in excess of 1.5% /xmol/£(31 /xg/d£). All of this work was carried out in women at the same stage of pregnancy, and the authors concluded that this dramatic drop in blood lead levels is a result of the water treatment since no other source of exposure could be identified. In Ayr (Scotland, UK) where the water supply is very plumbosolvent (having a pH of 4.5-5.5) and where high lead concentrations in tap water are reported, Sherlock, J. et al (1982) investigated 114 dwellings where mothers were living with children of less than 5 years of age. Dwellings in which water lead concentrations were above 110 ng/£ constituted the catchment area. All the infants had Pb-B levels >20 /xg/100ml, 55% had Pb-B levels > 30 /xg/100ml and 36% had Pb-B levels > 35 /xg/100ml, thus failjh^ to comply with the ECD reference levels (EEC, 1977). Pb-B levels of the mothers also failed to comply with the ECD reference levels. In Ayr, all three reference levels of the ECD were breached in the EEC blood lead screening survey carried out in 1981 (DOE, 1983) due to high concentrations of lead in drinking water. Sherlock, J.C. et al (1984) after the pH of the water supply was increased from (4.5-5.5) to about pH 8.5 by the addition of lime, investigated whether changes in water lead concentrations would be reflected in blood lead concentrations. the time of The median Pb-B level in women in 1980-1981 was 26 /xg/100ml and by^this study undertaken in .1982-1983, it had fallen to 13 /xg/100ml. The authors concluded that even relatively low concentrations of lead in water would have a marked effect on blood lead concentrations. Only two women in this study had higher Pb-B levels than expected, both had spent 73 considerable time removing old leaded paint from their houses. One woman’s Pb-B level rose from 8 to 24.5 /zg/d£, yet the water lead concenration in her dwelling had fallen from 40 to <10 figfi. The calcium concentration in the water supply at Ayr was 3 mg / i before water treatment began and 6 mg/£ after. It is interesting to note that heart disease and water hardness have a strong negative correlation. The British Regional Heart Study found a correlation of —0.67 (Pocock, S.J. et al, 1980). Scotland has a mortality rate from coronary disease which is one of the highest in the world (Smith, W.C.S. and Crombie, I.K., 1987). Two comparable series of medicolegal necropsies - one from very soft water (Glasgow) and one from a hard water area (London) — were compared for bones’ lead content by Crawford, M.D. and Crawford, T. (1969). Deaths were mainly from ischaemic heart disease. The lead values in the soft-water area were higher than those in the hard-water area, mean values being 93 ppm and 54 ppm. Using lead/calcium ratio x 10,000, the proportion of cases with ratios of 3.0 and over was greater in Glasgow than in London. Mean values for both bone calcium and magnesium were slightly lower in the soft water area, and the mean of both ions was lower among women than men. Accordingly, the quality of evidence that the lead burden, as measured by the concentration of lead in bones investigated in Germany by Drasch, G.A. et al (1987), has been reduced because of a reduction in the lead content of petrol is not sound. In Germany where lead concentrations in petrol were reduced in 1976 from 0.4 to 0.15g/£ producing 70% reduction in vehicle lead emission, it was found that the mean reduction in blood levels of inhabitants increased or remained unchanged in 40% of men and 50% of women (Sinn, W., 1981). No doubt eating and drinking habits have the utmost importance on the accumulation of lead in bones when exposure exceeds elimination. The lead concentrations in the bones of skeletons of mediaeval inhabitants of England were found to be greatly in excess of those of contemporary populations and greater than could be reasonably accounted for by the probable levels of lead exposure during life (Barry, P.S.I and 74 Connolly, R., 1981). In view of the inevitable changes that must occur over many centuries, it is doubtful whether the analysis of ancient remains can be expected to give results which might reliably represent a true in vivo level of lead absorption in past populations. Information has tended to master some scholars and not the other way around. If the information is not interpreted correctly, it can easily give rise to false conclusions. Authors must be aware of the confounding influence of soil contamination in their results. At two cities, Waldron, H.A. (1982) has found a significant correlation between the concentrations of lead in bones and soil taken from the same grave: this is a clear evidence for lead uptake after death. It was demonstrated beyond any doubt that lead is absorbed by bones post-mortem even in alkaline soils. El wood, P.C. et al (1984) investigated the possible contribution of the multiple sources of exposure to the levels of lead absorption. Surveys of random samples of women were conducted in 5 different areas of Wales representing different exposures to traffic. Women were selected because they reflect environmental lead levels more closely than men [sensitivity to lead is in the order of children > women > men (Roels, H. A. et al, 1976)]. Areas surveyed were: (i) Cardiff, a major city which has 30,000 to 40,000 vehicles/day (ii) Dwellings within 100 metres of an elevated motorway with 27,000 vehicles/day on the motorway and around 16,000 on the major roads in the area (iii) Dwellings beside major roads in three valleys in South Wales with around 15,000 vehicles/day (iv) Dwellings in cul-de-sacs off these valley roads in which there is no traffic 75 (v) A village with about 500 vehicles/day. A high response rate was successful and 90 per cent of the women in each area cooperated. In all cases the air lead levels were low, but they showed marked differences which were consistent with the traffic flow. Although pavement dust-lead concentrations showed statistically significant differences, these differences were small relative to the marked differences in traffic. However, house dust lead levels showed very little difference between areas, and the “random daytime” samples of water taken were all very low, and very few were above the guideline of 50 //g/£ in the latest recommendations from the World Health Organization (WHO, 1984a). Using regression models, Pb-B level as dependent on all environmental sources, it was estimated that the contribution from air was up to about 3.1 /ig/100ml, while that from water was up to 5.5 ^g/100ml. The contribution of dust to the regression was negligible. Although in none of the areas were high levels of lead detected in water (i.e. even in non- plumbosolvent water areas), water emerged as an important contributor to Pb-B levels. If dust on children’s hands estimated by a “wet wipe technique” is also considered, there is no consistent pattern between children living alongside a major road and those in cul-de-sac or a village. Only in the area of exceptionally high lead contamination (old lead mining) is there any large and significant correlation between dust and the lead on children’s hands. Results from the Glasgow duplicate diet study (Lacey, R.F. et al, 1985) which examined the effects of the ingestion of lead in the diet on Pb-B levels in infants from birth up to 12 weeks of age, have also confirmed that Pb-B levels increased significantly with increasing exposure 76 to lead in water, as well as the dependency of diet-lead on water lead. Thomas, H.F. et al (1979) have revealed the extent of the dependence of Pb-B level on water lead level. Two adjacent council housing estates situated on the outskirts of a small rural town were surveyed: (i) The Lead Estate consisting of 60 houses, 55 of which had 4 to 6 metres of external lead piping and 26 of which also had 1 to 2 metres of internal lead piping to the kitchen tap; it was built in about 1935. Lead pipes to the remaining 5 houses had been replaced with copper before this study, and thus served as a control for comparison. (ii) The Copper Estate comprising 75 houses and 20 old people maisonettes, was entirely coppered and built in 1968. Water for both estates was soft (total hardness 13 mg/£ CaCOg), acidic (pH = 5.6) and lead- free at source. Quality control for Pb-B analyses was exercised thoroughly. Water samples were : (i) daytime (first water sample out of the tap at the time of the visit) (ii) running (after the tap has been running moderately for 5 minutes) (iii) first flush (first water out of the tap in the morning) Pb-B levels were markedly higher in the lead estate than in the copper estate for both children and adults. The mean decrease of after pipe removal was approximately 30 per cent at 3 and 4 months and 50 per cent at 6 and 9 months. No other changes in lead exposure were apparent. 77 A survey in Wisbech, East Anglia (population 17000) which has a very hard water (over 300 fig/i CaCOg with an Average of 320 ppm and an average pH of 7.3) showed much lower levels of Pb-B at all levels of water lead than in subjects living in areas in North Wales with a soft water supply (Thomas, H.F. et al, 1981). Moderate amounts of calcium and phosphate in water considerably reduce the uptake of lead (Heard, M.J. and Chamberlain, A.C., 1982). This could be extrapolated as a possible contributing factor for the 20 to 30 per cent difference between Liverpool-Manchester and London levels for adults in the recent UK Pb-B levels monitoring programme (the London water is drawn largely from chalk-bearing strata which does not dissolve lead — Porritt, N., 1931). Pb-B levels in adults in Manchester and Liverpool were about 45 per cent higher than in London in the EEC survey in 1981 (DOE, 1983). In 1985, Pb-B levels of those in Manchester and Liverpool were only 20 to 30 per cent higher than those in London in the UK Pb-B levels monitoring programme (DOE, 1986). This was attributed to lead in drinking water arising from softer water supplies in the Northern cities. Treatment of the water supplies in these areas of plumbosolvent water has been effective in reducing the Pb-B levels by nearly 50 per cent. This drop in Pb-B levels is similar to the drop in Pb-B levels of approximately 50 per cent quoted in the study in Wales in which the removal of lead water pipes and their replacement with copper pipes has taken p&tce . (Thomas, H.F. et al, 1979) Therefore, the possibility of the large contribution of water lead to blood lead should be considered in the assessment of falling Pb-B levels. Evidence suggests that hard water may reduce the absorption of lead from sources other than water, such as food cooked in hard water, thus reflecting lower availability of lead from food and perhaps food eaten together with hard water. The proportion of lead in food which would come from water is likely to 78 be more than 15 per cent when lead in water exceeds 100 n g /l, whereas it would be only about 3 per cent with concentrations about the relatively common value of 20 fig/i (DHSS, 1980). However, other studies using radioactive tracer technique have shown that during cooking, vegetables and rice absorb up to 80 per cent of the water-borne lead (Little, P et al, 1981), thus acting rather like a sponge. The active accumulation of lead by foods from cooking water during the culinary process will thus increase the total quantity ingested in more than an additive manner. 79 4.5 Lead in Food as a Potential Pathway of Exposure Although food and drink have been recognized as the major sources of body lead since the early 1970’s (DOE, 1974), only inhaled lead has been widely studied as a major route of entry, while ingested lead has received minor attention. Any urban/rural gradient observed is attributed to lead in petrol (Caprio, R. J. et al, 1974). Nriagu, J.O. (1983) estimated that ancient wines had a lead concentration of between 300- c e 1500 figJl (i.e. 3x10°— 15x10° fig/i). It was cited that the Romans used to add some form of preservative with a high lead content, otherwise wine became totally undrinkable very quickly. “Sapa” was found to improve the quality of a poor wine and to prolong the length of time for which any wine could be kept; sapa was prepared by boiling raw grape syrup in a leaded vessel until its volume was reduced by a third or a half (Waldron, H.A., 1973). Dishes made of pewter (alloy of tin and lead) were used for eating food, and both food and wine were heavily contaminated by sweetness made from lead compounds, and water used to pass through lead pipes (Nriagu, J.O., 1983). He calculated their average Pb-B levels (i.e. Romans) to have been from 18 to 300 /ig/100ml with an average of at least 50 fig/ 100ml. Tetraalkyl compounds did not exist then. Although the primary source of lead for most people is the diet, yet data on heavy metal v rt. intakes by different population groups lacking. Accurate information about the individual intakes may be obtained by measurement of the metal concentrations in duplicate diets (Lacey, R.F. et al, 1985) or by measurement of faecal excretion of the metals. (Thompson, J. A., 1971). However, these methods are not often used in large population studies since they are tedious and expensive to conduct. In 80 addition, a major problem in evaluation of the potential hazards of dietary intake of metals is that little information exists about the chemical forms of metals in food or the amounts absorbed from the intestine (Sneddon, J., 1986). Growing children consume more food in proportion to body weight. Moreover, enhanced intestinal absorption in the young may further increase the risk (Alexander, F.W. et al, 1973). Reliable estimations of heavy metal intake by children and adolescents may be hindered by insufficient data on the heavy metal content of foods, or especially in children, by the lack of data on food consumption. (Mykkaiien, H. M. et al, 1986). Rabinowitz, M. B. et al (1977) studied the lead metabolism of a group of normal men in a hospital metabolic unit. Subjects ingested a constant diet, and samples of blood, urine, faeces and diet were analyzed periodically. Three men were fed daily a stable isotope tracer of 204Pb for 83 to 124 days in order to distinguish ingested from respired lead. Also, three men lived in rooms with filtered low lead air. The results indicated that these men absorbed O a mean of 14 ± 4 /ig/day of lead while exposed to the ambient levels of about 2 /ig/m J of airborne lead. About twice this amount was absorbed from the diet per day. One can clearly notice the importance of the contribution of food as a source of exposure compared to air. A recent study of dietary intakes of heavy metals by Finnish children has noted that lower lead intakes were observed among the rural children (Mykkanen, H. M. et al, 1986). Whether urban dwellers consume more canned food than rural dwellers is not clear. Most of the food eaten, both plant and animal is grown in rural areas where the levels of lead in the soil and in the atmosphere are low (Australian Academy of Sciences, 1981). In Britain, it has been estimated that in diets which contain an average proportion of canned foods, there is 15 per cent more lead than in similar diets with no canned foods (DHSS, 1980). The concentration of trace elements in Finnish foods is known to vary with geographical location 81 and use of fertilizers (Mykkanen, H. M. et al, 1986). Cation antagonism may affect plant growth. For example, land in Holland which had been dressed with copper to prevent copper deficiency often produced crops with a marked deficiency in manganese, although the soil had normal content ofMlfcganese (Albert, A., 1985). Mykkanen, H. M. et al (1986) have stated that the results may underestimate the true differences in the intakes of heavy metals between children living in rural areas and in urban and/or industrial areas, since the food consumption data used in their study were based on analyses of food samples representative of the entire country. There is clearly a need for further studies and detailed evaluation of food patterns associated with the risk of high intakes of heavy metals. Recent results from a cross-serf&onal study showed the concentration of lead in the blood of male workers aged 20 to 55 years, occupationally exposed to lead in a steel factory, to be negatively correlated with the daily nutritional content of diet (Yoshinori, I. et al, 1987). 82 4.6 Urban-Rural Pb-B Levels Comparison One wonders how a Pb-B level reported for children living in Sutton Coldfield (served as a control group area in the recent UK Pb-B levels monitoring programme — “an outer suburb of Birmingham where it was known that water was not plumbosolvent and that Pb-B concentrations were relatively low” — (Quinn, M.J. and Delves, H.T., 1987; DOE, 1978) as 13.1 /ig/100ml (mean) compares well with the Pb-B level reported for roadside workers in Birmingham exposed daily to motor vehicle exhaust reported as 13.1 fig/ 100ml (mean) (Cooke, R.A., 1986). In fact, its exactly the same figure. Interestingly enough, it compares well also with a Pb-B level from a survey of Pb-B levels from 19 locations in the United States reported as 13.2 //g/100ml (Kubota, J. and Losee, F., 1968). Stopps, G.J. (1969) found that Pb-B levels of people living in various places remote from civilization had group means of 12 to 23 /zg/100ml, values not significantly different from group means reported for people living in urban areas of highly industrialized countries. Elwood, P.C. et al (1985) conducted surveys on 6 areas: (i) Tory: population 115 off the north coastof Ireland (ii) Sark: population 500, one of the Channel Islands, 100km off the south coast of England. None of these islands has ever had motor traffic. (iii) Aran: has few motor cycles and one gasoline-driven minibus (iv) Jersey: population 76,000, one of the Channel Islands, has an intricate network of roads carrying heavy gasoline-driven traffic (v) Ebbwe Vale and Tredegar: at the north end of the Welsh Industrial valleys. This area was chosen to represent a typical industrial and residential area outside a major urban centre (vi) City of Cardiff: the capital city of Wales. 83 The results showed that neither geographic remoteness nor lack of exposure to ambient air appeared to explain the pattern shown in Pb-B levels in these population samples. The levels in the industrial area (Ebbw Vale) were closely similar to those in a traffic-less island (Tory), while another traffic-less island (Sark) had mean Pb-B levels which were similar to those on a heavy traffic island (Jersey). Pb-B levels on the more remote traffic-less island (Tory) were about 50 per cent higher than the other traffic-less island (Aran). This difference was confidently explained by higher consumption of canned food by Tory. There was no consistent pattern of Pb-B levels in relation to the environmental sources measured. From all what has preceded, it is clear that lead from petrol in air is only one of several sources of population exposure, yet its amazing how often a paper has appeared which tends to look at a particular factor in isolation (lead in petrol), attempting to show the importance of that factor, while ignoring the influence of others (Tera, 0 . et al, 1985; Rabinowitz, M. B. et al, 1984; Caprio, R.J. et al, 1974). The NHANES II data indicated a decline in nation wide average Pb-B levels in the United States during the period 1976-1980 of the survey. Pb-B mean levels fell from 15.8 to 10.0 /ig/100ml (Annest, J.L. et al, 1983). This was paralleled by a decrease in the use of leaded petrol. Highly significant associations were found between the declining blood-lead concentrations for the overall U.S. population and decreasing amounts of lead used in petrol in the United States during the same time period. Accordingly, the fall in Pb-B levels was attributed to lead in petrol! 84 CHAPTER 5 BLOOD-LEAD LEVELS DECLINE 5.1 Changes in Blood-Lead Levels Pb-B levels have been showing a downward trend in the past decade or so. Mean Pb-B levels for the group of children studied in the Greenwich survey (Millar, I.B. and Cooney, P.A., 1982) were 16.74 /ig/100ml and 13.97 /ig/100ml in the years 1978 and 1980 respectively, and the reduction was significant (p<0.01). Oxley, G.R. (1982) reported an analysis of Pb-B levels found in blood samples drawn as a part of pre-emj>&>yrnent medical examinations conducted by the Associated Octel company which manufactures and distributes lead alkyl compounds for the international oil industry during (1967-1969) and (1978-1980). Two different methods of blood analysis were used. Geometric mean Pb-B levels declined from 20.2 jig/lOOml to 16.6 /ig/100ml and the reduction was statistically significant. All subjects were adult males who had no occupational exposure to lead and may be considered as reflecting a trend in the general population. Elwood, P.C. (1983e) reported a downward time trend of Pb-B levels in adult women studied over 10 years in 8 surveys conducted in a variety of locations in Wales. Women included in the surveys were representative samples of residential areas. Overall mean Pb-B levels for the various surveys fell by more than 30 per cent. During the period of these surveys, the amount of lead in petrol in UK fell, but this was balanced by an increase in petrol consumption, thus the reduction of lead in petrol is not a possible reason for the decline in Pb-B levels. Elwood, P.C. and Toothill, C. (1986) reported further evidence of a fall in Pb-B levels, in which random samples (males and females) of residents in North Wales, some of whom had been seen in 1976, others in 1981 and were seen 85 again in 1984. Pb-B levels indicated that there had been a fall of about 5 per cent/year. Surveys of Pb-B concentrations carried out? in the UK under the EEC screening programme during 1979-1981 also described a fall of over 20 per cent in children of lead workers and children living near lead works (approximately 3.5 ^g/100ml) (Quinn, M.J., 1985). The purpose of the screening programme in 1979 was to detect undue lead exposure, and the fall was expected following efforts to reduce emissions. Overall, 80 per cent of children had lower levels in the 1981 survey. Pb-B concentrations in those living near major roads were not very different from those in the general population in the same area. Results from the 2 surveys (1979 and 1981) of children living near major roads showed that levels were considerably lower than for those exposed to lead in drinking water or to leadworks. There have been reductions in Pb-B levels of around 20 per cent (over 3 //g/100ml) in Glasgow, following remedial action by the water authorities, for both men and women (DOE, 1983). Treatment of water supplies has thus been effective since the highest Pb-B concentrations were found in areas with plumbosolvent water. Falling Pb-B levels have been reported also in New Zealand (Hinton, D. et al, 1986). Pb-B levels fell in adult males and females (>17 yell-s) by 42% and in school and pre-school children by 44% and 46% respectively. It was noted that reduction was accelerated during the last 3 years. In the USA, NHANES II showed a 37 per cent decrease during 1976-1980 (Annest, J.L. et al, 1982). Further evidence came from cord blood samples taken in Boston (USA) suggesting a fall in blood lead content of about 11 per cent/year between 1979 and 1981(Rabinowitz, M.B. and Needleman, H.L., 1982). 86 5.2 Epidemiological Observations Lack of appreciation of the probability concept in statistics has led to the absurd attitude that it is almost considered “unscientific” to believe in a difference which is statistically non significant (p>0.05) and to believe in a difference which is statistically significant (p<0.05). A recent study (Wulff, H.R. et al, 1987) suggested that the statistical knowledge of many readers in the medical profession is so limited that they can neither detect inadequate statistical analyses in published papers, nor interpret correctly the results of adequate ones, and this leads to the blind acceptance of statistically significant results. The epidemiologist who studies the association between a physical parameter and a long series of environmental factors must be expected, simply by chance, to find in every twentieth case that the association is “statistically significant” at p=0.05. That is a corollary of the definition of a p-value. However, it is impossible to know in a particular case whether the association is true or not (Wulff, H. R. et al, 1987). Epidemiology has been an invaluable instrument of public health in uncovering links between environmental factors and disease. The aim of carrying out an epidemiological survey is to test a hypothesis which is to be clearly defined before commencement, such as: the association between cigarette smoking and lung cancer, coronary heart disease and water hardness, elevated cholesterol and daily consumption of two cups of coffee, and what follows from this is a question mostly aimed at the public such as: High cholesterol = High cancer risk? (Silberner, J., 1987a) or, Coffee: Grounds for Concern? (Anon, 1985), or: Common Herbicide linked to Cancer (Anon, 1986a) and the list goes on and on, and recently sugar and mortality due to ischaemic heart disease (Campbell, M.J. et al, 1987). The association between dietary sucrose consumption and ischaemic heart disease has been studied*longf time ago with no or very little evidence found (Elwood, P.C. et al, 1970). In all these cases, the environmental 87 factor may not be the cuplrit, it simply denotes that it is a confounding factor in an association clouded by a multiplicity of other factors and in no way to be interpreted as a direct proof of cause-and-effect. In epidemiological surveys, expectations do influence observations sometime^ after formulating an a 'priori hypothesis. A person who wants very much something to be true often fools himself into thinking it is true. It is amazing how often a paper has appeared which seems to prove a hypothesis quite conclusively (Bryce-Smith, D., 1971a; Bryce-Smith, D., 1971b). Only upon cultivating critical faculty in asessing the papers we read, and not simply accepting the author’s conclusions, we can cite faulty research methodology (such as lack of control groups, proper random sampling, insufficient quality control etc.) and defective evidence. In the case of lead, it is impossible to disentangle the contribution of one individual confounding factor as a real causal factor, since the other contributing factors (diet, smoking, alcohol, occupation, nutritional factors, immune status and others) are not mutually exclusive. Simulation models and assumptions about parameters (such as wind patterns and air mixing zones in air quality studies) for approximating actual exposure conditions provide additional uncertainty because of their foundations on numerous assumptions about the behaviour of substances in the environment. Lead has been present in the environment long before 1923 when lead tetraalkyl additives have been discovered (being a natural component of the earth’s crust) and since the beginning of life. Removing lead from petrol will not remove lead from the envionment. The removal of lead from petrol was not justified either scientifically or economically at a time when the world is realizing that its total petroleum reserves may be used up before the end of this century unless consumption is reduced. However, environmental issues are highly 88 political in nature, and politicians seem to make the final decision. In my opinion, the heated correspondence concerned with the lead in petrol issue could have been better used in increasing public awarness and knowledge about nutritional health, this is if the goal to be achieved was public health. 89 5.3 U.K. Pb-B Levels Monitoring Programme 1984-1987 (Discussion of Results) The Department of the Environment in UK has been coordinating a programme of surveys to investigate changes in Pb-B levels over the period 1984-1987 in order to assess in broad terms the effect of the reduction in the maximum permissible lead content of petrol, from 0.4g/£ to 0.15 gf t (DOE, 1986; DOE, 1987; Quinn, M and Delves, H.T. 1987; Quinn, M. and Delves, H.T., 1988). The approach adopted was to include groups in the general population who were potentially the most exposed to lead from petrol; thus surveys were not conducted in areas where either it was known that water was plumbosolvent e.g. Scotland, or there were lead/zinc smelters or battery factories. In total, the surveys covered approximately 2500 people (around 1500 adults and 1000 children aged 6-7 years) distributed as such: (i) Exposed group: About 900 adults (roughly 50:50 male:female living in houses bordering heavily trafficked roads in major cities: London, Birmingham, Bristol, Liverpool, Manchester and Sheffield (see the map, fig. 5). About 80 per cent were resampled in 1985(58-96%). (ii) Occupationally exposed group: 300 police officers (adult males) in three police forces, predominantly on traffic duties, in the south-west of England. The survey of traffic police in Devon and Cornwall covered officers stationed in Exeter, Paignton and Plymouth. One force decided not to participate in 1985. In 1986, 2 police forces were surveyed. It was planned to include 100 taxi drivers, but this did not take place in 1984 and 1985, however it seems to have taken place in 1986. (Only brief details of the preliminary results for 1986 have been published at the time of preparation of this thesis (DOE, 1987). About 60 per cent of the police officers were resampled in 1985. 90 (iii) Control group: included a random sample from an outer suburb of Birmingham (Sutton Coldfield) where it was known that water was not plumbosolvent and Pb-B levels were relatively low, and a random sample of 300 adults from a rural village in the south-west of England (North Petherton) where it was known that air and Pb-B levels are low (Quinn, M.J. and Delves, H.T., 1987). No figure for the sample number in Sutton Coldfield was given, however, DOE(1986) cited a total figure of 400 adult controls. Resampling for the controls was slightly higher than the exposed (nearly 80%). (iv) Exposed group of children: This consisted of 1000 children aged 6-7 years who attend schools situated on heavily trafficked roads. The surveys of children took place in different areas from those of adults (Quinn, M. J. and Delves, H.T., 1988). For ethical reasons, each child was being sampled only once. Sampling employed the use of the electoral register, all blood samples taken were venous, and rigorous quality control has been exercised. Information on personal and environmental factors thought to affect Pb-B concentrations was collected by means of a questionnaire for both adults and children, such as age, sex, smoking and drinking habits. The design of these annual surveys was based on the experience of the large surveys carried out in 1979 and 1981 under the EEC Pb-B levels screening programme. Results of Pb-B concentrations in 1984 were in agreement with the results of the EEC Pb-B surveys ones (1979 and 1981) i.e. Pb-B concentrations were significantly related to several personal, social and environmental factors. (1) they were higher in men than women by about 30 per cent, but levels in boys and girls (aged 6 to 7 years) were about the same. Overall Pb-B concentrations in men were 30 to 35 per cent higher in males than in females in the EEC surveys (Quinn, M., 1985). Friberg, 91 L. and Vahter, M. (1983) - results of a UNEP/WHO global study - have shown that Pb-B levels of males were about 30 per cent higher than those of females. Other studies have also shown that Pb-B concentrations were influenced by sex (Elinder, C.G. et al, 1983; Zurlo, N. et al, 1970). Three explanations may be suggested for this difference: (a) In blood, 95 per cent of the lead is bound to the erythrocytes, (Clarkson, T.W. and Kench, J.E., 1958) and males have a higher number of red blood cells and higher haemoglobin levels than females Males Females PCV 0.4—0.54(40%—54%—using the 0.35—0.47(35%—47%— using old terminology) the old terminology) Hb(conc.) 13.5g/100ml—14.0 g/lOOml 11.5g/100ml—12.0g/100ml (Hugh-Jones, N.C., 1984) Roels, H. et al (1976) have stated that sex hormones can influence the haem biosynthetic pathway, and that a hormonal factor renders women more susceptible to lead exposure. (b) Barry, P.S.I. (1975) has noted that male adults contained over 30 per cent more lead in their bones than females (skeletal bones in males are larger in size than females which is reflected in body weight). However, he also found concentrations of lead in male soft tissues exceeding those of females by 30 per cent[90 per cent of the total body burdens of lead in both males and females is present in bones]. (c) Part of the difference is likely to be accounted for by the higher food consumption of men (WHO, 1977). (The daily intake is about 3000 calories for men and 2500 calories for women). This reflects the importance of dietary lead intake as a major factor. 92 The importance of food is detected also from another figure. Manual workers had an average Pb-B level about 4 per cent higher than non-manual workers. This does not necessarily reflect a small effect of social class as suggested by Quinn, M.J. and Delves, H.T. (1987), but rather more physical activity by manual workers who would consume more food and drink more water (water lead content and food lead content). Pb-B levels tended to rise with age in both men and women up to around 50 years of age. This was consistent with the findings of the EEC survey (Quinn, M.J., 1985). Quinn, M.J. (1985) stated that Pb-B levels of both boys and girls increased up to 12 years of age, however, the limited amount of data for children over 12 indicated that at or around puberty, levels rose in boys but not in girls. In women there was a slightly steeper increase than in men in those aged in their 40’s. Levels of Pb-B in men over 50 years of age showed relatively little change. Sartor, F. and Rondia, D. (1980) cited that the steadiness of mean Pb-B levels with age results from efficient homeostasis phenomena which can adapt, between certain limits, to various lead surrounding conditions. Schiitz, A. et al (1987) stated that the main lead pool is the skeleton, and Pb-B mirrors the slow compartment; there was an increase in the half-life of Pb-B (i.e. Decay rate = T^) with increasing age. They hypothesized that senile osteoporosis may add significantly to the mobilization of lead from the skeleton and thus cause a gradual increase in Pb-B with time, which then leads to a spuriously high T |. Men and women who smoke or drank the most showed very little changes. Conditions such as chronic alcoholism, acidosis, stresses associated with shock, infection and hypermetabolic states tend to increase bone turnover rate (Slavin, R.E. et al, 1988). Thus, Pb-B T^ is also 93 increased in this case. There is a tendency for Pb-B levels to increase with both smoking and drinking habits in both men and women. Quinn, M.J. (1985) cited Pb-B levels 10-15% higher in smokers than in non-smokers. This can be traced to lead and arsenic in leaf iabacco grown in soils on which lead arsenate sprays were formerly used. Pb-B levels were slightly higher in those living in older houses (pre-1945). Differences were of the order of 1.5 /zg/100ml. Pb-B levels fell in both those who lived in pre-1945 and in post-1945 dwellings during the surveys, however, it changed least in those who had been resident at their current address for more than 15 years. (Quinn, M.J. and Delves, H.T., 1987). This clearly reflects that the largest determinant of an average non-occupational exposure would be the indoor residential environment, since people spend most of their time indoors. For children, where there was possible exposure to lead ' an adult in the household, Pb-B concentrations were slightly, but not significantly higher. The mean Pb-B level in the family members of exposed workers (ceramics-related) was shown to be significantly elevated as compared with that of an unexposed group (Kaye, W. E. et al, 1987). The UK Pb-B monitoring programme found that Pb-B is neither associated with ethnic origin nor with socioeconomic status. However, the non-whites (African, West Indian, Indian, Pakistani, Bangladeshi) represented only 3 per cent of the sample compared to 97 per cent representation by the whites. Socioeconomic classes I and II were combined to form one class, and so did social classes III and IV. Results for 1984 have shown that of the 1400 adults sampled, only 24 were above the DHSS advisory action level (25^g/100ml), and their Pb-B concentrations were broadly comparable 94 with those in the EEC surveys in 1981 in groups from areas where there may have been a problem of undue exposure to lead. Pb-B levels of police officers (predominantly males) were not very different from the exposed groups, however, levels in the Greater Manchester force were higher than in the Metropolitan (London) force. Results for the control groups (Sutton Coldfield and North Petherton) were similar to those found in London. For children, the overall mean was 10 pg/lOOml. Children’s Pb-B levels were lower than those found in the children of lead-exposed workers in 1981. In 1985, Pb-B levels in Northern cities (Liverpool and Manchester) were 20 to 30 per cent higher, and this was attributed to softer water in the North as cited previously. For adults, but not for children (since it was not a follow-up cohort, but a random sample), it is possible to make detailed comparisons of changes in Pb-B concentrations although children of the same age were sampled at the same time of the year. In the exposed groups, the falls were 6 per cent for men and 9 per cent for women (just under 1 /zg/100ml), an overall fall of 10 per cent in 1985 (62 per cent of the men and 70 per cent of the women had lower levels in 1985). In 1986, the same pattern was seen, an overall average decline of 9 to 10 per cent (about 1 /ig/100ml). The control group in North Petherton showed very little change in 1985, paralleled by a similar “no significant change” in police officers on traffic duty. Both had nearly the same sample number (300) and came from the south-west of England. The other control area, Sutton Coldfield, showed a decline of 5 per cent for men and 2 per cent for women, the latter being non-significant. This control area seemed to be running parallel to the exposed groups area rather than to the North Petherton Control area, although lagging behind it in the rate 95 of decline in Pb-B levels. In 1986, both exposed and control groups showed similar rates of decline (9 to 10 per cent). Resampling in both of the exposed and control groups was 85 per cent. The two control areas showed a similar trend in 1986. The police officers group who in 1984 were not different from the exposed ones, and did not show any overall change in 1985 (50 per cent decrease in Manchester and 50 per cent increase in London), have shown an 18 per cent decline in 1986 (about 2 /ig/100ml - double those of the exposed which was about 1 /xg/100ml. Resampling in 1986 was 65%, while in 1985 it was 60%. By 1986, Pb-B levels of police officers on traffic duty were lower than those for the exposed and were similar to those of the controls (DOE, 1987). In fact, the figures cited for police officers have fallen below those of remote traffic-less islands as seen in table 6. Table 6: Comparison of Pb-B levels of Police Officers with other populations Locality Median Pb-B Level Mean London Mean Locality of of Police Officers Taxi Drivers Pb-B Remote Traffic- in 1986 Pb-B Level Level Less Islands (DOE, 1987) (Jones, R.D. in 1984 et al, 1972) (Elwood, P.C. et al, 1985) Devon and Cornwall 8.2 n g /d i 8.8 pg/d« 5.6 /ig/d£ Aran Greater Manchester 8.9 fig/di 8 .tyg/d* Tory Metropolitan (London) 8.3 fig.di 15.7 p g f d l Sark 96 The exposure patterns of these 300 police officers probably were fairly homogeneous and similar to those of the rest of the exposed adults, and were not distinguished by periods of unusually highly exposure, which would have been reflected in unusually high Pb-B levels at the commencement of the study, and prior to the reduction of lead in petrol. Traffic police are thought of as being occupationally heavily exposed to vehicle exhaust fumes by virtue of being on duty on the intersections and streets with heavy traffic. Another group of police officers engaged only in office duties in the same stations would have served the purpose of a control group; since all aspects of environmental exposure would be the same with the exception of petrol lead, and that would make an ideal case-control study, the two groups being ideally comparable. North Petherton and Sutton Coldfield did not seem to serve the purpose of the study as controls. Age, length of occupation and working hours per day were not provided. In general, individuals with chronic exposure to lead may be expected to have higher steady-state levels of Pb-B, and with less efficient clearance mechanism for Pb (O’Flaherty, E.J. et al, 1982). Accordingly, the Pb-B downward shift is curvilinear in nature, and the magnitude of the Pb-B decrement associated with the new lower air lead exposure is to a certain extent determined by the pre-established Pb-B level and by the duration of employment ( 0 ’Flaherty,E.J. et al, 1982). Thus, there is no reasonable explanation for the rate of falling of Pb-B levels to be almost twice as those of the exposed and control groups (18 per cent compared with 9 to 10 per cent or in absolute terms 2 /ig/100ml compared with 1 /ig/100ml decrement). The additional recruitment of 60 per cent in 1985 and 65 percent in 1986 (adulteration) might have contributed to these results to a certain extent, however, it was mentioned that groups of police officers who were supposed to be stationed in Devon and Cornwall were serving in Exeter, Paignton and Plymouth. 97 Although women are more sensitive to environmental lead exposure (exposed group consisted roughly of 50 males and 50 females), the policemen have shown a steeper decline of Pb-B levels than exposed women. If their Pb-B level was in a true steady state, the drop in Pb-B concentrations from one level to another cannot be of the same magnitude as that of children (16 per cent), not even if these policemen are new recruits into the police force. At the start of the surveys, it was stated that the control group of adults had Pb-B levels slightly below those of the exposed (DOE, 1987) (Pb-B levels in Sutton Coldfield were not very different from those in London — Quinn, M.J. and Delves, H.T., 1987). Pb-B levels of police officers on traffic duties (by definition exposed to petrol lead) were similar to those in the exposed group. The unexposed (controls) are, in fact, exposed to lead but in low concentrations so that they truly represent a low exposure group rather than a control, as designated by the study. This was reflected by the same rate of decline in Pb-B levels in 1985-1986 (about 10 per cent for both the exposed, as well as, the controls). The supposedly truly exposed (police officers and taxi drivers) seem to have been unexposed and did not serve the purpose of the study. A policeman on traffic duty is exposed on average to four times as much lead, depending on periods of duty. (Waller, R.E. et al, 1965). Although the decline in Pb-B levels of children was significant (16 per cent in 1986, and about 9 per cent in 1985 — a decline from 10 /ig/100ml in 1985 to 9 ^g/100ml in 1986) it does not follow that “petrol lead has made a slightly larger contribution to their body burden than those of the exposed adults” (DOE, 1987). Hinton, D. et al (1986) have cited a decline in Pb-B levels in 44 per cent and 46 per cent of school and pre-school children >9 months old respectively in New Zealand over the period of 1978-1985 at a time when the lead content of petrol (0.84 g /l ) and petrol sales remained unchanged. 98 Accordingly, no significant conclusions could be drawn regarding the exposure due to petrol lead. Mean Pb-B level for traffic controllers in Egypt (Alexandria) is 68.28 /ig/100ml (Ahmed, N.S et al, 1987), while that for Iran (Tehran) is 29.52 /zg/100ml (Farsam, H. et al, 1982); thus ftolj comparable to a London policeman (UK) Pb-B level of 8.3 /ig/100ml (Table 6 — DOE, 1987). Hinton, D. et al (1986) attributed the decline of Pb-B levels mostly to the systematic lowering of the lead content of the diet. Results from the Department of Scientific and Industrial Research in New Zealand indicated an approximate 24 per cent drop in dietary lead content and a reduction in canned food consumed from 14 per cent to 8 per cent, this reflecting wider use of plastics and freezer packs. New Zealand’s largest canning suppliers redesigned all but the A10 and 4 litre catering size cans to remove solder completely in favour of seam welding. These cans appeared in retail outlets in 1982. Also in 1981, some natural fruit juices were marketed in seven layer laminated foil packs instead of lead solder cans, and these were retailed in 1982. Lead solder was replaced by sudronic (resistance) welding for canned fruit juices in 1982 and for locally marked beer in January 1983. Evaporated milk has appeared in cartons and dried milk in foil-lined sachets. Elwood, P.C. (1983e) also pointed out that there has been a substantial reduction in lead content of most foodstuffs in UK, since 1970, and that the mean dietary intakes of lead in many foodstuffs have decreased. He cited figures from the Ministry of Agriculture, Fisheries and Food: 200 /zg/day as daily lead intake from food per adult in 1970-1972, which has come down to about 100 /ig/day per adult towards the end of 1970’s. He has also drawn attention to the increase in the use of frozen foodstuffs and the fall in the use of tinned foods, together with improved canning methods and other changes in the food industy which must have led 99 to substantial reductions in lead intake from dietary sources. Oxley, G.R. (1982) has also pointed out that substantial reduction in dietary lead intake has contributed to the falling Pb-B levels he observed. Elinder, C.G. et al (1983) have mentioned that canned foodstuffs may occasionally contain high concentrations of lead. In canned fruits and vegetables it was found that the lead concentration usually was 5 to 30 times higher than the normal concentration in fresh food items. Certain canned foodstuffs were found to have lead concentrations exceeding 1 mg/Kg (British legal limit for lead in food being 1 ftg/g fresh weight = 1 mg/kg). There were many aspects of variation in 1985 in children, police offcers and the two control areas (increases and decreases) and the full details for 1986 were not given. Thus, it was a non-uniform picture. The Frankfurt blood-lead study designed to investigate changes in Pb-B levels in the German population after reduction of lead in petrol from 0.4 - 0.15 g / i on January 1, 1976 has not come out with a uniform picture either - simultaneous increases and decreases (Sinn, W., 1980). 100 5.4 Conclusion We can, therefore, conclude with confidence that the blood lead level is governed to a large extent by a multiplicity of factors, which are independent of inhaled lead. No attention is paid as to how exposure from other sources might be varying. Policy makers could be accused of being overzealous in concentrating on one narrow aspect of the entire problem separating lead in petrol out for special attention. A point to be stressed is that those who laid down lead pipes could not have foreseen that a problem would occur forty to one hundred years in the future. I do not wish to blame them for present troubles because no one can foresee the consequences of actions ahead of time; and yet decisions must be made. If all information garnered by the various groups of experts, each working on their own research problems, needs to be passed into the decisionmaking machine, it obviously can only be in a highly compressed form. Policymakers are not equipped, and do not have time, for reading undigested reports of the findings of experts. Whatever the policymakers’ own training, they are bound to be deficient in a number of disciplines from which they are receiving expert advice. There is therefore the well-known problem of compressing technical findings without distorting them. Canned food is a major source of dietary lead, but in practice there are few controls which can be placed on it. Researching into the chemical composition of lead in canned food, the absorption rates of its various forms and their fate in the body and toxicity, is therefore “largely irrelevant” to the problem of controlling lead hazards. Options such as making canners use aluminium cans or cans with shorter seams to solder have not received serious attention. The feeling is that these cans are to be welcomed if they prove to be practicable and economic. 101 The control of dietary lead could be accomplished by more expensive controls on processing and packaging or by the addition to food of lead absorption inhibitors (discussej in detail in chapter 6), neither of which has much appeal to the food industry. Lead in food regulations were revised in 1979 in Britain, and levels in canned baby foods were reduced by setting an upper limit of 0.2 ppm. However, a wide range of canned food (0.3 million tons) is sold and yet there are insufficient data on lead content to give an accurate assessment of intake from this source (DHSS, 1980). If statutory levels are to be enforced, it may result in certain foods disappearing from the market because they are not legally to be sold (Collingride, D. and Douglas, J., 1984). Lead-free petrol might actually cause worse health problems than those from lead in petrol as we have seen in the case of Mexico where ozone has become the air pollutant number one through the emissions of greater amounts of nitrogen oxides and hydrocarbons. What is called for is one body to deal with lead which can achieve a genuine oversight of the problem. 102 CHAPTER 6 DIET, EXCRETION AND BODY LEAD CONTENT The adage “you are what you eat” applies perfectly well in maintaining the physiological lead balance in various geographical locations in connection with studies of the absorption and excretion of lead. 6.1 ______Intestinal Uptake of Lead Lead is absorbed by man mainly through the gastrointestinal tract and respiration tracts, occasionally through the skin, and rarely from subcutaneous tissues. Average dietary intake of lead is between 200-300 /ig/day (WHO, 1977), while the intake from air is approximately 15 /ig/day (Chamberlain, A.C. et al, 1978). The accumulated evidence on human exposure to lead indicates that for the population as a whole, the diet is the most important route of exposure (Barltrop, D. and Khoo, H.E., 1975; DHSS, 1980; MAFF, 1982). Stringer, C.A. et al (1974) had analyzed sixty-six human lung samples for lead concentrations, and found no significant variations with respect to place of residence or race. Lung tissue was selected for analysis because it reflects the lead that has been absorbed into the body and redeposited into the tissue in addition to any lead that has been deposited in the respiratory tract but not yet absorbed. No apparent accumulation of lead was observed in the lungs of rats exposed to lead, yet the high binding capacity of the intestinal tissue was seen to function as a protective mechanism, reducing the rate of lead absorption in both the developing and mature rats (Miller, G.D. et al, 1983). The available evidence from animal studies and limited human data indicates that the majority of metals are poorly absorbed from the intestinal tract and this may be our best defence, as metals from the environment mainly enter the body by gastrointestinal absorption, while the concentrations of metals in air are too low to contribute to the total body burden (Sneddon, J.M. 1986). To understand how food can alter the absorption of lead, it is necessary to consider the ways in which lead is transported across the 103 intestinal wall. The cell membrane of the epithelial cell is organized to produce innumerable rod-shaped projections into the lumen (microvilli) thereby vastly increasing the surface area available for absorption. Tight junctions between epithelial cells act as barriers to the movement of substances from the lumen into the intercellular spaces, and these junctions are however permeable to ions and are cation selective, so lead cations may diffuse across the epithelium via this paracellular route (Morton, A.P. et al, 1985). Very little is known about the physical or chemical properties of these “tight junctions”. It has been shown that lead transport by the small intestine is a linear, non-energy dependent process, which indicates that passive diffusion is the major pathway for lead absorption (Morton, A.P. et al, 1985). The percentage of lead absorbed by man was shown to be 10 per cent in the classical balance studies of Kehoe, R.A. (1961). Published values of percentage absorption ranging from about 1 per cent to 35 per cent for adults have been reported, however an overall value of 10 per cent has been assumed (RCEP, 1983; DHSS, 1980). The value for children is considered to be much higher — about 53 per cent (Alexander, F.W. et al, 1973). However, this assumes that lead in food is equally absorbed, although information shows that all lead in food is not equally absorbed. The uptake of lead from offal which often contains elevated concentrations of lead is the lowest of all at 2.8 per cent (Sherlock, J.C., 1987). According to Sherlock, J.C. (1987) this is likely to be due to the speciation — that is the chemical form of the lead in foods, and it may be that lead in offal is tightly bound to proteins in offal and it is this which makes the lead relatively unavailable for uptake by man. In fact, proteins which bind lead have been identified in the intestinal membrane (Morton, A.P. et al, 1985). Sherlock, J.C. (1987) failed to recognize that the major routes of excretion of trace elements are intestines and kidneys (Mertz, W., 1981). The richest sources 104 of many of the trace elements in animal products are the liver and kidneys (Davies, N.T., 1981). The greatest reduction in lead absorption from food was caused by minerals (Blake, K.C.,H. et al, 1983; Barltrop, D. and Khoo, H.E., 1975; Heard, M.J. and Chamberlain, A.C., 1982). Results have shown that absorption was enhanced to twenty times control value by diets deficient in minerals (Barltrop, D. and Khoo, H.E., 1976). In Western societies, meat consumption is high and meat is normally considered a rich source of trace elements, however, the richest sources of many trace elements namely liver and kidneys are often discarded and preference given to muscle which is generally of low trace elements content (Davies, N.T., 1981). Lead and other metals in different foods are solubilized to differing degrees when treated with enzymes and inorganic substances normally found in the human digestive system (Sherlock, J.C., 1987). The presence of food within the lumen of the gut provides ligands for the formation of both soluble and insoluble lead complexes; which complexes are formed will determine to what degree lead is absorbed. Certainly, food provides protection against lead absorption, and this is supported by the effect of meal times on intestinal uptake in man. The retention of lead ingested in a soluble form during a prolonged fast is about 60 per cent of the intake, while balanced meals eaten with lead (203Pb) reduced lead uptake to 4 per cent under the influence of food (James, H.M. et al, 1985). Heard, M.J. and Chamberlain, A.C. (1982) have found that the uptake of lead from the gastrointestinal tract of four human adult volunteers with no minerals averaged 63.3 per cent (range 58.6-66.7 per cent). Meat is estimated to provide 36% , 28% and 24% of the daily consumption of zinc, copper and iron respectively, and decreasing intake of meat because of its expense increases the risk of marginal trace element deficiencies (Aggett, P.G. and Davies, N.T., 1983). 105 White flour has a lower trace element content than wholemeal flour; some sources indicate that the As, Ni, Si and Sn content of 70% extraction flour are only 30-40%, 50%, 20-80% and 50-80% respectively of wholemeal flour, and commercial sucrose is a particularly poor source of trace elements (Davies, N.T., 1981). 106 6.2 Classification of Lead : An Essential metal or Contaminant Metal? The trace metals found in mammals are divided into 2 groups: metals considered to be essential for mammals (essential metals) and metals usually not detected in infant but present in adult and apparently acquired and accumulated from environmental contaminants (contaminant metals). From this classification, the following may be deduced. Most metals that have an ability to develop a tolerance belong to the contaminant metals, and metals that do not produce a tolerance belong to the essential metals. Metals such as zinc and iron which are present in a large quantity in the body not only produce tolerance but promote the reaction. (Yoshikawa, H. 1970). Research during the past three decades has identified at least six essential trace elements whose functions where previously unknown. These are: molybdenum, selenium, chromium, nickel, vanadium, silicon and arsenic. This suggests that additional elements could be proved essential by future research and the number of elements now accepted as essential should not be considered final (Mertz, W., 1981). Essential trace elements are required by man in amounts ranging from 50 fig to 18 fig per day acting as catalytic or structural components of larger molecules; they have specific functions and are indispensable for life (Mertz, W., 1981). Chromium, selenium and arsenic have previously been known only as toxic. An element is considered nutritionally essential when an animal species deprived of it develops reproducible features which can be prevented or reversed by supplementation with physiological amounts of that element (Aggett, P.J. and Davies, N.T., 1983). In depletion experiments with rats over generations, the essentiality of lead for growth and metabolism could be established. 107 Lead deficiency caused growth depressions, microcytic hypochromic anaemia, and disturbances in iron metabolism, activites of enzymes and concentrations of metabolites (Kirchgessner, M. and Reichlmayr-Lais, A. M., 1981). In an investigation of elevated blood- lead levels in 100 lead workers, the findings suggested that lead is a contributing factor to the causation of anaemia, this being hypochromic (reduced MCH) and microcytic (reduced MCV) (Faour, J.A., 1984). Anaemia is a common finding in cases of excessive lead exposure in humans (Toothill, C., 1977), but whether it also occurs under extreme conditions of lead deprivation is not known (i.e. in vivo). Parallel to anaemia in the case of lead-depleted rats, the iron concentration in the serum was reduced and the total iron binding capacity was increased (Kirchgessner, M. and Reichlmayr- Lais, A. M., 1981). Watson, R.J. et al (1958) found abnormally low serum iron values in 13 children with lead poisoning, and the total iron binding capacity of the serum was variable. No doubt, lead has a profound effect on red cell precursors in the bone marrow producing morphological changes by its action on the erythroblastic cells in the marrow (Waldron, H.A., 1966). There are a few observations indicating that lead may at low concentrations have a stimulant action on haemopoiesis; and that increases in haemoglobin concentration, red cell count and haematocrit ratio (i.e. PCV) observed during experiments on dogs and attributable to the ingestion of lead was unexpected (Maxfield, M.E. et al, 1972). The purpose of that experiment was to study the effect of haemorrhage on the blood regeneration (such as might happen during injuries or accidents due to blood loss) system in dogs initially fed with basic diets containing varying proportions of lead before blood withdrawal. The ability of the blood-forming mechanisms to manufacture haemoglobin and red cells was not measurably affected even when required to function at accelerated rates. 108 In fact lead in low concentrations has been shown to stimulate mitochondrial enzyme, 6- Aminolaevulinic acid synthetase (<$-ALA-S) (Chisolm, Jr.,J. J., 1964). Impairments of the homeostatic regulation manifested by iron-metabolism disturbances in lead-deficient rats compared to controls (Fe-concentration was 76% lower than controls in the livers and 30% lower in the spleens) and a reduced growth of 22% in the depleted group speak for the essential nature of lead (Kirchgessner, M. and Reichlmayr-Lais, A. M., 1981). The essential nature of an element is brought forth when in the case of a lacking amount of this element, the metabolic functions are disturbed to such an extent that a reduced growth results as primary deficiency symptom. There are many things other than lead which can be injurious in large amounts but valuable in small amounts including radiation. Indeed, this is true of nearly everything. Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man (Clements, M.R. et al, 1987). Without taking vitamin D in the form of cod liver oil or otherwise during the long sunless periods of the year, we couldn’t possibly survive, and the incidence of rickets would be at its height particularly in children, as well as delayed dentition (Paterson, D. and Darby, R., 1926). But if we get too much ultra-violet irradiation, it does serious damage. If we were to get all the ultra-violet radiation that we need in a year in just a few minutes while exposing our whole body, we would probably die. Several of the serious poisons can be good for us in small quantities. The most popular poison of past times was arsenic (As), and was the “solution” to domestic, marital inheritance and political problems (Mervyn Madge, A.G., 1987). Arsenic is a good tonic and its essentiality has been established in miniature pigs, goats, rats nad chicks. The most readily observed effect of As deprivation was an impairment of reproductive performance and increased perinatal mortality. In goats, they died suddenly without any previously visible symptoms other than a marginally reduced growth rate (Davies, N.T., 1981). A nutritional requirement for As in chicks has been demonstrated and preliminary observations suggest that there may be an interaction between As and Zn, indicating that As is necessary for the efficient utilization or metabolism of Zn (Davies, N.T., 1981). 109 Although arsenic is a poisonous element and large amounts kill, investigators have noted that arsenic has apparently effected a satisfactory recovery from a rather severe case of chronic selenium poisoning in dogs, and that a marked reduction in the deposition of lead in body tissues in the presence of arsenic as compared with the amount of lead desposited in the absence of arsenic was noted (Rhian, M. and Moxon, A., 1943). Elements with similar physicochemical properties may act antagonistically to each other at metabolically important sites. It is also well known that the presence of one element can interfere with the uptake of another, for example plants have benefited from the presence of calcium in soil by taking up less lead, thus reducing its deposition in vegetation (Jowett, D., 1964). We cannot do without vitamin D, but a gram or two is lethal if eaten all at once. Strychnine is a plant alkaloid which is highly poisonous, but when used in minute doses serves as a nerve stimulant. There is strong evidence that low level radiation can do good by improving the immune system, and some solid evidence exists that radiation in some circumstances might increase our expectation of life (Fremlin, J.H., 1984); while the Hiroshima results certainly showed that the number of cancers which were produced per 10,000 people increased with the amount of radiation dose from 10 rems upwards, they did not tell us very much what happened below that (Fremlin, J.H., 1984). In a group of uranium miners exposed to long-term occupational radiation, the activity of the pentose phosphate cycle was found to be enhanced, and this finding was interpreted as evidence for a change in the functional state of erythrocytes in exposed persons due to the effects of radiation on the genesis of red cells in the bone marrow (Vich, Z. et al, 1970). It is likely that there are changes in the metabolism of the red cells of individuals exposed to long term radiation, the effects of which are reduced by the increase of glucose oxidation via the pentose phosphate cycle. This might contribute to the maintenance of the fucntional efficiency of erythrocytes in respect of oxidation-reduction reactions and syntheses. If so, the 110 alteration in the rate of the pentose phosphate pathway may be regarded as due to the operation of compensatory mechanisms. The immune system gains a lot of exercise during most of our evolution. All babies are put through enormous immunity exercises - such as diarrhoeas and minor diseases - and those who survive have had their immune system trained to a fine point, and as a result could cope even with novel challenges a lot better. The biological response to environmental chemicals and drugs is frequently altered by prior exposure to the chemical, and adaptation to the toxic effects of lead have been demonstrated (Garber, B. and Wei, E., 1972). Yoshikawa, H. (1970) observed that mice developed resistance to the lethal effects of high doses of lead after pretreatment with a small dose of lead. The fact that we have evolved a repair system or compensation mechanism to low levels of lead but which fails at high levels is quite natural. Pretreatment of mice with a 10 mg/kg (ppm) dose of lead nitrate [PtyNOg^] at 4 days before challenge provided optimal effects against a large dose of lead (Garber, B. and Wei, E., 1972). No doubt, governments have played safe and now assume that even at the lowest concentrations of lead in the environment, there will be some risk in the exposure of the general population. However, what is not clear to me is why results of these studies have not been widely reported. The reason is probably that people went hunting through technical journals for something to support a view they already have; thus cooking books, masking evidences and misinterpreting others only to create public misunderstanding (Tucker, A., 1972; Rogers; R. 1982; Kollerstrom, N., 1982; Wilson, D., 1983). A surprising number of people became experts on lead; and published findings of scientific conclusions tended to present results as faits accomplis; which does not represent all details of the work performed. The resultant picture of the data becomes simplified by glossing over or discarding complications outside the “expert” realm. To give an example, “Research findings tell us that the inhibition of 5-ALA-D which forms the blood pigment haem is one of the best documented effects of lead at low dosage” (Wilson, D., 1983). In fact, inhibition of the erythrocyte enzyme 5-ALA-D is considered the most sensitive biological manifestation of lead exposure, but although a real in vivo phenomena (Roles, H. A. et al, 1974), the health significance of erythrocyte 5-ALA-D inhibition remains doubtful. Indeed, man appears to possess quite a large excess of ALA-D, since a marked inhibition is not accompanied by accumulation in vivo of 5-ALA, the physiological substrate of the enzyme (Roels, H. A.et al, 1976). The reserve capacity of ALA-D is large and its inhibition at low blood lead levels is not likely to interfere with haem synthesis (Waldron, H.A., 1974). Among 3 subjects with lead poisoning, all of whom exhibited severe inhibition of the enzyme 5-ALA-D, the suppression of ALA-D had had no effect on the synthesis of haem or coproporphyrin (Dowdle, E.B. et al, 1971). When ALA-D activity was inhibited in avian erythrocytes by pre incubation with 5xl0~lead, normal hiem synthesis from glycine 2^ C could be demonstrated in vitro despite apparent complete inhibition of enzyme activity. The results were interpreted by the authors as indicating the existence of an alternate pathway for the conversion of ALA to coproporphyrin and haem. Lead mines are a common feature of the landscape of Central and North Wales. An investigation was carried out to compare the characteristics of lead-tolerant populations of vegetation with those occupying more normal habitats. There were marked variations in lead tolerance between genotypes in lead mine populations (Jowett, D., 1964). 112 Tolerance could be acquired by a population which already did not possess it; population selection of ecotypes was a distinct character of adapting to their environment. This raises the point that vegetables grown near major motorways might develop lead-tolerant or resistant species through evolutionary response, and that the uptake of lead is greatly determined by the mineral content of the soil, particularly calcium and phosphorus. Root growth was better in solution with lead and calcium and phos^lio|"U.s than with lead alone (Jowett, D., 1964). As the world food supply dwindles, the most likely circumstance may be phosphorus deficiency, and most evidence now available indicates that probably most lead absorbed by plant roots is rapidly precipitated as a Pb-phosphate complex without translocation. The significance of the predominant Pb-phosphate complexation was seen in studies with corn and several tree species where greater uptake of lead was exhibited. (U.S.E.P.A., 1978). As increases in land usage for agriculture will likely come with cropping of marginal lands, many of which are low in phosphor ILS (this being the most important stress which have an impact on lead uptake) these observations will have future agricultural applicability since rural areas are known lead deposits. At the present time the urban population is increasing most rapidly, thereby making us more dependent on finite mineral deposits. Scorer, R.S. (1983a) has clearly pointed out that up to now population explosion has been accompanied by the occupation of almost virgin land, by increasing its productivity by means of machinery and fertilizers which are absolutely dependent on cheap fuel. However, the real crunch has not yet arrived because the source of cheap fuel is not yet exhausted, but that will not be long now-another decade or two he added. In 1981, the United Nations Food and Agricultural Organization published a study entitled “Agriculture : Towards 2000” (FAO, 1981) which assessed the agricultural future of 90 developing and 34 developed countries. The most pessimistic scenario was a continuation of 113 existing trends in agricultural production. The other two scenarios were more optimistic - one in which agriculture production would increase by 80%, and one in which it would double. They both assumed rapid modernization of agricultural production, mainly through investment in inputs such as fertilizers, irrigation and mechanization. Both optimistic scenarios assume stable economic, social and political structures particularly in “developing” countries which in fact ought to be called under-developed. The FAO studies have not contributed much to our understanding of food futures since assessments of the future of food supply and demand at global and regional scales must consider both the environmental and social constraints on agricultural production (Hekstra, G.P. and Liverman, D.M., 1986). Most of the Middle East is unsuitable for rainfed agriculture (desert soil). I wonder how much of the large-scale aid coming from the developed world eventually trickles down to the poor in under-developed countries. International Agencies using a slogan such as “Health for All by the Year 2000” as their driving force, don’t seem to leave their offices and go down to villages and listen to the problems of the poor people. m 6.3 Nutritional Factors and Susceptibility to Lead Toxicity Food contains many phosphate compounds, and inorganic phosphate, which when added to foods during processing reduce the bioavailability of iron, zinc and copper as do the major organic phosphate compounds encountered in human diets (phytate and casein). Phytate(myo-inositol 1, 2, 3, 4, 5, 6 - hexakis dihydrogen phosphate) is a phosphor compound found in all cereals, many legumes and nuts, some fruits, tubers and roots (Aggett, P.J. and Davies, N.T., 1983), which acts synergistically with calcium at near neutral pH in itro to precipitate zinc, magnesium, copper and manganese. The uptake of lead from the gastrointestinal tract of eight adult human volunteers ingesting lead with the two minerals together (200 mg Ca and 140 mg P) was reduced from 63.3% with no minerals to 10.6% when administered simultaneously, but neither mineral by itself was so effective as the two together (Heard, M.J. and Chamberlain, A.C., 1982). Blake, K.C.H. and Mann, M. (1983) also found that calcium and phosphor together reduced lead absorption considerably more than either calcium and phosphor alone. Stephens, R. and Waldron, H.A. (1975) reported that an adequate level of calcium and phosphor at a Ca/P ratio between 1 and 2 minimizes uptake of lead by rats. Turnlund, J. R. et al (1984) have found that Zn absorption has fallen to 34 ± 6.2% from the basal diet of young men confined to a metabolic unit to 17.5 ± 2.5% when 2.34g of phytate as sodium phytate were added, and to 33.8 ± 2.9% with 0.5g a —cellulose per Kg body weight. The decrease in Zn absorption was accompanied by increased faecal zinc and decreased urinary zinc, thus the results suggest that phytate inhibits Zn absorption with high levels of dietary phytate and could result in Zn deficiency in man. An investigation of the influence of dietary Zn on the toxicity of dietary Pb in young rats clearly indicated that as dietary Zn increased, the severity of Pb toxicity decreased (Cerklewski, F.L. and Forbes, R.M., 1976). Evidence included decreased lead conentration in blood, liver, kidneys and tibias, decreased excretion of delta-aminolaevulinic acid; decreased accumulation of free erythrocyte 115 porphyrins, decreased inhibition of kidney delta - aminolaevulinic acid dehydratase activity; and a decrease in apparent lead absorption. The study indicated that the protective effect of Zn on Pb toxicity is largely mediated by an inhibition of Pb absorption on the intestinal level. The reduced bioavailability of trace metals from plants may be attributed to their fibre content. It has been proposed that Zn and possibly iron and calcium bind to the hydroxyl groups of cellulose, and that phytate and fibre have additive effects in reducing the intestinal absorption of trace metals including Zn in man - (Aggett, P.J. and Davies, N.T., 1983). Foods of animal origin are better sources of chromium and zinc than food of vegetable origin (Mertz, W., 1981). It has been reported that plasma zinc concentrations of inner city children from Baltimore, USA stressed by low-income diet were markedly lower than those reported for middle-income population (Burtimovitz, G.P. and Purdy, W.C., 1978). Zinc is found in high protein, and therefore expensive foods such as red meat and shellfish. Zinc is an important nutrient essential for the function of over 160 metalloenzymes, including enzymes required for DNA and RNA synthesis. Apart from growth, zinc is important for the structure and function of membranes and for the development and maintenance of a competent immune system (Simmer, K. and Thompson, R.P.H., 1986) It is also involved in the mobilization of vitamin A (retinol) from the liver (Butrimovitz, G.P. and Purdy, W.C., 1978). Yamaguchi, M. et al (1980) studied the mechanism of action of Zn on the physiological function. Their results suggested that zinc is taken up by the liver cells and is accumulated in the mitochondria and acts as an activator on the function of mitochondria. It was suggested by Goyer, R. A. (1971) that lead impairs the function of respiratory enzymes involved in oxidative phosphorylation in the first part of the electron transport system in mitochondria. It was stated that the biochemical basis for this lead effect is not known, and has been suggested on theoretical grounds and on the basis of experiments in vitro that lead strongly inhibits the lipoamide dehydrogenase, an enzyme essential to pyruvic acid metabolism and electron 116 transport. The protective effect of Zn requires further investigation in this respect, bearing in mind that the liver is the main organ of detoxification. Its capacity to carry out various oxiditive transformations is largely due to its high cellular content and multiple species of the haem protein cytochrome P-450 (Maines, M. and Kappas, A., 1977); this cytochrome has proved to be of critical importance as the terminal oxidase in the metabolic disposition of a variety of endogenous and exogenous chemicals, including drugs, insecticides, carcinogens and various environmental pollutants. The effect of lead on foetal development in rats has been studied by Saxena D.K. et al (1987). These were fed a synthetic diet: (8% casein diet + drinking water, 8% casein diet -f 1 mg/ml lead acetate in drinking water, 21% casein diet + drinking water and 21% casein diet + 1 mg/ml lead acetate in drinking water). Intra uterine growth retardation, reduced number of pups, birth weight and survival rate were observed in lead exposed groups. Rats maintained on low protein diet and exposed to lead resulted in significantly high incidences of resorption sites, intra-uterine growth retardation and post-implementation loss. In other experiments, pregnant rats fed a marginally zinc deficient diet, 54% of implementation sites were absorbed and 98% of living young had congenital malformations; whereas rhesus monkeys fed a Zn-deficient diet developed signs of Zn deficiency during the last trimester when they had inadequate weight and impaired immune response (Simmer, K. and Thompson, R.P.H., 1986) Zinc deficiency may be more common in certain areas, such as the Middle East, and at times of increased demand such as pregnancy when the mother is unable to mobilize the small body stores of zinc to meet the increasing needs of the developing embryo (Simmer, K. and Thompson, R. P.H., 1986). Zinc appeared to have prevented the development of clinical signs of lead poisoning in young growing horses (Willoughby, R.A. et al, 1972). Trace mineral intake is reduced by the increased use of fats (Aggett, P.J. and Davies, N. T., 1983) and lead absorption is enhanced by diets of high fat content up to seven-fold (Barltrop, D. and Khoo, H.E., 1976). 117 Whether the inhabitants of rural areas consume more or less fat than those of urban areas probably needs to be looked into. In 38 subjects, 24 hours food and water deprivation during fasting led to a 2.5 fold increase in plasma free fatty acids (Home, T., et al, 1982); and this might partially account for the avid uptake of lead during a fast. The British National Survey of 1970-71 revealed a large intake of fat by subjects of high social strata (MAFF, 1973); recently a higher fibre intake was also reported for this group (Nelson, M. and Paul, A.A., 1981). On the other hand sucrose intake was lower in English men with high occupational status (Rose, G. and Marmot, M.G., 1981). The media has recently dramatized the role of dietary fat as a major health hazard and cause of heart disease. Recent reports have suggested a reduction in dietary fat, initially to about 34% of the total energy needs for adults, the remaining energy coming from alcohol (5%), protein (11%) and carbohydrates (50%) (Francis, D.E.M., 1984a; 1984b). Although high fat diets (>10%) increased lead uptake in rats, lower fat (0% and 2.5%) diets had no effect (Barltrop, D. and Khoo, H.E., 1976), and the role of fats in the absorption of lead and potentiating effect of low dietary minerals are difficult to explain properly. Lead absorption was also increased in low protein and high protein diets (Barltrop, D. and Khoo, H.E., 1975). A low fat diet, particularly as lean meat, should be regarded as more expensive than traditional diets, and many families will be unable to afford such a diet, especially as it is recommended for all members of the family. Many surveys in the USA and elsewhere have shown smaller intakes of energy, protein and 118 vitamins in subjects belonging to the lower social classes (Kaufmann, N.A. et al, 1982); mean intake of carbohydrates and starch being highest among Asian people. People who live in the poorest houses also tend to take up the least healthy employment, live in the worst environments and consume the poorest diets (McCarthy, P. et al, 1985). Ill health is associated with many factors , respiratory disorders may be the combined outcome of working in a dirty atmosphere, breathing polluted inner city air, smoking and living in a damp and draughty house. That members of the lower social classes suffer inferior standards of health compared with members of the upper social strata is a matter of concern. Elimination of poverty may not be an achievable ideal, but practical advice on how to feed a family on a limited budget is desperately needed. Scorer, R.S. (1979) quoted the following statement : “But worst of all, compaigns to remove the last traces of lead from the air take away effort from much more worthy causes connected with resources conservation, population control, improvement in diet and healthy active living”, which I perfectly agree with. In England, these differences among the social classes have lessened or disappeared in children, but could still be demonstated in adults as recently as 1980 (Nelson, M. and Paul, A.A., 1981). Changes in diet in mid-life appear to have little impact on coronary heart disease and it has been argued that dietary intervention should begin in childhood (Sanders, T.A.B., 1987b); to reduce the fat content of the diet, an apparently simple measure would be to use skimmed milk. Skimmed milk, has the disadvantage of too high a protein content. The findings of Barltrop, D. and Khoo, H.E. (1975) were that although the high fat, high protein and vitamin D contents of milk might be expected to increase lead absorption, this would be counteracted by the high mineral content. 119 The concentration of lead in processed milk and evaporated milk is higher than that of whole milk (WHO, 1977). Foods such as canned acidic foods, evaporated milk and oysters are considered high in lead content (Stone, C.L. et al, 1981); some dishes contain oyster sauce as an ingredient. 120 6.4 The Intake and Excretion of Lead by the Elderly The pulmonary lead concentrations of men in their ninth decade of life were significantly lower than those of men in their seventh and eighth decades (x = 0.78 ppm vs. x = 1.13 ppm, American post-mortem examination) (Stringer, C.A. et al, 1974). The authors speculated that this decrease is the result of a reduced bulk food intake along with a reduced tidal volume in the age group. This is of particular interest, since studies with nutrient intake and lead exposure in the geriatric population are extremely rare. Over 20 million individuals were 65 years and over in the 1970 census in USA and the number is rising about 3 to 4 million every decade (O’ Hanlon, P. and Kohrs, M.B., 1978). Bunker, V. W. et al (1984) carried out metabolic balance studies for lead and cadmium in 23 healthy elderly people aged 69.7 - 85.5 years while living in their own homes and eating self-selected diet. Mean intake of lead was 54.6 /ig/day with mean retention of —8.7 /xg/day. The negative balances observed in these elderly people were very different from the positive balances found previously in children (Alexander, F. W. et al, 1973). Mean blood-lead level was 13.8 /xg/100ml. The authors cited that there is no obvious reason for the negative balances obtained, and since the balances for nitrogen, calcium and zinc were in equilbrium or slightly positive, it is possible that tissue breakdown is occurring with aging. With advancing age, osteoporosis becomes more frequent especially with lack of exercise and inadequate calcium intake (Silbemer, J., 1987b), but the biology of bone is phenomenally complex, perhaps as complex as the biology of the immune system (Culliton, B.J., 1987). Caloric intake has been found to be inadequate and below the standard used in many studies; nutrients most frequently found deficient are energy and calcium in the diets of persons past 59 years (O’ Hanlon, P. and Kohrs, M.B., 1978). Loss of minerals is more likely in the elderly. My interpretation is that the digestive capacity of the elderly may be diminished (Nair, B.M. and Andersson, I., 1978) and they tend to consume more fibre in their diets in order to facilitate peristaltic movements of the bowel (Behall, K.M. et al, 1984), so lead 121 complexes with the calcium-cellulose and gets excreted. Moreover, doubt is cast on the traditional value of 10% retention of lead from diet described by Kehoe (Barltrop, D., 1979) particularly for the elderly; lead mostly gets eliminated without getting much absorbed. Accordingly, the excess lead excreted might not be necessarily mobilized from bones. The provisional tolerable weekly intake of lead for adults is 3 mg, equivalent to about 430 /zg/day (FAO/WHO, 1972). Average dietary intakes of lead of adults in UK are within the range 70-150 /zg/day, probably closer to the lower figure (DHSS, 1980). Accordingly, the average daily intake of lead in the study of the elderly people (54 /zg/day) is considered low. Schiitz, A. (1979) studying 29 elderly Swedish men and women using a duplicate diet technique found daily intakes of 30 /zg and 19 /zg, respectively. The Swedish are known for having low blood-lead levels. Elinder, C.G., et al (1983) obtained a median blood-lead level of 7.7 /zg/100ml for male nonsmokers, and 5.7 /zg/100ml for female non-smokers. The UNEP/WHO results gave the following figures for Stockholm: 7.5 /zg/100ml for male nonsmokers and 5.9 for female non-smokers (Friberg, L. and Vahter, M., 1983). Blood lead clearly depends significantly on diet and nutritional intake, and this has been verified in experiments on rats (Mylroie, A. A. et al, 1977). Schiitz, A. (1979) reported the dietary intake of lead in Finland of 113 /zg/day as the second lowest to the Swedish. Mykkanen, H. et al (1986) determined the intake of lead to be 49 /zg/day for a 3 years old child and 61 /zg/day for 15 years of age in Finland. 122 6.5 Dietary Intake of Lead In UK the average person’s total dietary intake has been reported as to lie between 250-500 /ig/week (Sherlock, J.C., 1985), equivalent to 35.7 /ig/day — 71.4 /ig/day. Lead intake from the average diet is likely to be near 24 /ig/day, say 30 /ig/day (Sherlock, J.C., 1987). The trend of dietary lead intake could be seen in table 6. 123 Table 6: Trend of Dietary Intakes of Lead WHO RCEP Sherlock, J.C. Sherlock, J.C. Bunker, V.W. Kehoe, R.A. Kolbye, A.C. Thompson, J.A. DHSS 1977 1983 1985 1987 et al, 1984 1961 et al, 1977 1971 (UK) 1980 (UK) (UK) UK UK UK (elderly) x=300 pg/day 57.4 pg/day 70-750 pg 70-150 pg U.S. Adults 18-year old x=274 pg/day Accepted x = 146 pg/d 200-300pg/day lOOpg/day 35.7-71.4pg/day 24-30pg/day 54.6pg/day American Men for UK adult 70-80 pg/day for adults in this figure Amount of The fact that for 2-4 year old several parts adopted lead excreted 69.7-85.5 faecal excretion of child of the world after daily in years old normal American with a MAFF(1982) UK Men is Women is possibility of representing 140-625pg 90-150 pg/day casts a very wide the period x=264pg ■ P- serious doubt on this range of 1975-81 (Thompson, figure (Tepper, L. B. 18-518pg/day J.A. 1971) and Levin, L.S., 1972) Cited in (WHO, 1977) Schutz, A., (Sweden) Finland Shunichi, A. Mahaffey, K.R. et al, DOE(1982b) Sherlock, J.C. Provisional 1979 — per day Schutz, A. 1973 1975 146pg/day et al, 1985 Tolerable elderly men 30 pg 1979 Dietary Intake 200-300 pg/day for children 15.7-21.4pg/day Intake elderly women 19 pg 113pg/day cited for 1955 by typical daily intake (110-150pg/wk) FAO/WHO, the Japanses of an American adult 1972) Mykkanen, H. adult is male. ~430pg/day et al, 1986 274pg/day (3mg/wk 49 pg/day for adults) for 3 years and 61 pg/day for a 15 years old Upper Limit Intake Suggested by Mahaffey, K.R., 1977 for infants 142pg/day (lmg/wk) It appears that lead intake by ingestion has sharply decreased in UK and this was reflected in the recent falling blood lead levels in Britain (DOE, 1987). Results for 1986 showed average falls from 1985 of around 10% for adults, 18% for police officers and 16% for children. The Metal Box Company which is the major manufacturer of cans in the UK has announced that they decided to phase out the use of lead solder in can making by 1985 in November, 1982 (RCEP, 1983). However, itfcworth mentioning that the figure cited as 24 /ig/day (Sherlock, J.C., 1987) seems to be unduly low although he gave an extra margin of safety, “say 30/ig”, concluding that food is an important source of lead intake but that it would be wrong to say food is the major source. The uncertainty as to how to deal with the occurrence of lead in various foods at concentrations below practical detection limits (in traces) reported as zero is likely to give an underestimate. Bearing in mind that a significant proportion of the food in UK diets is grown overseas (RCEP, 1983) and that the intake of fluids has a great effect (lead in a liquid is well absorbed - Sherlock, J.C., 1987), I thereby cast considerable doubt whether the actual intake of a person is going to be 24 /ig/day. An ordinary glass of wine (150-200 /ig-Schiitz, A., 1979) thus contains fivefold the amount of an average daily dietary intake, and drinking over an empty stomach might increase lead absorption to a great extent. Average lead concentrations in wine of 130-190 /ig/£ (range 60-255 /igft) and much higher values (299 /zg/£) have been reported (WHO, 1977). Diet, particularly for a child, is by far the most significant factor in lead exposure (USEPA, 1978). Solder used to seal food cans is reported to contain 98% of lead; and one out of 11 cans of sardines analyzed contained a horrifying 10 ppm of lead (Bryce-Smith, D. and Waldron, H.A., 1974). The effect of industrial effluents discharge on lead concentration in fish could be an explanation (also sewage disposal). The British legal limit for lead in food is 1 ppm (1/ig/g fresh weight — Gallacher, J.E.J. et al, 1984b). Pet canned-food was found to contain hundredfolds the legal limit, and if poor people resort to such an item of diet in times of crises (USEPA, 1978), this would add considerably to the body’s lead burden. 125 A famous Indian Restaurant in Kings Road, London, was shut down ten years ago when an MP dining in that restaurant happened to walk through the kitchen, just to see loads of pet food cans (Anon, A., Personal Communication). Very recently the environmental health officers in Bradford, Keighly and London Borough of Tower Hamlets spotted a product called “sikor” being sold as a mineral supplement to pregnant women according to traditional Bengali Practice. The Asian mineral “sikor” was found to contain quantities of lead ranging from 7-72 ppm (Anon., 1987a; Anon., 1987b). The recent outbreak of lead poisoning in the West Bank reminds us that lead in the environment may be a serious threat to health if it finds its way into diet. Raised blood lead concentrations in the Arab villagejnson the West Bank, some of which required hospital treatment in Jerusalem, appeared to have a common dietary item as the source of lead (Waldron, H.A., 1985). Ground flour from houses of affected families was found to contain lead in concentrations from 54-532 ppm compared with 10 ppm in locally ground flour from unaffected families. The cause was shown to be the usage of stone lead which has been poured into the gap between the mill stone and the housing of the driveshaft which was made of iron and was worn. Lead-glazed pottery continues to be produced in the Middle East by traditional methods and is still widely used as kitchenware and tableware in homes and restaurants (Acra, A. et al, 1981), and the problem is of particular importance to Lebanon, Syria and Jordan where the acidity in a wide variety of traditional foods is primarily due to the use of lemon juice and vinegar. Highly acidic salads and dips as “tabbouleh, fattoush, hommos and ful” are often served in lead-glazed tableware. When acidic foods or beverages come in contact with the lead glaze during storage, cooking or serving, they become contaminated with leached lead. Pickles and yoghurt are also stored, prepared and served in lead-glazed pottery. Of all the 350 earthenware tested, those produced in rural Lebanon by primitive methods were the least 126 likely to have glaze which is resistant to leaching of lead by acidic foods, and therefore were condemned as unfit for use as kitchenware. The mean value of lead leached from 275 primitive pottery utensils (extracted with 5% acetic acid for 1 hour) was 97.67 ± 63.47 mg/£, and only about 15% complied with the maximum limit of 7.0 mg/£ of extracted lead set by the US Food and Drug Administration (FDA) (Acra, A. et al, 1981). One case of a patient with lead poisoning drew attention to the dangers arising from the use of lead-glazed earthenware which the public is still by no means fully aware of. The patient’s blood lead gave results of 79 /zg/100ml and 59 /ig/100ml by two independent laboratories (Clark, K.G.A., 1972). Examination of the patient’s table and kitchenware finally produced a reddish-brown jug brought into use about five months beforehand as a serving-vessel for cider. Extraction (with 5% acetic acid for 4 hours - pH = 2.4) dissolved the equivalent of 455 mg/£ from the interior which was blackened and pitted. His wife’s blood lead was 69 /zg/100ml, his 2-year old son’s blood lead was 38 ^g/100ml and they all drank cider after it had stood in the jug. The jug was purchased in France, and its purpose was clearly functional rather than decorative; and many of the patient’s relatives and friends had drunk from it, including several who were medically qualified. Since it is difficult to make all food comply with the regulations stipulated (maximum lead content in food of 1 ppm, and 0.2 ppm for food prepared for young infants - DHSS, 1980), it would seem desirable that food manufacturers should be required to indicate the lead content of their products on the pack. Many manufacturers print the concentration of the nutrients their foods contain, and it is not less important that the content of what might be called “antinutrients” is given equal prominence (Waldron, H.A., 1975b). If this were done, then 127 even in the absence of adequate lead-in-food regulations, consumers could exercise choice in an area where they presently have none and preferentially select items low in lead if they so wished. The last British government report (RCEP, 1983) thought that controlling lead in petrol is within their power, but that enforcement of much more important regulations affecting the health of the public is not. To kick the weak and be soft with the strong could be one motto in life to follow for some people. Free school milk for all children was withdrawn in 1968, and the 1980 Education Act removed the obligation of Local Education Authorities to provide nutritionally balanced school meals (Sanders, T.A.B., 1987b). Wilson, D. (1983) justified the title of his book “The Lead scandal: The Fight to Save Children From Damage by Lead in Petrol” by defining the word “scandal” according to his own dictionary, to precisely quote his own words. Childhood lead poisoning is a complex social problem made up of inter-related medical, educational, economic and environmental components (Challop, R. et al, 1972). To worry seriously about trace amounts of lead in the air is not very sensible, but to worry about a sizeable proportion of the poor population living in sub-standard housing, built prior to World War II probably is very sensible indeed. The association between environmental pollution and human health is much more complicated than his dictionary tells him. Food preparation practices and modes of cooking differ among ethnic groups, and this may promote the accumulation of lead residues in foodstuffs and increases body lead burden. For example, liquors of cooked legumes and leafy vegetables (containing lead concentrated by evporation due to leaching from lead-glazed pottery) constitutes part of the meal in the Middle East (Acra, A. et al, 1981), which may not be the case elsewhere. The amount of lead absorbed on vegetables is dependent upon the concentration of lead in the water, type of 128 vegetable, salting of the water, water hardness, duration of cooking and the available surface area of the vegetable (Little, P. et al, 1981). Lesser quantities of lead were taken into carrots when cooked in solutions containing various concentrations of sodium chloride; cabbage, carrots, peas and macaroni showed a significant uptake of lead in excess of the quantity of lead originally present in the water during cooking (Moore, M.R. et al, 1979). Consumption of home grown food products by women resident in highly contaminated lead mining spoil resulted in Pb-B concentrations 50% higher than women living in a control area at some distance away (Galllacher, J.E.J. et al, 1984b). The data suggested that an increase in soil lead of 1000 /ig/g(ppm) is associated with an increase in Pb-B of about 4.2 /ig/100ml. Thus, vegetables can constitute an important pathway for lead in such populations, however for the general population as a whole, its not likely to constitute a major pathway. 129 6.6 The Kinetics and Pathways of Lead Excretion The kinetics of lead removal from different tissues in man using hydrophilic chelators as Ca- Na2EDTA (Calcium disodium ethylene diaminetetraacetic acid) has confirmed the complexity of lead metabolism. Results of Castellino, N. and Aloj, S. (1965) have shown that lead weakly bound to the red blood cells or extracellular lead was rapidly removed (by forming Pb-EDTA complex) but that lead strongly complexed inside the cells was removed only very slowly. It seemed unlikely that this removal was brought about by any direct action of the chelant on lead in the cells. They hypothesized that most likely by removing most of the extracellular lead, it increased the rate of transport out of the cells by increasing the concentration gradient. The slight effect on the excretion of lead fixed in the tissues was noted. Experiments on the lipophilic chelants [derivatives from EDTA given the codal name ICRF-Imperial Cancer Research Fund] which have the advantage of enhanced cell permeation were found to have lead excorporating properties (Witting, U. and Hultsch, E., 1981). Free or bound lead ions stored inside the cell could thus be eliminated more readily “from the site of their toxic action” as expressed by the authors. In fact blood plasma delivers lead to haem-forming tissues such as bone marrow, while lead in erythrocytes is less significant toxicologically (Marcus, A. H. and Schwartz, J., 1987). The result was that ICRF has shown some immunosuppressive and cytostatic effects (Witting, U. and Hultsch, E., 1981). They found that even lipophilic chelants failed to influence lead levels in the liver. When rats were exposed to lead in the diet, the highest concentration of lead in all soft tissues was that in the liver (Barltrop, D. and Khoo, H.E., 1975). The main lead-binding tissues are : liver, kidneys and bone (Van Barneveld, A.A. and Van den Hamer, C., 1985). The immunosuppressive phenomenon of lipophilic agents deserves special attention. Another undesirable effect of Ca-EDTA was observed whereby the plasma lead concentration 130 was increased, and that was attributed to mobilised lead from bone and not to any haemolytic effect of Ca-EDTA (Ishihara, N. et al, 1984). The renal concentration of lead has been found to be significantly higher after chelation therapy especially in animals with kidney dysfunction. The urinary pathway is the main route of elimination of the Pb-Chelant complex, and polyamino chelators (e.g. EDTA) have shown nephrotoxic effects (Tandon, S.K. et al, 1985). Another undesirable effect could be the increase in the intestinal absorption of lead by the oral use of EDTA as some authors have pointed out. Accordingly, recent investigations have tried to find out if there is any natural way of enhancing the excretion of lead. Three lead workers with moderately raised blood lead concentrations were compared with seven control subjects regarding the physiological effects of water immersion in water set at 35'c on diuresis. The subjects excreted a mean excess of water of 552 ml. The mean urinary volume increased from 2.11 ml/min during the pre-immersion period to 8.16 ml/min in the second hour of immersion, and this profound diuresis was similar to that of the seven normal subjects under identical conditions (Heywood, A. et al, 1986). It was found that there was a considerable increase in the rate of urinary lead excretion from 0.09 /ig/min. pre immersion to 0.40 ^ig/min. in the second hour of immersion in the lead workers, while the urinary lead concentrations of the normal subjects were too low to be measured. It was stated that immersion in water in a previous experiment with the same control conditions have shown profound diuresis and increased urinary excretion of calcium, and that these pronounced alterations in renal function probably occur because the hydrostatic pressure of the water produces a redistribution of extracellular fluid in the body. This produces a shift of about 700 ml of blood from the limbs to the thoracico-cardiac compartment, and the increase in extracellular fluid is thought to mediate the renal changes by hormonal mechanisms, particularly the atrial naturetic peptide, which is a recently discovered hormone. This is of great interest not only to the employers of lead workers in view of the cost, administrative problems, worker earnings during periods of medical removal from a job, but 131 also to the general public. Buchman, D.D., (1983) points out in her book on herbal medicine that apple cider vinegar placed in the bathwater will overcome body fatigue, and that it is useful externally to alleviate pain and help reduce sprains, but she doesn’t know why. In France, vinegar is largely made from wine, in the USA from cider; the active ingredient being about 5.5 per cent acetic acid which gives it its sour taste (Evers, N. and Elsdon, G.D., 1929). The relatively great susceptibility of lead to attack by acetic, citric, tartaric and other organic acids is largely due to the formation of very stable organo-lead complexes (Nriagu, J.O., 1978). Whether adding a cup of apple cider vinegar to bathwater increases urinary excretion of lead requires experimental investigation. Oral intake of vinegar could enhance the intestinal absorption of lead, since it is known that citric acid, for example, is considered a low molecular weight ligand which facilitates the absorption of zinc. At the near neutral pH of the small intestinal lumen, iron, zinc and copper form sparingly soluble complexes with carboxylic acids (citrate, malate, lactate and fumarate) therefore may maintain the metals in a water soluble form which enables them to diffuse to the mucosa where the low effective stability of some of these complexes then allows the rapid transfer of the metals to uptake sites on the enterocyte (Aggett, P.J. and Davies, N.T., 1983). Gastrointestinal absorption of lead occurs mainly in the duodenum and is thought to involve passive rather than active transport mechanisms (Goyer, R. A. 1978). Dental studies have shown that tartrate enhances the transport of calcium through the enamel to buried carious lesions, thus helping the process of remineralization of the tooth (Raloff, J., 1986a). This is another example of the process which could be relevant to the incorporation of lead in teeth. In one case of chronic plumbism (blood lead level = 75 /ig/100ml) of an explosives factory 132 worker, his excretion of lead was increased slightly by a low-calcium diet (from 0.11 mg/day on an ordinary diet to 0.17 mg/day on a low-calcium diet combined with the administration of ammonium chloride) and decreased to 0.11 mg/day when he was put on a high-calcium diet (Tompsett, S.L. and Anderson, A.B., 1939). However the physiological interaction between lead and calcium probably differs in cases of moderate and high or low exposure. One homeopathic experiment showed a highly significant increase in urinary lead excretion from lead-loaded rats with the homeopathic remedy plumbum metallicum 200 cH (centesimal potency consisting of lead in a dilution of 10—^^), yet the same results could not be reproduced in another experiment by the same authors (Fisher, P. et al, 1987). Homeopathic treatment rests on the basic principle ‘like cures like’ and its efficiency increases with increasing dilution. For example, one study has shown a significant reduction of active hay fever in patients when treated with a homeopathic preparation of mixed grass pollens (Turner, P., 1987). Homeopathic treatment generally aims at stimulating the immune system in order to detoxify the foreign agent or cope with it somehow such as renal clearance in the case of lead. It important to recognize that the immunoreactivity of an animal species varies with the dose, route of administration (e.g. subcutaneous administration of lead in rats does not apply to human exposure), exposure conditions (acute, semichronic, chronic) and duration of exposure relative to microbial challenge or antigenic stimulation. It should not be assumed that identical mechanisms operate in vitro and in vivo (Albahary, C. 1972). Significant immunosuppression occurred in an intraperitioneally-immunized group of newborn mice exposed for 28 days to 2.5 mg/m aerosolized Pb(NOg )2 (Hillam, R.P. and Ozkan, A.N., 1986). Yet, McRoberts, W. (1980) investigated 44 workmen in the demolition industry (where there was a potential lead hazard in cutting metal heavily coated with old lead-based paint), and the results obtained showed that blood lead concentrations above 30 /xg/100ml and especially above 50 /ig/100ml produce slight adverse effects on mean values for 133 haematological parameters. The effects were more marked in new entrants to the lead industry than in those who have worked for many years, suggesting that chronically exposed workers possess acquired tolerance to lead. This may be due to the presence of a low molecular weight binding protein in erythrocytes found in lead exposed workers but not in normal individuals (Raghavan, S.R.V. and Gonick, H.C., 1977). It is noteworthy that the mouse is a non-sweating animal (Hunter, J. M., 1977) and lead exposure as measured by the blood lead level does not tell us what proportion of the lead is actually retained (Morton, A. et al 1985; Willougby, C.E. and Wilkins, E.S., 1938; Witting, U. and Hultsch, E., 1981). Toxic manifestations are modulated by excretion, wherely equilibrium in lead distribution is rapidly attained. Nutrition is regarded also as an important factor which can modulate the results of animal experiments in toxicology (Hayashi. Y. et al, 1984; Kato, R., 1980). Although the relevance of toxic quantities of lead administered to experimental animals to the actual environmental levels to which man is exposed needs to be established, the results of such studies yield estimates that are not meaningless or erroneous, but are restrictive in interpretation. The importance of experimental design, certain dietary constituents, physiological conditions and statistical evaluations of data is to be stressed in reviews of bioavailability (Stone, C.L. et al, 1981). Cerklewski, F.L. (1983) found an enhanced accumulation of lead in the liver of rats fed a magnesium-deprived diet; yet in mice fed a Mg-deprived diet, no effect on lead uptake in the liver was observed (Van Barneveld, A.A and Van Den Hamer, C.J.A., 1985). The cat is resistant to the absorption of lead in large quantities and there are practically no references to lead poisoning in the cat (USEPA, 1978). I happened to come across only one in which a 10-year-old female cat was presented to a veterinary clinic in Australia with a 10- day history of inappetence, diarrhoea and intermittent vomi. ing, and the blood lead level m was 115.5 /ig/100ml. The lady who lived in the house was renovating it and had recently been burning and sanding old paint off the exterior walls (Watson, A.D.J., 1983). Feral pigeons have been used to monitor the impact of banning of lead in petrol in Tokyo, Japan (Ohi, G. et al, 1981) by measuring their blood lead levels, as if human metabolism is comparable to that of the pigeon ignoring all aspects of gastrointestinal absorption, diet and excretion mechanisms. Lead in petrol was banned in Japan in 1975 and pigeons in 1976 have still maintined high levels of lead in their blood in downtown Tokyo after the ban has been enforced. Tansy, M.F. and Roth, R.P. (1970) determined the lead content of various tissues and organs of two groups of wild pigeons, one was captured in rural Jefferson County in Pennsylvania, while the other was captured in the city of Philadelphia. The blood lead content of the two groups did not reflect a significant difference, yet still the authors advanced the proposition that “the most significant source of biological lead is probably atmospheric”. Although blood lead increases with age (DOE, 1983; DOE, 1986; DOE; 1987), urinary lead has also been found to increase with age (Staessen, J. et al, 1984). In a population with low lead exposure in a small Belgian town, urinary lead excretion was 4.5 /ig lead/g creatinine in youths and 6.5 /ig/g creatnine in adults while middle-aged Belgian workers with no occupational exposure showed a level of 14 /ig/g creatinine (Staessen, J. et al, 1984). Whether differences in excretion between men and women partially account for the higher Pb- B levels among men (30% higher — DOE, 1987) has hot been properly investigated. Lead metabolism in humans has only been studied in males. Watanabe, T. et al (1987) found higher levels of urinary lead among women [2.08 /ig/£(GM)] than men [1.81 /ig/£(GM)]. Urine samples were collected in this study from 1163 individuals living in 6 areas of Japan, 95% of which were for women. Yet, Staessen, J. et al (1984) found that over the age of 20, lead output was higher in male than in female subjects and increased with age until 50. Only 274 Belgian people aged 10 years or more were investigated, and determination was conducted on a 24 hour urinary sample; the proportion of men to women was not cited. Urinary lead level for adult men was 6.9 /ig/g creatinine compared to 6 /jg/gcrea.tinine for women. Its not possible to compare the Japanese with the Belgian results since they used different units of measurements. Although women have got a higher amount of adipose tissue than men, men are expected to sweat more because they do more muscular activity, and are also expected to excrete more urinary lead than women due to higher body lead content. However, the fact that differences in Pb-B levels between the two sexes occured only between the ages of 12 and 40 for females (Qiuinn, M.J., 1985; DOE, 1978) brings into attention the removal of appreciable amounts of lead from the female body via menstruation during this female age. It should be noted that different popultions excrete significantly different amounts of lead in urine, probably due to different diets, and this would partially account for variations in Pb-B levels among widely different populations. 136 6.7 Sweat as a Significant Pathway of Lead Excretion Scorer, R.S. (1980) raised the question of the effect of air pollution, and lead in particular, on cyclists in inner city areas. Physical exercise increases the basal metabolic rate, improves the blood circulation and aids efficient excretion by the lungs, kidneys (urine) and skin (sweat). The primary functions of the kidneys are to control the fluid and electrolyte balance of the body and to excrete metabolic waste products. Blood flow through the kidneys is higher than for any other organ; approximately 20 per cent of the cardiac output is delivered to the kidneys each minute (1200 ml blood) (Dougherty, J.C., 1973). During exercise, sufficient blood flows through the kidneys with enough pressure (osmotic pressure) to form a large volume of glomerular filtrate which leads to increased urinary excretion and with it waste products of metabolism. The concentrations of lead in sweat and urine are almost equal (Waldron, H.A., and Stofer, D., 1974; Kehoe, R.A., 1961); Thompson, J.A. (1971) figured out that the amount of lead absorbed daily from the respiratory tract approximates that excreted daily in sweat and hair using the following figures quoted by several authors in addition to her subjects Table 7: Relation between intake and output of lead in men Cone, of Pb Amount Percentage Amount Excreted Amount in air Inhaled Absorbed in sweat Excreted in Hair 3.2/ig/m3 30/igPb/day 25%—50% 12 fig/day 18/ig/g in the atmosphere Absorbed Daily output (ppm) of Fleet St., i.e.: Pb in urine: London 7.5/ig- 16/ig-30/ig 15/jg Pb (Waller, R.E. (Goldsmith, (Thompson, (Schroeder, et al, 1965 ) J.R. and J.A., 1971) H.A. and Hexter, A.C., Tipton, I.H., 1967) 1968) 137 Concentrations of lead in the hair of fishermen from the Subae River Basin in Brazil was reported as: 39.6ppm (GM) near a lead smelter, and fishermen with straight hair always presented higher concentrations of lead than those with curly hair (Carvalho, F. et al, 1984). If the respiratory intake in a highly polluted atmosphere with congested traffic is 30/ig, then most of it would be excreted in skin and hair. Rabinowitz, M.B. et al, (1976) determined the lead concentration in the sweat of five healthy human subjects, while studying their steady state kinetics of lead metabolism, to be 20% of that in urine (7 /ig Pb/£) while maintained on a lead - enriched diet. The difference in sweat excretion between Thompson, J.A., 1971 and Rabinowitz, M.B. et al, 1976, could be attributable to the fact that the major route of removal of lead from the body is biliary excretion, particularly ingested lead (Bornemann, L.D. and Colburn, W.A., 1985). Faecal excretion is much greater than urinary excretion, and for inorganic lead, the ratio of lead content is approximately 100:1 (Waldron, H.A. and Stofer, D., 1974). It is important to note that physical exercise generally improves appetite and digestion and aids efficient defecation (Spencer, M. and Tait, K.M., 1970). The frequency of bowel motions varied from individual to individual and was determining lead output (Thompson, J.A., 1971), and also Kehoe, R.A. (1961) noted that a greater degree of absorption had occurred when the retention of the contents of the alimentary tract was prolonged i.e. Infrequent faecal motions. Sweat is mostly water with some salt (sodium chloride) and waste products, and the average amount produced in twenty four hours is about one pint (540 mis) (Spencer, M. and Tait, K.M., 1970). This route of lead excretion is particularly important in hot climates. Blood lead levels were determined in 26 telephone cable solderers in a Kuwaiti firm, and only four workers showed Pb-B levels > 40/zg/100ml (Abu-Farsakh, F. A. F. et al, 1988). The authors cited that itisunlikely that blood lead values as high as 40 /zg/100ml could be due to inhalation of fumes or dust containing lead, but was a result of neglect of basic hygienic precautions such as eating or smoking without handwashing. It is likely that sweat in hot climates plays a greater role in the excretion of 138 lead. The lead hazard from cycling in streets with heavy traffic most probably lies in the bicycle wheels which pick up roadside soil, pavement dust and dirt especially when taken for parking inside the house (i.e. the kitchen). No significant difference was found in Pb-B levels between traffic personnel and normal men in Sweden long before the reduction of lead in petrol came into effect, and the activity of ALA—D enzyme in the red blood cells was significantly higher in traffic police then in normal men (Haeger-Aronsen, B., 1971); the same pattern was also observed in the recent UK Pb-B monitoring programme (Quinn, M.J. and Delves, H.T., 1988). This leads us to imply the greater physical fitness and activity of police officers as a contributing factor. Comparison of urban-rural Pb-B levels as well as civilized accultured versus remote populations seems to have completely ignored this factor (as well as other aspects of lifestyle including diet). Where there is no reticulated water supply, where the main meal of the day cannot be taken until the individual exerted himself in collecting it and where no roads or automobiles exist; such activities and others (i.e. gathering pieces of wood to make fire in primitive populations) create a muscular, physically fit person who is mentally healthy and is not peculiarly susceptible to a particular environmental factor. In contrast with the situation in urbanized communities, cardiovascular disease in general, hypertension and coronary heart disease in particular are claimed to be uncommon in Papua New Guinea (Sinnett, P.F. and Whyte, H.M., 1973; Maddocks, I., 1967; King, H. et al, 1985). In the population of Greenland, mainly Eskimos, death from cardiovascular disease is rare (Dyerberg, J. and Bang, H.O., 1979; Kroman, N. and Green, A., 1980; Kromhout, D. et al, 1985). Coronary heart diease is the main cause of death in men under the age of 65 in most western developed countries with the notable exception of Japan (Sanders, T.A.B., 1987a). Immigrants from Bangladesh living in the East End of London are reported as having a greater than expected incidence of myocardial infarction (Silman, A. J. et al, 1987). 139 The rate of large bowel cancer among population on a Western diet is high (North American, English, Scottish, etc.) compared to that in other populations (Japanese, Ugandan, etc.) (Huang, C.T.L. et al, 1978). It has been postulated that it is due to the dietary fibre’s protective effect against the development of colon cancer, diverticular disease, and atherosclerosis. Japanese studies have shown that lead excretion in faeces via bile may be enhanced by a large intake of fibre, thiamine and iron. (Ito, Y. et al, 1987b); the reason being that fibre inhibits intestinal absorption of various substances and stimulates their secretion into faeces (same effect observed in the elderly). The effect of dietary fibre on intestinal function and composition of lipids in the faeces such as bile acids and neutral sterols has been of considerable interest (Vahouny, G.V. et al, 1978). Dietary fibre has been defined as that part of plant material taken in our diet which is resistant to digestion by the secretion of the human gastrointestinal tract. It comprises a heterogenous group of carbohydrate compounds including cellulose, hemicellulose, pectin and a noncarbohydrate substance, lignin (Huang, C.T.L. et al, 1978). Transit time, the time necessary for food residues to move through the entire gastrointestinal tract and pass out in the faeces, has been reported to be shortened by the ingestion of large amounts of dietary fibre; and variation in faecal excretion of lead due to different elimination through bile and/or intestinal absorption has indicated a considerable interindividual difference in blood lead levels (Shutz, A., et al, 1987). Different excretion patterns among dietary groups reveal distinct characteristic metabolic features associated with diet and lifestyle (Turjman, N. et al, 1984) 140 6.8 Populations with Low Blood-Lead Levels The lowest blood lead levels in the industrialized countries of the world are those of the Japanese. Determinations of lead concentrations for more than 2500 blood samples collected from farmers in various parts of Japan established baselines for blood lead levels of 4.86 /ig/100ml (GM) for males and 3.21 /ig/100ml (GM) for females (Watanabe, T. et al, 1985). The UNEP/WHO study gave values of Pb-B for 200 teachers in Tokyo of 6.5 /ig/100ml(GM) for non-smoker males and 5.2 /ig/100ml for non-smoker females (Friberg, L. and Vahter, M., 1983). The Blood lead level of 3.21 yug/100ml for Japanese females is slightly lower than that of the concentration reported for 103 children living at the foothills of the Himalayas in Nepal of 3.4 /ig/100ml where the lead content in the air was found to be extremely negligible (Piomelli, S. et al, 1980), and comparable to that of 100 children living in a remote area in Papua New Guinea of 5.2 /ig/100ml (Poole, C. et al, 1980). The lowest blood lead level ever reported in the literature is 0.83 /xg/100ml for 90 unaccultured Yanomama primitive Indian tribe living in Southern Venezuela (Hecker, L.W. et al, 1974). However, not only lack of quality control casts doubt on this unique figure, but also the highly paradoxical levels of urinary lead being excreted, not to mention the decrease in the precision of blood analytical methods designed for measuring moderate blood lead levels. The precision of 8% reported by Hecker, L. W. et al (1974) based on 0.5m£ aliquots of blood digested with perchloric acid, followed by anodic stripping voltammetry (ASV) is one attributed to analytical methods used at considerably higher Pb-B levels than 0.83 /zg/100m£. At a value of 15 /ig/100m£, atomic absorption spectrophotometry (Delves Cup Technique) should achieve results within ± 10%, provided the quality control is meticulous (DHSS, 1980) . Moreover, no mention was made of blank determinations. The vegetable paints and other mineral pigments used on their body, as well as the continual use of the hallucinogen, ebene, could have contributed a lot to their excessive lead excretion. That 74 healthy male Japanese (20-55 years old) exposed to lead in the manufacturing processes of smelting and casting of iron in a steel factory showed blood lead levels averaging 13 /zg/100ml (range 5.6-35.6 pg/lOOml) is rather surprising and deserves attention (Ito, Y. et al, 1987a). For the sake of comparison, 10 out of 17 workers from a paint factory in Syria had Pb-B levels from 27 to 52 pg/100ml and only 3 persons had Pb-B levels < 25 pg/lOOml (Othman, I, 1985). The Japanese have constantly been showing low blood lead levels. The concentration of lead in the blood of 203 traffic policemen on patrol by car aged between 21-49 years belonging to the Hokkaido Police Force in Japan showed an average Pb-B of 9.60 /xg/100ml in 1973 (Saito, K. et al, 1973) before lead was banned from petrol in February, 1975 (Ohi, G. et al, 1981) . They have recently boasted of having the lowest concentration of lead in urine of 1.81 fig/1 (GM) for men and 2.08 fig/i(GM) for women in a study of 1163 urine samples collected from farmers in 6 non-polluted areas in various parts of Japan (Watanabe, T. et al, 1987); their levels being lower than those of Western Europe and the USA. Although the concentration of lead in urine (Pb-U) is not a better indicator of exposure than Pb-B, since it depends upon diuresis and specific gravity (ILO, 1983), it is an indication of the body lead content. Pb-U levels normally do not exceed 65 fig ft (ILO, 1983). 142 The Health and Safety Commission in Britain (1985) has specified that any lead—worker whose urinary lead concentration is equal to or greater than 150 /ig / i will have the test repeated and if the result of the repeat test is equal to or greater than 150 n%fi will be certified as unfit for work which exposes him to lead. A look to the past might give a hint. The whole body lead content of normal Japanese tissues was more than 22 mg (Sumino, K. et al, 1975), while that of the British subjects was 164.8 mg for males and 103.6 mg for females (Barry, P.S.I., 1975). It is probable that adult American persons could have less than 50 mg and more than 200 mg of lead in their bodies (Schroeder, H.A. and Tipton, I.H., 1968). Therefore, the Japanese have had lower body lead content than other populations since a very long time. The amount of dietary intake must have been lower than other populations, and indeed it was. The amount reported in 1955 was 274 /ig/day (Araki, S., 1973), which happened to be the same level as the dietary intake of British subjects (274 /ig/day) in 1971 (Thompson, J.A., 1971), in which the average amount of lead retained in the body was estimated to be 10 /xg/day. Everything points to the diet in retaining low amounts of lead. A Japanese-style diet is characterized by: 1. Low total energy 2. Relatively high dependence on carbohydrate as a source of energy 3. Equal quantities of animal and vegetable protein with more fish and shellfish as animal protein (Chiba, K. et al, 1985) 143 Table 8: Comparison of food Consumption in Japan and other Industrialized countries1 Japan U.S.A. The Netherlands FRG Total Energy (Kcal/day) 2568 3393 3421 3397 Energy from Crop 79 62 60 55 Products (%) Protein (g/day) 82.2 106.3 97.1 98.4 Animal Protein (%) 42 70 67 68 This Japanese-style diet is typical of the food that farmers eat. The food of the farmer is rather low in total energy (ca 2000 Kcal/day), about 64% of total energy being accounted for by carbohydates. Protein is obtained from vegetables and animals, with a larger proportion from fish. Intake of salted preserves in addition to fishes, shellfishes, roe and “tuskudani” (fish, shellfish, vegetables and seaweeds boiled down in soy) are reported (Ogata, M. et al, 1984). Details of the dietary assessment of a Highland population in New Guinea (Pb- B=5.2/zg/100ml) have shown certain similarities i.e. low total energy (2300 Kcal for males and 1770 Kcal for females), extremely high dependence on carbohydrates (90% of the calories mostly from sweet potatoes), extremely low intake of fat (only 3%) and protein intake was very low indeed (estimated to average 25g/day)(Sinnett, P.F. and Whyte, H.M., 1973). 1 Adapted from Chiba, K. et al (1985) — calculated from the Organization for Economic Cooperation and Development (OECD) Food Consumption Statistics 1964-1978, Paris, OECD, 1981. Such characteristics can be readily confirmed by a comparison of the y^ujtritional consumption patterns of Japan and other industrialized countries from table 8. 145 I can figure out the high levels of zinc consumed by the Japanese (particularly shellfish), minerals (seaweeds), and the high quality of the protein (sulphur-containing amino acids like cysteine and methionine) in addition to fibre (vegetables). One important observation is that the Activity of 6-aminolaevulinic acid dehydratase enzyme (ALA-D) in the Japanese, one of the enzymes participating in porphyrin synthesis which is highly sensitive to inhibition by lead, has showed values falling far outside the ranges of all other populations (Haeger- Aronson, B., 1971) as can be seen in the following table: Table 9: 6-ALA-D Activities in Different Populations Nationality 5-ALA-D Activity in R.B.C .2 American 28.327 Mean = 178 Italian 60.120 Mean = 90 Japanese 758.1082 Mean = 920 Dutch 29.111 Mean = 86 Finnish 50.190 Mean = 150 Swedish 121 for men 143 for women The in vitro addition of Zn has been found to have an activating effect for the erythrocyte ALA-D, and was observed to eliminate the lead-induced inhibition of the erythrocyte ALA-D activity; and the degree of elimination seemed to depend on the molar ratio (Zn/Pb) of both metal concentrations in the ALA-D assay (Tomokuni, K., 1979). The in Vivo significant effect of blood Zn on ALA-D has also been verified by others (Meredith, P.A. and Moore, Activity of ALAD in RBC is expressed as 10 /xmol of porphobilinogen (PBG) synthesized per ml of packed RBC per hour of incubation, since ALA-D catalyzes the condensation of 2 mol. of ALA to 1 mol. of PBG. (see fig. 6) 146 M.R., 1980). No doubt the intake of Zn among the Japanese must be very high, and Zn would have functions neither appreciated nor specified so far in man. Supplementary Zn significantly decreased cadmium, and increased iron in the liver (Yoshikawa, H., 1970). Another protective nutrient that fish is providing is selenium (Se) (Sanders, T.A.B. 1987a). The usual diet of Nepalese villagers consists primarily of rice, dhals (Indian pulses similar to lentils), corn and wheat supplemented by small amounts of milk and occasionally vegetables and fruits, the consumption of which being limited to seasonal availability. Protein intake is in the form of grains, beans and peanuts, while animals sources are negligible. (Brown, M.L. et al, 1968). No evidence of clinical avitaminosis was found among the persons examined, and what was evident is that thiamine and niacin intakes were generally high due largely to daily consumption of whole grain cereals in Nepal. Pulses are classified as good sources of the B group vitamins (except riboflavin), and have therefore a well-deserved reputation as a food which will protect against beriberi (thiamine deficiency disease) and have been described as “the poor man’s meat” (Davidson, S. et al, 1979). Pulses have a higher protein content than cereals. Marginal to low intakes of meat, poultry and eggs are also sometimes reported. The following table shows mean daily intakes in Nepal (Brown, M.L. et al, 1968) 147 Table 10: Average Daily Contents of Nutritional Intake among the Nepalese Mean Intake* Mean Intake** Nepal (Pb-B=3.4/ig/100ml Japanese (Pb-B= , adult males 4.86/ig/100ml .. for children) adult females 3.21/ig/ 100ml) Carbohydrates (g) 463 307 Calcium (mg) 357 580 Iron (mg) 12.6 10.9 Thiamine (mg) 2.1 1.37 Fat (g) 35 58.6 Protein (g) 60 80.9 Brown, M.L. et al, (1968) Average Intakes in the Japanese Population (1983), Ito, Y. et al (1987a) t Piomelli, S. et al (1980) ft Watanabe, T. et al (1985) Although the intake of calcium was low among the Nepalese, iron seems to have been slightly high, which could have compensated for the higher absorption effect anticipated by calcium deficiency; thus it seems that iron is much more important than calcium in decreasing the absorption of lead, especially in improving the immune system of the body. Thiamine intake was much higher than those of the Japanese which could have greatly enhanced the excretion of lead. 148 6.9 Interactions between Lead and Selenium Antagonistic toxic effects of Se and Pb were studied in growing rats (Rastogi, S.C. et al, 1976) and the enzymic activity of enzyme activities-were normal in rats receiving both Se and Pb. The enzyme activities assayed were however, depressed in the animals receiving either Pb or Se. The same was true regarding growth rate and food consumption. Evidence of a selenium-cadmium and selenium-arsenic metabolic antagonism has also been revealed (Holmberg, Jr., R.E. and Ferm, V.H., 1969). As both selenium and cadmium follow very closely the biochemical pathway of sulphur, selenium protects against cadmium by chelating with the cadmium bound to sulphur on sulphydryl thiol groups; this was the explanation given by the authors. The same mechanism of protection dependent on macromolecules containing sulphur groups might well apply to lead since it has a great affinity for -SH groups. Lead selenide (Pb Se), clausthalite, is used (in suspension) for cancer therapy. Epidemiological studies have suggested that low selenium intakes may be related to an increased incidence of cancer; Se is an integral part of the enzyme glutathione peroxidase and its depletion has been associated with progressive cardiomyopathy in children (Keshan disease) in China, where Se content of staple food is low (Levander, O.A. et al, 1983; McKenzie, R.L. et al, 1978). Dietary deficiency of Se and/or vitamin E is associated with muscular dystrophy, pancreatic degeneration and liver necrosis (Dutta, S.K. et al, 1983). There is a theory which says that “cancer is fundamentally a deficiency of pancreatic enzymes”, and a vital part of cancer therapy is to stimulate the liver to remove toxins from the body (Dickerson, J.W.T., 1986). Modifying the ionic environment of mouse ascites tumour cells showed that multiplication of cells was reduced by lowering the concentration of potassium in the medium (Dickerson, J.W.T., 1986), which is a characteristic attributable to lead. Erythrocytes from subjects exposed occupationally to inorganic lead lost potassium in vitro more readily than cells from people never knowingly exposed to lead (Hernberg, S. et al, 149 1967; Hasan, J. et al, 1967). A close relationship was observed in lead workers between osmotic fragility and intracellular potassium, but not in the controls (Karai, I.et al, 1982). Alcoholic subjects showed mean plasma levels of Se, and mean urinary excretion of selenium significantly lower as compared to control subjects at the time of admission to the hospital for treatment (Dutta, S. K. et al, 1983). Elderly subjects (over 70) had lower Se concentrations than young adults which might reflect either the reduced food intake, or the geographical variation in the levels of Se in soil in several parts of the world (McKenzie, R.L. et al, 1978). The author is a firm believer in the protection selenium provides against certain cancers, and has recently been taking 100 fig Se/day supplements. Se-rich foods are fish, liver and kidney. Finland, like most parts of Scandinavia has very low concentrations of Se in the low levels of soil. Since/Se might be a a risk factor both in cardiovascular disease and cancer; also the resistance to infection might be impaired (tested on Staphylococcus aureus), the issue has become a focus of public interest, and health and chemists’ shops* business of Se supplementation pills has boomed (Kiovistoinen, P., 1985). It seems to me that the Scandinavians are much more mindful of certain nutritional effects than Europeans, and this might have greatly contributed to their low Pb-B levels. Sweden enjoys a very high standard of living and the benefits of an advanced social welfare system. o With an area of 174,000 square miles (450,000 Km ), Sweden is about twice as large as UK, yet has a population of only about 8.3 million (Hurst, J., 1983). The enzyme glutathione peroxidase is one component of a sophisticated protective mechanism that prevents damage to living cells by the harmful effects of oxygen-derived free radicals (Diplock, A.T., 1985). Many carcinogens must undergo oxidation to metabolically activated intermediates such as m oxidative free radicals before they can damage body cells, and one of the chief intra-cellular systems for trapping free radicals and peroxides involves vitamin E and the selenium- containing enzyme glutathione peroxidase; thus selenium and other antioxidants seem to inhibit a peroxidation which may enhance attachment of carcinogens to DNA (Thomas, J.S., 1986). 151 6.10 The Effects of vitamin B Complex on Lead Toxicity The amount of lead excreted in faeces in rats increases with the amounts of thiamine (vitamin Bl) administered (Ito, Y. et al, 1987b). Bratton, G.R. et al (1981) have demonstrated prevention of tissue accumulation and clinical signs of lead poisoning in calves by treatment with Vitamin B^. Ito, Y. et al (1987a) results on occupationally exposed lead workers were in full agreement with-Hell'studies on rats, and lead excretion in faeces via bile was enhanced by a large intake of thiamine. Obviously thiamine has a role in the acceleration of lead removal and of lead excretion in faeces via bile. Thiamine as thiamine pyrophosphate serves as the coenzyme in over 24 enzyme systems, enzymes acting on pyruvic acid, acetaldehyde, alpha-keto acids, acetic acid and others (Sauberlich, H.E., 1967). Goyer, R.A. (1971) found a marked difference between the respiratory control ratio and the ADP:0 ratio of control and lead mitochondria when pyruvate was used as a substrate; the respiratory ratio being thought of as a measure of the physiologic intactness of respiratory enzymes involved in oxidative phosphorylation. The suggestion was given that lead strongly inhibits an enzyme essential to pyruvic acid metabolism (Goyer, R.A., 1971). Thiamine functions in the enzymatic breakdown of pyruvic acid and in the decarboxylation of a-ketoglutaric acid and other a-keto acids. One of the earliest observations of a biochemical abnormality in thiamine deficiency is that pyruvic acid accumulates in the tissues and its concentration rises in the circulating blood (Sauberlich, H.E., 1967). Thiamine is known to be a cofactor of pyruvic dehydrogenase and transketolase in the hexose monophosphate shunt in addition to its function in pyruvate utilization by animal tissues (Brin, M. et al, 1958). Erythrocyte transketolase is significantly decreased, and the effect becomes larger with continued depletion of thiamine (Hathcock, J.N., 1978). In mammalian tissues, the main action of transketolase appears to be related to ribulose 5- phosphate metabolism, and the overail system gives rise to the production of NADPH and 152 ribose from glucose (Sauberlich, H.E., 1967). Thus, the administration of thiamine may activate the active transport mechanism of (biliary) excretion of lead via the bile. The enhancement of lead excretion via the bile by thiamine seems to be due to its action on promoting ATP production in the glucose shunt, and in releasing lead from the liver (Ito, Y. et al, 1987b). The explanation for raised blood lead levels in chronic alcoholism may be related to inadequate dietary intake of thiamine (particularly in severe restriction cases such as in prisons) in such persons who for long periods drink heavily and eat poorly. Symptoms of alcoholism (i.e. peripheral neuritis, mental disturbances etc. .) are treated with boost doses of thiamine. White blood cells contain approximately 10 times more thiamine than erythrocytes (Sauberlich, H.E., 1967); and zinc deficiency results in 60% reduction in leucocyte zinc levels (Simmer, K. and Thompson, R.P.H., 1986). Faour, J.A. (1984) observed a tendency for leucocytes to increase in 100 lead-exposed workers with Pb-B levels>36/ig/100ml. King, E. and Thompson, A.R. (1961) found an increased lymphocyte count in 40 men who showed evidence of excessive lead absorption. White blood cells especially in the lungs are primarily responsible for phagocytosis, and chronic lead exposure seems to result in an activation of macrophages as indicated by a stimulated phagocytosis and increased acidic phosphatase levels (Ewers, U. et al, 1982). Immunopotentiation probably results in stimulating the phagocytic function of the reticuloendothelial system due to chronic exposure to lead, and increases the host’s non specific resistance to several bacterial and viral diseases. The possible relationship between leucocytes and lead metabolism requires extensive consideration and remains to be evaluated. White blood cells counts are used as indices of the effects of radiation on blood-producing organs and on the whole organism, constituting an easily available preventive measure (Vich, 153 Z. and Kriklava, J., 1970). The increase of serum immunoglobulins (IgA) with increasing Pb-B levels in lead workers has been reported; and elevated IgA levels in these groups of workers have been explained by a selective stimulation of components of the immunoglobulin system by certain occupationally related agents or by a more frequent antigenic stimulation of the mucous membranes of the respiratory tract (Ewers, U. et al, 1982). Bacterial infections of the gastrointestinal tract and oral vaccines normally produce a secretory immune response (usually IgA) in the intestine (Forrest, B.D., 1988). Simultaneous administration of vitamin B complex to rats with lead resulted not only in minimizing the accumulation of lead in blood and vital organs (reduced hepatic and renal uptake), but also in reduced blood and urinary biochemical alterations (Flora, S.J.S. et al, 1984). Prevention of lead nephrotoxicity was one of the effects of vitamin B complex, and the normal activities of the three renal enzymes (lactic dehydrogenase, glutamic oxaloacetic transaminase, and alkaline phosphatase) were remarkable. Although the administration of lead alone significantly inhibr^ej,, the activity of blood 6-ALA-D and lowered the haemoglobin level, these alterations were not significantly marked in animals treated with lead plus vitamin B complex. 6.11 Blood-Lead Levels of Greenlanders Inhibitants of Greenland are showing relatively high Pb-B levels although the Arctic area U s minimal car driving and industry. The finding of blood lead levels in East Greenland among Eskimos of 14.8/ig/100ml for males and 12.8/ig/100ml for females (Hansen, J.C. et al, 1983) equivalent to those found in industrialized countries [mean Pb-B value for Ann Arbor, Michigan in the USA was 14.6 /ig/100ml - (Hecker, L.H. et al, 1974)] is rather surprising. Q In a typical city, the airborne concentration is of the order of 1-2/ig/m , whereas in sites o remote from traffic, concentrations of about 0.0005 /ig/m are found (Waldron, H.A., 1979). Eskimo’s Pb-B levels were even higher than those of the Danish [Pb-B = 10.5 /ig/100ml for males and 7.7 /ig/100ml for females (Hansen, J.C. et al, 1983)]. Since the analytical method has been checked with regard to reproducibility as well as to accuracy, and that lead in drinking water could hardly be a source since it would influence Danes and Greenlanders equally, dietary intake would be likely to explain the difference. Greenlandish diet is characterized by being rich in protein, animal fat, zinc and iron, but low in calcium. Barton, J.C. et al (1978a) clearly demonstrated that iron decreases lead absorption because the two metals compete for similar binding sites on intestinal mucosal proteins, and the role of iron deficiency in increasing lead uptake has been demonstrated (Marcus, A. H. and Schwartz, J., 1987; Mahaffey, K.R., 1974). The iron content in Greenlandish food was found to be quite high, about 5 times higher than the accepted optimum intake (Hansen, J.C. et al ,1983). No reason could be found by the authors, and since there are one or two reports in the literature stating that blood lead increases with iron intake, they thought that this can possibly be the reason. 155 We have seen haemoglobin levels in the Nepalese population (Pb-B=3.4 /ig/100ml) averaging 16.1 g/lOOml in adult males, 15.1 g/lOOml in adult females and 15.1 g/lOOml in children (normal limit = 14.1 g/lOOml); these are values considered higher than those reported for most Western populations (Piomelli, S. et al, 1980). Since dietary intake of iron was slightly high, the high altitude effect cannot solely account for their high Hb levels, and excessive iron intake among Eskimos cannot be the cause of their high Pb-B levels. I shall try to make a detailed analysis of the diet and excretion patterns of the Eskimos. Generally, the arctic populations consume more protein, equal amounts of fats and less carbohydrates than Western populations. The high protein consumption has to do with the fact that meat — (from seals and whales) and to a lesser degree from fish, char (small fish of the salmon tribe) and game animals (caribou — is the predominant nutriment of this population (Bang, H.O. et al, 1976), and each subject was estimated to consume about 400 gms of seal and/or whale meat a day. It was seen that whale and seal meat was eaten every day, and the population is traditionally occupied mainly with sealing, whaling, fowling and to a lesser degree fishing and hunting. The average daily consumption per capita in the settlement was 134g bread, biscuits and rye flour, 31g rice, 42g potatoes and 164g sugar. Sugar was used abundantly, about 5 times a day, mostly in coffee or tea. Sugar in tea or coffee was the only form, of sucrose, and the small amounts of milk used with tea and coffee would provide a little calcium. Energy intake amounted to 2832 Kcal, 37% of the calories were found to originate from carbohydrates. The traditional diet could be supplemented by Danish Foods (Kromann, K. and Green, A., 1980). Its interesting that the fat intake of Eskimos was found to be similar to that of Danes, or even lower, although the internal parts of the seals and whales, namely the blubber and intestines, parts of which were eaten (Bang, H.O. et al, 1976). Seals are fish-eating mammals which appear to ingest vitamin D at levels that are toxic to 156 most mammals, however, they do not appear to suffer from vit. D toxicity even though their principal food, fish, is the highest known natural source of the vitamin (Keiver, K.M. et al, 1988). Fatty tissues accumulate a higher concentration of vit.D than nonfatty tissues and the blubber therefore would be expected to contain the highest proportion^which is why seals have a large capacity for storage of vit.D and/or its metabolites in their blubber mass. The large amount of adipose tissue in seals and its high lipid content may enable seals to accumulate more vitamin D than other mammals, thereby lowering plasma levels of vit D and its metabolite 25-OHD (25, hydroxycholecalciferol); thus reducing the half-life of plasma vit.D (Keiver, K.M. et al, 1988). It is estimated that human beings need about 400 international units/day, and the daily human requirement is about 0.01 mg. Food can contain as little as 0.02 ppm of vit. D and yet furnish an ample supply on the basis of the above estimate (Williams, R.J. and Lansford, E.M., 1967). Daily intake of vit.D in the seal was estimated at approximately 400,000 IU/day. If a little is good, more is better is not the case with vit.D even if food is obtainable at low cost. Absorbed vit. Dg [human beings respond to both vit.D 2(calciferol) and vit.Dg] is taken up mainly by the liver and excreted into bile. The passage of vit.D and its metabolites through the bile and hence into the intestine represents an obligatory stage for the enterohepatic circulation and faecal excretion of vit.D by man (Avioli, L.V. et al, 1967). Biliary obstruction among the Eskimos is certain to happen. Reports of an increased bleeding tendency in Eskimos were confirmed and results have indicated that this antithrombotic tendency is the result of substantially decreased platelet aggregation (Dyerberg, J. and Bang, H.O., 1979). A deficiency of vit.K, the fundamental importance of which in the blood-clotting process is well established, is hard to demonstrate in healthy people since vitamins of the k 2-series are formed by bacteria, notably those in the intestine. However, biliary obstruction or other condition where decreased intestinal absorption of lipids exists can give rise to vit.K deficiency (Conn, E.E. and Stumpf, P.K., 1976). 157 The blood clotting factors are all produced in the liver, and hence a deficiency in these factors occurs in liver disease. Vit.K deficiency is found in patients with intestinal malabsorption and in liver disease where there is biliary obstruction or fistula, since bile salts are required for Vit.K absorption (Hughes-Jones, N.C., 1984). Low death rates from coronary heart disease is well documented among Eskimos (Kromhout, D. et al, 1985). Intestinal malabsorption associated with biliary obstruction and steatorrhea may also play an essential role in the reported instances of bone disease complicating hepatic dysfunction (Avioli, L.V. et al, 1967). Prevalence of sucrose malabsorption in Eskimos, as well as early bone loss has been reported (Ellestad-Sayed, J.J. et al, 1978). Food in Greenland often causes retrosternal pains and ructus (Kromann, N. and Green, A., 1980). The intestinal absorption of lead in rats and chicks, like that of calcium, was shown to be stimulated by cholecalciferol; and associated with the cholecalciferol response is the induction of the Vit.D-induced calcium-binding protein (CaBP) (Edelstein, S. et al, 1984). In rats fed low calcium diet containing cholecalciferol, the synthesis of CaBP was increased, and the efficiency of absorption of both calcium and lead was increased (Edelstein, S. et al, 1984), and increased duodenal absorption of lead in response to increasing doses of Vit.D reflects biliary obstruction. It is in the duodenum where the bile mixes with the food and assists in the digestion of fats (Spencer, M. and Tait, K.M., 1970). The high protein, low carbohydrate diet of Eskimos also causes a strain on the kidney by overloading it, thus decreasing the efficiency of renal clearance of lead in the urine. The protein nitrogen is converted to urea nitrogen, and the blood urea nitrogen (BUN) - an end product of metabolism-rises, thus increasing the filtered load of urea. Soon, the high concentration of urea in the tubular fluid reaches osmotic pressures beyond which point the kidney can no longer reabsorb water as an osmotic diuresis results. There is no evidence 158 that high protein diets cause renal disease or impair renal function, except when there is associated water deprivation (Dougherty, J.C., 1973). Although few Eskimos drank soft drinks (Ellestad-Sayed, J.J. et al, 1978), beer and hard liquor were reported to be consumed (Hansen, J.C. et al, 1983) and the likely effect of renal insufficiency is expected to be minimal. 159 6.12 Bili SLry Excretion of Lead and the Protective Effects of Glutathione Pharmacokinetic models describing the disposition of lead in the rat have shown that at low lead doses, a large percentage of the dose was excreted through the bile, however as the dose increased, the biliary excretion mechanism became saturated, resulting in a back flux of lead into the liver and therefore lead gets distributed through the plasma into the bones where it subsequently accumulates; whereas at high lead doses the hepatic binding mechanism becomes saturated (Bornemann, L.D. and Colburn, W. A., 1985). Although the liver has an active transport mechanism for the excretion of metals against an apparent concentration gradient, it seems that body mechanisms for excreting lead are limited, otherwise increasing body lead concentrations would not be observed with aging and chronic lead poisoning would not occur. At low doses, a large percentage of the dose was bound in the liver, however as the dose increased and the binding sites became filled, a smaller percentage of the dose remained in the liver and the free lead shifted either into the bile or back into the plasma (Bornemann, L.D. and Colburn, W.A., 1985). Excretion of lead directly by passage through the intestinal walls of rats seems to be of much less importance, although the authors concluded that lead may not only appear in the gastrointestinal tract from bile (Castellino, N. et al, 1966). Biliary excretion in sheep accounted for the larger part excreted, and is the most important channel for lead excretion (Blaxter, K.L. and Cowie, A.T., 1946). One interesting observation made was that the normal bile volume of 450-500 ml per day increased to more than 950 ml following injection of 150 mg of lead as the acetate in normal saline into the bile. Lead toxicity has been shown to increase liver, kidney and erythrocyte GSH (reduced glutathione) levels in rats (McGowan, C. and Donaldson, W.E., 1987). The liver is an important site of GSH synthesis ( 7-L- glutamyl-L-cysteinylglycine- a tripeptide, cysteine being the rate-limiting amino acid-). Metal ions may regulate GSH possibly by increasing its rate of synthesis (Maines, M.D. and Kappas, A., 1977). The mobilization of GSH from organs such as the liver and skeletal 160 muscle and its degradation to component amino acids by the kidney provide an immediate source of amino acids for GSH resynthesis by the liver. This mechanism facilitates enhanced GSH turnover and is of paramount importance during exposure to toxicants where changes in organ GSH concentration occur such as with lead intoxication. The inhibition of enzymes by lead may be explained by the affinity of lead for essential sulphydryl groups (-SH) possessed by them (De Bruin, A., 1971). The antagonistic effect of SH agents on the regulatory actions of metals on cellular haem has been demonstrated; if the endogenous content of SH groups is increased by the oral agents such as cysteine before the injection of metals, the actions of metals on haem pathway enzymes (such as 6-ALA-D) are blocked (Maines, M.D. and Kappas, A., 1977). L-Cysteine as a thiol chelator of lead has been tested for efficacy to enhance urinary excretion of lead in rats; it was found ineffective compared to other chelators namely: D-Penicillamine (DPA), Diethyldithiocarbamate sodium (DDC), and amino chelators ethylenediaminetetraacetic acid (EDTA), Cyclohexylene diaminetetraacetic acid (CDTA) and Diethylenetriaminepentaacetic acid (DTA). However, it was found to raise the activity of blood 6-ALA-D (Tandon, S.K. et al, 1985). DDC is a potent metal chelator and is also used in nickel poisoning, the mitochondrion being the primary site of DDC-induced ultrastructural injury. The mechanism of DDC toxicity to rat cerebral astrocytes in culture involves a marked increase in the copper(Cu) content of these cells. Furthermore, exposure to DDC (35 /xg/ml for 1 hr) results in a 40% decrease in the activity of the selenoenzyme glutathione peroxidase (GSH-Px) (Trombetta, L.D. et al, 1988). The authors investigated the role of GSH, a major physiological reducing agent found in cytosol, mitochondria, plasma and bile, as a cellular antioxidant defense system in preventing or ameliorating DDC-induced injury. Post-treatment with lOmM (millimoles) GSH protected the cells from the lethal effects of DDC on cell function or at least stabilized function to the point at which repair could be initiated; the end product of this injury was observed as accumulation of lysosomal degradation products, particularly residual bodies. It has also restored both GSH-Px activity and Cu content to control levels within 24 hours. It has been shown that electrophilic redicals derived from endogenous or xenobiotic compounds can act as initiators in the chain of events which leads to the formation of such structures (residual bodies). This usually involves the attack of a toxic compound on the polyunsaturated fatty acids in the cellular membranes with consequent peroxidation of membrane lipids and loss of integrity. In fact, GSH conjugates with a variety of electrophilic toxic metabolites, rendering them harmless. It cannot enter hepatocytes, so precursors such as cysteine or methionine must be given; methionine and N-acetyl cysteine are used successfully in preventing paracetamol-induced liver necrosis (Sherlock, S., 1982) and interest in the hepatoprotective properties of cysteine, methionine and antithyroid drugs is rising tremendously. Increased cellular copper has been suggested to enhance lipid peroxidation; Cu can oxidize essential thiol groups affecting an imbalance in the cellular redox system (Trombetta, L.D. et al, 1988). Supplementary dietary copper as investigated in young male rats does not lessen the severity of lead toxicity but rather exaggerates it (Cerklewski, F.L. and Forbes, R.M., 1977). The effects of zinc supplementation on the copper status of healthy adult men suggsted that zinc supplements decreased the copper status of the experimental group, thus the antagonistic ffect of zinc on copper absorption was demonstrated (Fischer, P.W.F. et al, 1984). Copper is an essential element and is required in very small concentrations, unlike iron and zinc which are required in relatively high concentrations (Mertz, W., 1981). Lockett, C.J. and Arbuckle, D. (1987) stated that lead-induced anaemia may be prevented in rats by the administration of copper without quoting any level of concentration or source of reference. It was quoted that copper stimulates ferrochelatase activity and reverses the inhibition of 162 solubilized mitochondrial preparations of this enzyme produced by lead. The substitution of cystine for alanine (when 2 molecules of cysteine are oxidized, cystine is formed having an -S-S-linkage) in the low protein diet of lead-treated rats resulted in a drastic reduction of blood lead and liver and spleen, yet kidney lead and bone lead showed no significant decrease (Mylroie, A.A. et al, 1977). Accordingly, cystine prevented the accumulation of lead in blood and to a certain extent in the liver and spleen. Pretreatment of rats with cysteine prevented changes in the content of cytochrome P-450, and the results suggested that cysteine, a glutathione precursor, has a protective effect on chemical-induced liver injury produced by hepatotoxins such as CC(Tanaka, E. et al, 1984). Since hepatotoxic compounds consume and deplete glutathione by conjugation during their metabolic activation, the protective role of cysteine is probably by decreasing the rate of glutathione depletion. It is generally accepted that glutathione plays an important role in the body to protect from electrophilic attack by alkylating metabolites of drugs, and the degree of lipid peroxidation from CC£^ appears to have been markedly reduced by the presence of 10— cysteine (Tanaka, E. et al, 1984). Glutathione is now known to be involved in the incorporation of Fe by protoporphyrin (Albahary, C., 1972). A major factor in hepatic glutathione (GSH) homeostasis appears to be efflux of GSH from the liver into both bile and plasma (Stelzer, K.J. and Klaassen, C.D., 1985). The excretion of reduced GSH in bile was directly proportional to the hepatic reduced GSH concentration; approximately 20% of hepatic reduced GSH is exported into both blood and bile per hour in rats and thus a direct relationship between the degree of depletion of hepatic reduced GSH and the diminution of its output in bile exists (Kaplowitz, N. et al, 1983). Cobalt and Nickel cause an initial decrease of hepatic cellular content of GSH (in 6 hours) which is subsequently followed by an increase of 200 to 300 per cent above 163 normal (Maines, M.D. and Kappas, A., 1977). Accordingly, there is a great likelihood that reduced glutathione (GSH) could be a carrier for lead in bile, since also biliary calculi were found to contain lead (Blaxter, K.L. and Cowie., A.T., 1946). 164 6.13 High Blood-Lead Levels Signal Slow Excretion Mechanism That high blood lead levels do not necessarily reflect absorption but also signal slow excretion mechanism is not only exemplified by the Greenlanders, but also by individuals with glucose- 6-phosphate dehydrogenase enzyme erythrocyte deficiency. The former being associated with dietary factors, while the latter is associated with physiological and biochemical factors. Children with glucose-6-phosphate dehydrogenase (G-6-P.D.) deficiency were found to have higher blood lead levels than normal children under the same conditions of environmental exposure to lead, the effect being independent of geographical location (Mclntire, M.S. and Angle, C.R., 1972). All the children were black. Deficiency of this enzyme in red blood cells renders them particularly suspectible in vivo to haemolysis following the administration of various drugs such as : primaquine, furadantine, para-aminosalicylic acid, sulfanilamide and sulfapyridrine (Ramot, B. et al, 1959b), naphthalene and the ingestion of fava beans (Marks, P.A. and Gross, R.T., 1959). The incidence of this hereditary defect in erythrocytes varies considerably among different population groups. Thus, it is relatively common among Negroes, Caucasians of Italian, Greek and non-Ashkenazic (Eastern “oriental”) Jewish extraction (Marks, P.A. and Gross, R.T., 1959). Oriental Jewish extraction includes : sephardic Jews i.e. Spanish, Portugese, Moroccan, Turkish, Iraqi and other groups (Szeinberg, A. et al, 1958). On the other hand, the incidence of G-6-P.D. deficiency is low among subjects of Chinese and Japanese descent and is particularly rare among Ashkenazy Jews (Western) and certain other Western Europeans. It has been estimated that there may be as many as a hundred million people in the world who have diminished red cell concentrations of G-6-P.D.; the defective gene is present on the X chromosome, and thus the deficiency is mainly seen in males (XY where X is the abnormal chromosome) (Hughes-Jones, N.C., 1984). Low concentrations of G-6-PD results in a low concentration of the reducing compounds NADPH (reduced nicotinamide- \ adenine dinucleotide phosphate) and GSH; the purpose of these compounds is to maintain haemoglobin and other proteins in the reduced and active form (Hugh-Jones, N.C., 1984). The red cell requires a continuous supply of energy for the maintenance of surface structure, the sodium and potassium pumps and the maintenance of Hb in the reduced ferrous form. The energy is obtained from glucose which is transformed to lactic acid mainly through the anaerobic Embden - Mayerhof pathway. There is an alternative aerobic pathway, the pentose-phosphate shunt, starting with glucose-6-phosphate and requiring G-6-PD as the initial enzyme. A schematic diagram of the pathway of glucose metabolism in the red cell is shown in fig.7 Of the 180 or so known varieties of G-6-PD, only two are common and account for over 95% of cases. The most common is the African (or A-) type, where G-6-PD levels are reduced to about 10% of normal; in the less common Mediterranean type, the level is reduced to 1-3% and the resultant haemolytic anaemia is more severe (Hughes-Jones, N.C., 1984). Slightly decreased levels of G-6-PD were found in livers of affected individuals (Ramot, B. et al, 1959a) and Beutler, E. et al (1957) demonstrated that there is a relation between the drop in GSH and the appearance of haemolysis in vivo. Roels, H.A. et al (1975) have shown that there exists a significant negative correlation between GSH and log Pb-B in an epidemiological survey of 84 men employed in a Belgian lead producing plant, in which a control group of 26 persons have also been examined. Recent observations have demonstrated that GSH appears to be an intrinsic protector against the toxicity of heavy metals, playing an important role in the protection of red blood cells and preserving their integrity (Ochi, T. et al, 1988). The fact that G-6-PD present in mature erythrocytes catalyzes reactions providing a mechanism for glucose oxidation to C 09, with generation of NADPH and GSH, suggests its particular importance in the metabolic process of erythrocytes (Marks, P.A., 1958). The activity of this enzyme declines in the erythrocyte as a 166 function of age, even in deficient erythrocytes the younger red cell population has a higher enzyme level than the older cells (Ramot, B. et al, 1959a). Some investigators have found G-6-PD activity to be normal in the leucocytes of affected individuals (Marks, P.A. and Gross, R.T., 1959),while others have found it to be significantly lower than normal (Ramot, B., et al 1959b). People with low levels of G-6-PD in erythrocytes are thus poorly protected against drugs which are oxidants. When oxidants enter the red cell they first convert haemoglobin to methaemoglobin and finally denature it so that it precipitates in the red cell and can be demonstrated as Heinz bodies; and the formation of Heinz bodies can be used as a screening test for the presence of low concentrations of the enzyme in red cells (Hughes-Jones, N.C., 1984). The lack of haemoglobin in platelets might be related to their immunity to the damaging effect of drugs, or could be related to the short survival time of platelets in general and the great capacity of the marrow to compensate for the peripheral destruction (Ramot, B. et al, 1959a). An explanation of this finding is that a cell population with a low mean age, characteristic of platelets and leucocytes, has a higher enzyme activity than cells with a high mean age such as erythrocytes (Ramot, B. et al, 1959b). It is noteworthy that erythrocytes and platelets are non-nucleated cells and presumably unable to synthesize proteins (GSN is a tripeptide) thus could not compensate for an increased enzyme turnover, while the liver and leucocytes do have such a synthetic potential. Although synthesis in vitro of GSH in rat erythrocytes has been reported, the results of Hochberg, A. et al (1964) did not prove or disprove the ability of human erythrocytes to synthesize GSH in vitro, it has merely shown that the incorporation of glycine and glutamic acid into GSH of whole blood is concentration dependent. The finding by Szeinberg, A. et al (1958) that a connection exists between GSH instability to acetyl phenyl hydrazine drug in the erythrocytes of newborn (GSH being oxidized to GSSH in vivo) and their susceptibility to haemolysis by vitamin K substitutes in the newborn is of primary importance. There is an aspect of similarity between Greenlanders and subjects with erythrocytic G-6-PD 167 deficiency (i.e. low GSH levels) in that both are showing higher levels of body lead burden mainly due to reduced biliary excretion of lead probably via GSH. This is another illustration of the importance of excretion resulting in lower or higher Pb-B levels. The most recent and highly significant finding is that pretreatment of cultured Chinese hamster ovary cells with zinc has been shown to increase the level of cell GSH more than 3 times above the control values (Ochi, T. et al, 1988). Ochi, T. et al (1988) cited an unpublished observation that transport of cadmium into cells is known to be inhibited by the presence of zinc in cultured Chinese hamster ovary cells and also in Chinese hamster cells. The cytotoxicity of cadmium was markedly suppressed in the cells pretreated with zinc and the suppressive effect was dependent upon the duration of zinc pretreatment (i.e. upon the degree of formation of metallothioneins (MTs)-both GSH and MTs are synthesized from a common substrate, cysteine). Like lead, cadmium is generally considered to interact with essential sulphydryl groups which are integrated in a variety of functional molecules by forming irreversible and stable bonds. Accordingly, depletion of GSH in the cells must increase the chance for cadmium to interact with sulphydryl groups and essential metal ions, resulting in dysfunction. If the transport of lead into red blood cells is also inhibited by zinc, then we have explained the extremely low blood lead levels encountered among the Japanese population. A variety of “mild” environmental challenges (viral diseases such as influenza, mild oxidizing agents and others could undoubtedly augment the GSSH level at the expense of GSH in a G- 6-PD- deficient cell to a great extent (Kosower, N. S. and Kosower, E.M., 1970). McKerns, K.W. (1964) presented evidence that the principal mechanism by which adrenocorticotropic hormone (ACTH) stimulates the function of the adrenal cortex is by activation of G- 6-PD. Prasada Rao, K.S. and Ramana Rao, K.V. (1987) have found that the glucose level decreased considerably with a significant elevation in G- 6-PD activity levels in muscle, gill and liver tissues during sublethal methyl parathion-exposed fish tissues. The decreased tissue glucose levels during methyl parathion (organophosphate insecticide) exposure signifies their utilization for energy requirements to face the toxic stress. Increased levels of G- 6-PD activity in the tissues indicate higher operation of the hexose monophosphate pathway (HMP) under methyl parathion exposure, possibly to generate NADPH and pentose sugars. The NADPH is required for fatty acid synthesis and also plays an important role in the detoxification of organophosphate insecticides (Prasada Rao, K.S. and Ramana Rao, K.V., 1987). Since reduced fatty acid synthesis was reported during pesticide exposure, it is evident that NADPH in this case was diverted for the detoxification of methyl parathion. Besides producing NADPH, G-6-PD activity also contributes to the formation of pentose sugars, which are needed for the synthesis of nucleic acids. The authors reported increases in DNA and RNA and soluble proteins. This is justifiable since the soluble protein fraction represents enzymes, hormones and free peptides, and this increase in tissue proteins should represent a detoxification mechanism. It can be inferred that G-6-PD has a significant role in mitigating toxic stress, and the biological system tries to maintain higher G- 6-PD activity levels, producing more NADPH and pentose sugars for synthetic and detoxification purposes as an adaptive response. The red cell membrane is an organized structure consisting of lipids and proteins. It has been suggested that phospholipids might function as binding substances for the proteins, and that any change in their composition might lead to an instability of the membrane, and that the possibility exists that a G- 6-PD deficient erythrocyte must consist of an alteration of the cellular membrane (Szeinberg, A. et al, 1965). If we accept these premises, then such alterations due to insufficient NADPH generation by HMP, might well result in a weakening of the membrane and an increase in its sensitivity to destruction by oxidants. 169 6.14 The Influence of Iron Deficiency on Lead Absorption A disturbing feature of the DOE study in Birmingham on blood lead levels of pre-school children (aged between 1 and 4 years) was that Pb-B levels in this group were most similar to those found in adult males (overall mean Pb-B = 20.1 /ig/100ml — DOE, 1978), 15 results out of 429 (3.5%) had Pb-B levels equal to or greater than 35 //g/100ml. Since no more than 2% of any group should have Pb-B levels over 35/^g/ 100ml according to the EEC reference levels (EEC, 1977), the reference level in this survey was breached. All but one of these children were of Asian Origin, and repeated blood samples confirmed the previous findings. This has stimulated further surveys on Asian children. There was nothing to suggest that the environments of these children differed markedly from other children in the survey who were non-Asians. The response for this ethnic group was almost certainly nutritional in nature since in no case was airborne lead considered to be a factor (Barltrop, D., 1979). Since it is known that a substantial number of Asian children in the city have radiological rickets, it was tempting to suppose that a relative deficiency of calcium in the diet was producing an enhanced uptake of lead from the gut (Waldron, H.A., 1979). It was thought initially that extensive contamination with lead-rich dust, derived from old painted surfaces, together with the habit of pica, seemed to be responsible (DOE, 1978). Another survey was undertaken which confirmed the previous impression that a relatively high proportion of preschool children living in the inner city areas of Birmingham have high Pb-B levels, and that this is particularly so for children of Asian origin (Archer, A. et al, 1980). Lead-rich dust and paint is not itself a sufficient reason, as neither constitutes a hazard unless absorbed. Since half the children in the “high lead” and a similar proportion in the “low-lead” group were finger-suckers, and they both were in comparable environments with respect to lead, the role of pica in increasing lead absorption was ruled out. The 170 Q contribution of lead in air is also small since an atmospheric lead concentration of 2 fjg/m o (long-term mean concentrations in Birmingham rarely exceed 2 fig/m ) would be unlikely to raise the blood lead level by more than 4 /ig/100ml (Chamberlain, A.C. et al, 1978). The most plausible explanation given was that its due to a nutritional deficiency of either calcium or iron, since a substantial number of children in Birmingham are found with iron deficiency anaemia (Archer, A. et al, 1980). Since there is some evidence that Asian children in Birmingham have poor nutrition, dietary intake assessments for both calcium and iron were made by means of a questionnaire administered to the parents (Box, V. et al, 1981). The group as a whole (2-5 years of age) was relatively iron deficient but calcium intake was close to recommended levels. These findings were also confirmed later. Blood lead concentrations 'equal to or greater than 35 /ig/100ml were found in 47 out of 319 preschool children in Birminoharn (i.e. 14.7%) and almost exclusively in children of Asian parents (DOE, 1982b). Asian children were relatively iron deficient and approximately 11% were anaemic. What is noteworthy is that the dietary lead intake for the children from whom a duplicate diet was available showed a mean level of 146 /xg/day (range of 26 to 512 //g/day) (DOE, 1982b). This is considered an excessive intake especially for a young child whose exposure to lead in air is negligible since he spends most of his time indoors. The most recent lead intake level is reported as 24 /ig/day with a maximum of 30 jig/day (Sherlock, J.C., 1987). Sherlock, J.C. (1987) thinks its appropriate to say that food is an important source of lead intake, but it would be wrong to continue to say that food is the major source! I totally disagree with this view particularly for a young child aged 2 to 5 years for the following reasons: 1. Absorption of lead in children could increase up to 50% (Alexander, F.W. et al, 1973) 171 2. Lead intake is highest among the youngest age group ( ~ 3 years old) (Mykkanen, H. et al, 1986) 3. Nutrients intake among children depends on the educational level, nutritional awareness of the mother and is associated with the social class of the family (Kaufmann, N.A. et al, 1982) 4. Inclusion of a wide variety of individual food items into the daily diet reduces the intake of single foods containing high amounts of toxic metals. However, this cannot be afforded by all social strata. 5. The immune system of children does not induce efficient removal of lead from the body via excretion. Barltrop, D. (1979) pointed out that increased blood lead values may reflect variables such as place of residence or social disadvantage, and that factors other than atmospheric lead levels are of relatively greater importance in determining population Pb-B levels. London Brent Council has undertaken a comprehensive lead screening programme of the school children in the borough (Taylor, A., 1985). An observation which was not anticipated was the high proportion of Asian children who had increased concentrations of blood-lead (80% of all high blood lead results), particularly those under 7 yars of age. The pattern of iron deficiency was also observed in the Brent children with a relatively high incidence in the very young who are rapidly growing and may be fed with a limited range of foods. Since direct questioning of the families in Brent failed to produce evidence of widespread use of cosmetics or medicines, it is suspected that the traditional diets of Asian families might be expected to predispose towards iron deficiency. Although surveys in the United States have shown that Pb-B levels for black children are greater than those for Hispanics and whites (Billick, I. H. et al, 1979), their situation merely reflects the separate and distinct environmental conditions of the two groups. Such an explanation is not valid for the results 172 in Brent since the Indian families do not occupy discrete neighbourhoods to the exclusion of other groups and within the borough there are several identifiable communities (e.g. Irish, West Indian) who share the same housing and environmental features but were not “high lead” groups (Taylor, A. , 1985). We can infer the importance of iron deficiency from another observation in Brent results. The incidence of increased zinc proto-porphyrin (ZPP) levels in blood (the method used in this survey being capillary blood analysis, 4.6 fig ZPP/gHb taken as the upper limit) was age- associated. Those less than 7 years or greater than 16 years old were most likely to have high values, and two-thirds of the children with high ZPP were girls, this being particularly pronounced among the teenagers at secondary schools (Taylor, A., 1985). The conclusion of the recent DHSS study (1986) was that some children, especially girls, had low intakes of iron, calcium and riboflavin (Wenlock, R.W. et al, 1986). British studies of late adolescence revealed a tendency for low intakes of iron, thiamine and riboflavin (Benton, D. and Roberts, G., 1988). Adebonojo, F.O. (1974) found that in 14 to 18 years old urban black children, anaemia was twice as prevalent in girls as in boys in the United States. Concern about the vegetarian status of Asian people in Britain has been expressed; their food intake has been shown to be below DHSS recommendations in terms of energy, protein, iron and vitamin D (Rona, R.J. et al, 1987). Most severe deficiencies are seen among Hindu families; the percentage of vegetarians was very low in the Caucasian and Afro-Ca ribean children. It was also found that a lower education level was attained by mothers in the vegetarian groups than in the non-vegetarian groups. The fact that a child is encouraged to wash his or her hands before eating may be an indication of parental awareness of the need for cleanliness. Even if only a fraction of the lead from a child’s hands was transferred to the mouth either directly or via food, it could make a substantial contribution to lead intake (of about 20 fig - Sherlock, J.C. et al, 1985). Sherlock, J.C. et al (1985) found that Caucasian children had slightly higher Pb-B levels than Asian children (GM=9.7 /ig/100ml vs 8.1 /ig/100ml) in a 173 London borough which was not specified where 3 study groups, each numbering about 35 children were examined (age range 2.5-5 years). The three study groups were Caucasion, Asian vegetarian and Asian non-vegetarian. It was thought by the authors that lead intakes tended to be greater in the Caucasian group because the Caucasians consumed more food and drink than did the Asians. However, the Asian children had about one-half the plasma 25- OH vitamin D metabolite concentration of the Caucasian children. The Brent lead survey examined 25, 427 children aged 1-18 years far outnumbering the small survey of 105 children aged 2.5 -5 years by Sherlock, J.C., et al (1985). In a study of the incidence of rickets in London (Paterson, D. and Darby, R., 1926), the relationship between poverty and rickets was not confirmed since a high percentage of the infants of the poor were found to be receiving cod-liver oil. Skin pigmentation can reduce vitamin D formation (Clements, M.R. et al, 1987), and whether sweating varies between different races is not clear to me. Some black people use certain oils on their skin probably to soften it, and if this is done regularly, the pores of the skin could be clogged, thus hampering the flow of sweat with which lead is removed from the body. A characteristic sweat odour of some black people is often reported, which could be due to sebaceous glands or sweat glands and associated with skin pigmentation. In^case thefcoloured people sweat less, then they are likely to have slightly higher blood lead levels. It has been suggested that Negroes are more sensitive to salt than other groups, and differences in electrolyte intake and inherent responses are likely to be implicated (Simmons, D., 1983). For reasons that are not known, black men and women have greater bone mass than do Caucasians (Culliton, B.J., 1987); this could also favour accumulation of lead in their bodies. Thus, differences in racial groups are not resected to blood lead levels, but many other variants such as blood pressure, weight, obesity, osteoporosis and Vulnerability to cardiovascular disease have all been found different, due to both dietary and genetic factors. 174 Adebonojo, F.O. (1974) surveyed 1559 urban black children in the United States aged 6 months to 18 years for blood lead and haematological parameters. Two peaks of mean blood lead levels were identified. One peak (29.1 /ig/100ml) was found in the one-to-three year olds, and a second peak (28.1 /zg/100ml) in the six year olds. That blood lead levels were age-associated is in agreement with the Brent study, although black children from the United States appear to have higher levels than those in the United Kingdom including Asians. The main observation was that children who were anaemic (anaemic childen in their study have nutritional anaemia not due to metabolic disorders) tended to have higher blood lead values, on the average, than non-anaemic children. Hungry children are much more likely to be engaged in hand-to-mouth explorations and pica. Nutritional anaemia is one of the most widespread of all health problems, and the high frequency of nutritional anaemia among the urban and rural poor children is widely reported. Mackay, H., M. M. (1928) documented the impressive prevalence of nutritional anaemia 60 years ago among the poor children of London’s East End. Fullerton, H. W., et al (1944) found a high incidence of nutritional anaemia in the poor children of Aberdeen, Scotland. In other parts of the world the picture is the same. It is in the young children aged few months to 3 years that all the nutritional disadvantages of poverty are most striking, largely because their rate of growth is more rapid. It was found that Day Care children removed from their environment during the working hours and provided with nutritious meals at the Day Care Centre had significantly lower blood lead levels and higher haemoglobin values than those in a matched non-Day Care Control group (Adebonojo, F.O. and Strahs, S., 1974). The mean level of blood lead for 22 Day Care children was 18.9 /ig/100ml, while that for 15 non-Day Care Controls was 32 /zg/100ml; and the mean level for 134 other community children of the same age was 28.7 fig/ 100ml. Improved nutrition from balanced meals accounted for the reduction of Pb-B levels. The Day 175 Care children normally had higher daily intake of iron than the non-Day Care childen (0.7 mg vs 0.5 mg), although neither group was receiving the minimum recommended daily intake of lmg/kg/day for childen (Adebonojo, F.O. and Strahs, S., 1973). Mean daily caloric intake proved to be higher, mean red blood cell count value was higher (5.30x10° vs 4.87x10®) and red cell size was larger (MCV=72.6/i^ vs 67.0//*). Landrigan, P.J. et al (1976) evaluated the prevalence of lead absorption among children living near a lead smelter in the United States. Increased lead absorption was found in 99% of 1 to 9 years old children living within 1.6 kilometres of the Idaho smelter (>40/zg/100ml). However the authors inferred that inhalation alone could not account for the disproportionate elevations in lead levels since it was consistently seen among the younger and poorer children. In all areas with different distances from the smelters, lead levels were higher in 1 to 4 years old than in children 5 to 9 years old. Significantly higher Pb-B levels were found in children from the lower socioeconomic strata. Thus nutritional anaemia is a problem to be found in the poor predominantly young children. Margo, G. et al(1977) found that iron deficiency anaemia is common in 1 year old children (23%) as well as a biochemical deficiency of iron (53%). Iron-deficient children may absorb more lead than do iron-replete children, manifest a higher level of blood lead in plasma and hence in peripheral tissues, and also exhibit greater toxic reponse for a given blood lead concentration (Marcus, A.H. and Schwartz, J., 1987). Anaemia saps the energy of children, leaving many pasty-faced and listless. 176 6.15 Enhancement of Lead Absorption by Low Dietary Calcium Awareness of the metabolic relations between calcium and lead is not new. It was customary in Great Britain, and to a less extent in other countries, to provide workers in lead industries with free milk while working (Hunter, D., 1975). Results of exposing leaded erythrocytes to calcium in vitro indicated that post-treatment with calcium reduces the lead content of red cells (Ong, C.N. and Lee, W.R., 1980b). This observation suggests that calcium may influence the transportation of lead from cell to plasma, and that the concentraton of calcium in plasma or extracellular fluid may influence the activity of lead. Since the distribution patterns of the two nuclides 203Pb and 45Ca on erythrocyte membranes were similar (over 88% protein bound, less than 10% lipid bound and traces in the aqueous phase), a possible implication of this finding is that lead and calcium may compete for the same binding sites on the erythrocyte, seeming mostly bound to carboxyl groups (-COOH), whereas the-SH groups had a minor role in binding these cations (Ong, C.N. and Lee, W.R., 1980b). Sorrel, M. et al (1976) showed that children with a blood lead level greater than 60 /ig/100ml had a lower mean daily iii^ke of calcium and vitamin D than those with a normal range of blood lead. Other sites for interaction include competition for absorption in the gastrointestinal tract or excretion by the kidney or competition for storage sites in bone (Mahaffey, K.R., 1974). Low dietary calcium activates osteocytes and mobilizes bone lead (Hsu, F.S. et al, 1973). Aungst, B.J. and Fung, H.L. (1985) found that calcium-deficient rats apparently cleared blood lead at a rate nearly 40% slower than control rats, and that the systemic availability of orally administered lead was increased in rats on a low-calcium diet. Clearly the biggest difference between the two diets was the calcium content. Barton, J.C. et al (1978b) demonstrated earlier that the major effect of low dietary calcium is on lead retention, probably by reducing lead excretion and not by increasing gastrointestinal absorption, although the reduced rate of lead elimination was not quantified,. The exact mechanism by which calcium influences the metabolism of lead is till now not known (Ong, 177 C.N. and Lee, W.R., 1980b), and the nature of the interaction has been speculative because the effects of dietary calcium on the kinetics of lead disposition have not been adequately described (Aungst, B.J. and Fung, H.L., 1985). The mechanisms and control of excretion of lead by the kidney are not well understood (Goyer, R.A., 1978). In the course of transtubular flow of lead (being an important mode of excretion), a portion of the lead enters the nucleus, where it becomes bound into a lead-protein complex and is no longer diffusible, with the effect of maintaining a relatively low cytoplasmic concentration (Goyer, R.A., 1971). The lead-protein complexes or inclusion bodies in nuclei of proximal renal tubular lining cells occurring in persons with increased body burden of lead may influence the excretion of lead by retaining it in a non-diffusible form. Sequestration of lead into such bodies in the nuclei of kidney cells may have a protective value and can be a result of the tissue’s own effort to overcome lead toxicity (Katti, S.R. and Sathyanesan, A.G., 1987). Goyer, R.A. (1978) speculated that mobilization of lead to soft tissue, including the kidney, accompanied by increased metal-protein complex formation may, in fact, account in some degree for the increased retention of lead accompanying low dietary calcium. Excretion of lead in the urine reflects the recent absorption of lead (Grandjean, P., 1978), and in lead poisoning the increase in urinary lead is largely ligand or organic-bound lead (Goyer, R. A., 1971). Lead intoxication is known to enhance the urinary excretion of amino acids (Mykkanen, H.M. et al, 1982). The possible role of inclusion bodies in lead poisoning is that by providing the major site of intracellular binding, it is not free to diffuse within the cell in a soluble form, thus reducing the toxic effects of lead on sensitive cytoplasmic functions (McLachlin, J.R. et al, 1980). However the association of these inclusion bodies with dietary calcium intake remains highly 2-f speculative, although the energy-dependent uptake of Pb by mitochondria shares many of o_L the characteristics of the Ca accumulation reaction. The transient increase in the 178 cytoplasmic concentration of Ca 2+ which precedes the hormonal or electrical activation of 2+ calcium-mediated cell function is a result of the mobilization of Ca from intracellular stores, for example, mitochondria, or a change in the permeability of the plasma membrane to Ca 2+ (Pounds, J. G. and Mittelstaedt, R.A., 1982). For the most part, lead and calcium are associated with mitochondria; mitochondria in normoblasts being the site of haem synthesis (Hughes-Jones, N.C., 1984). The transient increase in cytosolic concentrations of free Ca permits the involvement of this ion in many biochemical and physiological phenomena such as cellular calcium metabolism, carbohydrate metabolism, amino acid transport, neurotransmitter release and other functions (Pounds, J.G. and Mittelstaedt, R.A., 1982). Aungst, B.J. and Fung, H. L. (1985) found that excess calcium (supplementary calcium) reduced blood lead clearance by approximately 25%. Since lead has many effects that are entirely unlike those of calcium, such as the inhibition of mitochondrial enzymes ( 6- ALA-D), the interactions between calcium and lead must play a part in explaining the toxicology of lead, but do not tell the whole story (Simons, T. J. B., 1986b). Van Barneveld, A. A. and Van den Hamer, C.J.A. (1985) gave supporting evidence from their experiments on rats that in soft water regions, the uptake of lead from drinking water could be increased because of the absence of calcium in the drinking water, particularly when dietary intake is low. The best source of calcium seems to be dairy products where its bioavailability is certain. Whether calcium is as bioavailable from green vegetables is not clear; calcium is not readily available from spinach (Culliton, B.J., 1987). Mahaffey, K.R. (1974) has pointed out that 5% to 15% of preschool children studied in different nutritional surveys have calcium intakes of less than 200 mg/day, or one-fourth the recommended daily allowances for children 2 to 3 years old. Since calcium deficiency potentially can result in elevated lead accumulation, maintenance of adequate dietary calcium levels appears extremely important in minimizing susceptibility to lead toxicity. 179 The addition of milk to the diet of population groups with suspected low dietary calcium intake would be a practical measure helping to reduce the possibility of increased lead absorption (Blake, K. C. H. and Mann, M., 1983). 180 6.16 Effects of Malnutrition on Susceptibility to Lead Poisoning The effects of malnutrition during early development on later lead poisoning in rats has been studied by Wapnir, R.A. et al (1980). Renal function, as measured by amino nitrogen and glucose, but not phosphate excretion was impaired in previously malnourished experimental rats, as compared to initially well nourished animals exposed simultaneously to lead. This may be the consequence of an impaired absorption of carbohydrate and certain amino acids in addition to an associated disturbance of electrolyte fluxes across the small intestinal mucosa. If a period of nutrition deprivation and exposure to lead are concomitant, the relationship is clear. A period of poor nutrition early in life can still be a detrimental factor for renal function, even when the lead adverse effects occur during conditions of nutritional adequacy. Thus, dietary components may play a significant role in susceptibility to lead poisoning (Mahaffey, K.R., 1974; Wapnir, R.A. et al, 1980). Diet affects immunocompetence, and its therefore possible that dietary modifications might be used to stimulate the body’s defense mechanisms (Dickerson, J.W.T., 1986) and enhance excretion. Psychological/emotional factors promote anorexia and may disrupt nutritional homeostasis to a greater or lower degree which puts the person at nutritional risk. Reversal of undesirable metabolic and nutritional disruptions regarding lead effects largely depends on elimination or marked alleviation of biochemical abnormalities. Vitamin C has been shown to possess similar lead chelating properties as equimolar amounts of EDTA and their combination is more effective than either of them (Tandon, K. et al, 1986). Being an antioxidant, it helps in keeping iron in its reduced state, thus becoming available for incorporation into haem. Ascorbic acid promotes iron absorption from the diet by reducing the negative effect of certain ligands such as phytates and tannins present in the diet 181 (Hallberg, L. et al, 1986). Fifty four Indian preschool children were chosen with Hb<10 g/lOOml and a predominantly microcytic, hypochromic red cell morphology (typical of lead- induced anaemia) for a study on the effect of consuming ascorbic acid with major meals, lunch and dinner (Seshadri, S. et al, 1985). Purely vegetarian diets were randomly divided equally into an experimental and a control group. The experimental group received lOOmg ascorbic acid twice a day for a period of 60 days, while the control group received sugar placebos. Initially iron intake ws 76% of the RDA, whereas ascorbic acid was 27% of the RDA. Since diets were purely vegetarian, it provided only non-haem iron indicating that the availablity of iron from such diets is low. There was a significant improvement in red cell morphology of the experimental group. At the end of the trial, 70% of them showed normal red cell morphology, thus demonstrating that supplements of ascorbic acid significantly improved the haematologic status of anaemic children. Blood lead concentrations in lead-exposed workers correlated significantly with intake of both vitamins, ascorbic acid and thiamine (Ito, Y., 1987b). Significant depletion of ascorbic acid occurred in the adrenals of lead-treated rats (Chowdhury, A.R. 1986). Hallberg, L. et al (1986) recommends an amount of 50 mg ascorbic acid in each main meal for optimal effects, this would increase iron absorption several times. Foods rich in ascorbic acid are fresh vegetable salads, cauliflower and orange juice. Studies showed an enhancing effect of ascorbic acid on the absorption of iron with different meals from about 60 to about 160 per cent, the variation in the percentage increase in iron absorption by ascorbic acid was not related to the iron content of the meals. (Hallberg, L. et al., 1986). Since the role of ascorbic acid in iron absorption would be to counteract the effect of naturally occurring ligands in the diet (phytates, tannins) which compete with intestinal receptors for iron, a high intake of ascorbic acid for vegetarians and elderly people consuming high fibre 182 diet is a necessity. Large doses of vitamin C (lOg) have been claimed to prolong survival in patients with advanced cancer (Dickerson, J.W.T., 1986). It has been shown that vitamin C deficiency decreases the activity of hepatic microsomal drug metabolizing enzymes in guinea pigs (liver is the main detoxification organ) amd increases the toxicity of several chemicals such as strychnine (Kato, R., 1980). The concentration of haemoglobin in blacks was found to be 0.5 to lg/lOOml lower than that of income-matched whites in several areas in the United States (Dallman, P.R. et al, 1978). Higher haemoglobin concentrations in normal white compared to normal black children noted in the United States adds to the difficulty of applying occupational lead standards across ethnic groups. In blacks there was a larger proportion of subjects with a low MCV(Dallman, P.R. et al, 1978). The capacity of the erythrocyte to serve as a reservoir for lead increases with improved iron status; this was a hypothesis recently suggested for experimental investigation (Marcus, A.H. and .Schwartz, J., 1987). When erythrocyte lead burdens approach that capacity there is a striking increase in the plasma lead concentration, with consequent large increases in erythrocyte protoporphyrin (EP). Iron inhibits erythrocyte uptake of lead, and lead competes for intracellular iron-binding sites, so it may limit intracellular accumulation of iron. Mean ferritin level among 120 black lead workers in a lead factory in South Africa monitored for 6 months was 196 figfi (Pb-B=61.8 /ig/100ml), that for black controls was 413 fxg/i (Pb-B = 19.8 /ig/100ml), while white controls showed a level of 152 pgfl (Pb-B=29.45 /ig/100ml). (Lockett, C.J. and Arbuckle, D., 1987). Ferritin is an iron-protein complex containing up to 23% of iron, formed in the intestinal mucosa and acts as an intermediary in the absorption of iron from the digestive tract. Apparently, as the level of lead increases, ferritin level decreases which might contribute to lead-induced anaemia cases. 183 This form of iron (ferritin) increases or decreases together with changes in the total body stores. Each 1 ngfi of ferritin in the plasma indicates that there are about 10 mg of stored iron; it has been shown that there is a direct relationship between serum ferritin levels and the amount of iron stored in the marrow (Hughes-Jones, N, C., 1984). Pyridoxine (Vitamin Bg) participates in the catalysis of the initial step of haemoglobin synthesis, aminolaevulinic acid synthetase being the enzyme which requires pyridoxal phosphate as a coenzyme. (Albahary, C., 1972). Pyridoxine deficiency could impair cadmium transport by the red blood cell or impair cadmium binding to Hb by interfering with the formation of the haem moiety; thus might affect not only the cadmium content of Hb, but also of other tissue substances such as myoglobin (Stowe, H.D. et al, 1974). Glycine Succinyl Co-A(active succinate) (Albahary, C., 1972, see fig. 6) ALA Synthetase + Pyridoxal Phosphate and Pantothenic acid V Delta Aminolaevulinic acid ALA-synthetase appears to be unaffected in lead poisoning, and there are indications that it is not inhibited by lead (De Bruin, A., 1971); thus no investigations have been carried out regarding the effect of pyridoxine on body lead burden. Pyridoxine is converted biologically (in the liver) into pyridoxal and pyridoxamine which are then phosphorylated to produce the coenzyme forms of the vitamin pyridoxal and pyridoxamine phosphate. Approximately 90% of pyridoxine administered to man is rapidly converted to 4—pyridoxic acid and excreted as such (Conn, E.E. and Stumpf, P.K. 1976). Pyridoxal phosphate is a cofactor for transamination reactions whereby an amino group (N ^ -) is transferred from an amino acid to an or-Keto acid thus forming a new amino acid and a new a-Keto acid: 184 NH9 H H 0 I I I II HOOC-CH2CH2CH-COOH HOOC-C-C-C-COOH (Glutamic acid) H H (a-Ketoglutaric acid) + q RYridoxal || Phosphate > + H3C-C-COOH NH9 (Pyruvic acid) I CH3-CH-COOH (Alanine) (Williams, R.S. and Lansford, E.M., 1967) Transamination reactions are important for the synthesis of amino acids from non-protein metabolites and for the degradation of amino acids for energy production. Pyridoxal phosphate is intimately involved in amino acid metabolism, and the dietary requirement for vitamin Bg increases as the protein content increases (Williams, R.S. and Lansford, E.M. 1967). The liver is generally considered to be one of the principal organs involved in protein synthesis (McConnell, K.P. and Roth, D.M., 1962), the main organ of detoxification (Maines, M.D. and Kappas, A., 1977) and a main depository for binding lead (Bornemann, L.D. and Colburn, W.A., 1985). This suggests some sort of unknown interaction between lead and vitamin Bg. Cereal grains are especially rich sources of the vitamin (Conn, E. and Stumpf, P.K., 1976). Lead anaemia has many of the features of sideroblastic anaemia, for example hypochromia, impaired maturation and defective haemoglobinization of red cells, raised serum iron, and erythroblasts containing iron-staining inclusion bodies (sideroblasts), and thus is classified as sideroblastic anaemia (Waldron, H.A., 1966) The chief site of the production of haemoglobin is in the erythroblasts in the bone marrow, 185 and the anaemia associated with the absorption of lead is induced primarily by the impairment of this biosynthesis (De Bruin, A., 1971). There is much evidence to associate a deficiency or abnormal metabolism of pyridoxine with sideroblastic anaemia; 50% of all patients with sideroblastic anaemia have low levels of pyridoxal phosphate and a similar number show disturbances in pyridoxine metabolism (Hardistry, R.M. and Weatherall, D.J., 1974). The effect of thyroxine seems to be reversed by increasing the dietary level of vitamin Bg, and it was suggested that thyroxine reduces coenzyme binding rendering the apoenzyme (the protein fraction) more susceptible to degradation (Szepesi, B. and Freedland, R.A., 1969). The rate of metabolism in the body is controlled by the secretion of the thyroid gland, thyroxine; while the parathyroid hormone controls the use of calcium in the body (Spencer, M. and Tait, K.M., 1970). Lead may affect the endocrine systems, particularly the thyroid, by lessening its activity and thus putting a brake on metabolic processes (Porritt, N. 1931). According to Porritt, N. (1931), the old doctors were not afraid to administer lead to their patients as an efficient weapon against hyperthyroidism, the officinal pil plumbi cum opi being their favourite prescription. Porritt, N. (1931) thinks that lead by slowing bodily processes and hindering metabolism would put pregnant women with their overcharged system at greater liability. It is known that 15% of normal women of child-bearing age are deficient in vitamin Bg (Davies, S. and Stewart, A., 1987). Depression is a very common part of the pre-menstrual syndrome, and as a result of taking the combined oral contraceptive; this has been shown to be alleviated by taking vitamin Bg supplements (Davies, S. and Stewart, A., 1987). Sandstead, H.H. et al (1969) have observed a decrease in the thyroid stimulating hormone reserves of lead intoxicated patients, and pointed out that other investigators have found that in vivo iodine uptake by the thyroid and thyroxin synthesis were decreased by lead. What is 186 interesting is that seasonal variation in hormone levels does appear to take peace in humans. Thyroid hormones showed a significant variation with season, total thyroxine (T^) and free having the highest levels in the summer, while triiodothyronine (Tg) had the highest levels in winter (Behall, K.M. et al, 1984). Since is biologically more active and was correlated with nutrient intake, its seasonal variation appears to be the more important of the thyroid hormones determined in this study. In the United States, hospitals and clinic records repeatedly showed that referrals of lead poisoning cases and admissions among children were clustered in the period May-September, and that there exists a seasonal peak incidence in the warmest months (Hunter, J.M., 1977). Summer outbreaks of lead poisoning have often been attributed to the enhancement of lead absorption with increased sunlight exposure and vitamin D synthesis. Barton, J.C. and Huster, W. J. (1987) concluded from radiolead absorption experiments on rats that significant seasonal changes in human vitamin D metabolism and calcium absorption occur, but vitamin D metabolites (primarily 25-hydroxyvitamin D) may not be important regulators of lead absorption. The seasonal maxima in blood concentrations of vitamin D metabolites may not stimulate lead absorption, but Vitamin D could precipitate or exacerbate plumbism by accelerating the release of lead from storage sites in bone (Barton, J.C. and Huster, W.J. , 1987). Hypercalcaemia, diminished intestinal absorption of calcium and greater urinary excretion of calcium are features of hyperthyroidism (Anon, 1970). It was cited by Adams, P.H. et al (1967) that the increased destruction of bone (manifested by net loss of calcium from the body) might be a direct effect of increased amounts of thyroid hormone. The relationship between calcium metabolism, bone and hormonal balance is quite complicated and poorly understood. 187 Its interesting that epidemiological studies have revealed the existence of seasonality of circulating blood lead levels in normal adult populations in Japan. Thus normal healthy persons had higher levels of lead in their blood in summertime than in wintertime in the year 1954 (Horiuchi, K. and Takada, I., 1954). In 1984, blood samples were collected from 505 examinees in 14 regions in Japan on several occasions, blood lead levels of the winter and summer measurements indicated that blood lead levels were higher in summer than in winter, although statistically insignificant (Watanabe, T. et al, 1985). The fact that lead was phased out of petrol in 1975 in Japan clearly rules out the influence of external atmospheric lead effects on seasonal blood lead fluctuations by increase in traffic volume. It seems most likely that seasonal fluctuations in lead absorption are due to internal factors, of most importance being the seasonal variation in hormonal levels. 188 6.17 Conclusion Lead intake from diet is not only affected by the amount of lead ingested, but more importantly by the content of very specific nutritional factors in the diet such as iron, zinc and vitamin C. Calcium intake would be increased for people living in hard water areas, however, the other nutritional factors of greater significance in inhibiting lead absorption and enhancing its excretion can only be obtained from diet. The higher blood lead levels of pre school children in Birmingham among Asians have been previously associated with the quantity of lead in the diet and application of cosmetics (i.e. surma)rather than iron deficiency. Trace element deficiency states in particular are predisposing factors for increased uptake of lead. Diet effects immunocompetence, and its possible to stimulate the body’s defence mechanisms in order to enhance lead excretion by dietary modification. Lead retention is probably caused by reduced lead excretion rather than increased lead absorption from the environment. Regardless of geographical location, the physiological lead balance maintained in various localities is so significantly different and accounts to a large extent for differences in blood lead content. This is in agreement with Willoughby, C. E. and Wilkins, E. S. (1938). The relation between lead intake and toxic effects is not a simple one, and suggests that this should be considered when establishing safe actual environmental lead exposure levels in humans via extrapolation of data from levels of exposure in animals and artificial conditions of human exposure in metabolic experiments. The assumption that 50% of lead in petrol ends up in the blood of human beings in the early seventies (Bryce-Smith, D. 1971a, Bryce-Smith, D., 1971b) was an untested assumption and has created much public misconception. The role of the food industry, nutritionists/dietitians and government is overwhelmingly great. Thornton, I. (1983) believes that petrol lead has and will continue to influence environmental lead levels far into 1 the future. Whilst others are under the superstition that lead in petrol is a ghoul to be cautioned against, I believe that the basic needs of a human being are: food, water and shelter. What we don’t understand, we tend to fear i.e. we are afraid of something if we are ignorant of it. The word “ghoul” comes originally from Arabic and is normally used to frighten children of an invisible gigantic monster so that they avoid doing bad things. It seems that the campaigns against lead in petrol have scared both children and adults. 190 CHAPTER 7 LOW-LEVEL LEAD EXPOSURE AND THE EVALUATION OF MENTAL SKILLS IN CHILDREN “If two people tell you your head is missing, touch it and see”. Research on the relation of lead to intelligence and learning abilities of children has been superfluous over the past decade. Given that high doses of lead leading to intoxication (i.e. Pb-B> 80 /ig/100 ml) are neurotoxic in effect, then by inference a hypothesis is generated that low to moderate lead absorption as commonly encountered by today’s young children may be associated with an increase in learning difficulties and behaviour problems. Diseases can be caused by excessive exposure to inorganic chemicals that may be beneficial or even be a metabolic requirement at low levels. A relationship has been established between skeletal fluorosis and the long-term elevated intake of fluoride (WHO, 1984b). The potential influence of low level lead exposure on child IQ (Intelligence quotient), educational attainment and behaviour has been investigated in many epidemiological studies. Recent research findings on the effects of lead on children’s cognitive and behavioural functioning have been reviewed in several papers and reports (MRC, 1984; Pocock, S.J. and Ashby, D., 1985; Smith, M., 1985; Lansdown, R., 1986; Yule, W., 1986). Evidence on the effects of lead on childhood IQs has been conflicting and in some studies contradictory. The “uncertainties” surrounding this complex mingling of statistical, medical, conceptual, methodological, psychological, ethical, political, and sociological components of the issue created much controversy and debate. We are sometimes tempted to blame 191 uncertainty for controversy. Scientists cannot be divided by a lack of facts which then force judgement, since the existence of uncertainty is the result of continual interpretation. If only we had more information, disagreements would vanish; this solution to social conflict is illusory in public issues (Campbell, B.L., 1985). The aim of this chapter is to unearth what may lie behind different findings. Inconclusive findings raise real doubts about the reality of the effect of lead on IQ when “removing out” the strong effects of confounding variables. On the other hand, the cognitive assessment procedures employed to measure neuropsychological functioning seem to be less adequate than has been expected, while measures of social factors used in such health studies are not appropriate. The weaknesses of the tools used in the evaluation will be clear from the sections to follow. I can describe the numerous attempts to relate IQ to lead as “a thicket of seemingly inconsistent and confusing findings, confounded variables, methodological differences, statistically questionable conclusions based on correlational thinking, unbridled v theoretical speculation, and, not surprisingly, considerable controversy . These were the words of Arthur Jensen describing “intelligence” testing (Raby, S., 1981). 192 7.1 What is IQ and What Do IQ Teats Measure? Psychometricians defined intelligence operationally as “whatever it is that IQ tests measure” due to their continuing failure to agree upon a substantive definition of “intelligence”. The fragile consensus among testers which such a definition permits would quickly dissolve if they attempted to specify the nature of the various mental skills tapped by IQ tests (Harwood, J., 1983). The pressure to abandon the search for a theory of intelligence in favour of constructing useable tests is nicely illustrated by the way in which Alfred Binet’s studies of intelligence developed (Eckberg, D.L., 1979). During the 1890’s, while searching for a unitary concept of intelligence which would discriminate bright from dull children, Binet had recognized the various kinds of mental operations by which individuals differ. Unfortunately such qualitative diversity made ranking very difficult: How can we measure the richness of inspiration, the accuracy of judgement, the ingenuity of the mind? By 1905, having nearly given up the search for a unitary intelligence several times, he was finally able to provide the Parisian school authorities in France with a test constructed on purely pragmatic grounds, such that children’s scores correlated with teacher’s estimates of their “intelligence”. Though Binet seems never to have fully resolved the tension between the one-dimensional nature of that which his tests measured and the diversity of mental qualities which he saw as constituting intelligence, the American psychologists who seized upon his tests so eagerly were more single-minded. In the US, Binet’s tests were refined as predictive tools, while his attempts at a rudimentary theory of mental ability disappeared from view. The attitude of American psychometrists such as Guilford and Thurstone (who are factor-analysts) is rather that intelligence consists of a large number of independent factors. In their view, a whole 193 battery of separate tests should be administered, in order to measure general intelligence (Heim, A. W., 1975). Psychologists have, for decades, laid an over-heavy load on factor-analysis. Factor-analysis is based on the manipulation of correlation coefficients, this being a useful mathematical “method of classification”. It is based on the assumption that intelligence consists of a number of different factors: a memory factor, a speech factor, a numerical factor etc. A problem in a test is said to have high factorial validity if it has a high correlation with other tests or problems which are considered to measure that particular factor (Liungman, C.G., 1975). The intelligence quotient used to be defined as the quotient of the mental age and the real (chronological) age, and multiplied by 100 to remove the decimal point. Nowadays, some tests that give separate scores on a variety of specific abilities such as vocabulary, verbal reasoning, verbal fluency, numerical ability, perceptual speed, memory and so on, and taking an overall average (Wilson, G. and Grylls, D., 1983). The average IQ is by definition 100, scores above 100 indicate a higher than average IQ and scores below 100 indicate a lower than average IQ. In association with the 1916 revision of the Binet Test, a classification of human being’s intelligence is seen in table 11: 194 Table 11: IQ Scores Classification IQ Classification (Liungman, C.G. 1975 > 140 Genius or near genius 120-140 Very superior intelligence 110-119 Superior intelligence 90-109 Normal or average intelligence 80-89 Dullness 70-79 Borderline deficiency Under 70 Definite feeble-mindedness According to some proponents of the genetically-determined intelligence, IQ scores help in predicting educational and occupational success, and this is the main purpose for which they are designed. Since the IQ gives a good indication of the occupational group that a person will end up in, though not of course the specific occupation, some occupations typical of various IQ levels are seen in table 12: 195 Table 12: Occupational Classification by IQ Scores (Wilson, G. and Grylls, D., 1983) IQ Occupation 140 Top Civil Servants, Professors and Research Scientists 130 Physicians and Surgeons, Lawyers and Engineers (Civil and Mechanical) 120 School Teachers, Pharmacists, Accountants, Nurses, Stenographers and Managers 110 Foremen, Clerks, Telephone Operators, Salesmen, Policemen and Electricians >100 Machine operators, Shopkeepers, Butchers, Welders and Sheet Metal Workers <100 Warehousemen, Carpenters, Cooks and Bakers, Small farmers, Truck and Van Drivers 90 Labourers, Gardeners, Upholsterers, Farmhands, Miners, Factory Packers and Sorters The vocabulary test tries to figure out if the child knows the word “Politician” (Wilson, G, and Grylls, D., 1983), yet it does not seem to have been classified by a certain IQ level! One of four pictures shows a gentleman wearing a coat, a hat and a bow-tie with a cigar in his mouth which ought to be identified as the correct answer (i.e. Politician). I? 6 This system of classification has the effect of forcing the personality of the subject into a strait-jacket. While testing’s task was to sort out wheat from chaff, eugenics pressed for state-regulated population-control measures, so that the right proportion of wheat and chaff would be reproduced (Harwood, J., 1983). This choice of metaphor is not unduly cynical; testers saw themselves essentially as social engineers, measuring the strength of human materials (Marks, R., 1981). Many selective American universities rely substantially upon mental ability test scores in their admission procedures (Harwood, J., 1983), and at the age of 11 children are sorted out as to which schools they should be going to in Britain on the basis of IQ testing (MacKintosh, N.J., 1986). Hitler assumed that the Germans, that is the tall, blond and blue-eyed people were superior (i.e. mentally) to others regardless of social group (Liungman, C.G., 1975). Education had to recognize intellectual differences, and Marks, R. (1981) believes that “it would be wasteful to train the Jews and Negroes identically”. It has been suggested that a reasonably high level of intelligence as tested is necessary — though not, of course sufficient — for people to prove acceptable to others in a position of leadership (Heim, A.W., 1975). Indeed the continued faith in and use of such tests, by psychologists, sociologists, industrialists and others is quite amazing. Even applying for a desired job seems to involve an IQ test. Psychological testing is a method of effecting differentiation, a way of sorting people out (i.e. a means of discrimination), “often to their advantage”, for a “happy employee is an efficient one”. The tests are devised by members of the upper middle class who naturally build their prejudices, whether these concern logical or social or ethical problems. They are used merely to inculcate and reinforce upper middle-class values and, hence maintain the existing hierarchical structure of society. IQ tests are an instrument of oppression against the poor, and they measure nothing more than conformity to white middle-class values; and the supposed demonstration of group differences in IQ, so far from establishing genetic differences between groups, merely provides proof that IQ tests are biased (Mackintosh, N. J., 1986). The notion of genetically inferior 197 races and genetically superior ones is not entertained. Variations in IQ between different racial groups do exist, but variations in the social conditions of different groups also exist. The whites were superior to the Indians in the Draw-a-Man Test but the opposite was true of the Draw-a-Horse Test among 11 years old children (Liungman, C.G., 1975). Maps drawn of home town or smaller neighbourhood revealed predictable individual differences, thus reflecting different amounts of experience with the relevant environment and how near or further away from slums they really are (Williams, S.M., 1987). Burner, J.S. and Goodman, C. C. (1947) have shown how the perception and judgement of children vary with the wealth of their parents (and subsequently repeated and confirmed by Carter, L.F. and Schooler, K., 1949). Three groups of 10-year olds were tested, individually, on their ability to reproduce the size of a coin, which they had just been shown. The three groups were, respectively, from well-to-do homes, from poor homes and from varied economic backgrounds. Coins of five denominations were used. The coins of higher denomination tended to be overestimated by all to a relatively greater extent than were coins of lower denomination, but the overestimation of large coins was greater by the children of poor parents than it was by the children of rich parents. Scorer, R.S. (1983b) gave an example of a similar phenomenon. An urban child can easily answer the question “If John set out for home with five pigs from market and lost three on the way how many would he have on arriving home?” A peasant child would regard the question as stupid, for he would not dare to go home until he’d found the ones he’d lost, and anyway he wouldn’t lose them in the first place. The question of arriving home with less than the five he set out with would not exist. The city dweller has no difficulty in answering such a stupid question. I myself wondered whether this was the real function of IQ tests in society. 198 I knew the words “primate” and “conifer” because it was part of my educational experiences (i.e. familiarity) but did not know the word “ecclesiastical” because its not part of my culture and never came across this word before. It does not follow that I am lacking in “fluid intelligence”. All intelligence tests assume some knowledge. Even a problem such as “ A rabbit is timid, a lion is .... ? required for its solution a certain family background and probably attendance at a kindergarten. How is someone who has grown up in the slums to know that a lion is brave? It might be more likely to occur to him that a lion is strong or savage. This means that children from lower social groups automatically get lower scores. Getting the child to draw a picture of a house gives insight into this. Old ragged dirty clothes, little food, very plain .... basement of cheap tenement house, hardly bare necessities differs from a well-to-do home showing abundant food, fine carpets, rugs, pictures and modern conveniences denoting luxurious living conditions. Familiarity with words in vocabulary tests is also another “culture index”. Portrait, t>arbe 199 In a vocabulary test, one child may define “sentence” as a group of words, while another as a penalty imposed by a judge. This difference exemplifies important dissimilarities in experiential background. Facts are matched on the basis of existing experiences. Thus a four year old child refused to have his chest X-rayed because the kind X-ray lady had told him that she would, when the procedure was over, show him his bones. His understanding of her comment was not at all as she had intended it to be! (Goodall, J., 1987). Its important to know how to express things to children in tests trying to match what the tester wants to get across with something already familiar to them, otherwise the deductions made as an IQ score can too easily be faulty. Children are quite likely to associate “hospital” with death if they had a relative or friend go there and not come back, while some may associate “hospital” with the place where Dad goes for work because he is a doctor. Things which are not at all the same may look the same to the child. This may be illustrated by putting identical levels of water into two tumblers, then pouring the water into a taller container and asking the child to comment on the relative volumes. A child up to about 6 \ years old is likely to say that there is more water in the taller container. An experienced child will give the right answer, but experience has to be gained. Currently, there is increasing anxiety among many children of ages 6-10 years that they may have AIDS, because there is so much publicity about it. One little girl was very worried because her teacher had told her that she was ignorant and, of course, all the advertisements say that we must not die of ignorance (Goodall, J., 1987). The observation subtest in which the task is to locate and say what is missing or wrong in the picture is not any better. 200 Thermometer reading is not correct in a luxurious house where a cat is resting warmly near a fire, the golf clubs ought not to be used as ski sticks and there should be four strings on a violin, not three etc. . Another subtest is that a child is asked to complete a pattern which requires familiarity with geometrical figures in looking for the relation on which the symmetry principle is based (e.g. Reven’s Matrices). They require a knowledge of the symmetry principle and the adoption of the convention that the symmetrical pattern is more correct than the asymmetrical. The intelligence factors tested (as thought by psychologists - verbal factor, logical factor, flexibility factor, numerical factor, spatial perception factor, discrimination factor and an analogy factor) are therefore not an expression of an inherent common structure of the brain or “thinking”. Differences in motivation probably play a major role in IQ variations in different ethnic groups. Negroes, who are convinced that the society is prejudiced against them, can foresee that any qualification they might be able to possess one day does not make them eligible for a job i.e. its highly unlikely they will get a respectable position in society, thus they develop an attitude of lethargy and stupidity. Probably many of them 201 Our life—our thoughts, what we hear, see, taste, feel in our emotions, dream and choose — is determined by what we have learned to be conscious of and to value (Scorer, R.S., 1964). Average black IQ in America is about 85 and average white IQ about 100, a difference of aJbout 15 points (Gould, S.J., 1988). An IQ test would be said to be biased against a particular group if the ability to answer its questions correctly depended on experiences denied to that group, or in other words, if their inability to answer the questions were a consequence of deprivation. Since performance on IQ tests is affected by environmental experiences, there is no such test which measures pure, innate intelligence divorced from the circumstances of one’s life. Due to social deprivation, black children had higher Pb-B levels than whites in New York (Billick, I.H. et al, 1979), but bringing their Pb-B level down will not improve their IQ scores unless educational and social reforms are undertaken since the same set of factors affecting their lead exposure are also affecting their performance on IQ tests. Much of the early investigations on lead and IQ were conducted on mainly socially disadvantaged children (Lansdown, R., 1986). It is very misleading to suppose that “perfect” matching can take place with respect to many social and environmental variables between one experimental group and a control one, for the control of one variable precludes matching with respect to very many others (Kamin, L., 1974) particularly in the case of lead. Since an individual’s social and cultural environment is at least as much determined by the influence of friends, teachers and neighbours, not to speak of newspapers, films and television, as of his parents as well, one should not connect the lower 202 score of Negroes with poorer quality of the brain or their Pb-B levels. Variations in the social conditions of different groups exist partly because of educational circumstances (to go to a special school bears a social stigma). Air-conditioning in the summer months is still generally restricted to the upper classes. All these factors lead to mental development and intellectual self-confidence. There is nothing to lead one to expect a higher average IQ in the Negro population. It is my view that children who had been reared in markedly wealthier homes will be conspicuously superior in IQ testing scores. No intelligence exists without knowledge, and IQ tests call for special knowledge which is presupposed to have been acquired by the testee. The adaptation of these tests to detect any negative effects of lead on learning abilities is dubious. The state of the art can hardly be regarded at present sis more than exploratory. Science progresses by ideas being put in the form of hypotheses that either stand or are refuted. In this vein, as we have no methods of measuring “intelligence’1, and since the markers of lead exposure are far from perfect, it seems hardly necessary to pursue further investigations of the lead-IQ relation. The misuse of resources, including the researcher’s time could be better employed on more valuable research activities. 203 7.2 Verbal or Performance Effects of Lead Typical intelligence tests with school-age children or adults measure largely verbal abilities; to a much lesser degree they also cover abilities to deal with numerical and other abstract symbols, for these are the abilities that predominate in school learning (Anastasi, A., 1976). The common finding that verbal IQ is more affected by lead than performance IQ by some studies (Yule, W. et al, 1981; Needleman, H.L., 1979) clearly reflects one defect in the IQ tests. Validity refers to the test’s ability to assess what is designed to assess. These batteries of tests used on populations to assess “minimal brain dysfunction” or “organic brain syndrome” are not designed for this purpose. Intelligence tests can be regarded as scholastic aptitude tests (Anastasi, A., 1976). Many important functions that intelligence tests have never undertaken to measure such as motivational, emotional and attitudinal variables are important determiners of achievement. The motivational makeup influences the kind and amount of learning that occurs. Specifically, it is the strength of the experience-producing drives that affects intellectual development. These drives are illustrated by exploratory and manipulatory activities, curiousity, the babbling of infants, play and others. The cumulative effects of these experiences in turn determines the individual’s intellectual level. Research on pre-school children, for example, indicates that the brain-injured tends to be deficient in all intellectual functions (Anastasi, A., 1976). One of the striking results of several studies on lead using IQ testing is that verbal rather than performance scores are depressed. Needleman, H.L. et al (1979); Perino, J. and Ernhart, C.B. (1974); Yule, W. et al (1981) and Winneke, G. et al (1983) all reported results in this direction. On the other hand this has not been a consistent finding, indeed one of the 204 puzzling sets of findings from various studies has been the lack of consistency in type of deficit. This was most apparent in the Needleman, H.L. et al (1979) and Marshall, E. (1983) studies, in its subsequent partial replications by Yule, W. et al (1981) and Lansdown, R. et al (1986) studies; Smith, M. et al (1983) and Pocock, S.J. et al (1987). The lead effect came and went, flip-flopping here and there. Ideally when considering an association between the suspected causal factor and the resulting effect, the overall evidence accumulated should be according to the following established criteria (WHO, 1987): (a) consistency of association, i.e. the repeated observation of the connection between chemical exposure and effects, under different circumstances; (b) strength of association, i.e., more intense exposure leads to more frequent or more severe effects; (c) specificity of association, i.e., similar signs and symptoms are not observed in the absence of the suspected agent. Clinical experience shows that verbal IQ is more sensitive to socioeconomic factors, while performance IQ is more vulnerable to neurotoxic insult such as excessive alcohol intake (Smith, M., 1985). Non-verbal thinking is found in animals. The pigeon has been recently the subject of cognitive experiments on brain development (McGonigle, B.O., 1987). The objective of the experiment is to try to understand the complexities of human recalling (i.e. memory). It is known from nature that the pigeon has got a good sense of spatial direction and recalling of 205 its nest where it has to come back after flying. It might serve the purpose of an experiment on lead in petrol and “IQ” for those who think it?is worth it. If there are physiological changes in the brain due to lead, then there should be a test which could detect functional changes, however, such a sensitive test (an indicator of subclinical neurotoxicity) does not exist. Performance tests can be affected before the appearance of clinical neurological symptoms (Valciukas, J.A. and Singer, R.M., 1982). The Wechsler Intelligence Scale for Children - revised version (WISC-R) was the test chosen for all studies on the neurotoxic effects of lead except that of Harvey, P.G. et al (1984) and Fulton, M. et al (1987). The British Ability Scales (BAS) test was used for these two studies. The advantages of WISC-R is that it is widely used, provides separate estimates of verbal and performance IQ, as well as a global score. WISC-R has been shown to be sensitive to a wide range of neurological insults, but also to social influences (Smith, M., 1985). It is difficult to assess the comparability of the American, English and German versions of the test, and so the apparent advantages of different studies using the same test are not as great as it might appear. WISC-R was published in 1974, and in the revised edition special efforts were made to replace or modify adult-oriented items so as to bring their content closer to common childhood experiences. In the Arithmetic subtest, for instance, “cigars” was changed to “candy bars” and items about a taxi and a card game were replaced. Several of the subtests were lengthened in order to increase reliability. With regard to content, the only subtest that does not appear in the adult scale is Mazes. The first edition of the WISC was criticized because its content was not sufficiently child-oriented. Reliability of any test is commonly agreed to reflect producing consistent results (Valciukas, J.A. and Singer, R.M., 1982). The standard error of the Full Scale IQ of WISC-R is 206 approximately 3 points, and the chances are 95 out of 100 that a child’s true WISC-R IQ differs from his obtained IQ by no more than ±6 points (Anastasi, A., 1976). We have constantly seen differences in this range: 0.65 point after controlling for confounding variables (Pocock, S.J. et al, 1987), 4^ points (Needleman, H.L. et al, 1979), 5 points before controlling for social factors (Smith, M. et al, 1983), 7 points Full Scale IQ without controlling for social factors (Yule. W. et al, 1981), all in favour of the low-lead groups which raises serious doubts whether any of these IQ points are attributed to low levels of lead in the body. This reflects another defect in the IQ tests. Only 35% of the total items in the WAIS test are completely knowledge-free, and special knowledge plays a large part in the results of WAIS (Liungman, C. G., 1975). This test has been used in testing parental intelligence (Needleman, H.L. et al, 1979) As to the validity of WISC-R, the difference tends to be slightly larger in Verbal than in Performance IQ and to decrease somewhat with age; and when children in the WISC standardization sample were classified according to father’s occupational level, the usual hierarchy of mean IQ’s was found (Anastasi, A., 1976). The adjusted mean IQ for children with fathers in non-manual occupations was 2.96 points higher than for those with fathers in skilled manual occupations, who in turn have a mean of 4.63 IQ points increase over those with fathers in semi-skilled or unskilled manual occupations (Pocock, S. J. et al, 1987). The authors concluded that parental IQ has the most important influence on the child’s IQ. What further complicates this matter is that not only psychologists have never agreed on a definition of intelligence and how to measure it, but also the threshold blood-lead level at which learning disability might occur continues to defy definition, as well as the indicator 207 chosen to monitor lead exposure. Levels of high and low Pb-B levels (and high and low tooth-lead levels) are arbitrarily chosen by investigators for comparison of IQ scores, as well as the size of the sample, social grouping and age selected not to mention the statistical methods employed. The third defect in IQ tests seems to be that of fairness to the sexes. A highly significant correlation (about 0.3) is claimed between brain size and intelligence (Raby, S., 1981). It is true that women have smaller brains than men. Women’s brains are smaller than one might expect from the fact that on average women weigh less than men. IQ test makers are said to have selected items in such a way that equal scores are achieved regardless of sex. The famous Wechsler test of adult intelligence includes the item “At what iemjierature does water boil?” That 70% of husbands and only 30% of wives could answer this test item in a study of 264 couples does not mean that men are more intelligent than women (Raby, S., 1981). Wilson, G. and Grylls, D. (1983) have stated that girls are particularly likely to excel in the areas of verbal abilities. Having seen that IQ tests are saturated with verbal abilities, one would expect girls to score higher than boys. Many broadcasters are males and they do their job perfectly well. Recently, Pocock, S.J. et al (1987) have found, by statistical analysis, that a statistically significant negative association exists between tooth lead level and IQ in males, whereas in females the association is actually slightly positive. The authors wondered whether boys are more sensitive to neurotoxins such as lead and stated that this issue merits further investigation. We have seen in this thesis that women are more sensitive to lead exposure than men (Roels, H. A. et al, 1976). 208 It is in fact expected to get such a result if girls truly excel in verbal abilities, probably due to more chatting done by girls than boys. “You become what you do” applies very well to mental practice effects. We use only 10% of our full mental capacities, often as little as 5%. These are the words of Albert Einstein, the greatest physicist. The 90% dormant could be awakened by stimulation, interest, motivation and encouragement. Needleman, H.L. (1987) inferred from Pocock’s reanalysis of childhood lead exposure data that males are more vulnerable to lead, neurotoxins in general and other insults to the central nervous system. Yet, Bryce-Smith, D. (1971c) in his assessments of mental health trends in Britain and its relation to lead has cited that women appear more prone to suffer mental illness in general than men. “Analysis of illness types suggests that depressive psychoses and personality and behaviour disorders have particularly tended to increase, especially in women” and the possibility of hidden effects of lead has been raised. Medical opinion argues that women’s proneness to mental collapse is due to their innate psychical and physical weakness (Porter, R., 1982). The high incidence of gonorrhoea in delinquent boys in America (Anon, 1978) hopefully would not be explained by the apparent sex effect of lead, but rather by promiscuity which explains their excess risk. While 2% lead acetate caused a permanently decreased growth of parietal cerebral cortex of rats, 1% lead caused a small but significant increase in the growth of parietal cerebral cortex (Olson, L. et al, 1984). These experiments have shown that lead increased the innervation of the cerebral cortex, so it might have had a beneficial effect in small doses. The effects of lead on the central nervous system are more complex than has so far been expected. 209 Wilson, D. (1983) in his book stated that Professor Derek Bryce-Smith of Reading University offered evidence to the Scarman enquiry into the Brixton riots in London laying at least part of the blame for the riots on the effects of lead pollution. This explanatory framework is too wooden to convince, and ought to be viewed in a different and more constructive way. Disadvantaged individuals are chronically dissatisfied and gloomy because of the quality of their life. If they were cheerful and optimistic, they would not make riots. Only recently alcohol has been implicated in delinquent acts such as football hooliganism and attempts were being made to regulate its consumption. Alcohol is the main preventable cause of trauma, impulsive crime, child and spouse abuse, birth defect and sociosexual difficulty (Comfort, A., 1984). Tucker, A. (1972) also quoted Professor Bryce-Smith stating: “This substance (i.e. lead) can send you mad”. One wonders just how infrequently conflicts with masters drove men out of their mind (Porter, R., 1982). The key to madness is not seated in the anatomy of the brain. Psychiatry, far from being an objective and universal science did not prove very successful in convincing the public of its credentials. The medico-scientific emphasis that insanity is a somatic disease continues to be viewed with suspicion. Short of slicing brains, they could only point to symptoms and behavioural abnormalities. Symptomatic connotations of being called “distracted”, “sad”, “light-headed”, “furious”, “aggressive”, “irritable”, and many other adjectives are considered as manifestations of personality disturbance. Psychiatrists claim the right to be judges of the mental health of the accused, yet in fact they are the means of shutting people up (Porter, R., 1982). Nriagu, J.O. (1983) gives some descriptions of lead in ancient history. “Get the lead out” was a familar term in American military and athletic life, that means: get rid of the stuff that is slowing you down and start moving. 210 It used to be associated with sluggishness and saturnism. David, 0 . et al (1972) associated raised levels of lead in the blood of children with hyperactivity, and that a large body-lead burden “may exert consequences that have been hitherto unrealized”. Their conclusion was : Despite the lack of proof of a causal relation between hyperactivity and lead, blood-lead levels and post-penicillamine urine-lead levels should be routine investigations in cases of hyperactivity. Hyperactivity is a symptom not a disease. We have seen the antagonistic effects of iron and lead particularly in low social strata. Anaemic children are listless and lacking in energy, thus there is no scientific reason for a symptom such as hyperactivity. Children are irritable and distracted if they are hungry or cold, not because of a certain level of lead in their blood. Needleman, H.L. et al (1979) unsurprisingly did not find an effect of tooth-lead on hyperactivity. One is forced to conclude that if there is any effect due to lead, there must be powerful interactions with factors related to individual and socioeconomic differences betweg^children. 211 7.3 Confirmation of a lead-IQ Hypothesis While Ratcliffe, J.M. (1977) found no statistically significant differences on developmental and behavioural scores when children aged 4-5^ years living near a lead smelter in Manchester were divided into two groups of Pb-B < 35 /ig/100ml and Pb-B > 35 /ig/100 ml, Fulton,M. et al (1987) found a significant relation between tests of ability and attainment with a mean Pb-B level of 10.4 /zg/100ml for children aged 6-9 years living in Edinburgh. Although the Edinburgh sample consisted of 855 boys and girls, while that of Manchester consisted of 47 boys and girls, one cannot consider any of the two studied inferences as valid evidence. As in many areas of medical research, the interpretation of studies of lead and IQ has been oversimplified by an undue reliance on significance testing for association. Conflicting results from similar studies (such as Needleman, H.L. (1979) and Smith, M. et al (1983)) can often be attributed to varying degrees of statistical competence (Altman, D., 1980). The ethical implications of publishing research containing incorrect or unfounded results or conclusions are little affected by the nature of the errors made, and are indeed much the same as the consequences of publishing spurious results. The cost in time and energy in trying to reproduce such results can be enormous. A study may have been perfectly conceived and executed, but if it is analyzed incorrectly then the consequences may be as serious so far a study that was fundamentally unsound throughout. Over-frequently simplifying purely psychosocial factors-multiple confounders-of such a great magnitude (Needleman, H.L. et al, 1979 removed out the influences of 39 non-lead factors affecting IQ) while ignoring our extremely inadequate knowledge of the physiologic and metabolic aspects of lead requires far more than a considerable faith in the sensitivity of the 212 statistical techniques used. The demonstration of a slight, but statistically significant correlation after clearing away extensive social influences using multivariate or multiple regression analyses, and inferring that lead causes brain damage is far-fetched. It was found that only 28% of a random sample of 149 analytical articles in American medical periodicals had sufficient statistical support for drawn conclusions (Gore, S.M. et al, 1977). We are studying complex phenomena whose mechanisms of action are not even vaguely understood. There is a tendency to place undue faith in the capabilities of the computer to provide the answers. We must bear in mind the subtleties of multiple factors (confounding effects), the fact that even random data will generally yield significant results. Although statistics and mathematical results may appear impressive, especially if put through a computer, we must remember that if the information or figures fed into the computer are incorrect, only nonsense will come out. “We cannot browse over the field of nature like cows at pasture” and in this context the computer is super-cow (Mike, V. and Good, R.A., 1977). P-values are only flags marking patterns of possible scientific significance, areas for further exploration on a selective basis. Correlation figures can only shed light on the problem, but cannot be regarded as a statistical litmus paper, scientifically sorting the good from the bad. Thus, statistics is not a set of sharp tools, and the computer cannot operate creatively where its terms of reference have not been precisely defined (Pickering, G., 1970). I do not intend to pillory the investigators concerned, but rather to draw attention to shortcomings. 213 Intellectual satisfaction is the personal driving force of the scientist. On the other hand, there is evidence that prior beliefs influence deductive inferences when they are formally irrelevant, and statistical evidence in favour of a hypothesis should be weighed by one’s belief in the hypothesis concerned (Evans, J. St B. T. et al, 1985). Prior beliefs tend to have a non- logical influence known as “belief bias” in deductive reasoning experiments. The magnitude of the effect of believability seems great. Campaigners on social issues find statistical significance as strong evidence and very impressive if their beliefs were congruent with the survey outcome. Kollerstrom, N. (1982) overweighed his “snippets of evidence” thus providing a single causal connection between lead and the brain in a very emotive and catchy title of a book: “Lead on the Brain : A Plain Guide to Britain’s No. 1 Pollutant”. The notion that lead causes “brain damage” is now a firmly established public belief sustained by constant reiteration in the lay and scientific press (Barltrop, D., 1985). This notion has persisted despite several studies that have found no consistent evidence (if any at all) and no apparent dose response relation; the IQ difference might reflect factors not related to lead exposure. Editors of newspapers and newsletters look for an eye-catching headline, and there is a tendency to sensationalise and summarise in short snappy phrases what can often be difficult and complex issues. “All Land Contaminated By Lead Within 10 km of Marble Arch” (Anon., 1988), “Poisoned Vegetables” (Anon., 1983a), “If Mercury Does Not Get You, Lead Probably Will” (Tucker, A., 1972), “Lead Report Brings New Alarm Over Petrol” (Anon., 1983b), “How Lead Levels Can Harm Kid’s Hearing” (Anon., 1986b), “Lead : The Debate Goes On But Not Over Science” (Budiansky, S., 1981), “Lead : Unknown Numbers of Children at Risk” (Anon., 1982) are just examples. Public misunderstanding can be easily created by environmental lobbies. The lead debate goes on, but not over science is anti-science, for we cannot trust experts. 214 Thus, the MRC (1984) conclusion that “available evidence suggests that a moderate elevation in body lead burden, as found in some British children, has little or no effect on IQ” has been seen by many as a denial of truth. Lobbies often fall back on the technique of maligning the integrity and ability of scientists. A more subtle approach is to contrast the views of contemporary scientists with those of yesteryear to show that scientisits were wrong before and they can be wrong in the future. This is illustrated by such a phrase — “scientists thought that asbestos was safe”, and we must have an inquiry. If lead has a potential for brain damage, why take the risk? Although journalists are not generally believed to be high-principled and truthful (some coming lower in population esteem than many other professions), such fallacious arguments strike terror into the hearts of the public. There have been instances where a person or group of persons, after learning of the symptoms of parathion (Cholinesterase-inhibiting or inactivating insecticidal compound: 0 — 0 —diethyl — 0 —paranitrophenyl thiophosphate-) poisoning, promptly became ill with a chain of symptoms consistent with parathion poisoning. The blood cholinesterase tests, by demonstrating entirely normal values, have served to quell such episodes of hysteria (Wolfsie, J.H. and Linden, N.J., 1957). It is not easy to convince the uninformed that his “poisoning” symptoms do not exist and bear no relationship whatsoever to the alleged effects of a particular chemical or compound. In 1970, sensational news was reported that Pb-B levels were unexpectedly high in residents living near a busy street in Tokyo; this report shocked the general public and then lead- workers in a newspaper company situated 3 kms away from the street (Araki, S. et al, 1982). The lead workers were informed of detailed knowledge on the health effects of lead through the trade union movement. Medical consultation rates of lead workers (both with high and 215 low Pb-B levels) was much higher than those for all employees in the company (i.e. non-lead workers) in the years of 1972, 1973 and 1974. Disease-specific consultation rates were also higher in lead workers for seven categories of diseases and injuries such as hypertensive disease and peptic ulcers. It was concluded that the industrial dispute over the health effects of lead might have been a major cause of the high consultation rate of lead workers. Lowering lead levels in petrol,for example is claimed to impose costs on a relatively wealthy group (i.e. motorists)and confers benefits on a poorer group (inner city pre-school children) by raising their IQ (Colllingridge, D., and Douglas, J., 1984). Yet another asks: how much is the taxpayer willing to pay, in order to raise the average intelligence of the population by, say 1% (Eisinger, J., 1986). Are the eyebrows to be corrected by pulling out the eyes? Public attitudes range from deeply rooted anxieties about personal and family safety, to a genuine concern for the welfare of future generations, or even to the pragmatic attitude of “not in my backyard”. People with a genuine concern for the environment and for the future of society readily pledge support for environmental campaigns. Such a person would find this piece of information very scientific: Signs of How Lead Toxicity Begins (Raloff, J., 1986b) Researchers at the University of California at Los Angeles believe they’ve uncovered evidence of how lead, at least initially damages the brain. Their tissue culture studies, involving mouse brain cells suggested that the membrane of these cells may be lead’s initial target. At low concentrations of lead, such as 40 /ig/100ml, they saw no cell changes. Lead toxicologist Bruce Fowler of the National institute of Environmental Health Sciences in Research Triangle Park, North Carolina (USA) characterized the work as “Potentially a Very Significant 216 Finding”. What the layman does not know is quite plentiful. Agricultural pesticides* residues in our food “may alter brain function” and have neurophyschological effects (Wolfsie, J.H. and Linden, N.J., 1957). Mercury can easily penetrate into brain through the blood brain barrier (BBB) and consequently brain damage results with long term exposure to high concentrations (Yoshida, M. et al, 1980). One of the fundamental characteristics of the mammalian brain is the BBB. By its selective isolation of circulating compounds in the blood from those produced by the brain, the BBB effectively maintains the brains homeostatic environment (Rosentein, J.M., 1987). Most chemotherapeutic agents cannot penetrate the BBB. In the case of lead, man is not exposed to organic lead compounds other than in certain occupational settings. Exposure to organic solvents can induce chronic effects on the brain, however the condition is not as well defined or understood (Waldron, H.A., 1986). There is lack of agreement among doctors on the definition of migraine headache because the description of migraine and its classification as headache is not clear in their own minds (Blau, J.N. 1984). Large verbal- performance IQ differences were observed on the WISC-R test between ^ ^ 8^Cchildren on theophylline therapy and normal children (Furukawa, C.T. et al, 1984). Smith, A.P. et al (1987) examined the effects of experimentally induced minor illnesses (colds and influenza) on the efficiency of human performance. Influenza impaired the ability to detect and respond quickly to stimuli appearing at irregular intervals (i.e. slow reaction time), but had no effect on a task requiring hand-eye coordination. In contrast to this , colds impaired hand-eye coordination (i.e. typing-motor activity) but had little effect on the detection tasks. 217 Our attitude towards environmental issues depends on the information that we receive and our ability to distinguish between fact and fiction. It is the responsibility of the media and environmental lobbies to put across the facts in a responsible and accurate way (Page, R.A., 1986). The evidence suggests that the attempts to reduce IQ to some simple property of the nervous system has not greatly increased our understanding of IQ (Mackintosh, N.J., 1986). Byers, R.K. and Lord, E.E. (1943) who first noted the intellectual and behavioural sequelae of chronic exposure to lead have mentioned that “the presence or absence of evidence of involvement of the nervous system bore no relation to the eventual intellectual development of the children; indeed the only truly successsful member of the group had the most severe encephalopathy encountered among the 20 children”. Experimental, cognitive psychology is meant to be in the business of understanding the human mind and developing theories of its operations. It is unfortunate that any campaign tends to centre on one section of the problem, and as the components of the problem become increasingly entwined, greater and greater weight is given to one of the parts at the expense of the others. The Campaign for lead-free air (CLEAR) has continuously tended to detract from other sources of lead, particularly food, water and paint and has led the public to believe that petrol exhausts were the only cause for concern. CLEAR organized an “International Symposium on Low-Level Lead Exposure and its Effects on Human Beings” that took place in London at the Institute of British Architects in May 1982. This event was sponsored by Pura Foods Ltd. After three days of discussions, Professor Michael Rutter (Child psychiatrist at the University of London, who was a member of the DHSS working party on lead, 1980) showed in an eloquent summary of the proceedings 218 just how simple it is. He drew together all the evidence, weighed it and reached the conclusion that it was now time to remove lead from petrol (Wilson, D., 1983). On the 17th and 18th of April 1986, another conference on lead “Lead in the Home Environment” was held at Imperial College, London. The event was organized by Ms. E. Culbard (then a member of Imperial College). The sponsors were : International Lead Zinc Research Organization (which sponsored the Isotopic Lead Experiment in Turin, Italy), DoE and the Society for Environmental Geochemistry and Health (a newly formed society). The conclusion of the two days* proceedings of the conference was addressed by Sir Richard Southwood (FRS), Professor of Zoology at Oxford University who was the chairman of the RCEP report (1983). The conclusion was : “Most uses of lead, other than as a petrol additive, do not cause it to be widely dispersed in the environment, so whilst point-sources (paint, plumbing, etc) must be tackled; lead additives must become a technology of the past. We know enough of the physiological effects of lead to be confident that today burdens should be minimised”! He further adds: In my opinion this conference marks a new phase in the study of man and lead (Thornton, I and Culbard, E., 1987). CLEAR also noted that their conclusion was a “turning point”. It is evident that food is not a major source of lead for them as clearly stated in one of their papers (Sherlock, J.C., 1987). I was surprised that a paper on “Recent Changes in Blood-Lead Levels” presented by Dr. P.C. Elwood - Director of the Medical Research Council - Epidemiology Unit - in South Wales was omitted in the published proceedings (Thornton, I and Culbard, E., 1987). To make a long story short: Let a Man Say What He Will, An 111 Man Will Turn it 111. 219 The subtle putative effect of lead on IQ is not only an artefact of analyses (Yule, W. et al (1981) compared with Lansdown, R. et al (1986) analysing data from the same study) but also a product of the IQ values which have been entirely invented. The pilot study undertaken to replicate the use of Needleman’s teacher questionnaire in relation to blood lead levels involved children who had been screened in the EEC Survey (Yule, W. et al, 1981). They found that “only 2| to 4^ per cent of the variance in intelligence is shared with Pb-B levels”. In 1986 (Lansdown, R. et al, 1986) the same group of researchers found that “In no case does lead account for a significant amount of residual variance in any of the measurements of IQ or attainment”. The Needleman study has been the centre of fierce controversy. The design was weak in many respects. The middle group was omitted, so that it was not possible to examine a dose effect relationship (only the highest and lowest 10th percentiles of dentine lead levels were compared - 58 and 100 children respectively - thus inflating the two extreme ends of the distribution and maximizing the possiblities of getting a statistically significant result): High attrition rate of the whole sample of 2146 whose teeth were analyzed (thus over 60% of the children in either group were not included in the results, and hence there exists some doubt as to how representative the results might be), the population studied being restricted to the age group shedding teeth and type of tooth analyzed (discussed under section 7.6) were also factors which undervalued the study. Subsequently the American Environmental Protection Agency commissioned an examination of the work (Marshall, E., 1983). This examination resulted in suggestions that the Needleman computer program contained errors, and there were questions on the controls for confounding variables as well as the method of selecting the sample. It was stated that the findings cannot be accepted as valid because of sampling and 220 statistical errors in the data. In fact there were several grounds for viewing Needleman’s study with some misgivings, and a replication of the findings was called for in Britain and later conducted by Smith, M. et al (1983). An effort to improve the educational and social environment is much better than pseudobiologizing the IQ values. Lead is to be phased out of petrol by 1990 (House of Lords, 1985); we look forward to a rise in the intellectual level of citizenry!!! 221 7.4 Social Factors and Lead Zielhuis, R. L. et al (1979) observed increasing Pb-B levels with decreasing socioeconomic status; young children of low socioeconomic class clearly constitute the actual group at risk. The effects of socioeconomic factors on IQ scores were observed in all of the studies on lead and IQ (Confounding Variables; verbal IQ and higher levels of lead found in children from lower socioeconomic backgrounds; children’s IQ of manual-working parents lower than those of non-manual parents, sample selection from particular social grouping and father’s occupation). The usual practice in health-related studies is to use occupation of the head of the family as a measure of family level. However, for women with no formal employment, no occupation can be recorded, as with the unemployed. Classifying a woman using the occupation of her husband or of the head of the family does not provide sufficient information about her which may be needed for analysis related to her health and education as well as to family health conditions. Awareness of the protective and preventive behaviour in reducing lead exposure to the child makes an enormous difference. Firstly, from a nutrition point of view as to how and what food to provide the child with, secondly as to ask the child not to put anything in his/her mouth and to keep the toddler at a distance where he could be watched, thirdly to ask the child to wash his/her hands before eating. In Western societies, educational levels of the husband and wife tend to be close. Regardless of the apparent net availability of lead in infant’s physical environment, parental behaviour was still significantly associated with infant blood-lead levels (Dietrich, K.N. et al, 1985). 222 Maternal involvement with the child, provision of appropriate playmate and emotional and verbal responsivity of the mother — were negatively correlated with lead exposure at all ages in this study. The strongest correlations occurred after the age of 6 months. The extent to which the mother keeps her child within visual distance range during her daily activities, structures her infants activities and takes a “teaching” attitude, all contributes to his early development. Those who receive less physical and social stimulation may engage in more hand-to-mouth behaviour and thus ingest larger quantities of lead-laden dust, soil, paint flakes, or other materials. The caretaker — child relationship has not been given emphasis in any of the lead studies. Occupation is an indicator of income which represents affordability, quality of the house and general family health conditions. A second group other than women for whom occupation presents a problem in classifying are retired persons. For such persons, the significance of occupation during lifetime or as the last occupation — in relation to income and current health status — seems to decline. Education has been suggested recently as a more sensitive social class measure in health studies (Zurayk, H. et al, 1987). Education of the mother could have possibly been the best among objective measures to represent social class rankings in studies on lead and IQ in children. Mild educational subnormality (with an IQ between 50 and 70) is believed to be predominantly socio-cultural in origin (Wedge, P. and Prosser, H., 1973; Fogelman, K., 1974). Such children are disproportionately concentrated among the lower socioeconomic groups, the retardation being linked to material deprivation, poor educational facilities, family instability and lack of mental stimulation. An Israeli report challenges this view and claims that the main cause of mental retardation may be brain damage as a result of 223 biological disturbances during pregnancy, delivery or infancy (Costeff, H. et al, 1983). Those in lower as compared to higher socioeconomic groups have higher rates of schizophrenia, are more depressed, more unhappy, more worried, more anxious and are less hopeful about the future. No doubt, this feeling will have adverse effects on learning and behaviour. Feeling secure has a great effect on mental achievements. Hypertension could be more associated with social class than with racial factors. Stressful life events have physiologic consequences (such as hormonal changes) that may compromise bodily defense to disease and increase susceptibility to illness. Coping styles with stresses could be observed in the lower classes by smoking more cigarettes. They have less access to medical resources (physicians and dentists) and if care is available, they tend not to benefit from that availability. Strong evidence has accumulated to date that social class is associated with mortality, morbidity and disability rates (Syme, S.L. and Berkman, L.F., 1976). High morbidity and mortality rates in infancy and childhood in the developing countries are often considered to be due largely to poor environmental sanitation, crowding and nutrition (Rahman, M. et al, 1985). Two out of every three in the world are extremely disadvantaged (Smith, J.J. Rev., 1986). The consequences of poverty are enormous and amelioration of its effects will be correspondingly difficult. Should the approach be medical or social? “The ideal has not been tried and found wanting. It has been found difficult and left untried”. 22k 7.5 Undernutrition and Intellectual Impairment Since brain function depends on the correct balance of nutrients reaching it, it is hardly surprising that diet and dietary supplementation can markedly affect a wide range of mental condrijons (Davies, S. and Stewart, A., 1987). McKhann, C.F. (1932) stated: “The neurologic manifestations of lead poisoning usually subside without serious consequences if the ingestion of lead is stopped and the removal of lead from the circulation and its deposition in inert form in the bones can be hastened by the use of a diet high in calcium together with the administration of cod liver oil or viosterol (an ergosterol subjected to ultraviolet radiation by which an antirachitic-vit.D0-potency, calciferol, is developed) to accelerate the laying down of new bone”. Although it was -j^ound that the presence of vit. D in the diet of the rat approximately doubled lead absorption from the gut, in animals with established lead poisoning vit. D behaves differently after lead administration has ceased, producing a fall in Pb-B concentration and a decreased loss of lead from bone (Stephens, R. and Waldron, H.A., 1975). Although milk might promote lead uptake (Stephens, R. and Waldron, H.A., 1975), I have argued against the withdrawal of free school milk in Chapter 6. Kello, D. and Kostial, K. (1973) showed that cow’s milk enhanced the absorption of a single dose. The rats were fed only milk over a period of two weeks. Metabolic changes in the animals could have occurred, so that the increased lead absorption may not be attributed completely to a gastrointestinal effect of milk on lead absorption. 225 Milk was found to reduce lead absorption in human subjects (Blake, K.C.H. and Mann, M., 1983). In children who are subnourished, a reduction in responsiveness and attentiveness is observed. In addition, the subnourished child is easily fatigued and unable to sustain either prolonged physical or mental effort (Birch, H.G., 1972). An adequate state of nutrition is essential for good attention and for appropriate and sensitive responsiveness to the environment. Sustained attention is an essential part of the learning process. One of the most obvious clinical manifestations of serious malnutrition in infancy is a dramatic combination of apathy and irritability. The infant is grossly unresponsive to his surroundings and obviously unable to profit from the objective opportunities for experience present in his surroundings. This unresponsiveness characterizes his position to people, as well as to objects. One of the first signs of recovery from illness is an improvement in mood and in responsiveness to people. The effects of mood and emotion on memory and recall were illustrated in a series of experiments by Jones, E.B., et al, 1987. Each one of us must have had similar experiences which lend support to this hypothesis. Dibble, M. et al (1965) found that among students drawn from a junior high school in New i i was York which jjgg 94% Negroes and^predominantly labouring class, 41% had come to school without breakfast. Breakfast is an English word meaning breaking the fast of the night. It is known that the stomach secretes hydrochloric acid for digestion and this ought to be neutralized by alkalinity (i.e. food) in the morning. With breakfast, cereals taken with milk have greatly reduced the lead promoting effect of milk in volunteer subjects due to its phytate content (James, H.M. et al, 1985). This is in disagreement with the fact that a high phytate content will minimize calcium absorption and hence, by a secondary effect, may promote the uptake of lead, however, the possibilities that lead has an equal affinity for phytate cannot be ruled out (Stephens, R. and Waldron, H.A., 1975) which seems to have been the case indeed. Even though whole milk may not be considered as a prophylactic agent for urban children from poor areas, it has to be seen in perspective. The midday meal seems to be the cheapest students are able to obtain. Different social strata consume different diets. In Britain, the final height attained by normal adults is related to social class. It was demonstrated that young men aged 16-19 years in social classes I and II are 3.5 cm taller on average than those in social classes IV and V, for women this difference is 3.4 cms (DHSS, 1984). The reasons for these differences are not fully understood but are believed to include diet. Intakes of vitamin C do relate to social class, and this vitamin is often taken to be a measure of dietary quality (Wenlock, R.W., 1987). Vitamin C intakes can be taken as probably indicating different dietary patterns by children in the different social classes, even though energy intakes are much the same. Vitamin C deficiency is associated with depression, lethargy and hysteria (Davies, S. and Stewart, A., 1987). Impairment of physical and mental development appeared to correlate with the duration of undernutrition in the first year of life (Chase, H.P. and Martin, H. P., 1970). The role of zinc in meeting the demands of the developing embryo is well known (Simmers, K. and Thompson, R. P. H., 1986). Evidence suggests that women who are not well-grown have 227 characteristics which negatively affect them as childbearers. An inadequate nutritional background in the mother places her child at elevated risk for damage at delivery (Birch, H.G., 1972). Since growth achievement is a function of health history and in particular nutrition, it is clear that the mother’s antecedent nutritional history when she herself was a child can and does significantly influence the intrauterine growth, development and vitality of her child. Stoch, M.B. and Smyth, P.M. (1963) have carried out a semi-longitudinal study of two groups of South African Negro children, one judged in early childhood to be grossly underweight due to malnutrition, and the other considered adequately nourished. At school age, the malnourished children as a group had a mean IQ which was 22.6 points lower than that of the comparison group. The authors wondered whether undernutrition in infancy could inhibit brain growth and subsequent intellectual development. Bellinger, D. et al (1987), which is the same group which carried out the Needleman study in 1979 assessed the relation between prenatal lead exposure, postnatal lead exposure and early cognitive development of children from birth to 2 years of age. The estimated difference between the overall performance of the low-lead exposure and high-lead exposure groups on the mental development index of the Bayley scales was 4.8 points. Scores were related to infant’s prenatal exposure, and the conclusion put forward was that the foetus may be adversely affected by intrauterine lead exposure regarding cognitive development. This study as well as the rest of similar studies reviewed by Davis, J.M. and Svendsgaard, D.J. (1987) ignore the fact that poor nutrition during pregnancy leads to a lower IQ in the offspring (Liungman, C.G., 1975). Moreover, the adequacy of the lead level in umbilical- cord blood as an indicator of intrauterine lead exposure has not been studied in detail. 228 Those dedicated to the improvement of man and his capacities would conduct a study such as that of Benton, D. and Roberts, G. (1988). The investigators examined the possibility that deficiency of dietary minerals and vitamins would prevent optimum psychological function. A multi-vitamin/mineral supplement or a placebo was administered double-blind for eight months to 60 children in Wales aged 12-13 years. The striking finding of the study was the increase in non-verbal intelligence in those receiving supplements. As noted previously, verbal intelligence relies on the individual’s unique cultural, educational and environmental experiences. If one were to argue that a primary requirement for normal intellectual development and for formal learning is the ability to process sensory information and to integrate such information across sense systems, the evidence indicates that both severe acute malnutrition in infancy as well as chronic sub-nutrition from birth into the school years results in defective information processing. Children in underdeveloped countries are more likely to suffer from such damage. Undernourished infants in the Katmandu Valley, Nepal, performed more poorly in the intelligence scales than did the well-nourished infants (Graves, P.L., 1978). Reduced exploratory behaviour was a confirmed feature in the undernourished infants. Exploratory activity would be subsequently reflected in exploratory as well as intellectual competence. Little that is useful emerges from such a lead — IQ sterile controversy. The scope of improvement in the food and nutrient intakes of school children is great. It should be important to understand the effect of poor nutrition on cognitive, social and emotional aspects of human behaviour. 229 7.6 Lead in teeth as an Index of Body Burden Needleman, H.L. et al (1972) suggested that deciduous teeth can be used as an indicator of lead intake, and possibly that of other trace elements in children, for the use of teeth has the advantage of reflecting long term exposure. Calcification of the deciduous teeth begins about the fourth month of foetal life. All deciduous teeth have begun to develop near the end of six months in utero. There is individual variation in time of calcification and eruption. The usual order of appearance of the deciduous teeth in the mouth Is as follows: 0) Central incisors (ii) Lateral incisors (iii) First molar (iv) Canine (v) Second Molar At the age of two or two and a half years, all the deciduous teeth are expected to be in use. from Needleman, H. L. et al (1979) collected shed teeth children at ages 6 to 7 years, Smith M. et al (1983) at the age of 6 years, Haavikko, K. -et al (1984) at ages 6 and 9 years and Ewers, U. et al (1979) at ages 5 to 12 yeais. Permanent teeth are expected to have fully erupted by the age of 12 years (Spencer, M. and Tait, K.M., 1970). 230 Subjects with no domestic or occupational contact with lead showed that the level of lead concentration was higher in the teeth situated in the front than those situated in the back of the buccal cavity, and those in the lower jaw higher than those in the upper jaw. Thus, Smith, M. et al (1983) suggested that the population to be sampled should be restricted to children shedding teeth of the same type and jaw position. It might be expected that lead accumulation would be greatest in those teeth present in the mouth the longest. However, Shapiro, I.M. et al (1975) in their study in which only one tooth per donor was analyzed, the earliest erupting teeth (incisors) were not found to contain greater quantities of lead than later erupting molars. Results of the analysis of just the dentine section of deciduous teeth of 289 school children in Christchurch, New Zealand suggested that the differences in lead concentration with the type of tooth, applies only to teeth with low levels of lead (Fergusson, J. E. et al, 1980). The general trend for tooth-lead content was: Canines > incisors > molars, the difference between canines and incisors being small. Mackie, A.C. et al (1977) suggested that canines be used in teeth-lead studies as far as possible for the following reasons: They are usually non-carious, they are often extracted for orthodontic reasons, and their roots are absorbed less than those of extracted incisors and molars. They are also the easiest teeth to clean and prepare for analysis. Amalgam from five teeth had a mean lead concentration of 33.4 /xg/g (Fergusson, J.E. et al, 1980). Needleman, H.L. et al (1979) analyzed incisors and canines, while Smith, M. et al (1983) 231 analyzed only central incisors. In the Smith study, the whole tooth crown was analyzed (this would consist of enamel and dentine), while in the Needleman study, a slice of the dentine section of tooth was analyzed. •a Fig. 8 shows the principal tissues offhuman tooth. Purchase, N.G. and Fergusson, J.E. (1986) results in New Zealand showed that the concentration of lead in permanent teeth follows the trend: circumpulpal dentine (secondary dentine)root dentine> coronal dentine>bulk enamel. The ratio of the concentration of lead in enamel to dentine and to circumpulpal dentine was found to be 1:2:6, and within the dentine the lead levels were highest in the root dentine. Previously, analysis of specific regions in the profile of lead concentration of teeth has shown the following pattern: surface enamel ^ bulk enamel < dentine circumpulpal dentine (Fergusson, J. E. et al, 1980). Contrary to that, analysis of lead concentrations in enamel and dentine of deciduous teeth of 105, 6 and 9 years old children living in two Finnish towns have shown that all but two teeth contained higher C0ncentr3tl0n of lead in enamel than in dentine (Haavikko, K. et al, 1984). Purchase, N.G. and Fergusson, J.E. (1986) have used carbon furnace atomic absorption spectrometry as a method of analysis, Haavikko, K. et al (1984) used proton-induced X-ray emission method, and Needlercan^H.L. et al (1979) used anodic stripping voltametv*^ • Different laboratories use different methods of analyses which produce quite significant variations. This makes it impossible in studies using teeth to make comparisons on the lead exposure of the populations studied. Blood analysis has the advantage of providing a measure which is comparable between studies, and is not constrained to the age of the child whose shed teeth are analysed or available for analysis during the period of conducting the study. Accordingly, the population which the survey of deciduous teeth attempts to sample is not in any real sense representative 232 of the region from which they were drawn. Exclusion of a number of results for reasons of inconsistency or dental caries leads to attrition in number of samples analysed which might turn out not to be representative of the group surveyed. The main disadvantage of blood is that it reflects predominantly current exposure, so unless serial blood measurements are obtained it is not possible to know whether a current lead measure accurately reflects past exposure. Blood-lead levels tend to increase with age (Quinn, M.J. and Delves, H.T., 1987; Quinn, M.J., 1985), however, no relationship exists between the concentration of lead in dentine and the age of the child when the tooth is shed (Fergusson, J.E. et al, 1980). Lead levels in teeth are generally higher in children than in adults (Grobler, S.R. et al, 1985) although for the special case of permanent teeth, lead elimination can be neglected as dental tissues once fully formed, do not undergo the remodelling process bones do, and have a minimal mineral turnover (Hunt, V.R. et al, 1964). The skeleton in the adult contains 90% of the lead burden, while that in the child contains 70% (RCEP, 1983). Using a model of a first-order kinetics of lead accumulation in teeth, the rate constant of lead transfer from blood to teeth is found to be independent of changes in Pb-B levels within the 10 to 25 /zg/100ml blood range (Steenhout, A., 1982). If lead uptake in teeth is not proportional to incremental increase of lead in blood, the tooth- lead level does not reflect environmental exposure to lead. The factors governing the transfer of lead from blood to teeth could possibly be due to biological effects. The lead content of bones was higher in a soft water area than in a hard water area (Crawford, M.D. and Crawford, T., 1969). It is not known whether the same 233 applies to teeth. The presence of high levels of calcium and phosphate resulted in formidable matrix effects in teeth (Clegg, D.E. et al, 1984). In the mouth, a process of demineralization and remineralization — a dissolving and reforming of tooth mineral—occurs constantly at the surface of teeth. This is a new hypothesis that has recently been under investigation (Raloff, J., 1986a), and seems more plausible to me. Plaque-forming bacteria, which thrive on the fermentable carbohydrates in food, create weak acids. It is these acids that demineralize teeth. Saliva contains the constituents needed to remineralize them again. Carious lesions, or caries, form when demineralization exceeds reminerS^ization. Surface enamel was analyzed for Pb, Cu, Fe, Zn and Ca. (Purchase, N.G. and Fergusson, J.E., 1986). Continued etching of the same spot demonstrated a fall off in the levels of the trace elements with increasing depth. The drop was most rapid within the first 1-2 \im, and was greatest when the lead concentration was highest. Calcium was estimated in the enamel to be 37%. In addition to the calcium, phosphate, fluoride and several additives have recently been tried as remineralizing rinse chemicals through the enamel (which acts as a molecular sieve) to reharden the deep-seated carious lesions. We have already seen the antagonistic effects of trace elements to lead deposition in the body particularly, Ca and Fe (discussed under chapter 6). The mean concentration ranges of the elements in the first etch of surface enamel were: 2 3 4 Pb(n = 13), 1100 /zg/g, Fe(n==9), 850 /zg/g, Zn (n = 10), 1030 /xg/g (Purchase, N.G. and Fergusson, J.E., 1986). The effect of milk on the development of teeth in children is well known. The effect of diet on lead retention in the body and its importance was discussed in chapter 6. Tooth development is a continuous process. There are periods when the tooth is metabolically active, and periods when it is passive. If lead absorption was increased during the period in which a particular tooth is active, then that tooth would come to have a higher concentration of lead than the others in the mouth (Mackie, A.C. et al, 1977). The authors stated that there is a possibility that lead may be absorbed directly from the mouth. Clemente, G.F. et al (1984) stated that smoking may have some influence on the lead (210pb) content of teeth. Male adults fiSLVe over 30% more lead in their bones than females (Barry, P.S.I., 1975), yet there is no significant difference in teeth —lead between men and women (Clemente, G.F. et al, 1984). The sex of the donar did not influence the levels of lead found in teeth in any of the studies conducted (Mackie, A. C. et al, 1977; Haavikko, H. et al, 1984; Clegg, D.E. et al, 1984; Ewers, U. et al, 1979). Accumulation of lead in circumpulpal dentine (the section having the highest lead concentration) is thought to occur under circumstances of sustained lead exposure (Maresky, L.S. and Grobler, S.R., 1987), yet there does not exist any standard upper limit. Haavikko, K. et al (1984) studied the geographical variation in tooth-lead levels between Helsinki, the capital city of Finland (assumed to represent high lead exposure), and Kuopio, a country town in the middle of Finland (with low or moderate lead exposure). Median values of dentine-lead concentration of children in 1971 were at the same level in Helsinki and Kuopio (2ppm and 2.9 ppm respectively) with the country town value tending to be higher, and changed only slightly compared with the children bom in 1974 (1.5 and 2.7 ppm 235 respectively). The enamel-lead concentration (4.2 ppm) in Helsinki children born in 1971 compared with 9.1 ppm in those born in 1974 had increased more than twofold. In Kuopio, hardly any change in enamel lead concentration was noted. There is no indication that lead concentration in teeth accurately reflects exposure. Wide variations in tooth-lead levels are reported in the literature with no possibility of assessing the significance of the results. Tooth lead levels were higher in Birmingham (England) than in either Sutton Coldfield or Wednesfield, and it was supposed that environmental levels are higher in Birmingham than in those areas (Mackie, A.C. et al, 1977). Sutton Coldfield is a residential area with little industry and small volume of traffic. It was used as a control area in the recent UK Blood- Lead Monitoring Program 1984-1987 to assess changes in Pb-B concentrations as a result of reducing the lead content of petrol. Median Pb-B level for men in Sutton Coldfield (Birmingham) was 10.5 /Jg/100ml, while the Pb-B level for taxi drivers in Lambeth (London) was 8.8 /ig/100ml (DOE, 1987). A sample of 289 school children in Christchurch (New Zealand) were divided into 2 groups: children living in post-1940 housing and non-industrial areas (mean Pb-T=4.8 //g/g), and children in pre-1940 housing and industrial areas (mean Pb-T=6.7 /ig/g). The difference in the means related to greater environmental lead in the latter area from paint and industry. Future studies on tooth-lead levels should focus on the physiological factors governing the transfer of lead from blood to teeth. The correlation between lead in bones and teeth would be of interest for further investigation. 236 7.7 Recent findings on Lead Exposure and Children’s Intelligence Since 1943 (Byers, R.K. and Lord, E.E., 1943), studies have looked for possible effects on children exposed to various levels of lead. Until 1979 published work related to studies which either investigated children exposed to specific sources of lead, such as children living near a smelter or lead work^or investigated Pb-B levels in mentally retarded children in relation to intellectual performance and behaviour. These studies have been reviewed by several authors (Gregory, R.J. and Mohan, P.J., 1977; Rutter, M., 1980). Some studies will not be considered here as they do not take account of many of the major methodological issues. Some studies used poor markers of lead exposure such as hair lead (Stellern, J. et al, 1982; Thatcher, R.W. et al, 1982). Results from studies with highly selected samples (Gillberg, C. et al, 1982) and inadequate control of confounding variables and statistical analyses cannot be used to either support or refute hypotheses about the effects of lead at low levels of exposure. Recent studies in Britain have been showing a striking consistency. The Birmingham studies (Harvey, P.G. et al, 1984) investigated young children — one sample aged 2.5 years and the other 5.5 years. Using a carefully selected random sample of 189 inner-city children all aged 2.5 years at time of testing, both psychometric measures and detailed behavioural observations were collected, together with extensive background information on their families. Initially, there was a significant correlation of —0.17 between Pb-B level and IQ. However, using multiple regression techniques (in preference to factorial-type analyses based on arbitrary groupings) to deal with confounding variables, the amount of variance in IQ accounted for by lead was less than 1%. In the older sample the correlations were lower. The results are of extremely great value for two reasons: (a) The greatest intakes of lead occur during the first few years of life (Purchase, N.G. and Fergusson, J.E., 1986) particularly regarding pica. 237 (b) The sample of venous blood was taken no later than 48 hours after psychometric testing which is rather unique in the literature. Yule, W. et al (1984) in their ratings of children’s behaviour used a Pb-B level that came from a single determination some 9 months prior to the teacher’s rating behaviour. The behavioural measures used by Harvey, P.G. et al (1984) were amongst the most sophisticated and detailed to be used in this area. The children were videotaped in two situations: free-play in a standard playroom and during psychometric testing. Data from the 2.5 years old children showed adequately reliable measures of the child’s behaviour in the two situations. Pb-B level showed no associations at all with any of the behavioural measures. The Harvey study reported indications of social class differences in apparent lead effects. The age of the house showed a marked and highly statistically significant relationship with blood lead: for children living in houses prior to 1939 the mean Pb-B level was 0.79 /imol/£ (16.4 /ig/100ml), and for those living in houses built after 1939 it was 0.66 /imol/£(13.7 /ig /100ml). Further support for this argument came from Lansdown, R. et al (1986). This study was undertaken to replicate an earlier one carried out in London (Yule, W. et al, 1981) in which 166 children aged 6 to 12 years, living within 1 km of a London factory were assessed in school. In the 1986 study, 194 childen living near an urban motorway were given the same battery of tests as well as extensive family interviews to determine background variables. The Pb-B levels used were those of the Greenwich study (Miller, I. B. and Cooney, P.A., 1982) where the mean Pb-B level of children at Deansfield School not residing at Rochester Way (14.02 /ig/100 ml) was significantly higher than those at the school and residing at Rochester Way (12.15 /ig/100ml). The total number of blood samples was 221 in the Greenwich study. Lansdown, R., et al 238 (1986) had 194 children (whose Pb-B levels were known) available for psychometric testing (87.8% participated). A second blood sample was taken from 162 children after the psychological assessment was completed, some 20 months elapsing between the 2 measures. Unlike the Yule, W. et al, H it. 1981 study in which children belonged predominantly toiworking class, the Lansdown, R. et al, 1986 sample contained a much higher proportion of middle class children. No significant relationships were found between lead and any of the ratings, even before controlling for social factors. The conclusion from this study is that there is no evidence of a significant effect of lead on IQ even though the 1981 study has shown significant effects, and even after partialling out social factors. No doubt the 1986 study has improved on the 1981 study by proper selection of the sample and ratings. Teachers7 ratings of behaviour were published in a separate article (Yule, W. et al, 1984) in which 3 .behaviour scales have been used: The NeedlBITian'S Questionnaire, The Rutter B(2) Questionnaire and the Conner’s Questionnaire. The fact that the effects of lead on behaviour stem from studies that were unable to control for confounding variables must raise real doubts about the reality of the effect (Yule, W. et al, 1984). Before controlling for social factors, there were significant differences between the lead groups on the IQ scores in favour of the low-lead group (Smith, M. et al, 1983). When social factors were controlled, the differences between groups reduced and were no longer statistically significant. Pocock, S.J. et al (1987) reexamined the data from the Institute of Child Health/University 239 of Southampton study (Smith, M. et al, 1983) to see if any residual lead-IQ association exists after allowance for confounding factors. Seventeen factors were shown to be associated with child IQ, the most important being the IQ of the mother, followed by family size and social class, and the quality of family relationships. There was no overall evidence that tooth lead concentrations were related to child IQ once these other factors were taken into account. Even so, it seems that the true influence of confounding factors on the lead-IQ relationship has not been fully accounted for. One notable omission in the survey was the effects of the father’s IQ which was not measured but which may have an important influence. Factors such as maternal IQ, the child’s ordinal position and father’s educational level are well known to be associated with IQ (Harvey, P.G. et al, 1984). Fulton, M. et al (1987) investigated the effect of Pb-B level on children’s ability and attainment in a sample of 855 children aged 6 to 9 years within central Edinburgh, Scotland. A significant negative relation between log Pb-B level and test scores was found. The Edinburgh study and the Birmingham study both used the British Ability Scales (BAS) for testing and multiple regression techniques for statistical analyses. However, although the Edinburgh study took into account 33 possible confounding variables, the selection of the potential confounders affecting children’s intelligence was rather odd. The only variable which showed an interaction with lead was parent’s “mental health score”, the effect of lead being greatest when the parent had evidence of mental health problems. This is a serious defect in the study if such children have been included in the psychometric testing in the first instance. It was stated that: “the results suggest that the relation between lead and attainment scores is strongest in the youngest age group and where the child’s interest score is low. 240 The geometric mean Pb-B level of the Edinburgh children was 10.4 //g/100ml while the arithmetic mean Pb-B level of the Birmingham children was 15.6 /ig/100ml with no significant effect on IQ. One parent (usually the mother) was interviewed at home, and ability assessment was conducted. Since the mental health score of the parent was an important determinant, one is forced to conclude that the negative effect of lead observed is rather due to this reason and not otherwise. The catalogue of supposed facts allied to uncertain arguments to produce doubtful conclusions could be continued. The quality of evidence about negative effects of lead on IQ is not as strong as Fulton, M. et al (1987) claim. The subject of lead and its possible effects on children’s intelligence and behaviour is one which has aroused a great deal of argument over recent years. It is not difficult to follow why lead may have been to blame for this. Lead in petrol is claimed to be a major culprit, and there seemed to be an easy solution on which to focus a campaign. There is now overwhelming evidence to show that when appropriate confounding variables, such as parental IQ, the standard of care in the home, etc., are taken into account, any possible lead effect is so small that it cannot be measured with any certainty. This is if, in fact, it exists at all. 241 CHAPTER 8 CONCLUDING COMMENTS No wonder the public is beginning to ask, Is Science a really good thing? Are we spending too much on science and are we spending on the right kinds of science? What contributions have the fruits of scientific knowledge made to humanity? It is always easy to call for more research on apparent findings thought to be causes of diseases. Let us do studies of what makes us survive and not only of what makes us die. Let us do case/control studies of healthy persons with ill persons as the control; let our prospective studies of populations focus on those who remain in good health rather than only those who become ill. Let us recognize that there will be multiple causes for health just as there are multiple causes for disease and that health like disease is a biologic spectrum. Let us recognize that establishing the proof of the causation of health will be more difficult and challenging than the causation of disease. “A penny spent on prevention is worth a pound spent on cure” has not been widely enough known and appreciated. Most people do not worry about their health until they lose it. A person may be too slow thinking to achieve scores in intelligence tests, and yet may have an extraordinary power to create and realize ideas. Since creativity cannot be measured by IQ tests, one wonders whether IQ tests are useful as practical selection tools. Studies #of high intellectuals in society and what has contributed to their intellect’s development have never been conducted, simply because they are thought of as “gifted” or “talented” or “inherently superior” 242 Intelligence being a by-product of the child’s relationship to his surroundings, we ought to learn more about how infants should be treated in order to have a well-developed intellect. The hypothesis that zinc is a cause of senile dementia (Davies, S. and Stewart, A., 1987) ought to be adequately investigated. It is a common assumption that aging often impairs the ability to think and reason; yet training techniques improved the performance of elderly subjects on tests of memory, reasoning and problem solving. These approaches remedy a loss of function or bolster the skills of people suffering no decline (as reported by Bower, B., 1986). This study indicates that decline in the elderly occurs because they don’t use acquired skills as much as they used to. This is a very important study and ought to be replicated. Reasoning skills in the elderly relate to everyday tasks such as understanding instructions on medicine bottles and food labels, spatial ability aids in navigating neighbourhoods and buildings and in reading road maps. Ideas and fears about the mentally handicapped or the mentally disordered have been changing continually. In 1926, intelligence tests were considered in many instances valuable tools for the practitioner in providing information as to prognosis and desirable procedure (Fordyce, A.D., 1926). New experts known as educational psychologists and mental welfare officers are now advocating the idea that handicapped children are able to learn and benefit from teachers in ordinary schools (Smith, J.J. Rev., 1986). I was told by a practising expert on mentally handicapped children who has been in the profession for over 12 years that: With appropriate training, even the mental abilities of children with Down’s Syndrome could be improved (Anon. B., Personal Communication). If we try to measure the IQ of a person living in the desert, it is highly unlikely that his score 243 will come anywhere near 100. Yet, he knows things about the desert (such as water holes and sense of direction) that we ourselves might not know. Therefore, he does not conform to our own particular standards of “normal”. The word normal is used in expressions such as: normal traffic flow, normal behaviour, normal weather etc. . Accordingly, conforming to what is normal is simply conforming to what is usual, and the lower the IQ, the greater the social problems. The IQ has become very much part of general assessment, yet in no way is success determined only by IQ; there are so many other factors. Scoring high grades at school is a poor measure of academic achievement, for exams can only test what you know not what can you do with your knowledge. Perhaps educational reforms should start with teachers. The teachers* attitude towards students and students’ attitude towards their teachers is of paramount importance in success. Those who feel there is nothing appealing in teaching must not be appointed as teachers. Phrases such as “he or she will never learn” or “does not understand” must never be used in addressing a child, for this implants an inferior intellectuality complex. The relationship between intelligence and attitude has recently been examined in a sample of white South African teacher trainees in Johannesburg (Katz, Y.J., 1988). An Israeli investigator tested IQ measures for correlations with religious principles and practices, traditionalism and anti-modernism factors to determine possible statistical significance! The IQ test is called D-48 test; an undated reference called “Pfeliminary Manual: The D-48 Test — Consulting Psychologists Press” seems to be the backing statement. The Social-Religious- Political (SRP) Scale questionnaire was compiled by the author to assess social, religious and political attitudes. No conclusions could be reached regarding the connection between attitudes and intelligence. However, the results seem to indicate that Africaans speakers high on religious principles had significantly higher scores on the intelligence measure than those Africaans speakers low on the same variable. Although the D-48 test is stated to be “essentially a non-verbal analysis test primarily measuring the g, or general, factor of intelligence”, all the attitudinal variables examined in this study were mediated by language. It appears that the IQ measures in this study were measuring conformity to principles and standards. If IQ test s ’ results are to claim superiority among certain religious groups in the future, it will be an utter disaster for the progress of science and humanity. There is no question that West Indian children in Britain on average obtain lower scores than whites (Mackintosh, N.J. and Mascie-Taylor, C.G.N., 1985). It can come as no surprise that West Indian children in Britain do live in relatively impoverished social circumstances. Analyses of data from the National Child Development Study and the Child Health and Education Study (Mackintosh, N.J. and Mascie-Taylor, C.G.N., 1985) revealed that their fathers were more often unemployed than the fathers of white childen, and that if employed they were more likely to be in manual occupations; that their family incomes were lower but their families larger; and that they lived in more serious conditions of overcrowding, with fewer amenities and in worse neighbourhoods. Although each study contained more than 10,000 white children to less than 150 West Indians, no white matches for all of the West Indians could be found; this says much for the social circumstances of the West Indians. Long-resident Asian children appear to obtain significantly higher scores than West Indians both on IQ tests and on measures of school attainment. Provided recent immigrants were excluded, Asian children obtained IQ scores at age 11 hardly lower than the white mean, and their reading and mathematics scores as well as their 245 performance on public examinations were equally good. The effect of length of residence in the UK on performance on a test should help to dispose of the myth that these tests are even remotely “culture-free”. Poor performance of West Indian children could be attributed to direct discrimination by society as a whole and schools and teachers in particular as well as cultural attitudes towards them. Lack of incentive also plays a major role among the West Indians. The Asian community seems to suffer less discrimination in Britain according to Mackintosh, N.J. (1986). The experience of schooling, perhaps through teachers’ disparaging attitudes is adversely affecting the educational performance of West Indian children. That is when they first arrive in school their performance is quite good, but that as they progress through school, so they fall further and further behind (Mackintosh, N.J., 1986). No doubt, personality which affects IQ, develops from the interaction of the living human organism with an environment that frustrates or encourages, and conditions its impulses. That intellectual differences between ethnic groups are largely due to differences in social circumstances could be easily seen in changes in IQ scores over the last two decades. The data which showed that long-resident Asian children were performing well were mostly obtained in the early 1970’s where the ranking followed this descending order: Indian, Pakistani and then West Indian children. However, in the 1980’s the following descending order was observed: Indian, West Indian and then Pakistani children (Table 13). 246 Table 13: IQ Scores of Ethnic Minorities in UK — Child Health and Education Study, 1980 (Mackintosh, N.J., 1986) IQ Scores Indian (n == 170) 95.6 West Indian (n = 125) 94.3 Pakistani (n = 91) 90.5 It appears that Pakistani children’s circumstances are becoming slightly worse than those of West Indians. An idea actually put to me by some people for a serious investigation is probably worth mentioning in this context. Soil and dust-lead levels data collected from the city of Leeds (England) are to be complemented by any necessary environmental data (which is missing or unknown) in order to formulate a mathematical model out of which it would be possible to predict the Pb-B levels of the Pakistani population living in Leeds. I believe that strange soil/dust sample results, based on a lack of knowledge of the multiplicity of determinants of Pb-B levels and intelligence are worthless. Strong support for an antiracial society is deemed necessary and we would like this notion to be firmly established among the public. I hope that I have been able to elucidate the use of pretended logic in a highly selective fashion to support a prejudice about a connection which is dubious. 247 Index (1975 - 100) 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 Source: Warren Spring Laboratory, Department of Trade and Industry Figure 1? Emissions Trends of hydrocarbons, carbon monoxide, nitrogen oxides and lead (DOE, 1986) 248 Figure 2: Fate of lead added to petrol in theliK {RCEP, 1983) Figures are in thousand tonnes per year and are approximations for 1981 iue 3: Figure Percentage of concentration at roadside itne rm oowy DS, 1980) (DHSS, Motorway from Distance aito o Aron La Cnetain with Concentrations Lead Airborne of Variation 0 5 2 AMBIENT SOIL SURFACE AND AIR GROUND WATER U"\ CM INHALED AIR Figure Principal pathway? df lead from the environment to human consumption (USFPA.,. 1986) ^ - Figure 5: Location of surveys Adults, living on major roads: adults, occupationally exposed to petrol lead adults controls children living on major roads (Quinn, M.CL and Delves, H.T., 1987) _ (jk Pb_B Levels Monitoring Programme 1984 - 1987. 252 Glycine + Succinyl CoA (active succinate) i + Pyridoxal Phosphate ( 1) i ALA 4-ALA dehyratase* ------>(2) ^ PBG (3) J, Polypyrrole (4) * UPG 3 URO I Uroporphyrinogen Decarboxylase ~ -» (5) V v CPG 3 COPRO I Coproporphyrinogen Decarboxylase - ( 6) V PPG 9 (7) PP 9 Ferrochelatase* (haem synthetase) - - » (8 ) F e (GSH) V Haem <-----globin V Haemoglobin There may be at least four stages in haem synthesis which lead inhibits. 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Scorer (Senior Research Fellow in Environmental Technology and Applied Mathematics at Imperial College) u )L L b s desi^heJ* aluL ■ SdjXit'ViSel $/\S Reject lh R&iLaJrck j Slid VLCCo\'lih I also wish to express my gratitude for the Hariri Foundation who has loan-funded the period of my research in London. I am glad to acknowledge the speed of Mrs. D. Abeysekera in typing this thesis << H^Ks >/"11 oj-t Ju. dtu. +• Pr-f- !• TL.trkt'.h (ck&it-K,o.i. «j- ft- 6*. T*di«i-') f H ^ °f aih-'iSSi“h ^ k,s r^ot ,fc LU I u, ^ -p-r11 rr*f- Scut- .1% b tKA ■ A i . -L Lai S„(L »he cU v.c* Va M e fe ^ /\k oVeYstsKS stu-A-eovThas 1 , a ^ ?dr . PU- # ts - fty ^ ? ex P L ] ) * 308