Sources of exposure to and public health implications of organophosphate pesticides

Kushik Jaga1and Chandrabhan Dharmani2

ABSTRACT Objective. To review the public health significance of organophosphate pesticide exposure in the United States of America. Since the situation of high organophosphate pesticide expo- sure and the concomitant health risks in the developing countries of the world is well known, this article seeks to highlight the public health significance of organophosphate exposure in the United States, where it is less common than in many other nations. Looking at the situa- tion in the United States would serve to further emphasize the seriousness of organophosphate pesticide-related health issues in developing countries. Methods. A search for journal articles on organophosphate pesticides and organophosphate exposure was done on the PubMed electronic bibliographic database system of the National Li- brary of Medicine of the United States. To supplement that search, information on organo- phosphate toxicity, biological monitoring, and regulation of pesticides was obtained from other published articles, textbooks, and relevant Internet sites. Results. Organophosphate pesticides are a group of chemicals that are mainly used in agri- culture. Organophosphates inhibit the activity of both the cholinesterase (ChE) enzymes—red blood cell (RBC) ChE and serum ChE—resulting in the cholinergic features of organophos- phate toxicity. A 50% reduction in serum ChE activity from the baseline is an indication of acute organophosphate toxicity. The RBC ChE activity, which is less rapidly depressed than the serum ChE activity, is a measure of chronic exposure to organophosphates. Exposures to organophosphates are broadly classified into two categories: occupational and environmental. Occupational exposures occur among agricultural workers (including migrant farmworkers), industrial workers, pest control exterminators, and other workers. Nonoccupational exposure affects a large segment of the general population in the United States. Residential exposures come from organophosphate pesticide use by exterminators and by household residents as well as from dietary and accidental exposures. Other environmental exposures occur in public places and areas close to farms, and exposures could also happen from organophosphate use in chemical warfare or terrorism. In the United States some organophosphate pesticides are re- stricted by the Environmental Protection Agency in order to protect humans, animals, and the environment. In addition, the Food Quality Protection Act regulates dietary exposure to pes- ticides, particularly for infants and children. Conclusions. Organophosphate pesticides continue to pose a risk to human health in the United States. Biological monitoring should be used to strictly regulate occupational expo- sures to organophosphates and thus protect the health and safety of workers. Among the pub- lic there should be an increased awareness of environmental exposure to organophosphates as well as of the threat of chemical warfare or terrorism.

Key words Pesticides; insecticides, organophosphate; occupational exposure; environmental exposure; environmental monitoring; government regulation; United States of America.

1 VA Hudson Valley Healthcare System, Montrose 10523, United States of America or to 51 Eiler Lane, 2 New York Medical College, School of Public Research Corporation, Montrose, New York, Irvington, New York 10533, United States of Health, Valhalla, New York, United States of United States of America. Send correspondence to: America; e-mail: [email protected] America. Kushik Jaga, P.O. Box 358, Elmsford, New York

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 171 ORGANOPHOSPHATES TABLE 1. A list of commonly used organophosphate insecticides registered by the Environmental Protection Agency of the United States of America, in- The organophosphate compounds cluding ones whose use is restricted are a group of insecticides that were Organophosphate insecticides Organophosphate insecticides (con.) first discovered in 1938 by a group of German chemists. Organophosphates Acephate Isofenphosa were introduced as nerve poisons or Azinphos-methyla Malathion a chemical warfare agents during World Bensulide Methamidophos Chlorethoxyphosa Methidathiona War II, and later they were developed Chlorpyrifosa Mevinphos into less potent chemicals (1, 2). The Coumaphosa Naled organophosphate compounds are Diazinona Phosmet used to destroy insects such as fleas, Dichlorvos Profenofosa Dicrotophos Propetamphos lice, flies, and mosquitoes (3). These Dimethoate Sulfoteppa chemicals are used for pest control on Disulfotona Sulprofosa crops in agriculture and on livestock, Ethiona Tebupirimiphos for other commercial purposes, and Ethopropa Temephos a a for domestic use, that is, by individu- Ethyl parathion Terbufos Fenamiphosa Tetrachlorvinphos als in their own homes (2, 3). Organo- Fenitrothiona Tribufos phosphates have gained popularity Fonofosa Trichlorfon worldwide in preference to organo- Source:Sullivan JB Jr., Blose J (2). chlorines, which are persistent and aUse of this organophosphate is restricted by the Environmental Protection Agency of the United States (4). more damaging to the environment. The organophosphates break down more rapidly than do organochlorines in the environment, they have a milder impact, and they are safer and less an area with less exposure. This in Organophosphate toxicity persistent (2, 3). A list of commonly turn would serve to further emphasize used organophosphate insecticides the seriousness of pesticide-related Organophosphate exposure occurs registered by the Environmental Pro- health issues in developing countries. among people who come into contact tection Agency (EPA) of the United We selected the United States for this with the chemicals as a result of their oc- States of America is given in Table 1. review. In that country, pesticide ex- cupation (3, 5), and the general popula- As also indicated in Table 1, the use of posure affects both persons born there tion is exposed by the entry and spread many organophosphate insecticides and immigrants. For instance, organo- of the chemicals into the environment has been restricted by the EPA in order phosphate exposure greatly impacts (1, 3). Exposure to organophosphates to prevent health risks (4). the health of Latin Americans em- occurs via inhalation, absorption into Pesticide exposure is a global public ployed as migrant farmworkers in the the skin, and ingestion (1, 2). The or- health issue. The World Health Organi- United States (7). ganophosphate insecticides bind with zation (WHO) has estimated that each The organophosphates are com- the cholinesterase (ChE) enzyme at the year there are some 3000000 cases monly used in the United States. neuromuscular junction and deactivate of acute pesticide poisonings, with Therefore, for the purpose of this re- or inhibit the activity of the enzyme by 220000 deaths. The majority of these view, a literature search on organo- irreversible phosphorylation. This re- incidents occur in developing countries phosphate pesticides was done on the sults in elevated levels of acetylcholine (5), particularly in Africa, Asia, and PubMed electronic bibliographic data- (ACh), which acts on the muscarinic re- Central and South America. In Central base system of the National Library of ceptors situated at cholinergic junctions America, for example, between 1992 Medicine of the United States. Publica- in skeletal nerve-muscular junctions, at and 2000 the importation of pesticides tions that described the sources of nicotinic receptors in autonomic gan- increased noticeably, the incidence rate organophosphate exposure were se- glia, and receptors in the central ner- of acute pesticide poisoning rose from lected. The relevant information from vous system (CNS) (2, 8). Both the red 6.3 per 100000 population to 19.5 per the literature was grouped into occu- blood cell (RBC) ChE activity and the 100 000 population, and the mortality pational exposures and into nonoccu- pseudo (or serum) ChE activity are rate climbed from 0.3 per 100000 pop- pational or environmental exposures. inhibited by organophosphates. The ulation to 2.1 per 100000 (6). In addition, information on organo- serum ChE enzyme is inhibited more Since the situation of high exposure phosphate toxicity, biological monitor- rapidly and is restored to the normal and health risks in developing nations ing, and regulation of pesticides was levels within 60 days, being an indicator is known, the objective of this article is retrieved from other published arti- of acute organophosphate poisoning. to highlight the public health signifi- cles, textbooks, and appropriate Inter- RBC ChE activity is depressed less cance of organophosphate exposure in net sites. rapidly by organophosphates and takes

172 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides several weeks to several months to re- People with chronic exposure to general safety from toxicity (14). Ac- turn to its normal level. The RBC ChE organophosphate insecticides at low cording to data from the Toxic Expo- enzyme is the preferred measurement to moderately high doses develop a sure Surveillance System of the Amer- for assessing chronic organophosphate pesticide-related illness. These mild to ican Association of Poison Control exposure, especially in workers exposed moderate symptoms of organophos- Centers, there were 10073 exposures to organophosphates (2, 3). phate toxicity include nausea, head- to organophosphate insecticides in High dose levels of organophosphate ache, dizziness, blurred vision, abdom- adults in the United States in the year insecticides cause acute intoxication as a inal pain, vomiting, and chest tightness, 2000 (15). Of those exposures, 9609 of result of increased activity of ACh at with ChE depression (2). Other risks of them were unintentional and 276 were muscarinic, nicotinic, and CNS recep- organophosphate exposure include re- intentional; 2720 cases were treated at tors. This manifests as acute cholinergic productive effects, spontaneous abor- health care facilities. signs and symptoms of organophos- tions, and fetal death (10). Both non- A simple classification of exposure phate poisoning, including gastro- Hodgkin’s lymphoma among farmers to organophosphates is: (a) occupa- intestinal upset, bronchospasm, miosis, and cancers in children have been re- tional exposure and (b) environmental urination, sweating, lacrimation, brady- ported as a result of organophosphate or nonoccupational exposure (2, 16). cardia, fasciculations, muscle weakness, exposure (11). The neurotoxicity of Unintentional, accidental, or suicidal hypertension, and CNS depression or organophosphates manifests as neu- poisoning can occur in both occupa- coma (2, 3). In the United States in 1999 robehavioral and neurophysiological tional and nonoccupational exposures more than 13 000 cases of organophos- effects in people who have experienced to organophosphates (17, 18). Homici- phate poisoning were reported to poi- acute organophosphate poisoning (12). dal poisoning would include suicide son centers, there were more than 3 000 Rosenstock et al. (13) found that agri- poisoning as well as intentional poi- cases seen in emergency departments, cultural workers in Nicaragua who had soning of one individual by another and 83 fatalities occurred (9). acute organophosphate intoxication (17). Chemical warfare with organo- Organophosphate poisoning is treated suffered from chronic neuropsycho- phosphates is a form of terrorism, with with atropine and pralidoxime (2, 5). logical effects. It is not clear whether homicidal poisoning targeted to affect Both substances are very effective in chronic low-dose exposure to organo- a large population (18). Various situa- reducing the cholinergic effects of phosphates causes any neurological tions of organophosphate exposure organophosphates. Atropine blocks impairment in exposed people (12). are outlined in Table 2. the ACh receptors, thereby preventing the action of ACh at respective sites. Pralidoxime, in contrast, reverses the SOURCES OF Occupational exposure ChE inhibition by reactivation of the ORGANOPHOSPHATE ChE enzyme. EXPOSURE Workers are exposed to pesticides in Following an acute cholinergic crisis, their workplaces as a result of their oc- an intermediate syndrome occurs 24 to Organophosphate exposure is a cupation. Irrespective of whether the 96 hours later, which results from major public health issue in terms of job involves pesticide use, the pres- presynaptic and postsynaptic neuro- health, morbidity, health care, and ence of the chemical in the work en- muscular dysfunction. This results in acute respiratory muscle paresis, pare- sis of the proximal limb and facial mus- cles, and cranial nerve palsies (1, 5). An organophosphate-induced delayed TABLE 2. Situations of occupational exposure and of nonoccupational expo- sure to organophosphates neuropathy occurs 2 to 3 weeks after an acute episode of poisoning. Common Environmental or features of this syndrome are CNS and Occupational exposure nonoccupational exposure peripheral nervous system effects of a mixed sensory-motor neuropathy. Agricultural workers Residential exposure: Manufacturing industry workers •resident use, exterminator use These cause progressive distal muscle Pesticide exterminators •dietary exposure weakness, ataxia in lower limbs, flaccid Greenhouse workers and florists •accidental exposurea paralysis, and spasticity (3, 5). The syn- Office workers Agricultural worker take-home exposure drome has been correlated with the in- Health care workers Close proximity to farms hibition of a neurotoxic esterase in the Veterinary employees Aerial spraying Prosectors performing autopsies Public places CNS, and not the ChE enzyme. The Store employees Contaminated organ donor extent of delayed polyneuropathy is Gulf War veterans Suicidal (intentional) poisoninga determined by the differences in struc- Chemical warfare tural activity of different organophos- aAccidental poisoning and suicide poisoning are possible in both occupational and nonoccupational phate insecticides (1). exposures.

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 173 vironment constitutes an occupational Ciesielski and colleagues (21) per- agricultural workers who handled pes- exposure. Workers who handle or- formed a study on organophosphate ticides. They also reported that out ganophosphates directly are at higher exposure and migrant farmworkers in of 486 farmworkers with pesticide- risk of exposure than are workers who the state of North Carolina in the early related illness, 13.1% of them reported do not handle pesticides directly. Most 1990s. In comparison to 42 nonfarm- use of organophosphate insecticides. occupational exposures to pesticides workers, 202 farmworkers had signifi- The main route of entry was by dermal are through inhalation or dermal ex- cantly lower RBC ChE activity, which exposure, and their symptoms in- posure, and in some instances by ocu- was measured in units (U) per gram volved more than one body system. lar exposure (2, 3). (g) of hemoglobin (Hb) in both groups. The RBC ChE activity in the farm- Pesticide manufacturing. Industrial Agricultural workers.Exposure to workers was 30.28 U/g Hb, compared exposure to organophosphates oc- organophosphate insecticides occurs to 32.3 U/g Hb in the nonfarmwork- curs in chemical plants that produce predominantly on farms (2, 3) or in or- ers. About 12% of the farmworkers organophosphate pesticides (5, 10). chards (19), where the insecticides are had very low RBC ChE activity. The While production workers in the in- used for pest control. In the 1990s in cholinergic symptoms reported by dustry are directly exposed to the the United States some 2.5 million to farmworkers correlated well with the chemicals, all other employees in the 5.0 million agricultural workers were reported organophosphate exposure. manufacturing plants can be exposed. exposed to organophosphate insecti- Accidental poisoning with organo- Workers in these plants face risk situa- cides (7). There are about 1.8 million to phosphates has occurred among agri- tions that are similar to the ones that 2.5 million hired farmworkers in the cultural workers. Much of the expo- occur in workers exposed to pesticides United States who have come from sure to pesticides has to do with on farms. Mexico, Central America, or South individual perceptions and knowl- Burns et al. (26) studied the morbid- America. During 1997–1998, 77% of edge of the risks of pesticide exposure ity of 496 employees exposed to the farmworkers in crop agriculture were and safety (23). Among migrant farm- chlorpyrifos organophosphate in their Mexican-born. One third of migrant workers their methods of handling work in a plant that manufactured the farmworkers are in the state of Califor- pesticides and their safety practices re- product. In comparison to control sub- nia. In just one of the 58 counties in flect their poor knowledge and under- jects, the exposed workers had signifi- California, Fresno County, more than standing of the health risks of pesti- cantly higher prevalences of diseases of 75000 pounds (34000 kg) of organo- cide exposure (24). the ear and mastoid process; acute res- phosphates were used in agriculture By working close to pesticide appli- piratory infections; general signs and in 1995; these products included chlor- cators, other farm laborers or employ- symptoms of dizziness, fever, malaise, pyrifos, diazinon, and malathion (20). ees and farm owners who themselves and fatigue; and ill-defined symptoms Workers who apply pesticides on do not handle pesticides may become of the digestive system. These symp- crops, livestock, or elsewhere are exposed (20, 25). Workers who grow toms were not exclusively attributed to called pesticide applicators (2, 21). and pick fruits, vegetables, or other organophosphate exposure. They are in direct contact with the crops come into contact with pesticide At an agricultural chemical com- chemicals by spraying the insecticide residues. Aerial spraying of pesticides pany in the United States, workers in selected locations. Exposure can on farms is another form of exposure were exposed to another organophos- also come from mixing, loading, or for all agricultural workers, including phate, mevinphos (27). The exposure transporting the chemicals (2). In some flaggers on the ground, who direct was primarily from the packaging of situations, exposure can occur from such spraying (25). In the study by the chemical in the hopper/bagging accidental spills of chemicals, leakage, Ciesielski et al. (21), 47% of the ag- operation. Four out of nine workers or faulty equipment. Workers exposed ricultural workers reported being reported some form of illness, and to pesticides are usually required to sprayed with pesticides or working they were treated at a hospital. Their wear personal protective equipment close to sprayed areas. cholinesterase levels were 50% below for safety reasons. This equipment in- With support from the EPA, the their baseline levels. The incidents cludes a mask, protective clothing, United States National Institute for Oc- were investigated by a team from the gloves, and boots. While preventable, cupational Health and Safety (NIOSH) United States Occupational Safety and exposure to organophosphates could has conducted surveillance of pesticide- Health Administration, which con- result from inadequate safety training related illness in some states (19). The firmed organophosphate toxicity as a or poor compliance with safety regula- most common agricultural worker ill- result of the occupational exposure to tions. Improper practices, such as in- ness reported to the California Health mevinphos. frequent changing of clothes, inade- Department in 1998–1999 was expo- quate washing, or eating and smoking sure to organophosphates. Das and Exterminators who use pesticides. Ex- while wearing contaminated clothing, colleagues (7) reported that there was terminators who use pesticides are a increase the probability of exposure to more pesticide-related illness among major group of workers with occupa- pesticides (22). field workers on farms than among tional exposure to organophosphates.

174 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides These workers apply pesticides in pesticide application is not a part of erinary technician was exposed while public places and in private residential the office worker’s job description. The opening a sealed package of organo- homes, often to control termites (28, frequency of exposure to pesticides phosphate insecticide. This exposure 29). Pest control services have also among office workers is not as high as resulted in cholinergic symptoms of been extended to lawn care and tree it is in agricultural workers or chemi- acute organophosphate poisoning such service in the United States (22). cal industry employees, but any single as headache, nausea, vomiting, diar- In the state of New York, there were or unusual exposure to pesticides rhea, and difficulty in breathing; the 13417 pesticide applicators who were among workers carries a potential symptoms were treated in a hospital certified to work on residential and health risk. The specific risk would de- (33). commercial properties in 1996 (22). In pend on the office environment, the In another case a pet groomer who a review of suspected and confirmed concentration of pesticide used, and was not wearing any protective cloth- pesticide poisonings of lawn care and whether or not office workers were ing was exposed to phosmet while tree service applicators that were re- present at the time of application. washing a dog in a tub (34). The orga- ported to the New York State Pesticide Hodgson (31) described an instance nophosphate was being used to de- Poisoning Registry from 1990 to 1993, where five workers in an office devel- stroy fleas on the dog. The 35-year-old 39 cases were identified, of which 28 oped symptoms compatible with orga- female worker developed severe cho- satisfied the criteria for a suspected nophosphate intoxication after an ap- linergic symptoms an hour after the or confirmed poisoning. Twenty-four plication of chlorpyrifos. Even though exposure. She immediately went to a workers had reported symptoms. The the workers’ initial ChE activity did hospital emergency department. How- most common pesticides applied were not correlate with the symptoms re- ever, her ChE levels were within nor- organophosphates, reported by 71% of ported, their RBC ChE levels increased mal limits, and she recovered without the workers. significantly over the 3 months follow- any treatment. She had used organo- In a survey of 191 pesticide applica- ing exposure. phosphates to wash the animal on sev- tors in the state of North Carolina who eral occasions during the preceding had worked for a median of 1.8 years Health care worker exposure (nosoco- year, without wearing any protective applying organophosphates against mial poisoning). Heath care workers clothing. termites and other pests, the average in hospital emergency departments urinary chlorpyrifos metabolite for 65 are at risk of exposure to organo- Autopsy of exposed patients. Prosec- of the recently exposed applicators phosphate pesticides by secondary tors are at risk of exposure when they was far higher than that of the general contamination from patients who have perform autopsies of patients who have United States population: 629.5 mg/L acute organophosphate poisoning. been exposed to organophosphate in- vs. 4.5 mg/L (29). In that same North The health care workers’ exposure oc- secticides. Handling bodies contami- Carolina area, 60% of the pest control curs by their close contact with and nated with such chemicals is a form of companies reported using pesticides handling of the patient. In a hospital exposure, which can be prevented by containing chlorpyrifos. in the state of Georgia in 2000, three using proper autopsy procedures and emergency department workers be- protective equipment and clothing (35). Greenhouse workers and florists. came ill after managing a patient who Pesticide exposure is also known had intentionally ingested an orga- Exposure in a retail store. Physicians among greenhouse workers. Their nophosphate insecticide (32). All in California reported four incidents work includes the use of pesticides on three workers subsequently developed of organophosphate exposure follow- flowers, other plants, and foliage (10). signs and symptoms of acute organo- ing spills in retail stores in 1986, where Fumigant pesticides are considered a phosphate poisoning, for which they the store employees tried to clean up potential health risk to employees of were treated. The importance of this the spills without wearing protective greenhouses. For example, in one case case report is the risk of organophos- clothing (28). While not common, this in the state of Texas in 1995 the worker phate exposure to the health care kind of exposure is clearly occupa- had used sulfotepp as a fumigant for workers from the patient and from the tional in nature since the employees’ flowers and had become ill during the workers’ not wearing protective cloth- exposure was at their workplace. fumigation despite wearing personal ing and gloves in the situation. Health protective equipment (30). care workers should be aware of and Gulf War veterans.The exposure to guard against any form of chemical ex- organophosphates among United Office workers. Workers in offices are posure from direct contact with conta- States military servicemen during the occasionally exposed to pesticides ap- minated patients. Gulf War of 1990–1991 is considered to plied by exterminators (25, 26). While be an occupational exposure. During unintended, it is considered a work- Veterinary exposure. Veterinary em- that conflict some Allied troops were related exposure because of the intro- ployees can be exposed to pesticides possibly exposed to organophosphate duction of a hazardous chemical into from the chemicals applied to animals nerve poisons such as sarin and cy- a work environment, even though the for pest control (10). In one case, a vet- closarin as a result of the destruction

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 175 of Iraqi munitions at Khamisiyah (36). American households use pesticides together with acute cholinergic signs Some 2900 United States Gulf War in the home (39). Organophosphate and symptoms. The patient died 3 veterans reported symptoms sugges- insecticides are used for killing bugs days later in the hospital despite max- tive of low-level sarin exposure 9 years in and around the house and in the imum ventilatory support (43). after that demolition event. It was con- garden (2, 40). In 2000 the National The extensive use of organophos- cluded that over 100 000 United States Center for Food and Agricultural Pol- phates in residential areas constitutes servicemen in Iraq at that time were icy, a private nonprofit research orga- a major form of exposure in the gen- possibly exposed to low levels of sarin nization based in Washington, D.C., eral population. When exterminators and cyclosarin by the Khamisiyah inci- estimated that up to 3 million pounds spray private homes or apartment dent (37, 38). The bombing of an am- (1.4 million kg) of chlorpyrifos was buildings with pesticides, the resi- munition storage facility at Muham- being used in the home-and-garden dents can be exposed (28, 39). Steen- madiyat, Iraq, may have exposed 76 market each year. Chlorpyrifos is used land and colleagues (29) reported that United States Special Forces troops to to destroy cockroaches, fleas, spiders, houses and lawns in the United States low levels of the organophosphate and flies indoors as well as mosqui- receive approximately 20 million chlor- nerve agents (38). toes, ticks, bees, and poison ivy out- pyrifos treatments annually and that doors (41). 82% of adults in the country have de- In one case, a 36-year-old female tectable levels of chlorpyrifos metabo- Environmental or nonoccupational was taken to the emergency depart- lites in their urine. Organophosphate exposures ment of a hospital with symptoms pesticides are present in the air in of acute organophosphate poisoning homes, so exposure can occur from in- Environmental or nonoccupational (42). The patient had an odor of pesti- halation (39, 44). exposure to organophosphates in indi- cide; she admitted to having sprayed In northern Manhattan and the viduals occurs in any place where the diazinon over her rose bushes earlier South Bronx, which are two sections exposure to pesticides is not a result of that day. She also sprayed a higher of New York City, 85% of 314 African- the person’s job or occupation. There concentration of pesticide around the American women and Dominican im- are numerous situations where expo- base of her home to prevent insect in- migrant women reported the use of sure to organophosphates occurs in festation in the house. During the ap- pest control measures in their homes the general population in places other plication, some of the diazinon spilled during their pregnancy (39). Thirty- than workplaces (16). Exposure to onto her skin and shirt, which she had five percent of the women reported the organophosphates can also be para- not changed. This was a clear case spraying of pesticides in their homes occupational, such as from living close of acute organophosphate poisoning by an exterminator. to a workplace that uses pesticides or from domestic use of diazinon. Organophosphates also settle on when workers bring home contami- While not very common, accidental various objects and items in a home, nated articles and thus expose their poisoning with organophosphates in thereby increasing the risk of expo- family members (14). the home is a possibility from house or sure. The organophosphates are pres- Environmental exposure to organo- garden use of pesticides. Exposure is ent in house dust and on floors, car- phosphates also carries the risks of likely to occur from spills, improper pets, toys, dinnerware, and tables and morbidity and mortality. The EPA’s use, or poor storage. Situations arise other furniture (41, 45). Exposure oc- Pesticide Incident Monitoring System where people who do not know they curs by inhalation or dermal contact. showed that incidents of organophos- are handling pesticides are exposed. The close contact with the pesticide phate poisoning from nonoccupa- This can happen when a pesticide could also result in ingestion of the tional exposures were highly preva- label is misread or a pesticide con- chemical by consumption of contami- lent during the period of 1966 to 1980 tainer is opened without reading the nated foods, including fruits and veg- (16). A review of pesticide mortality in label. Exposure can also come from etables and water and other beverages. the United States for the 1979–1998 mishandling, such as by transferring Diet is a significant source of organo- period reported that out of 364 deaths pesticides from their original packages phosphate exposure (45, 46). from pesticide poisoning, 28% were a into household containers, and from A survey in the state of Washington result of accidental exposures to or- the lack of compliance with instruc- found that contaminated fresh pro- ganophosphate insecticides (17). tions or safety warning labels (41). duce and fruit juice were a means of Adults can be exposed to high doses of exposure in consumers (45). Exposure organophosphates by accident. A 46- to organophosphates could occur Residential exposure. The use of orga- year-old man in the city of Philadel- when consumers failed to adequately nophosphates in private homes forms phia was accidentally exposed to wash fruits and vegetables that had a large part of the nonoccupational organophosphates, from which he de- been sprayed while growing. In the exposures in the general population veloped a florid acute respiratory dis- state of Maryland a survey of pesti- in the United States (16). Domestic use tress syndrome, with markedly de- cides in foods from September 1995 to of pesticides is common: 80%–90% of pressed serum and RBC ChE levels, September 1996 showed positive re-

176 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides sults for the presence of organophos- Close proximity to farms.Exposure disease transmission. The use of or- phates. Chlorpyrifos was detected in can often occur when organophos- ganophosphates against mosquitoes 38.3% of solid food samples and phate pesticides applied on farms drift carrying the West Nile virus has pro- malathion in 75.2% of duplicate plates into surrounding areas where people moted public and health-professional of food samples from 75 subjects (46). live. This form of exposure is termed awareness of the disease (51, 52). Children are an extremely vulnera- the “farm proximity pathway” (45). ble, high-risk group for pesticide expo- While the nearby residents’ exposure sure (45, 46). In fact, the Food Quality may not be to the extent it is among Exposure in public places. Exposure Protection Act, legislation that was ap- agricultural workers, their proximity to pesticides in public places is an un- proved in the United States in 1996, re- to an organophosphate source still expected, unintentional, nonoccupa- quires the EPA to place particular em- puts them at risk. tional form of exposure among the phasis on assessing potential risk from The study in the state of Washington general public (28). For example, peo- pesticides to infants and children (47). by Fenske et al. (45), which was men- ple can be exposed to organophos- In the metropolitan area of Seattle, tioned above, showed that children of phate insecticides applied by exter- Washington, during the spring and non-agricultural workers living close minators in such places as public fall of 1998, of 110 children from dif- to farms (up to 200 ft (61 m)) had de- restrooms, restaurants, hotels, schools, ferent families, nearly all the children tectable levels of dimethyl organo- churches, business offices, apartment had metabolites of organophosphate phosphate urinary metabolites, similar buildings, grocery stores, and hospi- insecticides present in their urine (45). to that in the children of agricultural tals (28, 53). Other such sites are public Much of the exposure was attributed workers. Those children of non-agri- gardens, parks, sidewalks with trees to a contaminated diet. However, the cultural workers had been exposed or other plants, gardens outside office children of parents who reported us- to organophosphates that included buildings, malls, and even entire mu- ing pesticides in the garden had higher azinphos-methyl, phosmet, chlorpyri- nicipalities. This form of exposure may concentrations of organophosphate fos, and ethyl parathion (45). be minor compared to other situations metabolites in their urine than did the described above. children of families who had not re- ported the use of pesticides in their Aerial spraying. The extensive spray- gardens. Children can also be exposed ing of pesticides from aircraft over res- Exposed organ donors. The mother of to organophosphates in the home if idential areas can be a source of expo- a 17-year-old male in the state of Geor- the pesticides are left within their sure in the general population if the gia found him having seizures, with reach; ingesting the chemicals could residents of the sprayed areas breathe an empty container of malathion at his result in severe acute organophos- in air that contains the organophos- bedside. He was hospitalized immedi- phate poisoning (41). phates (2). The aerial spraying of a ately and treated for acute organo- malathion bait to eradicate the phosphate poisoning (54). However, Mediterranean fruit fly covered a large the patient developed aspiration pneu- Agricultural worker take-home expo- urban area in Santa Clara County, Cal- monia and became comatose. Five sure (paraoccupational). Agricultural ifornia, in 1981. This project, carried days after entering the hospital, the workers who are exposed to pesticides out by the United States Department patient was declared brain dead, and in their work can also expose persons of Agriculture, caused much alarm his organs were removed. His liver at home if they return home with con- among the public. However, a subse- and kidneys were successfully trans- taminated clothing and then have quent survey showed that there was planted. In spite of the successful close contact with their children and no detectable increase in acute mor- transplantation in this case, the au- other family members and with house- bidity in the area’s population (49). In thors of the article pointed out that hold items. Children of agricultural contrast, with the aerial spraying of a poisoned organ donors are potential workers can face an increased risk of malathion bait in the Mediterranean sources of organophosphate exposure exposure to pesticides (14, 48). A study Fruit Fly Eradication Program in the for organ recipients. by Fenske et al. (45) in the state of state of Florida in 1998 there were 123 Washington showed that, in com- reports of probable or possible pesti- parison to children from reference cide-related cases of illness among the Suicide (intentional) poisoning. Most families, the children of agricultural general population (50). of the suicide cases involving orga- families had a higher exposure to During 1999–2000 the first outbreak nophosphate poisoning happen in de- organophosphates, as indicated by of West Nile virus in the United States veloping countries, particularly in Sri higher levels of metabolites of or- led to the aerial spraying of pesticides Lanka, and much less so in the United ganophosphate insecticides in their over New York City to combat the States (5). The Toxic Exposure Surveil- urine. Levels of organophosphates in virus-transmitting mosquitoes. Orga- lance System of the American Associ- house dust were also high in the nophosphates (mainly malathion) ation of Poison Control Centers has homes of the agricultural families. were also used as larvicides to prevent information on fatal exposures to or-

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 177 ganophosphate pesticides in the United A South African religious leader tivity, including the electrometric States. Four cases of suicide poisoning was allegedly a victim of poisoning method (of Michel), pH stat method occurred during the year 2000: one per- with an organophosphate over the (titrimetric), colorimetric method (of son ingested diazinon, and three peo- course of a trip from South Africa to Ellman), and, more recently, the gas ple ingested malathion (15). the United States via Namibia in 1989 chromatographic method (of Cran- The case of the 17-year-old male (59). On his arrival in Namibia, he mer) (2). A portable, battery-operated whose liver and kidneys were trans- was seen in a hospital, suffering from test kit is available to use in the field; it planted, as described above, appears to abdominal pain, nausea, vomiting, uses the colorimetric (Ellman) method be a suicidal poisoning with malathion diarrhea, and extreme weakness. His to measure ChE activity (60). Mc- (54). In the hospital the patient exhibited symptoms settled within 48 hours, Connell et al. (61) used the test kit to symptoms consistent with acute orga- after which he left for the United measure RBC ChE activity in workers nophosphate poisoning, and his initial States. Shortly after he arrived in the in a Mexican pesticide formulation plasma ChE activity was 1433 interna- United States, his symptoms reap- plant. tional units per liter (IU/L), vs. the nor- peared and he was admitted to a The serum ChE enzyme is produced mal level of 7500 to 14600 IU/L. hospital. In the hospital he had res- in the liver, and it is a more reliable In Texas an 80-year-old woman piratory arrest requiring intubation. measure for detecting acute organo- committed suicide by ingesting mala- He recovered, was discharged, and phosphate poisoning than is the RBC thion mixed with fruit juice (55). She then was readmitted within 24 hours ChE. Serum ChE activity is depressed developed a severe cholinergic crisis; with profound anxiety, confusion, by organophosphates very rapidly her condition deteriorated, with respi- hyperventilation, respiratory alkalo- and it is also restored to normal levels ratory and renal failure, and she died sis, and hypophosphatemia. A diag- quickly (2, 3). In the acute phase of 12 days later. The antemortem blood nosis of organophosphate poisoning organophosphate poisoning, serum level of malathion was extremely high, was confirmed by low ChE activity. ChE activity is usually depressed 23.9 mg/L. It was later concluded that he had within a few hours to a few days. been exposed to an organophosphate About 3% of the population has a ge- that had been placed in his suitcase by netic variation manifested by a serum Chemical warfare. The threat of terror- a member of a South African military ChE deficiency (2, 3). Pregnancy, acute ism is a serious public health concern unit. or chronic inflammatory conditions, in many countries around the world, malnutrition, and liver disease are with especially increased awareness in conditions that also affect serum ChE the United States (56). Since some BIOLOGICAL MONITORING OF activity. The depression of ChE caused organophosphates are nerve agents, CHOLINESTERASES by these conditions is not as great as they could be used by terrorists as that caused by organophosphate in- chemical warfare agents (18). These Biological monitoring of organo- secticides (2, 3). substances include tabun, sarin, phosphate pesticides includes a The RBC ChE, which is present in soman, VX, and GF. The “G” series method of surveillance for assessing nervous tissue and the RBCs, is the were labeled as such because of their exposure by measuring ChE activity in preferred measure for organophos- origin in Germany, while the “V” se- RBCs and serum (2, 3). This is applied phate toxicity (2, 5). It is depressed less ries represent venomous poisons (57). mainly to the workers exposed to rapidly by organophosphate insecti- These agents inhibit ChE activity and organophosphates. However, ChE ac- cides than is true for the serum ChE. result in widespread manifestations of tivity is measured to assess acute During the acute phase of organo- peripheral and central nervous system organophosphate toxicity from any ex- phosphate poisoning, the RBC ChE ac- dysfunction, which could be fatal (18). posure, including the nonoccupational tivity is usually not depressed. It takes An outbreak of sarin poisoning oc- situations, since ChE depression is di- a few hours to a few days for RBC ChE curred in a subway station in Tokyo in agnostic of organophosphate toxicity. activity to decrease, and about 60 to 90 1995, caused by the dispersal of the The two enzymes measured for bio- days for the depressed RBC ChE levels nerve agent by a terrorist group (58). logical monitoring are RBC ChE (EC to be restored to normal. A person On the day of the disaster, 641 victims 3.1.1.7 under the enzyme nomencla- with symptoms of organophosphate were seen at the St. Luke’s Interna- ture system of the International Union poisoning may not necessarily have tional Hospital in Tokyo. All the vic- of Biochemistry and Molecular Biol- low RBC ChE activity; it does not al- tims suffered from severe cholinergic ogy) and serum or pseudo ChE (EC ways correlate with acute cholinergic symptoms, with miosis, headache, 3.1.1.8). Both enzymes should be mea- symptoms. dyspnea, nausea, ocular pain, blurred sured; the findings of both tests are Workers exposed to organophos- vision, coughing, muscle weakness, significant and useful in assessing phate insecticides should ideally have and agitation. Some patients arrived organophosphate toxicity (2, 3). a preemployment or preexposure with cardiopulmonary or respiratory There are several methods used (baseline) ChE measurement. This arrest, and there were two deaths. for analyzing serum and RBC ChE ac- measurement is compared with a

178 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides TABLE 3. Guidelines for cholinesterase (ChE) levels in relation to exposure and 2 to 3 months after removal from symptoms of organophosphate toxicity organophosphate exposure would serve to make a comparison to the ini- ChE level (activity) Feature tial ChE activity. Any ChE measure- 75% to 100% of baseline Normal, asymptomatic ment done during a period of expo- 50% of baseline Symptoms present sure to organophosphates would be 20% to 50% of baseline Mild exposure, minimal symptoms the starting point. Subsequent ChE 10% to 20% of baseline Moderate exposure, muscle fasciculations, myosis measurements done, after the worker 0% to 10% of baseline Severe poisoning, life-threatening symptoms, acute cholinergic crisis is removed from the exposure, are compared to the ChE activity during Source:Sullivan JB Jr., Blose J (2) and Schenker MB, Albertson TE, Saiki CL (3). organophosphate exposure. A gradual increase in ChE activity over 2 to 3 months would indicate that the worker had been exposed to organo- phosphates (30) (Figure 2). postexposure ChE level to determine ChE levels might be below 75% of the The carbamate group of pesticides the extent of organophosphate toxicity. upper limit of the reference range. are also anticholinesterases, or ChE Table 3 describes the levels of ChE in- When a baseline level is not avail- inhibitors. The carbamate pesticides hibition or depression in relation to able for exposed workers, a series of inhibit ChE activity by a reversible organophosphate toxicity. A preexpo- ChE measurements over an interval of spontaneous hydrolysis and carbamy- sure or baseline ChE level for an indi- vidual represents normal ChE activity. This level can vary widely from per- son to person. A 50% reduction in ChE FIGURE1. Illustration of cholinesterase (ChE) depression that is greater than 50% in a activity from the baseline may result in worker but that still lies within the laboratory reference range acute cholinergic or toxic symptoms of organophosphate exposure (2, 3). The California Health Services Department has set threshold values of ChE activ- ity for removal of workers from con- tinued exposure to organophosphates. For RBC ChE activity it is set at 60% of the baseline, and for serum ChE it is 50% of baseline (62). Workers are al- lowed to return to work once their ChE levels reach 75% of their baseline levels (3). In many cases when the baseline values are not known, laboratory ref- erence ranges may be used. These val- ues differ among laboratories, and the FIGURE2. Increase in red blood cell (RBC) cholinesterase (ChE) activity after removal of a range is very wide, with a 300% worker from organophosphate exposure spread (5). People with a reduction in their ChE activity of more than 50% may have toxic symptoms of organo- phosphate exposure even though the value may still be within the reference range (that is, above the lower limit) (Figure 1). This means that some peo- ple have a higher baseline ChE level compared to other persons. Workers with long-term exposure to organo- phosphates have a chronically low RBC ChE activity, yielding a falsely low baseline level (2, 3). Therefore, the reference range would not be applica- ble in such cases, since the baseline

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 179 lation of acetylcholinesterase, with a factor for children as compared to ing on the 12 pesticides that are re- rapid onset of action. The clinical pic- adults (64). sponsible for the greatest morbidity ture of carbamate poisoning is very The Occupational Safety and Health and mortality from acute pesticide similar to that of organophosphate Administration (OSHA) of the United poisoning in Central America (6). toxicity, though less severe in nature. States regulates pesticide exposure The carbamate symptoms are of a among agricultural workers in order shorter duration, and there are fewer to prevent pesticide-related illness. DISCUSSION effects on the CNS. ChE activity in OSHA’s Field Sanitation Standard workers exposed to carbamate pesti- specifies the requirements for the pro- Organophosphate exposure is highly cides is as low as with organophos- vision of potable water, toilets, and prevalent in developing countries. In phate toxicity. This makes it difficult washing facilities on farms, in part as a the United States the EPA has restricted to distinguish between organophos- way to reduce pesticide exposure. many organophosphate insecticides phate and carbamate toxicity based on Since 1992 the EPA’s Worker Protec- because of their potential hazardous ef- ChE measurements, especially when tion Standard has aimed at reducing fects on human health and the environ- workers are exposed to both groups of the risk of pesticide poisonings and ment (4). There are various circum- pesticides (2, 5). injuries among agricultural workers. stances where people may be exposed This EPA regulation includes require- to organophosphates, but there is a ments for safety training, notification higher risk to workers through occupa- REGULATION OF PESTICIDES of pesticide poisonings, use of per- tional exposure than there is to the gen- sonal protective equipment, restricted eral population through environmental Internationally, the World Health entry intervals following pesticide ap- exposure. Nevertheless, widespread Organization (WHO) has a program plication, decontamination supplies, residential exposure to organophos- that promotes and coordinates policies, and emergency medical assistance (7). phates does pose some level of risk for strategies, and guidelines for the use of The EPA requires that restricted orga- a large segment of the general popula- pesticides in public health, including nophosphate pesticides be used only tion in the United States. in the areas of pesticide specifications, under the direct supervision of certi- Organophosphate exposures can safety issues, and effectiveness (63). In fied pesticide applicators who have produce acute toxicity, resulting in the United States, regulation of pesti- had appropriate training so as to pre- high morbidity and even death. The cides started in 1947 with the Federal vent any harm to themselves, to oth- toxicity of an organophosphate is de- Insecticide, Fungicide, and Rodenti- ers, and to the environment (4). termined by the exposure level of the cide Act (FIFRA), which advocated the The California Health Services De- organophosphate in the environment, manufacture, use, and distribution of partment has a policy that requires the dose absorbed, and the level of ChE pesticides. The FIFRA was amended medical supervision and regular mon- depression in an individual. The pesti- several times before 1970, when the itoring of ChE activity in workers cide-related illness that people suffer EPA became responsible for pesticide exposed to cholinesterase-inhibiting from chronic exposure to low to mod- regulation and registration (1, 2). The pesticides (62). The California policy erate doses of organophosphates is a Federal Food Drug and Cosmetic Act requires preexposure and postexpo- public health concern. This is more of (FFDCA) allows the EPA to establish, sure ChE testing to assess organo- an occupational health issue and is modify, or revoke acceptable pesticide phosphate toxicity and to determine most relevant to agricultural workers residue levels in foods. The United whether workers should be removed and workers in the pesticide manufac- States Food and Drug Administration from the exposure. turing industry. The long-term effects (FDA) ensures that the EPA-estab- The EPA has given serious consider- of organophosphates are of interest lished pesticide residue levels are not ation to the potential health risk of to researchers and scientists. Chronic exceeded in foods. chlorpyrifos exposure in children. The neurological sequelae of toxic exposure In 1996, the United States Congress use of this pesticide is restricted in to organophosphates have been re- amended the FIFRA and FFDCA, with terms of its use indoors as well as out- ported. Further studies are needed to the passage of the Food Quality Pro- doors in homes and public places (41). determine whether chronic low-dose tection Act (FQPA) (47). The FQPA es- Regulation of pesticides has also exposure to organophosphates results tablished a new safety standard for progressed in other nations of the in neurological and neurobehavioral pesticides in food that is intended to Western Hemisphere. For example, at effects in the exposed population. be more consistent and to offer better the XVI Special Meeting of the Health Persons from Latin America who protections for the public. A major fea- Sector of Central America and the Do- are employed as migrant farmworkers ture of the FQPA is the emphasis that minican Republic, held in Teguci- in the United States are an important it places on children’s health, includ- galpa, Honduras, in September 2000, population with occupational pesti- ing protecting them from pesticide ex- the ministers of health who met there cide exposure. Therefore, more mi- posure. In some situations the FQPA ratified an agreement on restrictions grant workers should be encouraged applies an additional 10-fold safety and prohibitions for pesticides, focus- to utilize the Migrant Health Program,

180 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides which operates as part of the Bureau of their work. This would be true, for ex- Based on the nature of their jobs, work- Primary Health Care of the Health Re- ample, for agricultural workers who ers in those two sectors may face dif- sources Services Administration of the suffer acute organophosphate poison- ferences in their potential exposure to United States Department of Health ing in their work. A physician examin- organophosphates. Both groups of and Human Services (7). The Migrant ing a person who has been exposed to workers are at high risk of exposure, Health Program provides comprehen- a pesticide should undertake the ex- so taking appropriate, adequate health sive primary care and preventive amination in an organized and me- and safety precautions is essential. health services to migrant workers and thodical manner in order to ensure ap- Organizing health and safety pro- their families throughout the United propriate treatment as well as to avoid grams to educate workers and making States. Since farmworkers are at high fraudulent compensation claims (25). provisions for emergency health care risk of organophosphate exposure, en- The California Health Services De- for cases of acute pesticide poisoning forcement of pesticide safety regula- partment has implemented certain are both important. Another compo- tions for workers on farms is needed. policies with regard to medical moni- nent of these efforts are the material Good occupational health practices in- toring for pesticide-related illness and safety data sheets that pesticide manu- volve such tasks as worker education ChE testing of workers. The regular bi- facturers provide. These sheets explain on the safe use of pesticides, super- ological monitoring of ChE activity in possible toxic effects and specific pre- vision of pesticide applications, wear- agricultural workers that is done in cautions to be taken. The sheets are ing of personal protective equipment, California could be a model for other available to workers and are placed at safety training, and strict compliance states (62). This system protects work- appropriate, easily visible locations with pesticide regulations (65). As a ers from toxic exposure by properly in workplaces (25). On farms in the part of health education, simple meth- removing them from further organo- United States, farm owners are respon- ods can be applied to better protect phosphate exposure and by only al- sible for providing information on haz- farmworkers from pesticide exposure lowing their return to the fields at an ardous pesticides to their workers. and to improve their knowledge of the appropriate time. A more practical ap- While the risks of organophosphate hazards of pesticide exposure. Self- proach would be to use a portable kit exposure are highest for agricultural explanatory signs or posters describ- to measure RBC ChE activity. It is con- workers and for workers in the chemi- ing pesticide exposure and health risks venient, reliable, and easier to use in cal industry, other workers need to should be placed at appropriate sites the field than sending blood samples be protected as well. For example, ex- on farms. Given the high Latin Ameri- to a laboratory for diagnosis. It may terminators using pesticides are vul- can migrant farmworker population, also be a more cost-effective method nerable to toxic exposures. Educating relevant information on pesticides for monitoring a large workforce for workers on pesticide toxicity is a very should be presented in Spanish in ad- organophosphate exposure. In addi- important tool for preventing toxic ex- dition to English. tion to biological monitoring for ChE posures (7). The most important con- Occupational health services for depression in workers, environmental cern in any occupational exposure to farmworkers should be easily accessi- monitoring of organophosphates with organophosphates is the single high- ble, most importantly antidotes for or- measurements in air, water, or soil by dose exposure, which could result in ganophosphate poisoning, either at- industrial hygienists on farms would an acute cholinergic crisis. Care should ropine or pralidoxime (7). Washing be useful (26). A major part of health be exercised in order to avoid a critical facilities and emergency first aid care care for agricultural workers is the sur- situation, with respiratory arrest or should also be provided. In cases where veillance of chronic pesticide-related CNS depression in exposed employ- there are no health personnel or health illness in the majority of workers with ees. Workers should be removed from services available on site, arrangements chronic exposure to organophosphates. an area where organophosphates are should be made for transporting any This requires regular monitoring of applied in their workplace, and they exposed worker to the nearest hospital symptoms of organophosphate ex- should be permitted to return only for emergency care (25). This service is posure reported by workers, to be when they are safe from hazardous critical for severe, life-threatening cases followed by appropriate health care pesticide exposure. This can be partic- of organophosphate poisoning with a management (7). Any action taken to ularly true for office workers, who are cholinergic crisis. reduce pesticide-related illness would not accustomed to or generally ex- In the United States, cases of acute improve the well-being and general posed to pesticides in the workplace organophosphate poisoning and pesti- health of agricultural workers, which (25). cide-related illnesses are considered to should be among the goals of any oc- Situations of occupational and envi- be notifiable conditions that health cupational health program. ronmental exposure to organophos- care providers must report to local and Principles and rules for health and phates differ in terms of the frequency state authorities. In addition, workers safety for organophosphate exposure of pesticide use, the level of awareness in the United States have a legal right are applicable to both workers in agri- and familiarity with pesticide use, and to workers’ compensation payments culture and workers in the organo- whether or not there is a system for for any injury or ill health caused by phosphate manufacturing industry. pesticide safety. In nonoccupational

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 181 situations the exposure is mainly cir- articles, and their diet. Organophos- is a likely preview of such a situation. cumstantial or accidental, without any phate toxicity in children could re- The nerve poisons could have adverse protection for people who are exposed. quire emergency treatment and care. effects on a large group of people if It is evident from the scientific litera- The extent of the organophosphate applied as chemical warfare agents. ture that exposure to organophos- toxicity in children would be deter- Bioterrorism is a threat to all humanity phates can affect people who come into mined by their general health, nutri- (56). Western nations are on a higher direct or indirect contact with the tional status, metabolic rate, immune level of alert for such attacks and have chemicals in any situation where the status, and the dose of exposure (44). tightened their security measures. It is pesticides are available or are intro- Children may not sustain the impact important that people be made aware duced. Thus, the general environmen- of a toxic exposure to organophos- of the possibility of nerve agents being tal exposure to organophosphates may phates as easily as adults would. Extra used in chemical warfare. In the event be lower in intensity than is true for oc- care should be taken when children that these agents are used against any cupational exposure, but that environ- are exposed to pesticides, especially population, the destruction will be evi- mental exposure may affect a larger children of parents who are exposed dent from a widespread cholinergic cri- segment of the population. to such chemicals at work. Such sec- sis. Large numbers of people will be se- Domestic use of organophosphates ondary contamination increases the verely affected, with serious illness and in the United States is frequent and health risks for children. fatalities. This will have a major impact widespread and presents a serious Organophosphates can be trans- on emergency health care resources, public health concern. Much of the do- ferred from a pregnant female to the facilities, and personnel, including mestic use of organophosphates by fetus via placental circulation, as has physicians, nurses, nurses’ aides, clini- housewives or other household mem- been shown experimentally in rats cal pathologists, and laboratory techni- bers is unsupervised. In addition, (66). In utero exposure to organophos- cians (18). Exposed victims will suffer there is often improper storage of the phates will later affect the newborn long-term effects from the toxic nerve substances, little use of personal pro- and the growing infant. One study (67) agent exposure, and there will also be tection equipment or clothing, and has shown that chlorpyrifos possibly psychological and traumatic effects on poor knowledge of organophosphate affected four children of mothers who the general population. Such an event toxicity. Residents using pesticides in had been exposed to the insecticide by will involve government security per- their homes may not read instruction their occupation during their pregnan- sonnel, firefighters, state and local au- labels properly, or they may not real- cies. The children were born with ex- thorities, police officers, and military ize the seriousness of the warnings of tensive and unusual patterns of birth personnel. Health authorities, govern- organophosphate toxicity. Further, the defects affecting the brain, eyes, ears, ment officials, local and state authori- extensive use of organophosphates by palate, teeth, heart, nipples, and geni- ties, and health care professionals have pesticide applicators in homes exposes talia. All four children also suffered a responsibility to alert and educate the a large population to hazardous chem- from mental and growth retardation. public now as well as to provide care icals. For safety, residents should be Maternal exposure to organophos- and services in the event of any chemi- temporarily evacuated from the af- phates is likely to affect the acetyl- cal warfare. fected houses or surroundings. cholinesterase present in fetal brains The treatment of patients with acute The presence of organophosphates as well as the fetal neural function (68). organophosphate poisoning is an im- in the diet is a major source of expo- Organophosphate exposure in fetuses, portant part in the health care of pesti- sure. People consuming contaminated neonates, and infants is an area of de- cide toxicity. Any person exposed to food and beverages are not aware of velopmental toxicology that requires an organophosphate insecticide faces this exposure, nor are the levels of con- further research. However, the EPA the risk of a significant ChE depres- tamination known. The full implemen- has already taken serious steps to re- sion, resulting in an acute cholinergic tation of FQPA will eventually reduce duce chlorpyrifos exposure in children crisis. However, with environmental such exposures among the general (40). That action was taken based on exposures in the general population, population and help to protect human animal studies that showed that chlor- there may be some delay in receiving health. pyrifos causes higher systemic toxicity emergency care, and physicians may The most vulnerable of all groups in neonates than in adults. not be aware of the exposure to are children and infants, who are at a Some organophosphate compounds organophosphates unless they are in- very high risk of organophosphate ex- considered to be nerve agents were ap- formed by the patient or the person posure. Children may not understand parently released in the Gulf War, af- accompanying the patient. Patients the risk of pesticide exposures and can fecting United States military person- with acute organophosphate toxicity be accidentally exposed in the home. nel. This group of organophosphate may be brought into the emergency Much has to do with their activities chemicals is very dangerous, and they room unconscious or in a comatose and behavior, including easy access to could be used for terrorist attacks. The state. Therefore, it is critical for physi- pesticides stored at home, contact with incident in the Tokyo subway station, cians to receive a proper history of ex- pesticide containers or contaminated which is described earlier in this article, posure in order to make a diagnosis

182 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides and select appropriate treatment (25). the United States. In order to prevent ities are key in ensuring public safety The laboratory finding of depressed the damaging effects of organophos- and providing protection from toxic ChE activity confirms the diagnosis phates on human health and the envi- pesticide exposure. Local health de- of organophosphate poisoning. There- ronment, national regulations in the partments, educational institutions, fore, it is vital that this investigation be United States should remain in place scientists, teachers, health care profes- done in emergency situations. The crit- and should be strictly followed. In ad- sionals, public health professionals, ical steps in these cases are the clinical dition, policies and regulations on and other concerned persons are key diagnosis of organophosphate toxicity, pesticide exposure, health, and safety to promoting health education and the immediate treatment of poisoning, should be implemented at the state alerting the public to the effects of and appropriate supportive care and and local government level. pesticide exposure. Ultimately, every- management of the patient. Employers whose workers are ex- thing rests on the individual being Organophosphate exposure is a posed to organophosphate insecticides cautious and careful when in close major public health issue in the United have a special responsibility. Ensuring contact with a pesticide. Adults should States, Central and South America, the safe use of pesticides and prevent- take responsibility for protecting chil- Africa, and Asia. Despite strict regula- ing toxic exposure among workers dren from pesticide exposure. tory laws and restrictions by the EPA, requires efficient administration and The high morbidity and mortality organophosphate exposure is still management in the workplace. Rules from organophosphate toxicity in de- highly prevalent in the United States. and regulations to prevent organo- veloping countries are well known. Various situations of nonoccupational phosphate toxicity should be under- Therefore, in order to emphasize the exposure to organophosphates have stood and administered by managers, health risks from organophosphate in- been described in this article. Some of administrators, safety officers, super- secticides, this article has focused on the circumstances are unlikely to oc- visors, team leaders, and union offi- organophosphates in the United States, cur, but are nevertheless clearly cases cials. Workers should also participate where there is less exposure. Given of exposure to organophosphates. No in controlling pesticide exposure. that organophosphate exposure is matter how uncommon or infrequent Good supervision in combination with highly prevalent and is still a major the situation might be, organophos- educating employees on the conse- public health issue in the United phate exposure is a health risk for the quences of hazardous exposures will States, this article clearly shows that general population. It is important that help workers put the principles of safe there is an even greater need for pub- public health professionals be more pesticide use into practice. lic health protection from pesticide informed of the potential effects of Since environmental exposure to toxicity in developing countries. Un- organophosphate exposure. Agricul- organophosphates is highly prevalent fortunately, economic limitations in tural workers, especially migrant in the United States, there is an in- the developing world will delay the workers from Latin America, are more creasing need to protect the general development and implementation of exposed to organophosphate pesti- population from pesticide toxicity. effective preventive measures for pes- cides than is the general population in Federal, state, and local health author- ticide toxicity.

REFERENCES

1.Ecobichon DJ. Toxic effects of pesticides. In: 5.He F. Neurotoxic effects of insecticides— 10.Sanborn MD, Cole D, Abelsohn A, Weir E. Klaassen CD, Doull J, eds. Casarett and current and future research review. Neuro- Identifying and managing adverse environ- Doull’s toxicology: the basic science of poi- toxicology 2000;21:839–845. mental health effects: 4. Pesticides. CMAJ sons. 5th ed. New York; 1996. Pp. 643–689. 6.Henao S, Arbelaez MP. Epidemiological situ- 2002;166:1431–1436. 2.Sullivan JB Jr., Blose J. Organophosphate and ation of acute pesticide poisoning in Central 11.Waddell BL, Zahm SH, Baris D, Weisenburger carbamate insecticides. In: Sullivan JB, America, 1992–2000. Epidemiol Bull 2002; DD, Holmes F, Burmeister LF, et al. Agricul- Krieger GR, eds. Hazardous materials toxi- 23(3);5–9. Available from: http://www.paho. tural use of organophosphate pesticides and cology: clinical principles of environmental org/English/SHA/be_v23n3-plaguicidas. the risk of non-Hodgkin’s lymphoma among health. Baltimore, Maryland, United States htm [Internet site]. Accessed 24 February male farmers (United States). Cancer Causes of America: Williams and Wilkins; 1992. Pp. 2003. Control 2001;12:509–517. 1015–1026. 7.Das R, Steege A, Baron S, Beckman J, Harrison 12.Ray DE, Richards PG. The potential for toxic 3.Schenker MB, Albertson TE, Saiki CL. Pesti- R. Pesticide-related illness among migrant effects of chronic low-dose exposure to orga- cides. In: Rom WN, ed. Environmental and farm workers in the United States. Int J Occup nophosphates. Toxicol Lett 2001;120:343–351. occupational medicine. Boston, Toronto, Lon- Environ Health 2001;7:303–312. 13.Rosenstock L, Keifer M, Daniell WE, Mc- don: Little, Brown and Company; 1992. Pp. 8.Kwong TC. Organophosphate pesticides: bio- Connell R, Claypoole K. Chronic central ner- 887–920. chemistry and clinical toxicology. Ther Drug vous system effects of acute organophosphate 4.Brown AE. Restricted use of pesticides [Inter- Monit 2002;24:144–149. pesticide intoxication. The Pesticide Health net site]. University of Maryland, Maryland 9.Riegel B. Organophosphate pesticides [Inter- Effects Study Group. Lancet 1991;338:223– Cooperative Extension. Available from: http:// net site]. Available from: http://www.krpc. 227. www.pesticide.umd.edu/leaflets/pil2.pdf com/proffed/op%5Cop.cfm. Accessed 6 Sep- 14.Fenske RA, Lu C, Barr D, Needham L. Chil- Accessed 9 August 2002. tember 2002. dren’s exposure to chlorpyrifos and parathion

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 183 in an agricultural community in central 32.Geller RJ, Singleton KL, Tarantino ML, Dren- 49.Kahn E, Berlin M, Deane M, Jackson RJ, Strat- Washington State. Environ Health Perspect zek CL, Toomey KE. Nosocomial poisoning ton JW. Assessment of acute health effects 2002;110:549–553. associated with emergency department treat- from the Medfly Eradication Project in Santa 15.Litovitz TL, Klein-Schwartz W, White S, ment of organophosphate toxicity—Georgia Clara, California. Arch Environ Health 1992; Cobaugh DJ, Youniss J, Omslaer JC, et al. 2000 2000. J Toxicol Clin Toxicol 2001;39:109–111. 47:279–284. annual report of the American Association of 33.Sidhu KS, Collisi MB. A case of an accidental 50.From the Centers for Disease Control and Pre- Poison Control Centers Toxic Exposure Sur- exposure to a veterinary insecticide product vention. Surveillance for acute pesticide- veillance System. Am J Emerg Med 2001; formulation. Vet Hum Toxicol 1989;31:63–64. related illness during the Medfly Eradication 19:337–395. 34.From the Centers for Disease Control and Program—Florida, 1998. JAMA 1999;282: 16.Muldoon SR, Hodgson MJ. Risk factors for Prevention. Illnesses associated with occupa- 2204–2206. nonoccupational organophosphate pesticide tional use of flea-control products—California, 51.Miller JR. The control of mosquito-borne dis- poisoning. J Occup Med 1992;34:38–41. Texas, and Washington, 1989–1997. JAMA eases in New York City. J Urban Health 2001; 17.Langley R, Sumner D. Pesticide mortality in 1999;282:125–126. 78:359–366. the United States 1979–1998. Vet Hum Toxicol 35.Nolte KB, Taylor DG, Richmond JY. Biosafety 52.Thier A. Balancing the risks: vector control 2002;44:101–105. considerations for autopsy. Am J Forensic and pesticide use in response to emerging ill- 18.Goozner B, Lutwick LI, Bourke E. Chemical Med Pathol 2002;23:107–122. ness. J Urban Health 2001;78:372–381. terrorism: a primer for 2002. J Assoc Acad 36.McCauley LA, Rischitelli G, Lambert WE, 53.Crinnion WJ. Environmental medicine, part 4: Minor Phys 2002;13:14–18. Lasarev M, Sticker DL, Spencer PS. Symptoms pesticides—biologically persistent and ubiq- 19.Engel LS, Seixas NS, Keifer MC, Longstreth of Gulf War veterans possibly exposed to uitous toxins. Altern Med Rev 2000;5:432–447. WT Jr., Checkoway H. Validity study of self- organophosphate chemical warfare agents at 54.Dribben WH, Kirk MA. Organ procurement reported pesticide exposure among orchard- Khamisiyah, Iraq. Int J Occup Environ Health and successful transplantation after mala- ists. J Expo Anal Environ Epidemiol 2001;11: 2001;7:79–89. thion poisoning. J Toxicol Clin Toxicol 2001; 359–368. 37.Landrigan PJ. Illness in Gulf War veterans. 39:633–636. 20.Mills PK, Zahn SH. Organophosphate pes- Causes and consequences. JAMA 1997;277(3): 55.Zivot U, Castorena JL, Garriott JC. A case of ticide residues in urine of farmworkers and 259–261. fatal ingestion of malathion. Am J Forensic their children in Fresno County, California. 38.United States of America, Department of Med Pathol 1993;14:51–53. Am J Ind Med 2001;40:571–577. Health and Human Services, Department 56.Blazes Dl, Lawler JV, Lazarus AA. When 21.Ciesielski S, Loomis DP, Mims SR, Auer A. of Defense, Department of Veteran Affairs. biotoxins are tools of terror. Early recognition Pesticide exposures, cholinesterase depres- Chemical warfare agents [Internet site]. Avail- of intentional poisoning can attenuate effects. sion, and symptoms among North Carolina able from: http://www.gulflink.osd.mil/ Postgrad Med 2002;112:89–92. migrant farmworkers. Am J Public Health medsearch/FocusAreas/chemical_warfare. 57.Su M, Hoffman RS. Biological and chemical 1994;84:446–451. shtml. Accessed 9 August 2002. hazards. Nerve agents: pathophysiology, as- 22.Gadon M. Pesticide poisonings in the lawn 39.Whyatt RM, Camann DE, Kinney PL, Reyes sessment, and management. Resid Staff Phy- care and tree service industries. A review of A, Ramirez J, Dietrich J, et al. Residential pes- sician 2002;48:25–33. cases in the New York State Pesticide Poison- ticide use during pregnancy among a cohort 58.Ohbu S, Yamashina A, Takasu N, Yamaguchi ing Registry. J Occup Environ Med 1996;38: of urban minority women. Environ Health T, Murai T, Nakano K, et al. Sarin poisoning on 794–799. Perspect 2002;110:507–514. Tokyo subway. South Med J 1997;90:587–593. 23.Perry MJ, Marbella A, Layde PM. Association 40.Lu C, Knutson DE, Fisker-Anderson J, Fenske 59.Bjornsdottir US, Smith D. South African reli- of pesticide safety knowledge with beliefs and RA. Biological monitoring survey of organo- gious leader with hyperventilation, hypo- intentions among farm pesticide applicators. phosphorus pesticide exposure among pre- phosphatemia, and respiratory arrest. Lancet J Occup Environ Med 2000;42:187–193. school children in the Seattle metropolitan area. 1999;354:2130. 24.Elmore RC, Arcury TA. Pesticide exposure Environ Health Perspect 2001;109:299–303. 60.Higgins GM, Muniz JF, McCauley LA. Moni- beliefs among Latino farmworkers in North 41.Lemus R, Abdelghani A. Chlorpyrifos: an un- toring acetylcholinesterase levels in migrant Carolina’s Christmas tree industry. Am J Ind welcome pesticide in our homes. Rev Environ agricultural workers and their children using Med 2001;40:153–160. Health 2000;15:421–433. a portable test kit. J Agric Saf Health 2001;7: 25.Lessenger JE. The pesticide-exposed worker: 42.Melum MF. Emergency organophosphate 35–49. an approach to the office evaluation. J Am toxicity. Am J Nurs 2001;101:57–58. 61.McConnell R, Cedillo L, Keifer M, Palomo Board Fam Pract 1993;6:33–41. 43.Kass R, Kochar G, Lippman M. Adult respira- MR. Monitoring organophosphate insecticide- 26.Burns CJ, Cartmill JB, Powers BS, Lee MK. tory distress syndrome from organophos- exposed workers for cholinesterase depres- Update of the morbidity experience of em- phate poisoning. Am J Emerg Med 1991;9:- sion. New technology for office or field use. ployees potentially exposed to chlorpyrifos. 32–33. J Occup Med 1992;34:34–37. Occup Environ Med 1998;55:65–70. 44.Lewis RG, Fortune CR, Blanchard FT, Ca- 62.Ames RG, Brown SK, Mengle DC, Kahn E, 27.Fox A, Castillon K. Employee exposure to mann DE. Movement and deposition of two Stratton JW, Jackson RJ. Protecting agricul- mevinphos—an organophosphate pesticide. organophosphorus pesticides within a resi- tural applicators from over-exposure to Appl Occup Environ Hyg 2001;16:506–508. dence after interior and exterior applications. cholinesterase-inhibiting pesticides: perspec- 28.Maddy KT, Edmiston S. Selected incidents J Air Waste Manag Assoc 2001;51:339–351. tives from the California programme. J Soc of illnesses and injuries related to exposure 45.Fenske RA, Kedan G, Lu C, Fisker-Andersen Occup Med 1989;39:85–92. to pesticides reported by physicians in Cali- JA, Curl CL. Assessment of organophospho- 63.Food and Agriculture Organization of the fornia in 1986. Vet Hum Toxicol 1988;30:246– rous pesticide exposure in the diets of pre- United Nations, World Health Organization. 254. school children in Washington State. J Expo Joint FAO/WHO meeting on pesticide 29.Steenland K, Dick RB, Howell RJ, Chrislip Anal Environ Epidemiol 2002;12:21–28. residues (JMPR) [Internet Site]. Available DW, Hines CJ, Reid TM, et al. Neurologic 46.MacIntosh DL, Kabiru CW, Ryan PB. Longi- from: http://www.who.int/pcs/jmpr/jmpr. function among termiticide applicators ex- tudinal investigation of dietary exposure to htm. Accessed 26 February 2003. posed to chlorpyrifos. Environ Health Per- selected pesticides. Environ Health Perspect 64.Kimmel CA, Makris SL. Recent developments spect 2000;108:293–300. 2001;109:145–150. in regulatory requirements for developmental 30.Acute pesticide poisoning associated with use 47.Suhre FB. Variability in pesticide residues— toxicology. Toxicol Lett 2001;120:73–82. of a sulfotepp fumigant in a greenhouse— the US experience. Food Addit Contam 2000; 65.Arcury TA, Quandt SA, Russell GB. Pesticide Texas, 1995. MMWR 1996;45(36):780–782. 17:497–501. safety among farmworkers: perceived risk 31.Hodgson MJ, Block GD, Parkinson DK. Or- 48.Renner R. Farm kids and chlorpyrifos. An and perceived control as factors reflecting en- ganophosphate poisoning in office workers. accurate assessment of exposure. Environ vironmental justice. Environ Health Perspect J Occup Med 1986;28:434–437. Health Perspect 2002;110:A257. 2002;110 Suppl 2:233–240.

184 Jaga and Dharmani • Exposure to and public health implications of organophosphate pesticides 66.Astroff AB, Young AD. The relationship be- 68.Banerjee J, Ghosh P, Mitra S, Ghosh N, Bhat- tween maternal and fetal effects following tacharya S. Inhibition of human fetal brain maternal organophosphate exposure during acetylcholinesterase: marker effect of neuro- gestation in the rat. Toxicol Ind Health 1998; toxicity. J Toxicol Environ Health 1991;33: Manuscript received 27 September 2002. Revised version 14:869–889. 283–290. accepted for publication 4 March 2003. 67.Sherman JD. Chlorpyrifos (Dursban)-associ- ated birth defects: report of four cases. Arch Environ Health 1996;51:5–8.

RESUMEN Objetivo. Repasar la importancia para la salud pública de la exposición a plaguici- das organofosforados en los Estados Unidos de América. En vista de que la situación en torno a dicha exposición y a los riesgos de salud que la acompañan en países en Fuentes de exposición desarrollo son asunto muy conocido en el mundo, este artículo busca resaltar la im- a plaguicidas portancia de la exposición a esos productos en los Estados Unidos, donde es menos organofosforados común que en muchos otros países. Esta ojeada a la situación en Estados Unidos sirve para resaltar aun más la gravedad de los problemas de salud que plantea la exposi- e implicaciones para ción a los plaguicidas organofosforados en los países en desarrollo. la salud pública Métodos. Se llevó a cabo una búsqueda de artículos de revistas sobre los plaguici- das organofosforados y la exposición a ellos que figurasen en PubMed, sistema bibli- ográfico electrónico de la Biblioteca Nacional de Medicina de los Estados Unidos. Con el fin de suplementar esa búsqueda, se obtuvo de artículos, libros y sitios en la Web información acerca de la toxicidad de los productos organofosforados, su control bi- ológico y su regulación. Resultados. Los plaguicidas organofosforados son un grupo de productos químicos que se usan principalmente en la agricultura. Dichos productos inhiben la actividad de ambas colinesterasas —la eritrocítica y la sérica—, lo cual explica las manifesta- ciones colinérgicas que acompañan a la intoxicación por los organofosforados. Una reducción de 50% de la actividad de la colinesterasa sérica con respecto a su valor basal indica que hay toxicidad aguda por efecto del producto organofosforado. La ac- tividad de la colinesterasa eritrocitaria, que se deprime con menos rapidez que la ac- tividad de la colinesterasa sérica, es indicadora de exposición crónica a productos organofosforados. La exposición a estas sustancias se clasifica en dos categorías gen- erales: la ocupacional y la ambiental. Las exposiciones ocupacionales se producen en agricultores (entre ellos los trabajadores itinerantes), obreros industriales, extermi- nadores de plagas y otros trabajadores. La exposición que no es de tipo ocupacional afecta a un amplio sector de la población general en Estados Unidos. Las exposiciones residenciales obedecen al uso de plaguicidas organofosforados por exterminadores de plagas y habitantes del hogar, o son de carácter alimentario o accidental. Otras ex- posiciones ambientales se observan en lugares públicos y en la vecindad de granjas, o bien como resultado del uso de productos organofosforados en casos de guerra química o de terrorismo. En Estados Unidos el uso de algunos plaguicidas organofos- forados se ve restringido por la Agencia de Protección Ambiental, habida cuenta de la necesidad de proteger a los seres humanos, los animales y el medio ambiente. Por otra parte, la Ley para la Protección de la Calidad de los Alimentos regula la exposi- ción alimentaria a los plaguicidas, especialmente en el caso de niños menores de un año y de mayor edad. Conclusiones. Los plaguicidas organofosforados siguen planteando un peligro para la salud de las personas en Estados Unidos. Es necesario realizar una vigilancia bi- ológica de estas sustancias a fin de controlar las exposiciones ocupacionales a ellas y de proteger la salud y seguridad de los trabajadores. Al público se le debe inculcar mayor conciencia del peligro que representa este tipo de exposición ambiental y de la posibilidad de una guerra o ataque terrorista.

Rev Panam Salud Publica/Pan Am J Public Health14(3), 2003 185