THE HEALTH RISKS of HERBICIDES in FORESTRY: a REVIEW of Thesctentific RECORD

HEO/F76/2JAL PUBLICATION 10 APRIL 1984 .43p3 AIJ0003O4BO]J906 10

DI94Rb

STAlE LIBRARY

THE HEALTH RISKS OF HERBICIDES IN FORESTRY: A REVIEW OF THESCtENTIFIC RECORD

JOHN I). WAISTAD FRANK N. DOST

FOREIT LAB

COLLEGE OF FORESTRY OREGON STATE UNIVERSITY Since 1941, the Forest Research Laboratory-- DISCLAIMER part of the College of Forestry at Oregon StateUniversity inCorvallis--has been The mention of trade names or commercial pro- studying forests end why they are like they ducts in this publication does not constitute are.A staff of more than 50 scientists con- endorsement or recommendation for use. ducts research to provide information for wise public and private decisions on managing and using Oregon's forest resources and operating its wood-using industries. Because of this research, Oregon's forests yield more TO ORDER COPIES in the way of wood products, water, forage, wildlife and recreation.Wood products are Copies of this and other Forest Research harvested, processed and used more effi- Laboratory publications are available from: ciently.Employment, productivity, and pro- fitility In industries dependent on forests Forest Research Laboratory are strengthened. And this research has College of Forestry helped Oregon to maintain a quality environ- Oregon State University ment for its people. Corvallis, OR 97331 Much research is done in the Laboratory's facilities on the campus.But field experi- Please include author(s), title and publica- ments in forest genetics, young-growth mana- tion number if known. gement, forest hydro logy, harvesting methods, and reforestation are conducted on 12,000 acres of College forests adjacent to the cam- pusand onlandsofpublicand private ACKNOWLEDGEMENTS cooperating agencies throughout the Pacific Northwest. Theauthorsthanktheircolleaguesfor contributing invaluable suggestions, correc- With these publications, the Forest Research tions, and skillstowardfinalizingthis Laboratorysupplies theresultsofits report. research to forest land owners and managers, Technical reviews were made by: to manufacturers and users of forest pro-Michael Newton, professor, Department of ducts, to leaders of government and industry, Forest Science, OSU; Logan A. Norris, USDA and to the general public. Forest Service, Pacific Northwest Forest and RangeExperimentStation,Corvallis; and Sheldon A. Wagner, professor, Department of Agricultural Chemistry, OSU, and Good THE AUTHORS Samaritan Hospital, Corvallis. JohnD. Walstadisassociateprofessor, Funding for 'publication of this report was Department of Forest Science, and Frank N. provided in part by the CRAFTS cooperative Dost is professor, Department of Agricultural research program in forest vegetation manage- Chemistry and Cooperative Extension Service, ment at the Forest Research Laboratory of Oregon State University, Corvallis. Oregon State University. THE HEALTH RISKS OF HERBICIDES IN FORESTRY: A REVIEW OF THE SCIENTIFIC RECORD

JOHN D. WALSTAD FRANK N. DOST CONTENTS

3 PREFACE 3 INTRODUCTION 4 TOXICOLOGY 10 REGULATORY CONTROL 11 TOXICITY DATA 12 FIELD STUDIES 12 OCCUPATIONAL CONTACT 13 EPIDEMIOLOGICAL STUDIES 14 PUBLIC CONTACT 15 FISH AND WILDLIFE CONTACT 16 TCDD (DIOXIN) 19 SCIENTIFIC REVIEWS 27 LITIGATION 28 CONCLUSION 29 BIBLIOGRAPHY 46 APPENDICES PRE FACE

For more than a decade now, the use of her- 2,L,5-T, and inappropriate disposal of bicides(especially phenoxy herbicides)in dioxin-contaminated wastes.Researchers and forestry has been thesubject ofintense physicians have also given expert testimony controversy. The debate has touched upon as the debate has moved into the courtrooms. many aspects of herbicides, ranging from eco- logyto economics. But atthe center of Enough studies have been completed in the discussion has been theissue of possible past fifteen years or more that itis timely adverse effects on human health. Members of to publish a review of the scientific record thescientificand medical community have regardingthehealthrisksofusingher- beenactivelyengaged inevaluatingthe bicides in forestry.This bulletin also pro- safety of herbicide use.This investigation vides a brief introduction to the methods of has been broadened as new questions have been toxicologyand theregulatorycontrolof raised or new information has come to light; toxic substances by government. We hope that for example, reports of illnessin Vietnam thisinformationwillbehelpfultothose veterans possibly connected with their expo- concerned with the use of herbicides in our sure to Agent Orange, miscarriages in coastal environment andparticularlyinforestry forestdwellersnearareastreatedwith operations.

INTRODUCTION

Herbicides are important tools used by forest One of several misconceptions surrounding managers to sustain the productivity of com- the use of herbicides in forest management is mercial forests. However, such economic con- that not enough is known about them to eva- siderations must not take precedence over luate their safety.However, a bibliography concerns for public health and environmental compiled by scientists at the Texas safety. Phenoxy herbicides have been the AgriculturalExperimentStationindicated focus of considerable public controversy and that even by 1977 there were over 870 scien- scientific scrutiny over the past decade. As tific articles on the toxicology of phenoxy a consequence, their safety has been periodi- herbicides(Diaz-Colon andBovey 1977). cally re-examined as new information or con- Seven othervolumesinthis bibliographic cernshave come tolight. Such risk seriescovertheliteraturepertainingto assessments are appropriate for any chemical fate in the environment, ecological effects, product in order to ensure thatits useis analyticalchemistry,effects on higher not likely to jeopardize human health or the plants, dioxins, interrelations with general environment. An overview of the microorganisms, and military uses (Bovey and methods of toxicology and regulatory control Diaz-Colon 1977, 1978a, b, c; Diaz-Colon and by government agencies will provide Bovey 1976,1978a, b). Itis estimated that backgroundinformationfortheissueof thereareoverkO,000publishedstudies safety. dealing with various aspects of the phenoxy herbicides (Council for Agricultural Science and Technology 1978).Of course, numbers of The risks to human health from herbicide use studies do not necessarily indicate depth of in forestry are evaluated in three ways in knowledge, but phenoxy herbicides are cer- this report.First, we present calculations tainly among the most intensively examined of the amounts of various herbicides, espe- chemical families. Bovey and Young (1980) cially phenoxies,which an average person have synthesized much of the information in would have toingestin order to meet or their textbook on phenoxy herbicides. exceed certain toxicological points of referenceestablishedthroughtestingof laboratory animals.Second, we analyze data from field studies that measured amounts of Regardless of the amount of information we herbicideintheenvironment orspecific have, however, we will never be able to state organisms. Third, we review the conclusions with absolute certaintythatthe use ofa of the many medical,scientific,andlegal given herbicide (or any chemical product, for reviews of herbicide safety conducted over that matter)isperfectly safe. The dif- the past decade. ficulty arises from several sources:

3 1. There are practicallimitsto the size Thus, it is impossible to prove beyond a sha- and scope of experiments that can be dow of doubt that a chemical product is going conducted in testing a chemical, inevi- to be safe under all conceivable uses. tablyleaving somepossibleeffects untested. One solutiontothis dilemma would beto simply forego the use of chemical products and not run the risk of encountering possible 2. The test results must be extrapolated to adverse effects. But this would mean the differentanimal species, to larger elimination of countless materials that have populations, or to different situations, contributed tothe overall health and well- which always leaves a chance that they being of our society. Antibiotics, crop fer- will respond differently than the speci- tili zers, pest-control chemicals, and fic test animals. household products come immediately to mind. Therefore, a more realistic approach isto conduct enough tests on these materials that 3. The tests themselves can be flawed, ina- a reasonable judgment can be made asto dequately designed, or misinterpreted. whether or not harmful effects are likely to occur for prescribed uses.Numerous toxicology laboratories and regulatory mechanisms 4. There is always the possibility of some have been established forthis purpose of unknown or unanticipated effect arising. risk assessment.

TOXICOLOGY

In order to provide a reasonable certainty of of primary valuein evaluating highly toxic safety,toxicologists determine the effects chemicals like modern insecticides, where the of chemicals on vital physiological functions principalhealthconcernisacuteillness of animals.Observable effects may be found from occupational exposure. However, the in such attributes as liver and kidney func- LD50 is also useful as a basis for comparing tion, reproductive success, nervous system the relative acute toxicities of various che- performance, metabolism, growth and develop- micals such as herbicides, insecticides, and ment, and survival. Various means of dosage household substances (Table 1). are used, such as oral, dermal, respiratory, or injection. Specific strains of mice and Whether the effects being studied are acute rats that are expected to be quite sensitive orchronic, theexperimentsareusually are usually selected for study.Some studies designed to establish the dose-response rela- may beshortinduration,seeking acute tionship and to discover the threshold dose effects; others may extend throughout the below which no effect can be detected.1 The lifetimeoftheanimal or evenintosub- no observable effect level (NOEL) is another sequent generations, looking for more subtle termthatisoftenusedinsteadofthe chronic or subchronic effects. Acute respon- threshold dose when describing toxicological ses are usually associated with higher doses; parameters. Althoughthe two terms are whereas chronic conditions are often, but not semantically different, they merely represent always,theresult of lower doses over a tThe threshold concept asit applies to carcinogens isstill longer time.The effects of a chemical may the subject of much debate (Maugh 1978). because it may be be both acute and chronic;it also may pro- impossible to do the experiments that would establish the validity of the concept for allcarcinogens.Nevertheless, duce a recoverableeffect,suchaslung itisquite clear that the threshold conceptisvalid for congestion, or produce irreversible effects, most toxicological responses, including at least some types such as birth defects (teratogenic), muta- of carcinogenesis (Cornfield 1977, Council for Agricultural Science and Technology 1977).There is no question that as tions (mutagenic), cancer (carcinogenic), and the dose of a carcinogen decreases, the probability of a death (lethal). carcinogenic effect decreases. Ifthat probability islow enough,it may be considered as virtually zero. From a prioritystandpoint,the Carcinogen Policy Group ofthe The lethal dose of such chemicals is usually Environmental Protection Agency (EPA) has decided not to expressed asthe LD50,the dosethatis pursue (for regulatory purposes) any chemical which presents lethalto50 percent of the animals treated a statistical cancer risk of less than one case in a million in a test.Information on the lethal dose is lifetimes (Anonymous 1981).

4 TABLE 1. ACUTE TOXICITIES OF VARIOUS CHEMICALS.

Oral LD50 Toxicity category1 (for rats) Oral LD50 extrapolation (Signal word on label) Chemical substance (mg/kg) (for 60-kg human2)

IV.Very slight 50,000 6.7L

Sugar 30,000 ( 1.8 gal) Fosamine 214,000 Ethyl alcohol 13,700 Picloram 8,200

lii. Slight (caution) Asularn, Simazine 5,000 670 mL

Glyphosate 14,300 ( 1.4 pt) Table salt 3,750 Bleach, dicamba 2,000 Atrazine 1,750 Aspirin, Vitamin B3 1,700 Hexazinone 1,690 Dalapon, Amitrole-T 1,000 2,4-DP 800 MSMA 700 2,4,5-TP, Triclopyr 650

II. Moderate 2,4,5-T 500 67 mL

(warning) 2,4-D 370 ( 0.3 cup) Caffeine 200 Paraquat 150

I.Severe (danger- Nicotine 50 6.7 mL poison) Dinoseb 40 ( 1 tsp) Strychnine (rodenticide) 30 Parathion (insecticide) 13 5 0.67 mL ( 11 drops) TCDD 0.01

1Categories, signal words, and L050 ranges are based ona classification system used by the EPA for labelling pesticides (Maxwell 1982).Mote the logarithmic scale; the range for each category is about 10 timesgreater than that for the previous category. Pesticide values were generally obtained from the Farm Chemicals Handbook (1982). The TCDDvalue was obtained from Schwetz et al.(1973).Values for other substances were obtained fromthe Merck Index (Windholz 1976). 2Quantities assume a liquid formulation of commercial herbicide product containing45 percent active ingredient. 1 for procedures involved in calculations. See Appendix two ways of viewing a similar portion of the Intake of chemicals normally occurs in three dose-response curve (Fig. 1). The thresholdbasic ways: oral(ingestion),respiratory doseisthelowest dose that producesan (inhalation), and dermal (absorption).2 Of effect, thereby implying thatno effect will these,the greatest potential for intake of appear at any lower dose.The NOEL, on the herbicide underoccupationalconditionsis otherhand,isthe highest dosewith no effect, thereby implying thatany higher dose 2A fourth route of chemical entry involvesdirect injection. may cause a response.The NOEL, being the This mode of administration is usually confined to Labora- more conservative of the two terms, has been tory situationswithtest animals, and haslittle,ifany, used in this report. practical merit for realistic occupational situations. exposed4 in various occupational or environmental circumstances. A safety factor of 100 means that the dose is1/100th of the NOEL. That figure is generally considered to be the minimum acceptable safety factor for pesticidesand istheoneusedinthis report. As a frame of reference, the safety 0.z factor(therapeuticindex) used forphar- 0 maceutical drugs may be 10 or less.In other w(I) words the medication might be used at a dose that is 1/10th (or more) of the harmful dose. Tables 2 and 3 illustrate how safety factors NOEL HRESHOLD DOSE are utilized to evaluate the risks associated with theintake of various herbicide con- I I 0 DOSE centrations. There islittle choice but to rely on animal FIGURE 1. CONCEPTUAL DIAGRAM OF THE experiments to assess potential human health DOSE-RESPONSE CURVE SHOWING THE risks.Fortunately, many other animal spe- RELATIONSHIP BETWEEN THE NO OBSERVABLE cies have physiological functions similar to EFFECT LEVEL (NOEL) AND THE THRESHOLD humans, thereby making them reliable indica- DOSE. tors of potential problems in humans.Thus, the battery of animal tests conducted nowadays (ranging from mice to monkeys and from through the skin.Instances have occurred of acute to chronic effects) has generally been oralintakeofherbicideswithresulting sufficient to detectpotential problems harm, but such cases have involved either before wide-spread use of a given chemical is suicidal intent or mistaken ingestion of con- permitted. centrated material from unlabeled containers. Because most chemicals are more potent when Occasionally, clinical and epidemiological ingested by mouth than when absorbed through data on human populations exposed in the past the skin, and because of the convenience of can be used in making regulatory decisions, adding such chemicals to the feed of testbut the discovery of adverse health effects animals,oraladministrationofdosesis inthis manneristragic. Almost always, often chosen for toxicologic testing. such effects have arisen from contact with Consequently, most of the data used in this chemical products that were introduced prior report are derived from studies involving to the present use of broad animal-screening oral dosage. protocols.Failure to follow adequate safety precautions has also been frequently impli- c a ted. A cautious evaluation of therisk3 of any given chemical includesa determination of The information from toxicologic studies must the safety factor associated with the amount be coupled with information on the likelihood of each dose.The safety factor is a number and degree of human exposure and intake in derived from dividing the NOEL (determined order to realistically assess the risk from laboratory animal tests and extrapolated inherent in the use of any chemical (Norris to body weights of human size) by the known 1971a). For example,itis entirely possible orestimated maximum dosefor humans to usea highly toxic chemicalsafely,if intake can be minimized or eliminated. On the other hand, even a relatively innocuous chemical canbedangerousifintakeis 3The terms "risk and hazard' are sometimes confused. excessive. According to Hohenemser et al.(1983), hazard is properly used to indicate threats to human health or things of value. For example, driving an automobile is classified a hazard. Risks, on the other hand,involve a probability of harm 'Exposure to herbicides" is sometimes erroneously resulting from exposure to a hazard.Thus, the lifetime interpreted to mean actual intake or absorption of a dose. risk of dying in an automobile accident is2 to 3 percent of "Exposureto herbicides" correctly means asituation of all ways of dying. proximity and potential for intake. TABLE 2.

HYPOTHETICAL DAILY INTAKE BY A 60-KG (132-LB) PERSON OF VARIOUS SUBSTANCES CONTAINING HERBICIDES THAT WOULD NOT EXCEED 1/100 OF THE CHRONIC OR SUBCHRONIC ORAL NO OBSERVABLE EFFECT LEVEL (NOEL) DETERMINED FROM LABORATORY STUDIES WITH TEST ANIMALS.1

Substanceand concentration of active ingredient Herbicide Chronic Commercial Aqueous Stream Ambient Animal or formulation3 spray water5 air6 meat7 subchronic (concentration mixture4 (0.1 ppm) (1 1.tg/m3)(0.1 ppm) oral NOEL2 as formulated) (24 g/L; (mg/kg/day) 2lb/bgal) ------Daily intake in metricunits/(English units)------

mL mL L m3 kg (drops) (drops) (gal) (yd3) (Ib)

2,4,5-T 10 0.013 0.25 60 6,000 60 (0.2) (4) (16) (8,000) (132)

2,4,5-TP 20 0.026 0.50 120 12,000 120 (0.4) (8) (32) (16,000) (264)

2,4-D 20 0.027 0.50 120 12,000 120 (0.4) (8) (32) (16,000) (264)

2,4-DP 10 0.013 0.25 60 6,000 60 (0.2) (4) (16) (8,000) (132)

Amitrole 10 0.028 0.25 60 6,000 60 (0.4) (4) (16) (8,000) (132)

Asulam 40 0.071 1.0 240 24,000 240 (1.1) (16) (64) (32,000) (528)

Atrazine 50 0.074 1.25 300 30,000 300 (1.2) (20) (80) (40,000) (660)

Dalapon-Na 50 0.04 g 1.25 300 30,000 300 (20) (80) (40,000) (660)

Dicamba 5 0.007 0.125 30 3,000 30 (0.12) (2) (8) (4,000) (66)

Dinoseb 5 0.01 0.125 30 3,000 30 (0.16) (2) (8) (4,000) (66)

Fosamine 30 0.043 0.75 180 18,000 180 (0.7) (12) (48) (24,000) (396)

Glyphosate 30 0.059 0.75 180 18,000 180 (0.9) (12) (48) (24,000) (396)

CONTI NUED

7 TABLE 2 (continued)

Substance and concentration of active ingredient Herbicide Chronic Commercial Aqueous Stream Ambient Animal or formulation spray water air meat subchronlc (concentration mixture (0.1 ppm) (1 g/m3) (0.1 ppm) oral NOEL as formulated) (24 g/L; (mg/kg/day) 2 lb/bgal) ------Daily intake in metric units/(English units) ------

mL mL L m3 kg (drops) (drops) (gal) (yd3) (Ib)

Hexazinone 25 0.06 0.625 150 15,000 150 (1.0) (10) (40) (20,000) (330)

MSMA 5 0.006 0.125 30 3,000 30 (0.10) (2) (8) (4,000) (66)

Picloram 20 0.058 0.50 120 12,000 120 (0.9) (8) (32) (16,000) (264)

Simazlne 50 0.038 g 1.25 300 30,000 300 (20) (80) (40,000) (660)

Triclopyr 30 0.041 0.75 180 18,000 180 (0.65) (12) (48) (24,000) (396)

1The values presented In Tables 2 and 3 are based on oral toxicity data. As such, they represent a "worst case" analysis when compared to dermal routes of exposure.See Appendices 1 and 3 for assumptions and examples of calculations used to derive these values.Note that a 100-fold safety factor has been used in preparing these tables.Also note that calculations in Appendix 1 assume that all of the herbicides listed are partitioned In stream water, atabient air, and animal meat in a similar fashion to the phenoxy herbicides, for which the data base is strongest.Abbreviations and metric/English equivalents used are described in Appendix 6. 2Chronic or schronic oral NOEL daily oral dose of herbicide which does not exceed the no observable effect level (e.g., for toxicity, fetotoxicity, teratogenicity, oncogenicity, rnutagenlcity, etc.) when administered orally over a relatively long period of time (e.g.. 90 days. two years, life-time, or multi-generations, depending on the test and animal species involved) or during a critical stage of development (e.g.. pregnancy).Expressed as mg of herbicide active ingredient per kg of body weight per day.Values used are conservative and are generally at or below the NOELs cited in Appendix 1;.

3Vaiues for concentration of herbicide activeingredient(ai)derived from the commercial product specificationsin Appendix 5. 4Assumes an aqueous spray mixture containing 21; g herbicide ai/L spray (2 lb herbicide ai/10 gal spray).This is a typical concentration for most of the herbicide mixtures applied in forestry. 5Concentration of 0.1 ppm represents the Nworst case" actual amount of phenoxy herbicide (2,4,5-T) that has been detected in stream water. More "typical" amounts found In secondary streams for short periods of time following application are generally 0.01; ppm or less.The "maximum hypothetical" concentration in a shallow stream 10 cm (4 in.) deep that has been directly sprayed would be about 2 ppm.See Appendix 2 for calculations involved and results of actual water monitoring. 6The concentration of 1.0 pg/rn3 represents the highest estimate of 2,1;,5-T in the air downwind from Pacific Northwest forest applications.The safety factor determined for such applications is so large it has been suggested that this avenue of exposure to 2.4,5-T did not constitute a measurable risk (Newton and Norris 1981).For example, a person at moderate labor will have a respiratory ventilation rate of 8-10 m3/day.Therefore, the lnte noted for 2,4,5-T in Table 1is 600 times greater than the daily total respiration and assumes that the material remains suspended in the air at the maximum concentration of 1.0 pg/rn3throughout the exposure period (an unlikely scenario).Recalling that the values given are already 1/100 of the NOEL, the actual safety factor for this situation with 2.4,5-T is at least 60,000. 7Residues of phenoxy herbicides have not been detected in venison from the Pacific Northwest, except for 0.021 mg 2,4,5-T/kg body weight found In the liver of one animal (Newton and Norris 1968).Thus, the 0.1 ppm value used here probably represents an amount far greater than amounts actually present. TABLE 3. HYPOTHETICAL DAILY INTAKE BY A 60-KG (132-LB) PERSON OF VARIOUS SUBSTANCES CONTAINING TCDD THAT WOULD NOT EXCEED 1/100 OF THE CHRONIC OR SUBCHRONIC ORAL NO OBSERVABLE EFFECT LEVEL (NOEL) DETERMINED FROM LABORATORY STUDIES WITH TEST ANIMALS.

Chronic or subchronic Substance containingTCDI) Basis for oral Aqueous NOEL for NOEL1 Commercial spray Stream Ambient Animal TCDD (pg/kg/day) formulation2mixture3water4 air5 meat6 ----Daily intake in metric units/(Englishunits)----

mL mL L m3 g (drops) (tsp) (gal) (yd3) (oz)

Rat 0.001 0.133 2.5 600 60,000 50 studies7 (2.1) (0.5) (158.4) (78,600) (1.75)

Rat and 0.01 1.33 25 6,000 600,000 500 monkey (21.3) (5) (1,584) (786,000) (17.5) studies8

2,4,5-T 0.03 4.0 75 18,000 1,800,000 1,500 RPAR (64) (15) (4,752) (2,358,000) (52.5) Position Document9

1See Table 2 note 2.It has been speculated by some scientists that the effects of a series of sublethal doses of TCDD can accumulate over time within an organism, eventually triggering a toxic response once a certain critical levelis reached (Meselson et al. 1978, Streisinger 1978).That is,they suggest that the dose required to elicit a toxic response is the same whether given as a single dose or spread out over an extended period of time,it is true that all chemicals have some degree of cumulative or additive effect in that any inlury produced requires some period of time for reversal or repair, and any additional doses added during that interval of time will add to the burden.Nevertheless, the period of time required between doses for reversal or repair to occur is finite, and generally ranges from minutes to many days. depending on the chemical and dose at which itIs given. Therefore, the time over which a chemical can gradually accumulate to the point where it suddenly has a toxic effect is not likely to be infinite, so that the time required for a toxic effect to be manifested is not likely to be strictly proportional to the dosege rate, as Streisinger (1978) speculates.No chemical at the present time is known to have such additive properties over long periods of time (U.S. Department of Agriculture 1978). indeed, studies with guinea pigs (Vos et al.1973) and rats (Vos and Moore 197l) exposed to TCDD have shown the opposite. These species can tolerate about three times the LD50dose of TCDD when the chemical is administered in small doses over several weeks.Thus, the case for additive effects of sublethal doses of TCDD over extended periods of time does not appear to be a strong one. If the incremental doses of TCDD were perpetually stored in an animal's body, one could perhaps make a stronger case for the plausibility of an additive or cumulative effect having a time frame dependent on the total dose.However, TCDD does not per- sist in this fashion.The excretion kinetics for TCDD are well defined, showing a half-life pattern in several animal species ranging from 12-35 days (Alien at al.1975. FrIes and Marrow 1975. Rose et al. 1976, Neal at ai.1982). 2Assumes a commercial herbicide such as Esteron2q5, which contains 45% 2,4,5-T ae (4 lb 2,4,5-T ae/gal product). The maximum level of TCDI) permitted in commercial herbicides (2,4,5-T and 2.4.5-TP) sold in international markets is generally 0.01 ppm on a 2,4,5-T ae basis.This concentration has been used in the calculations. The concentrations detected in present production are routinely less than 0.005 ppm.

CONT I NUED 3Assumes an aqueous spray mixture containing 24 g 2,4,5-T ae/L spray (2 lb 2,4,5-T ae/10 gal spray) made from commercial herbicide containing 0.01 ppm of TCDD.This Is a typical concentration of 2,14,5-1 for application of this herbicide in forestry. 4Based on a concentration of TCDD in stream water of 0.001 ppt or 1 x io6 ug/L (derived from watercontaining 0.1 ppm of 2,4,5-T, which in turn contains 0.01 ppm TCDD; note that this concentration represents a "worst case" situation). 5Based on a concentration of TCDD in antlent air of 0.01 x io6 pg/rn3 (derived from air containing an "upper limit" of 1 pg/rn3 of 2,I4,5-T, which in turn contains 0.01 ppm TCDD; note that this concentration represents a "worst case" situation). The safety factor determined from such a condition following forestry application is so large It has been suggested that this avenue of exposure to TCDD did not constitute a measurable risk (Newton and NorrIs 1981).For example, a person at moderate labor will have a respiratory ventilation rate of 8-10 m3/day.Therefore, the intake noted for TCDD at the lowest NOEL (0.001 pg/kg/day) In Table 3 is 6.000 times greater than the daily total respiration, providing a safety factor of at least 600,000. 6Assumes a 'worst case" concentration of 60 ppt, the maximum amount that was reported In the EPA beef fat survey (U.S. EPA 1977). ThIs survey was designed to detect TCDD In one of the most likely situations (i.e., lean cattle grazing on pastures recently treated with 2.4,5-T).

7Based on long-term toxicological studies with rats (Murray et al.1979, Kociba et al.1978,1979a, 1979b). This level was equivalent to approximately 22 ppt in the diet.Rhesus monkeys have tolerated oral doses of 2.I,5-T containing as much as 0.0005 pg TCDD/kg/day without any adverse effects (Douierty et al. 1975).Experiments by McNulty (1978) on rhesus monkeys indicated they could tolerate a total dose of 0.2-1.0 pg/kg before exhibiting adverse effects. 8i3ased on toxicological studies with rats (Kociba et al.1975) and rhesus monkeys (McNuity 1978).McNuity (1978) Indicated that in his study thislevel was equivalent to 200 ppt in the total diet.Leng (1978) clarified this interpretation. She pointed out that in the actual experiment the monkeys were force-fed by stomach tube using 10 rrL of corn oil three times per week for three weeks.The actual concentration of TCDD in the corn oil was calculated to be about 15,000 ppt (15 ppb) for this portion of the experiment. 9Basecl on the value used In the 2,4,5-1 RPAR Position Document 1(U.S. EPA 1978b).

REGULATORY CONTROL Regulatory agencies routinely use the results to complete and costs millions of dollars. of toxicologic testing to evaluate the risks Even after a product has been registered, any of using chemical products under different new factual information which comes to light conditions, whether they involve pesticides, concerning unreasonable adverse effects on food additives, drugs, industrial chemicals, human health or the environment may precipi- householdcleaners,orpollutants. By tate re-examination of the product.Finally, balancing potential harm against the antici- the law requires each pesticide product to go patedbenefits, a rationalbutadmittedly through the process of re-registration every subjective judgment can be made. five years.This process affords an additional opportunity toincorporate new find- The Federal Insecticide, Fungicide and ingsorrecommendationsintoregulatory Rodenticjde Act (FIFRA, as amended)is the actions. Proper training of pesticide appli- primary federal law for regulating pesticides cators and adequate enforcement of regula- intheUnitedStates. The Environmental tions governing pesticide use are important Protection Agency (EPA) has the authority for to ensure thatthe materialswill be used administering and enforcing this act, alongcorrectly. withdesignatedstateagencies. Product registration isa key factor of this act and Nevertheless, there are occasions when new is described as follows (U.S. EPA 1982a) concernssurfacethataresufficientto warrant a specialreview ofaparticular Under current law, pesticides marketed in pesticide product. Such was the case for this country must be registered with EPA. 2,4,5-T(2,4,5-trichlorophenoxyacetic acid) To registera product an applicant must whenthehighlytoxiccontaminant TCDD submit datatothe Agency adequateto (2, 3,7,8-tetrachlorodibenzo-2-dioxin) was demonstrate that the proposed use will not discovered. Both the EPA and the state regu- pose risks of unreasonable adverse effects latory agencies can take action to deal with on human health or the environment when such developments. Options for the EPA range used according to its approved labeling. from internal review by their own staff of toxicologists,chemists, andbiologiststo The batteryoftestsrequiredforinitial theformal proceedingsofSpecial Review registration of a pesticide takes many years(formerly known as Rebuttable Presumption

10 AgainstRegistration,RPAR),Suspension, State regulatory agencies have a concomitant Emergency Suspension, and Cancellation. In responsibilityforensuringsafe pesticide all of these activities,the agency can call use.They can impose use limitations beyond on a wide variety of scientific expertise, those specified by the EPA, provided local including the EPA Scientific Advisory Panel, conditions warrant such action; for example, the CancerAssessment Group, the Reproductive special driftcontrol measures can be Effects Assessment Group, the National Cancer required when applying certain herbicides Institute, and the NationalAcademyof near sensitive crops. Sciences.

TOXICITY DATA

Most forestry herbicides are classifiedin containing 0. 1 ppm (a "worst case" situation) theslightto moderate categories of acute of atrazine.5 toxicity (Table 1).They fall into the same categories as sugar, baby lotion, ethyl alcohol, table salt, liquid detergent and bleach, Since most herbicides used for forestrypur- aspirin, vitamins, and a number of other com- poses are applied only during short periods mon household chemicals.With the exception inthespring andfall,thepotentialfor of dinoseb, an herbicide sometimes used to chronic exposure to these materials is quite desiccate forest vegetation prior to limited. Furthermore, these materials are prescribed burning, they are not nearly as usually applied only once or twice during the toxicas thenicotinecommonly foundin rotationperiodofa givenforeststand, cigarette smoke, or certain insecticides like whichiscustomarily kO yearsormore. parathion,or some rodenticides containing Precautions taken during application, coupled strychnine. Theselattermaterialsare with factors such as dilution, plant uptake, designed to affect specific animal functions, adsorption, metabolism, and breakdown, such as the nervous and circulatory systems preclude the potential for exposure to unsafe of insects and rodents.Therefore, they are chronic and acute dosages. These safeguards inherently more toxic to humans than most applynotonly toherbicideapplicators herbicides, which are specifically designed dealingwithconcentratedandformulated toaffectplantfunctionslikegermination materials,buttothegeneralpublicand and photosynthesis.In any event, using com- other animalsin the vicinity of the treated mon sense, being adequately trained, heeding areas as well. label instructions and warnings, and complying diligentlywith pertinent regula- Researchers have summarized the toxicologi- tions are normally sufficient precautions to cal,medical, and environmental information prevent acute illness when using commercial herbicides, whether concentrated or mixed for available on phenoxy and other herbicides usedinforestry (Newton and Dost1981). application. Detailed reviews of the literature and analyses of the pharmacokinetics (metabolic fate) ofphenoxyherbicidesinanimalsystems From a chronictoxicitystandpoint,the greatest risk is associated with exposure to (including humans) have been prepared by Leng (1977) and Leng etal. (1982). A text by commercial herbicide concentrates (Table2). Wagner(1981)discusses clinical and toxico- For example, only about one drop of a commer- logicalaspectsof phenoxy herbicides and cial atrazine concentrate would be within the other agricultural chemicals.None of these safety tolerance of 1/100th of the NOEL for reportssuggeststhatthereis aserious daily, chronic ingestion.However, once the levelofriskresultingfromthe proper herbicides have been diluted and applied to application of forestry herbicides. the environment, huge quantities of water, air, or food from the area would have to be taken in daily to reach this same dose; for example,an adult would have to drink 300 5See Appendix 6 for a description of metric-Englishequiva- lents and abbreviations for the units involved. liters (80gallons) of stream water per day

11 FIEI.D STUDIES

Studies have been conducted measuring actual pg/L,or 4 pg/m3) to0.169 ig/L(or intake of herbicides, particularly phenoxies, 169 jig/rn3) on sampling devices placed in the by humans, fish, and wildlife in the forest. breathing zone of workers applying this her- Without exception, the amounts detected have bicide via backpack and mist blower methods. been far below levels that have toxicological The herbicide wasrarely detectedinair significance. Althoughthedata baseis samples collected near the breathing zone of substantial, certain gaps still remain in our workers involved in aerialapplication. understanding of some biochemical mechanisms Similarresultswere obtainedinastudy andtheimplicationsofherbicide-induced involving aerial application of 2,4-D (Lavy effectson forest ecology. Most ofthe 1980a).Aerial traces of the herbicide were reviewslistedinthe bibliography identify rarelydetectedon thesitesafterthe these needs, and currentresearch is completion of spraying. addressing many of them. Where 2,L4-D and 2,4,5-1 were detected in the urine of crew members, the doses calculated OCCUPATIONAL CONTACT were less than 0.1 milligrams per kilogram of body weight per day(Lavyetal.1980b, Severalstudieshavemeasuredthedose 1982a). Comparable amounts of 2,4-D have received by forestry workers applying 2,4-D also been detectedinthe urine ofagri- (2,4-dichlorophenoxyacetic acid) and 2,4,5-1 cultural workers applying this herbicide to (Lavy 1979a,b, 1980a,b; Lavy et al. 1980a,b, wheat fields (Nash et al.1982). Toxicolog- 1982a,b; Newton and Norris 1981).The Lavy ical interpretations by Ramsey et al.(1979, studiesinvolved three common methods of 1980) indicate that these doses are far below application: backpack spraying, tractor mist the NOEL established for laboratory animals; blowing, and helicopter spraying.The types calculated safety margins ranged from the of personnel sampled were backpack sprayers, hundreds to thousands (Hall 1979, 1980). pilots, mechanics, mixers, flaggers, supervisors, and observers. Because phenoxy her- Humans have experimentally ingested single bicides are excreted intact in urine doses of silvex and 2,4,5-1 as high as1 and relatively soon after intake,it was possible 5 mg/kg, respectively, without any immediate to determinetheactual dose of herbicide adverseeffects(Sauerhoffetal. 1977, received by analysis of theurine.6 Air Gehring etal.1973). As much as0.5 g sampling devices and cloth patches attached 2,4-D/day was ingested by one man over a to the workers' clothing were used to deter- 21-day period without observable ill effects mine possible routes of intake. (Kephart1945). There have been several suicide attempts with 2,4-D, at least three These studies found that the intake of her- ofwhich were successful(Nielsen etal. bicidesfrom forestry applicationsispri- 1965, Geldmacher et al.1966). Two indivi- marily restricted to those individuals duals have survived suicide attempts in which intimately involved in the operation: mixers, the doses, as judged by blood and urine con- backpack sprayers,pilots,and mechanics. centrations, were estimated to be about 100 Supervisors, flaggers, and observers rarely mg/kg and 400 mg/kg, respectively (Young and showed any herbicide dose in these studies. Haley 1977). Additional known cases Contact was minimized when protective apparel involving exposure of humans are discussed in was worn,such as rubber gloves, rubber Newton and Dost (1981), Leng et al.(1982), boots, and disposable coveralls,and when and Wagner (1981). hygienic precautionswere taken,such as washing hands before rest breaks. Leng et al.(1982) reviewed several studies Lavy (1979a) found amounts of 2,4,5-1 in the of occupational contactwith phenoxy her- bicidesanddeterminedthatthemaximum airranging from non-detectable(< 0.004 acquired dose of 2,4,5-T, for example, is not likely to exceed 0.1 mg/kg of body weight per 6Recent work by scientists at the USDA Agricultural Research work day. This worst-case doseiscon- Service(Selletal. 1982)has shown that 2,4-Disalso excreted via the sweat glands.Since the 2,4-D study by siderably above the acceptable daily intake Lavy et al.(1982a) was conducted in the early spring when (ADI) of 0.003 mg/kg/day temporarily adopted temperatures were relatively cool and under conditions where for2,4,5-1atthe 1979Joint Meeting on physical exertion was not very great, loss of 2,Ll-D through perspiration was not likely to have been very significant. Pesticide Residues of the Food and Agricultural Organization and theWorld

12 Health Organization (Commission to the viously with respect to applicators and their Council of the European Economic Community immediate families--individualswith a much 1982).This same dose of 2,4-D is well below greater likelihoodof contactthanthe the ADI of 0.3 mg/kg/day established by the general populations studied by Field and Kerr World Health Organization (Vettorazzi 1979). (1979)and Hanifyetal.(1981). Inany In any event, it would be prudent for routine event, both these researchers stressed the applicators of herbicides to follow the pre- fact that even where 2,4,5-T use and congeni- cautionsfoundbeneficialby Lavyetal. tal disorders appeared to be linked in their (1982a). studies, they did not establish a cause-and- effect relationship; nor were any correla- tions linked with actual or estimated doses. EPIDEMIOLOGICAL STUDIES The possible association of cancer to prior Epidemiology is the science that studies the contact with herbicides is more ambiguous. distributionofdisease in a population. Studies done in Sweden on railroad workers Since chemical applicators and their imme- (Axelson etal.1979),forest workers and diate families are much more likely than the sawmi ll/pulpmi II operators (Hardell and general population to be harmed by pestici- Sandstrom 1979, Hardell 1981), and a sample des, any medical problems associated with of patients selected from the Swedish Cancer pesticide contact should be apparent in that Registry (Erikkson et al.1979) suggest the occupational group. possibility of an association between substantial occupational exposure to phenoxy Epidemiological surveys of chemical applica- herbicides or chlorophenols and subsequent tors in the U.S. (Roan 1980, Carmelli et al. soft-tissuesarcomas7 (Milby et al. 1980). 1981, Honchar 1982,Williams 1983) and New Itishardto draw firm conclusions from Zealand (Smith et al.1981, 1982a) have been these studies for several reasons: the deter- unable to establish any link between occupa- mination of actual contact and resultant dose tionalexposure topesticides (including based on recall by patients and incomplete 2,14,5-T)and human reproduction problems. records; the difficulty of singling out one The same lack of a correlation between her- chemical or group of chemicals as the causal bicide use and birth defects has also held agent when exposure has occurred to a variety true for the general population of Hungary, of chemicals; and the diverse nature of the of which a relatively large percentage of the cancers involved, which suggests more than populationisinvolvedinagricultureand onetype ofcausal agent. Nevertheless, forestry, with a high rate of pesticide use additional health risk studies are warranted, (including 2,4,5-T) per capita (Thomas 1980).and several are currently under way.These are described in several documents: National Forest ProductsAssociation 1981, JRB However, another study (Field and Kerr 1979) Associates 1981, Shepard 1982.Other health found a significant correlation between the risk studies are being planned; for example, amount of 2,4,5-T usage in Australia and cer- the National Institute for Occupational taincongenitaldisorders,suchas anen- Safety and Health is investigatingsoft cephaly andmeningomyelocele(neural-tube birth defects)in the general population of tissue sarcoma epidemiology in the U.S. New South Wales.A similar epidemiological Other studies have failed to establish a link analysis of population birth defects in New between cancer or other illnesses and occupa- Zealand (Hanify et al.1981), while it found tional exposureto phenoxy herbicides and no association between 2,k,5-T use and such TCDD during manufacturing (Cook et al. 1980, neural-tubedefects,didfind a positive Ott et al.1980, Zack and Suskind 1980, May association between 2,4,5-T use and human 1982, Suskind 1982, Townsend et al. 1982) or talipesmalformation (clubfoot). These spraying(Riihimakietal.1978, 1982;van positive associations are somewhat puzzling Houdt et al.1982; Milham 1982; Smith et al. in llt of the laboratory studies done on 1982a). Eventheheavyuseof TCDD- animalsthatindicatethatothertypesof birth defects are more commonly associated 7Sarcomas are malignant growths arising from nonepithelial tissues of mesodermal embryonic origin (e.g., muscles, con- with 2,1,5-T or TCDD, notably cleft palate nectivetissues,bone,cartilage,lymphoidtissue,and and cystic kidney disease (Courtney and Moore reproductive, circulatory and excretory organs). Therefore, 1971). The resultsarealso puzzlingin soft-tissue sarcomas refer to those sarcomas not associated lightofthenegativefindingscited pre- with bone, cartilage, and other structural material.

13 contaminated Agent Orange by U.S. military 0.012 to 0.895 I.Ig/m3 in the air over a fall- forcesin Vietnam has been calculated by treatedreforestationunitintheSierra Stevens (1981)to be an unlikely cause for Nevada ofnortheasternCalifornia(appli- the systemic illnesses experienced by Vietnam cation rate of 3 lb/A, or 3.36 kg/ha). The veteransorforbirthdefectsintheir levelsdeclinedsharply bythethird day children, as claimed byBogen (1979). afterapplicationandwerenon-detectable Tentative support for this view comes from an (< 0.008 pg/rn3) by the third week. Within epidemiological study conducted by the U.S. aboutonekilometerofa forestsitein Air Force of military personnel engaged in western Oregon that was aerially sprayed with actually mixing and aerially applying Agent 2,4-D,2,4,5-T,and picloraminMay,air Orange in Vietnam from 1962-1971, an opera- samples collected beginning at one hour after tion conducted under the code name "Ranch spraying and for the next 57-hour period con- Hand." Thus far, the study has not detected tainedlessthan 0.2 pg/rn3 of the various any increasein soft tissue sarcoma, mor- herbicides (Norris 1980a). A closer sampling tality,organ abnormalities, or major birth stationlocatedat 152 metersfromthe defectsinoffspring ofthe "Ranch Hand" treated area briefly recorded a maximum of group when compared to a similar group that 1.8 pg/rn3, but none of the test tomato plants was not exposed to Agent Orange (Brown 1982, (very sensitive to herbicides) here or at the Assistant Secretary of Defense 1984). fartherstationweremarkedlydamaged. Furthermore, the results of a long-term air The issue of possible adverse health effects monitoring studyin the general vicinity of fromAgentOrange isstillunresolved, forestry herbicideapplicationsinwestern however, due to the difficulty of Oregon indicated that widespread con- establishing asingle causative relationship tamination of air from such operations was when so many confounding factors (e.g., con- not occurring(Norrisl980a). Only one tactwithotherchemicals,use of drugs, sample collected during a six month period stress-related syndromes) are involved, and (May-November) contained any herbicide (0.002 much of the information regarding dose levels pg/rn3 of 2,4-D), and this was collected long is lacking.A comprehensive study has been after the normal forestry spray season had launched to investigate whether Agent Orange ended, suggesting a sourceother than hascausedmedicalproblemsforVietnam forestry applications. veterans. The study, mandated by Congress in 1979, is sponsored by the Veterans Thus,theamountsof2,ZI-Dand2,4,5-T Administration and is being conducted by the detected in or near agricultural and forest federal Centers for Disease Control; defini- sitestreatedwiththesematerialshave tive results are not expected before 1987. generally been in the nanogram to microgram range or less per cubic meter of air.These levels are more than 1,000 times less than PUBLIC CONTACT the 10 mg/rn3 thresholdlimitvalue(8-hr time-weighted average) adopted for 2,k-D and 2,4,5-Tin the work place by the American Ina two-year survey conducted at several Conference of Governmental and Industrial agriculturalsites by the EPA,0.49-10.53 Hygienists (1977).They are also generally percent of 2,479 air samples contained phe-below the levels causing injury to non-target noxy herbicides, but only at very small, meanplants, such as crops and ornamentals. concentrations(0. 1-4. 1ng/m3)(Kutz1978). Earlier surveys support these findings (Bamesberger and Adams 1966). Even when In another two-year EPA survey (Kutz 1978) sampling was done during the spraying season conducted in major agricultural river basins in the wheat-growing region of Washington (a of the U.S.,less than 0.4 percent of the heavy-use area for 2,4-D), the average con- 2,500 water samples contained phenoxy her- centration of 2,4-D detected in the air was bicides,againatverylow concentrations only 0.1 pg/m3 (Adams et al. (maximum of 1.9 ppb). The amounts detected, 1964). if consumed by humans, would still be well belowtheacceptabledailyintake(ADI) Studies have also monitored the ambient air recommended bytheSafe Drinking Water in or near reforestation units treated with Committee of the National Academy of Sciences 2,4-D or 2,L4,5-T.Cheney et al. (not dated) (National Research Council 1977).A recent detected amounts of2,4,5-Tranging from nation-wide survey of rural drinking water

14 supplies by Cornell University researchers found virtually no 2,4-D, silvex, or insec-FISH AND WILDLIFE CONTACT ticides (Francis et al.1983). An EPA publication by Newton and Norgren Concentrations of phenoxy herbicides greater (1977) specifies recommended maximumcon- than 0.01 ppm are seldom found in streams centrations of silvicultural chemicals following conventional forestry applications (including herbicides) permissible in forest streams. The recommendations are based ona (Norris 1977, 1981).Concentrations as high detailed as 0.1 ppm have occasionally been detected, analysis of the sensitivityof aquatic and terrestrial animals, as wellas but these were recorded before the advent of plants,to various concentrations of silvi- strict regulations governing applicationpro- cultural chemicalsin water. cedures.Most water samples collected nowa- As mentioned days do not contain any detectable amounts at earlier,concentrationsofherbicidesin forest streams have rarely exceeded 0.01ppm the detectionlimit of 1 ppb. Any minute amounts which are present dissipate within 24 following forestry applications. Depending on the herbicide,thisisat or well below hours due to dilution, adsorption, and break- the maximum concentrations recommended for down (Norris 1981). These processes preclude safe use of water by aquatic and terrestrial intake by the general public of significant animals (Newton and Norgren 1977, Newton and amounts of herbicides from aquatic sources. Knight 1981). Phenoxy herbicides are only rarely detected in agricultural products such as rice, beef, The intake by terrestrial animals of phenoxy andmilk, andtheninonlyinsignificant herbicides is most likely to result fromcon- amounts (Council for Agricultural Science and sumption of or contact with recently treated Technology 1978, Bovey and Young 1980). Nor vegetation (Norris 1977). However, data from haveherbicidesgenerallybeenfoundin Norrisetal. (1977) indicatethatthe forest game animals in the Pacific Northwest average amount of herbicide measured imme- (Newton and Norris 1968). The maximum resi- diately after application of 2.24 kg due detected thus far in the edible tissue of 2,4,5-T/ha (2 lb/A) was about 50ppm on the game animals has been 0.021 mg/kg of 2,L(,5-T foliage, with much less present on the forest in the liver of one deer.The low exposure floor('36 mg/rn2) or in the soil(< 0.01 ppm). to and rapid excretion of herbicides bygame The herbicides rapidly disappear due animals probably prevents contamination of to a variety of natural processes, suchas wild meat to any significant extent. volatilization,runoff, leaching,degradation,weathering,absorption, growth dilu- The limited exposure of the general population, metabolism, excretion, and adsorption tion to phenoxy herbicides8 is further borne (Norris 1981). Thisdissipation,coupled out by preliminary results of the National withthetypicallyreducedpalatabilityof Human Monitoring Program, a cooperative the treated vegetation asit dies, precludes effort betweenthe EPAand theNational significant chronic exposure of roving ani- CenterforHealthStatisticsofthe U.S. mals to harmful amounts of phenoxy herbicides Public Health Service.Only trace amounts (< (Norris1977). Additionalinformation on 3.2 ppb) of phenoxy herbicides have been herbicideresiduesinwater,vegetation, detected in a fraction (< 0.2 percent) of the forest floor, and soil can be found in recent human urine samples collected thus far from reviews byShearer and Halter(1980), the general population (Kutz1978,Kutz et Ghassemi et al.(1981,1982), Norris (1981) al.1978). and otherpertinentarticlescitedinthe bibliography. 8The only noteworthy exception to thisstatement is a study done by Dougherty and Piotrowska (1976).A limited survey The review by Norris (1981) also summarizes of human urines and seminal fluids in Florida suggestedcon- the cases where a search was made for phenoxy tamination at the parts per billion levelwith 2,4,5-T and other chiorophenoxy compounds. However, the authors used herbicides in the bodies of wildlife suchas unconfirmed methodology and statedthat theiranalytical mussels, fish, birds, and other mammals.In procedures could not distinguish between various isomers of the scattered instances of positive results, the chiorophenoxy compounds.In fact, some of the organic polychioride chemicals detected in the study (and for which the amounts have generally ranged from <0.01 the molecular structure was given) have never been marketed. to 10 mg/kg (ppm of sample weight). As indi- False positives due to interferences from othersubstances cated are also possible atlow levels of detection, particularly in the section of this report dealing when using unproven methodology. with toxicity studies, consumption of these amounts by carnivorous animals would be well

15 below the chronic or subchronic (NOEL) toxi- tangible impacts have been limited to changes citylevels established forlaboratory ani- inhabitat--anunavoidableresultofany mals. silvicultural treatment (chemical as well as non-chemical) which favors one form of vege- Toxic effects on wildlife populations tation over others. Such effects can be followingherbicideapplication inforest beneficial to certain species of wildlife and management have not been scientifically docu- detrimental to others.The effects can also mented, thoughtherehavebeen a few beofrelativelyshort orlongduration, unpublished cases, such as rabbits allegedly dependingon the situation. Additional affected by a routine application of dinoseb information on thistopic can be foundin (Newton and Dost 1981) and several snowshoe Carter et al.(1976), Newton (1975), Newton hares thought to have been poisoned by MSMA and Norris (1976), Newton and Dost (1981), (Norris 19714). Other than such cases, any and Newton and Knight (1981).

TCDD (DIOXIN)

Much of the concern about herbicide use has 2,4,5-T is 2 kilograms of acid equivalent per arisen from a hiily toxic chemical called hectare( 2lb ae/A). If there were 0.01 TCDD (2, 3,7,8-tetrachlorodibenzo-2-dioxin)-- parts TCDD per million parts 2,4,5-T,9 then often simply called dioxin--thatisa con-no more than 0.02 x106 kg TCDD/ha (20 taminant onlyin 2,4,5-1 and silvex;itis TAg/ha) would be applied.Studies involving not in 2,4-D.Because the contamination is much hier concentrations of TCDD detected soslight,itisnot possibletoobtaina no measurable toxicological impact (Young et dose of TCDD that constitutes a risk to human al.1978). oranimalhealthfromconventionalagri- cultural and forestry applications of 2,L&,5-T Based on water monitoring studies showing a or silvex (Kenaga and Norris 1983).In fact, maximum concentration of 0.1 ppm 2,4,5-1, the the TCDD applied in such treatments probably TCDD concentrationinstreamsfollowing representslessrisk than the 2,4,5-T or forestry application would not exceed 0.001 silvex accompanyingit(Newton and Norris pptifa similar pattern of distributionis 1981);for example, compare the valuesin assumed (see Appendix 3). This would be well Table 2 withthe corresponding valuesin below known levels of biological significance Table 3.This conclusion is supported by the to aquatic orterrestrial organisms. For preponderance of scientific opinion on the example, Miller et al.(1973) determined that subject (Turner 1977, Council for a TCDD concentration in water of from 0.054 Agricultural Science and Technology 1978, to 0.54 ppt did not affect the survival of Ramel 1978, Bovey and Young 1980). However, young cohosalmontestedfor a 96-hour because of the controversy surrounding this period.The dose-response relationship was highly toxic substance, and because it beha- affected by both the size of the fish and the ves differently in the environment than its duration of the test. Data for other fish parent herbicides, TCDD warrantsspecial species and several aquatic invertebrate spe- attention (McConnell et al.1978a,b; Schwetz ciesliving in TCDD-contaminated water are et al. 1973). alsoavailable(Milleretal. 1973,Norris and Miller1974,l-Iawkesand Norris1977, One of the difficulties in studying TCDD is Norris 1981, Kenaga and Norris 1983).As a detecting it. Because itis so toxic, even generalrule, TCDD haslowsolubilityin parts pertrillionlevelsinenvironmental water (maximum of 200 ppt) and an affinity samples are cause for concern.Only a hand- forbindingtosoilparticles,silt, and ful of laboratories in the world are equipped other substrates; therefore, its mobility and with the analytical capability to detect such presence in water is so restricted (Council minute amounts of TCDD. Even with this capa- for Agricultural Science and Technology 1978) bility, however, one would still not expect that actual concentrations in water would be to detect TCDD from a conventional forestry even less than calculated. application of 2,4,5-T. The amounts would simply be too small to measure. For example, 9The actual concentrations detected in present production of the conventional forestry application rate of 2,L4,5-T and silvex are routinely less than 0.005 ppm.

16 An accidental explosion at an ICMESA chemical dirtfloor of ahorsearenaineastern plant on July10,1976 resulted in the con- Missouri. A soil sample taken from the arena tamination of about 18,000 ha of a densely andanalyzed bythefederalCentersfor populated area near Seveso, Italy (Pocchiari Disease Control indicated a TCDD level of etal. 1983). Concentrationsashighas 33,000 ppb (Sun 1983). Before the problem 212g TCDD/ha were found in the soil in Zone was diagnosed and the source of TCDD deter- A-North near the plant (Reggiani 1977).This mined,45horses died from the toxic effects is over ten million times the concentration of TCDD, and two children who played in the that might resultfrom a conventional area suffered a varietyofdisorders forestryapplicationof2,4,5-T. Itwas includingchloracne(Carteretal. 1975). estimated thatin the immediate vicinity of The children reportedly recovered (Beale et the plant an average TCDD level of 30 mg/ha at. 1977),buttheepisode was tragic, (Zone B) and 500 mg/ha (Zone A) was deposited nevertheless. Some of the levels recorded on the ground. Thisis1,500-25,000times from oiled roads at Times Beach, Missouri the amount that might result from a conven- have ranged from 100 to 900 ppb (Anonymous tional forestry application. Despite these 1982b). Bycomparison, a conventional relatively high concentrations of TCDD near forestry application of 2,4,5-T would deposit the plant,detailed medical examinations of less than 0.02 mg TCDD/ha. Assuming this was the exposed human population did not reveal all deposited and contained within the top any serious short-term adverse health effects 1.0cm of baresoilhavinga density of beyond temporary reactions such as chloracne, 1.0 g/cm3, then the concentration of TCDD the most definitive human symptom of exposure would belessthan0.2ppt. Thus,the to TCDD.Several studies indicate the possi- amounts found at Times Beach are from 500,000 bility of long-term effects on kidney func- to 4.5 million times greater. tion, bloodlipids, and the peripheral nervous system, but the relationship to TCDD Itis encouraging to note from the incidents exposure isstill ambiguous (Bruzzi 1983b). at Seveso and Missouri that no irreversible These potential effects notwithstanding, human health problems have occurred despite there has been no discernible increase in the relativelymassivelevelsofexposureto frequency of spontaneous abortions, cytogene- TCDD. Similar findings to those of Seveso tic normalities, clinical diseases, or mor- and Missouri have been reported for several tality(DeCarlietal. 1977,Tuchmann- otherindustrialaccidentsinvolving TCDD Duplessis 1977, Reggiani 1978, 1980, (Coulston and Pocchiari 1983, Dunagin 1983). Homberger et at.1979, Bruzzi 1983b). Exposure to TCDD resulting from forestry No clear pattern has yet emerged with respect applications of 2,L4,5-T or silvex would not tothepossibilityofbirthdefectsasso- be expected to have any adverse effects what- ciatedwiththeSeveso accident. Initial soever, since the amounts of TCDD applied and reportsindicatedno apparent increasein potentially internalized would beinfinitesi- major types of birth deformities (De Car Ii et mal in comparison.Furthermore, TCDD as a al.1977, Tuchmann-Duplessis 1977, Reggiani contaminant of 2,4,5-T degrades rapidly after 1978 and 1980, Homberger et al.1979).More application unless it is somehow incorporated recent analyses suggest an increase in cer- in the soil and protected from photochemical tain types of defects, but a decrease or no degradation (Crosby and Wong 1977, Norris changein others (Bruzzi 1983a). Further 1980a). studies are needed before definitive conclusions can be drawn.Meanwhile, it is obvious Generally, TCDD has not been detectedin that TCDD is not a strong teratogenic agent, environmental samples taken from withinor or there would have been a more consistent near 2,4,5-T-treated areas. Using various trend in the number and type of birth defects methods and equipment with minimum limits of observed (Tuchmann-Duplessis 1983). detection ranging from 1to 17 ppt, TCDD has not been found in deer or mountain beaver The inappropriate use or disposal of waste (Newton and Snyder 1978), fish, water, mud, petrochemical by-products contaminated with or human milk (Shadoff et al.1977, Norris high levels of TCDD has led to some unfor- 1980b, U.S. EPA 1980a), bovine milk (Mahie tunate situationsin Missouri,Illinois, New etal.1977),or beef fat(Kocheretal. York, and elsewhere.One notorious incident 1978). It has also not been found in eagles occurred in 1971 and involved the application (Wootson et al.1973) or waterfowl (Garcia of TCDD-contaminated waste oil sludge to the and Rhodes 1979); the limits of detection in

17 these avian studies were considerably higher TCDD has also been detected in fish, par- (1 to 50 ppb). ticularlycarp,collectedfromMichigan's Saginaw Bay and nearby rivers. Amounts have Failuretofind TCDDinthesekindsof ranged from 17 to 588 ppt, with most samples samples is not surprising in view of several inthe 100to 200pptrange(Anonymous factors: 1983b). The discharge of industrial wastes from plants manufacturing organic chemicals 1. The minute amounts of TCDD in 2,4,5-T. is the most likely source of this TCDD contamination. The U.S. Food and Drug 2. The rapid photochemical dechlorination Administration has recommended a tolerance and/orvolatilizationof TCDD,which level of 50 ppt in fish destined for human givesit a half-life of 2 to 12 hours in consumption (Anonymous 1983c). sunlight (Crosby and Wong 1977, Norris l980c). Many studies concerning TCDD in environmental samples are inexplicable, strongly disputed, 3. The tight bonding of TCDD to soil par- or remain unconfirmed by the scientific com- ticles and other inert substances, which munity. This is not a surprising situation, makes itrelativelyimmobileinthe given the trace amounts of TCDD being looked environment and, therefore, unlikely to for andthecomplexanalyticalchemistry leach through soils into ground water or involved. For example, Baughman and Meselson to be taken up by plants to any great (1973a,b) reported finding concentrations up extent (Helling et al.1973). to 800 pptin Vietnamese fish collectedin 1970 after extensive use of Agent Orange in There have been a few cases where TCDD has South Vietnam. However, the level of TCDD in been detected following 2,4,5-T applications, samples gathered in 1973 appeared to be lower but these have usually been the result of by an order of magnitude or more (Baughman exceptional circumstances.For example, the 1976). One explanationfortheapparent EPA analyzedbeeffatfromleancattle declinein TCDD residuesisthe fact that grazing on pasturesrecently treatedwith spraying of Agent Orangein Vietnam was 2,4,5-T (U.S. EPA 1977).Three of the 85 largelydiscontinued in 1970; butother samples of fat were definitely positive for possible explanations include differences in TCDD (20 to 60 ppt); five additional samples sampling procedures between the two dates and were suggestive of TCDD contamination, but the questionable accuracy of the analytical were below the reliable level of detection (5 technique, which was highly experimental at to10 ppt); the remainder had no detectable that point in time. TCDD. Liveristhe preferential organ of TCDD deposition, but, curiously, none of the In a similarcase,Meselson and O'Keefe 43 liver samples contained any TCDD at the (1977)claimedto have preliminary indica- levelof detection. As another example, tions of TCDD (10 to 40 ppt on a fat content Young et al.(1976,1978) detected TCDD at basis)in samples of human milk collected in concentrations ranging from less than 10 up Oregon and Texas.The Oregon Committee on to1,500 pptin the livers of some animals Synthetic Chemicals in the Environment collected live from a strip of land at Eglin strongly questioned the validity of the fin- Air Force Base that was used to calibrate the dings, since the analytical procedure did not spraying of Agent Orange (a 50:50 mixture of use EPA confirmed methodology (Hiatt 1977). 2,4-D and 2,4,5-1 n-butyl esters) by aircraft Furthermore, there are substantial questions destined for Vietnam. The study area had about the sample collection methodology used, received massive applications(1,120 kg/ha) the proximity of the reported values to the of 2,4,5-T that contained TCDD in excess of limitsof detection, and the unconventional 1 ppm. Analysisofthesoilwithinthe standards used for data evaluationinthis treated area indicated TCDD levels from less study (U.S. Department of Agriculture 1978). than 10 to 1,500 ppt 10 years after applica- Even if the results are accurate, Meselson et tion. When compared to the maximum con- al. (1978) concede that, "This possible asso- centration of TCDD (<0.2 ppt) that might be ciation(of TCDD residues) with the use of expectedinbaresoilfollowing a conven- 2,L4,5-Tdoesnotinvolve a large enough tionalapplication of 2,4,5-1 (2kg/ha),it number of samples to be statistically isevidentthatthe Eglin Air Force Base significant." A more thoroughfollow-up experience haslittle,ifany,relationto study by the EPA failed to detect any TCDD in forestry uses of 2,4,5-1. milksamplescollectedfrom 105 nursing

18 mothers in California, Oregon, and Washington Michigan and not fromAlsea, Oregon (U.S. EPA 1980a). The detection limitin (Anonymous 1983d). this study was 1 to 4 ppt. A teamofscientistswith Dow Chemical The EPA believed it detected trace amounts of Company has reported that chlorinated dioxins TCDD from a small percentage of forest animal (including TCDD) are natural products of com- samples (birds and mice) collected from the bustion and can originate from such sources Siuslaw National Forest in 1973-74. as refuse incinerators, fossil-fueled Unfortunately, theanalytical methodology powerhouses,gasolineand diesel powered used in this study was not precise enough at automobiles and trucks, fireplaces, charcoal the time to verify the presence of TCDD in grills,and cigarettes (Dow Communications 1978, Bumb et al. the samples collected (Norris 1981). 1980). However, a study Furthermore,the two laboratories that did by Kimble and Gross (1980) failed to detect follow-up confirmatory analyses had results any TCDD in the fly ash of a coal-fired power that varied widely; thus, there could not be plant, and efforts to resolve such discrepan- a consistent quantification of the amounts of cies over power plant sources of dioxin have TCDD which the EPA thought were present not beensuccessful(Crummett1980). A (Costle 1977). review by scientists in the Netherlands indicated that several types of polychiorinated dibenzo-Q-dioxins (such as TCDD) and diben- These examplesillustrate the difficulty of zofurans are produced by municipal incinera- obtaining definitive results when looking for tors (Lustenhouwer et al.1980). Previous such minute amounts of TCDD.Yet another work by Dow scientists had found that minute problem hassimply been the potentialfor amounts of TCDD (<1 ppt of TCDD per ppm of human error associated with processing the 2,4,5-T)were producedwhenvegetation large number of samples collected for TCDD recently treatedwith2,L4,5-Twas burned analysis over the years.In a recent court (Stehiand Lamparski1977). Norris and case an assertion was made that TCDD had been Pierovich(1978)have concludedthatthe detected at high concentrations in sediments "probabilityofsignificantproductionof collected by the EPA near Alsea, Oregon. The TCDD in the field from burning (vegetation amounts were uncharacteristically high,in treated with 2,4,5-T), however, is fact not achievable by any imaginable vanishingly small." forestry use or misuse, but a great deal of Additionalinformation on the environmental news coverage was nonetheless generated. The behavior and fate of TCDD can be found in the discrepancyturnedouttobecaused by reviews by Helling etal.(1973),National including,for purposes of laboratory effi- Research Councilof Canada(1978,1981), ciency, a few sludge samples from a manufac- Espositoetal.(1980),Newton and Dost turingsiteinMichiganalongwiththe (1981), Norris (1981), Coulston and Pocchiari "Oregon batch" when the samples were ana- (1983), and other pertinent articles lyzed. The laboratory report did not fully designated in the bibliography. Compilations identify the origin of each sample within the of laboratory,clinical,and epidemiological entirebatch,therebycreatingthefalse studies concerning TCDD are also available impression that some of the Oregon samples (World Health Organization 1978, Esposito et were contaminated with high levels of TCDD. al. 1980,Kimbrough1980,JRB Associates Afollow-upcheckonthesamplecodes 1981, Reggiani1981, Wagner 1981, Coulston revealed that all of the highly contaminated and Pocchiari 1983, Dunagin 1983, and other samples were from the manufacturing site in designated articles in the bibliography).

SCIENTIFIC REVIEWS

The popular press, news media, and other non- bicides, has prompted numerous reviews of the scientific literature have carried reports of subjectoverthepastdecadeormore. illhealth allegedto bea consequence of Recognized authorities in the fields of her- herbicide use (see, for example, Nader et al. bicide toxicology, medicine, physiology, and 1981).Thus, public concern over the safety ecology have investigated a wide assortment of herbicides, particularly the phenoxy her- of hypothetical and alleged adverse effects

19 to health and the environment.Although the esters) in Vietnam.Their report was issued specific findingsin each of these reviews in 1974 and stated: are not identical,the basic conclusion has been consistent:herbicides are safe when used as directed in forestry and agriculture. The National Academy of Sciences committee The following conclusory judgments, excerpted could find no conclusive evidence of asso- from these reviews, represent a consensus of ciation between exposure to herbicides and the expertise that is available on the sub- birth defects in humans (National Academy ject. of Sciences 1974).

In 1969thePresident'sScience Advisory Committee commissioned aselect Panel on The issue of exposure to pesticides Herbicides to conduct an in-depth review of (including herbicides)andimplicationsfor 2,4,5-T. Their report was issued in 1971 and human health also surfaced in British concluded: Columbiaintheearly1970's. ARoyal Commission ofInquiryintotheUseof Pesticides and Herbicides was appointed to A review of the environmental effects of lookintothematter. Theirreport was 2,4,5-T on non-target organisms reveals few issued in May, 1975 and containedthe harmful consequences of its recommended following statements concerning the evidence uses (P resident's Science Advisory regarding herbicides: Committee 1971). Phenoxy herbicides have been used on roads, rights-of-way, weed control programmes and In 1971 a review by the Advisory Committee on in agriculture. They have been used in 2,4,5-T to the Administrator of the EPA con- very low doses as a stop drop on apples. cerningallegedeffects on humanhealth The Commission could not find evidence of caused by 2,4,5-T concluded: human injury from these materials (Royal Commission ofInquiryintotheUse of Pesticides and Herbicides 1975). Current patterns of usage of 2,4,5-1 and its known fate in various compartments of the environment,including the plant and In 1975 the Council for Agricultural Science animal foods of man,are such that any and Technology commissioned a team of federal accumulation that might constitute a hazard and university experts to review the phenoxy to any aspect of human healthishighly herbicides.A report was issued in 1975 and unlikely. updatedin1978. The most recent edition stated: No evidence has been found of adverse effectson human reproductioninthree The phenoxy herbicides are predominantly separate locations, namely Vietnam; Globe, toxicto green plants and are much less Arizona; and Sweden, where pregnant women toxictomammals, birds,fish,reptiles, have allegedly been exposed to high levels shellfish,insects, worms, fungi and bac- of 2,4,5-T. teria. When properly used, they do not occur in soils and water at levels harmful On the basis of these observations,itis to animals and microorganisms. They do not concluded that, as presently produced and concentrate in food chains and do not per- as appliedaccordingtoregulationsin sist from year to year in croplands.They force prior to April 1970, 2,4,5-T repre- are detectable only rarely in food and then sentsnohazardtohumanreproduction only in insignificant amounts. (U.S. EPA 1971). A highly poisonous kind of dioxin called TCDD is an unavoidable contaminant in com- In the early 1970's Congress commissioned the mercialsuppliesof2,4,5-1andsilvex. National Academy of Sciencestoform an The amount present in currently produced international team toinvestigate claims of formulations of 2,4,5-1 and silvex is not birthdefects andotheradverseeffects enough to alter the toxicological proper- resulting from the use of Agent Orange (a ties of these preparations or to endanger 50:50 mixture of 2,4-D and 2,4,5-1 n-butyl human health or to affect plants or animals

20 in the environment (Council for insects, and soil living organisms. Agricultural Science and Technology 1978). Populations of particularinsects orsoil organisms may sometimes be temporarily reducedbutrecoveryisusuallyrapid In 1977 the Royal Swedish Academy of Sciences (Turner 1977). issuedits conclusions and recommendations concerning the health and environmental risks In 1977 the "Phenoxy Herbicide Investigation associatedwith phenoxy herbicides. The Team" was formed under the auspices of the principal findings were: California Department of Food and Agriculture to investigatea variety of adverse health Thereisnoevidencethatdioxinsare effects attributed to the use of phenoxy her- formed from phenoxy acid herbicides in the bicides in the North Coast regionof environment. California. Their report,issuedin1978, states the following: There is no evidence of bioaccumulation of phenoxy acids. Bioaccumulation of TCDD At the public hearings,allegations were resulting from normal use of 2,4,5-Tis made concerning grossreadilyapparent insignificant. effectsoftheherbicides, and these alleged gross effects were the target of a If the levels of TCDD in phenoxy acid her- subsequentinvestigation by the Phenoxy bicides remainbelow 0. 1 ppm, con- HerbicideInvestigation Team. None of siderations of health risks associated with these effects, such as human illness, ani- these products should be based primarily on mal deaths or deformities, plant damage, or the potential toxicity of the phenoxy acids environmental damage, could be attributed se and not on that of its contaminants to or associated with spraying of phenoxy (Royal Swedish Academy of Sciences 1977). herbicides. Similarly,nosubstantiation could be provided for any correlation bet- Dr. D. J. Turner of the British Agricultural ween geographical locations of residents in Research Council Weed Research Organization relationshiptothespraysiteandthe conducted an extensive literature review of etiology of disease.Examination of pesti- 2,4-D and 2,4,5-T.His report, published in cide illness reports from California physi- a 1977 BulletinoftheBritishForestry cians by this Department have not revealed Commission, summarizes the information as any significant health hazards that can be follows: attributedtothe phenoxy herbicidesas The properties, manufacture and uses of used today in California (California 2,4-D and 2,4,5-T are described and the Department of Food and Agriculture 1978). possible side effects of these herbicides are reviewed in detail.While concentrated The New Zealand Department of Health spon- preparations are moderately poisonous, the sored an investigationofbirthdefects diluted solutions which are used for most allegedtobeassociatedwith2,L4,5-Tin weed controltreatmentspresentlittle three separate areas in New Zealand. The direct hazard to humans and animals. In report was issued in 1977 and concluded: practice, foodstuffs and water supplies are unlikely to become contaminated.However, Inshort,the data permit the conclusion if contamination should occur, serious con- thatthereisnoevidencetoimplicate sequences are unlikely.Itis pointed out 2,4,5-T as a causal factorin human birth that (1) very large amounts of spray solu- defects.The accumulated data on 2,4,5-T tion or contaminated material are needed to and its TCDD contaminant are sufficient to produce toxic effects,(2)the compounds give a high assurance of safety in the nor- are usually rejected by animals, because of mal use of this material.This beliefis their unpleasanttaste and smell, (3) in accordance with the consensus of world- neither herbicideisa cumulative poison, wide scientific opinion (New Zealand and (4) 2,4-D and 2,4,5-T break down com- Department of Health 1977). parativelyrapidly in plantor animal tissues,soil and natural water. At the concentrations which will be encountered in The investigation ofasimilarset of cir- forests or on farmland, the herbicides have cumstancesin Australia during 1978 by the virtually no effect on most birds,fish, ConsultativeCouncilonCongenital Abnor-

21 malities for the Minister of Health produced thought to exceed certain toxicological cri- the following conclusions: teria established by the EPA.In the case of 2,4,5-1 and its contaminant TCDD, these cri- The cluster of babies with birth defects teria were carcinogenicity (causing cancer) born in Yarram in 1975-76 was not such as andteratogenicity(causing birth defects) to suggest that a specific local cause was (U.S. EPA1978b). Nevertheless,at that operative. pointintimethe Agency "does not think current use of the chemical poses an imminent Analysis of all information available oremergencythreattopeopleorthe showed no evidence that these birth defects environment" (U.S. EPA 1978a). User groups, werecaused byexposureto24-D or environmental groups, manufacturers, public 2,4,5-1. The normal agricultural use of agencies, universities, and individuals 2,4-D and 2,4,5-1 has not been shown to responded to the RPAR on 2,4,5-1. cause birth abnormalities in domestic animals nor is there evidence to connect such In December 1978 the EPA contracted with use with human birth abnormalities Texas Tech Universitytosynthesizethe (Australian Minister of Health 1978). information contained in some 3,000 documents received by the Agency as part of the RPAR An assessment of the toxicologic risk of phe- process.The report contained the following noxy herbicides as used in forest management summary abstract: was conducted by one of the authors of this reportwhileaffiliatedwiththeEnviron- It seems clear that 2,4,5-1 is effective as mental Health Sciences Center of Oregon State aselective herbicide,whichisof con- University (Dost 1978).The findings were siderable economic value to those who use presented in a report for the USDA Forest it. Italso seems clearthat the major Service (California-Pacific Region). Some of concern iswith contamination by dioxins, the principal conclusions reached were: the principal impurity being 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD).This The present knowledge of dioxin effects and dioxinisunquestionably extremely toxic, behaviorisnotsufficienttomake an butthedataconcerningseveral RPAR unqualified statement of reasonable safety. triggers,i.e.,oncogenicity,teratogeni- Several areas of needed research, suggested city,and mutagenicity do not appearto in a later segment of this report, should present a clear picture. Its presence in improve our level of confidence. 2,4,5-T,in our opinions, should be con- Nonetheless,itis my opinion that 2,4,5-1 sidered as a potential hazard even when the containing less than 0.02 ppm TCDD can be level is extremely low.However, the pre- usedsafelyinreforestationifcertain cise level at which TCDD presents a threat protectivepractices listed later are is not easily defined. It may well be in instituted. In brief, these involve abso- therange of 0.05 ppm. In general,it lute avoidance of spray intrusion across seems that 2,4,5-T can be used safely pro- property lines,identification and protec- vided that thelevel of dioxin impurities tion of dwellings and water supplies, re- issubjecttogood qualitycontrol,and entry discipline and adequate public that persons likely to receive the greatest information programs (Dost 1978). exposure,i.e.,applicators,take appro- nate safety precautions.It would appear Despite these numerous reviews of the risk that there are many gapsin our know- associated with 2,4,5-T, the public concern ledge about 2,4,5-1 so that more exten- over the use ofthis herbicide continued. sive studies, especially on trigger The controversy continued to emerge in public suspects, are warranted (Nau and Associates 1979). hearings, news mediastories,scientific meetings, courtrooms, and other forums. On February 28,1979 the EPA announced an emergency suspension of the use of 2,4,5-1 In April 1978, the EPA instituted yet another and silvex for forestry, rights-of-way and review of 2,4,5-I(and silvex) by filing a pasture uses (U.S. EPA 1979e). "Rebuttable Presumption Against Registration" Paradoxically,applicationstoricecrops, (RPAR). The RPAR process was intended tobe sugarcane, and rangelands were allowed to ascientific analysis of both the risks and continue.The primary basis for the suspen- benefits of particular pesticides which are sion was an alleged correlation between the

22 use of 2,4,5-1 and a series of miscarriages exposed as a result of such use are many near Alsea, Oregon (U.S. EPA 1979c).This times less than those which could produce findinghasbeencarefullyreviewedand any ill effects.On much the same grounds, thoroughly refuted by numerous expertsin the Committee is satisfied that there would epidemiology,clinicalmedicine,toxicology, be no risk to domestic animals. statisticsandotherpertinentspecialties (Agresti 1979, Australian National Health and The Advisory Committee has evaluated the Medical Research Council 1979a, Blau et al. above evidence on the acute and chronic 1979, Byerly and Tschirley 1979, Cook 1980, toxicity of TCDD:whilst accepting that it Coulston and Olajos1980, Lamm 1979,1980, is certainly one of the most toxic chemi- Mantel 1979, New Zealand Department of Health cals known, the Committee sees no reason to 1979,Smith1979,United Kingdom Advisory varyitsjudgment,first reached in1970 Committee on Pesticides 1980, Wagner et al. and subsequently re-examined, that the use 1979, Woods 1979). ofbrushkillerscontaining2,4,5-1con- taminated with TCDD can continue without Nevertheless, the EPA elected to proceed with risk, subject to the observance of a maxi- thecancellationprocesson2,4,5-1 and mum allowable level of TCDD in the trich- silvex (U.S. EPA l979a,b). This decision was lorophenol used forits manufacture(0. 1 made despite the recommendations of the EPA's ppm) (United Kingdom Advisory Committee on Scientific Advisory Panel which stated: Pesticides 1979).

After extensive review of the data we find InOctoberof1980,Environmental Health no evidence of an immediate or substantial Associates submitted a report to the National hazard to human health or to the environ- Forest Products Association summarizing the ment associated with the use of 2,4,5-1 or recent scientific literature.They found: Silvex on rice, rangeland, orchards, sugar cane, and the noncrop uses specified in the In summary, there is not complete agreement decision documents (U.S. EPA 1979d). among all scientists regarding the possible risks presented by approved applications of Unfortunately, the EPA's emergency suspension 2,4,5-1. However,results of available of 2,4,5-1 and silvex was widely interpreted fieldstudies,practicalworst-case sce- by the news media as "proof" that these herb- narios, and conclusions from several scien- icides caused miscarriages in Oregon. A New tificreview groups(includingthe EPA York Times article as recent as January 23, FIFRA SAP) appear to strongly support the 1983typifiesthemisconceptionsthatare notion that there is a substantial and suf- frequently conveyed by news articles on this ficient margin of safety to the community subject: associatedwithapprovedapplicationof 2,4,5-1 containing no more than 0.05 ppm The Environmental Protection Agency used TCDD (EPA FIFRA SAP 1979) or even 0. 1 ppm emergency powers in 1979 to ban virtually TCDD (McQueen etal.1977; Ramel1977) alluse of 2,4,5-1inthe United States (Milby et al.1980). after discovering a higher than normal rate ofspontaneousabortionsinanOregon The Australian government has continued its regionthat had been sprayed(emphasis scrutiny of both 2,4-D and 2,4,5-1. The added) (Biddle 1983). Queensland Cabinet commissioned aninter- departmental committee in November 1980 to InMarch1979the Advisory Committee on review, once again, the safety of these her- Pesticides for the United Kingdom conducted a bicides.Their report, issued in 1981, con- review of the safety of 2,4,5-1. The conclu- tained the following summary statement: sions of this committee were consistent with the aforementioned reviews: This Committee has extensively examined the medicalandscientificinformationabout On the basis of the available data on acute 2,4-D, 2,4,5-T and human health, and has and chronic toxicity of pure 2,4,5-1, the found that no evidence exists to suggest Advisory Committee concludes that, when that the continuation of present approved used as directed, brushkillers containing use of 2,4-D and 2,4,5-1 willin any way the chemical offer no hazard to users or to harm the health and well-being ofany mem- the general public, because the amounts of bersofthegeneralpublic(Queensland 2,4,5-Ttowhichindividualsmight be Cabinet 1981).

23 The State Pollution Control Commission of New tion,rainfall,dilution,biodegradation, South Wales (Australia) has, likewise, and other means. The phenoxies are essen- reassessed the safety of 2,4-D and 2,4,5-1. tially nontoxic to soil organisms at normal Anabstractoftheirreport, issuedin field rates and the soil microbial popula- November 1981, typifies the confident judg- tion is responsible for their rapid break- ment, tempered by recommendations for addi- down. tional precautions, that are frequently found in such reviews of herbicide safety: When used according tolabeled instructions, human health hazards associated with Itisconcluded thatifthese herbicides the worldwide use of phenoxy herbicides areusedinaccordancewithspecified have been insignificant (in our search of recommendations, theriskofadverse thousands of scientific articles on these environmentalimpactisslight,provided herbicides [spanning a period of 30 years], TCDD concentrations in 2,4,5-T products do we found less than two dozen documented not exceed thelegallimit of 0.1 mg/kg. medicalreportsofhumanintoxication). However, the high toxicity of TCDD,its Poisoninginman has occurred by self- propensity to bioaccumulate and the possi- ingestion or when grossly misused, but such bilityofenvironmental hazardsinpar- occurrences have been rare (Bovey and Young ticular situations are suggested as reasons 1980). for the adoption of a number of control measures, such as the elimination or reduc- In March 1981 the American Council on Science tion of TCDD concentrationsin2,4,5-T, andHealthcompletedanotherindependent closer monitoring of 2,4,5-1 productsin reviewofthe2,4,5-1issue.Theirfinal New South Wales and the replacement of positionstatement containedthefollowing 2,4,5-1 by other herbicides for selected conclusion: uses (NewSouthWalesStatePollution Control Commission 1981). Based on its review of the scientific evidence, the American Council on Science and In December 1980 theUnitedKingdom's Health(ACSH) concludesthatthereis Advisory Committee on Pesticides again insufficient evidence to support a ban on reviewed the safety of 2,4,5-T, including the 2,L4,5-T. No scientific reports presented evidence from the Alsea II study by the EPA, to date have shown any convincing rela- and came to the following conclusion: tionship betweenthetraditionaluseof 2,4,5-T and adversehealtheffectsin What we have had to consider in this Review humans (Hayes 1981). is whether there is any sound medical or scientific evidence that humans or other In October 1981 the AmericanMedical living creatures, or our environment, wouldAssociation published yet another independent come to any harm if cleared 2,4,5-1 her- studyofthe2,4,5-1issue. Among the bicides continue to be used in this countryconclusions reached in their study is that: for the recommended purposes and in the recommended way. We have found none While 2,4,5-1and 2,4-0 pesticides have (UnitedKingdom Advisory Committee on been used in agriculture, forest management, and commercial and residential Pesticides 1980). landscaping for over 30 years,thereis still no conclusiveevidencethatthey The authors of a text book on the subject of and/or TCDD are mutagenic, carcinogenic or phenoxy herbicides evaluated the environmen- teratogenicinman,northatthey have taland human health implications of using causedreproductivedifficultiesinthe phenoxy herbicides as follows: human (American Medical Association 1981). Extensive research indicated the phenoxies Despite allof these reassuring reviews of are rapidly degraded in the environment and product safety, efforts to resolve there- donotaccumulateinthefoodchain. registration questions have not succeeded to Market basket surveys indicated the phe- date. The EPA administrative cancellation noxies occur very infrequentlyin human hearings were suspendedin March 1981in food and in very small amounts. Phenoxy hopes that a negotiated settlement could be herbicides are lost from soil, plant, and reached between Dow Chemical USA (the pri- water sources by volatility, photodegrada- mary registrant at the time of products con-

24 taming 2,4,5-T and silvex) and the EPA. The detailed recommendations concerning par- attempt to reach a satisfactory compromise ticularlythe maximum permittedlevelof spanned almost three years and cost Dow in TCDD in2,4,5-T (0.005ppm) andthe excessof$10 millionbeforeitcollapsed avoidance of 2,4,5-1 residues in (Dow Communications 1983).On October 14, foodstuffs (Commission to the Council of 1983 Dow withdrew from the EPA hearings and the European Economic Community 1982). voluntarilycancelledallofitsregistra- tions of 2,4,5-T and silvex.In papers filed Although the registration status of 2,4,5-1 announcingitsdecisiontowithdraw, Dow isin a state of flux at the present time in stated: the U.S.anda few other countries, most countries still permit its use.For example, 2,4,5-T and silvex are safe, effective her- the herbicide is currently authorized for use bicidesthatneitherposenorthreaten in Australia, Belgium, Canada (on a unreasonable adverse effects on the provincial basis), Finland, France, Germany, environment andare therefore properly Ireland,Luxembourg,New Zealand,South registered underthe FIFRA. Scientific Africa, Spain, the United Kingdom, and most panels, regulatory authorities and judicial Latin American countries.The registration decision makers in thiscountry and of 2,4,5-1 has been withdrawn in Columbia, throughout the world, including EPA's own Denmark, Italy, Norway, the Netherlands and ScientificAdvisoryPanel inreviewing Sweden. The E.C.C. communique cited earlier partsofthisproceeding,have reached containsthefollowingpositionstatement similar conclusions (Anonymous 1983a). with respect to 2,4,5-1 registration: Dow had been the primary defender of 2,4,5-1 The Commission accepts the broad conclu- and silvex during the cancellation hearings. sionsoftheopinionoftheScientific After Dow's withdrawal, the EPA encouraged Committee for Pesticides and concludes that theremaining participantsinthelitigation onthe basis of existingscientificevi- to also withdraw (U.S. EPA 1983). No deci- dence a Community-wide prohibition of the sion by the parties involved had been made at marketing and use of 2,4,5-T herbicides this writing, and the hearings were stillin ..would not be justified (Commission abeyance. to the Council of the European Economic Community 1982). At the same time,the EPA announcedits intenttocancel allremainingusesof The focus of attention has shifted recently 2,4,5-1 and silvex (rice, sugarcane, range, from 2,4,5-1 to 2,4-D and picloram (an active orchards, and miscellaneous non-crop sites) ingredientinTordon products). Inan (U.S. EPA 1983). However, other registrants assessment of 2,L4-D safety conducted by the of2,4,5-1andsilvexhaverequested a Minnesota Department of Health in 1978, the hearing over this matter, so the registration situation was summarized as follows: status of these products islikely to remain in limbo for some time. A review of the literature of the toxicology of 2,4-D, the data from the 1977 moni- 2,4,5-1 continues to be scrutinized on the toringprogramsoftheChippewa and international level as well.For example, in Superior National Forests, and the calcula- May 1980 the Council of the European Economic tion of the estimated 2,4-D exposure to a Community directeditsscientific committee "maximally exposed individual," support the for pesticides to "review all available evi- conclusion that,although certain adverse dencetoestablish ascientific basisfor healtheffectsarenotlikelytooccur, possible community action" concerning there is significant doubt about some areas 2,4,5-T.The investigation by this committee of the toxicology of 2,4-D which precludes was completed in July 1981 and summarized in an absolute assumption of safety relating a communique as follows: to its use in forestry management (Minnesota Department of Health 1978). In summary, the Committee was satisfied that the marketing and proper agricultural The effects listed by the Minnesota use of 2,4,5-1 is not dangerous for humanDepartment of Health asunlikely to occur oranimalhealthorprejudicialtothe are: (1) acute toxicity,(2) chronic health environment.It made, however, a number of effects and (3) teratogenesis.The areas in

25 which an understanding of 2,4-D toxicology isunderway, theagencyhas takenthe was listed as deficient were:(1) mutageni- following position based on its review of the city,(2)carcinogenicity,(3)contaminants available information on the potential health and metabolites, (4) environmental and effects of 2,4-D. wildlife monitoring, and (5) acceptable daily intake levels. (a)The presently available information on the potential adverse health effects A review of 2,4-D conducted by the Department of 2,4-D does not support a regulatory of Health Services and Departmentof action to remove 2,4-D products from Industrial Relations as part of California's the market; Hazard Alert System made several recommendations: (b)Information from scientifically valid studiesdoesnotindicatethatthe 1. Current work practices are inadequate to continued use of 2,4-D poses an immi- protect against potential neurotoxicity. nent hazard or unreasonable adverse They should be reviewed and corrected. effect when used according tolabel precautions and directions for use. 2. The scientificdataaresufficiently suggestive of a carcinogenic effect, and (U.S. EPA 1980b) demonstrate a weak teratogenic effect, that 2,4-D use should be restricted to Despite these reassurances, pressure has con- areas in which human exposure can be tinued to build against 2,4-D. In the fall kept to the minimum.Contamination of of 1980 the Canadian government announced open water must be monitored and pre- that it had found dioxins in product samples vented.Broadcast methods of applica- of 2,4-D(U.S. EPA1981). Although the tionthatcoulddirectlyexposethe dioxins found were of limited toxicity, and general population should be strongly none of the highly toxic 2,3,7,8-tetrachloro discouraged. Greater consideration must dioxin (TCDD) wasfound,thesefindings begiventoalternativemethodsfor nevertheless prompted the Canadian government removing unwanted plants. to ban the sale by basic manufacturers of all such products shown to contain dioxins at or 3. Productscontaining2,4-Dshould be above 1 ppb. labeled to warn users of the herbicide's potential for causing neurotoxicity and The EPA quickly responded to this development howtoprotectagainstit. Present and analyzed several 2,4-D products from U.S. labels are inadequate. Educational manufacturing facilities.It issued a report information shouldbe providedfor in January 1981 which stated: anyone who works with the substance. EPAiscoordinatingitsreview activities 4. Home gardeners using products containing on 2,4-D with Agriculture Canada, but the 2,4-D should exercise care to avoid skin Agency says that there is no justification exposure to themselves or others. forregulatory actionto change current uses of 2,4-D in the United States because 5. Adequate tests in rodents should be con- products tested here were either dioxin- ducted following National Cancer freeorcontained extremelylowlevels Institute protocol to determine the car- (less than 100 ppb)... Based on the preli- cinogenicity of 2,4-D. Studies should minary analyses that the Agency has con- also be conducted to measure the 2,4-D ducted using available data,the concen- excretion in urine and peripheral nerve trations foundin U.S. manufacturing-use function in exposed workers. products do not appear to pose a health hazard (U.S. EPA 1981). (California Department of Health Services! Department of Industrial Relations 1980) The EPAiscontinuingtoinvestigatethe safety of2..14-D. On August 29, 1980it In response to these and other concerns, the required allregistrants of 2,4-D to supply EPA hasrequestedadditionaltoxicological dataconcerningchronichealtheffects. data in support of continued registration of These data are anticipated within one to four products containing 2,L4-D.While this effort years,dependingonthetypeofstudy

26 involved.The EPA has also recently deter- products.The article claims to link the use minedthattheproblemofdioxincon- of picloramwith a "siege"of cancerin tamination"appears to resultfromthe Cherokee County, N.C.In response to this manufacturing processes principally used in and similar press articles on picloram, the Canada rather than the United States" (U.S. EPA reviewed the data base and then issued EPA 1982b). Therefore, no change in the the following statement: registration status of 2,4-D was called for, and the agency concluded: In sum, the data on short term effects, environmental effects and genetic mutation, EPA's recent evaluations of 2,4-D do not as well as one NCI (NationalCancer indicate its currently registered uses pose Institute) cancer study, support the unreasonable risks to public health or the currentregistrationofpicloram. The environment. As with any pesticide chemi- registrant is conducting a new rat feeding cal,if evidence of such risks does arise, study to clarify the ambiguous results of the Agency will take appropriate action to (a) second NCI study.... We have no reduce or eliminate those risks (U.S. EPA current evidence that picloramis posing 1982b). risks of unreasonable adverse effects to human health or the environment, although The current position maintaining the more data is needed on long term effects to registrationof2,'4-Dissupported by a support this conclusion (U.S. EPA 1982a). recent comprehensive review of 2,4-D by a formerpesticidespecialistwiththe Dow Chemical Company: The statements cited in the previous reviews reflect the cautious effort of most scien- Considering the short-lived persistence of tists and regulatoryofficials toavoid 2,4-D in the environment; its rapid excre- making categorical pronouncements about her- tion unmetabolized in mammals and man; its bicide safety which mightlater be proven moderate acute oral toxicity;and thatit false by new information, or which might not is not present except occasionally in tra- apply to circumstances different than those ces in our environment,itis evident that evaluated (such as misuse of herbicides). As the approved uses of 2,4-D are not hazar- discussedearlier inthisreport,itis dous to people or the environment (Mullison impossible tostatewith absolute certainty 1981). that the use of such materials is safe under allforeseeableconditions,no matter how strongthedata base. Therefore,itis The March 15, 1982 issue of Inquiry Magazine appropriate to rely on the prudent judgments carried an article titled,"Agent White: it of qualified experts to establish thelikeli- kills weeds, bushes, trees--and maybe hood of adverse effects as a result of her- people.11 Agent White is an herbicide mixture bicideuse. Suitableactioncan then be used in Vietnam which contains picloram, an taken to avoid undesirable consequences where active ingredient also of Tordon® and Amdon® they are likely to occur. L!GATION

The issue of herbicide use in forestry has tiatingmajoractionsthat may affectthe been addressed inlitigation aswellasin environment. Theinterpretationofwhat scientific and regulatory reviews. Inthe constitutes a major federal action and the U.S.the cases to date have been strictlycorrect procedureforanalyzingsuchan confined to the argument of whether or not actionin environmental impact assessments federalagencieshavecompliedwiththe has been a source of much legal confusion and requirementssetforth intheNational ambiguity. Consequently, there have been Environmental Policy Act (NEPA) of 1969. The numerous temporary restraining orders and issue of herbicide risk 2L5 has not been injunctions against the use of herbicides by debated directly in these cases. federal agencies, pending the preparation of adequate environmental impact statements. NEPA requires all federal agencies to prepare environmental impact statements prior tomi-

27 A recent trialin Nova Scotia,Canada did . For this reason I feltitincumbent directlyaddresstheissueofherbicide upon me toset forth this detail of fact safety.This marked the first time that the and my own observations so as to make clear healthrisks of herbicide useinforestry thatallthe evidence available has been were debated and weighedina courtroom presented by the parties, and that, based situation. At issue were the risks asso- on this evidence, fully weighed and con- ciatedwithproposed usesof2,4-Dand sidered, this court is of the opinion that 2,4,5-T by Nova Scotia Forest Industries, these spraying operations can be carried Ltd. After hearing more than a month of outinsafetyandwithoutrisktothe expert testimony, Justice 0. Merlin Nunn of healthofthecitizensofthisprovince NovaScotia'sSupremeCourtissuedthe (Nunn, 1983). following opinion:

I am satisfiedthattheoverwhelming currentlyacceptedviewofresponsible scientistsisthat thereislittle evidence The status of herbicide product registrations that, for humans, either 2,L4-D or 2,L4,5-T and regulations are constantly changing due is mutagenic or carcinogenic and that TCDD to legal and regulatory actions.Prospective is not an effective carcinogen, and users of herbicide products are advised to further,that there are no-effect levels periodically check on local,state, provin- and safe levels for humans and wildlife for cial,and federal regulations governing the each of these substances. application of these materials.

CONCLUSION

Without exception, the amounts of herbicides Nevertheless,confidencebythegeneral detectedinthe environment have been far publicinthesafe use of herbicides has belowtheknownlevelsoftoxicological often been shaken. Thisispartially the significanceto humans,fish,wildlife, and resultofincompleteorinaccuratenews livestock. As a consequence,itisnot coverage of related events.Sensationalized surprising that there have been no substan- reporting has frequently left the public with tiated cases ofdirect,adversehealth a distorted view of the actual risks of her- effectsto humans oranimalswhen these bicide use.Such a discrepancy between per- materials have been used properly in agri- ceived and actualrisksassociatedwith culture and forestry. Similar analyses of herbicides extends to pesticides in general. the risk associated with TCDD in present pro- For example, a recent survey of college stu- duction of 2,4,5-Tand silvex revealthat dents (Upton 1982) indicated that they ranked this substanceis distributedin such small pesticides as thefourthmost hazardous amounts thatit,too, does not constitute an sourceofrisk among 30 alternatives. appreciable risk to human health.Even when Actuarial statistics, however, placed pesti- TCDD existed at much higher concentrations in cides in 28th position among the 30 choices. 2,4,5-T and silvex, no adverse effects attri- butable to this impurity have been confirmed Some ofthe publications presenting other consequent to proper applications. pointsof view and additionalissues con- cernedwithherbicides,and pesticidesin This bulletin has been based on the most general, are listed in Appendix 7.They are authoritative reviews of which we are aware not all pertinent to forestry, nor are they that evaluate the risks of using herbicides. necessarilyaccurate and comprehensive. These evaluations have been remarkably con- Regardless, these references do raise some sistent in their determination that importantquestions andprovidevaluable registered herbicides are safeto humans, insight into the complex technical and socio- wildlife, and livestock when used as economic aspects of pesticide use. Itis directed. Thisfindingisreassuringin hoped that our report will provide a solid lightof the importantrolethatthese foundationforevaluatingtheinformation materials play in sustaining the productivity presentedinthese alternative accounts of of agriculture and forestry. the herbicide issue.

28 BIBLIOGRAPHY

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37 * NATIONAL ACADEMY OF SCIENCES. * NEW ZEALAND DEPARTMENT OF 19714. The effects of herbicidesin HEALTH. 1979. An evaluation of the South Vietnam.Part A.Summary and tip reliminary report of assessment of a conclusions.Committee on the effects field investigation of six-year spon- of herbicides in Vietnam.Washington, taneous abortion rates in three Oregon D.C. areasinrelationto forest 2,L4,5-T spray practices."Division of Public NATIONAL FOREST PRODUCTS ASSOC- Health report. Wellington, New IATION. 1981. Forest Chemicals Zealand. Workbook. 3rd edition. Washington, D.C. NEWTON, M.1975. Constructive use of herbicides in forest management. NATIONAL RESEARCH COUNCIL. 1977. Journal of Forestry 73:329-336. Drinking water and health. Safe Drinking Water Committee. National + NEWTON, M., and F.N. DOST. 1981. Academy of Sciences, Washington, D.C. Environmentaleffectsofvegetation management practices on DNR forest + NATIONAL RESEARCH COUNCIL OF lands. State of Washington, CANADA. 19714.Picloram: The effects DepartmentofNaturalResources, of its use as a herbicide on environ- Olympia, Washington. mental quality. NRCC 136814. Associate committee on scientific cri- + NEWTON, M., and F.B. KNIGHT.1981. teria for environmental quality. Handbook of weed and insect control Ottawa, Canada. chemicals for forest resource managers. Timber Press, Beaverton, *NATIONAL RESEARCH COUNCIL OF Oregon. CANADA. 1978.Phenoxy herbicides their effects on environmental + NEWTON, M., andi.A. NORGREN. 1977. quality,with accompanying scientific Silvicultural chemicals and protection criteria for 2,3,7,8-tetrachloro- of water quality.U.S. EPA Report, dibenzo-Q-dioxin (TCDD). NRCC 16075. 910/ 9-77-036.Washington, D.C. Ottawa, Canada.

+ NEWTON, M., and L.A. NORRIS.1968. NATIONAL RESEARCH COUNCIL OF Herbicide residuesinblacktail deer CANADA. 1981. Polychlorinated from forests treated with 2,4,5-T and dibenzo-2-dioxins:criteria for their atrazine. Proceedings of the Western effects on man and his environment. Society of Weed Science 1968:32-34. NRCC 18574. Ottawa, Canada. + + NAU, C.A.,and Associates. 1979. NEWTON, M., and L.A. NORRIS.1976. Review summaries on 2,4,5-T/TCDD. Evaluating short- and long-term Report submittedtothe U.S.EPA. effects of herbicides on non-target School of Medicine, Texas Tech forest and range biota. Down to Earth University, Lubbock, Texas. 32(3) :18-26.

NEAL, R.A., et al.1982.The toxico- + NEWTON, M., and L.A. NORRIS. 1981. kinetics of 2,3,7,8-tetrachloro- Potential exposure of humans to dibenzo-2-dioxin in mammalian systems. 2,14,5-T and TCDD in the Oregon Coast Drug Metabolism Review 13:355-385. Range. Fundamental and Applied Toxicology 1:339-3146. *NEW SOUTH WALES STATE POLLUTION CONTROL COMMISSION. 1981. Envi- NEWTON, M., and S.P. SNYDER. 1978. ronmental impact of the chlorophenoxy Exposureofforestherbivoresto herbicides 2,4,5-T and 2,4-D. 2,3,7,8 tetrachlorodibenzo dioxin (TCDD)in areas sprayed with.2 * NEW ZEALAND DEPARTMENT OF 2,LI,5-T. Bulletin of Environmental HEALTH. 1977. 2,4,5-T and human Contamination and Toxicology 20:7143- birth defects. 750. + NORRIS, L.A. 1967. Chemical brush office report.USDA Forest Service. control and herbicide residues in the Pacific Northwest Forest and Range forest environment.Pages 103-123 in Experiment Station, Corvallis, Oregon. Herbicides and vegetation management (Also presented in direct testimony, in forests, ranges and noncrop lands. FIFRA docket Nos. 415 et al.The Dow Symposium Proceedings, Oregon State Chemical Company et al. vs. U.S. EPA, University, Corvallis. Washington, D.C.)

+ NORRIS, L.A. 1970. Degradation of + NORRIS, L.A. 1981. The movement, herbicides in the forest floor.Pages persistence, and fate of the phenoxy 397-411inTree growth andforest herbicides and TCDD inthe forest. soils.Edited by C.T. Youngberg and Residue Reviews 80:66-135. C.B. Davey. Oregon State University, Corvallis. NORRIS, L.A., and R.A. MILLER. 19714. The toxicityof2,3,7,8-tetrachloro- NORRIS, L.A.1971a. The behavior of dibenzo-2-dioxin(TCDD)inguppies chemicals in the forest.Pages 90-106 (Poecilia reticulatus Peters).Bulle- in Pesticides, pest control and safety tinofEnvironmentalContamination on forest range lands.Proceedings, and Toxicology 12(1):76-80. short course for pesticideapplicators. Oregon StateUniversity, NORRIS, L.A., M.L. MONTGOMERY, and Corvallis. E.R. JOHNSON. 1977. The persistence of2,4,5-1in a PacificNorthwest + NORRIS, L.A. 1971b.Chemical brush forest.Weed Science 25:417-422. control: assessing the hazard. Journal of Forestry 69:715-720. + NORRIS, L.A., andD.G. MOORE. 1970. The entry and fate of forest chemicals NORRIS, L.A.1974. The behavior and in streams. Pages 138-158 in Forest fate of organic arsenical herbicides landusesandstreamenvironment. intheforest: finalreporton Symposium Proceedings, Oregon State cooperativestudies. USDA Forest University, Corvallis. Service. Pacific Northwest Forest and Range Experiment Station, Corvallis, NORRIS, L.A.,andJ. PIEROVICH. 1978. Oregon. Thermal conversion of 2,4,5-1 toTCDD: analysis ofthe problem,exhibit6. + NORRIS, L.A. 1977. The behavior of InVegetation management with her- 2,4,5-T and TCDD in the environment. bicides. Final environmental state- Society of American Foresters, ment. USDA Forest Service, Pacific Proceedings: 252-255. Northwest Region, Portland, Oregon.

NORRIS, L.A.1980a.Herbicide resi- NUNN, D.M. 1983.Decision concern- dues in air, Alsea Basin 1977.USDA ing proposed use of 2,4-D and 2,4,5-1 Forest Service. Pacific Northwest by Nova Scotia Forest Industries, Ltd. Forest and Range Experiment Station, Trial Division, Supreme Court of Nova Corvallis, Oregon. Scotia, Canada.S. SN. No. 02555. NORRIS, L.A. 1980b. TCDD in fish from Oregon forest streams. OTT, M.G., B.B. HOLDER, and R.D. Unpublishedofficereport. USDA OLSON. 1980. A mortality analysis of Forest Service. Pacific Northwest employees engaged in the manufacture Forest and Range Experiment Station, of 2,4,5-Trichlorophenoxyacetic acid. Corvallis, Oregon.(Also presented in Journal of Occupational Medicine direct testimony, FIFRA docket Nos. 22:47-50. 415 et al.The Dow Chemical Company etal.vs.U.S.EPA,Washington, + PALMER, J.S. 1972. Toxicity of 45 D.C.) organic herbicidestocattle,sheep andchickens. USDA, Agricultural NORRIS, L.A. 1980c. TCDD persistence Research Service, Production Research in low light intensities.Unpublished Report 137.Washington, D.C.

39 PALMER, J.S., D.E. CLARK, and L.M. Natural Science Research Council, NFR, HUNT. 1964.Toxicological effects of Stockholm, Sweden. silvex on yearling cattle.Journal of the American Veterinary Medical RAMSEY, J.C., T.L. LAVY, and W.H. Association 144:750-755. BRAUN. 1979. Exposure of forest workers to 2,4,5-T:calculated dose PALMER, J.S., and R.D. RADELEFF. levels.Report submitted to the U.S. 1964. The toxicologic effects of cer- EPA as a supplemental response to the tainfungicides and herbicides on "Noticeofrebuttablepresumption sheep and cattle.Annals of the New against registration and continued York Academy of Science 111:729-736. registrationofpesticideproducts containing2,4,5-T." Dow Chemical + PALMER, J.S., and R.D. RADELEFF. USA, Midland, Michigan. 1969. The toxicity of some organic herbicides to cattle, sheep and RAMSEY, J.C.,etal. 1980. Dose chickens. USDA, Agricultural Research levels of 2,4-Din forest workers. Service, Production Research Report Determination of 2,LL-D exposure 106. Washington, D.C. receivedbyforestryapplicators. Project Completion Report to National PAYNTER, O.E., et al. 1960. Forest Products Association, Washing- Toxicology of dalapon sodium ton, D.C. (2, 2-dichloropropionicacid, sodium REGGIANI, G.1977.Medical problems salt). Journalof Agricultural and raised by the TCDD contamination in Food Chemistry 8:47-51. Seveso, Italy.5th international conference on occupational health in the PETERS, J.W., and R.M. COOK.1973. chemicalindustry(Medichem), San Effects of atrazine on reproduction in Francisco, California. rats. BulletinofEnvironmental Contamination and Toxicology.9:301- REGGIANI, G.1978. The estimation of 304. the TCDD toxic potential in the light of the Seveso accident.20th congress PIONKE, H.B., andG. CHESTERS. 1973. of the European Society for Pesticide sediment water interac- Toxicology, West Berlin, Germany. tions. JournalofEnvironmental Quality 2:29-45. REGGIANI, G. 1980. Acute human exposure to TCDD inSeveso, Italy. POCCHIARI, F., etal.1983. Environ- Journalof Toxicology and Environ- mental impact of the accidental release of tetrachlorodihenzo-p-dioxin mental Health 6:27-43. (TCDD) at Seveso (Italy).Pages 5-35 + REGGIANI, G. 1981. Toxicology of inAccidentalexposuretodioxins. 2,3,7,8 tetrachlorodibenzo Human health aspects. Edited by F. dioxin (TCDD): Short review of its Coulston and F. Pocchiari.Academic formation, occurrence, toxicology, and Press, New York. kinetics, discussing human health effects, safety measures, and dispo- PRESIDENT'S SCIENCE ADVISORY COMMITTEE. 1971. Reporton2,4,5-T. sal. Regulatory Toxicology and Pharm- Panel on Herbicides. U.S. Government acology 1:211-243. Printing Office, Washington, D.C. RIIHIMAKI, V., et al. 1978. Symp- tomatology,morbidityandmortality QUEENSLAND CABINET. 1981.Report experience of chlorinated phenoxy acid on 2,Ls-D and 2,4,5-T.Land Adminis- herbicide (2,4-D and 2,4,5-T) sprayers tration Commission, Queensland, inFinland: a clinicalandepide- Australia. miological study. Institute of Occu- pational Health, Helsinki, Finland. + RAMEL, C.(ed.) 1978. Chlorinated phenoxyacids and theirdioxins. RIIHIMAKI,V., S. ASP, and S. Ecology Bulletin/NFR 27:302.Swedish HERNBERG. 1982. Mortalityof

40 2, 4-dichlorophenoxyacetic acid and American Foresters, Proceedings: 2,4,5-trichlorophenoxyacetic acid her- 2 56-260. bicideapplicatorsinFinland. 3rd international symposium on chlorinated + SCHWETZ, B.A., et al. 1973. Toxi- dioxins and related compounds, cology of chlorinated dibenzo-2- Salzburg, Austria. (Abstract 54) dioxins. Environmental Health Per- spectives Experimental Issue 5:87-99. ROAN, C.C.1980. An investigation of NationalInstituteofEnvironmental thepossibleeffectsofpesticide HealthSciences,Research Triangle exposures on reproductive mortality Park, North Carolina. and morbidity.Part 1. Preliminary report:Comparisons between popula- SELL, C.R., J.C. MAITLEN, and W.A. tions of agricultural pilots and their ALLER. 1982. Perspiration as an siblingswho are not occupationally importantphysiologicalpathwayfor exposed to pesticides. Report sub- the elimination of 2,LI-dichloro- mittedtotheNationalAgricultural phenoxyaceticacidfromthe human Aviation Association.Hopes Consult- body. Paper delivered at the American ing, Inc., Aberdeen, Maryland. Chemical Society meeting, Las Vegas, Nevada. ROLL, R. 1971.Untersuchungen uber die teratogene.Wirkung von 2,4,5-T SHADOFF, L.A., R.A. HUMMEL, andL. bleMausen. FoodandCosmetics LAMPARSKI. 1977. A search for 2,3,7,8- Toxicology 9:671-676. tetrachlorodibenzo-2.-dioxin (TCDD) in an environment exposed annuallyto ROSE, J.Q., et al. 1976.The fate of 2,4, 5-trichlorophenoxy-acetic acid 2,3,7,8 tetrachlorodibenzo ester (2,L4,5-T) herbicides.Bulletin dioxin following single and repeated ofEnvironmentalContaminationand oral doses to the rat.Toxicology and Toxicology 18(4) :478-485. Applied Pharmacology 36:209-226. + SHEARER, R., and M. HALTER. 1980. + ROWE, V.K., and T.A. HUMAS. 1954. Literature reviews of four selected Summary of toxicological information herbicides: 2, 4-D, dichlobenil, diquat on 2,4-D and 2,4,5-T type herbicides and endothall.Water Quality Planning and an evaluation of the hazards to Division, Municipality of Metropolitan livestock associated withtheir use. Seattle, Washington. American Journal of Veterinary Research 15:622-629. SHEPARD, B.M.1982. A review of on- going epidemiologic researchinthe ROYAL COMMISSION OF INQUIRY INTO UnitedStateson the phenoxy her- THE USE OF PESTICIDES AND HERBI- bicidesand chlorinated dioxin con- CIDES. 1975. Final report to the taminants. 3rd international Commissioners. Vol.I.Province of symposium on chlorinated dioxins and British Columbia, Canada. related compounds, Salzburg, Austria. (Abstract 49) *ROYAL SWEDISH ACADEMY OFSCI- ENCES. 1977. Chlorinated phenoxy SINGER, J. 1980. Pesticide safety: acidsandtheirdioxins. Mode of guidelines for personnel protection. action, health risks, and environmen- USDA Forest Service, Methods tal effects. Conclusions and recom- Application Group, Davis, California. mendations.Stockholm, Sweden. SMITH, A.H. 1979.Seasonal analysis SAUERHOFF, M.W., et aI. 1977. Fate of Oregon data on spontaneous or- of silvex following oraladministra- tionsand 2,4,5-Tspraying. Paper tion to humans.Journal of Toxicology presented at ANZERCH, Annual and Environmental Health 3:941-952. Conference, Dunedin, New Zealand.

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SMITH, F.A., et aI. 1978. Three- + TURNER, D.J.1977. The safety of the generation reproductive study in rats herbicides 2,4-D and 2,4,5-T.British ingesting 2,4,5-trichiorophenoxyacetic Forestry Commission Bulletin 57. acidinthediet. Toxicology and Applied Pharmacology 45:293. + UNITED KINGDOM ADVISORY COMMIT- TEE ON PESTICIDES.1979. Review of SPARSCHU, G.L, et al. 1971. Study the safety for use in the U.K. of the oftheeffectsofhighlevelsof herbicide 2,4,5-T. Ministryof 2,4,5-trichlorophenoxyaceticacidon Agriculture, Fisheries and Food, fetal development in therat. Food London, England. and Cosmetics Toxicology 9:527-530. STEHL, R.H., and L.L. LAMPARSKI. *UNITED KINGDOM ADVISORY COMMIT 1977. Combustion of several 2,4,5- TEE ON PESTICIDES. 1980. Further trichlorophenoxy compounds: formation review of the safety for use in the of 2,3,7,8 tetrachlorodibenzo - U.K. of the herbicide 2,4,5-T. dioxin.Science 197: 1008-1009. Ministry of Agriculture, Fisheries and Food, London, England. STEVENS, K.M. 1981. Agent Orange toxicity:a quantitative perspective. *UNITED NATIONS, FOOD AND AGRI- Human Toxicology 1:31-39. CULTURE ORGANIZATION. 1980. 2,4,5-T Monograph. Dataandrecommen- STRE ISINGER, G.1978. Assessment of dations of thejoint meeting of the hazards posed by TCDD. Pages 101-103 F.A.O. panel of experts on pesticide in Symposium on the use of herbicides residues in food and the environment in forestry. Sponsored by the USDA and the W.H.O. expert group on pesti- and U.S.EPA.Arlington, Virginia. cideresidues. Document PB398. Department ofPrimary Industry, SUN, M. 1983. Missouri'scostly Canberra, Australia. dioxin lesson.Science 219:367-369. SUSKIND, R.R.1982. Long-term health UPTON, A.C. 1982. The biological effects of exposure to 2,4,5-T and/or effects of low-level ionizing itscontaminants. 3rdinternational radiation. Scientific American 246 symposium on chlorinated dioxins and (2) :41-49. related compounds, Salzburg, Austria. (Abstract 52) U.S. DEPARTMENT OF AGRICULTURE. 1978. Vegetationmanagementwith THOMAS, H.F. 1980.2,4,5-T use and herbicides.Final environmental sta- congenital malformation rates in tement. USDA Forest Service, Pacific Hungary.Lancet 2:214-215. Northwest Region, Portland, Oregon.

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45 APPEN DICES

APPENDIX 1

PROCEDURES FORCALCULATING HYPOTHETICAL AMOUNTSOF VARIOUS SUBSTANCES CONTAINING HERBICIDES THAT COULD BEINGESTED WITHOUT EXCEEDING CERTAIN TOXICOLOGICAL POINTS OF REFERENCE

A simple formula can be used to determine the hypothetical amounts of various substances, ranging from commercial herbicide concentrates to contaminated animal meat, that could be ingested without exceeding certain toxicological points of reference, such as the acute oral LD50 (lethal dose of a chemical which induces 50% mortality in a test population within a short period of time following ingestion) and the chronic or subchronic oral NOEL (the highest dose which causes no observable effect in test animals following long term intake of a chemical, or intake during a critical stage of development).Oral intake is used in this analysis, since chemicals are usually more potent via this route of exposure than by dermal absorption.The formula and an explanation of its components are given below, followed by a series of example situations.

Formula

X WxT C where:

X hypothetical amount that can be ingested without exceeding the LD50 (single dose) or NOEL (daily dose); W = body weight of animal involved; T = toxicological points of reference [e.g., LD50 or NOEL] expressed in milligrams of chemical per kilogram of body weight (i.e., mg/kg); C = concentration of herbicide active ingredient (ai)in the substance internalized.

Depending upon the substance internalized, the general parameters in the thove formula have the following specific dimensions:

Substance X W T C LD50 or NOEL 1. Commercial herbicide product a.liquid formulations mL product kg mg/kgmg/kg/daymg ai/mL product (e.g., emulsifiable concentrate, soluble concentrate, flowable powder concentrate) b. dry formulations (e.g., g product kg mg/kgmg/kg/daymg aug product wettable powders, soluble powders, granulars)

46 2.Aqueous spray mixture mL spray kg mg/kgmg/kg/daymg ai/mL spray 3. Environmental samples

a. stream water L water kg mg/kgmg/kg/dayppm (mg ai/L)

b. ambient air m3air kg mg/kgmg/kg/day mgai/m3 air

c. animal meat kg meat kg mg/kg mg/kg/dayppm (mg al/kg)

SITUATION 1 COMMERCIAL HERBICIDE PRODUCT LIQUID FORMULATION

Given:An emulsifiable concentrate of a commercial herbicide product containing45% al (i.e., 1450 mg ai/mL product); The herbicide has an acute oral LD50 of 500 mg/kg anda chronic or subchronic oral NOEL of 10 mg/kg/day;

A person weighing132lb(60kg).

Question 1:How much of the above product contains the equivalent of the LD50?

Solution: x 60kgx 500 mg/kg 1450 mg ai/mL product

X = 66.7mL product 4.5 thsp product

Question2: How much of the above product can be ingested daily without exceeding the NOEL?

Solution: x 60kg x 10 mq/kq/day 450 mg ai/mL product

X = 1.33mL product/day

0.27tsp product/day

(Note--With the application of a 100-fold safety factor, theamount would be0.0133mL product/day, or0.2drops/day.)

47 SITUATION 2 - COMMERCIAL HERBICIDE PRODUCT DRY FORMULATION

Given:A wettable powder formulation of a commercial herbicide product containing 80% ai (i.e., 800 mg aug product); The herbicide has an acute oral LD50 of 500 mg/kg and a chronic or subchronic oral NOEL of 10 mg/kg/day; A person weighing 132 lb (60 kg). Question 1:How much of the above product contains the equivalent of the LD50? Solution: x 60 kgx 500 mg/kg 800 mg aug product

X = 37.5 g product 1.3 oz product

Question 2:How much of the ove product can be ingested daily without exceeding the NOEL? Solution: x 60 kg x 10 mg/kg/day 800 mg ai/g product

X = 0.75 g product/day

(Note--With the application of a 100-fold safety factor, the amount would be 0.0075 g product/day.)

SITUATION 3 AQUEOUS SPRAY MIXTURE

Given:An aqueous spray mixture of an herbicide containing 2 lb ai/10 gal spray (2L1 mg ai/mL spray); The herbicide has an acute oral LD50 of 500 mg/kg and a chronic or subchronic oral NOEL of 10 mg/kg/day; A person weighing 132 lb (60 kg). Question 1:How much of the above spray mixture contains the equivalent of the LD50?

48 Solution: x 60 kgx 500 mg/kg 24 mg ai/mL spray mixture

X 1,250 mL spray mixture 1.3 qt spray mixture

Question 2:How much of the thove spray mixture can be ingested daily without exceeding the NOEL? Solution: x 60 kg x 10 mg/kg/day 24 mg ai/mL spray mixture

X = 25 mL spray mixture/day 1.7 tbsp spray mixture/day

(Note--With the application of a 100-fold safety factor, the amount would be 0.25 mL spray mixture/day, or 4 drops spray mixture/day.)

SITUATION 4 - STREAM WATER CONTAINING HERBICIDE

Given:A stream containing 0.1 ppm of herbicide (i.e., 0.1 mg ai/L stream water). (Note - This amount represents an actual "worst case" situation.See Appendix 2 for details); The herbicide has an acute oral LD50 of 500 mg/kg and a chronic or subchronic oral NOEL of 10 mg/kg/day; A person weighing 132 lb (60 kg). QuestIon 1:How much stream water contains the equivalent of the LD50? Solution: x 60 kgx 500 mg/kg 0. 1 mg ai/L stream water

X = 300,000 L stream water 79,200 gal stream water

Question 2:How much of the stream water can be ingested daily without exceeding the NOEL?

49 Solution: x= 60 kg x 10 mg/kg/day 0. 1 mg ai/L stream water

X = 6,000 L stream water/day 1,5814 gal stream water/day

(Note--With the application of a 100-fold safety factor, the amount would be 60 L stream water/day, or 15.8 gal stream water/day.)

SITUATION 5 AMBIENT AIR CONTAINING HERBICIDE

Given:Ambient air near a sprayed area containing 1.0ug ai/m3 (0.001 mg aiim3) of an herbicide. (Note This amount represents an "upper limit" as estimated by Newton and Norris 1981); The herbicide has an acute oral LD50 of 500 mg/kg anda chronic or subchronic oral NOEL of 10 mg/kg/day; A person weighing 132 lb (60 kg). Question 1:How much air contains the equivalent of the LD50? Solution: x 60 kgx 500 mg/kg 0.001 mg ai/m3

X = 30 x i06 m3 air 39.3 x 1Oyd3 air

Question 2:How much air can be inhaled daily without exceeding the NOEL? Solution: x 60 kg x 10 mg/kg/day 0.001 mg ai/m3

X = 600,000 m3 air/day 786,000 yd3 air/day

(Note--With the application of a 100-fold safety factor, the amount wouldbe 6,000 m3/day, or 7,860 yd3/day.)

50 SITUATION 6 -ANIMAL MEAT CONTAINING HERBICIDE

Given:Animal meat containing 0.1 ppm (i.e., 0.1 mg ailkg meat) of herbicide (Note This amount exceeds the maximum concentration reported by Newton and Norris 1981); The herbicide has an acute oral LD50 of 500 mg/kg and a chronic or subchronic oral NOEL of 10 mg/kg/day; A person weighing 132 lb (60 kg). Question 1:How much meat contains the equivalent of the LD50 level? Solution: x 60 kgx 500 mg/kg 0.1 mg ai/kg meat

X = 300,000 kg meat 661,380 lb meat

Question 2:How much meat can be ingested daily without exceeding the NOEL? Solution: x 60 kg x 10 mg/kg/day 0.1 mg ai/kg meat

X = 6,000 kg meat/day 13,228 lb meat/day

(Note--With the application of a 100-fold safety factor, the amount would be 60 kg meat/day, or 132 lb meat/day.)

APPENDIX 2

HERBICIDE CONCENTRATIONS IN STREAM WATER

I. HYPOTHETICAL MAXIMUM CONCENTRATION a. Assumptions: Application rate of 2 kg herbicide/ha (= 2 lb/A) Direct application to a shallow stream 10 cm (= 4 in.) deep, with complete mixing of the chemical throughout that depth. (Note Current forest practice rules in Oregon and many other states are designed to prevent the direct application of herbicides to waterways and areas of open water by requiring buffer strips and other precautions.)

51 b. Maximum concentration that would be expected under the conditions described above: 2 kg/ha = 2 kg/10,000 m2 = 2 kg/b4 m2 = 2 kg/b8 cm2 x 10 cm depth = 2 kg/b9 cm3 = 2 kg/b9 g = 2 kg/b6 kg = 2 ppm

2. ACTUAL DETERMINATIONS FROM WATER MONITORING

a. Concentrations of phenoxy herbicides such as 2,4,5-T greater than 0.01 ppm are seldom encountered in streams following conventional application in forest management (Norris 1977,1981). Historically, concentrations as high as 0.1 ppm have been detected, but these occurred before the advent of strict regulations governing application procedures. Most water samples collected nowadays do not contain detectable (>1 ppb) amounts. Any minute amounts which are present rapidly dissipate due to dilution, adsorption, and breakdown. b. Recommended maximum concentrations of certain herbicides permitted in streams of various size and use can be found in an EPA publication (Table 3, Newton and Norgren 1977), or in a recent handbook (Table 5-14, Newton and Knight 1981).For example, the drinking water standards for 2,14-D established by the U.S. Public Health Service allow a lifetime consumption of water containing up to 100 ppb of 2,4-D. In general, the amounts of herbicide actually detected in forest streams have been well below recommended concentration maxima for drinking and irrigation purposes.

APPENDIX 3

PROCEDURES FORCALCULATING HYPOTHETICAL AMOUNTSOF VARIOUS SUBSTANCES CONTAINING TCDD THAT COULD BE INGESTED WITHOUT EXCEEDING CERTAIN TOXICOLOGICAL POINTS OF REFERENCE

As in Appendix 1,a simple formula can be used to determine the hypothetical amounts of various substances containing TCDD (as a result of 2,4.5-T use) thatcould be ingested without exceeding certain toxicological points of reference.The formula isidenticalto that presented in Appendix 1, except that the dimensions formany of the parameters are different, due to the minute quantities of TCDD involved.

52 The specific dimensions for each of these parameters are given below:

Substance X W T C LD50 or NOEL

1. Commercial formulation mL product kg pg/kg pg/kg/day pg TCDD/mL product of 2,L4,5-T (e.g., liquid emulsifiable concentrate, water-soluble amine concentrate) 2. Aqueous spray mixture L spray kg pg/kg pg/kg/daypg TCDD/L spray made from 2,4,5-T 3. Environmental samples a. stream water L water kg pg/kg pg/kg/daypg TCDD/L water

b. ambient air m3 air kg pg/kg pg/kg/day pg TCDD/m3 air

c. animal meat kg meat kg pg/kg pg/kg/day pg TCDD/kg meat

SITUATION 1 COMMERCIAL HERBICIDE PRODUCT CONTAINING TCDD

Given: An emulsifiable concentrate of 2,4,5-T herbicide (e.g., Esteron245) containing 45% acid equivalent (ae) of 2,4,5-T (0.45 g 2,4,5-TImL product) which in turn contains 0.01 ppm TCDD (i.e., 0.0045 pg TCDD/mL product); TCDD has an acute oral LD50 of 0.6 pg/kg and a chronic or subchronic oral NOEL of 0.001 pg/kg/day; A person weighing 132 lb (60 kg).

Question 1:How much of the above product contains the equivalent of the LD50 for TCDD?

Solution: x 60 kgx 0.6pg/kg 0.0045 pg TCDD/mL product

X = 8,000 ni. product 2.1 gal product

53 Question 2:How much of the above product can be ingested daily without exceeding the NOEL for TCDD? Solution: x 60 kg x 0.001 pg/kg/day 0.0045 ig TCDD/mL product

X = 13.3 ITt. product/day 2.7 tsp product/day

(Note--With the application of a 100-fold safety factor, the amount would be 0.133 mL product/day, or 2.1 drops product/day.)

SITUATION 2 AQUEOUS SPRAY MIXTURE CONTAINING TCDD

Given: A commercial product of 2,4,5-T herbicide containing 0.01ppm TCDD which is diluted with water to form a spray mixture containing 2 lbae 2,4,5-TI10 gal spray mixture (24 g ae 2,4,5-T/L spray mixture), and which therefore contains 0.24 itg TCDD/L spray mixture; TCDD has an acute oral LD50 of 0.6 1g/kg anda chronic or subchronic oral NOEL of 0.001 jig/kg/day; A person weighing 132 lb (60 kg).

Question 1:How much of the above spray mixture contains the equivalent ofthe LD50 for TCDD? Solution: 60 kgx 0.6pg/kg x 0.24 ig TCDD/L spray mixture

X = 150 L spray mixture 39.6 gal spray mixture

Question 2:How much of the above spray mixture can be ingested daily without exceeding the NOEL for TCDD? Solution: x 60 kg x 0.001 ig/kg/day 0.24 ig TCDD/L spray mixture

X = 0.25 I.. spray mixture/day

= 1 cup spray mixture/day

(Note--With the application of a 100-fold safety factor,the amount would be 2.5 mLspray mixture/day, or 0.5 tsp spray mixture/day.)

54 SITUATION 3 STREAM WATER CONTAINING TCDD

Given: A commercial herbicide product of 2,4,5-T containing 0.01 ppm TCDD which is applied to a stream resulting in a 2,4,5-T concentration in the stream water of 0. 1 ppm (0.1 xiO_6g ae 2,4,5-T/mL stream water). (Note This amount represents an actual "worst case" situation.See Appendix 2 for details.) Therefore, the maximum amount of TCDD present would be 1.0 x pg TCDD/mL stream water, or 1.0 xiO_6pg TCDD/L stream water;

TCDD has an acute oral LD50 of0.6pg/kg and a chronic or subchronic oral NOEL of 0.001 pg/kg/day;

A person weighing 132 lb(60kg). Question 1:How much stream water contains the equivalent of the LD50 for TCDD? Solution: x 60kgx 0.6pglkg 1.0 x iO_6 pg TCDD/L stream water

X = 36 x 106 L spray mixture 9.5 x 106 gal stream water

Question 2:How much stream water can be ingested daily without exceeding the NOEL for TCDD? Solution: x 60 kg x 0.001 pg/kg/day 1.0 x iO_6ug TCDD/L stream water

X = 0.06 x 106L stream water/day

= 60,000L stream water/day 15,840 gal stream water/day

(Note--With the application of a 100-fold safety factor, the amount wouldbe600L stream water/day, or 158.4 gal stream water/day.)

SITUATION 4 - AMBIENT AIR CONTAINING TCDD

Given: A commercial herbicide product of 2,4,5-T containing 0.01ppm TCDD which is applied to an area resulting in an ambient air concentration ina nearby unsprayed area of 1.0 pg ae 2,4,5-T/m3 of air. (Note This amount represents an "upper limit" as estimated by Newton and Norris 1981).Therefore, the maximum amount of TCDD present would be0.01 x iO_6pg/m3;

55 TCDD has an acute oral LD50 of 0.6 pg/kg and a chronic or subchronic oral NOEL of 0.001 pg/kg/day; A person weighing 132 lb (60 kg). Question 1:How much air contains the equivalent of the LD50 for TCDD? Solution: x 60 kgx 0.6jg/kg 0.01 x iO_6 pg TCDD/m3 air

X 3,600 x 106 m3 air 4,716 x 106 yd3 air

Question 2:How much air can be inhaled daily without exceeding the NOEL for TCDD? Solution: x 60 kg x 0.001 pg/kg/day 0.01 x iO6 pg TCDD/m3 air

X = 6 x 106 m3 air/day 7.9 x 106 yd3 air/day

(Note--With the application of a 100-fold safety factor, the amount would be 60,000 m3 air/day, or 78,600 yd3 air/day.)

SITUATION 5 ANIMAL MEAT CONTAINING TCDD

Given: Animal meat comprised of 20% fat (i.e., 0.2 g fat/g meat) which containsa TCDD concentration of 60 ppt ("worst case" situation) in the fat.Therefore, this amounts to:

12 iO_12 g TCDD/g meat = 12 x iO_6 ug TCDD/g meat 12 x i- ug TCDD/kg meat; TCDD has an acute oral LD50 of 0.6 ug/kg and a chronic or subchronic oral NOEL of 0.001 ug/kg/day; A person weighing 132 lb (60 kg). QuestIon 1:How much meat contains the equivalent of the LD50 for TCDD? Solution: x 60 kgx O.6ug/kg 12 x i- ug TCDD/kg meat

X 3,000 kg meat 6,614 lb meat

56 Question 2:How much meat can be ingested daily without exceeding the NOEL for TCDD? Solution: x 60 kg x 0.001 ug/kg/day 12 x i0 ug TCDD/kg meat

X = 5 kg meat/day 11 lb meat/day

(Note--With the application of a 100-fold safety factor, the amount would be 50 g meat/day, or 1.75 oz meat/day.)

APPENDIX 4

REFERENCES USED IN ESTABLISHING THE NO OBSERVABLE EFFECT LEVEL OF VARIOUS HERBICIDES.

Herbicide Test Animals References 2,4,5-T rats Emerson et al.1971. Sparschu et al. 1971, Khera and Mckinley 1972, Schwetz 1977, Smith et al.1978, Kociba et al. 1979b mice RoIl 1971 dogs Drill and Hiratzka 1953 rhesus monkeys Dougherty et al. 1975 rabbits Emerson et al. 1971 sheep Binns and BaIls 1971 2,4,5-TP cattle Palmer et al.1964 sheep Palmer and Radeleff 1969

2,k-D rats Hansen et al.1971 swine Erne 1966 cattle Palmer and Radeleff 1964, Palmer 1972 dogs Hansen et al.1971

2,4-DP rats Weed Science Society of America 1983 Amitrole mice Lewis and Tatken 1980 Asulam unknown NOEL value based on personal communication with Rhone-Poulenc, manufacturer of AsuIox

Atrazine mice Mrak 1969, Innes et al.1969 rats Peters and Cook 1973

Dalapon-Na rats Paynter et al.1960, Emerson et al. 1971 dogs Paynter et al.1960

Dicamba rats and rabbits Velsicol 1981, Newton and Dost 1981

57 Herbicide Test Animals References

Dinoseb mice Gibson 1973 dogs and rats Weed Science Society of America 1983 Fosamine rats Haskell Laboratory 1979a, Weed Science Society of America 1983 Glyphosate rats, dogs, Federal Register, Dec. 5, 1978, Vol. and rabbits 43 (234):57000-57006; and Aug. 5, 1980, Vol. 145 (152):51768-51769. Hexazinone rats, mice, Haskell Laboratory 1979b; Federal and hamsters Register, Nov. 21,1980, Vol. 45 (227) :77030. MSMA unknown NOEL estimate based on approximately 1/100 of the LD50 value for rats Picloram rats National Research Council of Canada Ca. 1974 dogs Lynn 1965, McCollister and Leng 1969 Simazine unknown NOEL estimate based on data for atraz me Triclopyr rats and rabbits Weed Science Society of America 1983, and personal communication with L. E. Warren of Dow Chemical USA

APPENDIX 5

COMMERCIAL HERBICIDE PRODUCT SPECIFICATIONS The mention of trade names should not be construed as an endorsement of these products by Oregon State University.They are simply used to provide realistic examples for calculations. Herbicide ManufacturerActive ingredient(ai) Common nameTrade name % lb/ql 24,5-T Esteron 245 Dow Chemical 45.0 4 2,4,5-TP Kuron® Dow Chemical 45.8 4 2,4-D Esteron99® Concentrate Dow Chemical 144.9 4 2,4-OP Weedone 2,4-DP Union Carbide 44.7 4 Amitrole Amitrol T Union Carbide 21.6 2 Asulam Asulox® Rhone-Poulenc 314.0 3.34 Atrazine Aatrex 41.. Ciba-Geigy 40.8 4 Dalapon Dowpon® M Dow Chemical 714.0 Dicamba Banvel4-W.S. VeIsicol 140.6 Dinoseb Red-Top Contact WeedkillerWilbur-Ellis 30 Fosamine 3 Krenite° DuPont 41.5 Li Glyphosate Roundups Monsanto 30.7 3 Hexazinone VelparL Weedkiller DuPont 25 2 MSMA Trans-Vert® Union Carbide 51. 19 6.66 Pjcloram K Tordon Dow Chemical 20.8 2 Simazine Princep 80W Ciba-Geigy 80 Triclopyr Garlon® 4 Dow Chemical 144.3 4

58 APPENDIX 6

METRIC-ENGLISH EQUIVALENTS AND ABBREVIATIONS

Length Area cm = centimeter m2 = square meter

0.3937 inch (in.) = 1.196 square yards (yd2)

m = meter ha = hectare

= 100 cm = 10,000 m2

1.0936 yards (yd) = 2.4711 acres (A)

Mass Vo I ume

kg = kilogram L = liter

= 2.2046 pounds (lb) = 4.23 cups

g = gram = 2.11 pints (pt)

= i- kg 1.06 quarts (qt)

= 0.035 ounce (oz) = 0.264 gallon (gal)

mg = milligram mL = milliliter

= b-3 g = i3 L

= microgram = 16 drops

= 10-6g = 0.2 teaspoon (tsp)

ng = nanogram = 0.067 tablespoon (tbsp)

= g = 0.00423 cup

m3 = cubic meter Concentration = 1.31 cubic yards (yd3) ppm = part per million = 106

ppb = part per billion i0 ppt = part per tnII ion = 10-12

59 APPENDIX 7

SOME SOURCES OF OTHER POINTS OF VIEW AND ADDITIONAL ISSUES CONCERNED WITH HERBICIDES

EPSTEIN, S.S. 1978. The politics of cancer.Sierra Club Books, San Francisco, Cali- fornia. GREEN, K., and K. COHN.1982. Forests, herbicides andpeople. Acasestudyofphenoxyher- bicides In western Oregon.Council on Economic Priorities, New York. HAY, A. 1982. The chemical scythe.Lessons of 2,L&,5-T and dioxin.Plenum Publishing Corporation, New York. NADER, R., R. BROWNSTE IN, and J. RICHARD.1981. Who's poisoning America? Corporate pol- luters and their victimsinthe chemical age. Sierra Club Books, San Francisco, California.

SHEARER, R., and M. HALTER.1980.Literature reviews of four selected herbicides: 2,4-D, dichlobenil,diquat and endothall. Water Quality Planning Division,Municipality of Metropolitan Seattle, Washington.

VAN STRUM, C. 1983. A bitter fog:Herbicides and human rights.Sierra Club Books, San Francisco, California.

WARNOCK, J. W., and J. Lewis. 1978. The other face of 2,4-D. A citizens report.South Okanagan Environmental Coalition.Penticton, British Columbia, Canada. WHITESIDE, T.1979. The pendulum and the toxic cloud. The course of dioxin contamination. Yale University Press, New Haven, Connecticut.

60 WALSTAD, JOHN D., AND FRANK N. DOST. THE HEALTH RISKS OF HERBICIDESIN FORESTRY: A REVIEW OF THE SCIENTIFIC RECORD. Forest Research Laboratory, Oregon StateUniversity,Corvallis. SpecialPublica- tion 10. 60 p. This report focuses on the phenoxy herbicides2,4,5-Tand2,4-0,and the con- taminantTCDD(dioxin).Several other herbicides used in forestry are also evaluated.Toxicologic methods of determining a safe dose and the regulatory control process enforced by government agencies are explained. In order to estimate the health risks of various levels of occupational and environmental contact with herbicides, data from studies of herbicide toxicity in laboratory animals have been extrapolated to humans.Calculations based on body weight are presented which indicate that, once the herbicides are diluted and applied according to regulations and label directions,itis highly unlikely that humans or other animals could ingest or absorb enough sprayed materialto approach levels that might cause harm. An extensivelist of scientific reviews supports this view.

KEYWORDS: 2,4-0, 2,4,5-T, TCDD,dioxin, herbicides, phenoxies, toxicology, risk assessment, forest vegetation management, regulatory control.

WALSTAD, JOHN D., AND FRANK N. DOST. THE HEALTH RISKS OF HERBICIDES IN FORESTRY: A REVIEW OF THE SCIENTIFIC RECORD. Forest Research Laboratory, Oregon StateUniversity,Corvallis. SpecialPublica- tion 10. 60 p. This report focuses on the phenoxy herbicides2,t4,S-Tand2,4-D,and the con- taminantTCDO(dioxin).Several other herbicides used in forestry are also evaluated.Toxicologic methods of determining a safe dose and the regulatory control process enforced by government agencies are explained. In order to estimate the health risks of various levels of occupational and environmental contact with herbicides, data from studies of herbicide toxicity in laboratory animals have been extrapolated to humans.Calculations based on body weight are presented which indicate that, once the herbicides are diluted and applied according to regulations and label directions,itis highly un- lIkely that humans or other animals could ingest or absorb enough sprayed materialto approach levels that might cause harm. An extensivelist of scIentific reviews supports this view. KEYWORDS: 2,4-0, 2,4,5-T, TCDO,dioxin, herbicides, phenoxies, toxicology, risk assessment, forest vegetation management, regulatory control. OR HEO/F76/2 .48p3 :10c.3 Waistad, John Daniel, 1944 The health risks of herbicides in forestry--a

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