Research - Chemical and Biological Hazards SUMMARY Infectious disease remains a serious problem in U.S. agriculture in two distinct populations: o Migrant farm workers experiencing human-host illnesses, often episodic and exacerbated by substandard living and employment conditions. o All other farm workers experiencing sporadic, isolated illness that is most fre- quently zoonotic, vector-borne, or environ- mentally acquired in nature. REFERENCES Both populations may present risk of ex- posure to the non-farm population through personal contact, indirect exposure (enviro- nment or vector), or contamination of food produce. Obvious innovations and tech- nologies exist to improve disease recog- nition, management, and control for both groups specifically, and non-farm in- dividuals generally. The broad and varied scope of this problem is presented, including areas that should be targeted for additional research or enhanced program support.0 1. American Public Health Association, Control of Communicable Diseases in Man. Benensen AS ed, 15th Ed; 1990. 2. Amer Vet Med Association, Zoonoses Updates (published compilation), JAKU4. Amer Vet Med Ass'n, Shaumburg IL; 199Q. 3. Currier RW. Iowa Department of Public Health, Des Moines IA; March 1991. 4. Roberto RR. Personal communication. California Department of Health Services, Berkeley CA; April 1991. 5. Armstrong CW. Personal communication. Virginia Department of Health, Richmond VA; April 1991. 6. Ciesielski SD, Seed JR, Esposito DH, and Hunter N. The epidemiology of tuberculosis among North Carolina migrant farm workers. JAMA 265: 17151719; April 3, 1991. 7. Centers for Disease Control. A strategic plan for the elimination of tuberculosis in the United States. MMWR. 1989; 38: S-3. 8. Centers for Disease Control. Tuberculosis among foreign-born persons entering the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. M.. 1990; 39(No. RR18). 9. Davis JP. Personal communication. Wisconsin Division of Health, Madison WI. March 1991. 10. Proctor M. Unpublished investigation. Wisconsin Division of Health, Madison WI. 1990. 11. Proctor M. Internal agency report. Wisconsin Division of Health, Madison WI. 1990. 12. Centers for Disease Control: Poliomyelitis Surveillance Summary 1979, Issued April 1981. 13. Hutchins R. Personal communication. Tennessee Department of Health, Nashville TN. April 1991. 226 Papers and Proceedings Infectious Diseases, May 1, 1991 14. Stevens GA. Testimony prepared for the Occupational Safety and Health Administration on Proposed Field Sanitation Standards. Dehnarva Rural Ministries. July 1984. 15. Federal Register, 29 CFR Field Sanitation; Final Rule Vol52, No 84, p 16049-16096. May 1, 1987. 16. McChesney TC. Personal communication. Arkansas Department of Health, Little Rock AR. April 1991. 17. Centers for Disease Control. Summary of notifiable diseases, United States, 1989 . MMKQ. 1989 ; 38 ( 54 ) . 18. Potter ME, Kaufman AF, Blake PA, and Feldman RA. Unpasteurized milk: The hazards of a health fetish. JAMA. 252~1048-2052. Ott 1984. 19. Currier RW. Raw milk and human gastroenteric disease: problems resulting from sale of legalized raw milk. J of Pub Health Policy 2~226-234, Sept 1981. 20. Blazer MD, Sazie E, Williams LP. The influence of immunity on raw milk-associated Campylobacter infection. JAMA. 257: 43-46. Jan 1987 . 21. Vogt RL, et al. Liig environmental and human strains of Listeria monocytogenes with isoenzyme and ribosomal RNA typing. Eur J EpidemiolO392-299O:p 229-230. June 1990. 22. Shirely LA. Personal communication. North Dakota Department of Health. April 1991. 23. St Louis ME, Morse DL, Potter ME, et al. The emergence of grade A eggs as a major source of Salmonella enteritidis infections. JAMA. 259: 2103-2107. 1988. 24. Gunn R4 and Markakis G. Sahnonellosis associated with homemade ice cream. JAMA 240:1885-1886. 1978. 25. Currier RW, Rapp WF, Juranek DD. A community outbreak of trichinosis in Nebraska: report of an epidemiologic investigation. Nebraska Medical Journal. Jan-Feb, 1982. 26. Centers for Disease Control. Trichinella spirilis infection - United States, 1990. MMKR. 1991; 40 : 57-60. 27. Williams LP. Personal communication. Oregon Department of Health, Portland OR. April 1991. 28. Staff Epidemiologist. Personal communication. Utah Department of Health, Salt Lake City UT. April 1991. 29. Marx J. Unpublished data. Marshfield Clinic, Marshfield WI. April 1991. 30. California Morbidity. Mosquito-transmitted malaria in California: 1988-1989. Part 2 of 2. Nr 52, Jan 5, 1990. (Pub1 by Calii Department of Health Services.) 31. California Morbidity. Arboviral disease surveillance - California, 1989. Nr 21/22. June 1, 1990. 32. Fuortes L. Unpublished data. College of Medicine, Univ of Iowa, Iowa City IA. April 1991. 33. Wood C. Unpublished data. Kansas Department of Health and Environment, Topeka KS. April 1991. 34. Currier RW. Farm injury surveillance (SPRAINS Program) - unpublished data. Iowa Department of Public Health, Des Moines lA. Feb 1991. Surgeon General's Conference on Agricultural Safety and Health - 1991 227 Research - Chemical and Biological Hazards 35. Thoen CO. Zoonoses Update: Tuberculosis. JAKV.4 (Pub1 collection of Zoonoses Updates.) 132-135. 1990. 36. Currier RW. Zoonoses Update: Bruceiiosis. JAK'v&4 (Pub1 collection of Zoonoses Updates.) p 25-27. 1990. 37. Music S. Personal communication. Wyoming Department of Health, Cheyenne WY. March 1991. 38. Sasaki DM. Personal communication. Hawaii Department of Health, Honolulu HI. April 1991. 39. Williams LP. Personal communication. Oregon Department of Health, Portland OR. April 1991. 40. Durfee PT, Pullen MM, Currier RW and Parker RL. Human psittacosis associated with commercial processing of turkeys. JAK'U 167: 804-808. Nov 1, 1975. 41. Doll J. Personal communication. Arizona Department of Health, Phoenix, AZ, April 1991. 42. Smith KA. Personal communication. Ohio Department of Health, Columbus, OH, April 1991. 43. Iowa Department of Public Health. Bovine rabies in Iowa. Iowa Disease Bulletin. Feb 1991. 44. Centers for Disease Control. Rabies surveillance - 1988. Issued Aug 1989. 45. Martin RJ. Personal communication. Illinois Department of Health, Springfield, IL, April 1991. 46. Baer G. Personal communication. Centers for Disease Control, Atlanta, GA., 1990. 47. Currier RW. Unpublished data. Iowa Department of Public Health, Des Moines LA. 1990. 48. Sewell CM. Personal communication. New Mexico Health and Environment Department, Sante Fe NM. March 1991. 228 Papers and Proceedings Surgeon General's Conference on Agricultural Safety and Health FARM&FE 2000 . A National Coalition for local Action Convened by the National Institute ftr Occupational Safety and Health April 30 - May 3, 7991, Des Moines, Iowa AN OVERViEW OF POTENTIAL HEALTH HAZARDS AMONG FARMERS FROM USE OF PESTICIDES By Aaron Blair, Ph.D. Occupational Studies Section National Cancer Institute Beginning in the mid-1940's, pesticides have become an increasingly important weapon in the attempt to control troublesome agricultural pests. Conse- quently, agriculture has become a major consumer of pesticides and now accounts for about 65 percent of the total domestic use.' Pesticide use varies by the crops and livestock raised, but a majority of farmers report application of some. In a 1982 survey, approximately 75 percent of the farmers with crops and 70 percent with livestock used pesticides.' With 2 million farmers, 6 million additional farm family members, and nearly 3 million hired farm workers, there is a large number of persons with potential contact with pes- ticides through agricultural use.3 Use of pesticides has been an integral component of the agricultural revolution, which over the past 50 years has greatly increased yields. Losses that would occur without the use of pesticides are difficult to estimate, but they could be sizable." Despite efforts to tailor the toxicologic properties of pesticides to specific pests, the fundamental similarity of all organisms at the subcellular level raises concerns about potential pesticide exposure of a large segment of the population. Although we should not lose sight of the benefits pesticides provide, the purpose of this review is to evaluate the potential for, and evidence of, adverse health outcomes from pesticide exposure in humans. Acute effects have been well established, and the major focus of this presentation will be on chronic effects. ACUTE EFFECTS Effects from acute exposure to pesticides are well established, but statistics on injury and death from acute exposures are in- complete for the United States as a whole. Some results indicate that the number of fatalities fell between the 1950's and the 1970's? Based on extrapolation from a survey of a small number of hospitals, EPA estimated that there were fewer than 3,000 annual admissions to hospitals for pesticide poisoning.' In California, however, where physicians are required by law to report suspected pesticide poisonings to the Department of Food and Agriculture, approximately 2,000 poisonings have been reported annually in recent years.' About 50 percent of these were from occupational exposures. More effective reporting systems are needed before the magnitude of adverse health conditions from acute exposures can be well monitored. Assessments in agricul- ture should include migrant workers, farm laborers, and dependents of farmers, as well as farm operators. Surgeon General's Conference on Agricultural Safety and Health - 1991 229 Research - Chemical and Biological Hazards CHRONIC EFFECTS Of growing concern are chronic health outcomes that do not occur immediately after exposure, including carcinogenic, developmental, immunological, reproduc- tive, and neurological effects.&' The lengthy interval between exposure and chronic effects makes risk assessment for these outcomes more difficult to evaluate than acute effects. As testing procedures have improved, concern has increased over long-term health effects from pesticides. Today sig- nificant efforts are devoted toward ex- perimental and epidemiologic evaluation of pesticides. The quantity and quality of the data available, however, vary by disease outcome. Establishment of a formal testing program by the National Cancer Institute (NCI) in 1968 and continued by the National Toxicology Program (NTP) in 1978 gave carcinogenicity screening of chemicals, of which pesticides were an important con- cern, an early start. This experimental effort stimulated epidemiologic inves- tigation of pesticides and cancer. The availability of cancer registries also enhanced opportunities for cancer research by providing a readily available source of well-diagnosed cases. Registries for other chronic disease endpoints are only begin- ning to be established. Since we lack some of these resources, the occurrence of non- malignant chronic disease from pesticide exposure has not been evaluated as thoroughly. CARCINOGENIC EFFECTS Some 47 pesticides have been evaluated in the NCI-NTP bioassay program (Table I)." Information from other sources is available, but is not considered here because study protocols sometimes deviate from the preferred model and because the purpose of this paper is to provide an indication of hazards presented by pes- ticides and not to provide a comprehensive review of all available data. In the NCI-NTP assays, six pesticides, or 13 percent(chlordecone, dichlorvos, aminotrizole, sulfallate, dibromochloropropane (DBCP), and EDB) were positive in both sexes in mice and rats. Another 10 (21 percent) were positive in both sexes of one species (chlordane, chlorobenzilate, dieldrin, hep- tachlor, tetrachlorvinphos, toxaphene, nitrofen, captan, chlorthalonil, and dichloropropene). Five (11 percent) were positive in one sex of at least one species (aldrin, dicofol, piperonyl sulphoxide, chloramben, and trifluralin). For 19 (40 percent) there was no evidence of car- cinogenicity in any sex/species group and seven (15 percent) provided inadequate or equivocal evidence for carcinogenicity. Several of the pesticides positive in bioas- says are no longer on the market, or their use is severely restricted, but others are widely used. The 16 chemicals positive in both sexes in at least one species include organochlorine and organophosphate in- secticides, herbicides, fungicides, and fumigants, suggesting that no chemical class of pesticides can be considered problem free. Pesticides are selected for testing for various reasons, including suspicion of carcinogenicity. With 45 percent of the pesticides tested showing some evidence of carcinogenicity, the concern about chronic human exposure would seem well founded. 230 Papers and Proceedings An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 Table 1. Results of Carcinogenicity Testing of Pesticides from the National Toxicology Program of Bioassays in Mice and Rats (modified from reference 10). INSECTICIDES Aldicarb Aldrin Azinphosmethyl Chlordane Chlordecone Chlorobenzilate Coumaphos Diazinon Dichlorvos Dicofol Dieldren Dimethoate Dioxathion Endosulphan Endrin Fenthion Heptachlor Lindane Malathion Maloxon Methoxychlor Methyl parathion Mexacarbate Parathion Phosphamidon Photodieldrin Piperonyl butoxide Piperonyl sulphoxide Tetrachlorvinphos Toxaphene MICE I!!! v + + + + t t + I E t t + t t t RATS I!!! ? E E L t I HERBICIDES Aminotriazole Chlorambene Fluometuron Monuron Nitrofen Sulfallate Trifluralin FUNGICIDES Anilazine Captan Chlorthalonil Fenaminosulf 0-Phenylpheno-I Pentachloro- nitrobenzene Triphenyltin-OH M 7 t : + + t FUMIGANTS DBCP t Dichloropropene I EDB t E = Equivocal I = inadequate evidence M = Male F = Female MICE t t + RATS M . t : t t t t t Pesticides may exert their carcinogenic effects through several mechanisms, including mutation, inhibition of gap- junctional cellular communication, in vivo and in vitro tests, the nine chemicals were found to, be active in most assays. These included organophosphate insec- ticides (acephate, demeton, mono- pcroxisome proliferation, and other promotional activities." In an evaluation crotophos, and trichlorfon), phthalimide of genetic damage from 65 pesticides in 14 fungicides (captan and folpet), and thio- Surgeon General's Conference on Agricultural Safety and Health - 1991 231 Research - Chemical and Biological Hazards carbamate herbicides (diallate, sulfallate, and triallate).`* Another group of 26 chemicals were positive in some tests, but were generally less active than the nine chemicals above. Pesticides in this group included phenoxy herbicides (2,4-D and 2,4-DB); organo- phosphate insecticides (azinphos-methyl, crotoxyphos, disulfoton, and methyl parathion); ethylenebisdithiocarbamate fungicides (manzeb, maneb, mancozeb, and zineb); and pyrethroid insecticides (allet- hrin, chrysanthemic acid, and ethyl chysan- themate). Thirty pesticides gave no evidence of genetic toxicity. Some pesticides may influence the car- cinogenic process in an epigenetic manner. For example, inhibition of intercellular communication can disrupt development or promote cancer." Broad occupational surveys from around the world have noted rather consistent excesses of leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the brain, skin, lip, stomach, and prostate among farmers. A number of pesticides have been shown to inhibit gap junction intercellular com- munication including DDT, dieldrin, chlor- dane, heptachlor, Kepone, mirex, and endrin.14 Several of these pesticides have been shown to have a promotional effect on liver carcinogenesis in the rat.l' Peroxisome proliferation and the resultant increased generation of hydrogen peroxide represent another possible non-genotoxic carcinogenic mechanism. Phenoxy acid herbicides appear to be peroxisome proliferators in several rodent species." Much of the epidemiologic data available on the carcinogenicity of pesticides comes from studies of persons employed in agriculture. Broad occupational surveys from around the world have noted rather consistent excesses of leukemia, non-Hodgkin's lym- phoma, multiple myeloma, soft-tissue sar- coma, and cancers of the brain, skin, lip, stomach, and prostate among farmers."-" These excesses occur against a background of lower overall mortality, particularly for heart disease and other cancers including lung, colon, bladder, kidney, esophagus, and liver. This pattern of low mortality from most causes of death, but excesses for a few cancers, suggests a role for work- related factors. The low prevalence of smoking among farmers is probably related to their more favorable rates for heart disease and can- cers of the lung, esophagus, and bladder.15 High levels of physical fitness may contribute to their lower rates of colon cancer and heart disease." Case-control and other studies provide further evidence that farmers are at higher risk for selected cancers than the general population. In a recent survey of the literature," excesses among farmers were seen in 12 of 13 studies of leukemia, 12 of 15 studies of Hodgkin's disease, 14 of 19 studies of multiple myeloma, 18 of 29 studies of nqn-Hodgkin's lymphoma, three of three studies of lip cancer, three of three studies of skin cancer, five of seven studies of brain cancer, three of five studies of soft-tissue sarcoma, six of six studies of stomach cancer, and two of three studies of prostate cancer. 232 Papers and Proceedings The excesses for specific cancers among Although farmers come into contact with a farmers may have broad public health variety of potentially hazardous substances, implications, since several of the high-rate pesticides have received the most attention tumors appear to be increasing in the in epidemiologic studies, possibly because general population of many developed several pesticides are carcinogenic in countries.le Of special interest are the bi0assays.l' Early epidemiologic inves- rising rates for multiple myeloma, non- tigations evaluated cancer risks associated Hodgkin's lymphoma, melanoma, and with pesticide exposure in general. cancer of the brain. The International Agency for Research on In England and Wales" and the United Cancer (IARC) in a recent deliberation State?, prostate cancer has also been concluded that exposures occurring during increasing. Changes in diagnosis and the application of insecticides were reporting may account for some of the probably carcinogenic in man." Cohort increase for these tumors."*" studies of applicators and manufacturers of The rising rates for non-Hodgkin's lym- insecticides have tended to show excesses phoma, multiple myeloma, and leukemia in of cancers of the lung and the lymphatic agricultural areas of the central United and hematopoietic system, although some States, however, is a further indication of investigations show deficits.lO~ll the possible involvement of agricultural exposures. Excesses of cancer of the brain In these studies it was not possible to and lymphatic and hematopoietic system determine the specific chemicals accoun- have also been observed in rural farm ting for these excesses, but most subjects populations in Quebec."2 were employed during a time when or- ganochlorine insecticides were the Risks were correlated with pesticide usage chemicals used predominately. Although and were observed among women, as well many epidemiologic studies have evaluated as men, raising the possibility of effects cancer risks among farmers and other from nonoccupational exposure. The pesticide-exposed workers," only recently specific agricultural factors that might have there been attempts to assess risks account for the cancers excessive among from exposure to specific pesticides." farmers have not been definitively iden- tified, but a number of etiologic clues exist. Among those studies that have, soft-tissue sarcoma, Hodgkin's disease, non-Hodgkin's Exposures of interest include pesticides, lymphoma, leukemia, and lung cancer have fertilizers, fuels and engine exhausts, or- been associated with DDT;42"`28 non- ganic and inorganic dusts, solvents, Hodgkin's lymphoma with organophos- ultraviolet light, and zoonotic viruses.3 phates;25 soft-tissue sarcoma with a variety Many, perhaps even most, of the members of animal insecticide?; leukemia with of the general population may also have crotoxyphos, dichlorvos, famphur, pyreth- contact with some of these substances. rins, methoxychlor, and nicotine%; and non- Studies of farmers may, therefore, provide Hodgkin's lymphoma'5*29-33 and soft-tissue explanations for the rising incidence of cer- sarcoma34'38 with phenoxyacid herbicides. A tain cancers among the general population. potential problem for other cancers is suggested by an important study of workers engaged in the production of 2,4,5- An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 Surgeon General's Conference on Agricultural Safety and Health - 1991 233 Research - Chemical and Biological Hazards Table II. Pesticide Effects on the Immune System (modified from reference 39). Pesticide Species Summarv of Effects t ORQANOPHOSPHATES Methylparathion . . . . . Rabbit Thymus atrophy and reduced DTH response. Mouse Decreased host resistance to infection Salmonella typimurium. Parathion . . . . . . . . . . . . Mouse Altered colony forming activities of bone marrow stem cells. Malathion . . . . . . . . . . . Mouse Suppression of CTL response in vitro. b ORQANOCHLORINES DDT . , . . . . , . . , . . , , , . , Rabbit Thymus atrophy and reduced DTH response. Mirex . . . . . . . . . . . . . . . _ Chicken Decreased IgG levels. Hexachlorgbenzene . . Mouse increased sensitivity to endotoxin and malaria challenge. Rat Increased humoral immune responses to tetanus toxoid and delayed- type hypersensitivity to ovalbumin. Dieldrin . . . . . . . . . . . . . Mouse Decreased AFC response and increased susceptibility to viral infection. Chlordane . . . . . . . . . . . Mouse Decreased contact hypersensitivity after in utero exposure. Mouse Suppression of AFC responses and T-cell activity in a MLC reaction following in vitro exposure. p CHLOROPHENOXY COMPOUNDS Pentachlorophenol . . . Mouse Decreased host resistance to virus-induced tumor metastases. 2,4-D . I.. . . . . , . . , , . . . Mouse Enhanced T- and B-cell responses following dermal application. t CARBAMATES Carbofuran . . . . . . . . . . Rabbit Reduced DTH response. Mouse Decreased host resistance to Salmonella tvphimurium infection. Aldicarb . . . . . . . . . . . . . Mouse Decreased AFC response to sheep erythrocytes. Human Increased response to Candida antigen, increased number of lym- phocytes expressing CD8 markers and decreased CD4 + /CD8 + cell ratio. Mouse No alterations in AFC response, B- or T-lymphocyte mitogenesis, host resistance to influenza virus infection, CTL response or percentages of T-cells, T-cell subpopulations or B-cells. DTH = delayed-type hypersensitivity. CTL = cytotoxic T lymphocytes. AFC = antibody-forming cells. MLC = mixed lymphocyte culture. trichlorophenol and derivative herbicides, those employed for less than one year. products contaminated with 2,3,7,&tetra- chlorodibenzo-p-dioxin.3' In this report, 20 Risks were elevated for soft-tissue sar- years after first exposure, a significant 50 comas and cancers of the esophagus, stom- percent excess of total cancer occurred ach, intestines, larynx, lung, and prostate. among workers employed for more than In the 20-year latency category, lung can- one year while no excess occurred among cer increased with duration of exposure 234 Papers and Proceedings with standardized mortality ratios (SMRs) of 96, 126, 146, and 156 for duration of exposure categories of C 1 year, 1 to < 5 years, 5 to < 15 years, and 15 or more years, respectively. Immunologic evaluations of pesticide ex- posure in humans are in their infancy. Effects observed in animals are not always seen in human studies.40 For example, altered numbers of T-cells and a decreased ratio of CD4/CD8 T-cells were found in IMMUNOLOGIC EFFECTS women exposed to aldicarb-contaminated drinking water." In investigations of al- Pesticides have immune effects that are of dicarb in mice, one noted an inverse dose- interest in their own right, but they may related suppression of antibody response,44 also be an important mechanism in car- while the another study did not.45 cinogenesis. A critical role for suppression of immune responsiveness by pesticides has been demonstrated for infectious disease A critical role for suppression of im- and maybe for other diseases.39 mune responsiveness by pesticides has been demonstrated for infectious disease Pesticides have displayed a variety of ef- fects on the immune system (Table II), and maybe for other diseases. including suppression of cytotoxic T lym- phocyte (CTL) response by malathion, thymus atrophy and delayed-type hypersen- There is also the possibility of a linkage sitivity (DTH) response by methyl- between immunologic effects from pest- parathion and DDT, decreased antibody- icide exposure and cancer. It is well forming cells (AFC) responses from documented that patients with naturally dieldrin and chlordane, enhanced T-and B- occurring or medically induced immuno- cell responses by 2,4-D, and reduced DTH deficiencies experience striking excesses of and host resistance by carbofuran. As with non-Hodgkin's lymphoma.46M carcinogenicity, immunologic effects are observed from pesticides in various In addition, excesses of leukemia and chemical classes (organochlorines, or- stomach cancer have been observed among ganophosphates, carbamates, and phenoxy- persons with primary immunodeficiency acids). In vitro studies of human leukocyte syndromes, while increases of soft-tissue functions have also shown inhibition of sarcoma, melanoma of the skin, and blastogenic stimulation". squamous carcinomas of the skin and lip have been observed in renal transplant Lymphocyte PHA stimulation was reduced patients.""" The fact that several of the 10 percent by carbamates, 11 to 18 percent tumors excessive among farmers (e.g., non- by organophosphates, and 11 to 17 percent Hodgkin's lymphoma, leukemia, skin, lip, by organochlorines. Contact dermatitis and stomach) also occur among im- and allergic chemical dermatitis are well- munodepressed patients could be a coin- recognized health effects from pesticide cidence, but it may suggest that effects on exposure and can occur from exposure to the immune system play a role in farming- various insecticides, fungicides, and related cancers. fumigants.4uz Epidemiologic investigations of alterations of the immune system are difficult because An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 SUrQeon General's Conference on Agricultural Safety and Health - 1991 235 Research - Chemical and Biological Hazards of large interindividual variability and the confounding effects from infections, drug use and other factors that influence im- mune responses. Alterations in immune responses may also be short lived. Monitoring of the immune system over an extended period may be necessary to determine the relevance of any alterations to subsequent disease risk. Consequently, it may be necessary to rely primarily upon experimental investigations in the near future. Thomas, et aE.,"O note two impor- tant criteria in extrapolating experimental results to humans. b First, the pharmacologic pattern for the pesticide should be the same in humans as in the animal model. This is difficult to achieve because information on absorption, distribution, biotransformation and excre- tion for the chemical of interest is rarely available in both humans and the animal model. b Second, the human end point of interest must be appropriate for the species selected. NEUROTOXIC EFFECTS The nervous system of the pest is the tar- get for many pesticides, so the fact that there are acute neurotoxic effects in humans is not surprising. Anecdotal case reports and epidemiologic studies also suggest that some neurologic symptoms may persist for years.`l Chronic effects observed include tremors, anorexia, anemia, muscular weakness, hyperexcitability, EEG pattern changes, insomnia, irritability, convulsions, headache, dizziness, and depression. These occur from various insecticide class- es including organochlorines, organo- phosphates, and carbamates.S1 Many of the above symptoms developed among workers with prolonged exposure to Kepone (chlordecone) in the Hopewell incident.s2 The symptoms gradually disap- peared over an 18-month period, but symp- toms persisted after several years in seven of the 23 most severely affected patients.n Less information is available concerning neurotoxic effects from herbicide exposure. Neuromuscular rigidity has been observed in rats after phenoxyacid exposure (2,4-D and MCPA)SIV 55 and peripheral nerve con- duction velocities were slowed among workers engaged in the manufacture of 2,4-D and 2,4,5-T.= Other nervous system conditions may be associated with pesticide exposure. A case report of Guillain-Barre syndrome noted recent skin exposure to the cotton de- foliant, merphosn An association with spraying of pesticides was reported in a case-control study of idiopathic Parkinson's disease.JB Risk of Parkinson's disease was also associated with longer duration farming and exposure to pesticides in a study in Hong Kong.s In another case-control study, however, it was associated with a rural residence and drinking well water, but not with use of pesticides."0 The subjective end points noted in most human studies of neurologic conditions make epidemiologic investiga- tions difficult. Evaluation of these end points is generally not possible in animals. Closing the gap between the two approaches is critical for a thorough evaluation of neurotoxic effects of chronic pesticide exposure. 236 Papers and Proceedings REPRODUCTIVE EFFECTS Mattison et al. classify reproductive toxicants as direct-acting or indirect- acting.6l Direct-acting toxicants may increased estrone metabolisms by liver microsomal enzymes by lindane, reduced egg production by organophosphates, and reduced fertility by carbamates. resemble a biologically important molecule CONCLUSIONS and function as agonists or antagonists in the reproductive process. Experimental and epidemiologic inves- tigations indicate that pesticides can cause They may also have direct effects because a variety of adverse effects including car- of their chemical reactivity. Most cinogenicity, immunotoxicity, neurotoxicity, chemically-reactive substances are and reproductive cytotoxic, carcinogenic, or mutagenic. toxicity. From this brief review several points stand out. Indirect-acting reproductive toxicants include chemicals that must be meta- b First, the carcinogenicity of pesticides bolized to produce effects, those that inter- has been more thoroughly evaluated than fere with critical enzyme systems, or those other toxic effects and approximately 45 that enhance or suppress secretion or percent of the chemicals tested had an clearance of critical control chemicals. effect in at least one sex of one species in Some chemicals may act both directly and NCI-NTP bioassays. If this experience is indirectly. For example, activities for or- relevant to other end points, the potential ganochlorine insecticides are suspected to for any type of adverse outcome from act directly through estrogen receptors and pesticide exposure could be considerable. indirectly through prohormone hepatic induction. b Second, the specific pesticides that are positive in the various toxicologic tests do Reproductive effects of specific pesticides not appear to be restricted to a few have recently been reviewed by Mattison et chemical classes. Effects are noted from al., 1990."' Adverse outcomes in experi- insecticides (organochlorines, or- mental and/or epidemiologic investigations ganophosphates, carbamates, and pyreth- have been reported for DBCP, chlorde- rins), herbicides, and fungicides. cone, ethylene dibromide, and carbaryl in males and DDT, chlordecone, lindane, or- b Third, adverse outcomes have been ~~~a~~sosphates, and carbamates among noted in epidemiologic, as well as ex- . perimental investigations, indicating that humans are also at risk. Effects among males have included disrup- tion of spermatogenesis by DBCP, reduced RECOMMENDATIONS sperm motility and viability by chlorde- cone, abnormal sperm morphology and 1. Given the evidence for adverse health sterility by ethylene dibromide, and sperm outcomes from pesticides, enhanced efforts abnormalities by carbaryl. In animals, are needed to control exposures in agricul- studies have noted reduced egg shell thick- ture and elsewhere. nesses from DDT, reduced egg production and number of offspring from chlordecone, An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 Surgeon General's Conference on AgriClJkUral Safety and Health - 1991 237 Research - Chemical and Biological Hazards 2. More thorough evaluations (experime- ntal and epidemiologic) are needed to more fully characterize the potential ad- verse effects that may occur from pesticide exposures. 3. Epidemiologic investigations must focus on exposures to specific pesticides. This will require detailed exposure assessment procedures to characterize the type and intensity of exposures. 4. Studies of farm populations should receive a high priority given the widespread use of pesticides in agriculture and the potential for exposure among farmers and farmer laborers, and their dependents. Retrospective designs can be used to ad- dress specific questions, but prospective studies should also be initiated. Prospec- tive investigations provide the opportunity to obtain information on exposure as it occurs, which would eliminate the potential for response bias and would minimize exposure misclassification. Once exposures are well characterized, prospective designs can also be used to evaluate a number of adverse health outcomes, a highly efficient approach in these times of funding limitations.0 REFERENCES 1. Eichers T, Andrilenas PA, Anderson TW. Farmers' Use of Pesticides in 1976. U.S. Department of Agriculture. Agricultural Economic Report No. 418. Washington, D.C., 1978. 2. Duffy M. Pesticide Use and Practices, 1982. U.S. Department of Agriculture. Agriculture Information Bull. No. 462. Economic Research Service. U.S. Government Printing Office, Washington, DC., 1982. 3. National Coalition for Agricultural Safety and Health. AgricuZhue at Risk. A Report to the Nation. Institute of Agricultural Medicine and Occupational Health, University of Iowa, Iowa City, Iowa, 1989. 4. Ware GW. Pesticides: Chemical Tools. Freeman and Co., New York, NY. 1983. 5. Hayes WJ Jr, Vaughan WK. Mortality from pesticides in the United States in 1973 and 1974. Toxic01 AppI Phamacol42: 235-252, 1977. 6. EPA (Environmental Protection Agency). National study of hospital admitted pesticide poisonings. Washington, D.C. 1976. 7. Edmiston S, Maddy K Summary of illnesses and injuries reported in California by physicians in 1986 as potentially related to pesticides. Vet Hum Toxicol29: 391-397, 1987. 8. Sharp DS, Eskenazi B, Harrison R, Callas P, Smith AH. Delayed health hazards of pesticide exposure. Ann Rev Public Health 7: 441-471, 1986. 9. Baker SR, Wiion CF (Eds). The Effects of Pesticides on Human Health. Adv Modem Environ Toxicol Vol XVIII. Princeton Sci Pub1 Co, Inc. Princeton, NJ, 1990. 10. Hoover RN, Blair A. Cancer and pesticides. (In press). 11. Blair A, Axelson 0, Franklin C, Paynter OE, Pearce N, Stevenson D, Trosko JE, Vainio H, Williams G, Woods J, Zahm SH. Carcinogenic effects of pesticides. In: The Effects of Pesticides on Human Health. (Eds.) Baker SR, Wilkinson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc. Princeton, NJ: 201-260, 1990. 238 Papers and Proceedings An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 12. Garrett NE, Stack HF, Waters MD. Evaluation of the genetic activity profiles of 65 pesticides. Mutation Res 168: 301-325, 1986. 13. Trosko JE. A new paradigm is needed in toxicology evaluation. Environ Hutag 6: 767-769, 1984. 14. Trosko JE, Chang CC. Nongenotoxic mechanism in carcinogenesis: Role of inhibited intercellular communicati?n. In: New Directions in the Qualitative and Quantitative Aspects of Carcinogen Risk Assessment. (Eds.) Hart RW, Setlow RB. Banbury Rep. 31. Cold Spring Harbor, NY: 139-170, 1988. 15. Blair A, Malker H, Cantor KP, Burmeister L, Wiklund K. Cancer among farmers: A review. Scaltd J Work Environ Health 11: 397407, 1985. 16. Pearce N, Reif JS. Epidemiologic studies of cancer in agricultural workers. Am J Ind Mtid 18: 133-142, 1990. 17. Blair A, Zahm SH. Cancer among farmers. In: Health Hazard of Farming. Occupational Medicine - State of the Art Reviews. (Eds.) Cordes DH, Rea DF. Hanley and Be&s, Inc. Philadelphia, PA. (In press). 18. Davis DL, Hoe1 D, Fox J, Lopez A. International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and USA. Lancet 336: 474-481, 1990. 19. Office of Census and Population Surveys. Reviews of the National Cancer Registration System (Series MBA, No. 17). London: HM Stationery Office, 1990. 20. Devesa SS, Silverman DT, Young JL, Pollack ES, Brown CC, Horm JW, Percy CL, Myers MH, McKay Fw, Fraumeni JF Jr. Cancer incidence and mortality trends among whites in the United States, 1947-84. JNCI 79: 701-770, 1987. 21. Doll R, Peto R. The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. JNCI 66: 1191-1308, 1981. 22. IARC (International Agency for Research on Cancer): IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Occupational Exposure in Insecticide Application and Some Pesticides, Vol. 53. Lyon, France. (In press). 23. Axelson 0. Pesticides and cancer risks in agriculture. Med oncol Tumor Pharmacother 4: 207-217, 1987. 24. Zahm SH, Blair A, Holmes FF, Boysen CD, Robe1 RJ. A case-referent study of soft-tissue sarcoma and Hodgkin's disease - farming and insecticide use. Stand J Work Environ Health 14: 224-230, 1988. 25. Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A. A case-control study of non-Hodkgin's lymphoma and the herbicide &4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology 1:349-356, 1990. 26. Brown LM, Blair A, Gibson R, Everett GD, Cantor KP, Schuman LM, Burmeister LF, Van Lier SF, Dick F. Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. Cancer Res 50: 6585-6591, 1990. 27. Woods JS, Polissar L, Severson RK, Heuser LS, Rulander BG. Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington. JNCI 78: 899-910, 1987. Surgeofl General's Conference on Agricultural Safety and Health - 1991 239 Research - Chemical and Biological Hazards 28. Flodin U, Frederiksson M, Persson B, Axelson 0. Chronic lymphatic leukemia and engine exhausts, fresh wood, and DDT: A case-referent study. Br J Ind Med 45: 33-38, 1988. 29. Hoar SK, Blair A, Holmes FF, Boysen CD, Robe1 RJ, Hoover RN, Fraumeni JF Jr. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256: 1141-1147, 1986. 30. Hardell L, E&son M, Lenner P, Lungren E. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols, and phenoxy acids: A case-control study. Br J Cancer 43: 169--176,1981. 31. Persson B, Dahlander A, Fredriksson M, Brage HN, Ohlson CG, Axelson 0. Malignant lymphoma and occupational exposures. Br J Ind Med 46: 516-520, 1989. 32. Wigle DT, Semenciw RM, Wilkins K, Riedel D, Ritter L, Morrison HI, Mao Y. Mortality study of Canadian male farm operators: Non-Hodgkin's lymphoma mortality and agricultural practices in Saskatchewan. JNCI 82: 575-582, 1990 . 33. Bond GG, Wetterstroem NH, Roush GJ, McLaren EA, Lipps TE, Cook RR. Cause-specific mortality among employees engaged in the manufacture, formulation, or packaging of 2,4dichlorophenoxyacetic acid and related salts. Br J Ind Med 45: 98-105, 1988. 34. Hardell L, Sandstrom A. Case-control study: soft-tissue sarcoma and exposure to phenoxyacetic acids and chlorophenols. Br J Cancer 39: 711-717, 1979. 35. Eriksson M, Hardell L, Berg NO, Moller T, Axelson 0. Soft tissue sarcomas and exposure to chemical substances: A case referent study. Br J Ittd Med 38: 27-33, 1981. 36. Vineis P, Terracini B, Ciccone G, Cignetti A, Colombo E, Bonna A, Maffi L, Pisa R, Ricci P, Zanini E, Comba P. Phenoxy herbicides and soft-tissue sarcomas in female rice weeders: A population-based case- referent study. Stand J Work Environment Health 13: 9-17, 1986. 37. Lynge E. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. Br J Cancer 52: 259-270, 1985. 38. Fingerhut MA, Halperin WE, Marlow DA, Piacitelli LA, Honchar PA, Sweeney MH, Greife AL, Dill PA, Steenland R, Suruda AJ. Cancer mortality in workers exposed to 2,3,7,8tetrachlorodibenz-p-dioxin. N Engi J Med 324: 212-218, 1991. 39. Thomas PT, Busse WW, Kerkvliet NI, Luster MI, Munson AE, Murray M, Roberts D, Robinson M, Silkworth J, Sjoblad R, Smialowicz R. Immunologic effects. In: The Effects of Pesticides on Human Health. (Eds.) Baker SR, Wilkinson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc. Princeton, NJ: 261-295, 1990. 40. Thomas PT, Faith RE. Adult and prenatal toxicity induced by halogenated aromatic hydrocarbons. In: Immunotoxicology and Immunophatmacofogy. (Eds.) Dean J, Luster M, Munson A, and Amos H. Raven Press, New York, NY, 1985. 41. Lee TP, Moscati R, Park BH. Effects of pesticides on human leukocyte functions. Res Cotnm Ghan Palhol Pharmacol23:597-609, 1979. 42. Sullivan JB Jr. Immunological alterations and chemical exposure. Clinical Tox 27: 311-343, 1989. 240 Papers and Proceedings An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991 43. Fiore M, Ander CHA, Hong R, Golubjatnikov R, Seiser JE, Nordstrom D, Han&an L, Belluck D. Chronic exposure to aldicarb-contaminated groundwater and human immune function. Environ Res 41: 633-645, 1986. 44. Olson LJ, Erickson BJ, Hinsdill RD, Wyman JA, Porter WI', Binning LK, Bidgood RC, Nordheim EV. Aldicarb immunomodulation in mice: An inverse dose-response to parts per billion levels in drinking water. Arch Environ Confam Toxkoi 16: 433-439, 1987. 45. Thomas PT, Ratajczak HV, Eisenberg WC, Furedi-Machacek M, Ketels KV, Barbera PW. Evaluation of host resistance and immunity in mice exposed to the carbamate pesticide aldicarb. Fundam Appr Toxicol 9: 82-89, 1987. 46. Hoover R, Fraumeni JF Jr. Risk of cancer in renal transplant recipients. Lancet 2: 55-57, 1973. 47. Filipovich AH, Spector BD, Kersey J. Immunodeficiency in humans as a risk factor in the development of malignancy. Prev Med 9: 252-259, 1980. 48. Blohme I, Brynger H. Malignant disease in renal transplant patients. Transplanfarion 39: 23-25, 1985. 49. Penn I. Immunosuppression and skin cancer. Clin Plast Surg 7: 361, 1980. 50. Kinlen L, Doll R, Peto J. The incidence of tumors in human transplant recipients. Transplant Proc 15: 1039-1042, 1983. 51. Ecobichon DJ, Davies JE, Doull J, Ehrich M, Joy R. McHillan D, MacPhail R, Reiter LW, Slikker W Jr, and Tilson H. Neurotoxic effects of pesticides. In: The Ejfecti OfPesticides on Human Health. (Eds.) Baker SR, Wilkinson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc. Princeton, NJ: 131-199, 1990. 52. Taylor JR, Selhorst JB, Houff SA, Martinez AJ. Chlordecone intoxication in man. I. Chemical observations. Neurology 28: 626-630, 1978. 53. Taylor JR. Neurological manifestations in humans exposed to chlordecone: Follow-up results. Neurotoxicology 6: 231-236, 1985. 54. Squib RE, T&on HA, Mitchell CL. Neurobehavioral assessment of 2,4-dichlorophenoxyacetic acid (2,4- D) in rats. Neurobehav. Toxicoi Teratol5: 331-335, 1983. 55. Elo H, Ylitalo P. Distribution of 2-methyl-4 chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: Evidence for the involvement of the central nervous system in their toxicity. Toxicol Appl Phamacol51: 439-446, 1979. 56. Singer R, Moses M, Valciukas J, Lilis R, Selikoff IJ. Nerve conduction velocity studies of workers employed in the manufacture of phenoxy herbicides. Environ Res 29: 297-311, 1982. 57. Fisher JR. Guillain-Barr& syndrome following organophosphate poisoning. JAMA 238: 1950-1951, 1977. 58. Golbe LI, Farrell TM, Davis PH. Follow-up study of early lie protective and risk factors in Parkinson's disease. Movement Disorders 5: 66-70, 1990. 59. Ho SC, Woo J, Lee CM. Epidemiologic study of Parkinson's disease in Hong Kong. Neurology 39: 1314- 1318, 1989. Surgeon General's Conference on Agricultural Safety and Health - 1991 241 Research - Chemical and Biological Hazards 60. KoIIer W, Vetere-Overfield B, Gray C, Alexander C, Chin T, DolezaI J, Hassanein R, Tanner C. Environmental risk factors in Parkinson's disease. Neurology 40: 1218-1221, 1990. 61. Mattison DR, BogumiI RJ, Chapin R, Hatch M, Hendricks A, JarreII J, LaBarbera A, Schrader SM, Selevan S. Reproductive effects of pesticides. In: The Effects of Pesticides on Human Health7 (Eds.) Baker SR, Wilkihson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc. Princeton, NJ: 1297-1389, 1990. 62. Godon D, Lajoie P, Thouez J, Nadeau D. Pesticides et cancers en milieu ruraI agricole au Quebec: Interpretation geographique. Sot Sci Med 29: 819-833, 1989. 242 Papers and Proceedings Surgeon General's Confemnce on Agricultuml Safety and Health FM&&FE 2000 . A National Coalition for Local Action Convened by the National Institute f0f Occupational Safety and Health April 30 - May 3, 7991, Des Moines, Iowa GASES, VAPORS, LIQUIDS, AND DRUGS By WZliam Popendorf, Ph.D., C.I.H. Institute of Agricultural Medicine, University of Iowa INTRODUCTION A wide range of gaseous and liquid hazards exists in agriculture (Table I).l*' Virtually all of the gaseous hazards from which we can anticipate health effects exist in one form or another in general industry. While we know of their existence in agriculture, only a few of these hazards have been surveyed in farm settings. We do not know how frequently (on the aver- age) farmers are exposed to individual agents. We do not know the range of con- centrations of such exposures. We do not know the extent of the health effects ex- cept for the occasional severe case report or fatality. And if we really did know these para- meters, we face yet another challenge; how to translate them into "agricultural hygiene," the industrial hygiene paradigm of "anticipation, recognition, evaluation, and control" learned in general industry over the past 50 years., As we begin to apply this paradigm, another challenge is to understand the limitations of rote transfer-ml of this paradigm from general industry to agriculture without also understanding its nature and its culture. This presentation will begin with a review of some of these agents, their sources on the farm, and some of the limitations of the traditional hierarchy of controlling these hazards either at their source, along the pathway of the exposure route, or at the receiver (in this case the farmer or farm worker). A discussion of health ef- fects will be minimized except for agents that are by-and-large unique to agriculture. Table I. Typical Toxic Agricultural Liquids, Gases, and Vapors. Ammonia ............................. from urine, urea, and anhydrous Carbon dioxide ...................... animal respiration and combustion Carbon monoxide ................... combustion sources Hydrogen sulfide .................... manure gas Nitrogen dioxide ..................... from fresh silage Oxygen Depletion ................... asphyxiation in confined spaces Pesticides ............................. primarily dermal absorption hazards except fumigants Welding ............................... fumes and gases Fuel storage .......................... leaks and fires Fuel and waste oil ................... skin cancers and dermatitis Ltquified Propane [LPI gas ........ fires Liquified anhydrous ammonia ..... dermal injury Surgeon General's Conference on Agricultural Safety and Health - 1991 243 Research - Chemical and Blologlcal Hazards DEFINITIONS I feel obliged to define a few terms and concepts ingrained into industrial hygiene folklore. The first (Figure 1) is the para- digm of anticipation, recognition, evalua- tion, and control. Historically, this process began with the recognition of adverse health effects existent within a working population. Anticipation Is the prospective application of dose-response knowledge generated either in the laboratory or in other industries. Recognition requires the commitment of farmers, interested farm groups, and governmental agencies to survey both the farming environment and the health status of farmers. Evaluation must develop new ways to interpret surveillance data from the farm set- ting for the agricultural population. Control includes not only "hazard com- munication" but also modified sources and interruptions in the pathways of exposure before the farmer, with or without personal protection, is dosed. 1 Figure 1. The Agricultural Hygiene Paradigm. Today, we can anticipate (and hopefully avoid) adverse health effects based on toxicology or prior experiences in other work settings. To evaluate the degree of risk, we have developed a system of "per- formance based" exposure limits guidelines (guidelines called Threshold Limit Values [TLVs] and their regulatory equivalents called Permissible Exposure Limits [PELs]), the goal of which is to prevent 244 adverse health effects by keeping expo- sures and doses to acceptable low levels without specifying the method or "work practices" to achieve those levels. The second is a concept that adverse health effects are the culmination of an often-complex chain of events beginning with the agent emanating into the working environment from a sometimes nebulous source and traveling through a physical pathway to create either an airborne, dermal, or even oral dose; the dose is generally dependant upon the duration of exposure and the degree of personal pro- tection being used by the worker; the agent may act at the site of contact or be absorbed into the body and be transported to some biological target organ where it acts toxicologically to create a clinically identifiable effect. Over the years, a hierarchy of control options has been inculcated into the profession whereby controlling the source is the preferred option, controlling the pathway between the source and worker is the second option, and controlling the re- ceiver is the third and least preferred op- tion. Hygienists believe that respirators or other forms of personal protective equip- ment are not a quick cure-all, contrary to popular belief. And even when they are recommended, good practice dictates (and OSHA now requires) that the respirator should be selected based on the measured level of exposure. GASES AND VAPORS The following history of silo gas is representative of the fragmented progres- sion of anticipation, recognition, evalua- tion, and control of a potentially common agricultural health hazard. Papers and Proceedings Gases, Vapors, Liquids, and Drugs, May 1, 1991 Occupational hazards associated with silo gas were first reported in 1914 via case studies of four fatalities of farmers working in and among their freshly filled silos. Their deaths were attributed to carbon dioxide (CO,). It was not until the 1950's (30 to 40 years later) that investigations revealed the presence and importance of nitrogen dioxide (N01).46 The major portion of toxic NO, appears to be produced from organic nitrates, aggravated by the addition of heavy nitrate fertilizer and/or drought conditions.6 The process of NO, production begins within hours of ensilage, peaks in three to seven days, but may last for up to two weeks. Levels of NO, as high as 200 ppm have been reported seven days after fill- ing;" this is well over its current TLV of 3 ppm (with a 5 ppm STEL). Our broad understanding of the magnitude and frequency of this hazard is limited by a lack of systematic environmental surveil- lance and poor reporting of farm injuries and fatalities. Our understanding of its overall impact on the health of farmers is further limited by the difficulty in diag- nosing nonfatal cases of the disease due to the multiple and usually latent phases of its clinical manifestations.`l' Thus, the severe and fatal cases of silo fillers' disease that are reported probably represent the tip of the proverbial iceberg. A few systematic surveys have recently been made of chronic gaseous hazards in modern semi-enclosed animal production buildings. Mulhausen" found that air quality in poultry barns frequently ex- ceeded exposure limits of 25 ppm for am- monia (NH,) during fall and winter and sometimes even exceeded its S'I'EL of 35 ppm; H,S was undetected. Donham et al." l3 surveyed similar swine barns and found 50 percent exceeded the TLC for ammonia; many of these buildings also ex- ceeded the TLC for CO, H,S, and CO (from un-vented space heaters). Source: urine (urea)-wet floors, slats, gutters, etc. Anticipated Health Hazards: Irritating to eyes, nose, trachea (wet body parts) . . . . . . . . . . IO-15 ppm TLV = recommended exposure limit (for gas) . . . . . . . . . . . . . . . . . . . . . . 25 ppm Absorbed into an aerosol may provoke bronchitis, asthma, or other pulmonary effects . . . . . . . . . . . . . . . . , ~20 ppm Figure 2. Ammonia (NH,). At these concentrations, ammonia by itself would only be a strong irritant to the eyes, nose, and throat. However, in both poultry and swine farm settings, it may be impor- tant to consider the simultaneous presence of both ammonia and organic dust aerosols at levels often in excess of 5 mg/m3. The hypothesis here is that the pulmonary damage caused by ammonia could be con- siderably greater if the gas were adsorbed onto a respirable-sized aerosol (Figure 2). In addition to hydrogen sulfide, mercap- tans and organic acids (such as methyl and ethyl-mercaptan, carbonyl-sulfide, skatole, and propionic, butyric, and valeric acids) have been identified in the gases emanating from the anaerobic decay of manure typically stored in a pit under most Surgeon General's Conference on Agricultural Safety and Health - 1991 245 Research - Chemical and Biological Hazards hog and some dairy barns.14dU It should be acknowledged that under normal barn conditions, hydrogen sulfide is not at levels of great health concern (Figure ,).I2 I3 Source: anaerobic manure digestion Anticipated Health Hazards: Threshold of odor detection . . . . . . 0.1-0.2 ppm Offensive odor . . , . . . . . . . . . . . . . . . . . . 3-5 ppm TLV = recommended exposure limit , , . . . , . . . , , . . . . . . . . . . . . . . . . . . 10 ppm Olfactory paralysis (cannot be smelled) . . . . . . . . . . .25-100 ppm Serious eye injury (gas eye) . . . . .50-100 ppm Bronchitis (dry cough) . . . . . . . . . loo-150 ppm Pneumonitis and pulmonary edema . , . . , , . . . . . . . . . . . . . . . . 200500 ppm Rapid respiratory arrest (death) . . > 1000 ppm Figure 3. Hydrogen Sulfide (H,S). However, when the manure is agitated prior to pump-out to be returned to the fields as fertilizer, it is rapidly released into the air above the frothing liquid.lsW19 During agitation, the author has measured levels of H,S as high as 300 ppm at pig breathing height and 1500 ppm in the pit (Figure 4). o Methyl-mercaptan o Propionic acid o Ethyl-mercaptan o Butyric acid o Carbonyl-sulfide o Valerie acid o Skatole Figure 4. Mercaptans and Organic Acids As- sociated with Hydrogen Sulfide from Manure. Manure gas deaths often involve multiple victims during futile rescue attempts.17,20 As was the case with silo gas, manure gas deaths even as recently as 1989 are sometimes m&diagnosed as asphyxiation from methane.M Control of agricultural respiratory hazards should rely first on reduction at the source, second on ventilation or some other physical barrier to its movement, and third on personal protection. Control of the source of most of the above agents will require further research before the process of gas generation is sufficiently understood to be reduced or avoided. High rates of ventilation of farm shops or animal confinement building is often resisted by operators who prefer to conserve heat in cold winter climates, and if too much ventilation were installed without consideration of make-up air re- quirements, high levels of CO could be drawn back down heater exhaust vents (Figure 5). Source: improperly adjusted heaters or no make-up air Anticipated Health Hazards: TLV = recommended exposure limit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 ppm Induces spontaneous abortions in swine . . . . . . . . . . . . . . . . . . . . 100-l 50 ppm Asphyxiation dependent upon duration of exposure . . . . . . . . (2-3 hours at 500 ppm) cl5 mins >2000 ppm Figure 5. Carbon Monoxide (CO). As in any other industry, the use of respirators should be considered a temp- orary and supplemental protection. In agri- culture there are no trained persons avail- able to assist in the selection, fit, or main- tenance of respirators. Thus, when pur- chased at all, respirators are selected 246 Papers and Proceedings without knowledge of measured levels of exposure and often without even the benefit of an adequate "work practices" evaluation as shall be discussed below. Table II. Major Groups of Field-Use Agricultural Pesticides. INSECTICIDES LIQUIDS Pesticides are formulated as solids (such as granules and wettable powders), liquids, and gases and vapors (mostly fumigants). Pesticides can present a hazard to applica- tors,21-P to harvesters re-entering a sprayed field, 24* 25 and to rural residents via air, water, and even food contamination.s28 Organophospates . . . . . . . . . . . . . . . Counter, Parathion, Guthion, Lorsban, Rabon Carbamate . . . . . . . . .._........ . . ..Temik, Furidan, Lannate, Sevin Organochlorines . . . . . . . . . . . . . . , . , Dieldrin, Lindane, Chlordane HERBICIDES Phenoxy-aiiphatic acids . . . . . ...2.4-D. 2,4,5-T, Trioxone Bipyridyis . . . . . . . . . . . . . . . . . . . . . _ Paraquat, Diquat Triazines . . . . . . . . . . . . . . . . . . . . . . . . . . Atrasine, Blasex, AAtrex OTHER/MISCELLANEOUS Thiocarbamates (fungicides) . Thiram, AAtack, Mabam, Maneb, Zineb Arsenicals (herbicides) , . . . . . Paris Green, Cacodyiic acid Acentaniiides (herbicides) . . . . . Alachlor, Lasso, Ramrod Dicarboximides (fungicides) . . . Difolitan, Captan Dinitrotoluidine (herbicides) . . . Amex, Prowl, Treflan Toxicologically, the major field- use pesticides can be broken down into six major chemical groups shown in Table II. Most of these agricultural chemicals present dermal hazards either from ab- sorption directly through intact skin and/or from dermatitis. Some of these insect- icides are also used indoors, especially in greenhouses were exposure is often higher,. Gases, Vapors, Liquids, and Drugs, May 1, 1991 Common Commercial Names There are two additional groups of non- field agricultural chemicals: one is fumigants (such as phosphine [usually aluminum phosphide or Phostoxin] or a volatile organic like carbon disulfide or ethylene dichloride) used in produce storage areas, and the other is disinfectants (such as chlorine, quaternary ammonia compounds, organic iodides, and cresol- based compounds) used in indoor animal production facilities.' Certain of these chemicals present respiratory hazards par- ticularly when used in combinations; other of these liquid chemicals present a risk of contact or an allergic dermatitis.30 While a review of pesticide toxicities is being presented separately, they are presented here because they demonstrate an approach to anticipation, recognition, evaluation, and control quite different from general industry. Some level of an- ticipation was available from the time of registration, but much of that interest was directed toward consumers rather than users who are exposed at much higher lev- els. Given that starting point, it is unfortunate that the recognition of hazards to users has often been a protracted process, in some ways no better than the history of many chemicals used in general industry. How- ever, evaluation of exposure, when it final- ly started to be conducted, was not site nor user specific but was conducted in re- sponse to more recent EPA pesticide regis- tration requirements. EPA then promulgated what amounts to a "use practices standard" in the form of Surgeon General's Conference on Agricultural Safety and Health - 1991 247 Research - Chemical and Biological Hazards label instructions, which specify the ways the chemical can be safely and legally used. The implication is that if all users follow these instructions, exposure will be sufficiently low to prevent adverse health effects. This process contrasts sharply with general industry where employers are ex- pected to "assure a workplace free from recognized hazards." Controls under these circumstances have also differed from general industry. It can be argued that the registration process is itself a form of controlling the source, screening out chemicals deemed too hazar- dous for agricultural use and restricting certain others to "licensed users." In that sense, a form of hazard com- munication was adopted by agriculture a little before general industry. However, the EPA registration and labelling process has yet to address the machinery control- ling the pathway of exposure. When it comes to personal protection, control has for a long time been mis- directed at airborne versus the dermal route of exposure; and those respiratory controls which are specified, were estab- lished without a decision logic common to general industry for over 30 years3'p3'. I am happy to report that EPA is currently developing a respirator selection decision logic at least consistent with a "use prac- tices standard." One might ask why a "use practices stan- dard" versus a "performance standard" approach used in agriculture. The one asking the question must not be a farmer. Even if the administrative and support structure were in place to conduct on-site monitoring at each farm or "place of employment," the activities, working en- vironments, and chemical exposure levels in most agricultural settings vary suf- ficiently by season, day, and even by hour as to make such measurements moot, which is not to say that measurements and even performance standards have no place in agriculture. For instance, work in animal production facilities is amenable to the application of traditional TLVs, environmental monitoring, and respirator selection criteria. "Use practice standards" have their own limitations; they must account for many variables, thus often making them overly restrictive conducive to low compliance. It remains a challenge for the future to define the conditions favoring either form of standard or to determine if either is even adequate. The other category of agricultural chemicals is fertilizers. Anhydrous am- monia is the most heavily used fertilizer in production agriculture. Anhydrous am- monia is hazardous to the skin and especially to the eyes because it is highly hygroscopic, highly caustic, and extremely cold (-280F under pressure). Almost any eye contact with this chemical will result in permanent blindness." In- haling high concentrations of ammonia can result is severe damage to the upper respiratory tract, resulting in bronchiectasis as a possible sequela." Most of the occupational injuries from anhydrous ammonia occur because of faulty couplings, bleeder valves, shutyoff valves, broken hoses, or plugged applicator tips. In addition to an established program of preventive maintenance, a pro-active hazard communication for both commer- cial and private applicators is essential to establish consistent wearing of eye protec- 248 Papers and Proceedings Gases, Vapors, Liquids, and Drugs, May 1, 1991 Table III. Skin Conditions of Agricultural Workers (adapted from reference 2). Classification of Skin Condition Irritant contact dermatitis . . . . . . . . . . . . . . . . . Allergic contact dermatitis . . . . . . ._. . . . . Photo-contact dermatitis . . . . , . . , . . . . . . . . . Sun-induced dermatoses ................. Infectious dermatoses ..................... Heat-induced dermatoses ................ Arthropod-induced dermatoses .......... Aaents (examblesl ammonia fertilizers animal feed additiies vegetable crops and bulb plants insecticides, herbicides, and fumigants herbicides and insecticides antibiotic feed additives plants creosota feed additive plants containing furocoumarins sunlight cattle, swine, and sheep moist and hot environments chiggers, bees, and wasps tion and ensuring the availability of clean water to flush eyes and skin in case of contact. In addition to their fire hazard and intrin- sic toxicity, many of the liquids involved in agriculture can produce dermatitis (Table III). Compared to other occupational groups, farmers have a proportionately higher prevalence of skin diseases."," Irritant contact dermatitis is perhaps the most common type of agricultural der- matoses.3539 Irritant substances are ubi- quitous and include ammonia fertilizers, several pesticides, soaps, petroleum products, and solvents. Avoidance schemes must include work practices to eliminate or reduce exposure to the most irritative substances and/or the use of personal protection equipment. Allergic contact dermatitis is typified by Poison ivy or poison oak reactions. These are exquisite sensitizers as are certain herbicides and pes- ticides? These reactions are more difficult to control, because suscep- tible farmers are ex- quisitely sensitive to very small amounts of offen- ding liquids. VETERINARY DRUGS Veterinary drugs are broadly divided into two classes of biologicals and antibiotics (Table IV). Biologicals are made from living products to enhance the immunity of an animal to a specific infectious disease or diseases. Users of biologicals are at risk of either accidental inoculation or splashing the product into the eyes, mucous membrane, or broken skin. Users at risk include not only veterinarians and their assistants, but also farmers, ranchers, and their employees, except for certain diseases for which a government-regulated control program is in effect (e.g., brucellosis, rabies, pseudorabies). The most frequent reports of occupational illnesses associated with biologicals involve veterinarians, whether splashing brucellosis strain 19 in their eyes or accidental inoculating themselves. Symptoms may include infection, inflammation, severe localized swelling and pain, and/or an allergic reaction. The infection mimics the acute infection seen from acquisition of the disease directly from either cattle or swine. Disability may last for days to weeks in the worst cases."' Surgeon General's Conference on Agricultural Safety and Health - 1991 249 Research - Chemical and Biological Hazards Table IV. Veterinary Drugs Potentially Hazardous to Users. Biologicals Brucellosis strain 19 Newcastle disease vaccine Contagious exthyma (orf) vaccine Jhone's disease bacterin Escherichia co/i bacterins Erysipelas vaccines Antibiotics Penicillin Tetracycline Sulfamethazine Erythromycin Virginiamycin Other products that have been associated with occupational illnesses include New- castle disease vaccine, contagious ecthyma vaccine, Jhone's disease bacterin, ES- clzetichia coli bacterins, and erysipelas vaccines. Newcastle disease and con- tagious ecthyma (orf) vaccines are live products used in chickens and sheep, respectively. Workers may contaminate their eyes with Newcastle vaccine as it is being applied inside poultry buildings via a nebulizer, resulting in a moderate conjunctivitis with influenza-like systemic symptoms. Orf vac- cine can cause the same pox-like lesions at the site of inoculation as a naturally ac- quired infection. Both of these diseases are self-limited and disability will only last for a few days, unless the orf lesions are numerous.41342 Injuries induced by the bacterins for Jhone's and E. Coli, and by most erysipelas vaccines are limited to the inflammatory response induced by the adjuvants. Control of these hazards again resides largely in "use practice standards," good animal handling techniques and facilities to prevent the uncontrolled and untimely movements of stressed animals." The use of pneumatic syringes, lock-on needle hubs, and multiple dose syringes will also help reduce injuries. Eye protection is indicated in many instan- ces. A full-face respirator is recommended while aerosolizing vaccines such as New- castle, but the other components of a full respirator program are rarely instituted. Antibiotics are products derived or syn- thesized from living organisms, mainly mold species of the genus streptowtyces. Antibiotics are used to treat infectious diseases therapeutically or to improve the rate of gain and feed efficiency in cattle, swine, and poultry. Again not only veterinarians but also live- stock producers and feed manufactures and formulators are exposed to these agents via aerosols of antibiotic-containing feeds within livestock buildings or via aerosols or direct contact while preparing feeds either on the farm or in feed manu- facturing plants. The two main occupa- tional hazards are allergic reactions and the development of antibiotic-resistant infections. The main products used as feed additives include penicillin, tetracycline, sul- famethazine, erythromycin, and vir- giniamycin. These same products plus many more are used therapeutically. Pen- icillin is the primary agent that may induce an allergic reaction manifest in the form of a skin reaction from direct contact, or 250 Papers and Proceedings