1. Pesticide Illness Part 4 Chronic Health Effects Laws and Regulations Prepared by: Rupali Das, MD, MPH, California Department of Health Services, Michael O’Malley, MD, MPH, University of California, Davis, Laura Styles, MPH, Public Health Institute

2. 2 Pesticides Chronic Health Effects  Respiratory (asthma)  Neurological  Reproductive and Developmental  Carcinogenic

3. 3 Chronic Toxicity of Pesticides Chronic Toxicity of Pesticides  Types of chronic effects –Cumulative effects of low level exposures –Persistent effects of acute exposure  Individual evaluations –Epidemiologic studies –Specific associations –Classification of reproductive, cancer toxicity

4. 4 Chronic Effect Studies: Design & Interpretation  Pre-exposure information absent  Exposure difficult to measure  Selection of control groups important  Multiple, variable compounds  Confounders, unknown exposures

5. 5 Pesticides and Asthma, Children  Increase in pediatric asthma  Suspected factors –Air pollution –Genetics –Hygiene hypothesis –Chemicals, including pesticides

6. 6 Pesticides and Asthma, Adults  Farmer occupation –Canada (Hoppin et al. 2002) –US (Senthilselvan et al. 1992)  Case reports –Pyrethrin, tetramethrin, allethrin, chlorothalonil, fluazinam

7. 7 Chronic Neurologic Effects of Pesticides Organophosphates Increased vibration sense; Motor, sensor neuropathy; Cognitive, affective deficits Methyl bromide, sulfuryl fluoride Olfactory, cognitive, behavioral deficits Paraquat, others Parkinson’s Disease?

8. 8 Case Subway Rider Exposed to Sarin  35 year-old man exposed to sarin with severe dyspnea, convulsions  Comatose, slightly cyanotic; miosis; profuse muscarinic symptoms Source: EHP/NIEHS

9. 9 Subway Rider Exposed to Sarin Neurobehavioral Status at 6 months  Test results –No global intellectual impairment –Performance impairments –Retrograde amnesia –Passivity and shallow affect  Mild neurobehavioral dysfunction

10. 10 MPTP MPP + Paraquat Parkinson’s Disease Association with Paraquat

11. 11 Parkinson’s Disease Pesticide Theory  Direct toxins –Neurotoxins  Dieldrin, rotenone –Mitochondrial toxins  Chlordane, paraquat, permethrin  Modulators of metabolism –DDT, organophosphates, pyrethrins

12. 12 Parkinson’s Disease Postulated Causes  20% family history  Environmental associations –Farmer occupation –Any occupational pesticide exposure –Living on a farm  Pesticides –Initiator, promoter, or effect modifier?

13. 13  Endpoints –Reproductive –Developmental  Exposure –Maternal –Paternal Reproductive & Developmental Effects of Pesticide Exposure

14. 14 Reproductive & Developmental Effects Maternal Exposure  Agricultural exposure –Spontaneous abortions & fetal death –Congenital malformations  Greenhouse workers –Reduced fecundability –Excess stillbirths

15. 15 Reproductive & Developmental Effects Paternal Exposure  Documented –Azospermia, Oligospermia  Dibromochloropropane (DBCP)  Suggested –Reduced sex ratio (M/F) –Spontaneous abortion, preterm delivery

16. 16  Occupation surrogate for exposure  Poor exposure assessment  Exposure usually to multiple pesticides  Timing of exposure uncertain  Control for other toxins may be poor Reproductive & Developmental Effects Methodological Problems

17. 17 34 year-old woman with spontaneous abortion at 17 weeks gestation Smokes ½ pack/day; occasional home pesticide use; 2 healthy children Fetal pathology: one stub for leg, shortened umbilical cord, no genitals. Case W oman with Spontaneous Abortion

18. 18 Woman with Spontaneous Abortion Occupational History  Seasonal worker in seed-retailing  Became pregnant one month after starting work.  Husband is a postal worker

19. 19 Woman with Spontaneous Abortion Maternal Exposure History  Occupational –Captan: animal teratogen –Carboxin: growth suppression, high doses –Chlorpyrifos: no evidence –Methoxychlor: teratogen; estrogenic –Thiram: reduced growth at high doses  Home –Permethrin: reduced fertility, high doses

20. 20 Pesticides and Cancer  Animal data –High dose laboratory studies  Human data –Epidemiological studies

21. 21 Postulated Mechanisms of Pesticide Carcinogenicity Mechanism Pesticide Examples Genotoxicity Captan, DBCP Tumor promotion Organochlorines Hormonal action Atrazine, ziram Immunotoxicity Aldicarb, 2,4-D Peroxisome proliferation 2,4-D, 2,4,5-T

22. 22  Insecticides: dichlorvos, organochlorines  Herbicides: amitrole, cyanazine  Fumigants: ethylene oxide, formaldehyde  Fungicides: captan, maneb, zineb  Growth regulators: daminozide Pesticide Animal Carcinogens

23. 23 Pesticides & Cancer in Farmers  Low mortality due to other causes  Elevated risks for cancer  Most studies on male farmers  Limited data on specific exposures  Other hazards

24. 24 Pesticides and Cancer Associations: Human Epidemiologic Studies  Lindane: Lymphoma  Dichlorvos, methoxyclor: Leukemia  2,4-D, diazinon: Non-Hodgkin’s lymphoma  Atrazine: Ovarian  Arsenicals: Lung, skin

25. 25 Pesticides Associated with Cancer: Organophospates, Carbamates  Non-Hodgkin’s lymphoma –Organophosphates –Carbamates  Lung cancer  Leukemia

26. 26 Pesticides Associated with Cancer: Chlorophenoxy Herbicides  Non-Hodgkin’s lymphoma –Farmers, gardeners  Soft tissue sarcoma

27. 27 Pesticides and Childhood Cancer  Malignancies linked to pesticides –Leukemia –Brain cancer –Non-Hodgkin’s lymphoma –Wilm’s tumor –Ewing’s sarcoma

28. 28 Pesticides and Childhood Cancer Childhood Pesticide Exposure  Widespread home pesticide use  Pet products, insecticidal shampoos  Vertical concentration gradient  Deposit on toys, furniture

29. 29 Pesticides and Childhood Cancer Risk Factors  Parental home/garden pesticide use  Parental occupational exposure  Prenatal exposure Source: USDA

30. 30 Human Pesticide Cancer Studies: Methodological Issues  Case definition may not be precise  Recall bias  Small samples  Crude exposure assessment  Timing of exposure cannot be confirmed  Genetic-environmental interactions

31. 31 Summary Chronic Pesticide Illness  Risks depend on pesticide –Neurological disease: Organophosphates –Cancer: Chlorophenoxy herbicides –Reproductive toxicity: Methyl bromide  Preventing illness –Targeted use reduction –Worker protection –Reduced home use

32. 32 Pesticide Laws and Regulations  Federal –Federal Insecticide, Fungicide, and Rodenticide Act (1972) –Federal Food, Drug, and Cosmetic Act (1939) –Worker Protection Standard (1992) –Food Quality Protection Act (1996)  State laws vary

33. 33 Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)  Control of distribution, sale, use  Gives US EPA authority to –Study pesticide consequences –Require pesticide purchase registration  Requires –Pesticide applicator certification –Registration, proper labeling

34. 34 Federal Food, Drug, and Cosmetic Act (FFDCA)  Allows US EPA to establish tolerances for pesticides in food  Small fraction of marketed food tested for pesticide residue

35. 35 Worker Protection Standard  Reduce farmworker pesticide illness  Hazard training and communication, decontamination facilities, notification, emergency medical care

36. 36 Food Quality Protection Act (FQPA)  Health-based standard for pesticides in foods  Requires US EPA to review tolerances for pesticide tolerances in food  Focus on children

37. 37