Dichlorvos (DDVP) Risk Characterization Document - California ...

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Executive Summary INTRODUCTION This Risk Characterization Document for dichlorvos (DDVP) addresses potential human exposures from its use in California. Oncogenic, genotoxic, and neurotoxic effects have been identified in animal studies. DDVP is listed under California Proposition 65, the Safe Drinking Water and Toxic Enforcement Act of 1986, as a chemical known to the State of California to cause cancer. DDVP is an insecticide used for space spray treatment of food processing, handling, and storage plants; feedlots; stockyards; corrals; holding pens; animal buildings; poultry houses; as well as residential, commercial and institutional buildings. It is also used in flea collars for pets. The direct food uses are on vegetables grown in greenhouses, on livestock, and processed food items to control pests. Humans may be exposed to DDVP through inhalation, direct contact on the skin, and the diet. THE RISK ASSESSMENT PROCESS The risk assessment process consists of four aspects: hazard identification, dose response assessment, exposure evaluation, and risk characterization. Hazard identification entails review and evaluation of the toxicological properties of each pesticide. The dose-response assessment then considers the toxicological properties and estimates the amount which could potentially cause an adverse effect. The amount which will not result in an observable or measurable effect is the no-observed-effect level, NOEL. A basic premise of toxicology is that at a high enough dose, virtually all substances will cause some toxic manifestation. Chemicals are often referred to as "dangerous" or "safe", as though these concepts were absolutes. In reality, these terms describe chemicals which require low or high dosages, respectively, to cause toxic effects. Toxicological activity is determined in a battery of experimental studies which define the types of toxic effects which can be caused, and the exposure levels (doses) at which effects may be seen. State and federal testing requirements mandate that substances be tested in laboratory animals at doses high enough to produce toxic effects, even if such levels are many times higher than those to which people might be exposed. The exposure assessment includes an estimation of the potential exposure through the occupational, residential, and dietary routes on an acute (one time) and chronic (long-term and lifetime) basis. The levels of exposure are determined by the amount of pesticide residue in the air or on specific commodities and processed foods, and the exposure rates by inhalation or ingestion. The risk characterization integrates the toxic effects observed in the laboratory studies, conducted with high dosages of pesticide, to potential human exposures to low dosages of pesticide residues in the air and diet. The potential for possible non-cancer adverse health effects in human population after acute and chronic exposures (long-term and lifetime) is generally expressed as the margin of safety, which is the ratio of the dosage which produced no effects in laboratory studies to the estimated exposure dosage. For cancer effects after potential lifetime exposures, the probability of risk is calculated as the product of the cancer potency of the pesticide and the estimated exposure dosage. BACKGROUND INFORMATION DDVP is currently in Special Review, a process by the U.S. Environmental Protection Agency (USEPA) to determine the risk and benefit for the use of the pesticide. The major concerns are the inhibition of cholinesterase (ChE) activity, cancer, and nerve damage effects observed in animal studies. Cholinesterase is an essential enzyme in the body for the degradation of acetylcholine, a i
transmitter of signals from the nerve to another nerve or muscles. The inhibition of ChE results in cholinergic signs such as salivation, diarrhea, tremors, respiratory failure, and death due to the accumulation of acetylcholine and over-stimulation of nerves or muscles. USEPA has proposed the revocation of DDVP tolerances for processed commodities because of concerns on DDVP-induced cancer in experimental animals. TOXICOLOGY Cholinergic signs (tremors and diarrhea) and death in experimental animals were the most sensitive endpoints for the acute toxicity of DDVP after inhalation and oral exposures. The dose (the noobserved-effect level or NOEL) at which death and cholinergic signs did not occur was used to quantitate the hazard for potential one-time exposure to humans. The long-term (chronic) health hazard to humans from repeated exposures to DDVP was evaluated based on the inhibition of cholinesterase activity in the brain observed in both inhalation and oral studies. The cancer risk from lifetime exposure was evaluated based on the finding of leukemia in rats after chronic oral exposure. EXPOSURE ANALYSIS The potential exposure scenarios of humans to DDVP include the work place, home, and the food. Workers are exposed to DDVP in the work place due to warehouse fumigation, livestock applications, and structural applications. The general population is exposed to DDVP in the home from the uses as directed spray, fogger, flea collars, and no-pest strips; as well as in the diet from the use of DDVP on vegetables, livestock, and processed foods. The worker exposure was also assessed in combination with exposure at home (from home use and in the diet). RISK EVALUATION A margin of safety (MOS) of at least 100 is generally considered sufficient to be protective of human health. The following exposure groups have MOSs greater than 100: chronic exposure of residents after structural fumigation; acute and chronic exposures of pet owners to flea collars; acute dietary exposure of all population subgroups; and chronic dietary exposure of all subgroups, except children 1 to 6 years old. The following exposure groups have MOSs less than 100 for non-oncogenic effects: acute, chronic, and lifetime exposures for all workers exposed to DDVP only at work and in combination with exposure at home; acute exposure of residents after structural fumigation; acute, chronic, and lifetime exposures of residents to home-use foggers; acute and chronic exposures of children to no-pest strips; and chronic dietary exposure of children 1 to 6 years old. For oncogenic effects, the excess lifetime oncogenic risks of the workers, residents, and the general population exposed to DDVP at work, at home, or in the diet and in combinations were greater than the benchmark oncogenic risk level of 1 x 10 -6 which is generally considered protective of human health. The MOSs for the acute exposure to DDVP on vegetables and livestock products at tolerance levels are greater than 100. ii
Page 1: DICHLORVOS (DDVP) RISK CHARACTERIZA
Page 5 and 6: Contributors and Acknowledgments Pr
Page 7 and 8: List of Tables Pages 1. The acute t
Page 9 and 10: hematocrit) in rats. From studies w
Page 11 and 12: II. INTRODUCTION The human health r
Page 13 and 14: food service facilities); hand-held
Page 15 and 16: G. ENVIRONMENTAL FATE Summary: DDVP
Page 17 and 18: III. TOXICOLOGY PROFILE Pharmacokin
Page 19 and 20: Inhalation - Rat Carworth Farm stra
Page 21 and 22: DIMETHYL PHOSPHATE Oral - Rat Rats
Page 23 and 24: B. ACUTE TOXICITY Summary: The acut
Page 25 and 26: Oral - Human One hundred and eight
Page 27 and 28: Table 1. The acute toxicity of DDVP
Page 29 and 30: Table 1. The acute toxicity of DDVP
Page 31 and 32: Table 2. Selected no-observed-effec
Page 33 and 34: dose-related manner. At a dosage of
Page 35 and 36: pretreatment levels, respectively.
Page 37 and 38: Table 3. Selected no-observed-effec
Page 39 and 40: Gavage - Rat In a study conducted b
Page 41 and 42: ate (Appendix D) and the assumption
Page 43 and 44: Gavage - Mouse In a study conducted
Page 45 and 46: Capsules - Dog DDVP (97.3-99.5% pur
Page 47 and 48: Table 9. The no-observed-effect lev
Page 49 and 50: Mice exposed to DDVP by inhalation
Page 51 and 52: F. REPRODUCTIVE TOXICITY Summary: E
Page 53 and 54:
Table 11. The dosages and the inhib
Page 55 and 56:
G. DEVELOPMENTAL TOXICITY Summary:
Page 57 and 58:
levels not verified, too few pregna
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H. NEUROTOXICITY Summary: Possible
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IV. RISK ASSESSMENT A. HAZARD IDENT
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Acute Toxicity Inhalation The criti
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ates were not statistically signifi
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In mice, there were dose-related in
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B. EXPOSURE ASSESSMENT The exposure
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The U.S. Department of Agriculture
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Acute Exposure Estimates of potenti
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Table 19. Commodity contribution of
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C. RISK CHARACTERIZATION The potent
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Table 23. The margins of safety for
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Table 25. The margins of safety of
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label between treatment and the ava
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VI. TOLERANCE ASSESSMENT A. BACKGRO
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VII. CONCLUSIONS The toxicological
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Bomhard, E., and M. Rinke, 1994. Fr
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DPR, 1992. Sampling for pesticide r
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Horn, K.-H., B. Teichmann, and T. S
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NTP (National Toxicology Program),
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TAS, 1992a. Exposure 4 . Detailed
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Warf Institute Inc., 1977c. Acute e
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APPENDIX A U.S. ENVIRONMENTAL PROTE
Page 103 and 104:
APPENDIX B Department of Pesticide
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TABLE 2: Percent DDVP Dermal Absorp
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RESIDENT EXPOSURES Environmental mo
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post-treatment, respectively. Glove
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Ross, J.H., H.R. Fong, , T. Thongsi
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APPENDIX C NALED TOXICOLOGY OF NALE
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APPENDIX D CALCULATION EQUATIONS 1.
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APPENDIX E ONCOGENICITY POTENCY CAL
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APPENDIX E (continued) ONCOGENICITY
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