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

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APPENDIX C (continued) TRICHLORFON TOXICOLOGY OF NALED AND TRICHLORFON Trichlorfon, dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate, is an organophosphate with insecticidal activity. It is used on crops, ornamentals, forests, and turf. It is also used for pest control of structures. In 1990 in <strong>California</strong>, 12,000 pounds of trichlorfon were applied primarily on alfalfa (43%) and on landscape maintenance (28%) (DPR, 1991). Acute toxicity The rat oral LD 50 is approximately 250 mg/kg. The dermal LD 50 in rats is > 5000 mg/kg, and in rabbits is >2100 mg/kg. No neurotoxicity was observed in chickens given a single dose of trichlorfon up to 300 mg/kg subcutaneously, or up to 200 mg/kg by oral administration. Subchronic and chronic toxicity The Toxicology Summary (June 11, 1993) shows a data gap for a reproductive toxicity study in the rat; the study was considered upgradeable. No adverse effects were observed in the monkey chronic, mouse oncogenicity, and neurotoxicity studies. Developmental effects (primarily skeletal malformations) were observed at maternally toxic doses. In the rat chronic and oncogenicity study, rats exposed to trichlorfon in the diet for 2 years showed small intestine hyperplasia, chronic nephropathy, cysts and calcification in the kidney, increased serum cholesterol, and increased specific gravity in the urine. The NOEL was 92.2 ppm. The NOEL was 273 ppm for the inhibition of brain and plasma ChE activities. The oncogenicity data for dietary exposure in rats were considered equivocal. The interpretation of the increased incidence of mononuclear cell leukemia in female rats was complicated by low concurrent control incidence. Exposure of rats to trichlorfon in the diet during reproduction resulted in decreased parental body weight, decreased number of live pups/litter, reduced fertility, and lowered body weight gain of parents and pups, and the NOEL was 300 ppm. Genotoxicity Trichlorfon was mutagenic in the microbial assays with Salmonella strain TA100, Saccharomyces cerevisiae, E. coli (WP2 uvrA) and (WP2 hcr), and in mouse lymphoma cells. Chromosomal damage was observed in the sister chromatid exchange assay with Chinese Hamster bone marrow cells, human lymphocytes, and Chinese Hamster ovary cells. No adverse effects were observed in the mouse dominant lethal and unscheduled DNA synthesis assays.
APPENDIX D CALCULATION EQUATIONS 1. Dosage estimation for animals from an inhalation study (exposure level in ppm): mg/kgdaymg/m 3 ×respiration rate(m 3 hours exposed days exposed/week /kgday)× × ×AF 24 hours 7 days For this equation, 1 ug/L in air is equivalent to 1 mg/m 3 . The term for number of days exposed per week/7 days is used in the calculation only for studies when the animals were not dosed every day. The dosage was not corrected for absorption (absorption factor, AF). Only the dosages used in the calculation of MOS are corrected for 50% inhalation absorption rate. The default respiration rates used are: 0.46 m 3 /kg-day for children, 0.26 m 3 /kg-day for human adults, 0.96 m 3 /kg-day for rats, 0.54 m 3 /kg-day for rabbits, and 1.80 m 3 /kg-day for mice (Zielhuis and van der Kreek, 1979). For example: Using the NOEL of 1.25 ug/L from Thorpe et al. (1971b) where rabbits were exposed to <strong>DDVP</strong> daily, 1.25 mg × 0.54 m 3 m 3 kgday × 23 hours 24 hours 0.65 mg/kgday 2. Dosage estimation for animals in a dietary study (exposure level expressed as ppm in the diet): ug/kgday ppm (ug/g) xFR(g/day) x 1 body weight (kg) x days exposed/week 7days The food consumption rate (FR) is derived either from the reports or the standard default is used. The standard default is based on body weight, 15% for mouse, 5% for rat, and 3% for rabbit.
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DICHLORVOS (DDVP) RISK CHARACTERIZA
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transmitter of signals from the ner
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Contributors and Acknowledgments Pr
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List of Tables Pages 1. The acute t
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hematocrit) in rats. From studies w
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II. INTRODUCTION The human health r
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food service facilities); hand-held
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G. ENVIRONMENTAL FATE Summary: DDVP
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III. TOXICOLOGY PROFILE Pharmacokin
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Inhalation - Rat Carworth Farm stra
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DIMETHYL PHOSPHATE Oral - Rat Rats
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B. ACUTE TOXICITY Summary: The acut
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Oral - Human One hundred and eight
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Table 1. The acute toxicity of DDVP
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Table 1. The acute toxicity of DDVP
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Table 2. Selected no-observed-effec
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dose-related manner. At a dosage of
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pretreatment levels, respectively.
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Table 3. Selected no-observed-effec
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Gavage - Rat In a study conducted b
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ate (Appendix D) and the assumption
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Gavage - Mouse In a study conducted
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Capsules - Dog DDVP (97.3-99.5% pur
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Table 9. The no-observed-effect lev
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Mice exposed to DDVP by inhalation
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F. REPRODUCTIVE TOXICITY Summary: E
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Table 11. The dosages and the inhib
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G. DEVELOPMENTAL TOXICITY Summary:
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levels not verified, too few pregna
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H. NEUROTOXICITY Summary: Possible
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IV. RISK ASSESSMENT A. HAZARD IDENT
Page 63 and 64: Acute Toxicity Inhalation The criti
Page 65 and 66: ates were not statistically signifi
Page 67 and 68: In mice, there were dose-related in
Page 69 and 70: B. EXPOSURE ASSESSMENT The exposure
Page 71 and 72: The U.S. Department of Agriculture
Page 73 and 74: Acute Exposure Estimates of potenti
Page 75 and 76: Table 19. Commodity contribution of
Page 77 and 78: C. RISK CHARACTERIZATION The potent
Page 79 and 80: Table 23. The margins of safety for
Page 81 and 82: Table 25. The margins of safety of
Page 83 and 84: label between treatment and the ava
Page 85 and 86: VI. TOLERANCE ASSESSMENT A. BACKGRO
Page 87 and 88: VII. CONCLUSIONS The toxicological
Page 89 and 90: Bomhard, E., and M. Rinke, 1994. Fr
Page 91 and 92: DPR, 1992. Sampling for pesticide r
Page 93 and 94: Horn, K.-H., B. Teichmann, and T. S
Page 95 and 96: NTP (National Toxicology Program),
Page 97 and 98: TAS, 1992a. Exposure 4 . Detailed
Page 99 and 100: Warf Institute Inc., 1977c. Acute e
Page 101 and 102: APPENDIX A U.S. ENVIRONMENTAL PROTE
Page 103 and 104: APPENDIX B Department of Pesticide
Page 105 and 106: TABLE 2: Percent DDVP Dermal Absorp
Page 107 and 108: RESIDENT EXPOSURES Environmental mo
Page 109 and 110: post-treatment, respectively. Glove
Page 111 and 112: Ross, J.H., H.R. Fong, , T. Thongsi
Page 113: APPENDIX C NALED TOXICOLOGY OF NALE
Page 117 and 118: APPENDIX E ONCOGENICITY POTENCY CAL
Page 119: APPENDIX E (continued) ONCOGENICITY
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