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

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No clinical signs were reported; however, Tyl et al. (1992) suggested that the signs could have been missed because rats were nocturnal animals and the consumption of DDVP in the water was highest at night. There were dose-related decreases in the plasma, erythrocyte, and brain ChE activities of all F 0 and F 1 adults, and the levels of inhibition at 20 and 80 ppm were statistically significant (p @ 0.05) (Table 11). The inhibition of ChE activity was greater in the females than in the males because the females were exposed to DDVP for a longer time (during gestation and lactation also) and their dosages were higher. The NOAEL for plasma, erythrocyte, and brain ChE inhibition was 5 ppm (0.5 mg/kg-day for the males and 1.1 mg/kg-day for the females). It should be noted that a LOEL of 5 ppm may be established for the inhibition of erythrocyte ChE activity of the F 0 females and F 1 both sexes as well as plasma ChE activity for the F 1 males. There was no evidence of pathological effects in the reproductive organs. The only significant effect observed in the pups was the reduction in the body weights of the 80 ppm F 1 pups on postnatal days 14 and 21. After weaning the F 2 a litters, the F 1 females were exposed to DDVP again and mated with untreated males for the F 2 b litters. There was a reduction (not statistically significant) of fertility at 80 ppm. The number of "abnormal" cycles in the 80 ppm F 1 females was significantly higher (68%) than in the controls (16%). The NOEL for reproductive toxicity and non-cholinergic endpoints was 20 ppm (2.7 mg/kg-day estimated from the premating dosage for females) based on the reduction of water consumption, body weight, fertility, and estrous cycling. This study was considered acceptable to DPR according to FIFRA guidelines. Inhalation - Mouse Crl:CD-1 mice (number of mice used not specified) were exposed to DDVP by inhalation during breeding (Casebolt et al., 1990). Resin strips (1 by 2.5 inch, 2 by 2.5 inch, and 4 by 2.5 inch) were placed in the food hopper 4 days prior to mating and continued throughout pregnancy. The air concentrations measured on day 1 were 1.9 ± 1.2, 3 ± 2.2, and 4.6 ± 2.0 mg/m 3 for the three sizes of strips, respectively, but were not maintained throughout the experiment. The estimated dosages for the three air concentrations of day 1 were 3.4, 5.7, and 8.3 mg/kg-day. There were no effects on the reproductive performances as determined by litter frequency and mean litter size. No clinical signs were observed. Plasma ChE activity of the treated dams were depressed on days 4 and 7, but not on day 14. The plasma ChE activity was maximally inhibited on day 4 to 10%, 7%, and 6% of control values for 1.9, 3, and 4.6 mg/m 3 groups, respectively. 45
Table 11. The dosages and the inhibition of cholinesterase activity in rats treated with DDVP a . Dosages mg/kg-day premating premating F 0 and F 1 F 0 and F 1 gestation lactation ppm males females females females 5.0 0.48-0.5 0.65-0.66 0.56-0.59 0.93-1.1 20.0 1.92-1.95 2.43-2.67 2.12-2.42 4.3-4.6 80.0 6.90-7.53 9.37-9.47 7.04-8.15 13.2-17.5 Cholinesterase inhibition F 0 generation ChE activity as % of Control b ppm mg/kg-day c Brain ChE Plasma ChE Erythrocyte ChE M F M F M F M F 5 0.5 1.1 99 94 96 88 93 77* 20 1.9 4.6 85* 74* 71* 45* 71* 61* 80 7.5 17.5 47* 41* 59* 17* 43* 40* F 1 generation ChE activity as % of Control b ppm mg/kg-day c Brain ChE Plasma ChE Erythrocyte ChE M F M F M F M F 5 0.5 1.1 101 98 85* 91 86* 83* 20 1.9 4.6 94* 68* 74* 46* 68* 58* 80 7.5 17.5 60* 40* 42* 19* 45* 42* a/ b/ c/ Data were from Tyl et al. (1992). Values are expressed as the mean % of control values. The values for female and males are presented as M or F, respectively. Statistical significance (*, p @ 0.05) was determined by the analysis of variance by ANOVA or Dunnett's test as reported. The dosages were based on the highest value of the range during premating for males, and during lactation for females. 46
Page 1 and 2: DICHLORVOS (DDVP) RISK CHARACTERIZA
Page 3 and 4: transmitter of signals from the ner
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: F. REPRODUCTIVE TOXICITY Summary: E
Page 55 and 56: G. DEVELOPMENTAL TOXICITY Summary:
Page 57 and 58: levels not verified, too few pregna
Page 59 and 60: H. NEUROTOXICITY Summary: Possible
Page 61 and 62: 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 and 114:
APPENDIX C NALED TOXICOLOGY OF NALE
Page 115 and 116:
APPENDIX D CALCULATION EQUATIONS 1.
Page 117 and 118:
APPENDIX E ONCOGENICITY POTENCY CAL
Page 119:
APPENDIX E (continued) ONCOGENICITY
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