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

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Table of Contents Pages List of Tables ................................................................. vi I. Summary .................................................................... 1 II. Introduction ................................................................. 4 A. Chemical Identification . ..................................................... 4 B. Regulatory History . ........................................................ 5 C. Technical and Product Formulations ........................................... 6 D. Usage ................................................................... 6 E. Illness Reports ............................................................ 6 F. Physical and Chemical Properties . ............................................ 7 G. Environmental Fate ......................................................... 8 III. Toxicology Profile . ........................................................... 10 A. Pharmacokinetics . ........................................................ 10 B. Acute Toxicity . ........................................................... 16 C. Subchronic Toxicity ........................................................ 25 D. Chronic Toxicity and Oncogenicity . ........................................... 31 E. Genotoxicity . ............................................................ 41 F. Reproductive Toxicity . ..................................................... 44 G. Developmental Toxicity. .................................................... 48 H. Neurotoxicity . ............................................................ 52 I. Immunotoxicity ........................................................... 53 IV. Risk Assessment . ........................................................... 54 A. Hazard Identification . ...................................................... 54 B. Exposure Assessment . .................................................... 62 C. Risk Characterization . ..................................................... 70 V. Risk Appraisal . .............................................................. 75 VI. Tolerance Assessment . ....................................................... 78 VII. Conclusions . ............................................................... 80 VIII. References . ................................................................ 81 IX. Appendices . ................................................................ 93 A. U.S. Environmental Protection Agency Tolerances for DDVP B. Occupational Exposure Assessment C. Toxicology of Naled and Trichlorfon D. Calculation Equations E. Oncogenicity Potency Calculations v
List of Tables Pages 1. The acute toxicity of DDVP . ........................................................ 20 2. Selected NOELs and LOELs of DDVP for sublethal acute effects from acute studies . .......... 24 3. Selected NOELs and LOELs of DDVP from subchronic studies. ............................ 30 4. The incidences of tumors in rats treated with DDVP by gavage for 2 years . .................. 32 5. The mean body weights of rats treated with DDVP by inhalation for 2 years. .................. 35 6. Brain cholinesterase inhibition in rats treated with DDVP by inhalation for 2 years . ............. 35 7. The incidences of forestomach tumors in mice treated with DDVP by gavage for 2 years . ....... 37 8. Clinical signs and brain cholinesterase inhibition in dogs treated with DDVP in capsules for 1 year . 39 9. The NOELs and LOELs of DDVP from chronic studies. ................................... 40 10. Selected genotoxicity studies of DDVP . .............................................. 43 11. The dosages and the inhibition of cholinesterase activity in rats treated with DDVP ............ 46 12. Selected NOELs and LOELs of DDVP from reproductive toxicity studies. ................... 47 13. Selected NOELs and LOELs of DDVP from developmental toxicity studies. .................. 51 14. Comparison of brain cholinesterase inhibition under different durations of exposure. .......... 55 15. The maximum likelihood estimates and 95% upper confidence limit for tumors in rodents exposed to DDVP ............................................................ 61 16. Estimated occupational and residential exposures to DDVP . ............................. 62 17. DDVP residue database .......................................................... 65 18. Potential acute and chronic dietary exposures to DDVP ................................. 67 19. Commodity contribution of chronic dietary exposure to DDVP............................. 68 20. Potential acute combined occupational and residential exposures to DDVP .69 21. Potential chronic combined occupational and residential exposures to DDVP . ............... 69 22. The definitive NOELs and potency factors for risk characterization ......................... 70 23. The margins of safety for potential acute and chronic occupational and residential exposures to DDVP . .................................................................... 72 24. The margins of safety for potential acute and chronic dietary exposures to DDVP ............. 73 25. The margins of safety for potential acute and chronic combined occupational and residential exposures to DDVP . ......................................................... 74 vi
Page 1 and 2: DICHLORVOS (DDVP) RISK CHARACTERIZA
Page 3 and 4: transmitter of signals from the ner
Page 5: Contributors and Acknowledgments Pr
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
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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