Dichlorvos (DDVP) Risk Characterization Document - California ...
Dichlorvos (DDVP) Risk Characterization Document - California ... Dichlorvos (DDVP) Risk Characterization Document - California ...
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:
Table of Contents<br />
Pages<br />
List of Tables ................................................................. vi<br />
I. Summary .................................................................... 1<br />
II. Introduction ................................................................. 4<br />
A. Chemical Identification . ..................................................... 4<br />
B. Regulatory History . ........................................................ 5<br />
C. Technical and Product Formulations ........................................... 6<br />
D. Usage ................................................................... 6<br />
E. Illness Reports ............................................................ 6<br />
F. Physical and Chemical Properties . ............................................ 7<br />
G. Environmental Fate ......................................................... 8<br />
III. Toxicology Profile . ........................................................... 10<br />
A. Pharmacokinetics . ........................................................ 10<br />
B. Acute Toxicity . ........................................................... 16<br />
C. Subchronic Toxicity ........................................................ 25<br />
D. Chronic Toxicity and Oncogenicity . ........................................... 31<br />
E. Genotoxicity . ............................................................ 41<br />
F. Reproductive Toxicity . ..................................................... 44<br />
G. Developmental Toxicity. .................................................... 48<br />
H. Neurotoxicity . ............................................................ 52<br />
I. Immunotoxicity ........................................................... 53<br />
IV. <strong>Risk</strong> Assessment . ........................................................... 54<br />
A. Hazard Identification . ...................................................... 54<br />
B. Exposure Assessment . .................................................... 62<br />
C. <strong>Risk</strong> <strong>Characterization</strong> . ..................................................... 70<br />
V. <strong>Risk</strong> Appraisal . .............................................................. 75<br />
VI. Tolerance Assessment . ....................................................... 78<br />
VII. Conclusions . ............................................................... 80<br />
VIII. References . ................................................................ 81<br />
IX. Appendices . ................................................................ 93<br />
A. U.S. Environmental Protection Agency Tolerances for <strong>DDVP</strong><br />
B. Occupational Exposure Assessment<br />
C. Toxicology of Naled and Trichlorfon<br />
D. Calculation Equations<br />
E. Oncogenicity Potency Calculations<br />
v
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