Dichlorvos (DDVP) Risk Characterization Document - California ...
Dichlorvos (DDVP) Risk Characterization Document - California ... Dichlorvos (DDVP) Risk Characterization Document - California ...
Direct applications of DDVP ( 32 P, 67-78% purity) to cotton seedlings showed that 50% of the dose volatilized within the first 5 minutes (Casida et al., 1962). The half-life of DDVP in the seedling was 1.2 hours, and DDVP was metabolized by hydrolysis. In an absorption study with peas, cotton, and corn seedlings, DDVP was transported into the plants and subsequently hydrolyzed. The hydrolysis rates follow first order kinetics with half-lives of 3, 9, and 9 hours, respectively for the three plants studied. DDVP, used as a fogger in greenhouses, was released as a 10% aerosol (1 gram DDVP/1000 ft 3 ) in greenhouses with tomatoes, lettuce, cucumbers, and radishes (Beroza and Hill, 1968). Air samples showed that DDVP concentrations decreased rapidly. Within 15 minutes, the air concentration decreased from the initial 35 ug/L to 1.5 ug/L. After 135 minutes, the average air level was 0.12 ug/L. Samples for each vegetable were collected after the release of DDVP into the air. The highest residue for tomatoes was 0.023 ppm after 88 hours, for lettuce was 0.026 ppm after 160 hours, for cucumbers was 0.055 ppm after 160 hours, and for radishes was 0.003 ppm (MDL= 0.003 ppm). Because of the limited number of samples analyzed per time period after application and because the levels were similar, all the residue values for each commodity were averaged, and the results from this study were used for the dietary exposure assessment. 9
III. TOXICOLOGY PROFILE Pharmacokinetics and toxicological studies of DDVP are summarized in this section. Studies involving cattle and other farm animals are included since DDVP is used directly on livestock. Acceptability of the studies (except for genotoxicity studies) where noted, is determined by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) guidelines. The acceptability of the genotoxicity studies by the Department of Pesticide Regulation (DPR) is based on the Toxic Substances Control Act guidelines (Federal Register, 1985 and 1987). The toxicology summary for studies reviewed for SB 950, The Birth Defect Prevention Act of 1984, is available upon request to the Registration Branch. DDVP is also the metabolite of the pesticides naled and trichlorfon. A summary of the toxicology of naled and trichlorfon is presented in Appendix C. The animal inhalation toxicity studies reviewed in this document were conducted with whole-body exposure (except where noted). Therefore, the internal dose under these exposure conditions may be higher than that calculated based on the air concentration. Additional exposure to DDVP by oral ingestion due to licking of the fur, dermal absorption, and contamination of food and water are possible. Blair et al. (1976) estimated that the retained dose by all routes was 2 times that for noseonly inhalation exposure. However, the estimate could not be verified because data were not presented in the report. Equations in Appendix D are used for the conversion of nominal concentrations in the inhalation studies and diet studies to "adjusted dosages" by accounting for respiration and dosing regimen such that the dosages are expressed in mg/kg-day units and averaged for 24 hours and 7 days of exposure. An example of the calculation is also provided in Appendix D. The dosages listed in the summary tables (Tables 2, 3, 9, 12, and 13) are adjusted dosages to allow comparisons of the noobserved-effect levels (NOELs) and lowest-observed-effect levels (LOELs) between studies. A. PHARMACOKINETICS Summary: DDVP was rapidly absorbed by the oral, intravenous, intraperitoneal, and inhalation routes and slowly absorbed by the dermal route. After absorption, radioactivity distributed to major organs including the liver and kidneys. DDVP was metabolized completely by ester hydrolysis and demethylation. Initial metabolites were mono- and dimethyl- phosphates, and desmethyl DDVP. Once formed, they may be further metabolized with final metabolites either incorporated into tissues or excreted. Major routes of excretion were in the urine and in the exhaled air, while to a lesser extent in the feces and milk. Excretion routes, tissue distribution, and urinary metabolites in rats were similar following inhalation or oral exposures to DDVP. The biotransformation pathways of DDVP in rats are presented in Figure 1. DDVP Oral - Rat DDVP ( 14 C- and 32 P-labelled, 10 mg/kg, 78 and 67-78% purity, respectively) was rapidly absorbed following gavage administration to albino rats (strain not specified) (Casida et al., 1962). After absorption, the primary site of metabolism was the liver, and the metabolism of DDVP was rapid. At 0.25 hour after treatment, the tissues (liver, kidneys, and blood) contained primarily hydrolysis products and less than 5% as DDVP. Radioactivity was also found in the bone which is likely due to the deposition of phosphoric acid in the bone. Routes of excretion for DDVP were exhaled air, urine, and feces. After 24 hours, the percentage of radioactivity in the exhaled air as CO 2 was 16%. Urinary metabolites included desmethyl DDVP, mono- and dimethyl phosphates, inorganic phosphate, and dichloroethyl glucuronide. Over 80% of the radioactivity in the urine collected 3 hours after treatment were mono- and dimethyl phosphates. Only about 10% of the dose excreted in the feces was water- 10
- Page 1 and 2: DICHLORVOS (DDVP) RISK CHARACTERIZA
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- Page 21 and 22: DIMETHYL PHOSPHATE Oral - Rat Rats
- Page 23 and 24: B. ACUTE TOXICITY Summary: The acut
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- 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.
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- Page 41 and 42: ate (Appendix D) and the assumption
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- 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
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- Page 61 and 62: IV. RISK ASSESSMENT A. HAZARD IDENT
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Direct applications of <strong>DDVP</strong> ( 32 P, 67-78% purity) to cotton seedlings showed that 50% of the dose<br />
volatilized within the first 5 minutes (Casida et al., 1962). The half-life of <strong>DDVP</strong> in the seedling was<br />
1.2 hours, and <strong>DDVP</strong> was metabolized by hydrolysis. In an absorption study with peas, cotton, and<br />
corn seedlings, <strong>DDVP</strong> was transported into the plants and subsequently hydrolyzed. The hydrolysis<br />
rates follow first order kinetics with half-lives of 3, 9, and 9 hours, respectively for the three plants<br />
studied.<br />
<strong>DDVP</strong>, used as a fogger in greenhouses, was released as a 10% aerosol (1 gram <strong>DDVP</strong>/1000 ft 3 ) in<br />
greenhouses with tomatoes, lettuce, cucumbers, and radishes (Beroza and Hill, 1968). Air samples<br />
showed that <strong>DDVP</strong> concentrations decreased rapidly. Within 15 minutes, the air concentration<br />
decreased from the initial 35 ug/L to 1.5 ug/L. After 135 minutes, the average air level was 0.12 ug/L.<br />
Samples for each vegetable were collected after the release of <strong>DDVP</strong> into the air. The highest<br />
residue for tomatoes was 0.023 ppm after 88 hours, for lettuce was 0.026 ppm after 160 hours, for<br />
cucumbers was 0.055 ppm after 160 hours, and for radishes was 0.003 ppm (MDL= 0.003 ppm).<br />
Because of the limited number of samples analyzed per time period after application and because the<br />
levels were similar, all the residue values for each commodity were averaged, and the results from<br />
this study were used for the dietary exposure assessment.<br />
9
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