Application for the Reassessment of a Hazardous Substance under ...

4.4 Elimination:CalDRP (1996) reported:―Rats (strain not specified) were given DDVP ( 14 C and 36 Cl, purity notspecified; 0.99 mg/male rat and 0.72 mg/female rat) by gavage (Hutson etal., 1971). Urine, feces, and exhaled air were collected every day for 4 days.Radioactivity in tissues was also determined. Additional female rats wereused for the determination of metabolites in the urine and the liver. Therewas no difference in the excretion patterns between sexes. After 4 days(daily result not given), the percentages of administered doses in the urine,feces, and exhaled air were 12.8-18.2%, 3.4-4.8%, 36.8-38.8%, respectively.The identified urinary metabolites included hippuric acid (8.3% of totalurinary radioactivity), desmethyl-DDVP (10.9%), and 2,2-dichloroethyl-Bd-glucopyranosiduronicacid (27%), while no unmetabolized DDVP,dichloroacetaldehyde or dichloroacetic acid was found. Of the tissuesexamined, the highest level of radioactivity (4.4-5.0% of dose) was in theliver. Analysis of the liver tissue showed that 75% of the radioactivity wasassociated with glycine, serine, and cystine in the protein hydrolysatefraction.‖ (Originals not sighted; CalDPR, 1996)The APVMA (2008a) reported:―In a series of experiments, [ 14 C-vinyl]dichlorvos was given by gavage tomale and female mice (0.2 mg, approximately 8 mg/kg bw), and Syrianhamsters (0.22-0.56 mg, approximately 4 mg/kg bw), and to 1 man orally (5mg in 100 mL orange juice, approximately 70 μg/kg bw) and another byinhalation (38 mg/m3 unlabelled dichlorvos for 105 min). Elimination ratesand urinary excretion were compared with results obtained from a secondexperiment using rats. Overall, the data indicated that the rates and routes ofelimination were largely similar (predominantly air and urine) in all speciesand there was no marked sex difference in laboratory animals. Followingoral dosing of mice and rats with [ 14 C-methoxy]dichlorvos, the majorurinary metabolite was dimethyl phosphate (~70% of urinary radioactivityand 40% of the dose). Desmethyl dichlorvos constituted 4% of total urinaryradioactivity in rats and 28% in mice. Minor metabolites present at less than2% of total urinary radioactivity were S-methyl-L-cysteine (both species),S-methyl-L-cysteine oxide and methylmercapturic acid (mouse only), andmethylmercapturic acid S-oxide (rat only). Two other minorchromatographic peaks could not be identified. Following oral dosing with[ 14 Cvinyl] dichlorvos hippuric acid, desmethyl dichlorvos and urea weredetected in the urine of mice and the man, with only hippuric acid measuredin hamsters. A dichloroethanol conjugate in the urine of the man exposed todichlorvos by inhalation was detectable but not quantifiable because ofinterference from endogenous peaks. (Hutson and Hoadly 1972a & b)‖(Originals not sighted; APVMA, 2008a)―Cheng (1989 & 1991) examined the metabolism and tissue distribution of[vinyl-1- 14 C] dimethyl dichlorovinylphosphate ( 14 C-dichlorvos) in rats. Fiverats/sex/group were administered 14 C-dichlorvos as a single intravenousDichlorvos reassessment – application Page 168 of 436