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

4.3 Metabolism:found in tissues of rats exposed to 10 mg/m3 for 4 h[ours], or in blood ortissues exposed to 0.05 or 0.5 mg/m 3 for 14 days. Following intravenousinjection, little or no dichlorvos was found in rat liver, fat, testes or brain.Dichlorvos was detected in blood in only one of three rats at 10 and 30 minpostdose. Overall, the results indicated that dichlorvos was rapidlymetabolised in vivo.‖ (Originals not sighted; APVMA, 2008a)CalDRP (1996) reported:―After absorption, the primary site of metabolism was the liver, and themetabolism of DDVP was rapid. At 0.25 hour after treatment, the tissues(liver, kidneys, and blood) contained primarily hydrolysis products and lessthan 5% as DDVP. Radioactivity was also found in the bone which is likelydue to the deposition of phosphoric acid in the bone. Routes of excretion forDDVP were exhaled air, urine, and feces. After 24 hours, the percentage ofradioactivity in the exhaled air as CO 2 was 16%. Urinary metabolitesincluded desmethyl DDVP, mono- and dimethyl phosphates, inorganicphosphate, and dichloroethyl glucuronide. Over 80% of the radioactivity inthe urine collected 3 hours after treatment were mono- and dimethylphosphates. Only about 10% of the dose excreted in the feces was watersoluble DDVP derivatives. Other metabolites included inorganic phosphate,two-carbon fragments (glycine and serine), phosphate ions, and chlorideions.‖ (Originals not sighted; CalDPR, 1996)The APVMA (2008a) reported:―Hutson et al. (1971) investigated the metabolic fate of [ 14 C-vinyl]dichlorvos in rats following oral, inhalational and intraperitonealexposure. Respired air accounted for the greatest proportion of eliminated14 C and most was recovered within 24 hours following inhalationalexposure (head only). After 4 days, the highest tissue levels occurred in thecarcass and skin (~38 and 26%, respectively of the total amount of 14CO 2 ).Analysis of metabolites following oral dosing with [ 14 C-vinyl]-labelled or[ 36 Cl]-labelled dichlorvos detected free 36 Cl and at least 7 metabolites.Identified metabolites included hippuric acid (8.3%), desmethyl dichlorvos(10.9%) and dichloroethanol glucuronide (27%). The presence ofdichloroacetaldehyde could not be demonstrated. No parent compound wasidentified. The majority of 14 C in the livers from rats given a single oral doseof [ 14 C-vinyl]dichlorvos was detected in the protein fraction (as glycine andserine). Urinary metabolites detected following intraperitonealadministration of [ 14 C-vinyl]dichlorvos included hippuric acid anddesmethyl dichlorvos (2-5%) and dichloroethanol glucuronide (76%).Following inhalational exposure, identifiable urinary metabolites alsoincluded hippuric acid (9.3%) and desmethyl dichlorvos (4.3%), and urea(5.3%). No unchanged dichlorvos was found in the urine following dosingby either the oral or inhalational routes.‖ (Originals not sighted; APVMA,2008a)Dichlorvos reassessment – application Page 167 of 436