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

measured and it was not possible to determine the inhaled dose from the datapresented. Animals were supplied with food but not water and were removed fromthe chambers for 1 h[our]/day when water was supplied. Incoming and exhaust airwas monitored for dichlorvos by measuring total phosphorus. All animals in alltrials exposed to dichlorvos in the air died, with symptoms including slowlaboured respiration, sialorrhoea and paleness of ears and feet. Under the mostsevere exposure, these signs appeared within 2 h[ours], with average survival time6.9 and 10.1 h[ours] in males and females respectively.―Kimmerle G (1966) Letter re. DDVP (Lo-No. 271) inhalation study. Bayer AGInstitute of Toxicology, 56 Wuppertal-Elberfeld. Ref. Dr.Ki/Sp dated 7thDecember 1966.―A single-page note reported on the LC 50 of dichlorvos in male rats (the sourceand purity of dichlorvos and strain of rat were not provided). Groups of 20animals were exposed to analysed dichlorvos aerosol concentrations of 0.209-1.244 mg/L for 1 h[our], or 0.063-0.544 g/L for 4 h[ours]. In addition, 2 groups ofrats received (theoretical) 0.049 or 0.109 mg/L for 4 h[ours]/d[ay] for 5consecutive days. The 1-h[our] LC 50 was 0.455 mg/L (455 mg/m3), and the 4-h[our] LC 50 was 0.340 mg/L (340 mg/m3). Adverse signs were observed in 3/20rats at 0.319 mg/L and in most animals exposed to 0.479 mg/L or more for 1 h,and in all animals exposed to 0.082 mg/L or more for 4 h[ours]. There were noclinical signs and no animals died in the repeat-dose section of the study.―Macdonald R (1982) Toxicology of consumer products: the acute (4 h)inhalation toxicology of dichlorvos in rats and mice. Document No SBGR.82.145.Lab: Shell Research Ltd, Sittingbourne, UK. Sponsor: Temana. Report date:March 1982 QA study.―Groups of 10 animals (5/sex, CF1 mice and Wistar rats, both from Shell'sTunstall Laboratory) were subjected to head-only exposure to vapour containingdichlorvos (Windmill Plastics Ltd; batch No. ST82/016; 97.8% purity) for 4h[ours]. Observations on health and behaviour were made during and for 14 daysafter exposure. All mice exposed to 218 mg/m 3 (the only dose tested) survived.Adverse signs were body tremors and lethargy, with 3 mice displaying hind limbparesis and all showing splayed gaits. The clinical signs reversed by the secondday. In male rats, 3/10 animals exposed to 250 mg/m 3 (saturated air) died while all10 animals exposed to 210 mg/m 3 died. Subsequent exposure to 142 and 85mg/m 3 resulted in one male death at the lowest concentration. Two furtherexperiments were performed, using concentrations of 206 and 198 mg/m 3 , with nodeaths observed. Adverse signs in rats were observed at the highestconcentrations, and included ataxia and hypersensitivity to noise, both clearingrapidly after exposure. Lethargy persisted for up to 3 days in survivors. Dead ratsshowed signs of respiratory failure but no treatment-related effects were seen insurvivors sacrificed after 14 days. In conclusion, the LC 50 (4 h[our]) fordichlorvos in mice was >218 mg/m 3 and in rats was >206 mg/m 3 . Considerablevariability was evident, with all animals exposed to 210 mg/m 3 dying but nodeaths observed at 206 mg/m 3 .‖ (Originals not sighted; APVMA, 2006a)WHO (1992) reported:Dichlorvos reassessment – application Page 177 of 436