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

The APVMA (2008a) reported a chronic inhalation study in rats:―Blair D, Dix KM & Hunt PF (1974) Two year inhalation exposure of rats todichlorvos vapour. Report No. TLGR.0026.74. Lab: Tunstall Laboratory, ShellResearch Ltd, Sittingbourne Research Center, UK. Report date: June 1974.―Blair D, Dix KM, Hunt PF, Thorpe E, Stevenson DE & Walker AIT (1976)Dichlorvos - a 2-year inhalation carcinogenesis study in rats. Arch. Toxicol. 35:281-294.―Materials and Methods―Carworth Farm E (CFE) rats (50/sex/group) were exposed individually to airconcentrations of dichlorvos (SNC Pernis, unspecified location; batch No.unspecified; >97% purity) at 0, 0.05, 0.5 or 5 mg/m 3 for 23 h[our]/d[ay] for 2years. Achieved mean concentrations were 0, 0.05, 0.48 and 4.70 mg/m 3 ,respectively. Trimethyl phosphate was also present at 0, 0.007 and 0.04 mg/m 3 inthe low-, mid- and high-dose atmospheres, respectively, as was DCA[dichloroacetaldehyde] at 0.007, 0.013 and 0.028 mg/m 3 . The method ofapplication meant that the rats were exposed dermally, orally (via contaminationof food and water, cage interior and grooming fur), as well as by inhalation.―Rats were housed individually in metal wire cages and fed ad libitum with Diet86 pellets (Charles River, UK). Body weights and feed intake were measuredmonthly and behaviour was monitored daily. Rats dying during the course of thestudy were necropsied where possible. Haematology (Hb, erythrocyte, totalleucocyte and differential leucocyte counts, prothrombin time, and kaolincephalincoagulation time) and clinical chemistry (protein, urea, Na, K, glucoseand Cl concentrations, and plasma AP, AST and ALT activities) were examinedin blood samples collected at necropsy. RBC and plasma ChE activities weremeasured at the same time.―Necropsies were performed on all animals sacrificed at the end of the treatmentperiod. Major organs (brain, heart, liver, spleen and kidneys) were weighed andthese along with additional tissues (anterior pituitary, thyroid, adrenals, mammarygland, pancreas, skin, reticulo-endothelial system, tongue, nasal cavity, trachea,skeletal muscle, and eye and lachrymal gland) were examined microscopically.The left half of each brain was used for examination of ChE activity. Additionalbrain samples were provided to an independent laboratory (B. Holmstedt,Karolinska Intitutet, Stockholm) for assessment of acetylcholine and cholineconcentrations.―Statistical analysis consisted of analysis of variance with Student t-test or χ2 testfor comparison between treated and control groups.―ResultsDichlorvos reassessment – application Page 205 of 436