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

levels, analytical dichlorvos concentrations were 0.08, 0.80, 8.0, 80 and 400ppm after 12 h[ours], declining to 0.022, 0.224, 2.24, 22 and 112 ppm after156 h[ours], respectively. Average concentrations of dichlorvos were 0.047,0.467, 4.67, 46.7 and 234 ppm. The average DCA content present was0.014, 0.114, 0.887, 6.86 and 28.6 ppm in these groups, respectively.“Mortalities, clinical signs and bodyweight effects: There was no treatmentrelatedeffect on mortalities, clinical signs or bodyweight gain.“Haematology, clinical chemistry and urinalysis: There was no treatmentrelatedeffect on any heamatology, clinical chemistry or urinary parameter.ChE activity: Plasma and RBC ChE activities were measured 13 timesduring the study, with no significant effects observed in the three lowestdose groups. In the 100 ppm group, plasma and RBC ChE activities werereduced to 60-90% and to 50-90% of controls in males and females,respectively. In the 500 ppm group, activities were reduced to 20-70% and20-60%, respectively. Activities tended to increase as the study progressed.At termination, brain ChE activity was significantly decreased only in the500 ppm group, by 45-47% in rats sacrificed after 6 months, declining to 5-15% in those sacrificed after 24 months.“Pathology: There was no treatment-related effect on organ weights of ratssacrificed at scheduled intervals or at termination, and there were notreatment-related macroscopic lesions. Histology revealed hepatocellularfatty vacuolisation in all 500 ppm rats, and in approximately 80% of femalesand 62% of males at 100 ppm. This was only evident in animals sacrificedafter 18 or 24 months. All neoplastic lesions were benign, with mostoccurring in the mammary and pituitary glands of both sexes without dosedependency.There were no tumours that occurred only at the high-dose.Overall, no treatment-related effects were observed on the incidence ortiming of tumours.“Conclusion: The NOEL following 2-years of dietary exposure todichlorvos was 10 ppm (mean analytical concentration of 4.67 ppm;equivalent to 0.23 mg/kg bw/d[ay]) based on the inhibition of plasma andRBC ChE activity at and above 100 ppm (mean analytical concentration46.7 ppm; equivalent to 2.3 mg/kg bw/d[ay]). Hepatocellular abnormalitieswere evident at 100 and 500 ppm, but these were insufficient to indicateimpairment of normal liver function.‖ (Original not sighted; APVMA,2008a)The ATSDR (1997) reported:“In a 90-day study in female Sherman rats, groups of 10 animals wereexposed to doses ranging from 0 to 69.9 mg/kg [b.w.]/day in their feed(Durham et al. 1957). Two animals from each group were bled on days3, 11, 60, and 90, and serum cholinesterase and erythrocyteacetylcholinesterase were determined. Clinical signs of neurologicaltoxicity were not noted in any dosage group. Cholinesterase data waspresented graphically so the percentage inhibition of theDichlorvos reassessment – application Page 236 of 436