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

eceiving dichlorvos by capsule for 52 weeks at up to 3 mg/kg [b.w.]/day(AMVAC Chemical Corp. 1990). Male reproductive tissues examined were thetestes, prostate, and epididymides; female tissues examined were the cervix,ovaries, uterus, and vagina.“In a reproductive toxicity study involving male CF-1 mice, groups of 16 micewere exposed to atmospheres containing dichlorvos at 0, 30, or 55 mg/m 3 for16 hours (0, 3.3, or 6.1 ppm) (Dean and Thorpe 1972). Following dosing, eachmale mouse was caged with 3 randomly selected females for 7 days; thisprocedure was repeated weekly for a total of 8 weeks. Thirteen days after thepresumed mating (which occurred by the middle of the week), the femalemice were sacrificed and the uteri removed for examination. There were nodifferences between control and treated mice in the number of early fetaldeaths, late fetal deaths, or live fetuses found in the pregnant females. Thepercentages of pregnancies for females mated to males exposed to 30 or 55mg/m 3 (3.3 or 6.1 ppm) for 16 hours ranged from 67 to 88% and 63-92%,respectively; for controls, the percentages ranged from 73 to 88%. Underthese exposure conditions, dichlorvos did not appear to affect the fertility ofmale CF-1 mice. [NOAEL = 6.1 ppm, highest concentration tested.]“In another experiment in this study, similar results were obtained for malemice exposed for 4 weeks to atmospheres containing 2.1 or 5.8 mg/m 3 (0.23or 0.64, respectively) dichlorvos for 23 hours a day (Dean and Thorpe 1972).[NOAEL = 0.64 mg/m 3 , highest concentration tested.] (Originals not sighted;ATSDR, 1997)WHO (1993) reported:―Male and female Crl:CD3-1 mice were exposed to dichlorvos concentrations of0, 1.9, 3.0 or 4.6 mg/m 3 , generated from dichlorvos-impregnated PVC strips intheir cages. Exposure began 4 days prior to formation of breeding groups (3females and 1 male) and continued throughout pregnancy. Signs of intoxicationwere not observed. Plasma ChE activity was significantly inhibited (by 90%, 93%and 95% in the 1.9, 3.0 and 4.6 mg/m 3 groups, respectively) when measured onday 4 after beginning of treatment. Gestation length, number of litters, litterfrequency and mean litter size were comparable to controls. No grossly detectablecongenital anomalies were detected in any of the offspring (Casebolt et al., 1990).―A 3-generation, 2-litter/generation reproduction study in rats summarized byWHO (1988) was negative at doses up to 235 ppm in the diet, equivalent to 12mg/kg bw/day (Witherup et al., 1965). [The low dose rate is noted.]―Groups of 14 male NMRI/Han mice received either a single oral dose of 40mg/kg bw dichlorvos in olive oil or 18 daily oral doses of 0 or 10 mg/kg bwdichlorvos in olive oil. On days 9, 18, 27, 36, 54 and 63, two animals from eachgroup were killed and their testes examined histologically. A significant increasein the number of damaged seminiferous tubules (desquamation, decreases in cellpopulation, "holes") was observed in both dichlorvos groups. The supportingSertoli cells were also damaged, which may have resulted in the above effects. InDichlorvos reassessment – application Page 214 of 436