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

addition, there was an increase in the number and hypertrophy of Leydig cells. Noexplanation was given for these effects (Krause & Homola, 1972, 1974).―An increased incidence, just above background, of sperm abnormalities, wasobserved in a screening study on hybrid mice given five daily i.p. injections of 10mg/kg bw dichlorvos (approximately half the LD 50 ). At lower doses, 1 mg/kg bw,the number of sperm abnormalities was either similar to or lower than those in thecontrols (Wyrobek & Bruce, 1975).―Groups of 16 male juvenile Wistar rats received either 20 mg/kg bw dichlorvosin olive oil on days 4 and 5, 10 mg/kg bw dichlorvos in olive oil daily from days 4to 23, or 0.1 ml olive oil daily from days 4 to 23. On days 6, 12, 18, 26, 34, and50 of life, two rats from each group were sacrificed. Histological examination ofthe testes showed slight reduction in the number of spermatogenic cells andLeydig cells. All changes were reversed by the 50th day of life. It was assumedthat a reduction in testosterone synthesis resulted in damage to the spermatogeniccells (Krause et al., 1976).―In a subsequent experiment measurement of testosterone concentrations in thetestes, and luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations in serum showed no differences between treated animals and oliveoiltreated controls (Krause, 1977). However, in this study the use of a differentdosing regimen (10 mg/kg bw by gavage every other day for 2 weeks) prevented astrict comparison with the earlier study by Krause et al. (1976).―Fifty-five male Wistar rats (aged 5 months) were orally administered dichlorvosat levels of 5 or 10 mg/kg bw every other day for 8 weeks. Eleven rats werekilled every 4 weeks. No change was seen in body-weight gain or testes weight.The score values of the seminal cellular system decreased after 4-8 weeks oftreatment, but were restored 8 weeks after the end of treatment (Fujita et al.,1977).‖ (Originals not sighted; WHO, 1993)15 DEVELOPMENTAL TOXICITY 6.8HSNO Classification: Developmental toxicity – NoKEY STUDY:• Type of study:• Species:• Strain:• Sex/Numbers:Rat teratogenicity study;Rat;CD® SD rats;25 females/group;• Test material: Dichlorvos (Lot No. 802097; 96.86%);• Dose levels:0, 0.1, 3.0, or 21.0 mg/kg b.w./day;Dichlorvos reassessment – application Page 215 of 436