DEVELOPMENTAL TOXICITY STUDY OF CLARIFIED SLURRY OIL (CSO) IN THE RAT

Pregnant CD rats were exposed dermally to 0.05, 1, 10, 50, and 250 mg/ kg/day of Clarified Slurry Oil (CSO) on Days 0-19 of gestation to dete rmine its potential developmental toxicity. Untreated and vehicle cont rols were included in the study. Day 20 of gestation Caesarean-derived fetuses were examined for gross, external, and visceral or skeletal a lterations. Dosages of 1 mg/kg/day and higher significantly decreased maternal body weight, body weight gain, feed consumption, gravid uteri ne weight, and live litter size and significantly increased resorption rate. These dosages also significantly reduced fetal weights and reta rded development of the brain, kidney, thoracic and caudal vertebrae, metacarpals, and hindpaw phalanges in dosage groups with live fetuses (high dosage group dams resorbed all conceptuses). The 50- and 250-mg/ kg/day dosage group dams had only placentas and/or dark red viscous fl uid in the uterus or vagina and significant body weight loss (associat ed with resorption). The highest dosage also caused emaciation, slight dehydration, and swollen dark anogenital areas. These results indicat e that CSO produces adverse developmental effects at maternally toxic dosages. The maternal and developmental NOAELs (no observed adverse ef fect levels) were 0.05 mg/kg/day. In a second study, groups of 10 mate d female rats were exposed to ''pulse'' exposures and dosages of 1, 50 , or 250 mg/kg/day of CSO applied dermally for 2- or 3-day intervals t hat spanned the gestation period. All dosages reduced maternal feed co nsumption and body weight gain during the treatment period. Dosages of 50 and 250 mg/kg/day also produced early resorptions when administere d on Days 6 through 8 and 9 through 11 of gestation. However, no incre ase in fetal alterations occurred, indicating that the effects on embr yo-fetal development were due to early death and not to the death of m alformed conceptuses. (C) 1995 Society of Toxicology