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 determine its potential developmental toxicity. Untreated and vehicle controls were included in the study. Day 20 of gestation Caesarean-derived fetuses were examined for gross, external, and visceral or skeletal alterations. Dosages of 1 mg/kg/day and higher significantly decreased maternal body weight, body weight gain, feed consumption, gravid uterine weight, and live litter size and significantly increased resorption rate. These dosages also significantly reduced fetal weights and retarded 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 fluid in the uterus or vagina and significant body weight loss (associated with resorption). The highest dosage also caused emaciation, slight dehydration, and swollen dark anogenital areas. These results indicate that CSO produces adverse developmental effects at maternally toxic dosages. The maternal and developmental NOAELs (no observed adverse effect levels) were 0.05 mg/kg/day. In a second study, groups of 10 mated 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 that spanned the gestation period. All dosages reduced maternal feed consumption and body weight gain during the treatment period. Dosages of 50 and 250 mg/kg/day also produced early resorptions when administered on Days 6 through 8 and 9 through 11 of gestation. However, no increase in fetal alterations occurred, indicating that the effects on embryo-fetal development were due to early death and not to the death of malformed conceptuses.
Hoberman
A M
AM
Argus Research Labs, Inc., Horsham, Pennsylvania 19044, USA.
Christian
M S
MS
Lovre
S
S
Roth
R
R
Koschier
F
F
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000287:Administration, Topical; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000633:toxicity*; D003877:Dermatitis, Contact / Q000473:pathology; D004435:Eating / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D008098:Litter Size / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010578:Petroleum / Q000633:toxicity*; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000473:pathology; D013723:Teratogens / Q000633:toxicity*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D015430:Weight Gain / Q000187:drug effects
D002227:Carbazoles; D010578:Petroleum; D011083:Polycyclic Compounds; D013723:Teratogens; C052511:clarified slurry oil