title: Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil.
abstract: Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).
mesh_terms: D000279:Administration, Cutaneous; D000741:Anemia, Aplastic / Q000139:chemically induced; D000818:Animals; D001682:Biological Availability; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002227:Carbazoles; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D010578:Petroleum / Q000633:toxicity*; D011083:Polycyclic Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption
chemical_list: D002227:Carbazoles; D010578:Petroleum; D011083:Polycyclic Compounds; C052511:clarified slurry oil