Short-Term Toxicity of Bitumen Upgrading Products in the Rat Following Repeated Dermal Exposure

Abstract

Short-Term Toxicity of Bitumen Upgrading Products in the Rat Following Repeated Dermal Exposure. Poon, R., Chu, I., Villeneuve, D.C., and Valli, V. E. (1994). Fundam. Appl. Toxicol. 23, 237-250. Light gas oil (B-LGO), heavy gas oil No. 1 (B-HGOI), and heavy gas oil No. 2 (B-HGOII) fractions of bitumen upgrading products (BUPs) were applied on the dorsal skin of rats at 25 mg/kg bw/day (low dose), 100 mg/kg bw/day (intermediate dose), and 400 mg/kg bw/day (high dose) for 4 weeks. Control animals received normal saline while positive controls received a medium boiling coal liquefaction product (CLP) at 100 and 400 mg/kg bw/day. Reduced food consumption and growth suppression were observed in males and females treated with B-HGOI, B-HGOII, and CLP, but only in males receiving B-LGO. Increased relative spleen, kidney, and liver weights were observed in animals treated with B-HGOI, B-HGOII, and CLP, but not in control or LGO groups. A dose-related increase in absolute and relative liver weight was most marked in animals receiving B-HGOII where a significant increase was observed starting at the low dose, followed by those receiving B-HGOI and CLP. Appearance of pale foci on the splenic capsule and increases in spleen/body weight ratio were limited to animals receiving B-HGOI and B-HGOII. Decreases in hematocrit and RBC and increase in percentage of reticulocytes were observed in animals of both sexes receiving B-HGOI and B-HGOII. Female rats appeared to be more severely affected because significant decreases in hemoglobin and RBC were observed in animals receiving the low dose of B-HGOII and the intermediate dose of B-HGO-I. Increased serum cholesterol was observed in B-HGOII-treated females at all dose levels, and in males starting at the intermediate dose. Histological changes were observed in the thymus gland, where moderate to marked cortical atrophy was noted in male and female rats receiving the high dose of B-HGOI and B-HGOII, and in the bone marrow, where the most significant abnormality was the presence of focal myelofibrosis in some male rats treated with B-HGOI and B-HGOII. Mild to moderate histological changes were found in the thyroid, liver, and spleen of rats of all treatment groups. Changes in the skin included moderate hyperkeratosis in females receiving high doses of B-LGO and in animals of both sexes receiving high doses of B-HGOI, and moderate to marked epidermal hyperplasia in rats receiving high doses of B-HGOI. Based on these multiple endpoints, the severity of systemic toxicity was B-HGOII > B-HGOI > CLP ⩾ B-LGO. The NOEL was about 25 mg/kg bw/day for B-LGO and lower than 25 mg/ kg bw/day for B-HGOI and B-HGOII.