SHORT-TERM TOXICITY OF BITUMEN UPGRADING PRODUCTS IN THE RAT FOLLOWING REPEATED DERMAL EXPOSURE

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 a pplied on the dorsal skin of rats at 25 mg/kg bw/day (low dose), 100 m g/kg bw/day (intermediate dose), and 400 mg/kg bw/day (high dose) for 4 weeks. Control animals received normal saline while positive control s received a medium boiling coal liquefaction product (CLP) at 100 and 400 mg/kg bw/day. Reduced food consumption and growth suppression wer e 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-HGO II, and CLP, but not in control or LGO groups. A dose-related increase in absolute and relative liver weight was most marked in animals rece iving B-HGOII where a significant increase was observed starting at th e low dose, followed by those receiving B-HGOI and CLP. Appearance of pale foci on the splenic capsule and increases in spleen/body weight r atio were limited to animals receiving B-HGOI and B-HGOII. Decreases i n 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 decrea ses in hemoglobin and RBC were observed in animals receiving the low d ose of B-HGOII and the intermediate dose of B-HGO-I. Increased serum c holesterol 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 a trophy 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 a bnormality was the presence of focal my elofibrosis 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 femal es receiving high doses of B-LGO and in animals of both sexes receivin g high doses of B-HGOI, and moderate to marked epidermal hyperplasia i n rats receiving high doses of B-HGOI. Based on these multiple endpoin ts, the severity of systemic toxicity was B-HGOII > B-HGOI > CLP great er than or equal to B-LGO. The NOEL was about 25 mg/kg bw/day for B-LG O and lower than 25 mg/kg bw/day for B-HGOI and B-HGOII. (C) 1994 Soci ety of Toxicology.