SYSTEMIC TOXICITY OF A BITUMEN UPGRADING PRODUCT IN THE RAT FOLLOWINGSUBCHRONIC DERMAL EXPOSURE

The subchronic toxicity following dermal exposure to a synthetic fuel, heavy gas oil No. 2 fraction of bitumen upgrading product (B-HGO II) was studied in the rat. B-HGO II was applied on the dorsal skin of rat s at doses of 8, 20, 50 and 125 mg/kg bw/day daily for 13 weeks. Contr ol animals received normal saline and positive controls received a med ium-boiling coal liquefaction product (CLP) at 125 mg/kg bw/day. Both male and female rats in the treatment groups had reduced body weight g ain, and males in the highest dose group were terminated in the 5th we ek due to overt toxicity. Increased liver weight relative to body weig ht was observed in males and females starting at 8 mg/kg. Increased re lative heart and spleen weights were observed in males and females sta rting at the two intermediate doses (20, 50 mg/kg). Increased relative kidney weight was detected in males at 50 mg/kg and females at 125 mg /kg. Increased serum cholesterol was observed in both sexes starting a t 50 mg/kg while elevated serum glucose was present in females startin g at 8 mg/kg. Significant changes in AH, APDM and EROD activities were observed in treated rats of both sexes. Reduced red blood cell counts were detected in males starting at 8 mg/kg and females at 20 mg/kg. M icroscopic examination of blood smears, spleen and hemosiderin accumul ation patterns, as well as analysis of FEP and serum TIBC levels indic ated that the cause of anemia was primarily intravascular hemolysis an d secondarily iron deficiency, Marked thymic atrophy and thyroid abnor malities were the most prominent histological changes followed by chan ges in bone marrow (myelofibrosis) and liver. Both B-HGO II and CLP (p ositive control) caused kidney changes characterized by cytoplasmic in clusions and lesions in the tubular cells, which were observed in 50 m g/kg males but not in the females. B-HGO II was considered to be toxic at a subchronic dermal exposure level as low as 8 mg/kg/day.