Systemic toxicity of a bitumen upgrading product in the rat following subchronic dermal exposure

Abstract

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 rats at doses of 8, 20, 50 and 125 mg/kg bw/day daily for 13 weeks. Control animals received normal saline and positive controls received a medium-boiling coal liquefaction product (CLP) at 125 mg/kg bw/day. Both male and female rats in the treatment groups had reduced body weight gain, and males in the highest dose group were terminated in the 5th week due to overt toxicity. Increased liver weight relative to body weight was observed in males and females starting at 8 mg/kg. Increased relative heart and spleen weights were observed in males and females starting 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 at 50 mg/kg while elevated serum glucose was present in females starting 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. Microscopic examination of blood smears, spleen and hemosiderin accumulation patterns, as well as analysis of FEP and serum TIBC levels indicated that the cause of anemia was primarily intravascular hemolysis and secondarily iron deficiency. Marked thymic atrophy and thyroid abnormalities were the most prominent histological changes followed by changes in bone marrow (myelofibrosis) and liver. Both B-HGO II and CLP (positive control) caused kidney changes characterized by cytoplasmic inclusions and lesions in the tubular cells, which were observed in 50 mg/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.