Short-term oral toxicity of gasohol in female rats.
The systemic toxicity of gasohol (10% ethanol in gasoline by volume) in female rats following 4-week oral administration was studied. Female Sprague-Dawley rats (198+/-14 g) were divided into four groups of ten animals each. The low- and medium-dose groups received by gavage corn oil containing gasoline/ethanol at 16/1.8 and 160/18 (mg kg(-1) body weight), respectively, for 28 consecutive days. The high-dose animals were administered gasoline/ethanol at 1600/180 mg kg(-1) on the first day and the dose was reduced to 800/90 mg kg(-1) for the rest of the study period. Control animals received corn oil only. Urine was obtained from all rats after weeks 1, 2 and 4 for biochemical analysis. At termination of the study, kidneys of four rats from each group were examined by electron microscopy. Body weight gains, organ weights, tissue and organ histopathology, serum biochemistry, hematology, liver enzymes and biochemistry were determined in the remaining six animals of each group. No treatment-related changes were observed in the following endpoints: body weight gain or relative weights of the brain, lungs, liver, kidneys, spleen and thymus. A significant increase in pentoxyresorufin O-deethylase (PROD) and benzoylresorufin O-dealkylase (BROD) activities was detected in the high-dose animals, whereas ethoxyresorufin O-deethylase (EROD) activity was unchanged. Treatment with gasohol did not produce any significant changes in hematology and serum clinical chemistry parameters. Biomarkers of oxidative stress such as serum and liver thiobarbituric acid reactive substances (TBARS) and liver glutathione also were unaffected by treatments. Urinary ascorbic acid was elevated markedly in the medium- and high-dose groups following the first, second and fourth weeks of treatment. Urine hippuric acid was increased significantly in the high-dose groups. A dose-related increase in urinary aldehydes also was observed in animals after the first, second and fourth week of treatment. Interestingly, a separate 1-week dosing study revealed that the increase in urinary aldehydes was associated with gasoline and not with ethanol treatment. In the high-dose animals slight increases in urinary protein and N-acetylglucosaminidase activity were observed after week 1 but not after week 2 or week 4. No histopathological changes were detected in the liver, kidneys, stomach, brain, lungs or other tissues examined. Electron microscopic examination of the kidneys also did not reveal any abnormalities. It was concluded that short-term oral administration of gasoline/ethanol at 800/90 mg kg(-1) produced a biochemical response in the liver but no adverse effects in the kidneys and lungs. The biological significance of elevated urinary aldehydes at gasoline/ethanol concentrations of 160/18 mg kg(-1) and higher remains to be studied.
Poon
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Safe Environments Directorate, Health Canada, Ottawa, Canada, K1A 0L2. raymond_poon@hc-sc.gc.ca
Yagminas
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A
Singh
A
A
Valli
V E
VE
Chu
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I
D000284:Administration, Oral; D000447:Aldehydes / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008854:Microscopy, Electron; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D000447:Aldehydes; D015415:Biomarkers; D002274:Carcinogens, Environmental; D005742:Gasoline; D012997:Solvents; D000431:Ethanol