title: Effects of multiple exposures of small doses of Pembina Cardium crude oil and diesel in rats.
abstract: In lands used for agricultural purposes, petroleum- or diesel-contaminated wastes and accidental spills of crude oil at some drilling sites pose exposure risks for occupational public, livestock, and wildlife. This study has assessed the effects of an Alberta crude oil, Pembina Cardium crude oil (PCCO), and a commercial diesel fuel #2 (CDF-2) in Sprague-Dawley rats after repeated exposures at small dose levels. Rats were given by gavage on day 1, 3, 5, and 8 specified dosages of either the control vehicle, methylcellulose (MC) (1.25 ml/kg), or PCCO (0.25-1.25 ml/kg), or CDF-2 (1.25 ml/kg). Exposure of rats to these dose levels of the test substances caused no overt symptoms of intoxication. A small but statistically significant increase in liver somatic index was observed in rats exposed to 1.25 ml/kg doses of PCCO and CDF-2; however, kidney somatic index was not significantly affected by these treatments. Blood analyses for hematological and clinical indicators of systemic impairments did not show any significant changes (p > 0.05) between the control and PCCO- or CDF-2-exposed rats. Biochemical assessment of liver and kidney tissues showed that compared to the control group, the PCCO- and CDF-2-exposed groups had a marked and significant increase (p < 0.05) in the hepatic activity of ethoxyresorufin-O-deethylase (EROD, a cytochrome P-450 [CYP] 1A1/A2-linked enzyme). In PCCO-exposed rats, the induction of EROD was dose-dependent. Exposure of rats with PCCO and CDF-2 also caused dose-related increases from the unexposed (control) or MC dosed rats in (1) hepatic activities of aryl hydrocarbon hydroxylase (AHH, a CYP 1A1-linked enzyme), ethoxycoumarin-O-deethylase (ECOD, a CYP 2B/1A-linked enzyme), glutathione transferase (GT), and NADPH-catalyzed microsomal lipid peroxidation; and (ii) ECOD activity in kidneys. The induction of hepatic CYP-linked enzymatic activities by PCCO and CDF-2 could be due to de novo synthesis of selected isoforms, as evidenced by the relative differences in the inhibition of EROD activity with 7,8-benzoflavone or metyrapone.
authors.affiliation: Toxicology Unit, Alberta Research Council, Postal Bag 4000, Vegreville, Alberta, T9C 1T4 Canada. susana@arc.ab.ca
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: R W
authors.initials: RW
authors.lastname: Coppock
authors.forename: M M
authors.initials: MM
authors.lastname: Schuler
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000009:adverse effects*; D004790:Enzyme Induction; D005742:Gasoline / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010578:Petroleum / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004785:Environmental Pollutants; D005742:Gasoline; D010578:Petroleum; D019363:Cytochrome P-450 CYP1A1