Hepatotoxicity and BMDL derivation in rats under combined exposure to eight kinds of polycyclic aromatic hydrocarbons

Abstract

ObjectiveTo investigate the hepatotoxicity induced by the combined exposure of eight types of PAHs （PAH8） in rats， the lower limit of the 95% confidence interval of benchmark dose （BMDL） of PAH8-induced hepatotoxicity was determined using the benchmark dose （BMD） method.MethodsMale SD rats were randomly divided into five groups （10 rats in each group） and were exposed to PAH8 at doses of 0， 10， 50， 250， and 1 000 μg/kg·BW， respectively. Rats were sacrificed after 30 d， and organ coefficients were calculated. Liver pathological examination and oil-red O staining were performed. Serum alanine aminotransferase， aspartate aminotransferase， malondialdehyde， glutathione peroxidase （GSH-Px）， triglyceride （TG）， total cholesterol （TC） levels， and liver TG and TC levels were measured. Hepatotoxicity data with statistical significance， toxicological significance， and dose-effect trend were selected. BMD analysis was performed using the BMDS 3.2 software. BMDL values of PAH8-induced hepatotoxicity in rats were obtained by choosing the optimal fitting model.ResultsThe liver coefficient of the 1 000 μg/kg·BW group was significantly higher than that in the control group （P0.05）. Liver TC content was used for BMD analysis， and the BMDL and BMD of PAH8 based on the Hill model were 47.61 and 213.52 μg/kg·BW， respectively. The non-observed adverse effect level and lowest observed adverse effect level of PAH8 were 250 and 1 000 μg/kg·BW， respectively.ConclusionCombined exposure to PAH8 caused abnormal lipid accumulation in the liver， and the BMDL value of liver toxicity in PAH8 rats was 47.61 μg/kg·BW， which was lower than the NOAEL/LOAEL.

Keywords

• polycyclic aromatic hydrocarbons
• combination exposure
• hepatotoxicity
• benchmark dose