Hepatotoxicity and BMDL derivation in rats under combined exposure to eight kinds of polycyclic aromatic hydrocarbons
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1.School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Food Nutrition and Safety, Huazhong University of Science and Technology,Hubei Wuhan 430030, China;2.China National Center for Food Safety Risk Assessment, Beijing 100022, China

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R155

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    Abstract:

    Objective To 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.Methods Male 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.Results The liver coefficient of the 1 000 μg/kg·BW group was significantly higher than that in the control group (P<0.05). After PAH8 exposure, some rats showed pathological changes, such as cell edema, inflammatory infiltration, and liver steatosis. Serum GSH-Px in the 10-250 μg/kg·BW group was significantly higher than that in the control group (P<0.01) but significantly decreased in the 1 000 μg/kg·BW group (P<0.001). The TC content in the liver showed a dose-dependent trend and increased significantly in the 1 000 μg/kg·BW group (P<0.001). No significant changes in other indexes were observed compared with the control group (P>0.05). 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.Conclusion Combined 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.

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YANG Miao, LU Yuxuan, CAO Xin, MAO Kanmin, MAO Weifeng, HAO Liping. Hepatotoxicity and BMDL derivation in rats under combined exposure to eight kinds of polycyclic aromatic hydrocarbons[J].中国食品卫生杂志,2023,35(6):813-819.

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  • Received:October 06,2022
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  • Online: September 25,2023
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