Objective To calculate benchmark dose (BMD) and benchmark dose lower limit (BMDL) of sub-chronic hepatotoxicity in mouse induced by vinyl chloride at low concentrations, and provide data for related risk assessment.
Methods Forty-eight ICR male mice were randomly classified into three exposed groups160 (high concentration), 80 (medium concentration), and 40 (low concentration) mg/m3 of vinyl chloride and one negative control group, with 12 mice in each group. All mice received static inhalation of designated dosages of vinyl chloride for 10 weeks, 5 episodes per week and 2 hours per episode. Body weight change, liver histopathology, liver coefficient, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and liver triglyceride (TG) and cholesterol (CHO) were evaluated and recorded. All data were screened for the requirement of BMD method and fitted into four dose-effect models (including Hill, Linear, Polynomial, and Power models) as continuous variables using the BMDS 2.7 software. BMD and BMDL were obtained from the optimal model.
Results Compared with the control and the low concentration groups without abnormal liver histopathological change, the medium and high concentration groups showed obvious hepatocyte edema, eosinophilic change, and inflammatory cell infiltration. There were no differences in initial body weight, terminal body weight, liver coefficient, serum ALT, serum AST, and liver TG between the exposed groups and the control group (P>0.05). Intrahepatic CHO level was significantly elevated in both the high concentration group(1 836.86±179.89) mmol/g and the medium concentration group(1 944.20±213.45) mmol/g compared with the low concentration group(1 176.65±73.91) mmol/g and the control group(1 085.10±211.95) mmol/g (P < 0.05). The BMD and BMDL were 38.96 mg/m3 and 16.48 mg/m3 respectively by the optimal Hill model. No observed adverse effect level (NOAEL) was 40 mg/m3.
Conclusion Lipometabolic disturbance is induced in mouse by low-concentration sub-chronic vinyl chloride exposure, and the related BMD and BMDL are lower than the NOAEL.
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