Study on Hepatotoxicity of Benzophenone-3 at Environmental Concentration in Postpartum Mice

Benzophenone-3 (BP-3), a widely used ultraviolet absorber in various scenarios, exhibits estrogenic toxicity at environmental concentrations-as demonstrated in our prior work. Given the importance of hepatic metabolism and the limitations of previous hepatotoxicity research (high-dose models, lack of mammalian data, etc.), we evaluated BP-3's hepatic effects on postpartum mice at environmentally relevant levels. Postpartum mice were exposed to BP-3 via drinking water from postpartum day 1 (PPD1) to PPD35. Groups solvent control (0.001% DMSO), 10-1000 nM BP-3, and diethylstilbestrol (DES) were established. Basic growth performance, histopathological changes, and a range of molecular indicators were assessed. The results showed that BP-3 exposure induced dose-dependent increases in liver weight, histopathological alterations (sinusoidal dilation, hepatocyte edema, and necrosis), and significant upregulation of oxidative stress markers (<i>Ros</i>, <i>Mda</i>), chemokines (<i>Ccl27a</i>/<i>b</i>), and inflammatory factors (<i>Tnf-α</i>, <i>Il-6</i>, <i>Nf-κb</i>) at the mRNA level (all <i>p</i> < 0.05). Conversely, levels of antioxidant enzymes (<i>Cat</i>, <i>Sod1/2</i>) and anti-inflammatory factor <i>Ho-1</i> were markedly decreased (<i>p</i> < 0.05). A clear dose-effect relationship was confirmed using the Integrated Biomarker Response (IBR) framework. This pioneering study establishes the hepatotoxicity of environmentally relevant BP-3 levels in mammals and offers methodological insights for endocrine disruptor assessment.