Jang Ji-Hun, Jeong Seung-Hyun
College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do, 57922, Republic of Korea.
College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do, 57922, Republic of Korea; College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon-Si, 57922, Republic of Korea.
Environ Pollut. 2024 Nov 1;360:124613. doi: 10.1016/j.envpol.2024.124613. Epub 2024 Jul 24.
4-tert-octylphenol (4-tert-OP) is an ecologically hazardous substance, and exposure to it in the environment has been consistently reported in the past. Despite the hazards and widespread exposure to 4-tert-OP, tools for scientific assessment of 4-tert-OP exposure risk level in humans are lacking. The main purpose of this study was to develop a physiologically-based-toxicokinetic (PBTK) model for 4-tert-OP and to perform quantitative risk assessment of 4-tert-OP in various population groups using the established model. Based on the results of toxicokinetic experiments on male rats, the PBTK model for 4-tert-OP was established and verified, and this was converted to a model for humans through interspecies extrapolation. Based on the previously reported no-observed-adverse-effect-levels for rats, it was possible to estimate the 4-tert-OP reference dose in humans through reverse dosimetry using the model. Biomonitoring data derived from various population groups were applied to the human PBTK model to calculate external exposures and margin of safety for 4-tert-OP for each population group. The PBTK model established in this study adequately explained the toxicokinetic experimental values at acceptable levels and was able to quantitatively predict the 4-tert-OP exposure level in the testes related to male reproductive toxicity. In addition, the degree of external exposure to 4-tert-OP could be scientifically estimated based on biomonitoring values derived from various biological matrices. The reference doses for systemic and reproductive toxicity caused by 4-tert-OP in male humans were calculated to be 0.16 and 1.12 mg/kg/day, respectively. The mean external exposure to 4-tert-OP in each population group estimated based on plasma and urine biomonitoring data was 0.04-66.24 mg/kg/day, showing very large exposure diversity between groups. Exposure risks to 4-tert-OP in populations ranged from safe to risky, suggesting the need for continued monitoring and risk management of 4-tert-OP worldwide. This study provides valuable scientific insight regarding the 4-tert-OP human risk assessment.
4-叔辛基苯酚（4-tert-OP）是一种具有生态危害的物质，过去一直有关于其在环境中暴露情况的报道。尽管4-叔辛基苯酚存在危害且广泛暴露，但缺乏用于科学评估人类4-叔辛基苯酚暴露风险水平的工具。本研究的主要目的是建立一个基于生理学的4-叔辛基苯酚毒代动力学（PBTK）模型，并使用该模型对不同人群进行4-叔辛基苯酚的定量风险评估。基于雄性大鼠的毒代动力学实验结果，建立并验证了4-叔辛基苯酚的PBTK模型，并通过种间外推将其转换为人类模型。根据先前报道的大鼠未观察到不良反应水平，利用该模型通过反向剂量测定法可以估计人类的4-叔辛基苯酚参考剂量。将来自不同人群的生物监测数据应用于人类PBTK模型，以计算每个群体的4-叔辛基苯酚外部暴露量和安全边际。本研究建立的PBTK模型在可接受水平上充分解释了毒代动力学实验值，并能够定量预测与雄性生殖毒性相关的睾丸中4-叔辛基苯酚的暴露水平。此外，基于来自各种生物基质的生物监测值，可以科学地估计4-叔辛基苯酚的外部暴露程度。男性人群中4-叔辛基苯酚引起的全身毒性和生殖毒性的参考剂量分别计算为0.16和1.12毫克/千克/天。根据血浆和尿液生物监测数据估计，每个群体中4-叔辛基苯酚的平均外部暴露量为0.04 - 66.24毫克/千克/天，各群体之间的暴露差异非常大。人群中4-叔辛基苯酚的暴露风险从安全到危险不等，这表明全球范围内需要持续监测和管理4-叔辛基苯酚。本研究为4-叔辛基苯酚的人类风险评估提供了有价值的科学见解。
