STATISTICAL MODELS IN TOXICOLOGY AND BIOCHEMISTRY

工作总结：该项目旨在增加我们对毒理学和生物化学中数学和统计模型的使用和应用的理解，并实施这些数学模型以帮助解释当前的研究结果。研究工作探索了不同的生物学领域，包括致癌作用，药理学，发育生物学，神经学，免疫学和内分泌学。主要成就包括（1）评估暴露于工频电场和磁场的风险（2）推导致癌性数据分析方法，包括乳头状瘤、癌和维持组织大小的数据（3）新的致癌性随机模型（4）开发了将PBPK模型、癌前病变数据细胞标记数据和肿瘤发病率数据（5）正在日本人口中验证城市地区死亡率/发病率模型（6）开发了暴露评估模型（7）建立并通过实验验证了描述大鼠发情周期和女性月经周期的数学模型（8）开发了评估基准剂量适当性的方法，（9）继续通过将可靠的科学应用于诸如接触四氯二苯并对二恶英、黄曲霉毒素和内分泌干扰物等关键环境问题，协助科学改进风险评估方法。- 风险评估二恶英磁场生物数学毒理学癌症模型剂量反应

Summary of Work: This project is intended to increase our understanding of the use and application of mathematical and statistical models in toxicology and biochemistry and to implement these mathematical models to aid in explaining current research findings. The research effort explores a diverse range of biological areas, including carcinogenesis, pharmacology, developmental biology, neurology, immunology and endocrinology. Major accomplishments include (1) evaluation of the risks from exposure to pwer-line frequency electric and magnetic fields (2) the derivation of methods for the analysis of carcinogenicity data including data on papillomas, carcinomas and maintaining tissue size (3) new stochastic models of carcinogenesis (4) methods were developed for linking PBPK models, premalignant lesion data, cell labelling data and tumor incidence data (5) models for mortality/morbidity in urban areas are being validated in a Japanese population (6) exposure assessment models have been developed (7) built and experimentally validated a mathematical model describing the estrus cycle in rats and menstrual cycle in women (8) developed methods for evaluating the adequacy of benchmark doses, (9) continued to aid in the scientific improvement of risk assessment methods through the application of sound science to key environmental issues such as exposure to TCDD, aflatoxins and endocrine disruptors. - risk assessment dioxin magnetic fields biomathematics toxicokinetics cancer modeling dose-response