Kuo Dave T F, Chen Ciara C
Department of Architecture and Civil Engineering, City University of Hong Kong, Hong Kong, China.
City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
Environ Toxicol Chem. 2021 Jan;40(1):57-71. doi: 10.1002/etc.4898. Epub 2020 Dec 15.
A bioconcentration factor (BCF) database and a toxicokinetic model considering only biota-water partitioning and biotransformation were constructed for neutral organic chemicals in midge. The database contained quality-reviewed BCF and toxicokinetic data with variability constrained to within 0.5 to 1 log unit. Diverse conditions in exposure duration, flow set-up, substrate presence, temperature, and taxonomic classification did not translate into substantial variability in BCF, uptake rate constant (k ), or depuration rate constant (k ), and no systematic bias was observed in BCFs derived in unlabeled versus radiolabeled studies. Substance-specific biotransformation rate constants k were derived by difference between the calculated biota-water partitioning coefficient (K ) and experimental BCF for developing a midge biotransformation model. Experimental midge BCF was modeled as BCF = K /(1 + k k ) with log k (k in h ) = -0.37 log K - 0.06T (in K) + 18.87 (root mean square error [RMSE] = 0.60), log k (k in L kg h ) = -0.0747 W (body weight in mg ) + 2.35 (RMSE = 0.48). The K value was estimated using midge biochemical composition and established polyparameter linear free energy relationships, and the diffusive elimination rate constant (k ) was computed as k = k /K The BCF model predicted >85% of BCFs that associated with neutral organic compounds (log K = 1.46 - 7.75) to within 1 log-unit error margin and had comparable accuracy similar to amphipod or fish models. A number of outliers and critical limitations of the k model were identified and examined, and they largely reflected the inherent limitation of difference-derived k , the lack of chemical diversity, and inadequate temperature variation in existing data. Future modeling efforts can benefit from more BCF and toxicokinetic observations of BCF on structurally diverse chemicals for model training, validation, and diagnosis. Environ Toxicol Chem 2021;40:57-71. © 2020 SETAC.
构建了一个生物浓缩因子（BCF）数据库以及一个仅考虑摇蚊体内生物群 - 水分配和生物转化的毒理学动力学模型，用于研究中性有机化学物质。该数据库包含经质量审查的BCF和毒理学动力学数据，其变异性限制在0.5至1个对数单位以内。暴露持续时间、水流设置、底物存在、温度和分类学分类等多种条件并未导致BCF、摄取速率常数（k）或净化速率常数（k）出现显著变异，并且在未标记研究与放射性标记研究中得出的BCF未观察到系统偏差。通过计算生物群 - 水分配系数（K）与实验BCF之间的差异，得出物质特异性生物转化速率常数k，以建立摇蚊生物转化模型。实验摇蚊BCF被建模为BCF = K /(1 + k k)，其中log k（k的单位为h）= -0.37 log K - 0.06T（T的单位为K）+ 18.87（均方根误差[RMSE] = 0.60），log k（k的单位为L kg h）= -0.0747W（W为体重，单位为mg）+ 2.35（RMSE = 0.48）。K值使用摇蚊生化组成和已建立的多参数线性自由能关系进行估算，扩散消除速率常数（k）计算为k = k /K。该BCF模型预测与中性有机化合物（log K = 1.46 - 7.75）相关的BCF中，超过85%的误差在1个对数单位以内，并且具有与双壳类动物或鱼类模型相当的准确性。识别并检查了k模型的一些异常值和关键局限性，它们在很大程度上反映了差异衍生k的固有局限性、化学多样性的缺乏以及现有数据中温度变化不足的问题。未来的建模工作可以受益于对结构多样的化学物质进行更多的BCF和BCF毒理学动力学观测，以用于模型训练、验证和诊断。《环境毒理学与化学》2021年；40:57 - 71。© 2020 SETAC。
