PUBLICATION
Human Apparent Volume of Distribution Predicts Bioaccumulation of Ionizable Organic Chemicals in Zebrafish Embryos
- Authors
- Zhang, L., Brooks, B.W., Liu, F., Zhou, Z., Li, H., You, J.
- ID
- ZDB-PUB-220728-35
- Date
- 2022
- Source
- Environmental science & technology 56(16): 11547-11558 (Journal)
- Registered Authors
- Keywords
- bioaccumulation, bioconcentration, ionizable organic chemicals, predictive model, zebrafish
- MeSH Terms
-
- Animals
- Bioaccumulation
- Humans
- Organic Chemicals/chemistry
- Toxicokinetics
- Water Pollutants, Chemical*/chemistry
- Zebrafish*
- PubMed
- 35896009 Full text @ Env. Sci. Tech.
Citation
Zhang, L., Brooks, B.W., Liu, F., Zhou, Z., Li, H., You, J. (2022) Human Apparent Volume of Distribution Predicts Bioaccumulation of Ionizable Organic Chemicals in Zebrafish Embryos. Environmental science & technology. 56(16):11547-11558.
Abstract
Chemicals with elevated bioaccumulation profiles present potential hazards to public health and the environment. Ionizable organic compounds (IOCs) increasingly represent a large proportion of commercial chemicals; however, historical approaches for bioaccumulation determinations are mainly developed for neutral chemicals, which were not appropriate for IOCs. Herein, we employed the zebrafish embryo, a common vertebrate model in environmental and biomedical studies, to elucidate toxicokinetics and bioconcentration of eight IOCs with diverse physicochemical properties and pharmacokinetic parameters. At an environmentally relevant pH (7.5), most IOCs exhibited rapid uptake and depuration in zebrafish, suggesting the ionized forms of IOCs are readily bioavailable. Bioconcentration factors (BCF) of these IOCs ranged from 0.0530 to 250 L·kg-1 wet weight. The human pharmacokinetic proportionality factor, apparent volume of distribution (VD), better predicted the BCF of selected IOCs than more commonly used hydrophobicity-based parameters (e.g., pH-dependent octanol-water distribution ratio, Dow). Predictive bioaccumulation models for IOCs were constructed and validated using VD alone or with Dow. Significant relationships between fish BCF and human VD, which is readily available for pharmaceuticals, highlighted the utility of biologically based "read-across" approaches for predicting bioaccumulative potential of IOCs. Our novel findings thus provided an understanding of the partitioning behavior and improved predictive bioconcentration modeling for IOCs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping