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A cell‐free testing platform to screen chemicals of potential neurotoxic concern across twenty vertebrate species
Author(s) -
Arini Adeline,
Mittal Krittika,
Dornbos Peter,
Head Jessica,
Rutkiewicz Jennifer,
Basu Niladri
Publication year - 2017
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.3880
Subject(s) - neurochemical , in vitro toxicology , chemistry , environmental chemistry , pesticide , biology , in vitro , biochemistry , ecology , neuroscience
There is global demand for new in vitro testing tools for ecological risk assessment. The objective of the present study was to apply a set of cell‐free neurochemical assays to screen many chemicals across many species in a relatively high‐throughput manner. The platform assessed 7 receptors and enzymes that mediate neurotransmission of γ‐aminobutyric acid, dopamine, glutamate, and acetylcholine. Each assay was optimized to work across 20 vertebrate species (5 fish, 5 birds, 7 mammalian wildlife, 3 biomedical species including humans). We tested the screening assay platform against 80 chemicals (23 pharmaceuticals and personal care products, 20 metal[loid]s, 22 polycyclic aromatic hydrocarbons and halogenated organic compounds, 15 pesticides). In total, 10 800 species–chemical–assay combinations were tested, and significant differences were found in 4041 cases. All 7 assays were significantly affected by at least one chemical in each species tested. Among the 80 chemicals tested, nearly all resulted in a significant impact on at least one species and one assay. The 5 most active chemicals were prochloraz, HgCl 2 , Sn, benzo[ a ]pyrene, and vinclozolin. Clustering analyses revealed groupings according to chemicals, species, and chemical–assay combinations. The results show that cell‐free assays can screen a large number of samples in a short period of time in a cost‐effective manner in a range of animals not easily studied using traditional approaches. Strengths and limitations of this approach are discussed, as well as next steps. Environ Toxicol Chem 2017;36:3081–3090. © 2017 SETAC