Alternative Vertebrate and Invertebrate Model Organisms Show Similar Sensitivity as Rodents to a Diverse Set of Chemicals

Current regulations aimed at safeguarding human health and the environment from chemical risks require toxicity testing, while regulatory bodies worldwide are phasing out the use of protected animals. Here, we systematically produced toxicity data from five alternative nonmammalian model organisms and a human cell line to demonstrate similarities and differences among distantly related species in their responses to chemical exposure (concentration range 1.8 pM to 2.1 M). We show that <i>Daphnia magna</i> and <i>Danio rerio</i> embryos are affected by more chemicals than <i>Xenopus laevis</i> embryos, <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>. Lethality/immotility data assembled 72 diverse chemicals into 11 clusters, revealing species-specific outcomes and showing differential enrichment of the clusters for certain chemical structures and modes of action. The ranked relative toxicities of chemicals across the model organisms were highly correlated (Spearman's correlation, maximum rho = 0.86, <i>p</i>-value = 0; minimum rho = 0.57, <i>p</i>-value = 0.000312), and their average toxicity values closely matched published values for rodents (rat: rho = 0.88, <i>p</i> = 2.8e-06; mouse: rho = 0.88, <i>p</i> = 2.7e-06). Our findings suggest that chemical toxicity under standardized experimental conditions is broadly conserved across a phylogenetically diverse set of model organisms, providing a conservative estimate of mammalian toxicity.

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Publication Details

Journal
Environmental Science & Technology
Published
2025-11-24
DOI
https://doi.org/10.1021/acs.est.5c10177
Primary Topic
Environmental Toxicology and Ecotoxicology
Type
article
Field-Weighted Citation Impact
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article

Alternative Vertebrate and Invertebrate Model Organisms Show Similar Sensitivity as Rodents to a Diverse Set of Chemicals

Nathan Keith, Shannon R. Smoot, Gavin Rhys Lloyd, Carsten Weiß et al.
Environmental Science & Technology
Environmental Toxicology and Ecotoxicology
article

Alternative Vertebrate and Invertebrate Model Organisms Show Similar Sensitivity as Rodents to a Diverse Set of Chemicals

Nathan Keith, Shannon R. Smoot, Gavin Rhys Lloyd, Carsten Weiß, Thomas C. Kaufman, Thomas Dickmeis, Gaëlle Hayot, Jason M. Tennessen, Andrew J. Tindall, Jonathan H. Freedman, Stefan Scholz, Luisa Orsini, Riccardo Massei, Christina A. Cramer von Clausbruch, Marianne Barnard, Gaurav D. Diwan, John K. Colbourne, Rubén Martínez, Joseph R. Shaw, Uwe Strähle, Robert B. Russell, Stephen Glaholt
article en

Abstract

Current regulations aimed at safeguarding human health and the environment from chemical risks require toxicity testing, while regulatory bodies worldwide are phasing out the use of protected animals. Here, we systematically produced toxicity data from five alternative nonmammalian model organisms and a human cell line to demonstrate similarities and differences among distantly related species in their responses to chemical exposure (concentration range 1.8 pM to 2.1 M). We show that <i>Daphnia magna</i> and <i>Danio rerio</i> embryos are affected by more chemicals than <i>Xenopus laevis</i> embryos, <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>. Lethality/immotility data assembled 72 diverse chemicals into 11 clusters, revealing species-specific outcomes and showing differential enrichment of the clusters for certain chemical structures and modes of action. The ranked relative toxicities of chemicals across the model organisms were highly correlated (Spearman's correlation, maximum rho = 0.86, <i>p</i>-value = 0; minimum rho = 0.57, <i>p</i>-value = 0.000312), and their average toxicity values closely matched published values for rodents (rat: rho = 0.88, <i>p</i> = 2.8e-06; mouse: rho = 0.88, <i>p</i> = 2.7e-06). Our findings suggest that chemical toxicity under standardized experimental conditions is broadly conserved across a phylogenetically diverse set of model organisms, providing a conservative estimate of mammalian toxicity.

Environmental Science & TechnologyVol. 59(48)
University of North Carolina at Chapel Hill (US), Helmholtz Centre for Environmental Research (DE), Heidelberg University (DE), Applied Materials (United Kingdom) (GB), The Edgbaston Hospital (GB), RealTimePurity (United States) (US), Watchfrog (France) (FR), Institute of Public Affairs (PL), Indiana University Bloomington (US), Leitat Technological Center (ES), Centre for Social Justice (GB), Indiana University (US), University of Birmingham (GB)
Openalex Percentile: Top 55%
Environmental Toxicology and Ecotoxicology
DOISourceOpenAlex
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