title: Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.
abstract: Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos.
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Permoserstr. 15, 04318 Leipzig, Germany. Electronic address: stefan.scholz@ufz.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ortmann
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Klüver
authors.affiliation: L'ORÉAL Advanced Research, Environmental Research Department, 1 avenue Eugène Schueller, 93601 Aulnay sous Bois, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Léonard
mesh_terms: D032761:Animal Experimentation; D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D062067:Chemical Safety / Q000379:methods*; D005399:Fishes; D015386:Hazardous Substances / Q000009:adverse effects*; D006801:Humans; D007928:Lethal Dose 50; D008962:Models, Theoretical; D051381:Rats; D012449:Safety; D023382:Toxicity Tests, Acute / Q000379:methods*; D014480:United Nations
chemical_list: D015386:Hazardous Substances
keywords: 3Rs; Acute systemic toxicity; Animal experiments; Fish embryo test; Global harmonisation system; LD(50)