The short-term toxicity and metabolome of Benzene.

A 14-day rat study with plasma metabolomics was conducted to evaluate the toxicity of Benzene. Wistar rats were orally administered Benzene daily at doses of 0, 300 and 1,000mg/kg bw. The study identified liver and kidneys as target organs of Benzene toxicity and found reductions in total white blood cells, absolute lymphocyte and eosinophil cell counts, and increased relative monocyte counts suggesting bone marrow as a target organ. The study also confirmed liver as a target organ using metabolomics, which showed indications of a stress reaction in rats and changes in metabolites suggestive of a metabolic disorder. The metabolomics investigations did not find any other toxicologically relevant modes of action, and the observed metabolite changes were not associated with markers for mitochondrial dysfunction. The study concludes that integration of omics technologies, such as metabolomics, in regulatory toxicity studies is possible, confirms existing knowledge and adds additional information that can be used for mechanistic understanding of observed toxicity.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Frank Faulhammer: is employed by BASF including stock ownership Bennard van Ravenzwaay: declares to have no known financial or personal relationships that could have appeared to influence the work reported in this paper A. Robert Schnatter: declares to have no known financial or personal relationships that could have appeared to influence the work reported in this paper Martijn Rooseboom: is employed by Shell including stock ownership Hennicke Kamp: is managing director of BASF Metabolome Solutions, a company that is offering metabolome analysis for various applications including toxicology research to external clients and BASF. He is employed by BASF including stock ownership Burkhard Flick: declares to have no known financial or personal relationships that could have appeared to influence the work reported in this paper Varun Giri: is employed by BASF including stock ownership Saskia Sperber: is employed by BASF including stock ownership Larry G Higgins and Michael G Penman: Penman Consulting provide consultancy services to the LOA REACH Consortium, and this article reflects the positions developed in the course of this work Neslihan Aygun Kocabas: is employed by TotalEnergies including stock ownership.