title: Molecular mechanisms of amitraz mammalian toxicity: a comprehensive review of existing data.
abstract: Amitraz is a formamidine pesticide widely used as an insecticide and acaricide. Amitraz poisoning cases in humans and animals are still being described to date, which is a cause of concern for health authorities. Amitraz was reported not to pose unreasonable risks or adverse effects to humans or the environment unlike the other commercialized member of the formamidine family, chlordimeform, which was removed from the market because of carcinogenic effects in animal studies. Amitraz was classified as a nonquantifiable "Suggestive Evidence of Carcinogenicity" and not genotoxic, but recently, it has been reported that it could induce genotoxic effects. Moreover, ever since the previously published evaluations made by the Environmental Protection Agency (EPA) and the Joint Meeting of Pesticide Residues (JMPR) there have been new reported data on amitraz toxicity related to genotoxicity, oxidative stress, cell death, immunotoxicty, endocrine disruption, and developmental toxicity which indicate that the risk of this compound could be underestimated. Furthermore, there is missing information about the dose-response relationship for some mechanisms and toxic effects described for amitraz and its metabolites, the mechanism of action by which several toxic effects are produced, and amitraz pharmacokinetics on different species. According to this, the new information reported should be taken into account, and more studies should be performed to fill in the gaps of missing information for a complete hazard identification and therefore an exhaustive risk assessment of amitraz. This review is aimed at updating the current knowledge on molecular mechanisms of amitraz mammalian toxicity, pointing out the missing information, providing some possible explanation of the mechanism by which some toxic effects observed are produced, and suggesting future direction of its research. To our knowledge, this is the first review on the molecular mechanisms of amitraz toxicity.
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: del Pino
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Paula Viviana
authors.initials: PV
authors.lastname: Moyano-Cires
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Anadon
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Díaz
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Lobo
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Miguel Andrés
authors.initials: MA
authors.lastname: Capo
authors.affiliation: †Departament of Toxicology and Pharmacology, Veterinary School, and ‡Department of Toxicology and Legal Medicine, Medicine School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Frejo
mesh_terms: D000818:Animals; D006801:Humans; D014052:Toluidines / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D014052:Toluidines; C014983:amitraz