Pyriproxyfen does not cause microcephaly or malformations in a preclinical mammalian model
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RESEARCH ARTICLE
Pyriproxyfen does not cause microcephaly or malformations in a preclinical mammalian model Juliana Miron Vani 1,2 & Laynna de Carvalho Schweich-Adami 1,2 & Sarah Alves Auharek 3 & Andréia Conceição Millan Brochado Antoniolli-Silva 1,2 & Rodrigo Juliano Oliveira 1,2,4,5 Received: 9 May 2019 / Accepted: 12 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Pyriproxyfen is used in Brazil to combat epidemics of Dengue Fever, Chikungunya Fever, and Zika virus. This study assessed the effects of pyriproxyfen on reproductive performance, embryo-fetal development, head measurements, and DNA integrity in a preclinical model. Thirty pregnant mice were divided into three groups (n = 10): control (drinking water—0.1 ml/10 g (body weight—b.w., gavage) and treated with pyriproxyfen 0.0002 mg/kg and 0.0021 mg/kg (b.w., gavage) during the gestational period. Analysis of biometric, reproductive performance and embryo-fetal development parameters related to control presented no significant differences, suggesting no maternal or embryo-fetal toxicity. Head measurements showed no differences except an increase in anterior/posterior measurement and glabella/external occipital protuberance. Analysis of DNA integrity showed an increase in micronucleus only at 72 h for the lowest dose group. Thus, we infer that pyriproxyfen is not related to the occurrence of microcephaly, nor does it alter reproductive performance, embryo-fetal development or DNA integrity. Keywords Larvicide . Reproductive performance . Embryo-fetal development . Teratogenesis . Genotoxicity
Introduction Since 2014, the larvicide pyriproxyfen has been used to combat epidemics of Dengue Fever, Chikungunya Fever, and Zika Virus in Brazil by indication of the Ministry of Health (WHO 2020; Brasil 2014). This compound has a pyridine base, which is classified as a juvenile hormone analog that regulates a wide range of processes in mosquito development, including for Aedes aegypti (Albuquerque et al. 2016; Dzieciolowska et al. 2017).
In Brazil, the increase in microcephaly cases was concomitant with the Zika Virus epidemic and the use of pyriproxyfen. Because of these simultaneous occurrences, a group of Argentine researchers raised the hypothesis that pyriproxyfen was correlated with the development of microcephaly (REDUAS 2020). This finding corroborates the study by Parens et al. (2017) that suggest the correlation between the use of pyriproxyfen and the development of microcephaly and/or neurological changes in humans. However, studies from Saegusa (1988) and Sumitomo (n.d) initially indicated the absence of a correlation between the
Responsible Editor: Philippe Garrigues * Rodrigo Juliano Oliveira [email protected]
3
Faculdade de Medicina do Mucuri, Universidade Federal dos Vales do Jequitinhonha e do Mucuri – UFVJM, Teofilo Otoni, MG, Brazil
1
Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica – CeTroGen, Hospital Universitário Maria Aparecida Pedrossian – HUMAP, Universidade Federa
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