A possible link between pyriproxyfen and microcephaly
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Abstract
The Zika virus is the primary suspect in the large increase in microcephaly cases in 2015-6 in Brazil, however its role is unconfirmed despite individual cases of viral infections found in neural tissue. Here we consider the alternative that the insecticide pyriproxyfen, used in Brazilian drinking water for mosquito control, may actually be the cause. Pyriproxifen is an analog of juvenile hormone, which corresponds in mammals to regulatory molecules including retinoic acid, a vitamin A metabolite, with which it has cross-reactivity and whose application during development causes microcephaly. Methoprene, another juvenile hormone analog approved as an insecticide has metabolites that bind to the retinoid X receptor, and causes developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via activation of the retinoid X receptor. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly--incomplete formation of the anterior cerebral hemispheres--in rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented--it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, where it is not. Given this combination of information we strongly recommend that the use of pyriproxyfen in Brazil be suspended pending further investigation.
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2016. A possible link between pyriproxyfen and microcephaly. PeerJ Preprints 4:e1959v1 https://doi.org/10.7287/peerj.preprints.1959v1Author comment
The cause of over 6,000 suspected microcephaly cases in Brazil is being investigated. The primary suspect is the Zika epidemic. An alternative that has been widely dismissed is the larvicide pyriproxyfen, used in drinking water for mosquito control. Pyriproxifen is a juvenile hormone analog, which has cross-reactivity with retinoic acid, whose application during mammalian development causes microcephaly. Several other juvenile hormone analogs have been shown to cause microcephaly and other birth defects. Despite regulatory approval, toxicology studies are very limited; in the most relevant study one out of twelve exposed rat pups was found to have significantly low brain weight. We advise stopping the use of pyriproxyfen in Brazil pending better determination of its developmental toxicity.
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Dan Evans wrote the paper, reviewed drafts of the paper.
Fred Nijhout wrote the paper, reviewed drafts of the paper.
Raphael Parens wrote the paper, reviewed drafts of the paper.
Alfredo J Morales wrote the paper, reviewed drafts of the paper.
Yaneer Bar-Yam wrote the paper, reviewed drafts of the paper.
Data Deposition
The following information was supplied regarding data availability:
The research in this article did not generate any raw data.
Funding
The authors received no funding for this work.
