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A Possible Link Between Pyriproxyfen and Microcephaly

Dan Evans, Fred Nijhout, Raphael Parens, Alfredo J. Morales, Yaneer Bar-Yam
doi: https://doi.org/10.1101/048538
Dan Evans
*New England Complex Systems Institute, 210 Broadway Suite 101, Cambridge MA 02139,
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Fred Nijhout
‡Department of Biology, Duke University, Durham, NC 27708
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Raphael Parens
*New England Complex Systems Institute, 210 Broadway Suite 101, Cambridge MA 02139,
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Alfredo J. Morales
*New England Complex Systems Institute, 210 Broadway Suite 101, Cambridge MA 02139,
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Yaneer Bar-Yam
*New England Complex Systems Institute, 210 Broadway Suite 101, Cambridge MA 02139,
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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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 13, 2016.
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A Possible Link Between Pyriproxyfen and Microcephaly
Dan Evans, Fred Nijhout, Raphael Parens, Alfredo J. Morales, Yaneer Bar-Yam
bioRxiv 048538; doi: https://doi.org/10.1101/048538
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A Possible Link Between Pyriproxyfen and Microcephaly
Dan Evans, Fred Nijhout, Raphael Parens, Alfredo J. Morales, Yaneer Bar-Yam
bioRxiv 048538; doi: https://doi.org/10.1101/048538

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