A Possible Link Between Pyriproxyfen and Microcephaly

TL;DR

This paper explores the hypothesis that the insecticide pyriproxyfen, used in Brazilian drinking water, may be linked to the rise in microcephaly cases, drawing parallels with other retinoid-related developmental toxins.

Contribution

It presents a biological plausibility argument and reviews existing evidence suggesting pyriproxyfen's potential role in causing microcephaly, advocating for suspension of its use pending further research.

Findings

Pyriproxyfen is a juvenile hormone analog with cross-reactivity to mammalian retinoids.

Manufacturer tests showed some evidence of developmental toxicity in rats.

Brazil's unprecedented use of pyriproxyfen in water supplies correlates with microcephaly outbreaks.

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.