ORIGINAL ABSTRACT

Glyphosate (G) is the active ingredient of the most widely used herbicide products. It targets the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which lacks in humans, suggesting to confer a low mammalian toxicity to G-based herbicides (GBHs). Despite this, the use of G is currently under intense debate. Many studies indicating its hazard and toxicity on non-target organisms are emerging, and associations between GBHs and immune-endocrine disturbances have been described. This review aims to investigate, based on recent epidemiological studies and studies performed in vitro and in vivo in animals, the possible association between GBHs and immune-endocrine alterations. Published data suggest that GBHs have endocrine disrupting potentiality targeting sex and thyroid hormones, although its relevance for humans will require further investigations. Evidence of immunotoxicity are limited compared to those on endocrine effects, but overall highlight possible noxious effects, including lung inflammation and rhinitis. An attractive hypothesis could be the one that connects microbiota dysbiosis with possible immune-endocrine outcomes. Indeed, several intestinal microorganisms express the enzyme EPSPS and, studies are emerging that highlight a possible G-induced dysbiosis. Considering the wide use of GBHs in agriculture, further studies investigating their noxious effects at levels relevant for human exposure should be performed. A critical analysis of emerging evidence of G toxicity is required to better characterize its safety profile. In addition, attention should be paid to the differences between G alone and its formulations, which, containing substances able to increase G absorption, may present a different toxicity profile.