Changes in Rat Mammary Tissue Architecture Following Pregnancy/Lactation Exposure to Glyphosate Alone or with 2,4-D and Dicamba.

The current study aimed to assess the possible endocrine disruptor effects on rat mammary tissue and reproductive organs during pregnancy and lactation when exposed to low doses of glyphosate and its combination with 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba. The study involved the exposure of pregnant Wistar rats to various regulatory-relevant doses of glyphosate, ranging from gestational day 6 until fine of the lactation period. Glyphosate doses corresponded to the European Union's glyphosate-acceptable daily intake (ADI; 0.5mg/kg bw/day) and no observed adverse effect level (NOAEL; 50mg/kg bw/day). The dose of the mixture of glyphosate, dicamba, and 2,4-D was at the European Union ADI for each herbicide namely 0.5, 0.002, and 0.3mg/kg bw/day, respectively. In the animals exposed to glyphosate NOAEL serum estradiol levels were increased compared to untreated animals, along with an upregulation of TNF-?, MMP-2, and MMP-9 as measured in mammary gland homogenates compared to non-treated animals. Moreover, in this group, a focally acute inflammatory infiltrate was observed in the mammary gland. Our study showed that short-term exposure to glyphosate at doses that are set as safe by regulators and thus without risk corroborated with a particular physiological state as gestation and lactation, can give rise to inflammatory changes in breast tissue in rats. These findings support the need for further evaluation of glyphosate and mixtures of glyphosate with other pesticides for public health protection, especially for those categories vulnerable to the potential endocrine disruptor properties of these pesticides such as pregnant women, newborns, and children.

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.