Abstract
Exposure to endocrine-disrupting compounds (EDCs) during pregnancy can result in negative health effects in later generations, including sex changes and feminization. The present study assessed the feminization effects on male offspring rats of three EDCs: Dienestrol (DIES), Linuron (LIN), and Flutamide (FLU). Sexually mature female rats were exposed from gestation day (GD) 6 until postnatal day (PND) 21 to: 0.37, 0.75, 1.5, 3.12 or 6.25 μg/kg/day of DIES, 1.5, 3, 6, 12.5, 25 or 50 mg/kg/day of LIN, 3.5, 6.7, 12.5, 25 or 50 mg/kg/day of FLU, and the following mixtures: FLU + DIES (mg/kg/day+μg/kg/day), 3.5 + 0.37, or 3.5 + 3, 25 + 0.37, or 25 + 3; FLU + LIN (mg/kg/day + mg/kg/day), 3.5 + 12.5, or 25 + 12.5; and DIES + LIN (μg/kg/day + mg/kg/day), 0.37 + 12.5, or 3 + 12.5. Anogenital distance (AGD), nipple retention (NR) and cryptorchidism were evaluated. FLU produced a decrease of AGD, an increase of NR, and an increase of cryptorchidism at the highest dose. None of these three endpoints were significantly affected by LIN or DIES treatments alone. Combinations of FLU + LIN and FLU + DIES increased NR, and decreased AGD, while DIES + LIN did not produce any effects in male pups. Results show that FLU is able to induce feminization in male pups, while binary combinations of LIN and DIES did not modify the effects produced by FLU.
Highlights
Many chemicals are essential components of a number of products that are part of our daily lives
Taking the above into account, the aim of the current study was to assess the feminization effects in offspring male rats whose mothers were exposed to DIES, LIN and FLU either individually or in binary mixtures, in order to evaluate whether these compounds act additively
Dienestrol has been found in bovine muscle (Malone et al, 2009) and even in seawater (He et al, 2016)
Summary
Many chemicals are essential components of a number of products that are part of our daily lives. Exposure to some of these chemicals can cause adverse health effects Though many of these single chemicals are tested regarding their toxicological profile this is not the case for mixtures of chemicals and especially under real-life exposure scenarios (Tsatsakis et al, 2016, 2019; Tsatsakis, 2020; Docea et al, 2018; Kostoff et al, 2018; Hernández et al, 2020). This is why testing of chemical mixture is of great importance. The presence of EDCs in both the environment and foodstuffs has raised concerns about the potentially harmful effects of exposure to such chemicals (ECHA, 2018a; Roszko et al, 2018)
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