Klopcic Ivana, Dolenc Marija Sollner
Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia Aškerceva 7.
Toxicol Sci. 2017 Mar 1;156(1):240-251. doi: 10.1093/toxsci/kfw253.
Personal care products are used increasingly, resulting in growing concern concerning their potential disruption of normal hormonal functions. Recent results on the bioaccumulation of cosmetic ingredients in wildlife and humans point to the need for an in-depth analysis for endocrine activity, in particular with respect to their influence on the androgen (AR), glucocorticoid (GR), and thyroid hormone receptors (TRs). Furthermore, humans are commonly exposed simultaneously to complex mixtures of endocrine active compounds. We have therefore examined 3 frequently used cosmetic ingredients: 2-methylresorcinol (2MR), butylated hydroxyanisole (BHA) and avobenzone (AVB), for (anti)-androgen-, (anti)-glucocorticoid-, and (anti)-thyroid hormone-like activities. Their binary and ternary mixtures at EC50 or IC50 concentrations have also been examined for anti-androgen-, glucocorticoid-, and thyroid hormone-like activities. In the MDA-kb2 reporter cell line, compounds possessed anti-androgen-, glucocorticoid-, and anti-glucocorticoid-like activities (except AVB). A new cell line, GH3.TRE-Luc, was used to evaluate anti-thyroid and thyroid hormone-like activities. The combinations 2MR + BHA and 2MR + BHA + AVB have glucocorticoid-like activity: only 2MR + AVB has anti-androgen-like activity. On the other hand, binary and ternary mixtures of compounds showed no thyroid hormone-like activity. Thus, in addition to identifying new endocrine disrupting compounds, it is also necessary to determine the effects of their mixtures in order to assess fully their risk to human health.
个人护理产品的使用日益增加，这引发了人们对其可能干扰正常激素功能的日益担忧。近期关于化妆品成分在野生动物和人类体内生物累积的研究结果表明，有必要对内分泌活性进行深入分析，特别是它们对雄激素受体（AR）、糖皮质激素受体（GR）和甲状腺激素受体（TRs）的影响。此外，人类通常同时接触内分泌活性化合物的复杂混合物。因此，我们检测了3种常用的化妆品成分：2-甲基间苯二酚（2MR）、丁基羟基茴香醚（BHA）和阿伏苯宗（AVB）的（抗）雄激素、（抗）糖皮质激素和（抗）甲状腺激素样活性。还检测了它们在EC50或IC50浓度下的二元和三元混合物的抗雄激素、糖皮质激素和甲状腺激素样活性。在MDA-kb2报告细胞系中，这些化合物具有抗雄激素、糖皮质激素和抗糖皮质激素样活性（阿伏苯宗除外）。一种新的细胞系GH3.TRE-Luc被用于评估抗甲状腺和甲状腺激素样活性。2MR + BHA以及2MR + BHA + AVB组合具有糖皮质激素样活性：只有2MR + AVB具有抗雄激素样活性。另一方面，这些化合物的二元和三元混合物没有显示出甲状腺激素样活性。因此，除了识别新的内分泌干扰化合物外，还需要确定它们混合物的影响，以便全面评估其对人类健康的风险。
