Endocrine Activity of AVB, 2MR, BHA, and Their Mixtures

Toxicol Sci. 2017 Mar 1;156(1):240-251. doi: 10.1093/toxsci/kfw253.

Abstract

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.

Keywords: androgen receptor; cosmetic ingredients; effects of mixtures.; endocrine disruption; glucocorticoid receptor; thyroid hormone receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / toxicity
  • Androgen Receptor Antagonists / adverse effects
  • Androgen Receptor Antagonists / toxicity
  • Animals
  • Antithyroid Agents / adverse effects
  • Antithyroid Agents / toxicity
  • Butylated Hydroxyanisole / adverse effects
  • Butylated Hydroxyanisole / toxicity*
  • Cell Line, Transformed
  • Complex Mixtures / adverse effects
  • Complex Mixtures / toxicity
  • Cosmetics / toxicity*
  • Dermatologic Agents / adverse effects
  • Endocrine Disruptors / adverse effects
  • Endocrine Disruptors / toxicity*
  • Female
  • Genes, Reporter / drug effects
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / metabolism
  • Humans
  • Kinetics
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / metabolism
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Propiophenones / adverse effects
  • Propiophenones / toxicity*
  • Rats
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Thyroid Hormone / antagonists & inhibitors
  • Receptors, Thyroid Hormone / metabolism
  • Resorcinols / adverse effects
  • Resorcinols / toxicity*

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Antithyroid Agents
  • Complex Mixtures
  • Cosmetics
  • Dermatologic Agents
  • Endocrine Disruptors
  • Glucocorticoids
  • Propiophenones
  • Receptors, Glucocorticoid
  • Receptors, Thyroid Hormone
  • Resorcinols
  • Butylated Hydroxyanisole
  • 2-methylresorcinol
  • avobenzone