In an article published on February 16, 2017 in the peer-reviewed journal Genes & Nutrition, Daniele Marcoccia and colleagues from Istituto Superiore di Sanita (ISS), Italy, review food components and food contaminants that can act as (anti)androgenic molecules. Androgens are steroid hormones that in males regulate sexual differentiation, pubertal development, spermatogenesis, and maintenance of secondary sexual characteristics. Androgens also act in several non-reproductive tissues, such as bone, muscle, and fat tissues, as well as the central nervous system.

Various endocrine disrupting chemicals (EDCs) are known to interfere with androgen actions in reproductive and non-reproductive tissues. These compounds include both chemicals of natural origin, such as plant polyphenols, as well as synthetic chemicals such as industrial solvents and lubricants, plasticizers, additives, pesticides, and pharmaceuticals.

Among the food packaging-relevant chemicals, the authors focused on bisphenol A (BPA, CAS 80-05-7), and several phthalates, and reviewed the evidence of their interference with the androgen receptor function or actions. The authors further drew attention to the fact that “a large number of [androgen receptor] antagonists from a wide variety of sources and exposure routes have the ability of acting together at the receptor to produce joint effects at very low concentrations that individually do not induce observable AR antagonistic effects.” For example, a 2014 study showed a complete suppression of androgenic effects by the mixture of the different androgen receptor antagonists combined at individual concentrations known to inhibit the action of the reference androgen by as low as 1%.

A study published on November 18, 2016 in the peer-reviewed journal Chemical Research in Toxicology assessed the list of ToxCast/Tox21 chemicals able to interact with the androgen receptor.  Nicole Kleinstreuer and colleagues from the U.S. National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed a computational model based on 11 in vitro assays for the androgen receptor activity available in ToxCast. Among the 1855 chemicals run through this model, 1461 were predicted to be inactive on the androgen receptor pathway, and 174 had inconclusive low scores. The remaining 220 chemicals were predicted to be either androgen receptor agonists (33 chemicals) or antagonists (192 chemicals); 5 chemicals shared both activities. Among these chemicals were several phthalates, parabens and phenols known to be used in food packaging and other consumer products.

References

Marcoccia, D., et al. (2017). «Food components and contaminants as (anti)androgenic molecules.» Genes & Nutrition 12:6

Kleinstreuer, N., et al. (2016). “Development and validation of a computational model for androgen receptor activity.Chemical Research in Toxicology (published November 18, 2016).

Orton, F., et al. (2014). “Mixture effects at very low doses with combinations of anti-androgenic pesticides, antioxidants, industrial pollutant and chemicals used in personal care products.Toxicology and Applied Pharmacology 2783: 201-208.

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