Chemicals impairing thyroid: a worthy concern for European risk assessors

Endocrine disrupting chemicals (EDC) are a concern for European risk assessors; those targeting thyroid are a subgroup that currently undergo an even closer scrutiny.

A European workshop on thyroid disruption has been held on March 2017 in the premises of the French Agency for Food, Environmental and Occupational Health & Safety – ANSES. The workshop participants (more than 70 alltogether) were from EU, OECD, EU and non-EU national authorities, industry, academia and non-governmental organisations.

There are several reasons why chemicals that may target thyroid deserve attention. Thyroid is a key regulator of growth and metabolism for vertebrates; the developing organism is particularly susceptible to thyroid dysfunction which, may, nevertheless, affect all lifestages; diet, and in particular iodine intake, is critical for thyroid function, indeed even mild iodine deficiency may increase the susceptibility to chemically-induced disruption, as pointed out in the opinion on the contaminant perchlorate issued by the European Food Safety Authority on 2014;  finally, a substantial number of EDC do target the thyroid, with persistent pollutants (polychlorinated biphenyls, brominated flame retardants, perfluorinated substances) amd pesticides (fipronil, mancozeb, etc.) featuring prominently.

The European workshop

The European workshop discussed the interpretation of experimental laboratory studies, wildlife field data as well as human epidemiological data in relation to the identification of thyroid disrupting substances; moreover the meeting strove to identify ways forward in addressing knowledge gaps. Experiments with chemicals indicate that the regulation of thyroid homeostasis can be more complex and less linear than previously thought. For instance, increases in pituitary-secreted thyroid stimulating hormone are expected to occur as a consequence of recuded circulating thyroid hormone; however, certain chemicals (e.g., brominated or perfluorinated substances) can induce thyroid hormone insufficiency without subsequent increases in the stimulating hormone, thus supporting the recent evidence that thyroid hormone action may be regulated (or disrupted) also peripherally, without involvement of the pituitary control.

Clearance of thyroid hormones

One peripheral mechanism is the clearance of thyroid hormones by the liver which, therefore, plays a major role in the maintenance of thyroid homeostasis; thus, hepatic metabolism of hormones should be considered as a further potential target of chemicals leading to disruption. These seemingly academic issues are in fact relevant to build consistent and science-based critera in order to identify EDC that impair thyroid function: since EDC are substances of high concern in the current European legislations on chemicals, the identification of a substance as an EDC is directly linked with regulatory measures intended to restrict or replace its use8s).

Endocrine Disrupting Chemicals

EDC are substances causing adverse effects by altering hormone homeostasis. Then, can changes in serum hormone levels be regarded as adverse per se? Or they are just reversible effects without lasting consequences? This is another question relevant to EDC identification. The Workshop outlined that more knowledge is required in order to link the patterns of hormone changes, as observed in both rodent toxicological and human epidemiological studies, to biomarkers of adversity in main systems and organs regulated by the thyroid. These include, first, brain development (morphology, function, expression of thyroid hormone-dependent genes), but also basal metabolism (lipid metabolism and the cardiovascular system). Nvertheless, changes in serum thyroxine (hormone T4) levels in rodents, especially during pregnancy or also postnatal development, should be regarded as an adverse effect, due to the impact of even moderate hypothyroidism on the developing brain. Of course, data should be interpreted together with other available information, e.g., to rule out apparent “endocrine” changes that are secondary to general toxicity. Thus, whereas criteria  for toxicological and epidemiological studies need improvements, current data sets allow to identify thyroid-disrupting EDC.

The workshsop report is available at the portal of EU Publications

thyroid disruption final report

 

Alberto Mantovani,

Istituto Superiore di Sanità, Roma – Italy

alberto.mantovani@iss.it

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