Summary and Abbreviations

Summary

215.                This paper presents an overview of the in vivo data for thyroid toxicity. It does not contain an overall summary and conclusions as these will be provided once the review of in vitro and epidemiological data has taken place. A review of authoritative body opinions and evaluation of adversity will also be undertaken. Nevertheless, some key points to note are discussed below.

216.                All seven PFAS showed decreases in TH levels (including in offspring) but generally without an associated rise in TSH levels, and there were sex differences in response. There is disagreement between researchers about the biological significance of these findings.

217.                Thyroid morphology was examined in 18 of the 27 studies on the seven PFAS, but adverse findings (follicular epithelial cell hyperplasia and hypertrophy) were only found in four studies on four different PFAS, of which only one study measured TH and showed it to be reduced. The significance of these morphological changes in these studies is uncertain as it is suggested that they could be secondary to liver hypertrophy and the induction of metabolic liver enzymes leading to an increase in T4 and TSH. Moreover, as T4 in rodents has a short half-life, they are more sensitive, hence this effect may not be relevant to non-rodent species.

218.                Authoritative bodies such as the Agency for Toxic Substances and Disease Registry (ATSDR) based their point of departure (POD) on effects on thyroid pathology, while the United States Environmental Protection Agency (US EPA) consider reduced TH levels to be an indication of adverse effects. These opinions will be explored in future papers.

219.                Overall, the in vivo evidence indicates that low doses of PFAS can produce adverse effects on levels of thyroid hormones (without affecting TSH levels), and at higher doses, can produce morphological alterations in the thyroid. However, some of the findings are inconsistent, sex-specific and difficult to interpret in terms of adversity and human relevance.

Questions on which the views of the Committee are sought

220.             Members are invited to consider the following questions:

i).     Are there any specific papers that the subgroup would like to review in more detail?

iii)     Would a discussion of adversity and human relevance be useful at this stage, or should this await a consideration of epidemiological data?

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August 2023 List of Abbreviations and Technical terms