Abstract
The effects of chemicals on the thyroid gland have received increasing attention in recent years, as epidemiological studies have shown a link between inadequate levels of circulating thyroid hormones (TH) in pregnant women and reduced intelligence in their offspring. This evidence has led the OECD to revise its test guidelines since 2016 to include endpoints such as blood TH concentrations and thyroid histopathology for relevant toxicity tests. This highlights the increasing importance of accumulating historical control data (HCD) for these endpoints in order to properly assess the effects of chemicals on the thyroid. Meanwhile, the revisions to the test guidelines have also added appropriate standards for the levels of phytoestrogens in rodent diets, which should be kept below 350 μg/g diet as genistein equivalent. This appears to be aimed at improving the power to detect effects by disrupting the estrogenic modality. However, one type of phytoestrogen, genistein, is known to have inhibitory effects on thyroid peroxidase activity and the other potential effects on the thyroid system, suggesting that this revision may not be negligible for the evaluation of thyroid effects.We have investigated whether differences in the basal experimental conditions, specifically rat colonies and dietary components, may have an impact on study results, and have therefore collected HCD. As part of this effort, we present here the data on thyroid-related endpoints in male and female Wistar Hannover GALAS rats (CLEA Japan, Inc.) from two different colonies maintained in Japan and Thailand, which were fed a normal diet (MF) or a diet with reduced levels of phytoestrogens (NIH-07PLD, both manufactured by Oriental Yeast Co., Ltd.) for two generations. The results showed that there were only limited effects of the different diets on the serum THs concentration, thyroid weight, or the incidence of histopathological findings in the thyroid. In contrast, clear effects were found for the colony difference, with the serum T4 concentration of the Japanese rats being higher than that of the Thai rats, and this trend was maintained over three generations (P, F1, and F2). We also discuss a lesson from these results that data can vary significantly depending on the lots of animals.
