Thyroid disruptors

Endocrine disruptors (EDs) pose a serious threat to human health and the environment and require a comprehensive evaluation to be identified. The identification of EDs require a substantial amount of data, both in vitro and in vivo, due to the current scientific criteria in the EU. At the same time, the EU strives to reduce animal testing due to concerns regarding animal welfare and sensitivity of animal studies to adequately detect adverse effects relevant for human health. Perfluorooctane sulfonic acid (PFOS) is a persistent organic pollutant that is suspected to be an ED based on academic research, however it is not identified as such from a regulatory perspective...

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS)...

Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six-week-old male and female Sprague-Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days...

In recent years, environmental epidemiology and toxicology have seen a growing interest in the environmental factors that contribute to the increased prevalence of neurodevelopmental disorders, with the purpose of establishing appropriate prevention strategies. A literature review was performed, and 192 articles covering the topic of endocrine disruptors and neurodevelopmental disorders were found, focusing on polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol A, and pesticides. This study contributes to analyzing their effect on the molecular mechanism in maternal and infant thyroid function, essential for infant neurodevelopment, and whose alteration has been associated with various neurodevelopmental disorders...

Thyroid hormones are involved in many biological processes such as neurogenesis, metabolism, and development. However, compounds called endocrine disruptors can alter thyroid hormone signaling and induce unwanted effects on human and ecosystems health. Regulatory tests have been developed to detect these compounds but need to be significantly improved by proposing novel endpoints and key events. The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD test guideline no. 248) is one such test. It is based on Xenopus laevis tadpoles, a particularly sensitive model system for studying the physiology and disruption of thyroid hormone signaling: amphibian metamorphosis is a spectacular (thus easy to monitor) life cycle transition governed by thyroid hormones...

BACKGROUND: The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation and persistence in the environment and animals as well as for their hazardous health effects. As a result, new congeners of PFAS have rapidly replaced the so-called "old long-chain PFAS" (mainly PFOA and PFOS), currently out-of-law and banned by most countries. These compounds derive from the original structure of "old long-chain PFAS", by cutting or making little conformational changes to their structure, thus obtaining new molecules with similar industrial applications...

Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition...

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks...

BACKGROUND: Epidemiological data regarding thyroid diseases are lacking, in particular for occupationally exposed populations. OBJECTIVES: To compare the risk of hypothyroidism and hyperthyroidism between farming activities within the complete population of French farm managers (FMs). METHODS: Digital health data from retrospective administrative databases, including insurance claims and electronic health/medical records, was employed. This cohort data spanned the entirety of French farm managers (FMs) who had undertaken work at least once from 2002 to 2016...

Worldwide, disorders of the thyroid gland are a growing concern; such can be caused by exposure to contaminants, including agrochemicals used in conventional agriculture, which act as endocrine disruptors. The purpose of this study is to evaluate whether or not exposure to an environment with conventional agriculture leads to thyroid disruption. Mus musculus were used as bioindicator species, captured in two sites: a farm where conventional agriculture is practiced, and a place without agriculture. Thyroid histomorphometric and morphologic data were analyzed...

Thyroid disease has been rapidly increasing, but its causes remain unclear. At present, many studies have focused on the relationship between environmental endocrine disruptors (EEDs) and the pathogenesis of thyroid disease. Herein, we summarize such studies exploring the effects of exposure to common EEDs on thyrotoxicosis, finding that EEDs appear to contribute to the pathogenesis of thyroid-related diseases such as thyroid cancer, goiter, thyroiditis, hyperthyroidism, and hypothyroidism. To explore this causative effect in detail, we have analyzed the following three aspects of how EEDs are believed to exert their impacts on the occurrence and development of thyroid disease: (1) damage to the thyroid tissue structure, including disrupted mitochondria and the stratification of thyroid follicular epithelial cells; (2) disruption of thyroid hormone signaling, including thyroid hormone synthesis and secretion disorders, destruction of normal function of the hypothalamus-pituitary-thyroid axis, disturbed estrogen signaling in the body, alterations to the level of thyroid-stimulating hormone, inhibition of the release of thyroglobulin from thyroid cells, and reductions in the levels of sodium iodide co-transporters, thyroid peroxidase, deiodinase, and transthyretin; and (3) molecular mechanisms underlying the disruption of thyroid function, including competitive binding to T3 and T4 receptors, disturbance of the hypothalamic-pituitary-thyroid axis, activation of the ERK and Akt pathways, oxidative stress, regulation of the expression of the proto-oncogene k-Ras, tumor suppressor gene PTEN, and thyroid TSHR gene, and induction of autophagy in thyroid cells...

INTRODUCTION: depressive symptoms may develop in subclinical hypothyroidism and their presence usually facilitates recognition and the establishment of replacement treatment; however, recent studies have found no association between the two. Be-sides, thyroid function can be affected by endocrine disruptors and some of them, such as chlorates, can be found in the water we drink. OBJECTIVES: to know if the type of water consumed may influence the development of depressive symptoms in patients with subclinical hypothyroidism...

In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). "We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g., hand disinfectants, disinfection of animals' teats/udder, embalming fluids before cremation, etc.) that contain molecular iodine (I2), entirely neglecting [see the 2013 ECHA Regulation (EU) n°528/2012 describing iodine as being of "great importance for human health"...

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural origins that are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests...

Cadmium (Cd) exposure is a persistent pollution problem, necessitating caution in using cadmium-expelling complexing agents. Currently, there is no targeted therapy to treat Cd poisoning. The thyroid gland is a major endocrine organ that directly regulates thyroid hormones involved in various physiological processes and is a target organ for Cd accumulation. Herein, the effects of Cd exposure on swine thyroid glands were investigated. Six-week-old male pigs were randomly divided into the Cd and control groups...

Microbial bioremediation can provide an environmentally friendly and scalable solution to treat contaminated soil and water. However, microbes have yet to optimize pathways for degrading persistent anthropogenic pollutants, in particular organohalides. In this work, we first expand our repertoire of enzymes useful for bioremediation. By screening a panel of cobalamin (B12 )-dependent reductive dehalogenases, we identified previously unreported enzymes that dechlorinate perchloroethene and regioselectively deiodinate the thyroidal disruptor 2,4,6-triiodophenol...

BACKGROUND: N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats. METHODS: Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube...

Phthalate and non-phthalate plasticizers are used in polymer materials, such as plastic and rubber. It has recently been found that diisobutyl adipate (DIBA), which is considered an environmentally safe non-phthalate plasticizer, potentially acts as a thyroid disruptor in fish. Here, we investigated the sexual hormone effects of DIBA based on the expression levels of genes that respond to endocrine disruption and sexual hormone activity in the livers and gonads, and on gonadal sexual differentiation in Japanese medaka...

OBJECTIVE: to estimate the risk of thyroid cancer incidence in the population of Ukraine in connection with its exposure to radioactive iodine fallout of Chornobyl origin and the use of pesticides in agricultural production in the country. OBJECT OF STUDY: Incidence rates of thyroid cancer in the population of Ukraine in 2001-2019, average regional radiation doses absorbed by the thyroid because of the Chornobyl accident, the volume of use of various groups of pesticides in the regions of Ukraine...

BACKGROUND: Thyroid carcinoma (THCA), the most common endocrine neoplasm, typically exhibits an indolent behavior. However, in some instances, lymph node metastasis (LNM) may occur in the early stages, with the underlying mechanisms not yet fully understood. MATERIALS AND METHODS: LNM potential was defined as the tumor's capability to metastasize to lymph nodes at an early stage, even when the tumor volume is small. We performed differential expression analysis using the 'Limma' R package and conducted enrichment analyses using the Metascape tool...