Thyroid hormone disrupting potentials of benzisothiazolinone in embryo-larval zebrafish and rat pituitary GH3 cell line.

Benzisothiazolinone (BIT), one of the most widely used antimicrobial agents in consumer products, has frequently been detected in the water environment. The present study was conducted to determine the adverse effects of BIT on the thyroid neuroendocrine system of zebrafish embryos/larvae. Rat pituitary (GH3) cell line was employed to support the underlying mechanism of thyroid hormone disrupting effects. Significant coagulation and hatching delay were observed in embryos exposed to 30 µg/L of BIT, which in turn remarkably decreased hatchability and larval survival. In BIT-exposed larvae, tshß, tshr, and trh genes were significantly upregulated along with a decrease in thyroxine and triiodothyronine content, indicating that BIT decreased thyroid hormones and increased thyrotropin-releasing hormone and thyroid stimulating hormone secretion through a feedback circuit. The downregulation of trα and deio2 genes in the zebrafish larvae suggests the inhibition of thyroid hormone receptors and deiodination. Similar to the results in zebrafish, upregulation of tshß and downregulation of trα, trß, deio1, and deio2 genes were observed in GH3 cells. Our observations suggest that BIT can decrease the level of thyroid hormones by influencing central regulation, receptor binding, and deiodination.

Zebrafish (Danio rerio) as a model organism for screening nephrotoxic chemicals and related mechanisms.

Because of essential role in homeostasis of the body fluid and excretion of wastes, kidney damage can lead to severe impacts on health and survival of humans. For most chemicals, nephrotoxic potentials and associated mechanisms are unclear. Hence, fast and sensitive screening measures for nephrotoxic chemicals are required. In this study, the utility of zebrafish (Danio rerio) was evaluated for the investigation of chemical-induced kidney toxicity and associated modes of toxicity, based on the literature review. Zebrafish has a well-understood biology, and many overlapping physiological characteristics with mammals. One such characteristic is its kidneys, of which histology and functions are similar to those of mammals, although unique differences of zebrafish kidneys, such as kidney marrow, should be noted. Moreover, the zebrafish kidney is simpler in structure and easy to observe. For these advantages, zebrafish has been increasingly used as an experimental model for screening nephrotoxicity of chemicals and for understanding related mechanisms. Multiple endpoints of zebrafish model, from functional level, i.e., glomerular filtration, to transcriptional changes of key genes, have been assessed to identify chemical-induced kidney toxicities, and to elucidate underlying mechanisms. The most frequently studied mechanisms of chemical-induced nephrotoxicity in zebrafish include oxidative stress, inflammation, DNA damage, apoptosis, fibrosis, and cell death. To date, several pharmaceuticals, oxidizing agents, natural products, biocides, alcohols, and consumer chemicals have been demonstrated to exert different types of kidney toxicities in zebrafish. The present review shows that zebrafish model can be efficiently employed for quick and reliable assessment of kidney damage potentials of chemicals, and related toxic mechanisms. The toxicological information obtained from this model can be utilized for identification of nephrotoxic chemicals and hence for protection of public health.

Occurrence of major organic UV filters in aquatic environments and their endocrine disruption potentials: A mini-review.

Organic UV filters are frequently used in daily life, and hence are ubiquitously detected in the aquatic environment worldwide. Most monitoring efforts and toxicological studies are, however, limited to a few chemicals like benzophenone-3 (BP-3). In the present study, we chose other major organic UV filters, such as avobenzone (AVB), homosalate (HS), octisalate (OS), and octocrylene (OC), and reviewed information on their use, environmental occurrences, and endocrine disruption effects, available to date. Organic UV filters are used in high volume in many consumer applications, not only in sunscreen products but also in cosmetics, personal care products, home products, and food packaging. Environmental monitoring worldwide reveals that recreational coastal waters are among the hot spots of their contamination. An increasing number of experimental studies indicate that organic UV filters such as octinoxate (OMC), AVB, and HS may cause disruptions in sex hormones. Avobenzene and OMC can also influence thyroid function in experimental models. Observations in human population are rarely made, but OMC and OC have been associated with decreased androgenicity and increase of polycystic ovary syndrome, respectively. Further investigations are warranted to fill the knowledge gaps identified in the present study, to help develop relevant safety screening measures for organic UV filters. Integr Environ Assess Manag 2021;17:940-950. © 2021 SETAC.

Pharmaceutical residues in streams near concentrated animal feeding operations of Korea - Occurrences and associated ecological risks.

Concentrated animal feeding operations (CAFOs) have been suggested to be the most significant source of pharmaceutical release into the environment. However, limited information is available on the occurrence of veterinary pharmaceutical residues and the associated ecological risks to the aquatic environment near CAFO areas. In this study, ten commonly used veterinary antibiotics, including sulfonamides, tetracyclines, and cephalosporins, along with three analgesics, were measured in water samples collected from the streams that run near two CAFOs in Korea in 2013 (n = 16) and 2014 (n = 10). In addition, the associated ecological risks were estimated by calculating risk quotient. The pharmaceuticals were detected in a higher amount in the samples collected downstream from the CAFO than in those collected upstream. Acetaminophen, sulfamethazine, sulfathiazole, and oxytetracycline were detected at maximum concentrations of 38.8 µg/L, 21.3 µg/L, 17.4 µg/L, and 16.9 µg/L, respectively. Relatively higher concentrations of pharmaceuticals were observed in locations adjacent to the CAFO and the downstream area, suggesting the influence of the CAFO. Except for acetaminophen, lower concentrations of the target pharmaceuticals were detected in the samples collected during the high-flow season. The concentrations of most of the target pharmaceuticals exceeded the risk quotient of one, suggesting potential ecological effects in the areas affected by CAFOs. Our observations show that the water environment near a CAFO could be heavily affected by veterinary pharmaceuticals and analgesic drugs that are also frequently used among humans. Hence, the ecological consequences of pharmaceutical residues in the water bodies near CAFOs warrant further investigation.

Thyroid endocrine disruption in male zebrafish following exposure to binary mixture of bisphenol AF and sulfamethoxazole.

Thyroid endocrine disruption by bisphenol AF (BPAF) alone or in combination with sulfamethoxazole (SMX) exposure was evaluated in adult male zebrafish. Changes in thyroid gene transcription were examined using microarrays and were linked to effects on thyroxine hormone production and transcription of genes related to the hypothalamic-pituitary-thyroid axis. BPAF alone or in combination with SMX affected genes related to thyroid hormone production and receptor activity, thyroid gland development, and deiodinase activity. Increases in thyroxine levels, and gene transcription were more pronounced in the BPAF and SMX mixture group than in the BPAF group. Significant down-regulation of trh and tshß genes in the brain suggested a negative feedback response resulting in increased thyroxine levels. The present study indicated that BPAF exposure alone alters transcription of genes associated with the thyroid endocrine system, and combination with SMX could increase the endocrine disrupting effect of BPAF.

Effects of tris(2-butoxyethyl) phosphate exposure on endocrine systems and reproduction of zebrafish (Danio rerio).

Tris(2-butoxyethyl) phosphate (TBEOP), a widely used organophosphate flame retardant, has frequently been detected both in the environment and the biota. However, limited information is available on the effects of TBEOP on the endocrine system and its underlying mechanisms. We exposed adult zebrafish pairs to TBEOP at concentrations of 0, 2.1, 11, and 118 µg/L for 21 d, and investigated the effects on gene transcription and hormone production related to the hypothalamic-pituitary-gonadal (HPG) axis, and on reproduction. The adverse effects on the F1 generation were further examined. In male fish, plasma concentrations of 17ß-estradiol were significantly increased along with up-regulation of cyp19a. Exposure to TBEOP at 118 µg/L led to a significant decrease in average egg production. Exposure of the F0 generation to TBEOP delayed hatching and lowered hatching rates in the F1 generation. The results demonstrate that exposure to TBEOP at environmentally relevant concentration levels could affect the sex hormone balance by altering regulatory circuits of the HPG axis, eventually leading to disruption of reproductive performance and the development of offspring.

Major benzophenone concentrations and influence of food consumption among the general population in Korea, and the association with oxidative stress biomarker.

Benzophenones (BPs) have been used as sunscreen agents and as ultraviolet stabilizers in plastic surface coatings for food packaging. However, few studies have been performed to examine the level of human exposure to BPs and the potential sources of such exposure. We evaluated the exposure levels to six major BPs (BP-1, BP-2, BP-3, BP-4, BP-8, and 4-hydroxybenzophenone (4-OH-BP)) among the adult population in two cities in Korea, and investigated the potential dietary sources of the BPs. Urinary levels of malondialdehyde (MDA) as an oxidative stress biomarker as well as their association with the levels of BPs were also analyzed. Among the six BPs analyzed, 4-OH-BP, BP-1, BP-3, and BP-4 were detected in 77%, 49%, 27%, and 21% of the population, respectively. BP concentrations were relatively higher in younger (people in their 20s and 30s) cosmetic users and leaner women. Even after the adjustment of age, body mass index, and cosmetic use, the consumption of frozen storage food, instant noodles, and instant coffee was significantly correlated with urinary BPs, and these associations were sex-dependent. No significant correlation was observed between the levels of BPs and levels of MDA. The results of the present study will be useful for developing plans of public health management of BPs.

Effects of Barium Chloride Exposure on Hormones and Genes of the Hypothalamic-Pituitary-Gonad Axis, and Reproduction of Zebrafish (Danio rerio).

Adult zebrafish pairs were exposed to sub-lethal concentrations of BaCl2 for 21 days, and the effects on reproduction, sex steroid hormones, and transcription of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. The adverse effects on performances of F1 generation were further examined with or without subsequent exposure to BaCl2. Egg production was significantly decreased, and parental exposure to BaCl2 resulted in lesser rates of hatching. In males, exposure to BaCl2 resulted in greater concentrations of E2 along with greater mRNA expression of cyp19a. The results demonstrated that BaCl2 could modulate gene transcriptions and hormone production of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.