Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3-1 cells.

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3-1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3-1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3-1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

Effects of iodoacetic acid drinking water disinfection byproduct on the gut microbiota and its metabolism in rats.

Iodoacetic acid (IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects of IAA on gut microbiota and its metabolism are still unknown, especially the association between gut microbiota and the metabolism and toxicity of IAA. In this study, female and male Sprague-Dawley rats were exposed to IAA at 0 and 16 mg/kg bw/day daily for 8 weeks by oral gavage. Results of 16S rRNA gene sequencing showed that IAA could alter the diversity, relative abundance and function of gut microbiota in female and male rats. IAA also increased the abundance of genes related to steroid hormone biosynthesis in the gut microbiota of male rats. Moreover, metabolomics profiling revealed that IAA could significantly disturb 6 and 13 metabolites in the feces of female and male rats, respectively. In female rats, the level of androstanediol increased in the IAA treatment group. These results were consistent with our previous findings, where IAA was identified as an androgen disruptor. Additionally, the perturbed gut microbiota and altered metabolites were correlated with each other. The results of this study indicated that IAA could disturb gut microbiota and its metabolism. These changes in gut microbiota and its metabolism were associated with the reproductive and developmental toxicity of IAA.

Androgenic and Teratogenic Effects of Iodoacetic Acid Drinking Water Disinfection Byproduct in Vitro and in Vivo.

Iodoacetic acid (IAA) is the most genotoxic iodinated disinfection byproduct known in drinking water. Previous studies have shown that IAA may be an endocrine disruptor. However, whether IAA has reproductive and developmental toxicity remains unclear. In this study, the reproductive and developmental toxicity of IAA was evaluated using a battery of in vitro and in vivo reproductive/developmental toxicity screening tests. The results of E-Screen, uterotrophic, and H295R steroidogenesis assays were negative. The Hershberger bioassay revealed that IAA could induce significant increases in absolute and relative weights of paired Cowper's glands. Moreover, there was an increasing trend in the relative weights of the ventral prostate. The micromass test showed that IAA could inhibit the differentiation of midbrain and limb bud cells. A reproductive/developmental toxicity screening test showed that IAA resulted in significantly increased relative weights of testis and seminal vesicles plus coagulating glands in parental male rats, with a dose-response relationship. IAA could not only induce head congestion in offspring but also decrease litter weight, viability index, and anogenital distance index of male pups on postnatal day 4. All these results indicated that IAA had reproductive and developmental toxicity.

Occurrence and toxicity of halobenzoquinones as drinking water disinfection byproducts.

Halobenzoquinones (HBQs) are emerging unregulated drinking water disinfection byproducts (DBPs) that are more toxic than regulated DBPs. This study aimed to determine the distribution and formation of HBQs in drinking water from water treatment plants in China, compare their chronic cytotoxicity and their induction of chromosomal damage in Chinese hamster ovary cells, and analyze the correlation of HBQ toxicity with their physicochemical parameters. Two HBQs, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) and 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), were detected in finished water and tap water in China. The concentrations were in the ranges of <2.6-19.70 ng/L for 2,6-DCBQ and <0.38-1.8 ng/L for 2,6-DBBQ. Chemical oxygen demand and residual chlorine were positively correlated with HBQ formation. The HBQ concentration was lower in a drinking water treatment plant using chlorine dioxide. High Ca2+ in tap water decreased the HBQ level. The rank order of HBQ by cytotoxicity was 2-chloro-1,4-benzoquinone > 2,3-diiodo-1,4-benzoquinone > 2,6-diiodo-1,4-benzoquinone > 2,6-dibromo-1,4-benzoquinone > 2,5-dibromo-1,4-benzoquinone > 2,5-dichloro-1,4-benzoquinone > 2,6-dichloro-1,4-benzoquinone > tetrachloro-1,4-benzoquinone > 2,3,6-trichloro-1,4-benzoquinone, and for their genotoxicity, 2,5-dichloro-1,4-benzoquinone > 2,6-dichloro-1,4-benzoquinone > 2,3-diiodo-1,4-benzoquinone > 2,6-diiodo-1,4-benzoquinone > tetrachloro-1,4-benzoquinone > 2,5-dibromo-1,4-benzoquinone > 2,6-dibromo-1,4-benzoquinone > 2,3,6-trichloro-1,4-benzoquinone. The cytotoxicity of six dihalo-HBQs was negatively correlated with the octanol-water partition coefficient (r = -0.971, P < 0.05), molar refractivity (r = -0.956, P < 0.05), energy of the highest occupied molecular orbital (EHOMO) (r = -0.943, P < 0.05), and polar surface area (r = -0.829, P < 0.05). The genotoxicity of these three pairs of dihalo-HBQ isomers followed the same order as their EHOMO values. This study reveals the occurrence and formation of HBQs in drinking water in China and systematically evaluates the chromosomal damage caused by nine HBQs in mammalian cells.

Occurrence and formation of halobenzoquinones in indoor and outdoor swimming pool waters of Nanning City, Southwest China.

Disinfection byproducts (DBPs) in swimming pool have elicited increasing worldwide concern due to their potential health risks. However, only trihalomethanes (THMs) are regulated by several local governing bodies. Studies indicated that specific unregulated DBP classes would drive disinfected water toxicity in addition to THMs. Halobenzoquinones (HBQs), a type of emerging unregulated DBPs, have been shown to be possible bladder cancer carcinogens. This study aimed to determine the distribution and formation of HBQs in indoor and outdoor swimming pool waters of Nanning City, Southwest China. Seven HBQs in water from seven public indoor and outdoor swimming pools were examined using an effective ultra-performance liquid chromatography-tandem mass spectrometry method. Results suggest the presence of 2,6-dichloro-1,4-benzoquinone in all the swimming pool waters in the range of 4.56-45.30 ng/L. Furthermore, 2,6-dibromo-1,4-benzoquinone and 3,4,5,6-tetrachloro-1,2-benzoquinone (TetraC-1,2-BQ) were detected in two pools at concentrations of < 0.38-14.20 and < 0.54-2.60 ng/L, respectively. The swimming pool water featured higher HBQs than input tap water, and TetraC-1,2-BQ was only detected in pool water. Higher HBQ levels were observed in the indoor pools than in the outdoor pools. These findings demonstrate that low NH3-N, high chloride, humic acid, chemical oxygen demand, and UV254 in the indoor pools increased the HBQ formation. This study is the first to reveal the occurrence and formation of HBQs in water from Chinese indoor and outdoor swimming pools. The findings should be useful in the management of these governing factors and HBQ controls in swimming pools.