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

Abstract

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.

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

“…Thus, IAA also inhibits several enzymes in many cells and biological pathways, since it is an inhibitor of cysteine-dependent enzymes at the active site [ 38 ]. In addition to glycolysis and specific GAPDH inhibition, it also induces in vivo toxicity [ 39 ]. In future, it might require further proof on gintonin effects against ROS using another model system.…”

Research Progress of the Endocrine-Disrupting Effects of Disinfection Byproducts

“…Iodoacetic acid (IAA) was observed to show AR binding in vitro [50]. Despite the discrepancies between this result and others, studies have still demonstrated that IAA is a potential disruptor of human AR (hAR) [51]. The differences in research results may be due to factors such as the selection of species of cells and diverse endpoints.…”

“…The available literature was further refined by considering whether MIEs were defined or not. Finally, 32 studies related to the endocrine system-disrupting effects of DBPs were selected in the present investigation [ 28 , 49 , 50 , 51 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. As expected, most of the research on the endocrine-related detrimental effects of various DBPs were published in the last ten years even though the first publication dated back to 2003 (only seven publications from 2000 to 2009 and 25 from 2010 until now) ( Figure 1 ).…”

“…The endocrine hormones of organisms such as thyroid hormones (THs), estrogen, and androgen regulate many critical physiological processes, e.g., growth and metamorphosis [ 49 , 50 , 51 ]. However, it is well known that a number of anthropogenic substances named endocrine-disrupting chemicals (EDCs) can elicit potential endocrine-disrupting effects on human and wildlife [ 52 , 53 , 54 ].…”

Mini Review: Advances in 2-Haloacid Dehalogenases

“…Haloacetic acids are the second most prominent class of disinfection by-products, and are frequently detected in surface and drinking water systems. These compounds have genotoxic, mutagenic, cytotoxic, and tumorigenic effects in humans (Kim et al, 2020;Long et al, 2021;. In metabolically engineered Burkholderia species, the degradation activity of haloacetic acids can be increased by 4-8 times (Su et al, 2013).…”