The occurrence of antimicrobial agent triclosan (TCS) in the global aquatic and terrestrial environment is an emerging concern. While risk assessment for TCS is available in certain countries, no ...studies have attempted to assess the risk of TCS worldwide. This could be due to lack of method to characterize the global exposure. The present study therefore proposed a probabilistic-based approach to approximate the percent-ranked measured environmental concentrations (MECs) by estimating exposure concentration distribution (ECD) for different environmental compartments on a global scale, incorporating approximate 1200 single MECs. Hazard of TCS was assessed from species sensitivity distribution as well as predicted no effect concentrations (PNECs) derived from ecotoxicological and toxicological endpoints. We draw on experiences from previous risk assessment exercises and present a holistic approach for characterizing the risk of TCS to microorganism in sewage treatment plant, aquatic and soil organisms, avian and mammalian species, and humans. Using the approach, we estimated risk of TCS to organisms dwelling in sediment and living in surface waters, and the risk quotients (MEC/PNEC) were within the range of 0.95 – 33.3 and 0.49 – 9.5, respectively. While the risk quotients for other environmental compartments were below a value of 1, there are large uncertainties likely due to an insufficient dataset of exposure and hazard of TCS.
•Probabilistic-based approach using MECs well represents the global exposure to TCS.•Hazard of TCS can be characterized via construction of SSD curve.•Aquatic and sediment-dwelling species are under threat from exposure to TCS.•High uncertainty exists in the risk assessment of TCS on organisms living in soil.
Tris(2-chloroisopropyl) phosphate (TCIPP) is an organophosphate flame retardant detected in the environment and eggs, feathers, and livers. Early-developmental-stage avian embryos are vulnerable to ...the toxic effects of chemicals. However, studies on the specific effects of TCIPP on avian embryonic development are limited. We aimed to investigate the toxicity of TCIPP in early chicken embryos using a previously developed shell-less incubation system. Fertilized chicken (Gallus gallus domesticus) eggs (n = 220) were exposed to 50 or 500 nmol TCIPP/(g egg) or dimethyl sulfoxide (DMSO) as a vehicle control on Day 0 of incubation. Development of 198 embryos was monitored from Days 3–9 of incubation, and 22 embryos on Day 4 and 74 embryos on Day 9 were dissected. Messenger RNA expression levels for several genes were measured in embryos on Day 4. Both TCIPP-exposed groups showed a significant reduction in survival rate. Imaging analyses revealed significant decreases in body length, head and bill length, eye diameter, and forelimb and hindlimb length in both TCIPP-treated groups. TCIPP exposure significantly impaired the development of extraembryonic blood vessels and the production of red blood cells. A TCIPP-dose-dependent decreasing trend in heart rate was observed on Days 4–7. The somitic angle increased significantly on Days 4–6, and embryos with curved somites showed cleavage in the back and gaps between somites, resulting in asymmetrical somite formation. A significant correlation was found between the somitic angle and FGF8 expression levels, suggesting that TCIPP exposure affects somite formation through an altered FGF-signaling pathway. Embryos with somitic deformities in TCIPP-exposed groups had significantly reduced survival rates, indicating that abnormal segment formation directly increased mortality. Finally, eye weight and ocular luminosity values were significantly reduced, suggesting that TCIPP may also affect eye development. Overall, these findings highlight severe toxic effects of TCIPP on avian embryonic development, including in vascularization, cardiac function, and somite and ocular development.
Display omitted
•We studied TCIPP developmental toxicity on chicken embryos in a shell-less system.•TCIPP exposure led to reduced survival rates and impaired blood vessel development.•TCIPP exposure led to a decrease in heart rate and somite formation abnormalities.•Abnormal segment formation may cause mortality in TCIPP-exposed embryos.•TCIPP significantly affected eye development by reducing eye weight and luminosity.
Cetaceans accumulate high levels of environmental pollutants, yet their toxicological studies have been difficult due to technical and ethical issues. It is essential to identify and fill the current ...knowledge gaps in the
assays available for cetaceans. The present study establishes a novel
assay that uses the fibroblasts of a finless porpoise (
) (FF) stranded in the Seto Inland Sea (SIS) to answer questions about the cytotoxicity and risks of environmental pollutants. FF were treated with 17 compounds including polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane and their metabolites (DDTs) and evaluated for cytotoxicity, viability, and apoptosis. The results of FF were compared with those of human fibroblasts (HF). The relative potencies of the test compounds were comparable between the two species, as EC
of these compounds significantly correlated for FF and HF. Exposure-activity ratios (EARs) revealed that accumulation of PCBs and DDTs are likely to pose adverse effects at the cellular level in the SIS finless porpoises, as their tissue concentrations exceeded EC
values obtained in this study. This study successfully evaluated the risks of environmental pollutants using cetacean fibroblasts isolated by a non-invasive method that may be applied to various cetacean species and compounds.
Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from ...S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.
Short-chain chlorinated paraffins (SCCPs) are listed as a category of globally controlled persistent organic pollutants (POPs) by the Stockholm Convention in 2017. However, SCCP toxicity, ...particularly their developmental toxicity in avian embryos, has not been well studied. In this study, we observed the early development of chicken embryos (Gallus gallus domesticus) by applying a shell-less (ex-ovo) incubation system developed in our previous studies. After exposing embryos at Hamburger Hamilton stage (HHS) 1 to SCCPs (control, 0.1% DMSO; SCCPs-L, 200 ng/g; SCCPs-M, 2000 ng/g; SCCPs-H, 20,000 ng/g), we observed the development of embryos from the 3rd to 9th incubation day. Exposure to SCCPs-M and -H induced a significant reduction in survival, with an LD50 of 3100 ng/g on the 9th incubation day. Significant dose-dependent decreases in body length were observed from days 4–9. We also found that SCCPs-H decreased the blood vessel length and branch number on the 4th incubation day. Additionally, SCCPs-H significantly reduced the heart rate on the 4th and 5th incubation days. These findings suggest that SCCPs may have potential of developmental and cardiovascular toxicity during the early stages of chicken embryos. Quantitative PCR of the mRNA of genes related to embryonic development showed that SLC16A10 (a triiodothyronine transporter) level decreased in the SCCPs-H group, showing a significant positive correlation with the body length of embryos. THRA level, a thyroid hormone receptor, was significantly decreased in the SCCPs-H group, whereas that of DIO3 level, a deiodinase was significantly increased. These results suggest that SCCPs exposure induces developmental delays via the thyroxine signaling pathway. Analysis of thyroid hormones (THs) in blood plasma also indicated a significant reduction in thyroxine (T4) levels in the SCCPs-H group on the 9th incubation day of embryos. In conclusion, SCCPs induce developmental toxicity by disrupting thyroid functions at the early-life stage of chicken embryos.
Display omitted
•Ex-ovo developmental toxicity of SCCPs on early chicken embryos was investigated.•SCCPs exposure resulted in an LD50 of 3100 ng/g on the 9th incubation day.•SCCPs exposure also induced developmental delay in embryos.•Downregulation of SLC16A10 and THRA may be responsible for the developmental delay.•T4 level decrease may be caused by upregulation of DIO3.
Our previous studies demonstrated that prenatal bisphenol A (BPA) exposure affected the hepatic transcriptome and lipidome in rat offspring in a sex- and age-dependent manner. In this study, we ...investigated the effects of gestational exposure to BPA on the rat dams, after weaning period, and compared them with those of their offspring. Our results showed alterations in hepatic transcriptome related to insulin signaling, circadian rhythm, and infectious disease pathways in BPA-treated dams even 4 weeks after the exposure, whereas slight modifications on the lipid profile were found. Alterations in lipid and transcriptome profiles were more prominent in the prenatally BPA-exposed offspring at postnatal day (PND) 1 and 21 than those in the dams, suggesting that in utero exposure to BPA is more serious than exposure in the adulthood. Cryptochrome-1 (Cry1) and peroxisome proliferator-activated receptor delta (Ppard) were commonly altered in both dams and offspring. Nevertheless, the results of DIABLO (Data Integration Analysis for Biomarker discovery using Latent cOmponents), showed that multi-omics data successfully distinguished the exposed dams from the corresponding controls and their offspring with a high level of accuracy. The accuracy rates in BPA50 models (including control and 50 μg BPA/kg bw/day exposed groups) were smaller than those in BPA5000 models (control and 5000 μg BPA/kg bw/day exposed groups), suggesting dose-dependent severity in BPA effects. Palmitic acid and genes related to circadian rhythm, insulin responses, and lipid metabolism (e.g., 1-acylglycerol-3-phosphate O-acyltransferase 2 (Agpat2), B-cell CLL/lymphoma 10 (Bcl10), Cry1, Harvey rat sarcoma virus oncogene (Hras), and NLR family member X1 (Nlrx1)) were identified through DIABLO models as novel biomarkers of effects of BPA across two generations.
Display omitted
•Effects of gestational BPA exposure were compared between rat dams and their offspring.•BPA exposure had no notable effects on the physiology and plasma parameters in dams.•At the multi-omics levels, the dams had less impacts than their offspring.•Nevertheless, BPA affected dams' circadian rhythm, immune response, and insulin resistance.•Multi-variates analysis successfully distinguished the multi-omics effects between generations.
Bisphenol A (BPA) is a well-known endocrine disruptor that has obesogenic properties. We have previously reported sex- and age-dependent changes in hepatic transcriptome and proteome of several lipid ...homeostasis-related genes in rat offspring prenatally exposed to BPA. To further understand the impacts of prenatal BPA exposure, we analyzed lipidomic profiles in the postnatal day (PND) 21 and 60 rats using a high-resolution QTOF mass spectrometer coupled with a HPLC system. We found that the total lipid content was significantly decreased in PND21 females prenatally exposed to 5000 μg/kg bw/day of BPA. Levels of total fatty acids, acylcarnitines, and monoacylglycerols significantly increased in both female and male BPA-exposed rats at PND21. An elevation in total cholesterol esters and reductions in triacylglycerols and monogalactosyl diacylglycerols were found only in PND21 females prenatally exposed to BPA. Interestingly, opposite responses were observed for phospholipids and sphingolipids between PND21 females and males following BPA exposure. The effects on the body weight and total lipid content were mitigated in the latter stage, although the alterations of lipid profiles continued until PND60. A Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) revealed a high correlation of the lipidome with our previously published transcriptome data. DIABLO also identified potential biomarkers of prenatal exposure to BPA; glycerol-3-phosphate dehydrogenase 1 (Gpd1) and glyceronephosphate O-acyltransferase (Gnpat), which are involved in the glycerophospholipid metabolism, in females and males, respectively. Collectively, we highlighted the sex- and age-dependent effects of prenatal BPA exposure on hepatic lipid homeostasis in rat offspring.
Display omitted
•Prenatal BPA exposure posed sex- and age-dependent effects on lipidome of rat offspring.•The lipidome profile was highly correlated with the transcriptome profile.•The effects of prenatal BPA exposure were profound at postnatal day (PND) 21.•However, the effects were mitigated at PND60.•Gpd1 and Gnpat may be potential biomarkers of prenatal BPA exposure.
Prenatal hydroxylated polychlorinated biphenyls (OH-PCBs) exposure may disrupt fetal brain development during the critical period of thyroid hormone (TH) action. However, there are limited studies on ...the OH-PCB transfer to the fetal brain, particularly in primates. In this study, we selected the Japanese macaque (Macaca fuscata) as a model animal for the fetal transfer of OH-PCBs in humans and revealed OH-PCB concentrations and their relationships in maternal and fetal blood, liver, and brain. l-thyroxine (T4)-like OH-PCBs including 4OH-CB187, a major congener in humans, were found in high proportions in the blood, liver, brain, and placenta of pregnant Japanese macaques. OH-PCBs were detected in the fetal brain and liver in the first trimester, indicating their transfer to the brain in the early pregnancy stage. 4OH-CB187 and 4OH-CB202 were the major congeners found in fetal brain, indicating that these T4-like OH-PCBs are transported from maternal blood to the fetal brain via the placenta. These results indicate that further studies are needed on the effects of OH-PCBs on the developing fetal brain.
This work aimed at predicting the toxic effects of phenolic compounds in Ba River on the health of female sharpbelly (Hemiculter lucidus) by the de novo transcriptomic analysis of the liver. ...Sharpbelly, a native fish living in freshwater ecosystem of East Asia, were sampled upstream, near, and downstream of a wastewater discharge to the Ba river. Based on the occurrence of bisphenol A (BPA), nonylphenol (NP), and 4-tert-octylphenol (4-t-OP) in the water and fish sampled from each site, up-, mid-, and down-stream were interpreted as control, high, and low treatment groups, respectively. In the mid-stream group the Fulton’s condition factor (CF) and body weight were remarkably increased by approximate 20%; the gonado-somatic index (GSI) and hepatosomatic index (HSI) in mid-stream fish showed a similar increasing trend but lacking of statistical difference. Exposure to wastewater effluent caused 160 and 162 differentially expressed genes (DEGs) in up-mid and down-mid stream groups, respectively. Two sets of DEGs were primarily enriched in the signaling pathways of drug metabolism, endocrine system, cellular process, and lipid metabolism in the mid-stream sharpbelly, which may alter the fish behavior, disrupt the reproductive function, and lead to hypothyroidism, hepatic steatosis, etc. Taken together, our results linked the disrupted signaling pathways with activities of phenolic compounds to predict the potential effects of wastewater effluent on the health of wild fish.
Display omitted
•First study on the de novo transcriptome of a wild fish species in East Asia.•Transcriptomic changes in each group was in line with the BPA and NP concentrations.•Pathways enriched in the fish near WWTP effluent outfall may be disrupted by BPA and NP.•Behavioral alteration, hepatic steatosis, and hypothyroidism may occur in wild fish caused by WWTP effluent.
Baikal seals (Pusa sibirica) are vulnerable to high levels of organic pollutants. Here, we evaluated the transactivation potencies of bisphenols (BPs) and hydroxylated polychlorinated biphenyls ...(OH-PCBs) via the Baikal seal estrogen receptor α and β (bsERα and bsERβ) using in vitro and in silico approaches. In vitro reporter gene assays showed that most BPs and OH-PCBs exhibited estrogenic activity with bsER sub-type-specific potency. Among the BPs tested, bisphenol AF showed the lowest EC50 for both bsERs. 4′-OH-CB50 and 4′-OH-CB30 showed the lowest EC50 among OH-PCBs tested for bsERα and bsERβ, respectively. 4-((4-Isopropoxyphenyl)-sulfonyl)phenol, 4′-OH-CB72, and 4′-OH-CB121 showed weak bsERα-specific transactivation. Only 4-OH-CB107 did not affect both bsERs. In silico docking simulations revealed the binding affinities of these chemicals to bsERs and partially explained the in vitro results. Using the in silico simulations and molecular descriptors as explanatory variables and the in vitro results as objective variables, the quantitative structure-activity relationship (QSAR) models constructed for classification and regression accurately separated bsER-active compounds from non-active compounds and predicted the in vitro bsERα- and bsERβ-transactivation potencies, respectively. The QSAR models also suggested that chemical polarity, van der Waals surface area, bridging atom structure, position of the phenolic-OH group, and ligand interactions with key residues of the ligand binding pocket are critical variables to account for the bsER transactivation potency of the test compounds. We also succeeded in constructing computational models for predicting in vitro transactivation potencies of mouse ERs in the same manner, demonstrating the applicability of our approach independent of species-specific responses.
Display omitted
•Most bisphenols and OH-PCBs transactivated in vitro-expressed Baikal seal ERs.•Bisphenols with more para-hydroxyl groups were more potent.•Para-OH-PCBs exhibited the strongest activity.•In silico docking simulations partially explained the Baikal seal ER potencies.•QSAR models from docking analyses and molecular descriptors predicted in vitro results well.
PDF
