Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Extended exposure to tetrabromobisphenol A-bis(2,3-dibromopropyl ether) leads to subfertility in male mice at the late reproductive age.

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a commonly used brominated flame retardant as a decabromodiphenyl ether substitute, has been detected in various environmental compartments, but its health hazards remain largely unknown. Our recent study showed that low-dose exposure of male mice to TBBPA-BDBPE from postnatal day (PND) 0 to 56 caused remarkable damage to the microtubule skeleton in Sertoli cells and the blood-testis barrier (BTB) but exerted little effect on conventional reproductive endpoints in adulthood. To investigate whether TBBPA-BDBPE may cause severe reproductive impairments at late reproductive age, here, we extended exposure of historically administrated male mice to 8-month age and allowed them to mate with non-treated females for the evaluation of fertility, followed by a general examination for the reproductive system. As expected, we found that 8-month exposure to 50 µg/kg/d as well as 1000 µg/kg/d TBBPA-BDBPE caused severe damage to the reproductive system, including reduced sperm counts, increased sperm abnormality, histological alterations of testes. Moreover, microtubule damage and BTB-related impairment were still observed following 8-month exposure. Noticeably, high-dose TBBPA-BDBPE-treated mice had fewer offspring with a female-biased sex ratio. All results show that long-term exposure to TBBPA-BDBPE caused severe reproductive impairment, including poor fertility at late reproductive age. It is therefore concluded that slight testicular injuries in early life can contribute to reproductive impairment at late reproductive age, highlighting that alterations in certain non-conventional endpoints should be noticed as well as conventional endpoints in future reproductive toxicity studies.

Comparison of Dechlorane Plus Concentrations in Sequential Blood Samples of Pregnant Women in Taizhou, China.

To develop an appropriate sampling strategy to assess the intrauterine exposure to dechlorane plus (DP), we investigated DP levels in sequential maternal blood samples collected in three trimesters of pregnancy, respectively, from women living in Taizhou. The median concentration of DPs (sum of syn-DP and anti-DP) in all samples was 30.5 pg g−1 wet-weight and 5.01 ng g−1 lipid-adjusted weight, respectively. The trimester-related DP concentrations were consistently strongly correlated (p < 0.01), indicating that a single measurement of DP levels could represent intrauterine exposure without sampling from the same female repeatedly; however, the wet-weight levels significantly increased across trimesters (p < 0.05), while the lipid-adjusted levels did not significantly vary. Notably, whether lipid-adjusted weight or wet-weight levels, the variation extent of DP across trimesters was found to be less than 41%, and those for other persistent organic pollutants (POPs) reported in the literature were also limited to 100%. The limitation in variation extents indicated that, regardless of the time of blood collection during pregnancy and how the levels were expressed, a single measurement could be extended to screen for exposure risk if necessary. Our study provides different strategies for sampling the maternal blood to serve the requirement for assessment of in utero exposure to DP.

Placental transfer of dechlorane plus in mother-infant pairs in an e-waste recycling area (Wenling, China).

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the transfer of DP across the placenta. The concentration ratio in the cord serum and maternal serum was estimated to be 0.45 for syn-DP and 0.35 for anti-DP, indicating the placenta partially limited DP transfer with a greater extent for anti-DP. The DP concentrations in the maternal serum, placenta, and cord serum strongly correlated, indicating that DP could transfer between the tissues. The DP concentrations in the matched samples could be predicted from each other. The anti-DP/total DP concentration ratios in the placentas and cord sera were significantly different from those in the maternal sera, suggesting that DP stereoselectively bioaccumulates in human tissues. When the congener concentrations of polybrominated diphenyl ethers (PBDEs) were used as control variables, DP and total triiodothyronine concentrations were associated in the sera from mothers who had lived in Wenling for over 20 years.

Covalent adduct formation of histone with organophosphorus pesticides in vitro.

It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs.

Postnatal exposure to low-dose tetrabromobisphenol A increases the susceptibility of mammal testes to chemical-induced spermatogenic stress in adulthood.

There is increasing data showing that some environmental chemicals can increase susceptibility to follow-up stress or injuries, possibly thereby contributing to certain clinical and subclinical diseases. Previous studies reported that tetrabromobisphenol A (TBBPA), one of the most used brominated flame retardants, exerted little male reproductive toxicity in terms of conventional endpoints but affected testis development and thereby caused testicular alterations at the molecular and cellular levels. Here, we aimed to reveal whether developmental exposure to TBBPA can increase testicular susceptibility to follow-up stress in adulthood. For this purpose, newborn mice were exposed to 50 or 500 µg/kg/d TBBPA for 56 days to confirm adverse effects on testes, followed by a single intraperitoneal injection of 3 mg/kg busulfan (BSF) to induce spermatogenic stress. Four weeks after BSF injection, TBBPA-treated mice exhibited severe pathological alterations, including reduced testis weight, damaged testicular histological structure, declined sperm count, apoptosis of spermatogenic cells, while no remarkable damage was observed in mice without historical exposure to TBBPA. These results demonstrate that historical exposure to TBBPA, either 50 or 500 µg/kg/d, increased the susceptibility of mouse testes to BSF-induced spermatogenic stress, resulting in severe adverse reproductive outcomes. Further analysis indicates that TBBPA-caused microtubule and microfilament damage, along with spermatogonia and spermatocyte reduction, could contributed to the increased susceptibility of testes, suggesting that these non-conventional reproductive lesions caused by chemicals should not be ignored. This is the first study to investigate the reproductive hazard of chemicals from the perspective of testicular susceptibility to stress, thereby opening a new avenue to identify environmental chemicals possibly contributing to male infertility and subfertility.

Profile of organochlorine pesticides in soil cores from some hotspot areas of Beijing, China.

For the valid use of urban land and the safety of public health, an extensive contamination survey of organochlorine pesticides from five soil cores was conducted in the highly urbanized areas of Beijing in China. For topsoils in five soil cores, level of ∑HCHs and ∑DDTs varied from 0.174 to 4,783 ng g(-1) and 0.62 to 57,849 ng g(-1), respectively. The profile in topsoil of cores displayed that levels of pollutants in four soil cores from the urban areas with dense population are higher than that from outskirts. The depth characteristics of pollutants indicated that the level of ∑HCHs and ∑DDTs in BY and WU was close to/below the background value of soil in China (50 ng g(-1)), but those in some soil samples from A, B and ZX core, especially A and B, was above the threshold value for the soil safety (1,000 ng g(-1)). In views of the usage history of the land and profiles of contaminants, the source in A and B probably came from the dumped waste chemical materials in the old chemical factories. The study of soil cores sampled revealed the existence of chemical "time bomb" in urban regions of Beijing. Also, the finding indicated the absolute necessity of assessing the soil quality with the unprecedented land use changes in the big city community.

[High rates of HBsAg loss and seroconversion result from prolonged course of pegasys treatment].

OBJECTIVE: HBsAg loss and seroconversion in patients with chronic hepatitis B leads to long-lasting good clinical outcomes. The aim of this paper was to investigate to improve the rate of HBsAg loss and seroconversion in chronic hepatitis B patients by prolonged treatment of PEG-IFNa-2a. 217 cases of HBeAg-positive or negative patients were collected from inpatient and outpatient in Beijing Ditan Hospital from May 2005 to October 2009 and subcutaneous injection of 135 ug or 180 ug PEGASYS were given once a week according to body weights. The drug doses were adjusted according to the neutrophilic granulocyte and platelet counts during treatment course. Quantitative HBV DNA test was conducted using a commercially available real-time fluorescence quantitative PCR kit. The serum HBsAg/anti-HBs and HBeAg/anti-HBe were quantitatively detected by Abbott i 2000 chemiluminescent kit before and during treatment every three months. Patients with HBsAg steadily decreased and reached serum HBsAg level below 200 IU/ml after 48 weeks of treatment would receive prolonged treatment. Patients with more than 12 weeks of treatment entered into analysis. Main efficacy of prolonged treatment was evaluated by the incidences of HBsAg loss and seroconversion. RESULTS: The treatment courses of the 217 patients ranged from 12.0 to 197.6 weeks with an average of 53.1+/-33.4 weeks, 118 cases took more than 48 weeks and another 89 cases less than 48 weeks. 13.4% (29/217) of patients achieved HBsAg loss or HBsAg seroconversion with treatment courses from 17.6 to 197.6 weeks (average 75.4+/-42.8 weeks). Among these 29 patients 24 (82.8%) received more than 48 weeks of treatment, but the treatment courses of HBV DNA reached undetectable level were 20.8+/-8.9 weeks. In this study, 9.5% (14/148) of HBeAg-positive patients achieved HBsAg loss or seroconversion, all of them treated more than 48 weeks, from 48 to 194 weeks, average 81.32+/-39.36 weeks. 21.7% (15/69) of HBeAg-negative patients achieved HBsAg loss or seroconversion, significantly higher than that of HBeAg-positive patients (9.5%) (x2 = 6.129, P = 0.013). The average treatment course for HBeAg-negative patients with HBsAg loss was 70.2+/-48.0 weeks, shorter than that of HBeAg-positive patients with HBsAg loss (81.3+/-39.4 weeks), but no significant difference (t = -0.522, P = 0.602) found between. CONCLUSION: Higher rate of HBsAg loss and seroconversion could be obtained by individual extended treatment courses in patients with rapid HBV DNA and HBsAg response to PEG-IFNa-2a treatment and the HBeAg-negative patients could got higher rate of HBsAg loss than HBeAg-positive patients.

Measurement of polychlorinated biphenyls with hand wipes and matched serum collected from Chinese E-waste dismantling workers: Exposure estimates and implications.

To date, dermal/hand-to-mouth exposure to chemicals in the e-waste recycling environment has not been sufficiently understood, and the importance of dermal absorption of chemicals in e-waste dismantling workers remains controversial. In this study, we utilized hand wipes and matched sera to characterize dermal/hand-to-mouth exposure to PCBs for e-waste dismantling workers, and potential effects on thyroid hormones were also assessed. PCB loadings in hand wipes varied from 0.829-265 ng wipe-1 (11.3-2850 ng m-2 wipe-1), with 37.2 ng wipe-1 (432 ng m-2 wipe-1) as the median value. Serum concentrations of PCBs ranged from 32.3-3410 ng g-1 lipid weight (lw) with 364 ng g-1 lw as the median value. Between wipes and sera, lower-chlorinated congeners (e.g. CB-28, -66, -74, -99,-105 and -118) showed significant associations (p < 0.01), but higher-chlorinated congeners (e.g. CB-138, -153, -156, -170, and -180) did not. These lower-chlorinated CBs were the major contributors to estimated dermal/hand-to-mouth average daily doses (ADDs) and the hazard index (HI). Correspondingly, their estimated contributions to serum levels by dermal absorption were also significant, with the contribution of CB-28 being as high as 21.4%. As a consequence, dermal absorption of some low-chlorinated congeners was a non-negligible route for e-waste dismantling workers. Although insignificant association was shown between serum PCBs and thyroid hormones, the potential health risk should be of concern due to the high levels of PCBs observed in workers' sera.

Mercury contamination in the topsoil and subsoil of urban areas of Beijing, China.

Mercury contamination is a serious problem in Chinese cities. In the present study, mercury contamination was evaluated in topsoil and subsoil samples collected in an urban area of Beijing. The level of total mercury in topsoil ranged from 12.1 to 8,487 ng g(-1), and a significant correlation (R = 0.58145, p < 0.0001) with polycyclic aromatic hydrocarbons was observed. Higher levels were generally observed in the suburbs and urban centers, with the highest levels being observed in the urban centers. The fraction of water soluble, ion exchangeable, Fe-Mn in the oxide-bound and organic phase was 0.78%, 0.18%, 0.25% and 3.42%, respectively. For subsoils, the level of total mercury ranged from 7.0 to 924.6 ng g(-1), and the higher levels were primarily located in the suburbs. This study showed that mercury has possibly affected the environmental quality of soil and groundwater in urban areas of Beijing.

Profiles of organochlorine pesticides in earthworms from urban leisure areas of Beijing, China.

In this study, organochlorine pesticides (HCHs and DDTs) in earthworm and soil contacted closely with it were determined for the purpose of the risk assessment of chemicals in the urban leisure environment. The level of total hexachlorocyclohexanes and (HCHs) and dichlorodiphenyltrichloroethanes (DDTs) in earthworms was 0.6500-44.78 ng g(-1) and 18.97-1.112 x 104 ng g(-1), respectively. Absolutely high levels of DDT and its metabolites in earthworm and correlative soils samples, and the bioaccumulation factor (BAF) of DDTs probably presents certain risk to the higher trophic organisms through its food chain, especially birds.

Bioaccumulation and transfer characteristics of dechlorane plus in human adipose tissue and blood stream and the underlying mechanisms.

In this study, bioaccumulation and transfer characteristics of dechlorane plus (DP) were examined between human adipose tissue and matched maternal serum, and the possible transfer mechanism between tissues was further discussed. The median level of total DP was 971 pg g-1 wet weight (ww) and 1.22 ng g-1 lipid weight (lw) in adipose tissue, respectively, and was 34.7 pg g-1 ww and 3.98 ng g-1 lw for serum, respectively. DP wet levels' positive association with fat contents of five types of human tissues indicated that DP distribution might be related to lipid-driven mechanism. However, the lipid-adjusted adipose-serum partitioning ratios were estimated to be 0.35 for syn-DP and 0.35 for anti-DP, accordingly, which implied that the DP distribution between serum and adipose tissues, was not only regulated by the tissue lipid contents. Both the internal mono-dechlorination of anti-DP, and stereo-selective behavior of DP isomers were not found in DP transfer from blood to adipose tissue. The marginal positive relationship was observed between serum levels and apolipoprotein A concentrations (p = 0.095 for total DP and 0.045 for syn-DP), and neither association was found between serum levels and thyroid hormone concentrations (THs). To our best knowledge, this is the first report about the accumulation relationship of DP between human adipose tissue and blood stream with the corresponding distribution-related mechanism.

2,2',4,4'-tetrabromodipheny ether (BDE-47) disrupts gonadal development of the Africa clawed frog (Xenopus laevis).

Previous studies have shown that BDE-47, one of the most abundant polybrominated diphenyl ethers (PBDEs) congeners, has a weak estrogenic activity, but it has remained unclear whether BDE-47 disrupts gonadal development and causes male-to-female sex reversal in lower vertebrates, with limited and controversial data. The present study aimed to determine the effects of BDE-47 on gonadal development in Xenopus laevis, a model amphibian species for studying adverse effects of estrogenic chemicals on reproductive development. X. laevis at stage 45/46 were exposed to BDE-47 (0.5, 5, 50 nM) in semi-static system, with 1 nM 17ß-estradiol (E2) as the positive control. When reaching stage 53, tadpoles were examined for gonadal morphology, histology and sex-dimorphic gene expression. The phenotypic sex (gonadal morphology and histology) of each BDE-47-treated tadpole matched its genetic sex, showing no sex-reversal, whereas one half of genetic males treated with E2 displayed ovarian-like features. However, some genetic males (26%) in the 50 nM BDE-47 treatment group were found to contain more germ cells clumping together in the medulla, along with an increasing tendency of the gonad length/kidney length ratio in males, resembling feminizing outcomes of E2. These observations seem to suggest that BDE-47 exerted weak feminizing effects. However, BDE-47 induced increases in expression of both female-biased genes and male-biased genes in two sexes, which disagrees with feminizing outcomes, suggesting complicated effects of BDE-47 on gonadal development. Taken together, all results demonstrate that nanomolar BDE-47 disrupted gonadal development and exerted weak feminizing effects, but not resulted in male-to-female sex reversal in X. laevis.

Transfer of dechlorane plus between human breast milk and adipose tissue and comparison with legacy lipophilic compounds.

In this study, levels of dechlorane plus (DP) in breast milk and matched adipose tissue samples were measured from 54 women living in Wenling, China. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured simultaneously for comparison. The levels of ∑DPs/∑PBDEs varied from less than one to several dozens of ng g-1 lipid weight (lw) in matrices and the levels of ∑PCBs varied between several to hundreds of ng g-1 lw. In the same matrix, ∑DPs and ∑PCBs/∑PBDEs showed a significant relationship (p < 0.05), indicating that they shared common sources. Accordingly, there was a strong association of lipid-adjusted concentrations of individual compounds (BDE-209 excluded) between matrices (p < 0.001), suggesting that breast milk could be a proxy for adipose tissue in human bioburden monitoring of these compounds. The predicted lipid-adjusted milk/adipose ratios varied from 0.62 to 1.5 but showed significant differences (p<0.001) between compounds, suggesting a compound-specific transfer between milk lipids and adipose tissue lipids. Specifically, the milk/adipose ratios for syn-DP and anti-DP (-1.40 and 1.3, respectively) were significantly higher than those of CB congeners and hexa/hepta-BDE congeners (p < 0.05). In addition, unlike PCBs/PBDEs (excluding BDE-209), DP's hydrophobicity might not be responsible for its preferable distribution in milk lipids. Instead, the interaction with nonlipid factors played a key role. The fraction of anti-DP between the two kinds of matrices was not significantly different, suggesting that the biochemical transfer processes may not be efficient enough to distinguish DP isomers. Nevertheless, the congener patterns of PCBs/PBDEs gave a clue about the compound-specific transfer between milk and adipose tissue. To our knowledge, this is the first to report the relationships of DP between adipose tissue and breast milk. These results could provide useful and in-depth information on biomonitoring of DP and facilitate the understanding of the accumulation and excretion potentials of DP and its distribution-related mechanism in humans.

Levels and chiral signatures of organochlorine pesticides in urban soils of Yinchuan, China.

In this study, residual level and enantiomeric composition of typical organochlorine pesticides (OCPs) were surveyed in urban soils of Yinchuan, China. The median levels of summation Sigma HCHs and summation Sigma DDTs were 0.852 and 2.24 ng/g, respectively, which suggested little risk for ecological environment and human health in the study area. Both chiral alpha-HCH and o,p'-DDT displayed the non-racemic signatures in all samples. The isomer ratios of summation Sigma HCHs and summation Sigma DDTs combined with enantiomer fractions (EFs) of alpha-HCH and o,p'-DDT, suggested that contamination source of HCHs derived from historical HCHs (including technical HCHs and Lindane) and that of DDTs originated from old source with the usage of mixed technical DDTs and dicofol.

Contamination of soils with organochlorine pesticides in urban parks in Beijing, China.

Urban parks are an integral component of healthy urban living. Since they are frequently visited, an understanding of the environmental quality of these urban facilities is crucial. Here, a study was conducted on the contamination of soils in the parks of Beijing. Organochlorine pesticides (OCPs), which have the potential to cause endocrine disturbances, were considered study objectives. Hexachlorocyclohexanes (HCHs) were found at concentrations of 0.2490-197.0 ng g(-1) and dichlorodiphenyltrichloroethanes (DDTs) were found at concentrations of 5.942-1039 ng g(-1) in the soils investigated. The preliminary pollution assessment indicated that DDTs have caused high pollution levels in the soils of some parks. Analysis of the sources of contamination showed that HCHs in the soils were derived from an old mixed source of technical HCHs and lindane and that DDTs, which were suspected to have recent application to the soils at some sites, were derived mainly from a mixture of technical DDTs and dicofol containing DDT impurities. An independent sample t-test proved that pesticides containing DDTs had been used in large amounts in the soils of parks before 1983 (p<0.05) and that the levels of DDTs in the soils of parks administered by the Beijing municipal government were significantly higher than the levels in those administered by the district government (p<0.05). However, the main difference in this situation needs to be further studied. This study suggested that open spaces like urban parks were not as sound as was expected and that there was potential for exposure of visitors/workers in the parks to organochlorine pesticides.

Comparative genome and transcriptome analyses reveal adaptations to opportunistic infections in woody plant degrading pathogens of Botryosphaeriaceae.

Botryosphaeriaceae are an important fungal family that cause woody plant diseases worldwide. Recent studies have established a correlation between environmental factors and disease expression; however, less is known about factors that trigger these diseases. The current study reports on the 43.3 Mb de novo genome of Lasiodiplodia theobromae and five other genomes of Botryosphaeriaceae pathogens. Botryosphaeriaceous genomes showed an expansion of gene families associated with cell wall degradation, nutrient uptake, secondary metabolism and membrane transport, which contribute to adaptations for wood degradation. Transcriptome analysis revealed that genes involved in carbohydrate catabolism, pectin, starch and sucrose metabolism, and pentose and glucuronate interconversion pathways were induced during infection. Furthermore, genes in carbohydrate-binding modules, lysine motif domain and the glycosyl hydrolase gene families were induced by high temperature. Among these genes, overexpression of two selected putative lignocellulase genes led to increased virulence in the transformants. These results demonstrate the importance of high temperatures in opportunistic infections. This study also presents a set of Botryosphaeriaceae-specific effectors responsible for the identification of virulence-related pathogen-associated molecular patterns and demonstrates their active participation in suppressing hypersensitive responses. Together, these findings significantly expand our understanding of the determinants of pathogenicity or virulence in Botryosphaeriaceae and provide new insights for developing management strategies against them.

Tetrabromoethylcyclohexane affects gonadal differentiation and development in the frog Pelophylax nigromaculatus.

Tetrabromoethylcyclohexane (TBECH), an additive brominated flame retardant, has been shown to have an androgenic activity in vitro. In the present study, we aimed to investigate the effects of TBECH on gonadal differentiation and development in the frog Pelophylax nigromaculatus, an amphibian species sensitive to androgenic chemicals, and to assess the androgenic activity of TBECH in vivo. P. nigromaculatus tadpoles were exposed to TBECH (1, 10, 100nM) from Gosner stage 24 to complete metamorphosis, and to 5α-dihydrotestosterone (DHT) as a positive control. We found that 1nM DHT resulted in 100% males, while the sex ratio in the solvent control group was close to 1:1. In all the TBECH treatment groups, sexually ambiguous gonads based on gross morphology and intersexualities with testicular and ovarian histological structures were found, but no abnormality occurred in the solvent control. In the 1, 10, 100nM TBECH treatment groups, the female percentages were 52%, 31%, 17%, with 36%, 56%, 66% for males and 12%, 13%, 17% for abnormal sexes, respectively. X2-test revealed significant differences in sex ratios between the three TBECH groups and the solvent control group, and the sex ratios in the two higher concentration groups were male-biased. These observations show that TBECH has a masculinizing effect on gonadal differentiation and development in P. nigromaculatus, suggesting an androgenic activity of TBECH in vivo. To our knowledge, this is the first study demonstrating that TBECH could induce gonadal masculinization in an animal, which raises new concerns for reproductive risk of TBECH exposure.

Partitioning of polybrominated biphenyl ethers from mother to fetus and potential health-related implications.

Presently, knowledge on the partitioning of polybrominated biphenyl ethers (PBDEs) from mother to fetus and the relationship between PBDE exposure and the levels of thyroid hormones (THs) needs to be extended further. In the present study, we investigated the concentrations of PBDEs in paired mother-fetus samples from 72 pregnant women in Wenling, China. The detection of PBDE concentration suggested that the expectant women living in Wenling for over 20 years might be highly exposed to PBDEs, which is largely ascribed to e-waste recycling activities in the local environment. The median concentration ratios between paired cord serum and maternal serum for higher-brominated BDEs were smaller than those for lower-brominated BDEs (p < 0.05). This result indicated that the placenta could hinder the transfer of PBDEs from mother to fetus, and the hindrance effect increased with higher-brominated congeners. Median ratios of paired placenta vs. maternal serum concentrations varied in a narrow range (0.15-0.25), with significantly lower value for BDE-209 than that for BDE-28 (p < 0.01). The extent of transplacental transfer was larger than that of placental retention for eight BDE congeners (p < 0.01). The concentration of BDE congeners among the paired samples could be fitted by equations, implying that their distribution could be predicted for each other (p < 0.001). There was a significant association between BDE-153 and TT4 levels in maternal serum from Wenling local residents (p < 0.05), suggesting potential implications for fetal development and their mothers' health in e-waste recycling environment. In addition, it was found that the relationship between BDEs and TH levels was likely affected by the exposure duration of the population to PBDEs.