Comprehensive review on Haloalkane dehalogenase (LinB): a ß-hexachlorocyclohexane (HCH) degrading enzyme.

Haloalkane dehalogenase, LinB, is a member of the α/ß hydrolase family of enzymes. It has a wide range of halogenated substrates, but, has been mostly studied in context of degradation of hexachlorocyclohexane (HCH) isomers, especially ß-HCH (5-12% of total HCH isomers), which is the most recalcitrant and persistent among all the HCH isomers. LinB was identified to directly act on ß-HCH in a one or two step transformation which decreases its toxicity manifold. Thereafter, many studies focused on LinB including its structure determination using X-ray crystallographic studies, structure comparison with other haloalkane dehalogenases, substrate specificity and kinetic studies, protein engineering and site-directed mutagenesis studies in search of better catalytic activity of the enzyme. LinB was mainly identified and characterized in bacteria belonging to sphingomonads. Detailed sequence comparison of LinB from different sphingomonads further revealed the residues critical for its activity and ability to catalyze either one or two step transformation of ß-HCH. Association of LinB with IS6100 elements is also being discussed in detail in sphingomonads. In this review, we summarized vigorous efforts done by different research groups on LinB for developing better bioremediation strategies against HCH contamination. Also, kinetic studies, protein engineering and site directed mutagenesis studies discussed here forms the basis of further exploration of LinB's role as an efficient enzyme in bioremediation projects.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

STAT3 Pathways Contribute to ß-HCH Interference with Anticancer Tyrosine Kinase Inhibitors.

Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, ß-hexachlorocyclohexane (ß-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. ß-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with ß-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that ß-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.

Conductive Materials on Biocathodes Altered the Electron-Transfer Paths and Modulated γ-HCH Dechlorination and CH4 Production in Microbial Electrochemical Systems.

Adding conductive materials to the cathode of a microbial electrochemical system (MES) can alter the route of interspecies electron transfer and the kinetics of reduction reactions. We tested reductive dechlorination of γ-hexachlorocyclohexane (γ-HCH), along with CH4 production, in MES systems whose cathodes were coated with conductive magnetite nanoparticles (NaFe), biochar (BC), magnetic biochar (FeBC), or anti-conductive silica biochar (SiBC). Coating with NaFe enriched electroactive microorganisms, boosted electro-bioreduction, and accelerated γ-HCH dechlorination and CH4 production. In contrast, BC only accelerated dechlorination, while FeBC only accelerated methanogenesis, because of their assemblies of functional taxa that selectively transferred electrons to those electron sinks. SiBC, which decreased electro-bioreduction, yielded the highest CH4 production and increased methanogens and the mcrA gene. This study provides a strategy to selectively control the distribution of electrons between reductive dechlorination and methanogenesis by adding conductive or anti-conductive materials to the MES's cathode. If the goal is to maximize dechlorination and minimize methane generation, then BC is the optimal conductive material. If the goal is to accelerate electro-bioreduction, then the best addition is NaFe. If the goal is to increase the rate of methanogenesis, adding anti-conductive SiBC is the best.

Revelation of bioremediation approaches for hexachlorocyclohexane degradation in soil.

This review elucidates different bioremediation approaches used for degradation of HCH from contaminated sites. It highlights the significance of degradative pathways, microbial diversity and impact of different environmental factors for developing viable bioremediation strategies. The application of innovative biotechnological approaches and a thorough understanding of HCH biodegradation pathways show great promise for the creation of long-term solutions to HCH pollution and the restoration of polluted soil ecosystems. Bioremediation technologies viz. biostimulation, bioaugmentation, phytoremediation have been considered till date for treating HCH-contaminated sites. Different bacterial and fungal strains have been reported for degradation of HCH residues. However, these methods are limited to γ-HCH degradation, at laboratory scale and achieving lower success rate for large scale demonstration trials. This review presents a theoretical background for degradation of different HCH isomers in soil through plants, microbes and through their cooperative interactions. This work briefly overviews the substantial contamination of the environment by HCH residues, along with spontaneous evolution of degradation pathways through various HCH degrading microbes. Bioremediation mechanism and pathways of HCH degradation through plants and microbes have been discussed thoroughly. Through molecular and genetic investigations, the complex metabolic pathways used by these microbes, including reductive dechlorination, hydrolysis, and ring cleavage, has been clarified. This study seeks to give a thorough summary of recent discoveries and developments in bioremediation methods for soil HCH degradation. Numerous microbial consortia, including fungi, plants, and bacteria have been recognised as important participants in the transformation of HCH.

Integrated soil washing and bioreactor systems for the treatment of hexachlorocyclohexane contaminated soil: A review on enhanced degradation mechanisms, and factors affecting soil washing and bioreactor performances.

Investigations about the remediation of Hexachlorocyclohexane (HCH), a persistent organic pollutant of global concern, have been extensively reported to treat the HCH contaminated soil. The difficulty arising due to desorption and long ageing procedures of this hydrophobic organic compound in the soil, make it necessary to exploit techniques like soil washing or addition of surfactants, for enhancing the mass transfer rate of hydrophobic compounds. However, this technique gives rise to the generation of a large quantity of waste solution containing the pollutant and various other toxic substances. Moreover, it is challenging to deal with the complex soil washing solution, and thus a follow-up treatment of such washing solution is essentially required before its discharge. This follow-up treatment could be the bioreactor system to efficiently treat the pollutant in the wash solution, thereby reducing the amount of contaminated soil that has to be treated. Among many suggested remediation methods and treatment technologies, integrated soil washing and post-treatment with the bioreactor system could be an environmentally viable method for the remediation of HCH contaminated sites. This review focuses on the soil washing procedures applied so far for the HCH contaminated soil and various factors affecting the efficiency of separation of the target pollutant. Furthermore, the environmental and reactor design-related factors are also discussed for degradation of HCH in the reactor system. Finally, advantages and environmental feasibility of this proposed combined technology and the challenges that need to be encountered are envisaged.

Hydoxylated ß- and δ-Hexacholorocyclohexane metabolites infer influential intrinsic atomic pathways interaction to elicit oxidative stress-induced apoptosis for bio-toxicity.

Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to ß-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment.

Influence of delta-hexachlorocyclohexane (δ-HCH) to Phytophthora ×alni resistant Alnus glutinosa genotypes - Evaluation of physiological parameters and remediation potential.

Hexachlorocyclohexanes (HCHs) are persistent organochlorine pesticides with the adverse effects on human health and the environment. The effect of delta-isomer of hexachlorocyclohexane (δ-HCH) on germination, growth parameters and physiological parameters was studied in different Alnus glutinosa (L.) Gaertn. progeny of resistant genotypes to pathogen Phytophthora ×alni. Two experiments were performed: a short-term experiment to determine the effect of δ-HCH on total germination (GT), germination energy (GE), speed of germination (SG), shoot length and biomass of seedlings, and a long-term experiment devoted to remediation aspects. In addition, changes in the hormonal system of alders were monitored in both cases. Significant differences were found between the treated and control group in most of the evaluated characteristics. Also, the content of studied phytohormones differs between groups. Furthermore, the obtained results indicate genetically determined variability in response to δ-HCH. Of the six tested, the Brezové and Turany progeny seem to be suitable candidates for phytoremediation because of the adaptation to stress conditions or high remediation efficiency. The rest of tested progeny seems to be unsuitable due to higher mortality, lower remediation efficiency and higher levels of stress hormones resulting in significant decrease in biomass and plant height. Moreover, results indicate the role of the plant as a remediation accelerator, probably through released exudates, and a positive effect on the soil microbiome as the presence of plants increased the remediation efficiency by 20.85 - 35.89%. The obtained research findings may be helpful in better understanding the processes involved in removing these pesticides from the soil. Further research should be focused on rhizosphere microbiome, mechanism of in-plant isomerization and metabolites identification.

Biodegradation of technical hexachlorocyclohexane by Cupriavidus malaysiensis.

Lindane (γ-Hexachlorocyclohexane) has been used extensively as a pesticide all over the world. The production of Lindane entails the formation of four major Hexachlorocyclohexane (HCH) isomers, that is, alpha, beta, gamma, and delta as muck. These have been used as Technical HCH in developing countries as an inexpensive alternate source. However, HCH isomers pose a severe environmental hazard due to their highly persistent nature and toxicity. In this study, the effect of HCH application on the soil microbial diversity was studied. The species which could persist even after prolonged exposure at high HCH concentration, was isolated, screened, and enriched as potential t-HCH degraders. The selected isolate could degrade 88.05%, 92.19%, 91.54%, and 82.85% of the alpha, gamma, beta, and delta isomers, respectively at 100 mg/L HCH concentration. Identification of the isolate by 16s rRNA sequencing was similar to Cupriavidus malaysiensis. To the best of the authors' knowledge, this is the first study to observe this particular strain's ability to simultaneously degrade the four isomers, especially the most recalcitrant beta isomer. Therefore, the degradative capability of this strain, as a sole carbon source at higher HCH concentration (100 mg/l), can be exploited for bioremediation of HCH contaminated sites.

ß-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B.

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on ß-hexachlorocyclohexane (ß-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of ß-HCH, already established in our previous studies, the aim of this work is to assess whether ß-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM ß-HCH. The obtained results strongly support the carcinogenic potential of ß-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize ß-HCH, which appears to be a full-fledged carcinogenic agent.

Role of Basic Surface Groups of Activated Carbon in Chlordecone and ß-Hexachlorocyclohexane Adsorption: A Molecular Modelling Study.

The influence of nitrogen-containing surface groups (SGs) onto activated carbon (AC) over the adsorption of chlordecone (CLD) and ß-hexachlorocyclohexane (ß-HCH) was characterized by a molecular modelling study, considering pH (single protonated SGs) and hydration effect (up to three water molecules). The interactions of both pollutants with amines and pyridine as basic SGs of AC were studied, applying the multiple minima hypersurface (MMH) methodology and using PM7 semiempirical Hamiltonian. Representative structures from MMH were reoptimized using the M06-2X density functional theory. The quantum theory of atoms in molecules (QTAIM) was used to characterize the interaction types in order understanding the adsorption process. A favorable association of both pesticides with the amines and pyridine SGs onto AC was observed at all pH ranges, both in the absence and presence of water molecules. However, a greater association of both pollutants with the primary amine was found under an acidic pH condition. QTAIM results show that the interactions of CLD and ß-HCH with the SGs onto AC are governed by Cl···C interactions of chlorine atoms of both pesticides with the graphitic surface. Electrostatic interactions (H-bonds) were observed when water molecules were added to the systems. A physisorption mechanism is suggested for CLD and ß-HCH adsorption on nitrogen-containing SGs of AC.

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by ß-Hexachlorocyclohexane-Activated Signaling Pathways.

The ß-isomer of hexachlorocyclohexane (ß-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of ß-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating ß-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting ß-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from ß-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

Health risk assessment of hexachlorocyclohexane in soil, water and plants in the agricultural area of Potohar region, Punjab, Pakistan.

In this study analysis of soil, water and plant residue samples is presented to evaluate the contamination levels and possible health risks. Hexachlorocyclohexane (HCH) is a persistent organic pollutant used as a pesticide in agricultural sector for pest control in order to obtain higher productivity. For analysis soil, water and crop residue samples were collected from different agricultural areas of the northern Punjab region of Pakistan. The investigation of the samples shows significant levels of HCH residues in all types of samples. Gas chromatography-mass spectrometry analysis was used to assess the higher residue levels of HCH in the samples. The concentration of HCH residues detected in samples ranged from 2.43 to 8.88 µg/g in soil, nd -5.87 µg/l in water and nd - 4.87 µg/g in plants. The presence of HCH residues in soil, water and plant samples was beyond the recommended quality guidelines. Human health risk was evaluated for cancer and non-cancer risks through dietary and non-dietary exposure routes. The hazard index was HI > 1 in children and HI < 1 in adults, while the non-dietary incremental lifetime cancer risks (ILCR) were beyond the internationally acceptable limit of 1 × 10-5. Hence, results of the present investigation concluded the presence of high levels of HCH residues in samples and pose high health risk to the inhabitants. These findings are alarming and apprise the concerned departments for the remediation of contamination and proper implementation of environmental laws in the area.

Exposure to DDT and HCH congeners and associated potential health risks through khat (Catha edulis) consumption among adults in South Wollo, Ethiopia.

Khat (Catha edulis) chewing is widespread in the region of East Africa. Even low levels of organochlorine pesticides (OCPs) in khat could induce public health concern. In a market-based study, from five popular khat varieties, a total of 35 composite khat samples were analyzed for dichlorodiphenyltrichloroethane (DDT) and its main transformation products, and four hexachlorocyclohexane (HCH) isomers. Extraction was carried out by quick, easy, cheap, effective, rugged and safe method (QuEChERS). OCP concentrations were determined by head space solid phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME-GC-MS). Every sample contained ß-HCH above the maximum residue limit set by the European Commission. For total DDT, this was the case for 25.7% of the samples. The ratios of (p,p'-DDD + p,p'-DDE) to p,p'-DDT were less than one for 85% of khat samples, demonstrating recent use of DDT in khat farmlands. Conversely, the ratio of ß-HCH to total HCH varied from 0.56 to 0.96, implying historical input of technical HCH. Assuming a daily chewable portion of 100 g, dietary intakes of p,p'-DDT, total DDT and total HCH by adults ranged from 3.12 to 57.9, 6.49 to 80.2 and 39.2 to 51.9 ng (kg body weight)-1 day-1, respectively. These levels are below acceptable levels suggested by international organizations. Chewing khat showed lower non-cancer health risk, but showed relatively higher cancer risk in terms of OCPs. Because khat is chewed without being subjected to any treatment, uncertainties associated with estimated intakes and health risks should be low. Therefore, this practice is of great concern.

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

Metabolomics study and meta-analysis on the association between maternal pesticide exposome and birth outcomes.

BACKGROUND: Pregnant women are exposed to a number of pesticides which are widely used in China. Their potential risks on reproduction and infants are still unknown. OBJECTIVE: We aimed to investigate whether infant's birth weight and length of gestation were associated with levels of various pesticides in maternal blood based on Nanjing Medical University (NMU) affiliated hospitals data and meta-analysis, and also to explore the possible intermediate metabolomics pathways. METHODS: Eligible subjects (n = 102) were included in this study from the affiliated hospitals of NMU. Gas chromatography tandem mass spectrometry (GC/MS) and Q-Exactive mass spectrometer (QE) were used to detect 37 pesticides (9 organophosphorus pesticides, 7 organochlorine pesticides, 5 carbamate pesticides, and 16 others) and 161 metabolites (53 in animo acid metabolism 47 in lipid metabolism, 18 in carbohydrate metabolism, 14 in nucleotide metabolism and 29 in other metabolisms) in maternal blood, respectively. Multi-linear regression and Bayesian kernel machine regression (BKMR) were performed to identify the association of single/mixed pesticide exposure in maternal blood with birth weight and length of gestation. Moreover, we conducted a meta-analysis including additional 2497 subjects to evaluate whether exposure to key pesticide, ß-hexachlorocyclohexane (ß-HCH) was associated with decreased birth weight globally. Mediation analysis was used to explore the metabolic alteration mediating the association between key pesticide exposure and birth outcomes. RESULTS: We found that decreased birth weight was significantly associated with increasing levels of mecarbam and ß-HCH. We did not find any association between length of gestation and these pesticides. Among pesticides with detection rate more than 50%, BKMR analysis found an overall negative association of mixed pesticides exposure with birth weight, and verified that ß-HCH was the key pesticide for such effect. Meta-analysis revealed a significantly negative association between exposure to ß-HCH and birth weight. Metabolomics identified three metabolites and five metabolites as significant mediators for the effect of mecarbam and ß-HCH, respectively, among which glyceraldehyde and its related glycerolipid metabolism and thyroxine and its related thyroid hormone metabolism were found to be the mostly enriched mediating metabolic pathway. CONCLUSIONS: Based on the comprehensive pesticide exposome and metabolome wide associational study combined with meta-analysis, we found that prenatal exposure to ß-HCH and mecarbam decreased birth weight via disrupting thyroid hormone metabolism and glyceraldehyde metabolism, providing new insights into the toxic effects of exposure to pesticides on birth outcomes.

Predictors of Beta-Hexachlorocyclohexane blood levels among people living close to a chemical plant and an illegal dumping site.

BACKGROUND: Hexachlorocyclohexane is a synthetic chemical with several isomers, including ß-Hexachlorocyclohexane (ß-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of ß-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population. The aim of the study was to evaluate the determinants of ß-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified. METHODS: The program involved all people living within 1 km of the river. A descriptive analysis of ß-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) ß-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering. RESULTS: A total of 602 subjects (87.2%) agreed to participate in the surveillance. The ß-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14-1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65-15.15), obese (GMR: 1.63, 95%CI: 1.28-2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15-1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00-2.14 and GMRwash: 1.48, 95%CI: 1.17-1.87) were associated with higher ß-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47-0.86). The focus on specific foods showed that the most important factors were eggs and beef. CONCLUSIONS: The study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.

Association of in utero hexachlorocyclohexane exposure with gestational age.

As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014-2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude ß = -1.017, confidence interval (CI): - 2.017, - 0.018 for α-HCH, crude ß = -1.068, CI: - 2.067, - 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted ß = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted ß = -1.365, CI: -2.414, -0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth.

Metabolic synergies in the biotransformation of organic and metallic toxic compounds by a saprotrophic soil fungus.

The saprotrophic fungus Penicillium griseofulvum was chosen as model organism to study responses to a mixture of hexachlorocyclohexane (HCH) isomers (α-HCH, ß-HCH, γ-HCH, δ-HCH) and potentially toxic metals (vanadium, lead) in solid and liquid media. The P. griseofulvum FBL 500 strain was isolated from polluted soil containing high concentrations of HCH isomers and potentially toxic elements (Pb, V). Experiments were performed in order to analyse the tolerance/resistance of this fungus to xenobiotics and to shed further light on fungal potential in inorganic and organic biotransformations. The aim was to examine the ecological and bioremedial potential of this fungus verifying the presence of mechanisms that allow it to transform HCH isomers and metals under different extreme test conditions. To our knowledge, this work is the first to provide evidence on the biotransformation of HCH mixtures, in combination with toxic metals, by a saprotrophic non-white-rot fungus and on the metabolic synergies involved.

Anaerobic biotransformation of hexachlorocyclohexane isomers by Dehalococcoides species and an enrichment culture.

The biotransformation of hexachlorocyclohexane isomers (HCH) by two Dehalococcoides mccartyi strains (195 and BTF08) and an enrichment culture was investigated and compared to conversion by the obligate anaerobic strain Clostridium pasteurianum strain DSMZ 525. The D. mccartyi strains preferentially transformed γ-HCH over α-HCH and δ-HCH isomers while ß-HCH biotransformation was not significant. In case of the enrichment culture, γ-HCH was preferentially transformed over the δ-HCH, ß-HCH and α-HCH isomers. Major observed metabolites in both cases were tetrachlorocyclohexene and as end products monochlorobenzene (MCB) and benzene. Dechlorination of the γ-HCH isomer was linked to an increase in cell numbers for strain 195. γ-HCH transformation was linked to considerable carbon stable isotope fractionation with the enrichment factor εc = - 5.5 ± 0.8‰ for D. mccartyi strain 195, εc = - 3.1 ± 0.4‰ for the enrichment culture and εc = - 4.1 ± 0.6‰ for co-metabolic transformation by C. pasteurianum.