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1.  Evaluation of urinary porphyrin excretion in neonates born to mothers exposed to airborne hexachlorobenzene. 
Environmental Health Perspectives  2002;110(2):205-209.
The existence of a link between hexachlorobenzene (HCB) and porphyria cutanea tarda has been known for a long time. However, the epidemiologic data on effects on health caused by prenatal exposure have not provided convincing evidence that HCB alters porphyrin metabolism. Our objectives were to analyze urinary porphyrin excretion and HCB in maternal serum and fetal cord blood in neonates born in a village (Flix) near a chlorinated solvent factory, to detect possible adverse effects in urinary porphyrin excretion caused by prenatal exposure, and to assess their relationship with HCB blood levels. We conducted a cross-sectional study in the Porphyria Unit at a tertiary care facility in Barcelona, Spain, and the Pediatric Unit of the Móra d'Ebre Hospital, the reference hospital of the study area. We included in the study all neonates (n = 68) born in Móra d'Ebre Hospital 1997-1999 and their mothers. We obtained 68 urine specimens of singleton neonates on the third day after birth to test for urinary porphyrin excretion. We obtained 52 fetal cord blood and 56 maternal serum samples for HCB analysis. Total urinary porphyrins were quantified using spectrofluorometry. Porphyrin profile was determined by HPLC. Serum HCB was analyzed by gas chromatography coupled with electron capture detection. In total population, median HCB levels were 1.08 ng/mL in cord blood and 3.31 ng/mL in maternal serum. Total urinary porphyrin concentration was 37.87 micromol/mol creatinine. Coproporphyrin I and coproporphyrin III were the major porphyrins excreted. We found no positive relationship between urinary porphyrin excretion and HCB levels. However, we observed an association between maternal smoking and coproporphyrin excretion. Although high environmental levels of HCB are reported in the town of Flix, we found no alteration in urinary porphyrin excretion.
PMCID: PMC1240737  PMID: 11836151
2.  Study on the Effect of Electrochemical Dechlorination Reduction of Hexachlorobenzene Using Different Cathodes 
Hexachlorobenzene (HCB) is a persistent organic pollutant and poses great threat on ecosystem and human health. In order to investigate the degradation law of HCB, a RuO2/Ti material was used as the anode, meanwhile, zinc, stainless steel, graphite, and RuO2/Ti were used as the cathode, respectively. The gas chromatography (GC) was used to analyze the electrochemical products of HCB on different cathodes. The results showed that the cathode materials significantly affected the dechlorination efficiency of HCB, and the degradation of HCB was reductive dechlorination which occurred only on the cathode. During the reductive process, chlorine atoms were replaced one by one on various intermediates such as pentachlorobenzene, tetrachlorobenzene, and trichlorobenzene occurred; the trichlorobenzene was obtained when zinc was used as cathode. The rapid dechlorination of HCB suggested that the electrochemical method using zinc or stainless steel as cathode could be used for remediation of polychlorinated aromatic compounds in the environment. The dechlorination approach of HCB by stainless steel cathode could be proposed.
doi:10.1155/2014/371510
PMCID: PMC4065699  PMID: 24995145
3.  Hexachlorobenzene and octachlorostyrene in plasma of aluminium foundry workers using hexachloroethane for degassing. 
OBJECTIVES: To study the load of selected organochlorine compounds in the blood of aluminium foundry workers who use hexachloroethane as a degassing agent for aluminium and to measure some possible effects on internal organs. METHODS: Plasma from nine male aluminium foundry workers with past experience of use of hexachloroethane and 18 controls (two controls per exposed case) matched for residence, sex, age, and socioeconomic status was analysed for hexachlorobenzene (HCB), (P-HCB), and octachlorostyrene (P-OCS) with low resolution gas chromatography-mass spectrometry. Serum samples from the same subjects were analysed for standard kidney, pancreas, and liver function variables. Analysis of variance (ANOVA) with the triplets retained, a non-parametric test, and linear regression were used for the analysis. RESULTS: A fourfold increase of mean P-HCB was found among the exposed subjects compared with the controls (313.1 v 66.9 ng/g lipid; P < 0.01; (ANOVA model)). For P-OCS this difference was even larger (54.6 v 0.7 ng/g lipid; P < 0.01). Results were still significant (P < 0.05) with non-parametric testing. Within the exposed group there was a good correlation between the ln P-HCB (r = 0.80) and ln P-OCS (r = 0.91), respectively, with the cumulative number of years of exposure to hexachloroethane. No significant difference in kidney, pancreas, or liver function was found between the two groups. CONCLUSIONS: Aluminium degassing with hexachloroethane may increase the body burden of selected organochlorine compounds as reflected by HCB and OCS measurements. With the inherent limitations of this investigation no signs of subclinical organ toxicity were found.
PMCID: PMC1128987  PMID: 9326166
4.  Human Milk, Environmental Toxins and Pollution of Our Infants: Disturbing Findings during the First Six Months of Life 
Background:
Toxic organochlorine compounds (OC) are transmitted from mother to infant during lactation. OC are ingested by and stored in their offspring. Different harmful effects later in life have been attributed to the body pollution with these OC, although these findings are still discussed in an argumentative manner, since first other investigators could demonstrate beneficial effects of breast-feeding despite elevated OC concentrations, and second the benefits of breast-feeding are an unchallenged fact, especially in those countries, where infant formulas are not available. It was the aim of the present study to determine the lactational uptake of different OC (polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), and DDE) in breast-fed vs. bottle-fed infants up to six months of age.
Methods:
With the written informed consent of the parents, blood samples were taken from each ten breast-fed and bottle-fed infants, respectively. The specimens were immediately centrifuged, and serum was stored in glass tubes without an anticoagulant up to analysis. Three higher-chlorinated PCB congeners (IUPAC Nos. 138, 153, and 180), HCB, and DDE, the main metabolite of DDT in mammals, were determined with capillary gas chromatography with electron capture detection. In addition, reliability was tested with gas chromatography-mass spectrometry. Possible correlations of OC with personal data were tested with a standard multivariate regression model. Differences between study groups were tested on mean differences with Wilcoxons test for independent samples.
Results:
We could demonstrate that breast-fed infants have significantly (p<0.0001) elevated serum concentrations of all OC as early as at the age of six weeks (90%), which over and above nearly doubled further until the age of six months. (Median (μg/L); A=six weeks; B=six months): PCB 138, A: 0.40 vs. 0.09; B: 0.72 vs. 0.07; PCB 153, A: 0.57 vs. 0.11; B: 0.99 vs. 0.09; PCB 180, A: 0.33 vs. 0.04; B: 0.58 vs. 0.02; PCB (sum of the three PCB congeners), A: 1.19 vs. 0.29; B: 2.28 vs. 0.18; HCB, A: 0.13 vs. 0.04; B: 0.43 vs. 0.07; DDE, A: 1.05 vs. 0.18; B: 1.90 vs. 0.19.
Conclusions:
The discussion about the benefits of breast-feeding should be reconsidered again, with special emphasis on the question, whether the recommendations for breast-feeding can unreservedly be maintained for the future throughout the world, especially in face of the availability of infant formulas in industrialized vs. Third World countries, respectively.
PMCID: PMC3614598  PMID: 23674980
breast-feeding; organochlorine compounds; environmental pollutants; dietary toxicology; children
5.  Organochlorines, lead, and mercury in Akwesasne Mohawk youth. 
Environmental Health Perspectives  2003;111(7):954-961.
Most humans have detectable body burdens of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p'-dichlorophenyldichloroethylene p,p'-DDE), a metabolite of p,p'-dichlorodiphenyltrichloroethane (DDT). Native American communities may be at increased risk of exposure through subsistence-based diets and greater physical contact with contaminated soil and water. In this article we describe the levels of toxicants (PCBs, p,p'-DDE, HCB, mirex, lead, and mercury) among youth 10-17 years old (n = 271) of the Akwesasne Mohawk Nation. Ultratrace, congener-specific PCB analysis of human serum quantitated 83 PCB congeners (plus 18 as pairs/triplets), in addition to p,p'-DDE, HCB, and mirex, and included all major Aroclor-derived congeners typically present in human samples. Twenty congeners (in 16 chromatographic peaks) were detected in 50% or more of the individuals sampled [geometric mean (GM) of the sum of these congeners = 0.66 ppb]. Thirteen congeners (in 10 peaks) were detected in 75% or more of the samples (GM = 0.51 ppb). Of the 20 congeners detected in 50% or more of the samples, 17 had five or more chlorine substitutions. International Union for Pure and Applied Chemistry congeners 118, 101(+90), and 153 were detected in nearly all participants (GM = 0.06 ppb, 0.05 ppb, 0.09 ppb, respectively). p,p'-DDE and HCB were detected in 100% and 98% of the samples (GM: p,p'-DDE = 0.37 ppb; HCB = 0.03 ppb). Mirex was detected in approximately 46% of the samples (GM = 0.02 ppb). No cases of elevated lead level were observed. One participant had a mercury level marginally higher than the U.S. Environmental Protection Agency's current level of concern (0.50 microg/dL). Although differences in analytic methods and participant ages limit comparability, toxicant levels from the Mohawk youth are lower than those associated with severe food contamination (Yusho and Yu-cheng) but similar to other chronically exposed groups.
PMCID: PMC1241531  PMID: 12782498
6.  Role of “Dehalococcoides” spp. in the Anaerobic Transformation of Hexachlorobenzene in European Rivers▿† 
Applied and Environmental Microbiology  2011;77(13):4437-4445.
The diffuse pollution by chlorinated organic compounds in river basins is a concern, due to their potential adverse effects on human health and the environment. Organohalides, like hexachlorobenzene (HCB), are recalcitrant to aerobic microbial degradation, and “Dehalococcoides” spp. are the only known microorganisms capable of anaerobic transformation of these compounds coupled to their growth. In this study, sediments from four European rivers were studied in order to determine their HCB dechlorination capacities and the role of Dehalococcoides spp. in this process. Only a weak correlation was observed between Dehalococcoides species abundance and HCB transformation rates from different locations. In one of these locations, in the Ebro River sediment, HCB dechlorination could be linked to Dehalococcoides species growth and activity by 16S rRNA-based molecular methods. Furthermore, HCB dechlorination activity in this sediment was found over the full range of ambient temperatures that this sediment can be exposed to during different seasons throughout the year. The sediment contained several reductive dehalogenase (rdh) genes, and analysis of their transcription revealed the dominance of cbrA, previously shown to encode a trichlorobenzene reductive dehalogenase. This study investigated the role of Dehalococcoides spp. in HCB dechlorination in river sediments and evaluated if the current knowledge of rdh genes could be used to assess HCB bioremediation potential.
doi:10.1128/AEM.01940-10
PMCID: PMC3127731  PMID: 21571884
7.  Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population. 
Environmental Health Perspectives  2000;108(7):595-598.
A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.
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PMCID: PMC1638186  PMID: 10903610
8.  Association between serum concentrations of hexachlorobenzene and polychlorobiphenyls with thyroid hormone and liver enzymes in a sample of the general population 
OBJECTIVES—Hexachlorobenzene (HCB) is a highly lipophilic organochlorine compound of widespread environmental occurrence, that accumulates in the biological system. It affects the porphyrine metabolism, thyroid hormones, and the liver function in animals. Although HCB is one of the most common organochlorine compound in humans, little investigation on its health effects has been done. Polychlorobiphenyls (PCBs) are also widespread toxic environmental contaminants. The aim of the present study was to investigate the association of serum HCB and PCB concentrations with thyroid hormone status and liver enzymes in human.
METHODS—Thyroid stimulating hormone (TSH), total and free thyroxine (T4), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were measured as biological markers of thyroid and liver function in a rural population sample older than 14 years (n=192, except for TSH with n=608) highly exposed to HCB. Serum concentrations of HCB were measured by gas chromatography coupled to electron capture detection.
RESULTS—After adjustment for confounding variables, there was a significant negative association between serum HCB concentrations and total T4 (a decrease of 0.32 µg/dl per each unit, ln ng/ml, of increase of HCB) and a positive association with GGT (a relative increase of 10 % per each ln unit of increase of HCB), although most subjects (92%) were within the normal range for both T4 and GGT. These associations were not modified after adjustment for total lipid content or for other organochlorine compounds. The association of T4 and GGT with PCB was smaller although significant. No association was found with the other biochemical markers.
CONCLUSIONS—These results suggest that the internal dose of HCB of this population may reflect a subtle metabolic effect on thyroid function and an enzymatic induction activity. Further studies are needed to evaluate the health impact of these effects in more susceptible populations, such as infants.


Keywords: hexachlorobenzene; environmental exposure; thyroid; liver enzymes
doi:10.1136/oem.58.3.172
PMCID: PMC1740109  PMID: 11171930
9.  Systemic air embolism during percutaneous core needle biopsy of the lung: frequency and risk factors 
Background
Detection of risk factors for an air embolism in the left atrium, left ventricle, or systemic circulation (systemic air embolism, SAE) during a percutaneous core needle biopsy (PCNB) of the thorax.
Methods
In a retrospective observational study, all PCNBs of the thorax in 610 patients between 2007 and 2009 were analyzed. The SmartStep™ technique (General Electric) was used for the biopsy, with which the examiner can prepare a batch of three 1.25-mm or 2.5-mm collimated slices within a second using a foot switch in the CT room to check the needle position. The image data thus generated and the control CT scans that followed were examined retrospectively for the presence of intravascular air. Intravascular air was defined as two or more adjacent voxels with absorption values of < -200 HU in the left atrium, left ventricle, aorta, or arteries during or after the procedure. The univariate statistical analysis of categorical variables was made using 2 by 2 tables and the Fisher test. The groups were compared using the Mann-Whitney test. Finally, a multivariate logistic regression analysis was used to identify independent risk factors for the occurrence of an SAE.
Results
The radiological incidence of an SAE during a PCNB was 3.8% (23/610 patients), whereas the clinically apparent incidence was 0.49%. Two patients developed clinical symptoms consisting of transient hemiplegia or transient amaurosis; one died due to a fatal SAE of the coronary arteries. The mortality was thus 0.16%. The depth of the needle in the lesion (Wald: 6.859), endotracheal anesthesia (Wald: 5.721), location of the lesion above the level of the left atrium (Wald: 5.159), and prone position of the patients (Wald: 4.317) were independent risk factors for the incidence of an SAE (p < 0.05 each). Using explorative criteria, the acute angle of the needle to the tumor surface, and the transition of ventilated lung were independent factors. The frequency of biopsies, needle penetration depth, and tumor location near the diaphragm or in the lower lobe also played a subordinate role, not however, the needle penetration depth through the lung.
Conclusion
If possible, the PCNB should be performed under local anesthesia. We recommend avoiding endotracheal anesthesia and prone position. Whenever possible, patients should be positioned on the back in such a way that the tumor is lower than the left atrium. The tip of the needle should be within the tumor during the biopsy procedure.
doi:10.1186/1471-2466-12-2
PMCID: PMC3608336  PMID: 22309812
Transthoracal biopsy; Computed tomography; Air embolism; Risk analysis; cutting biopsy; Lung Cancer; Smart-Step™
10.  Serum organochlorines and urinary porphyrin pattern in a population highly exposed to hexachlorobenzene 
Background
Porphyria cutanea tarda (PCT) is caused by hexachlorobenzene (HCB) in several species of laboratory mammals, but the human evidence is contradictory. In a study among adults of a population highly exposed to HCB (Flix, Catalonia, Spain), the prevalence of PCT was not increased. We aimed at analysing the association of individual urinary porphyrins with the serum concentrations of HCB and other organochlorine compounds in this highly exposed population.
Methods
A cross-sectional study on total porphyrins was carried out in 1994 on 604 inhabitants of the general population of Flix, older than 14 years. Of them, 241 subjects (comprising a random sample and the subgroup with the highest exposure) were included for the present study. The porphyrin profile was determined by high-pressure liquid chromatography. Serum concentrations of HCB, as well as common organochlorine compounds, were determined by gas chromatography coupled to electron capture detection.
Results
Coproporphyrin I (CPI) and coproporphyrin III (CPIII) were the major porphyrins excreted, while uroporphyrins I and III were only detected in 2% and 36% of the subjects respectively, and heptaporphyrins I and III in 1% and 6%, respectively. CPI and CPIII decreased with increasing HCB concentrations (p < 0.05). This negative association was not explained by age, alcohol, smoking, or other organochlorine compounds. No association was found between uroporphyrin I and III excretion, nor heptaporphyrin excretion, and HCB. CPIII increased with smoking (p < 0.05).
Conclusion
HCB exposure in this highly exposed population did not increase urinary concentrations of individual porphyrins.
doi:10.1186/1476-069X-1-1
PMCID: PMC131010  PMID: 12495451
coproporphyrin I; coproporphyrin III; hexachlorobenzene; organochlorinated compounds; porphyria; uroporphyrin
11.  Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies. 
Environmental Health Perspectives  2001;109(2):173-178.
Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.
PMCID: PMC1240639  PMID: 11266329
12.  Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population. 
Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.
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PMCID: PMC1469858  PMID: 9074885
13.  Organochlorine in the serum of inhabitants living near an electrochemical factory 
OBJECTIVES: To measure the impact of occupational and lifestyle factors on concentrations of organochlorine compounds in a general population sample living near an electrochemical factory with a high airborne concentration of hexachlorobenzene (HCB). METHODS: Serum samples from 608 people (328 selected from a random sample) were collected in 1994. Information on lifestyles, occupation, and medical condition was obtained by questionnaire. RESULTS: HCB and polychlorinated biphenyls (PCBs) were detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed by dichlorodiphenyl dichloroethane (DDE) and beta-hexachlorocyclohexane (beta-HCH), found in 98.7% and 87.3% of the samples respectively (means 4.6 ng/ml and 2.5 ng/ml, respectively). Concentrations of HCB were the highest ever reported. Occupation in the factory was the main determinant of the variation in concentrations of HCB (regression coefficients 1.52 (SEM 0.14) in 1n (HCB) for workers in the production department, and 2.13 (0.23) for workers in maintenance department) and explained the highest concentrations of HCB found in men of middle age. In retired workers, concentrations of HCB declined with time since retirement. The PCBs, dichlorodiphenyl trichloroethane (DDT), and beta-HCH were independent of the occupation and concentrations were similar to those found in other populations. Concentrations of beta-HCH and DDE in the whole population, and HCB among non-workers, were higher in women than in men. Concentrations of all measured organochlorine compounds increased with age and body mass index. Consumption of locally caught fish was an independent determinant of HCB and PCB concentrations. CONCLUSIONS: This population incorporated HCB directly through occupation in the electrochemical factory, by airborne pollution, and consumption of locally caught fish. Concentrations of other common organochlorine compounds were not higher than expected. Environmental exposures to these compounds deserve attention due to their persistence and potential health effects.
 
PMCID: PMC1757711  PMID: 10448322
14.  Meconium and neurotoxicants: searching for a prenatal exposure timing 
Archives of Disease in Childhood  2006;91(8):642-646.
Background
Exposure to organochlorine compounds (OCs) has been a subject of interest in recent years, given their potential neurotoxicity. Meconium is easily available and accumulates neurotoxicants and/or metabolites from the 12th week of gestation.
Aims
To determine whether neurotoxicants, specifically OCs, could be detected in serially collected meconium, and to compare the results with those obtained in cord blood samples.
Methods
A sample of cord blood and three serial stool samples were analysed in 10 newborns. Pentachlorobenzene (PeCB), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane (p,p′‐DDT) and its metabolite dichlorodiphenyl dichloroethylene (p,p′‐DDE), and hexachlorocyclohexane isomers (α‐, β‐, γ‐, and δ‐HCH) were analysed by gas chromatography.
Results
From serial stool collection and analysis in newborns, there was an increase in the concentrations of HCB, p,p′‐DDE, PCBs, and β‐HCH between the first and last stools of the newborn. Levels of DDT diminished as pregnancy progressed. Concentrations in cord blood were positively associated with concentrations in meconium for p,p′‐DDE and β‐HCH.
Conclusions
Meconium is a very useful instrument for the investigation of fetal exposure to neurotoxicants; serial collection and analysis of meconium should estimate the timing and degree of in utero exposure of the fetus to neurotoxicants. Analysis and interpretation of neurotoxicants in meconium results is a complex process. Measurement in meconium of a wide range of neurotoxic substances should facilitate early identification of harmful exposures, and enable rehabilitation and instigation of preventive measures.
doi:10.1136/adc.2005.084129
PMCID: PMC2083026  PMID: 16624883
biological markers; environmental pollutants; meconium, neurotoxicity syndromes; prenatal exposure
15.  Association of Hexachlorobenzene (HCB), Dichlorodiphenyltrichloroethane (DDT), and Dichlorodiphenyldichloroethylene (DDE) with in Vitro Fertilization (IVF) Outcomes 
Environmental Health Perspectives  2011;120(2):316-320.
Background: Hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) are persistent chlorinated pesticides with endocrine activity that may adversely affect the early stages of human reproduction.
Objective: Our goal was to determine the association of serum levels of HCB, DDT, and DDE with implantation failure, chemical pregnancy, and spontaneous abortion in women undergoing in vitro fertilization (IVF) from 1994 to 2003.
Methods: Levels of HCB and congeners of DDT and DDE were measured in serum collected during the follicular phase. Multivariable-adjusted statistical models accommodating multiple outcomes and multiple cycles per woman were used to estimate the relation between serum pesticide levels and IVF outcomes.
Results: A total of 720 women with a mean ± SD age 35.4 ± 4.2 years at enrollment contributed 774 IVF cycles. All samples had detectable levels of HCB, DDT, and DDE, with median levels of 0.087 ng/g serum for HCB, 1.12 ng/g serum for total DDT, and 1.04 ng/g serum for p,p´-DDE. Compared with the lowest quartile (Q1) of HCB, the lipid- and multivariable-adjusted odds ratio (OR) for failed implantation was significantly elevated for those with higher HCB quartiles [Q2–Q4; adjusted ORs: for Q2, 1.71; 95% confidence interval (CI): 1.03, 2.82; for Q3, 2.30; 95% CI: 1.39, 3.81; for Q4, 2.32; 95% CI: 1.38, 3.90] and showed a significantly increasing trend (p = 0.001). No statistically significant associations were observed between DDT/DDE and IVF outcomes or between HCB and chemical pregnancy or spontaneous abortion.
Conclusions: Serum HCB concentrations were on average lower than that of the general U.S. population and associated with failed implantation among women undergoing IVF.
doi:10.1289/ehp.1103696
PMCID: PMC3279437  PMID: 22204795
assisted reproduction; dichlorodiphenyldichloroethylene; dichlorodiphenyltrichloroethane; hexachlorobenzene; prospective cohort
16.  The role of the immune system in hexachlorobenzene-induced toxicity. 
Environmental Health Perspectives  1999;107(Suppl 5):783-792.
Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxicity of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic properties in laboratory animals and probably also in man. Oral exposure of rats to HCB showed stimulatory effects on spleen and lymph node weights and histology, increased serum IgM levels, and an enhancement of several parameters of immune function. Moreover, more recent studies indicate that HCB-induced effects in the rat may be related to autoimmunity. In Wistar rats exposed to HCB, IgM antibodies against several autoantigens were elevated; in the Lewis rat, HCB differently modulated two experimental models of autoimmune disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whether these skin and lung lesions can be related to HCB-induced immunomodulation, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differences and correlation of skin lesions with immune parameters suggest a specific involvement of the immune system in HCB-induced skin lesions. The induction of lung lesions by HCB was thymus independent. Thymus-dependent T cells were not likely to be required for the induction of skin lesions, although T cells enhanced the rate of induction and the progression of the skin lesions. No deposition of autoantibodies was observed in nonlesional or lesional skin of HCB-treated rats. Therefore, we concluded that it is unlikely that the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T- and B-cell activation, is involved in the HCB-induced immunopathology in the rat. Such a thymus-independent immunopathology is remarkable, as HCB strongly modulates T-cell-mediated immune parameters. This points at a very complex mechanism and possible involvement of multiple factors in the immunopathology of HCB.
Images
PMCID: PMC1566236  PMID: 10502545
17.  Microcystin-Degrading Activity of an Indigenous Bacterial Strain Stenotrophomonas acidaminiphila MC-LTH2 Isolated from Lake Taihu 
PLoS ONE  2014;9(1):e86216.
Microcystin-LR (MC-LR) and microcystin-RR (MC-RR) produced by harmful cyanobacterial blooms (HCBs) pose substantial threats to the ecosystem and public health due to their potential hepatotoxicity. Degradation of microcystins (MCs) by indigenous bacteria represents a promising method for removing MCs from fresh water without harming the aquatic environment, but only a few microcystin (MC)-degrading bacteria have been isolated and had their mechanisms reported. This study aimed to isolate indigenous bacteria from Lake Taihu, and investigate the capability and mechanism of MC degradation by these bacteria. During a Microcystis bloom, an indigenous MC-degrading bacterium designated MC-LTH2 was successfully isolated from Lake Taihu, and identified as Stenotrophomonas acidaminiphila based on phylogenetic analysis. In the presence of MC-LR together with MC-RR, the strain MC-LTH2 was capable of totally degrading both simultaneously in 8 days, at rates of 3.0 mg/(L⋅d) and 5.6 mg/(L⋅d), respectively. The degradation rates of MCs were dependent on temperature, pH, and initial MC concentration. Adda (3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid) was detected as an intermediate degradation product of MCs using high performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). To the best of our knowledge, this is the first report of Stenotrophomonas acidaminiphila capable of degrading two MC analogues and other compounds containing Adda residue completely under various conditions, although the mlrA gene in the strain was not detected. These results indicate the Stenotrophomonas acidaminiphila strain MC-LTH2 possesses a significant potential to be used in bioremediation of water bodies contaminated by MC-LR and MC-RR, and is potentially involved in the degradation of MCs during the disappearance of the HCBs in Lake Taihu.
doi:10.1371/journal.pone.0086216
PMCID: PMC3887098  PMID: 24416455
18.  Chemical Control of Nematodes and Soil-borne Plant-Pathogenic Fungi on Cabbage Tranplants 
Journal of Nematology  1979;11(2):138-1434.
Six general-purpose fumigants and one fungicide were applied by different methods and evaluated for control of nematode-fungus complexes on cabbage grown for transplant production. All chemicals reduced populations of nematodes and soil-borne fungi but varied greatly in effectiveness. Methyl bromide + chloropicrin (98% methyl bromide + 2% chloropicrin) (MBR-CP gas), DD + methyl isothiocyanate (DD-MENCS), methyl bromide + chloropicrin (67% methyl bromide + 31.75% cbloropicrin) (MBR-CP gel), and chloropicrin were more effective than sodium methyl dithiocarbamate (metham), pentachloronitrobenzene (PCNB), and potassium N-hydroxy-methyl-N-methyldithiocarbamate (Bunema) against Meloidogyne incognita. Populations of Pythium spp. and Fusarium spp. were reduced markedly by all treatments except PCNB. Plant growth, uniformity, and yield were greater when nematodes and fungi were controlled.
PMCID: PMC2617953  PMID: 19305547
Brassica oleracea; root-knot nematodes
19.  Genetics and sequence analysis of the pcnB locus, an Escherichia coli gene involved in plasmid copy number control. 
Journal of Bacteriology  1989;171(3):1254-1261.
Mutations at the Escherichia coli pcnB locus reduce the copy number of ColE1-like plasmids. We isolated additional mutations in this gene and conducted a preliminary characterization of its product. F-prime elements carrying the pcnB region were constructed and used to show that the mutations were recessive. The wild-type pcnB gene was cloned into a low-copy-number plasmid, and its nucleotide sequence was determined. The sequence analysis indicated that pcnB is probably the first gene in an operon that contains one or more additional genes of unknown function. The pcnB locus should encode a polypeptide of 47,349 daltons (Da). A protein of this size was observed in minicells carrying a pcnB+ plasmid, and transposon insertions and deletions that truncated this protein generally abolished pcnB function. One exceptional transposon insertion at the promoter-distal end of the pcnB gene truncated the 47-kDa protein by about 20% but did not abolish complementation activity, indicating that the C-terminus of the PcnB product is dispensable. The deduced amino acid sequence of PcnB revealed numerous charged residues and, with 10% arginines, an overall basic character, suggesting that PcnB might interact with DNA or RNA in a structural capacity. Disruption of the pcnB gene by insertional mutagenesis caused a reduction in growth rate, indicating that PcnB has an important cellular function.
Images
PMCID: PMC209738  PMID: 2537812
20.  Mass Spectrometry-based Proteomics of Human Cannabinoid Receptor 2: Covalent Cysteine 6.47(257)-Ligand Interaction Affording Megagonist Receptor Activation 
Journal of proteome research  2011;10(10):4789-4798.
The lack of experimental characterization of the structures and ligand-binding motifs of therapeutic G-protein coupled receptors (GPCRs) hampers rational drug discovery. The human cannabinoid receptor 2 (hCB2R) is a class-A GPCR and promising therapeutic target for small-molecule cannabinergic agonists as medicines. Prior mutational and modeling data constitute provisional evidence that AM-841, a high-affinity classical cannabinoid, interacts with cysteine C6.47(257) in hCB2R transmembrane helix 6 (TMH6) to afford improved hCB2R selectivity and unprecedented agonist potency. We now apply bottom-up mass spectrometry (MS)-based proteomics to define directly the hCB2R-AM-841 interaction at the amino-acid level. Recombinant hCB2R, overexpressed as an N-terminal FLAG-tagged/C-terminal 6His-tagged protein (FLAG-hCB2R-6His) with a baculovirus system, was solubilized and purified by immunochromatography as functional receptor. A multiplex multiple reaction monitoring (MRM)-MS method was developed that allowed us to observe unambiguously all seven discrete TMH peptides in the tryptic digest of purified FLAG-hCB2R-6His and demonstrate that AM-841 modifies hCB2R TMH6 exclusively. High-resolution mass spectra of the TMH6 tryptic peptide obtained by Q-TOF MS/MS analysis demonstrated that AM-841 covalently and selectively modifies hCB2R at TMH6 cysteine C6.47(257). These data demonstrate how integration of MS-based proteomics into a ligand-assisted protein structure (LAPS) experimental paradigm can offer guidance to structure-enabled GPCR agonist design.
doi:10.1021/pr2005583
PMCID: PMC3189276  PMID: 21861534
agonist; covalent probe; drug discovery; electrospray ionization; GPCR; ligand binding domain; multiple reaction monitoring; protein structural biology
21.  Exposure to Hexachlorobenzene during Pregnancy and Children’s Social Behavior at 4 Years of Age 
Environmental Health Perspectives  2006;115(3):447-450.
Background
Hexachlorobenzene (HCB) is an organochlorine chemical that has been used in agriculture and industrial processes. Behavioral impairment after HCB exposure has been described in animal models, but little information is available in humans.
Objectives
Our goal was to study the association of prenatal exposure to HCB with the social behavior of preschool children.
Methods
Two birth cohorts in Ribera d’Ebre and Menorca (Spain) were set up between 1997 and 1999 (n = 475). The California Preschool Social Competence Scale and the Attention-Deficit Hyperactivity Disorder (ADHD) were scored by each 4-year-old child’s teacher. Organochlorine compounds were measured in cord serum. Children’s diet and parental sociodemographic information were obtained through questionnaire.
Results
Children with concentrations of HCB > 1.5 ng/mL at birth had a statistically significant increased risk of having poor Social Competence [relative risk (RR) = 4.04; 95% confidence interval (CI), 1.76–9.58] and ADHD (RR = 2.71; 95% CI, 1.05–6.96) scores. No association was found between HCB and the cognitive and psychomotor performance of these children.
Conclusions
Prenatal exposure to current concentrations of HCB in Spain is associated with a decrease in the behavioral competence at preschool ages. These results should be considered when evaluating the potential neurotoxicologic effects of HCB.
doi:10.1289/ehp.9314
PMCID: PMC1849941  PMID: 17431497
behavior; children; cord serum; HCB; hexachlorobenzene; hyperactivity; prenatal exposure; social competence
22.  Organochlorines in Swedish women: determinants of serum concentrations. 
Environmental Health Perspectives  2003;111(3):349-355.
We studied associations between lifestyle/medical factors and lipid-adjusted serum concentrations of seven polychlorinated biphenyl (PCB) congeners and five chlorinated pesticides/metabolites among 205 Swedish women (54-75 years old). Serum concentrations were significantly associated with age, body mass index, body weight change, diabetes mellitus, consumption of fatty fish, and place of residence. The findings suggest that lifestyle/medical factors may confound results in epidemiologic studies when they are related to both serum concentrations and disease. Moreover, disease itself may influence serum concentrations of some organochlorines, as indicated by the negative associations between recent weight change and serum concentrations of some PCB congeners, p,p -dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) and the positive association between diabetes mellitus and HCB concentrations. Age was the only determinant that showed a consistent association with all compounds studied (positive); otherwise associations with single determinants varied among compounds even within the PCB group. This shows that the studied organochlorines should not be treated as a homogeneous group of compounds in epidemiologic studies.
PMCID: PMC1241393  PMID: 12611665
23.  Relationship of Thyroid Hormone Levels to Levels of Polychlorinated Biphenyls, Lead, p,p′- DDE, and Other Toxicants in Akwesasne Mohawk Youth 
Environmental Health Perspectives  2008;116(6):806-813.
Background
It is well documented that acute exposure to high levels of persistent organic pollutants, such as polychlorinated biphenyls (PCBs), p,p′-dichlorophenyldichloroethylene (p,p′-DDE), and hexachlorobenzene (HCB), can affect human health including thyroid function. Chronic exposure to multiple toxicants is common but difficult to analyze, and most prior studies have focused on adults or newborns, creating a gap in our understanding of multitoxicant effects among adolescents.
Objective
We investigated whether levels of PCBs, p,p′-DDE, HCB, mirex, lead, and mercury reflecting past chronic exposure are associated with alterations in levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), total thyroxine (TT4), and free thyroxine (FT4) among older children and adolescents.
Methods
The sample consists of youth from the Akwesasne Mohawk Nation (n = 232) who reside in proximity to several industries that have contaminated the local environment. We used multiple regression analysis to examine the effect of PCB groupings, p,p′-DDE, HCB, lead, and mercury on thyroid hormones after adjusting for sociodemographic covariates and controlling for all other toxicants.
Results
Exposure to PCBs affects the thyroid hormone profile in adolescents. The group of persistent PCBs was positively associated with TSH but inversely related to FT4. Nonpersistent PCBs were significantly and negatively related to FT4 only. HCB was negatively associated with T4, and lead was positively associated with T3. Breast-fed adolescents had higher levels of persistent PCBs and p,p′-DDE but not of nonpersistent PCBs or any other toxicant when compared with non-breast-fed adolescents. Though having lower levels of persistent PCBs and p,p′-DDE, non-breast-fed adolescents exhibited significant relationships between persistent PCBs and TSH and FT4, but breast-fed adolescents did not. It appears that PCBs from breast milk obscure the relationship between prenatal PCB exposure and thyroid function by adding random variation in PCB levels.
Conclusion
Our results demonstrate a reduction in thyroid function in adolescents in relation to their current serum levels of PCBs. These observations are consistent with the hypothesis that pre-natal exposure to PCBs alters thyroid function in a long-lasting manner but does not exclude the possibility that postnatal exposure is influential also.
doi:10.1289/ehp.10490
PMCID: PMC2430238  PMID: 18560538
adolescents; hexachlorobenzene; mercury; mirex; Mohawk; Native American; PCBs; POPs; p,p′-dichlorophenyldichloroethylene; thyroid; thyroid hormones
24.  Complete degradation of polychlorinated hydrocarbons by a two-stage biofilm reactor. 
Applied and Environmental Microbiology  1991;57(12):3418-3422.
A two-stage anaerobic-aerobic biofilm reactor successfully degraded a mixture of chlorinated organic compounds to water-soluble metabolic intermediates and carbon dioxide. Reductive dechlorination of hexachlorobenzene (HCB), tetrachloroethylene (PCE), and chloroform (CF) occurred on all tested primary carbon sources such as glucose, methanol, and acetate. However, the extent of dechlorination was maximum when the anaerobic biofilm column was fed acetate as a primary carbon source. HCB, PCE, and CF were dechlorinated to the levels of tri- and dichlorinated products (99, 80, and 32%, respectively) with acetate in the feed. This is important, since these less-chlorinated compounds can be metabolized by the aerobic biofilm. The effluent from the anaerobic biofilm column was fed directly into the aerobic column. After both columns, the total amount transformed into nonvolatile intermediates and carbon dioxide was 94, 96, and 83% for [14C]HCB, [14C]trichloroethylene, and [14C]CF, respectively. This research shows the potential application of this novel two-stage bioreactor system for treating groundwaters and industrial effluents composed of highly chlorinated aliphatic and aromatic hydrocarbons.
PMCID: PMC183990  PMID: 1785918
25.  Tracking Functional Guilds: “Dehalococcoides” spp. in European River Basins Contaminated with Hexachlorobenzene▿ †  
Applied and Environmental Microbiology  2009;75(14):4696-4704.
Hexachlorobenzene (HCB) has been widely used in chemical manufacturing processes and as a pesticide. Due to its resistance to biological degradation, HCB has mainly accumulated in freshwater bodies and agricultural soils. “Dehalococcoides” spp., anaerobic dechlorinating bacteria that are capable of degrading HCB, were previously isolated from river sediments. Yet there is limited knowledge about the abundance, diversity, and activity of this genus in the environment. This study focused on the molecular analysis of the composition and abundance of active Dehalococcoides spp. in HCB-contaminated European river basins. 16S rRNA-based real-time quantitative PCR and denaturing gradient gel electrophoresis in combination with multivariate statistics were applied. Moreover, a functional gene array was used to determine reductive dehalogenase (rdh) gene diversity. Spatial and temporal fluctuations were observed not only in the abundance of Dehalococcoides spp. but also in the composition of the populations and rdh gene diversity. Multivariate statistics revealed that Dehalococcoides sp. abundance is primarily affected by spatial differences, whereas species composition is under the influence of several environmental parameters, such as seasonal changes, total organic carbon and/or nitrogen content, and HCB contamination. This study provides new insight into the natural occurrence and dynamics of active Dehalococcoides spp. in HCB-contaminated river basins.
doi:10.1128/AEM.02829-08
PMCID: PMC2708439  PMID: 19376891

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