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.

Serum levels of Organochlorine Pesticides and Breast Cancer Risk in Iranian Women.

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Blood Concentrations of Persistent Organic Pollutants and Unhealthy Metabolic Phenotypes in Normal-Weight, Overweight, and Obese Individuals.

Factors underlying metabolic phenotypes, such as the metabolically healthy but obese phenotype, remain unclear. Differences in metabolic phenotypes-particularly, among individuals with a similar body mass index-could be related to concentrations of persistent organic pollutants (POPs). To our knowledge, no studies have analyzed POPs and metabolic phenotypes in normal-weight persons. We investigated the relationships between serum concentrations of POPs and metabolic phenotypes in 860 normal-weight, overweight, and obese participants in the 2002 Catalan Health Interview Survey (Spain). POP concentrations were significantly higher in metabolically unhealthy than in metabolically healthy individuals. In models adjusting for body mass index and other confounders, hexachlorobenzene, ß-hexachlorocyclohexane, and polychlorinated biphenyls were associated with the unhealthy metabolic phenotype and metabolic syndrome. Among normal-weight individuals, the adjusted prevalence ratio of having an unhealthy phenotype for the upper category of the sum of orders of the 6 mentioned POPs (all individually associated with metabolic phenotypes) was 4.1 (95% confidence interval: 1.7, 10.0). Among overweight and obese individuals, the corresponding prevalence ratio for the sum of polychlorinated biphenyls was 1.4 (95% confidence interval: 1.0, 1.8). Our results supported the hypothesis that POP concentrations are associated with unhealthy metabolic phenotypes, not only in obese and overweight individuals but also (and probably more strongly) in normal-weight individuals.

Veterinary utility of dried blood spots for analysis of toxic chlorinated hydrocarbons.

Dried blood spots (DBS) on filter paper provide a simple and convenient means of collecting, storing and shipping samples for veterinary diagnostics related to toxin exposures. This paper presents validation data on analysis of DBS for chlorinated persistent organic pollutants, specifically 4,4'-dichloro-diphenyl-trichloroethane (4,4'-DDT) and its breakdown product 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE), lindane and a representative polychlorinated biphenyl (PCB) congener PCB-153. Analysis was by gas chromatography with electron capture detection (GC-ECD). The method required one 12.5 mm diameter spot representing application of 50 µL of blood, and working limits of detection (LOD) for each of the compounds was 5 ppb. Data are presented on development and description of the method, assay precision, LOD and quantitation, linearity, accuracy, specificity, effects of long-term storage and ruggedness. The method was also applied to 27 avian DBS, and 4,4'-DDE was detected in the majority of samples.

Background biomonitoring of residue levels of 137 pesticides in the blood plasma of the general population in Beijing.

Due to the widespread use of pesticides, human exposure to pesticides is possible and can potentially cause adverse impacts on public health. We measured 137 pesticides including organophosphorus, organochlorine, pyrethroid and carbamate pesticides together with various herbicides in 100 human blood samples collected from the general population in Beijing. The samples were analysed by triple quadrupole tandem gas chromatography-mass spectrometry. In total, 24 organochlorine pesticides, 5 pyrethroid pesticides and 6 organophosphorus pesticides were detected. The detection rates of HCB, α-HCH, ß-HCH, γ-HCH, p,p'-DDE and quintozene were 99, 96, 74, 72, 96 and 95%, respectively. No statistically significant gender difference in the blood concentrations of the pesticides was found. Consistent with the trend of the increasing ß-HCH, p,p'-DDE and quintozene concentrations with age, a strong positive correlation between the age and concentrations of ß-BHC, p,p'-DDE and quintozene was observed.

Predicting pregnancy outcomes using longitudinal information: a penalized splines mixed-effects model approach.

We propose a semiparametric nonlinear mixed-effects model (SNMM) using penalized splines to classify longitudinal data and improve the prediction of a binary outcome. The work is motivated by a study in which different hormone levels were measured during the early stages of pregnancy, and the challenge is using this information to predict normal versus abnormal pregnancy outcomes. The aim of this paper is to compare models and estimation strategies on the basis of alternative formulations of SNMMs depending on the characteristics of the data set under consideration. For our motivating example, we address the classification problem using a particular case of the SNMM in which the parameter space has a finite dimensional component (fixed effects and variance components) and an infinite dimensional component (unknown function) that need to be estimated. The nonparametric component of the model is estimated using penalized splines. For the parametric component, we compare the advantages of using random effects versus direct modeling of the correlation structure of the errors. Numerical studies show that our approach improves over other existing methods for the analysis of this type of data. Furthermore, the results obtained using our method support the idea that explicit modeling of the serial correlation of the error term improves the prediction accuracy with respect to a model with random effects, but independent errors. Copyright © 2017 John Wiley & Sons, Ltd.

Concentrations of organochlorine pesticides in pooled human serum by age and gender.

Organochlorine pesticides (OCPs) have been used for many decades in Australia with cessation of selected persistent and bioaccumulative OCPs ranging from the 1970s to as recently as 2007. The specific aims of this study were to use samples representative of an Australian population to assess age and gender differences in the concentration of OCPs in human blood sera and to investigate temporal trends in these chemicals. Serum was collected from de-identified, surplus pathology samples over five time periods (2002/03, 2006/07, 2008/09, 2010/11 and 2012/13), with 183 serum pools made from 12,175 individual samples; 26 pools in 2002/03, 85 pools in 2006/07 and 24 pools each in 2008/09, 2010/11 and 2012/13. Samples were analyzed for hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), γ -hexachlorocyclohexane (lindane) (γ-HCH), oxy-chlordane, trans-nonachlor, p,p'-DDE, o,p'-DDT, p,p'-DDT and Mirex. Stratification criteria included gender and age (0-4; 5-15; 16-30; 31-45; 46-60; and >60 years) with age additionally stratified by adults >16 years and children 0-4 and 5-15 years. All pools from all collection periods had detectable concentrations of OCPs with a detection frequency of >60% for HCB, ß-HCH, trans-nonachlor, p,p'-DDT and p,p'-DDE. The overall OCP concentrations increased with age with the highest concentrations in the >60 years groups. Females did not have higher mean OCP concentrations than males except for HCB concentrations (p=0.0006). Temporal trends showed overall decreasing serum concentrations by collection period with the exception of an increase in OCP concentrations between 2006/07 and 2008/09. Excluding this data point, HCB decreased from year to year by 7-76%; ß-HCH concentrations decreased by 14 - 38%; trans-nonachlor concentrations decreased by 10 - 65%; p,p'-DDE concentrations decreased by 6 - 52%; and p,p'-DDT concentrations decreased by 7 - 30%. The results indicate that OCP concentrations have decreased over time as is to be expected following the phase out of these chemicals in Australia.

Organochlorine pesticides levels and associated factors in a group of blood donors in São Paulo, Brazil.

The use of organochlorine pesticides (OCPs) is a worldwide public health concern given that high levels of these compounds in humans and animals can lead to serious health problems. This study aimed to evaluate the levels of 15 organochlorine pesticides in the serum of 547 blood donors in the São Paulo metropolitan region (SPMR) in 2009 and to investigate factors associated with higher levels of these compounds. The OCPs were determined by gas chromatography with micro electron capture detection. Multiple ordinal logistic regression models were employed to determine the factors associated with higher levels. Only ß-HCH and p,p'-DDE had a significant number of samples above the limit of quantification. Factors associated with higher levels of ß-HCH were age within 26 to 35 years (OR = 3.1 [1.05-9.09]), age within 36 to 45 years (OR = 18.27 [6.89-48.91]), and female gender (OR = 0.44 [0.24-0.82] for men). p,p'-DDE levels were associated with age within 26 to 35 years (OR = 2.65 [1.20-3.45]), age within 36 to 45 years (OR = 4.59 [2.64-7.92]), female gender (OR = 0.86 [0.43-0.94] for men), and previous work with pesticides (OR = 2.88 [1.22-6.84]). Lower levels of p,p'-DDE were associated with an income of 3 to 5 minimum wages (OR = 0.38 [0.19-0.75]) and with intake of foods from animal origin up to twice a week (OR = 0.15 [0.03-0.72]) and more than twice a week (OR = 0.10 [0.02-0.47]). The results of this study indicate that the study group was not exposed to high levels of OCPs.

Organochlorine Pesticides in Gonad, Brain, and Blood of Mice in Two Agricultural Areas of Sinaloa.

The adverse effect of pesticides on non-target wildlife and human health is a primary concern in the world, but in Mexico, we do not know which wildlife species are at the greatest risk. The aim of this study was to determine organochlorine pesticides in mice of two agricultural fields in Sinaloa, Culiacan and Guasave. Procedures of extraction, analysis, and quantification were followed according to the modified EPA 8081b method. In three mouse tissues (gonad, brain, and blood), γBHC and decachlorobiphenyl with a frequency higher than 50% and endosulfan sulfate with 43% were observed. The wildlife fauna living in agricultural areas are at great risk due to: (1) diversity of the chemicals used for pest control, like mice, and (2) variety of organochlorine pesticides in direct or indirect contact with non-target organisms, affecting the health of animals and humans (toxic effects and accumulation).

Selected Organochlorines in Human Blood and Urine in the South of the Russian Far East.

The trace OCP concentrations, such as α-, ß-, and γ-HCH, DDT and its metabolites (DDD and DDE) in blood and urine of residents from the south of the Russian Far East was revealed. A large range of OCPs was found in the urine: α- and γ-isomers of HCH, DDT and DDE. The only ß-HCH was detected in the blood; this indicates its persistence and the difficulty of excretion this substance from the organism. The total trace OCP concentration, found in the biological fluids of residents of the south of the Russian Far East, providing further evidence that these organic contaminants persist in the environment.

Organochlorine Pesticides in the Ferruginous Pygmy Owl (Glaucidium brasilianum) in Chiapas, Mexico.

Concentrations of organochlorine pesticides were quantified in samples of feathers (n = 17) and blood (n = 15) of the ferruginous pygmy owl (Glaucidium brasilianum). The individuals were captured near the Protected Natural Area Cerro Sonsonate, Chiapas, Mexico, between February and June 2014. In both tissues, pesticides belonging to seven organochlorine chemical families were detected. However, the organochlorine pesticide concentrations differed between feathers and blood. The highest concentrations of hexachlorocyclohexanes were found in feathers (0.63 ± 0.89 µg/g), whereas the highest concentrations of ΣDrines were found in blood (0.31 ± 0.47 µg/mL). By using the summed concentrations for each of the seven families of pesticides found in feathers, we did not find any significant correlation between the pesticides and pectoral muscle or body weight (p > 0.15). The ΣDDT group was the only pesticide family that showed a positive correlation with owl body weight (r = 0.60, p = 0.05); the concentrations of these pesticides were also high in feather and blood tissues (r = 0.87, p = 0.02). Our results confirm that ferruginous pygmy owls in the study area are exposed to these pesticides.

Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: a case study of lindane-induced neurotoxicity.

Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans. Time- and concentration-dependent lindane dosimetry was determined in primary cultures of rat cortical neurons in vitro using "faux" (without electrodes) microelectrode arrays (MEAs). In vivo data were derived from literature values, and physiologically based pharmacokinetic (PBPK) modeling was used to extrapolate from rat to human. The previously determined EC50 for increased firing rates in primary cultures of cortical neurons was 0.6µg/ml. Media and cell lindane concentrations at the EC50 were 0.4µg/ml and 7.1µg/ml, respectively, and cellular lindane accumulation was time- and concentration-dependent. Rat blood and brain lindane levels during seizures were 1.7-1.9µg/ml and 5-11µg/ml, respectively. Brain lindane levels associated with seizures in rats and those predicted for humans (average=7µg/ml) by PBPK modeling were very similar to in vitro concentrations detected in cortical cells at the EC50 dose. PBPK model predictions matched literature data and timing. These findings indicate that in vitro MEA results are predictive of in vivo responses to lindane and demonstrate a successful modeling approach for IVIVE of rat and human neurotoxicity.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 µg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

Hematological and hepatic alterations in Brazilian population heavily exposed to organochlorine pesticides.

The aim of this study was to investigate the frequency of hematological and hepatic alterations and possible association with serum levels of beta-hexachlorocyclohexane (beta-HCH), p,p'-DDE, and hexachlorobenzene (HCB) among residents in an area heavily contaminated with organochlorine (OC) pesticides. A cross-sectional study was conducted in 415 male and 432 female residents aged >14 years. Serum samples were collected and analyzed for OC pesticides concentrations and biochemical parameters. Frequencies of hematological and hepatic alterations were calculated for each gender. Association between beta-HCH, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene), and HCB levels and presence of alterations was determined by logistic regression stratified by gender and controlling for confounders. Highest frequencies were observed for eosinophilia (23% men and 18% women), low hemoglobin (12% men and 15% women), and low erythrocyte count (12% men). High levels of bilirubin, glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) were observed, respectively, in 10, 11, and 12% of men and <10% of women. Gamma-glutamyl transferase (GGT) was elevated in 26 and 25% of males and females, respectively. Multivariate analysis revealed associations between eosinophilia and beta-HCH in men (OR = 1.06, 95%CI = 1.01-1.12) and women (OR = 1.05, 96%CI = 0.99-1.11), p,p'-DDE in men (OR = 1.03, 95%CI = 0.99-1.06) and women (OR = 1.02, 95%CI = 0.99-1.06), and HCB in women (OR = 1.54, 95%IC = 0.85-4.45). Beta-HCH was found to be associated with increased risk of elevated bilirubin in females (OR = 1.18, 95%CI = 1.07-1.29) and males (OR = 4.21, 95%CI = 1.87-9.47 for fourth vs. first quintile). Thus, OC pesticides may exert adverse effects on hematopoietic tissue and liver in populations chronically exposed to high levels of these compounds.

Inverse correlation among organochlorine pesticide levels to total lipid serum contents: a preliminary study in Veracruz, México.

Organochlorine pesticides, due to their hydrophobic nature and persistence, accumulate in tissues rich in lipids, which had been used as a biomarker for environmental pollution. In humans, organochlorine pesticides are continuously circulating and equilibrating among body compartments. The objective of the study was to evaluate the concentrations of organochlorine pesticides in blood serum and compare their levels to the total lipid contents in Veracruz, México inhabitants. Our hypothesis is that concentrations of organochlorine pesticides will increase just as lipid concentrations. Levels of organochlorine pesticides were divided in ascending tertils according to their total lipid content. The linear trend model applied surprisingly reveals that the average level of all organochlorine pesticides decreases as the lipid concentration increases. From one tertil to the next ß-HCH, it shows a decrease of -3.19 mg kg(-1) on lipid basis, pp.'DDE levels decrease by -3.70 mg kg(-1) on lipid basis and pp.'DDT levels decrease -1.13 mg kg(-1) on lipid basis. We conclude that the levels and the orderly sequence of organochlorine pesticide distributions in the blood serum maintain an inverse relationship to total lipid blood serum concentrations.

Levels of organochlorine pesticides in the blood of people living in areas of intensive pesticide use in Sudan.

Ninety-six human blood samples were collected from six locations that represent areas of intensive pesticide use in Sudan, which included irrigated cotton schemes (Wad Medani, Hasaheesa, Elmanagil, and Elfaw) and sugarcane schemes (Kenana and Gunaid). Blood samples were analyzed for organochlorine pesticide residues by gas liquid chromatography (GLC) equipped with an electron capture detector (ECD). Residues of p,p'-dichlorodiphenyldichloroethylene (DDE), heptachlor epoxide, γ-HCH, and dieldrin were detected in blood from all locations surveyed. Aldrin was not detected in any of the samples analyzed, probably due to its conversion to dieldrin. The levels of total organochlorine burden detected were higher in the blood from people in the irrigated cotton schemes (mean 261 ng ml(-1), range 38-641 ng ml(-1)) than in the blood of people from the irrigated sugarcane schemes (mean 204 ng ml(-1), range 59-365 ng ml(-1)). The highest levels of heptachlor epoxide (170 ng ml(-1)) and γ-HCH (92 ng ml(-1)) were observed in blood samples from Hasaheesa, while the highest levels of DDE (618 ng ml(-1)) and dieldrin (82 ng ml(-1)) were observed in blood samples from Wad Medani and Kenana, respectively. The organochlorine levels in blood samples seemed to decrease with increasing distance from the old irrigated cotton schemes (Wad Medani, Hasaheesa, and Elmanagil) where the heavy application of these pesticides took place historically.

Organochlorine pesticide levels in maternal blood and placental tissue with reference to preterm birth: a recent trend in North Indian population.

Organochlorine pesticides (OCPs) have been widely used in public health and agriculture programs in developed as well as developing countries, including India. Being xenoestrogenic in nature, OCPs may act as endocrine disruptors leading to preterm birth (PTB) through disturbance of normal estrogen-progesterone ratio. PTB is the leading cause of neonatal deaths worldwide. Therefore, the present study is aimed to determine the extent to which persistent environmental chemicals may accumulate in pregnant women and placenta and ascertain possible associations between exposure level and period of gestation (POG), baby weight, and/or placental weight in PTB cases. Maternal blood and placenta samples of PTB cases (n = 50) and subjects of term delivery as controls (n = 50) were collected. OCP residue levels were estimated by the gas chromatography system equipped with an electron capture detector. Significantly higher levels of α-hexachlorocyclohexane (α-HCH), ß-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethane (DDD), and dichlorodiphenyldichloroethylene (DDE) were found in maternal blood of PTB cases as compared to control. Significantly higher levels of DDE and dichlorodiphenyltrichloroethane (DDT) were also found in placental tissue of PTB cases as compared to control group. There was a statistically significant negative correlation between maternal blood level of α-HCH and birth-weight (r = -0.299) and POG (r = -0.234). γ-Hexachlorocyclohexane (γ-HCH) and dieldrin had a negative correlation with placental weight (r = -0.401 and -0.256, respectively), and DDE and ß-HCH had a negative correlation with POG (r = -0.251 and -0.229, respectively). The presence of OCPs in maternal blood and placental tissue represents prenatal exposure hazard for fetuses due to chronic bioaccumulation and poor elimination with possible deleterious effect on health.

Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population.

OBJECTIVES: It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. METHODS: This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. RESULTS: We found a statistically significant association between AD and high levels of ß-hexachlorocyclohexane (ß-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION: This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with ß-HCH, dieldrin, and copper to influence the risk of AD.

Gene-environment interaction in preterm delivery with special reference to organochlorine pesticides.

We investigated the association between glutathione S-transferases mu1 (GSTM1), theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs) level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected at the time of delivery/after delivery. Women occupationally exposed to OCPs and other high-risk factors such as anemia, hypertension and dietary habit were excluded. The OCP levels were estimated by gas chromatography, and polymorphic analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and PCR-restriction fragment length polymorphism, respectively. The frequency of GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the controls. Significantly high levels of α-hexachlorocyclohexane (HCH), γ-HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane and p'p'-DDE were found in the cord blood of PTD cases compared with the controls. A significant association was seen between ß-HCH and GSTM1 genotype when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and period of gestation (POG) was ascertained. A significant reduction in POG was observed. Similarly, cord blood dieldrin levels were significantly associated with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that higher levels of OCPs in pregnant women may be associated with increased risk of 'idiopathic' PTD. Furthermore, this study shows that the interaction between high OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the risk of PTD, thus providing evidence for a gene-environment interaction in pregnant women.