Associations of serum persistent organic pollutant concentrations with incident diabetes in midlife women: The Study of Women's Health Across the Nation Multi-Pollutant Study.

BACKGROUND: Organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that can negatively impact metabolic health through pathways including endocrine disruption. Few studies have evaluated diabetes risk associated with PBDEs. Little is known about the joint effect of exposure to POP mixtures on diabetes risk. OBJECTIVES: We investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women. METHODS: We measured lipid-standardized serum concentrations of 34 PCBs, 19 OCPs, and 14 PBDEs in 1040 midlife women aged 45-56 years from the Study of Women's Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC). RESULTS: For most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB 123. A doubling of PBDE 47 was associated with 1.11 (1.00, 1.24) times the risk of T2D. QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR = 1.04 [0.53, 2.07]). CONCLUSION: Exposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.

Blood levels of persistent organic pollutants among women in France in the 90's: Main profiles and individual determinants.

CONTEXT AND OBJECTIVES: Persistent organic pollutants (POPs) are a group of organic chemical compounds potentially toxic to human health. The objectives of this study were 1) to describe the levels of POPs biomarkers in blood samples from French women collected during the 1990s and to compare them with levels measured in two more recent French studies, 2) to identify POPs exposure profiles, and 3) to explore their main determinants. METHODS: 73 POPs biomarkers were measured in the blood of 468 women from the French E3N cohort (aged 45-73 years), collected between 1994 and 1999: 28 per- and polyfluoroalkyl substances, 27 organochlorine pesticides, 14 polychlorinated biphenyls and 4 polybrominated diphenyl ethers. POPs biomarker levels were described and compared with levels measured in two more recent French studies conducted by the French National Public Health Agency, the ENNS and Esteban studies. Principal component analysis was performed on POPs quantified in at least 75% of samples to identify the main exposure profiles. Linear regression models were used to estimate the associations between anthropometric, socio-demographic and lifestyle characteristics and exposure to these profiles. RESULTS: Among the 73 biomarkers measured, 41 were quantified in more than 75% of samples. Levels of most pollutants that were also measured in the Esteban of ENNS studies have decreased over time. Six POPs exposure profiles were revealed, explaining 62.1% of the total variance. Most of the characteristics studied were associated with adherence to at least one of these profiles. CONCLUSION: This study highlighted that most of the pollutants for which a comparison was possible decreased over the 10 or 20 years following the E3N blood collection, and identified those which, on the contrary, tended to increase. The health effects of the profiles identified could be assessed in future studies. The determinants identified should be confirmed in larger populations.

Diabetes mellitus and serum organochlorine pesticides mixtures in Mexican women.

BACKGROUND: Very recently, it has been reported that exposure to different mixtures of organochlorine pesticides (OCP) is associated with the development of diabetes mellitus (DM). In Mexico, DM is a public health problem that might be related to the historical intense use of OCP. We aimed to evaluate, the association between DM and serum concentrations of OCP mixtures, and identify the main contributors within them. METHODS: We conducted a secondary cross-sectional analysis on the control group from a breast cancer population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We identified 214 self-reported diabetic women and 694 non-diabetics. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We determined 24 OCP and metabolites in serum by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of DM and exposure to multiple OCP, and the contribution of each compound within the mixture. RESULTS: We found a positive adjusted association between DM and an OCP mixture (OR: 2.63, 95%CI: 1.85, 3.74), whose primary contribution arose from p, p'-DDE (mean weight 23.3%), HCB (mean weight 17.3%), trans nonachlor (mean weight 15.4%), o, p'-DDE (mean weight 7.3%), heptachlor epoxide (mean weight 5.9%), oxychlordane (mean weight 4.7%), and heptachlor (mean weight 4.5%). In addition, these OCP along with p, p'-DDT and cis chlordane, were of concern and remained associated when excluding hypertensive women from the analysis (OR 2.55; 95% CI 1.56, 4.18). CONCLUSIONS: Our results indicate, for the first time in a Latin-American population, that the concomitant exposure to multiple OCP is associated with DM. Further research is needed since the composition of OCP mixtures may vary according to regional pesticides use patterns.

Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships.

BACKGROUND: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation. RESULTS: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (ß = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (ß = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (ß = 23 g; 95% CI: -25, 71) compared to those with higher educational status (ß = -9 g; 95% CI: -24, 6). CONCLUSIONS: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.

Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights in Sanliurfa, Turkey.

BACKGROUND: Controversy surrounds the impact of persistent organic pollutants (POPs) on fetal development. This study aimed to investigate levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in umbilical cord blood from Sanliurfa mothers in Turkey, exploring associations with gestational age and birth weight. METHODS: Participants included voluntary mothers pregnant with a single fetus, providing details on maternal factors. Cord blood samples were collected immediately after delivery. Samples were extracted with a modified QuEChERS method, and OCPs (17 pesticides) and PCBs (11 congeners) compound levels were analyzed with a gas chromatograph/mass spectrometry. Detection frequencies and levels of POPs by single pollutant type and pollutant groups were calculated and compared according to gestational duration and birth weight. We used partial least squares discriminant analysis to identify the key chemicals and distinguish their respective statuses. RESULTS: Among 120 infants, 35 were preterm but appropriate for gestational age, 35 were term but small for gestational age (SGA), and 50 were term and appropriate for gestational age (AGA). Beta HCH, Oxy-Chlordan, and PCB 28, were not detected in cord blood samples. Half of the samples contained at least 4 types of OCPs, with a median OCP level of 38.44 ng/g. Among the DDT, 2,4'-DDE was found at the highest concentration in cord plasma samples. The PCB congeners with a frequency exceeding 50% were ranked in the following order: 151, 149, 138, 146. The median level of ∑PCBs was 5.93 ng/g. Male infants born at term with SGA status exhibited lower levels of ∑DDTs, ∑OCPs compared to male infants born preterm or at term with AGA status. Di-ortho-substituted PCBs and hexachlorinated PCBs were higher in male infants born at term with SGA status than male infants born preterm with AGA status. CONCLUSION: Overall, exposure to DDT and PCBs demonstrates varying effects depending on gestational duration and birth weight, with exposure levels also differing by gender. This underscores the necessity for studies across diverse populations that investigate the combined effects of multiple pollutant exposures on gestational age, birth weight, and gender simultaneously.

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.

Changes of organochlorine compound concentrations in maternal serum during pregnancy and comparison to serum cord blood composition.

The concentrations of organochlorine compounds (OCs), including pentachlorobenzene, hexachlorobenzene (HCB), hexachlorocyclohexanes (α-, ß-, γ- and δ-HCH), polychlorobiphenyls (PCBs 28, 52, 101, 118, 138, 153 and 180), DDT and metabolites, were measured in maternal serum samples collected at the first trimester of pregnancy, at delivery and in umbilical cord from a cohort of mother-newborn pairs from Tarragona (Spain) (n = 50), representing general population of a Mediterranean area from Southern Europe. The observed concentrations were generally low in comparison with previous studies in other world areas. Higher OC concentrations were observed in the maternal serum collected at delivery than in the first trimester and the cord blood concentrations were lower than the maternal levels. These results show for the first time a small but statistically significant increase in maternal venous concentration of OCs between the first trimester and delivery when measured in ng/ml. HCB, ß-HCH and the PCB congeners in cord blood were significantly correlated with the concentrations of these compounds in maternal venous blood and the coefficients were stronger for the samples collected at delivery which was consistent with OC transfer from mother to foetus. In the case of DDT compounds, only 4,4'-DDT showed maternal-cord blood correlation which documented the low metabolic capacity of newborns for OC transformation, e.g. DDT into DDE. Maternal age was the most significant driver of the observed maternal venous OC concentrations in both periods, older ages involving higher concentrations. Higher body mass index was only significantly correlated with higher 4,4'-DDE concentrations in maternal venous blood and cord blood. In some cases, social class and education level were significantly correlated with OC concentrations, e.g. 4,4'-DDE in maternal venous blood from the first trimester and cord blood and PCB153 in maternal venous blood at delivery. In these cases, highest concentrations were found in the women with highest education level and most affluent social class. Comparison of the maternal OC concentrations of this cohort with those observed in 2002 in population of the same geographic area and age range shows decreases between two and ten times over this fourteen-year period.

Serum concentrations of DDE, PCBs, and other persistent organic pollutants and mammographic breast density in Triana, Alabama, a highly exposed population.

INTRODUCTION: Although some persistent organic pollutants (POPs) are considered human carcinogens, results from studies evaluating exposures and breast cancer risk have been inconsistent, potentially related to varying ages at exposure. Additionally, few studies evaluated the association between POPs exposure and mammographic breast density (MBD), an intermediate biomarker of breast cancer risk. We carried out a cross-sectional study to investigate associations between serum POPs concentrations and MBD measured in 1998 in female residents of Triana, Alabama, in a predominately African American population with high POPs exposures, particularly to p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane). METHODS: We measured lipid-adjusted serum concentrations (ng/g lipid) of p,p'-DDT and its main metabolite p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), polychlorinated biphenyls (PCBs), ß-hexachlorocyclohexane (ß-HCCH), heptachlor epoxide, oxychlordane, trans-nonachlor, mirex, and aldrin for each woman in our study (n = 210). We also measured two MBD metrics, percent MBD (%MBD) and area of MBD (aMBD). Using adjusted Spearman correlation coefficients (rs) we evaluated correlations between %MBD and aMBD with individual POPs in the overall population and by age group (19-40, 41-54, and 55-91 years) and also estimated adjusted mean measures of MBD with 95% confidence intervals across tertiles of analytes using generalized linear models (GLM). We calculated p-values for multiplicative interaction by age group using GLM. Additional analyses excluded women with current hormone replacement therapy (HRT) use and evaluated early-life exposure (prior to age 18) during the heaviest contamination period in Triana (1947-90). RESULTS: Among all women, we found no correlation between p,p'-DDE and %MBD, but after age stratification and exclusion of HRT users, there was a suggestion of a difference by age group, with younger women having a weak positive correlation (rs = 0.12, p = 0.37) and older women having a weak negative correlation (rs = -0.12, p = 0.43); pinteraction = 0.06. In contrast, PCBs were weakly positively correlated with %MBD among all women, with the correlation magnitudes increasing after excluding current HRT users (rs-total PCBs = 0.17, p = 0.03). After age stratification and exclusion of HRT users, correlations for PCBs were higher among younger and middle-age women, with only a handful of these correlations being statistically significant. For ß-HCCH, the strongest finding was a negative correlation among older women (rs = -0.26, p = 0.07). Correlations were positive predominantly in the younger age group for heptachlor epoxide (rs = 0.27, p = 0.04), oxychlordane (rs = 0.35, p = 0.006), and trans-nonachlor (rs = 0.37, p = 0.003), and largely null for the middle and older age groups; pinteraction range: 0.03-0.05. Similar patterns were found in GLM analyses using tertiles of exposure and aMBD as the metric for MBD. Women exposed during the heaviest chemical contamination period in Triana prior to age 18 had positive correlations between %MBD and PCBs, heptachlor epoxide, mirex, oxychlordane, and trans-nonachlor. CONCLUSIONS: In this population, despite high exposures to p,p'-DDT and thus high serum concentrations of its main metabolite, p,p'-DDE, we did not find strong evidence of a positive association with MBD. In fact, there was some evidence of a negative association among older women for p,p'-DDE; a similar pattern was found for ß-HCCH. However, younger women with higher serum levels of PCBs, heptachlor epoxide, oxychlordane, and trans-nonachlor, who were likely exposed in early life, had higher MBD. These findings should be replicated in larger studies.

Contaminants, prolactin and parental care in an Arctic seabird: Contrasted associations of perfluoroalkyl substances and organochlorine compounds with egg-turning behavior.

Incubating eggs represents a trade-off for parent birds between spending enough time fasting to take care of the clutch and to get enough nutrients for self-maintenance. It is believed that the pituitary hormone prolactin plays an important role in such allocation processes. Incubation does not solely imply the active warming of the eggs but also the active egg-turning to facilitate absorption of albumen by the embryo, reduce malposition and prevent the embryo from adhering to the inner shell membrane. However, how prolactin secretion is related to egg-turning behaviors is presently poorly addressed. In addition, several environmental contaminants can affect parental care behaviors through their endocrine disrupting properties but the effects of such contaminants on egg-turning behaviors remain so far unexplored. Using artificial eggs equipped with miniaturized data loggers, we investigated the relationships between egg-turning behaviors, prolactin secretion and contaminants burden in Arctic black-legged kittiwakes (Rissa tridactyla). Specifically, we examined the relationships between blood concentrations of poly- and perfluoroalkyl substances (PFASs), organochlorines (OCs), mercury (Hg), plasma prolactin levels and both egg-turning frequency and angular change. We also incorporated baseline corticosterone levels since this glucocorticoid is known to affect parental care. Plasma prolactin levels were positively related to angular change in female kittiwakes while corticosterone was not related to egg-turning behaviors in either sex. Hg was not related to egg-turning behaviors in either sex. We found contrasting associations between OCs and PFASs, since polychlorinated biphenyls (PCBs) were negatively associated with angular change in females, contrary to linear perfluorooctanesulfonate (PFOSlin) and perfluoroalkyl carboxylic acids (PFCAs) which were positively related to egg-turning frequency and angular change in both sexes. Additionally, PFASs concentrations were positively related to prolactin levels in female kittiwake. The possible stimulation of prolactin secretion by PFASs could therefore make adult kittiwakes to allocate more time taking care of their eggs, and thus possibly modify the trade-off between spending enough time caring for the clutch and obtaining enough nutrients at sea.

Organochlorine Pesticides Residues in Blood of Peridomestic Populations of Virginia Opossum (Didelphis virginiana) from Ex-Henequen Rural Localities of Yucatan, Mexico.

Organochlorine pesticides (OCPs) have been used for many decades, both for the control of pests in agriculture and for the control of vectors of human and animal diseases. Several recent studies have reported significant concentrations of these compounds in multiple environmental substrates due to their persistence, as well as the effect they have on ecosystem health, human health, and wildlife populations. In the present study, organochlorine pesticide residues were determined and quantified in 260 blood samples from different populations of the Virginia opossum (Didelphis virginiana) from 11 rural ex-henequen sites of the state of Yucatan, Mexico. The organochlorine groups detected, following an order of predominance and concentration, were: ΣDienes (0.0557 ppm) > ΣDDTs (0.0481 ppm) > ΣEndosulfans (0.0376 ppm) > and ΣHCHs (0.0319 ppm). The highest levels of OCPs were recorded in the opossums captured in the towns of Chicxulub and Cacalchen. In 6 of the 11 localities, the OCPs detected in the opossums showed significant differences in concentration, whereas the opossums in 4 of the 11 localities did not present this difference. The results confirm the presence and persistence of OCPs in the rural environmental of Yucatan due to both the misuse and abuse of the OCPs by rural populations. In addition, the synanthropic characteristics and abundant populations of D. virginiana in the Yucatecan region make it a good candidate to serve as a biomonitor of environmental pollution in the Yucatan Peninsula. This could aid in assessing the effects exposure to pesticides and other contaminants have on the health of the Yucatecan population, whether short, medium, or long term.

Association Between Leukocyte Telomere Length and Serum Concentrations of PCBs and Organochlorine Pesticides.

Exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) through food, water, and air occurred during the life, which may change telomere length (TL) in peripheral blood leukocytes. The present study was designed to investigate the association between TL and serum levels of PCBs and OCPs in Tehran male's population. Whole blood samples were randomly taken from 300 adult males, aged between 25 and 40 years. TL was determined by real-time PCR to measure the number of the telomere (T) repeats to the number of a single-copy gene (S). We applied the multivariate linear regression model to compare the effect of each lipid adjusted serum levels of PCBs and OCPs congener on the TL, with adjustment for age, body mass index, education, smoking, and food patterns. Each doubling of the nondioxin-like PCBs, dioxin-like PCBs, and OCPs levels were associated with 1.9% [95% confidence interval (CI) - 0.70 to 5.40%], 2.5% (95% CI 0.30-8.3%), and - 2.4% (95% CI - 0.70 to - 6.2%) variation in the TL, respectively. The percent difference in the TL with exposure to nondioxin-like PCBs, dioxin-like PCBs, and OCPs for participants with older than age 37 years were 6.45% (95% CI 2.81-16.50%), 4.52% (95% CI 1.60-10.54%), and - 7.44% (95% CI - 1.55 to - 15.51%), respectively. Exposures to nondioxin-like PCBs (except for PCB 28 and 52) with high chlorine in structure and dioxin-like PCBs were related to longer TLs. Conversely, serum levels of OCPs can be associated with oxidative stress and systemic inflammation that lead to telomere shortening.

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus.

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.

Organochlorine and organophosphorus pesticides and bladder cancer: A case-control study.

BACKGROUND: Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC). METHODS: This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (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) in serum was carried out using an FID-equipped gas-chromatography system. RESULTS: AChE activity was significantly lower, ARE activity and TAC were declined but it was not statistically significant, however, α-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4-DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes and the years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients. CONCLUSION: Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.

Performance of atmospheric pressure gas chromatography-tandem mass spectrometry for the analysis of organochlorine pesticides in human serum.

A novel method of atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS) for the analysis of organochlorine pesticides (OCPs) in human serum was developed. Better sensitivity and selectivity were achieved compared to conventional gas chromatography-mass spectrometry (GC-MS) and GC-MS/MS. The limits of detection (LODs) of OCPs ranged from 0.22 to 0.90 pg/mL for the analysis in serum samples. The recoveries and repeatability of the developed method were evaluated from the analysis of spiked serum at three levels (0.05, 0.5, and 5 ng/mL). The recoveries ranged from 84.5 to 118.2%, and the relative standard deviations (RSDs) were less than 20%. The developed APGC-MS/MS method was applied to measure OCPs in pooled human serum from the interlaboratory comparison study. The obtained results of OCPs were within the acceptable ranges. The method has been successfully applied to the analysis of OCPs in human serum samples with the sample volume of up to 100 µL. Graphical abstract.

Association of serum levels of p,p'- Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and non-agricultural (non-Delta) regions of Mississippi.

Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p'- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p'- dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p'- dichlorodiphenyldichloroethylene; DDT, p,p'- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.

Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study.

OBJECTIVES: Among the numerous agents, genetic factors and environmental elements such as pesticides have an important role in colorectal cancer (CRC) incidence. The present study aimed to investigate the probable-role of some organochlorine pesticides (OCPs) and organophosphorous pesticides (OPPs) in patients with CRC. METHODS: In this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4DDT and 4,4DDT) were measured by gas chromatography (GC) method. Serum levels of malondialdehyde (MDA), and total antioxidant capacity (TAC) as well as the enzyme activity of acetylcholinesterase (AChE) and arylesterase activity of Paraoxonase-1 (PON-1) were evaluated in all participants. The methylation specific PCR (MSP) assay was used for determining the methylation status of CpG island of p16 and MGMT genes in CRC patients. RESULTS: The mean serum levels of each OCPs were significantly higher in the patient group compared to the control group (P < 0.001). The AChE and arylesterase activity of PON-1 in the patient group were significantly lower than the control group (P < 0.001). The mean serum levels of MDA and TAC in the serum of the patient group were significantly higher than the control group (P < 0.001 and P < 0.002, respectively). The current findings demonstrated significantly hypermethylation of p16 promoter in CRC patients. CONCLUSION: Regarding the higher levels of OCPs in CRC patients, along with hypermethylation of the p16 promoter gene, diminishing in AChE and PON-1 activity and increasing in oxidative stress factors, the role of OCPs and OPPs in the CRC progression in the South-East of Iran may be assumed.

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.

Temporal trends of legacy and emerging persistent organic pollutants in inuit preschoolers from Northern Quebec (Canada).

In this study, we report the temporal trends of persistent organic pollutants (POPs) in 181 preschool Inuit children from Nunavik and the influence of confounding factors on blood contaminant levels. From 2006 to 2010, no significant trends were detected in Σpolychlorinated biphenyls (ΣPCBs), Σorganochlorine pesticides (ΣOPs), Σtoxaphene, and Σper- and polyfluoroalkyl substances (ΣPFASs). On the contrary, significant downward trends ranging from 9.3% to 14.3% per year were found for polybrominated diphenyl ethers (PBDEs). Breastfeeding was significantly associated with increased levels of POPs. Age was positively and significantly related to ΣPCBs, ΣOPs and Σtoxaphene. Compared with girls, boys had significantly higher concentrations of ΣPBDEs, but lower concentrations of ΣPFASs. Weight-for-height or body mass index z-scores were negatively and significantly related to ΣPCBs and ΣOPs. Passive smoking was positively and significantly associated with ΣOPs and Σtoxaphene. In conclusion, continued efforts to reduce contaminant exposure are needed to protect children's health and development.

Biomonitoring Organochlorine Pesticides in Didelphis virginiana from Yucatan, Mexico by GC-ECD.

The aim of the present work was to apply a validated methodology for the detection of organochlorine pesticides in Didelphis virginiana (Virginia opossum) serum samples collected in Yucatan, Mexico. Recent studies performed to investigate the presence of Organochlorines (OCLs) in water, human blood and milk, and animal tissues from Yucatan have shown that the OCLs concentrations are high and can be associated with potential human health risk. Since opossum is considered an important synanthropic species in Yucatan, 40 opossum serum samples were analyzed by gas chromatography with electron capture detector. The most common OCLs found in opossum sera were lindanes, chlordanes, drines, and endosulfan. Heptachlor, heptachlor epoxide, and lindanes were found at the highest concentrations, while dichlorodiphenyl trichloroethane and its metabolites were found at the lowest concentrations in the samples. The good linearity, precision, and accuracy obtained in the evaluated parameters in the extraction and chromatographic methods support its application for the monitoring of OCLs pesticides in populations of opossums and other wild species in Yucatan.