DDE Exposure Research Articles

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.

Exposure to p,p′-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice

Approximately 8.3% of the United States (U.S.) population have either diagnosed or undiagnosed diabetes mellitus. Out of all the cases of diabetes mellitus, approximately 90–95% of these cases are type 2 diabetes mellitus (T2D). Although the exact cause of T2D remains elusive, predisposing factors include age, weight, poor diet, and a sedentary lifestyle. Until recently the association between exposure to environmental contaminants and the occurrence of diabetes had been unexplored. However, recent epidemiological studies have revealed that elevated serum concentrations of certain persistent organic pollutants (POPs), especially organochlorine pesticides, are positively associated with increased prevalence of T2D and insulin resistance. The current study seeks to investigate if this association is causative or coincidental. Male C57BL/6H mice were exposed to DDE (2.0mg/kg or 0.4mg/kg) or vehicle (corn oil; 1mL/kg) for 5 days via oral gavage; fasting blood glucose, glucose tolerance, and insulin challenge tests were performed following a 7 day resting period. Exposure to DDE caused significant hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up to 21 days following cessation of DDE administration. Intraperitoneal glucose tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and adipose tissue following insulin challenge were comparable between vehicle and DDE treated animals. To determine the direct effect of exposure to DDE on glucose uptake, in vitro glucose uptake assays following DDE exposure were performed in L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to DDE does produce fasting hyperglycemia, but this fasting hyperglycemia does not appear to be mediated by insulin resistance. Thus, the current study reveals that subacute exposure to DDE does alter systemic glucose homeostasis and may be a contributing factor to the development of hyperglycemia associated with diabetes.

Prenatal exposure to DDE and PCB153 and infant’s respiratory health: A European study

Background Recent epidemiological data suggest that early-life exposure to persistent organic pollutants can adversely influence immune and respiratory system development, but epidemiological evidence is still limited. Aims To study the association between prenatal exposure to DDE and PCB153 and occurrence of respiratory symptoms in children from 10 European birth cohorts participating in the CHICOS and ENRIECO projects. Methods A total of 4483 children with information on PBC153 and DDE exposure and at least one respiratory health outcome were included: bronchitis, wheeze and acute otitis media before two years of age and wheeze over two years of age. As cohorts measured DDE and PCB153 in different matrixes (maternal or cord blood and breastmilk), conversion factors were applied to harmonize exposure to cord blood levels. We performed random effects meta-analyses using Poisson regression models. Exposure was introduced as a continuous variable (log transformed) and comparing high versus low (tertile) categories. Results DDE and PCB153 exposure as continuous were associated with bronchitis [RR per log unit increase of ng/L exposure (95%CI)=1.08 (1.00,1.16) and 1.09 (1.01,1.18), respectively]. Similar results were found when comparing high versus low exposure groups. However, in this case the risk of wheeze below two years was increased [RR highest vs lowest tertile: 1.17 (1.03,1.33)]. There were no associations with wheeze over two years or acute otitis media. Results obtained for DDE exposure were robust to the exclusion of one cohort at the time, whereas PCB153 results were more driven by one highly exposed cohort. Conclusions This meta-analysis, studying the largest number of children thus far, suggests that prenatal DDE and PCB153 exposures may be associated with respiratory health symptoms in young children. Harmonization of outcome assessment is important in order to facilitate pooling of data in further follow-ups at older ages. This would allow a better assessment of long-term effects of these exposures.

PCBs, p,p’-DDE and birth outcomes in 11 European birth cohorts: dose-response relationship and effect modifiers

Background: Low-level exposure to polychlorinated biphenyls (PCB) is inversely associated with fetal growth, but the dose-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Aims: To explore the dose-response relationship between PCB-153 and p-p’-DDE and selected pregnancy outcomes, and to evaluate if no-effect threshold and susceptible subgroups exist. Methods: We used a pooled dataset of 8702 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationship between organochlorine compounds and pregnancy outcomes and analysis of interactions were performed. Results: We observed an inverse linear dose-response relationship between prenatal exposure to PCB-153 at levels below 1200 ng/L and birth weight (?=-200 g/µg PCB-153, 95%CI: -338, -62). No threshold or no-effect levels at very low PCB-153 concentrations were identified. The greatest reductions on birth weight were found in girls and in children born from smoking and non-Caucasian mothers. We also found a small but statistically significant alteration in gender ratio for PCB-153 (OR: 1.019; 95%CI: 1.001, 1.038) and p,p’-DDE exposure (OR: 0.992; 95%CI: 0.999, 0.996), corresponding to an increase and a decrease in the proportion of girls, respectively. Conclusions: This study suggests that the association between low-level exposure to PCB-153 and birth weight follows an inverse linear relationship. Our study also suggests that gender, maternal smoking, and ethnicity are effect modifiers of such association. Whether weak associations between PCB-153/p,p’-DDE and gender ratio reflects biological mechanisms remains to be established.

223 Motor development following prenatal exposure to p,p-DDE and CB-153: A follow-up study of Inuit and European children aged 5–9 years

ObjectivesBoth PCB and DDE are lipophilic compounds which bio-accumulate in adipose tissue and cross the placental barrier. Prior studies of the association between prenatal exposure to PCB and DDE and...

Association between thyroid function and selected organochlorine pesticides: Data from NHANES 2001–2002

Exposure to organochlorine pesticides (OCP) has been shown to be associated with adverse thyroid function. The impact of exposure to selected OCPs on total serum thyroxine (TT4) and thyroid stimulating hormone (TSH) was evaluated by analyzing data from the 2001–2002 National Health and Nutrition Examination Survey. Oxychlordane, p,p′-DDE, trans-nonachlor, and heptachlor epoxide were selected for analysis. Regression models with logs of TSH and TT4 as dependent variables and OCP exposure, race/ethnicity, iodine and smoking status, total lipids and others as independent variables were fitted. TSH levels increased (p<0.05) with increase in trans-nonachlor exposure for 20–39year old iodine deficient males. TSH levels were higher when oxychlordane exposure was low than when the exposure was medium or high for 20–39year old iodine deficient females (p<0.05). For iodine deficient females, TT4 levels were lower when p,p′-DDE exposure was low than when it was medium (p<0.05). For non-Hispanic blacks (NHB), TT4 levels decreased with increase in exposure to heptachlor epoxide (p<0.05). For iodine replete males, TSH levels increased with increase in trans-nonachlor exposure (p<0.05). For iodine replete females, (i) Mexican Americans (MA) had higher TSH levels when the exposure to oxychlordane was medium than when the exposure was low; (ii) for 60+years old, there was a positive association between TSH and heptachlor epoxide levels; and (iii) TT4 levels had an inverse association with trans-nonachlor and oxychlordane. In general though not always, (i) TSH and TT4 levels were lowest for the 20–39years old and highest for the 60+years old (p<=0.05), (ii) TSH and TT4 levels for iodine deficient males and females were lowest for NHB, highest for MA, and in-between for non-Hispanic white, and (iii) non-smokers had higher TSH and TT4 levels than smokers and in general, statistically significantly so.

DDT, DDE, and 1-hydroxypyrene levels in children (in blood and urine samples) from Chiapas and Oaxaca, Mexico

The aim of this study was to evaluate the DDT, DDE, and 1-hydroxypyrene exposure levels of children living in communities located in southeastern Mexico. The study communities were Lacanja and Victoria in Chiapas state and Ventanilla in Oaxaca state. Children living in Lacanja had total blood DDT levels (mean ± SD, 29,039.6 ± 11,261.4 ng/g lipid) that were significantly higher than those of children in Victoria (10,220.5 ± 7,893.1 ng/g lipid) and Ventanilla (11,659.7 ± 6,683.7 ng/g lipid). With respect to the 1-hydroxypyrene levels in urine samples, the levels in Lacanja (4.8 ± 4.1 μg/L or 4.5 ± 3.9 μmol/mol creatinine) and Victoria (4.6 ± 3.8 μg/L or 3.9 ± 3.0 μmol/mol Cr) were significantly higher than levels found in Ventanilla (3.6 ± 1.4 μg/L or 2.5 ± 0.5 μmol/mol Cr). In conclusion, our data indicate high levels of exposure in children living in the communities studied in this work. The evidence found in this study could be further used as a trigger to revisit local policies on environmental exposures.

Effects of p,p′-DDE on the mRNA and protein expressions of vimentin, N-cadherin and FSHR in rats testes: An in vivo and in vitro study

To elucidate the mechanism underlying the testicular effects of 1,1-dichloro-2,2bis(p-chlorophenyl)ethylene (p,p′-DDE), the expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor mRNA and proteins were measured in vivo and in vitro. Sprague-Dawley rats were dosed with p,p′-DDE at 0, 20, 60 and 100mg/kg every other day by intraperitoneal injection for 10 days, and Sertoli cells were treated with p,p′-DDE (0, 10, 30, and 50μM) for 24h. Results indicated that the survival rate of Sertoli cells was decreased with increasing doses of p,p′-DDE. In vitro and in vivo studies, p,p′-DDE could increase the expression of neural cadherin, follicle-stimulating hormone receptor mRNA, while decrease the levels of vimentin, neural cadherin and follicle-stimulating hormone receptor proteins. Moreover, immunohistochemistry analysis revealed that the protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in pubertal rat testes were disrupted by treatment with p,p′-DDE. Taken together, these results suggested that p,p′-DDE exposure could induce testicular toxicity through the changes of the mRNA and protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in vitro and in vivo.

Prenatal p,p´ -DDE Exposure and Neurodevelopment among Children 3.5–5 Years of Age

Background: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited.Objectives: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42–60 months of age.Methods: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children’s Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available.Results: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of –1.37, –0.88, –0.84, and –0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed.Conclusions: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control.

Differential Effect of DDT, DDE, and DDD on COX‐2 Expression in the Human Trophoblast Derived HTR‐8/SVneo Cells

The purpose of this study was to investigate the effect of 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) isomers on COX-2 expression in a human trophoblast-derived cell line. Cultured HTR-8/SVneo trophoblast cells were exposed to DDT isomers and its metabolites for 24 h, and COX-2 mRNA and protein expression were assessed by RT-PCR, Western blotting, and ELISA. Prostaglandin E₂ production was also measured by ELISA. Both COX-2 mRNA and protein were detected under control (unexposed) conditions in the HTR-8/SVneo cell line. COX-2 protein expression and prostaglandin E₂ production but not COX-2 mRNA levels increased only after DDE and DDD isomers exposure. It is concluded that DDE and DDD exposure induce the expression of COX-2 protein, leading to increased prostaglandin E2 production. Interestingly, the regulation of COX-2 by these organochlorines pesticides appears to be at the translational level.

Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N=1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure. Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores. Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (β [95%CI]=−1.36 [−2.61, −0.11]). Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life. Results of the present study suggest that, although breastfeeding increases children's blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure.

Accelerated Mammary Tumor Onset in a HER2/ Neu Mouse Model Exposed to DDT Metabolites Locally Delivered to the Mammary Gland

Background: The association of DDT (dichlorodiphenyltrichloroethane) with breast cancer is controversial, but animal studies directly linking DDT to risk are lacking. Concerns with DDT reside in its environmental persistence, bioaccumulation in breast adipose tissue, and endocrine-disrupting actions. Whereas most attention has been focused on estrogenic congeners, we tested the cancer-inducing potential of the antiandrogen, p,p´-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the most prevalent and persistent DDT metabolite.Objectives: We aimed to determine whether developmental exposure to p,p´-DDE stored in adipose tissue surrounding the cancer-prone mammary epithelium of MMTV-Neu mice influences tumor development.Methods: For localized delivery, Elvax 40P pellets containing p,p´-DDE were implanted into the mammary fat pads of prepubertal female mice. We compared mammary tumor development with p,p´-DDE with development in response to its estrogenic isomer, o,p´-DDE [1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethylene], and a mixture of both isomers.Results: p,p´-DDE implants significantly accelerated mammary tumor onset compared with vehicle Elvax implants. o,p´-DDE had similar results, but only at ≤ 10 months of age. Lipid-adjusted levels of p,p´-DDE in mammary adipose tissue and serum in young mice were within the ranges of human exposure, whereas concentrations in aged mice were low to undetectable. Exposure to a 2:1 ratio of p,p´-DDE:o,p´-DDE did not result in the younger latency observed with the individual isomers.Conclusions: p,p´-DDE exposure at concentrations relevant to human exposure accelerates mammary carcinogenesis in mice, possibly through hormonal and/or other actions. These data suggest that DDE exposure would promote, but not cause, mammary tumorigenesis. Developmental exposure in immature mammary tissue continues to affect tumor onset even after p,p´-DDE levels have declined. Future studies are needed to determine whether early exposure to p,p´-DDE correspondingly predisposes women to early-onset breast cancer.

Raf-1 is dually down regulated by p,p′-DDE via reduced thyroid hormone and activated ERK

Raf-1 is the best characterized member of the mammalian raf family. The raf-1 kinase has many important physiological functions but its regulation is complex. 1,1-Dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p′-DDE), a major and important metabolite of organochlorine pesticide DDT, is a widespread environmental pollutant. Previous studies have reported that p,p′-DDE influences the MAPK pathway, but little details are known regarding how the raf-1 activity is influenced and regulated by p,p′-DDE in those events. And here, we used 20 male rats that received different doses of p,p′-DDE (0, 20, 60, 100mg/kg b.wt) every other day by intraperitoneal injection for 10days. Results showed that the raf-1 mRNA and protein expressions showed significant down-regulation. The thyroxine (T4) level and the protein kinase C alpha (PKCα) mRNA expression declined, but the raf kinase inhibitory protein (RKIP) up regulated. In addition, the p,p′-DDE-induced oxidative stress resulted in declines of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities. The elevations of ERK mRNA level and phosphorylated ERK protein expression were also observed. Taken together, these results suggest that the raf-1 is dually down regulated by p,p′-DDE via two pathways. One pathway is that the p,p′-DDE exposure elevates RKIP level by decreasing T4 and PKCα level, and the increased RKIP eventually down regulates the raf-1. The other is that the p,p′-DDE exposure activates the ERK by oxidative stress, and the activated ERK down regulates the raf-1 through the negative feedback phosphorylation.

Prenatal dichlorodiphenyldichloroethylene (DDE) exposure and child growth during the first year of life

BackgroundDue to its long-term persistence in the environment and its ability to cross the placental barrier, prenatal p,p′-dichlorodiphenyldichloroethene (DDE) exposure continues to be a public health concern. This study aimed to evaluate the association between prenatal DDE exposure and child growth, at birth and during the first year of life. Methods253 pregnant women were recruited between January 2001 and June 2005 in a prospective cohort in Morelos, Mexico. Serum levels of DDE were measured during each trimester of pregnancy by gas chromatography with an electron capture detector. Using the generalized mixed-effects models, the association between DDE and child growth parameters (weight-for-age, length-for-age, weight-for-length, BMI-for-age and head circumference-for-age Z-scores) from birth to 1 year of age was assessed. Maternal dietary intake was considered as covariable among others. ResultsDDE levels were 6.3±2.8ng/mL (first trimester), 6.6±2.9ng/mL (second trimester), and 7.6±2.9ng/mL (third trimester). After adjusting for potential confounder variables, no significant associations were observed with prenatal DDE exposure and each of the selected parameters. ConclusionsOur results show no evidence of an association between prenatal DDE exposure and child growth during the first year of life.

Pre-natal exposure to dichlorodiphenyldichloroethylene and infant lower respiratory tract infections and wheeze

The aim of our study was to examine whether pre-natal exposure to dichlorodiphenyldichloroethylene (DDE) increases the risk of lower respiratory tract infections (LRTIs) and wheeze in infants. The study is based on a birth cohort of 1,455 mother-child pairs. Maternal serum concentrations of DDE, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) were measured during pregnancy. Parental reports on LRTI and wheeze were obtained when children were 12-14 months old. 35.4% of children developed at least one LRTI episode and 33.6% at least one wheezing episode during their first 12-14 months of life. Median DDE, PCBs and HCB concentrations were 116.3, 113.7 and 46.4 ng · g(-1) lipid, respectively. DDE concentrations were associated with LRTI risk (relative risk (RR) per 10% increase 1.11, 95% CI 1.00-1.22), also after adjustment for PCBs and HCB. In all quartiles of DDE exposure, the risk of LRTI was increased compared with the lowest quartile, but the increase was statistically significant only in the third quartile (RR 1.33, 95% CI 1.08-1.62). No association was observed for PCBs and HCB. Results were similar for wheeze. This study suggests that pre-natal DDE exposure is associated with a higher risk of LRTI and wheeze in infants independently of exposure to other organochlorine compounds.

Prenatal Concentrations of Polychlorinated Biphenyls, DDE, and DDT and Overweight in Children: A Prospective Birth Cohort Study

Background: Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent.Objectives: We explored whether prenatal organochlorine compound (OC) concentrations [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT)] were associated with overweight at 6.5 years of age and whether child sex or fat intakes modified these associations.Methods: We studied 344 children from a Spanish birth cohort established in 1997–1998. Overweight at 6.5 years was defined as a body mass index (BMI) z-score ≥ 85th percentile of the World Health Organization reference. Cord blood OC concentrations were measured and treated as categorical variables (tertiles). Children’s diet was assessed by food frequency questionnaire. Relative risks (RRs) were estimated using generalized linear models.Results: After multivariable adjustment, we found an increased RR of overweight in the third tertile of PCB exposure [RR = 1.70; 95% confidence interval (CI): 1.09, 2.64] and the second tertile of DDE exposure (RR = 1.67; 95% CI: 1.10, 2.55), but no association with DDT exposure in the population overall. Associations between overweight and PCB and DDE concentrations were strongest in girls (p-interaction between 0.01 and 0.28); DDT was associated with overweight only in boys. For DDT we observed stronger associations in children with fat intakes at or above compared with below the median, but this interaction was not significant (p-interaction > 0.05).Conclusions: This study suggests that prenatal OC exposures may be associated with overweight in children and that sex and high-fat intake may influence susceptibility.

Variability in DDT-induced apoptosis in Mexican indigenous populations

Context: In previous studies, we showed that DDT and its metabolites are able to induce apoptosis of peripheral blood mononuclear cells (PBMC) “in vitro” and “in vivo”, by a mechanism involving oxidative stress.Objective: The objective of this study was to evaluate the mechanism by which DDT induces apoptosis in PBMC in children exposed to DDT and its metabolites.Materials and methods: Eligibility criteria included children who: (1) have lived in the selected community since birth, (2) were between 6 and 14 years of age at the time of the study, (3) had not been exposed to medicaments or tobacco smoke, and (4) had had no infectious diseases in the month prior to the study. DDT and its metabolites were quantified using gas chromatography with an electron capture detector, PBMC apoptosis was measured using the TUNEL assay, DNA damage and oxidative damage were studied using the comet assay.Results: Apoptosis correlated to DDE exposure (p = 0.040), as previously found. DNA damage also correlated to DDT (p = 0.005) and DDE (p = 0.004) levels. However, neither exposure to DDT or DDE and oxidative damage, nor oxidative damage and apoptosis, were significantly correlated. Children living in Lacanja, Chiapas, one of the communities studied in this work, had the highest levels of exposure to DDT and its metabolites, yet had the lowest percentage of apoptosis.Conclusion: Resistance to DDE-induced apoptosis was found in children from one community. Further studies are needed in order to understand the mechanism involved in this apoptosis resistance.

Altered developmental timing in early life stages of Antarctic krill (Euphausia superba) exposed to p,p′-DDE

Persistent organic pollutants (POPs) are persistent, toxic and bioaccumulative anthropogenic organic chemicals, capable of undergoing long range environmental transport to remote areas including the Antarctic. p,p′-dichlorodiphenyl dichloroethylene (p,p′-DDE) has been identified as a dominant POP accumulating in Antarctic krill (Euphausia superba), which is a key Southern Ocean species. This study examined the developmental toxicity of p,p′-DDE via aqueous exposure to Antarctic krill larvae. p,p′-DDE exposure was found to stimulate developmental timing in the first three larval stages of Antarctic krill, while extended monitoring of larvae after a five day exposure period had ended, revealed delayed inhibitory responses during development to the fourth larval stage. Stimulatory responses were observed from the lowest p,p′-DDE body residue tested of 10.1±3.0μmol/kg (3.2±0.95mg/kg) preserved wet weight, which is comparable to findings for temperate species and an order of magnitude lower than the exposure level found to cause sublethal behavioural effects in Antarctic krill. The delayed responses included increased mortality, which had doubled in the highest p,p′-DDE treatment (95±8.9% mortality at 20μg/L p,p′-DDE) compared to the solvent control (44±11% mortality) 2weeks after end of exposure. Development of surviving metanauplius larvae to calyptopis 1 larvae was delayed by 2days in p,p′-DDE exposed larvae compared with untreated larvae. Finally, the developmental success of surviving p,p′-DDE exposed larvae was reduced by 50 to 75% compared to the solvent control (100% developmental success). The lowest observed effect concentration for all delayed effects was 1μg/L, the lowest exposure concentration tested. These findings demonstrate the importance of delayed and indirect effects of toxicant exposure. Further, the findings of this study are important for environmental risk assessment of POPs in the Southern Ocean ecosystem and strongly highlight the significance of developmental endpoints for ecotoxicological testing.

PRENATAL EXPOSURE TO ORGANOCHLORINE COMPOUNDS (OCs) IN RELATION TO BIRTHWEIGHT AND DURATION OF GESTATION: THE SPANISH INMA PROJECT

Background and aims: To evaluate associations between prenatal organochlorine compounds (OC) exposure and birthweight and duration of gestation in a population with low exposure levels. Methods: The analysis included 1527 mother-child pairs from three sub-cohorts of the INMA project (www.proyectoinma.org) recruited during pregnancy between 2003-2008. Polychlorinated biphenyls (PCBs 138, 153, 180 and the total), p,p´-dichlorodiphenyldichloroethylene (p,p’-DDE), hexachlorobenzene (HCB) and •-hexachlorocyclohexane were measured in maternal serum obtained in weeks 10-13 of gestation. Multivariable linear regression was used to assess the association between the exposure to these compounds and birthweight and gestation duration adjusting for potential confounders. Results: The mean (sd) gestational age was 39.7 (1.6) weeks and mean birthweight 3254.8 (465.7) grams. After multivariate adjustment including other OCs, the increase levels of p,p’-DDE were significantly negatively associated with gestation duration among male infants (•=-0.129; 95%CI: -0.251 to -0.007), but not among females. Among infants of both sexes whose mothers smoked during pregnancy (31,7% of the sample), p,p’-DDE was also associated with shorter gestation duration after multivariable adjustment (•=-0.192; 95%CI: -0.356 to -0.028) and PCBs were associated with significant reductions in birthweight among infants (•=-50.474; 95%CI: -99.442 to -1.506); these associations were marginally non-significant after adjusting for other OCs. When OCs were categorized in quartiles, the main differences were found betwen the first and the fourth quartile (p,p’-DDE: •0.43 vs. &gt;0.16 •g/L; •PCBs: •0.43 vs. &gt;0.91 •g/L). Conclusions: Results suggest infants of women who smoke during pregnancy may be vulnerable to adverse effects of low-level p,p’-DDE exposure on the duration of gestation and to effects of PCB exposure on birthweight. Overall, boys also appeared to be more susceptible than girls to negative effects of p,p’-DDE on the duration of gestation.

THE RELATIONSHIP OF ENVIRONMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AND P,P’-DDE WITH HUMAN SPERM SEXCHROMOSOME DISOMY

Background and Aims: Chromosomal abnormalities contribute substantially to reproductive problems, yet environmental risk factors have not been well investigated. We evaluated associations between PCBs and p,p’-DDE exposure with sperm sex-chromosome disomy. Methods: We conducted a cross-sectional study of 192 men from subfertile couples. Multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX, YY, XY, and total sex chromosome disomy in sperm, using a semi-automated scoring method. Serum was analyzed for concentrations of 57 PCB congeners and p,p’-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles controlling for potential confounders and semen parameters. Results: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex chromosome disomy. After adjustment, total sex chromosome disomy IRR for the highest vs. lowest quartile of serum DDE exposure was 1.27 (95% CI: 1.22-1.33). IRRs showed significantly increasing trends for increasing quartiles of p,p’-DDE in XX, XY, and total sex chromosome disomy. There was a significant increase in IRRs of YY, XY, and total sex chromosome disomy for increasing quartiles of the ∑4prevalent PCBs (118, 138, 156, and 180) and ∑estrogenic PCBs (44, 49, 52, 101, 187, 174, 177, 157/201). There was also an increase in XY and total sex chromosome disomy for increasing quartiles of ∑dioxin-like PCBs (95/66, 74, 77/110, 105/141, 118, 156, 167, 128, 138, 170). For XX disomy, however, IRRs decreased significantly with increasing quartiles for all PCB summary measures examined (∑4prevalent, ∑estrogenic, and ∑dioxin-like). Conclusions: Our findings suggest DDE may be associated with increased XX, XY and total sex chromosome disomy, while PCB exposures may be associated with increased YY, XY and total sex chromosome disomy, but decreased XX disomy. These findings require confirmation in further studies.