Metabolite Of Dichlorodiphenyltrichloroethane Research Articles

Adaptation of Brown Adipose Tissue in Response to Chronic Exposure to the Environmental Pollutant 1,1-Dichloro-2,2-bis(p-chlorophenyl) Ethylene (DDE) and/or a High-Fat Diet in Male Wistar Rats.

Brown adipose tissue (BAT) participates in thermogenesis and energy homeostasis. Studies on factors capable of influencing BAT function, such as a high-fat diet (HFD) or exposure to environmental pollutants, could be useful for finding metabolic targets for maintaining energy homeostasis. We evaluated the effect of chronic exposure to dichlorodiphenyldichloroethylene (DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), and/or a HFD on BAT morphology, mitochondrial mass, dynamics, and oxidative stress in rats. To this end, male Wistar rats were treated for 4 weeks with a standard diet, or a HFD alone, or together with DDE. An increase in paucilocular adipocytes and the lipid droplet size were observed in HFD-treated rats, which was associated with a reduction in mitochondrial mass and in mitochondrial fragmentation, as well as with increased oxidative stress and upregulation of the superoxide dismutase-2. DDE administration mimics most of the effects induced by a HFD on BAT, and it aggravates the increase in the lipid droplet size when administered together with a HFD. Considering the known role of oxidative stress in altering BAT functionality, it could underlie the ability of both DDE and a HFD to induce similar metabolic adaptations in BAT, leading to reduced tissue thermogenesis, which can result in a predisposition to the onset of energy homeostasis disorders.

Effects of chronic dichlorodiphenyldichloroethylene exposure on testosterone secretion and steroidogenic pathway in the male gonad.

Endocrine disrupting chemicals are present in the environment and/or in consumer products. These agents have the capacity to mimic and/or antagonize endogenous hormones and thus perturb the endocrine axis. The male reproductive tract expresses steroid hormone (androgen and estrogen) receptors at high levels and is a major target for endocrine disrupting chemicals. In this study, Long-Evans male rats were exposed to dichlorodiphenyldichloroethylene, a metabolite of dichlorodiphenyltrichloroethane and a chemical present in the environment, in drinking water at 0.1 and 10μg/L for 4 weeks. At the end of exposure, we measured steroid hormone secretion and analyzed steroidogenic proteins, including 17β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, steroidogenic acute regulatory protein, aromatase, and the LH receptor. We also analyzed Leydig cell apoptosis (poly-(ADP-ribose) polymerase) and caspase-3 in the testes. Testicular testosterone (T) and 17β-estradiol (E2) were both affected by exposure to dichlorodiphenyldichloroethylene by displaying altered steroidogenic enzyme expression. Dichlorodiphenyldichloroethylene exposure also increased the expression of enzymes mediating the pathway for programmed cell death, including caspase 3, pro-caspase 3, PARP, and cleaved PARP. Altogether, the present results demonstrate that dichlorodiphenyldichloroethylene directly and/or indirectly can target specific proteins involved in steroid hormone production in the male gonad and suggest that exposure to environmentally relevant dichlorodiphenyldichloroethylene levels has implications for male reproductive development and function.

Evaluating the fate and potential health risks of organochlorine pesticides and triclosan in soil, sediment, and water from Asa Dam River, Ilorin Kwara State, Nigeria.

The quest for safe water due to exponential population growth and climate change has stressed the existing available water source. It is crucial to establish the present pollution level of the Asa River and the health risk it may pose to the people. Samples were collected along the Asa River, Ilorin, Kwara State, Nigeria, and treated using standard methods as stipulated by United States Environmental Protection Agency. The treated samples were analyzed and quantified for dieldrin, endrin, dichlorodiphenyltrichloroethane metabolites, mirex, hexachlorocyclohexane, hexachlorobenzene, and triclosan using the gas chromatography-mass spectrometry. The result showed that the levels of organochlorine pesticides (OCPs) ranged from 0.0045-0.947μg/kg, 0.0036-0.093μg/kg, and 0.001-0.007μg/L in sediment, soil, and water samples, respectively. While the mean concentration of triclosan is 3.78μg/kg, 2.995μg/kg, and 0.064μg/L in sediment, soil, and water samples, respectively. The levels of OCPs were lower than the limits in drinking water as set by World Health Organization and European Union. Health risk assessment for both children and adults was evaluated using non-carcinogenic and carcinogenic risk with the hazard quotient (HQ) and was found to be greater than unity (> 1) in children for the targeted OCPs. Associated cancer risk for OCPs ranged from low cancer risk to moderate risk for humans. The adverse ecological effects of OCPs showed to be very rare to occur and frequent effects may not likely occur except for HCH.

English

Dichlorodiphenyltrichloroethane (DDT) levels and its metabolites are reported in 75 soil and 75 vegetable samples from the vicinity of homesteads sprayed with DDT during indoor residual spraying (IRS) pilot exercise, carried out in 2008 in Apac and Oyam districts, Uganda as a measure to control malaria. The samples were randomly and conveniently collected in 2020 from selected villages of the districts, extracted using solid dispersion and multi-residue methods for soil and vegetable samples, respectively and analyzed using GC-ECD and GC-MS. DDT residues were detected in all samples collected. The ΣDDT (µg kg-1) in all indoor house dust, outdoor soil samples from villages of Apac and Oyam districts and control areas were 69.9±20.9 and 8.9±4.7, 113.4±22.6 and 15.4±4.3, and 1.13±0.27 and 1.8±0.9, respectively. ΣDDT were significantly higher (p < 0.05) in the study areas than the control areas. In vegetables, ∑DDT (µg kg-1) ranged between 1.7±0.3 and 8.3±4.0 and 2.3±0.4 and 11.4±7.5 in the study and control areas, respectively. Abelmoschus esculentus and Gynandropsis gynandra had the highest levels. The results suggest that IRS had an effect on DDT levels in the environment. However, ∑DDT in vegetables were significantly below (P < 0.05) the EU EMRL, thus, the results raise no concern regarding the potential health effects of DDT to the residents. Nevertheless, due to bioaccumulation effects of DDT, to control malaria, measures like Ecohealth rather than IRS of DDT should be embraced. Key words: Dichlorodiphenyltrichloroethane metabolites, indoor residual spraying.

Contemporary pollution of surface sediments from the Algarve shelf, Portugal

The present-day human footprint is traceable in all environments. Growing urban centers, tourism, agricultural and industrial activities in combination with fishery, aquacultures and intense naval traffic, result in a large output of pollutants onto coastal regions. The Algarve shelf (Portugal) is one exemplary highly affected coastal system. With this study the contemporary pollution was followed in eighteen offshore surface sediment samples. Heavy metals (e.g., Cr, Pb, Cu, Hg) and organic contaminants, such as linear alkylbenzenes, dichlorodiphenyltrichloroethane metabolites, polycyclic aromatic hydrocarbons, and hopanes, have been identified and quantified, that pose hazardous effects on the marine environment and biota. This study correlates spatial distribution patterns with the pollutant composition, potential sources and pathways, each sample's grain size, and local influences, such as discharging river systems and ocean currents. This study presents a blueprint-study that allows the methodological adaption to new shelf systems with regionally different ocean current-driven distribution patterns of anthropogenic pollutants.

Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins.

Dichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has not yet been analysed. Mitochondrial fusion and fission processes are critical to maintaining the mitochondrial network and allowing the cell to respond to external stressors such as environmental pollutants. Fusion processes are associated with optimizing mitochondrial function, whereas fission processes are associated with removing damaged mitochondria. We assessed the effects of different DDE doses, ranging between 0.5 and 100 µM, on cell viability and mitochondrial fusion/fission proteins in an in vitro hepatic cell model (human hepatocarcinomatous cells, HepG2); the DDE induced a decrease in cell viability in a dose-dependent manner, and its effect was enhanced in conditions of coincubation with dietary fatty acids. Fusion protein markers exhibited an inverted U-shape dose-response curve, showing the highest content in the 2.5–25 μM DDE dose range. The fission protein marker was found to increase significantly, leading to an increased fission/fusion ratio with high DDE doses. The low DDE doses elicited cell adaption by stimulating mitochondrial dynamics machinery, whereas high DDE doses induced cell viability loss associated with mitochondrial dynamics to shift toward fission. Present results are helpful to clarify the mechanisms underlying the cell fate towards survival or death in response to increasing doses of environmental pollutants.

Historical and post-ban releases of organochlorine pesticides recorded in sediment deposits in an agricultural watershed, France

Agricultural use of organochlorine pesticides (OCPs) increased during the twentieth century but many of them have been progressively banned several decades after their introduction. Nevertheless, these lipophilic chemical compounds may persist in soils and sediments. From sediment deposits, it is possible to reconstruct the chronology of OCP releases in relation to former applications through time. Nevertheless, long-term fate of OCPs i.e. source, transfer, and storage through the watershed, is also related to the OCPs-sediment characteristics interactions, and our study showed the significant links between OCPs and labile or refractory organic matter. From sediment cores collected in a mainly agricultural watershed, the Eure River watershed (France), aldrin and lindane widespread applications during the 1950s–1970s have been recorded. While lindane applications declined after that date, according to the temporal trend of the stable isomer of hexachlorocyclohexane (β-HCH), α-, and γ-HCH have been recorded at significant levels in the 2000s, suggesting first local post-ban applications. Nevertheless, the relationships between these OCPs and labile organic matter resulted in an overestimation of the post-ban releases. Also, the detection of stable metabolites of dichlorodiphenyltrichloroethane (DDT) (i.e. 4,4′-DDE) and heptachlor (i.e. heptachlor epoxide) several decades after their ban, revealed the role of old deep soils erosion in the chronology of OCP releases and thus the reemergence of stable transformation products from historical OCPs.

Identification of common genetic variants associated with serum concentrations of p, p′-DDE in non-occupational populations in eastern China

Dichlorodiphenyldichloroethylene (DDE) is the major and most stable toxic metabolite of dichlorodiphenyltrichloroethane (DDT), a well-known organochlorine pesticide banned worldwide in the 1980s. However, it remains easy to detect in humans, and internal levels vary widely among individuals. In the present study, a genome-wide association study (GWAS) (511 subjects) and two replications (812 and 1030 subjects) were performed in non-occupational populations in eastern China. An estimated dietary intake (EDI) of p, p′-DDT and p, p′-DDE was calculated by a food frequency questionnaire (FFQ) and the determination of 195 food and 85 drinking water samples. In addition, functional verifications of susceptible loci were performed by dual-luciferase reporter, immunoblotting and metabolic activity assays in vitro. p, p′-DDT and p, p′-DDE were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). A common loci rs3181842 (high linkage equilibrium with rs2279345) in CYP2B6 at 19p13.2 were found to be strongly associated with low serum levels of p, p′-DDE in this population in GWAS and were verified by two replications and combined analysis of 2353 subjects (P = 1.00 × 10-22). In addition, p, p′-DDE levels were significantly lower in subjects with the rs3181842 C allele than in those carrying the normal genotype, even in individuals with similar EDIs of p, p′-DDT. Furthermore, the rs3181842 C allele functionally led to low CYP2B6 expression and activity, resulting in a low metabolic capacity for the formation of p, p′-DDE from p, p′-DDT. The study highlighted that CYP2B6 variants were more relevant than environmental exposure to internal p, p′-DDE exposure, which is important information for DDT risk assessments.

Dichlorodiphenyltrichloroethane metabolites inhibit DNMT1 activity which confers methylation-specific modulation of the sex determination pathway.

Dichlorodiphenyltrichloroethane (DDT) poses a significant health risk to humans which is associated with genomic DNA hypomethylation. However, the mechanism and biological consequences remain poorly understood. Invitro assays confirmed that the DDT metabolites 2,2-bis(p-chlorophenyl)-acetic acid (DDA) and 1-chloro-2,2-bis-(p-chlorophenyl)ethylene (DDMU), but not other DDT metabolites, significantly inhibited DNA methyltransferase 1 (DNMT1) activity, leading to genomic hypomethylation in cell culture assays. DNMT1 as a target for DNA hypomethylation induced by DDT metabolites was also confirmed using cell cultures in which DNMT1 was silenced or highly expressed. DDA and DDMU can modify methylation markers in the promoter regions of sexual development-related genes, and change the expression of Sox9 and Oct4 in embryonic stem cells. Molecular docking indicated that DDA and DDMU bound to DNMT1 with high binding affinity. Molecular dynamic simulation revealed that DDA and DDMU acted as allosteric modulators that reshaped the conformation of the catalytic domain of DNMT1. These findings provide a new insight into DDT-induced abnormalities in sexual development and demonstrate that selective binding to DNMT1 by DDA and DDMU can interfere with human DNMT1 activity and regulate the expression of the Sox9 and Oct4 genes.

Physiological Adaptation to Simultaneous Chronic Exposure to High-Fat Diet and Dichlorodipheniletylhene (DDE) in Wistar Rat Testis.

Environmental chemicals can be introduced by consuming contaminated foods. The environmental chemical dichlorodiphenyldichloroethylene (DDE), a persistent metabolite of dichlorodiphenyltrichloroethane (DDT), can affect spermatogenesis. Our study aims to evaluate, by using spectrophotometric analyses, western blot, and immunohistochemistry, the adaptive responses in testis of adult rats treated with a non-toxic dose of DDE, alone or in association with a high-fat diet (HFD). Four experimental groups were performed: N (normal diet); D (HFD); D + DDE (HFD + DDE); N + DDE (normal diet + DDE). D group showed a reduction in antioxidant capacity, and increases in lipid peroxidation, apoptosis, and proliferation associated with morphological impairment. A reduction in androgen receptor (AR) and serum testosterone levels were also found. DDE-treated groups exhibited higher lipid peroxidation levels compared to N and D, associated with pronounced defect in antioxidant capacity, apoptosis, cellular proliferation, as well as with tissue damage. Moreover, decreases in AR and serum testosterone levels were found in DDE-treated groups vs. N and D. In conclusion, HFD and DDE produced cellular stress leading to antioxidant impairment, apoptosis, and decreases in AR and serum testosterone levels associated with tissue damage. Cellular proliferation could be used as an adaptation to counterbalance the occurred damage, maintaining a pool of tubules that follow physiological maturation.

Oxidative stress and mitochondrial uncoupling protein 2 expression in hepatic steatosis induced by exposure to xenobiotic DDE and high fat diet in male Wistar rats.

Oxidative stress plays a key role in steatohepatitis induced by both xenobiotic agents and high fat diet (HFD). The present study aimed to evaluate hepatic oxidative stress and anti-oxidant systems response in rats exposed to HFD and/or non-toxic dose of dichlorodiphenyldichloroethylene (DDE), the first metabolite of dichlorodiphenyltrichloroethane. Groups of 8 rats were so treated for 4 weeks: 1- standard diet (N group); 2- standard diet plus DDE (10 mg/kg b.w.) (N+DDE group); 3- HFD (D group); 4- HFD plus DDE (D+DDE group). Oxidative stress was analyzed by determining malondialdehyde as lipid peroxidation product, while the anti-oxidant systems were evaluating by measuring the levels of the principal cytosolic and mitochondrial antioxidant proteins and enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), glutathione peroxidase 1 (GPx1) and uncoupling protein 2 (UCP2) involved in the control of hepatic reactive oxygens species (ROS) accumulation. The results showed malondialdehyde accumulation in livers of all groups, confirming the pro-oxidant effects of both HFD and DDE, but with a greater effect of DDE in absence of HFD. In addition, we found different levels of the analyzed anti-oxidant systems in the different groups. DDE mainly induced UCP2 and SOD2, while HFD mainly induced GPx1. Noteworthy, in the condition of simultaneous exposure to DDE and HFD, the anti-oxidant response was more similar to the one induced by HFD than to the response induced by DDE. Present findings confirmed that both HFD and xenobiotic exposure induced hepatic oxidative stress and showed that the anti-oxidant defense response was not the same in the diverse groups, suggesting that UCP2 induction could be an adaptive response to limit excessive ROS damage, mainly in condition of xenobiotic exposure.

Levels of organochlorine pesticide residues in fresh water fishes of three bird sanctuaries in Tamil Nadu, India.

Organochlorine pesticide (OCP) residues were determined in nine species of fresh water fishes caught from three bird sanctuaries in Tamil Nadu, India. A total of 302 fishes were analyzed for various types of OCPS. OCPs, namely hexachlorocyclohexane (HCH), dichloro diphenyl trichloroethane (DDT), heptachlor epoxide, endosulfan, and dieldrin were detected among various species of fishes. Among the various OCPs analyzed, HCH was the most frequently detected pesticides. Among the HCH isomers, β HCH contributed more than 50% to the Σ HCH. p,p' DDT, the metabolites of DDT, had high percentage of occurrence. Among the cyclodiene insecticide residues, endosulfan was detected in more than 60% of the fishes. Varying levels of ΣOCPs (a sum of Σ HCH, Σ DDT, Σ endosulfan, heptachlor epoxide, and dieldrin) were detected in various fish species, although it was not significant (p > 0.05). However, significant variations in OCPs were observed among location and between seasons (p < 0.05). However, continuous monitoring is recommended to facilitate the early identification of risks not only to the fishes, but also to fish-eating birds breeding in these sanctuaries.

Sources and transformation pathways for dichlorodiphenyltrichloroethane (DDT) and metabolites in soils from Northwest Fujian, China.

Dicofol (2,2,2-trichloro-1,1-bis-(p-chlorophenyl)ethanol) found in the environment is not only a miticide originated from commercial use, but also a metabolite of dichlorodiphenyltrichloroethane (DDT), which is often overlooked. To verify the sources and transformation pathways of DDT and related metabolites in soils, we measured p,p'-(dicofol+DBP) (sum of p,p'-dicofol and 4,4'-dichlorobenzophenone), DDT and six metabolites in soils from Northwest Fujian, China. The ratios of 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDT)/1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDT) and the mass balance demonstrated that p,p'-(dicofol+DBP) predominantly originated from p,p'-DDT transformation rather than from actual dicofol application. p,p'-(dicofol+DBP) accounted for 45.0% as the primary metabolites of DDT in this study, more than 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDD), which might lead to large overestimations of the fresh DDT input by using the traditional ratio of (∑2DDD+∑2DDE)/∑2DDT (with all o,p'- and p,p'- isomers included). In paddy fields where the conditions alternate between aerobic (dry period) and anaerobic (wet period), both p,p'-DDD and p,p'-DDE were likely to degrade to 1-chloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDMU), which further transformed to 2,2-bis(p-chlorophenyl)ethylene (p,p'-DDNU). Degradation of p,p'-DDMU to p,p'-DDNU mainly occurred in waterlogged paddy soils. However, p,p'-DDNU might not transform to other higher-order metabolites in aerobic surface soils. Overall, our study confirmed p,p'-(dicofol+DBP) as metabolites of p,p'-DDT, suggested DDE and DDD were parallel precursors of DDMU, and further verified the transformation pathways of DDT in surface soils.

Pesticides exposure through environment and risk of pre-term birth: a study from Agra city

Pre-term birth is an increasingly prevalent complex condition with multiple risk factors including environmental pollutants. Evidences linking organochlorine pesticides with adverse pregnancy outcomes are inconsistent for link between organochlorine pesticides and adverse pregnancy outcomes. We performed a case–control study of 50 cases of full-term births and 40 cases of pre-term births in this study. Placental organochlorine pesticides like metabolites of dichlorodiphenyltrichloroethane that is, (p,p-DDE, p,p-DDT and o,p-DDD) and isomers of hexachlorocyclohexane (α, β, γ and δ HCH) were analyzed by gas chromatography. Although the mean levels of pesticide were found higher in the placenta of the women with pre-term delivery cases placentas, but only α-HCH, total-HCH, p,p-DDE and total-DDT were found statistically significant. It was observed that pesticide exposed women were approximately 1.7 times more likely to deliver pre-term baby as compare to pregnant women that were not exposed to any pesticides. We also observed that increasing maternal age reduced the risk of having pre-term birth (OR = 0.99). Among all pesticides, α-HCH was found to be strongest isomer to induce premature baby birth (p < 0.001). This study found that pregnant women’s age and chronic disease, baby’s weight at the time of birth and α-HCH were important risk factors for pre-term births.

Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area

BackgroundDichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy. ObjectiveTo evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy. Materials and MethodsWe analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age ≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models. ResultsThirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH >2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (β=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis. ConclusionsOur findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.

Biomonitoring of persistent organic pollutants in Egypt using Taphozous perforatus (Chiroptera: Emballonuridae)

Organochlorine pesticides (OCP) and polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants (POPs) that have chronic toxicity, tendency to contaminate the environment, and transfer into the food chain. This study was conducted to explore the use of bats as bioindicators to help understanding the time trend of POPs at the present time. Liver and kidney tissues from the Egyptian tomb bat (Taphozous perforatus) were subjected to the QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction prior to quantification by LC-MS/MS analyses. DDT (dichlorodiphenyl trichloroethane) metabolites (e.g., o,p’-DDT, p,p’-DDD, p,p’-DDE), PCB congeners (e.g., PCB 118, PCB 138, PCB 180), hexachlorobenzene (HCB), dicofol and sulphur were found in variable concentrations in the tissues of T. perforatus. Their concentration levels were affected with the bat sex and the season of sampling. Liver and kidneys were found to contain 0.39 µg/g wet weights of DDTs and 0.11 µg/g wet weights of PCBs. Concentration of the compound dichlorodiphenyl ethane (p,p’-DDE) predominated over the other DDT metabolites; giving rise to the DDE/∑DDT ratio of 0.82 as an indicative of pronounced decline in new DDT inputs to the environment. Also, concentration of the PCB 138 predominated that of the other congeners. There were correlations between liver and kidney concentrations of OCP and PCBs in both of them. It was concluded that these pollutants are still detectable in the environment; however in low concentration levels and far from lethal toxicity. Nevertheless, these findings may encourage the use of other bat species from urban and rural regions, as well as agricultural and industrial locations, as bioindicators.

Three cycles of human biomonitoring in Flanders - Time trends observed in the Flemish Environment and Health Study.

To follow time trends in exposure to environmental chemicals, three successive campaigns of the Flemish Environment and Health Study (FLEHS) have recruited and sampled in total 5825 participants between 2002 and 2014. Cord samples from newborns, urine and blood samples from 14 to 15 years old adolescents and from adults between 50 and 65 years old were analysed in geographical representative samples of the Flemish population. The data of the different campaigns were considered per age group and per biomarker after adjustment for predefined covariates to take into account differences in characteristics of the study populations over time. Geometric means were calculated. Multiple linear regression was used to evaluate time trends. The concentration of serum biomarkers for persistent organic pollutants (POPs), such as marker polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) expressed per g lipid, decreased significantly with time. The levels of DDE in all age groups and those of PCBs in cord and adolescent serum samples were almost halved in a time period of ten years. HCB levels were reduced by a factor of 4 in adolescents and in adults. Mean serum concentrations of the more recently regulated perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were significantly lower in cord samples of 2013 compared to samples of 2007. The decline was more pronounced for PFOS than for PFOA. In the same period, mean metabolite levels of di-2-ethylhexyl phthalate (DEHP) and of di-n-butyl phthalate (DBP) decreased significantly in urine samples of adolescents with sharper declines for DEHP than for DBP. Cadmium and lead levels in cord and adolescent blood samples were significantly lower in the recent campaigns than 10 years before. Also the mean urinary cadmium level in adults was 35% lower compared to adult samples of 2002. Such favourable trends were not observed for arsenic and thallium measured in cord blood. Similar, the concentrations of 1-hydroxypyrene, a marker for exposure to polycyclic aromatic hydrocarbons (PAHs), was not lower in urine from adolescents sampled in 2013 compared to 2003. In contrast, concentrations of t,t'-muconic acid, a marker of benzene exposure, showed clearly reduced levels. The FLEHS program shows that concentrations of well-regulated chemicals especially traditional POPs and cadmium and lead are decreasing in the population of Flanders. Response to regulatory measures seems to happen rapid, since concentrations in humans of specific regulated perfluorinated compounds and phthalates were significantly reduced in five years time. Biomarker concentrations for arsenic, thallium, and polyaromatic hydrocarbons are not decreasing in this time span and further follow up is warranted.

Examination of factors dominating the sediment-water diffusion flux of DDT-related compounds measured by passive sampling in an urbanized estuarine bay

The fate of hydrophobic organic compounds in aquatic environment are largely determined by their exchange at sediment-water interface, which is highly dynamic and subject to rapidly evolving environmental conditions. In turn, environmental conditions may be governed by both physicochemical parameters and anthropogenic events. To examine the importance of various impact factors, passive sampling devices were deployed at the seafloor of Hailing Bay, an urbanized estuarine bay in Guangdong Province of South China to measure the sediment-water diffusion fluxes of several metabolites of dichlorodiphenyltrichloroethane (DDT), p,p′-DDE, p,p′-DDD and o,p′-DDD. The physicochemical properties of water (temperature, pH, salinity and dissolved oxygen) and surface sediment (sediment organic matter, physical composition, pH, water content, colony forming unit and catalase activity) were also measured. The results showed that the diffusion fluxes of o,p′-DDD, p,p′-DDD and p,p′-DDE at sites A1 and A2 near a fishing boat maintenance facility ranged from 0.42 to 4.73 ng m−2 d−1 (from sediment to overlying water), whereas those at offshore sites varied between −0.03 and −3.02 ng m−2 d−1 (from overlying water to sediment), implicating A1 and A2 as the sources of the target compounds. The distribution patterns of the diffusion fluxes of the target compounds were different from those of water and sediment parameters (water temperature, salinity, sediment texture, pH, colony forming unit and catalase activity) at six sampling sites. This finding suggested that none of these parameters were critical in dictating the sediment-water diffusion fluxes. Besides, decreases in the contents of kerogen and black carbon by 6.7% and 11% would enhance the diffusion fluxes of the target compounds by 11–14% and 12–23%, respectively, at site A1, indicating that kerogen and black carbon were the key factors in mediating the sediment–water diffusion fluxes of DDT-related compounds in field environments.

Exposure to p,p'-DDE Induces Morphological Changes and Activation of the PKCα-p38-C/EBPβ Pathway in Human Promyelocytic HL-60 Cells.

Dichlorodiphenyldichloroethylene (p,p′-DDE), the most persistent metabolite of dichlorodiphenyltrichloroethane (DDT), is still present in the human population. Both are present in the bone marrow of patients with bone marrow disorders, but thus far there are no studies that assess the capability of p,p′-DDE to affect myeloid cells. The aim of this study was to determine the effect of p,p′-DDE on promyelocytic cell differentiation and intracellular pathways related to this event. p,p′-DDE induced morphological changes compatible with promyelocytic differentiation in a concentration-dependent manner. The p,p′-DDE effect on [Ca2+]i, C/EBPβ protein levels, PKCα and p38 activation, and the role of oxidative stress or PLA2 was assayed. Exposure to 1.9 μg/mL of p,p′-DDE increased [Ca2+]i, PKCα, p38, and C/EBPβ protein levels; the increase of nuclear C/EBPβ protein was dependent on p38. PKCα phosphorylation was dependent on PLA2 and p,p′-DDE-induced oxidative stress. p38 phosphorylation induced by p,p′-DDE was dependent on PLA2, PKC activation, and oxidative stress. These effects of p,p′-DDE at concentrations found in human bone marrow may induce alterations in immature myeloid cells and could affect their cellular homeostasis. In order to establish the risk from exposure to p,p′-DDE on the development of bone marrow disorders in humans, these effects deserve further study.

Common Pesticide, Dichlorodiphenyltrichloroethane (DDT), Increases Amyloid-β Levels by Impairing the Function of ABCA1 and IDE: Implication for Alzheimer's Disease.

While early-onset familial Alzheimer's disease (AD) is caused by a genetic mutation, the vast majority of late-onset AD is likely caused by the combination of genetic and environmental factors. Unlike genetic studies, potential environmental factors affecting AD pathogenesis have not yet been thoroughly investigated. Among environmental factors, pesticides seem to be one of critical environmental contributors to late-onset AD. Recent studies reported that the serum and brains of AD patients have dramatically higher levels of a metabolite of dichlorodiphenyltrichloroethane (DDT). While these epidemiological studies provided initial clues to the environmental risks potentially contributing to disease pathogenesis, a functional approach is required to determine whether they actually have a causal role in disease development. In our study, we addressed this critical knowledge gap by investigating possible mechanisms by which DDT affects amyloid-β (Aβ) levels. We treated H4-AβPPswe or H4 cells with DDT to analyze its effect on Aβ metabolism using Aβ production, clearance, and degradation assays. We found that DDT significantly increased the levels of amyloid-β protein precursor (AβPP) and β-site AβPP-cleaving enzyme1 (BACE1), affecting Aβ synthesis pathway in H4-AβPPswe cells. Additionally, DDT impaired the clearance and extracellular degradation of Aβ peptides. Most importantly, we identified for the first time that ATP-binding cassette transporter A1 (ABCA1) and insulin-degrading enzyme (IDE) are the downstream target genes adversely affected by DDT. Our findings provide insight into the molecular mechanisms by which DDT exposure may increase the risk of AD, and it further supports that ABCA1 and IDE may be potential therapeutic targets.