Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Systematic investigation of organochlorine pesticides and polychlorinated biphenyls blood levels in Greek children from the Rhea birth cohort suggests historical exposure to DDT and through diet to DDE.

The blood levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been thoroughly investigated in Greek children from the Rhea birth cohort study. This investigation aimed to assess exposure levels, explore their possible relationship with children's age and sex, and indicate potential sources of exposure. Exposure patterns and common sources of PCBs and OCPs were analyzed using bivariate and multivariate statistics. A total of 947 blood samples from study participants were analyzed for OCP and PCB exposure, with 375 samples collected at 4 years old, 239 at 6.5 years old, and 333 at 11 years old. Elevated levels of DDE were observed in 6.5-year-old children compared to corresponding levels in other European countries. Higher levels of DDE were found in 4-year-old children, with the lowest concentrations in the 11-year-old group. The DDT/DDE ratio was consistently less than 1 among all the examined subjects. These results indicate exposure to DDT and DDE both in utero and through breastfeeding and dietary intake. For the entire cohort population, the highest concentration was determined for PCB 28, followed by PCBs 138, 153, and 180. The sum of the six indicator PCBs implied low exposure levels for the majority of the cohort population. Spearman correlations revealed strong associations between PCBs and OCPs, while principal component analysis identified two different groupings of exposure. DDE exhibited a correlation with a series of PCBs (153, 156, 163, 180), indicating a combined OCP-PCB source, and an anticorrelation with others (52, 28, 101), implying a separate and competing source.

Diffusion of organochlorine (OCPs) and cypermethrin pesticides from rohu (Labeo rohita) internal organs to edible tissues during ice storage: a threat to human health.

The migration of organochlorine pesticides (OCPs) and cypermethrin residues from internal organs to edible tissues of ice-held Labeo rohita (rohu) was investigated in this study. The liver (246 µg/kg) had the highest level of ∑OCP residues, followed by the gills (226 µg/kg), intestine (167 µg/kg), and muscle tissue (54 µg/kg). The predominant OCPs in the liver and gut were endosulfan (53-66 µg/kg), endrin (45-53 µg/kg), and dichloro-diphenyl-trichloroethane (DDT; 26-35 µg/kg). The ∑OCP residues in muscle increased to 152 µg/kg when the entire rohu was stored in ice, but they decreased to 129 µg/kg in gill tissues. On days 5 and 9, the total OCPs in the liver increased to 317 µg/kg and 933 µg/kg, respectively. Beyond day 5 of storage, total internal organ disintegration had led to an abnormal increase in OCP residues of liver-like mass. Despite a threefold increase in overall OCP residues by day 9, accumulation of benzene hexachloride (BHC) and heptachlor was sixfold, endrin and DDT were fourfold, aldrin was threefold, and endosulfan and cypermethrin were both twofold. Endosulfan, DDT, endrin, and heptachlor were similarly lost in the gills at a rate of 40%, while aldrin and BHC were also lost at 60 and 30%, respectively. The accumulation of OCP residues in tissues has been attributed to particular types of fatty acid derivatives. The study concluded that while pesticide diffusion to edible tissues can occur during ice storage, the levels observed were well below the allowable limit for endosulfan, endrin, and DDT.

Monk seals (Monachus monachus) in the Mediterranean Sea: The threat of organochlorine contaminants and polycyclic aromatic hydrocarbons.

The Mediterranean monk seal (Monachus monachus) is an emblematic species of conservation concern. Anthropogenic pressures have led to severe population declines and significant fragmentation of the remaining populations. Because of their close relationship with coastal areas, Mediterranean monk seals may be potentially exposed to pollution from agricultural sources, as well as from oil tanker spills. Although monitoring of pollution has long been considered a priority for this species, data on monk seal contamination levels are scarce. In this study, 55 blubber samples of all genders and age classes collected during necropsies (1995-2013) from seals of the Eastern Mediterranean subpopulation were analyzed for organochlorine compounds (OCs), i.e., hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDTs), and polycyclic aromatic hydrocarbons (PAHs). Overall, PCBs > DDTs ≫ PAHs > HCB in all samples. Results showed a significant downward trend over the 19-year period for DDTs and HCB. No marked pattern was found for PAHs, even though relative abundance of cancerogenic PAH fraction rose in recent years. PCB levels in subadult specimens increased noticeably over time despite worldwide ban. Our findings did not suggest recent releases of DDT or new pesticides (e.g., Dicofol) in the environment, but may indicate an improper disposal of ancient storages of PCBs or a remobilization from reservoirs. OC levels exceeded thresholds that are commonly associated with immunosuppression and reproductive impairment in other pinnipeds. Hence, OCs could be responsible of potential toxicological effects in this subpopulation. This study represents the first report on PAH and one of the few reports on OC bioaccumulation in Mediterranean monk seals. Based on the levels found in the blubber of monk seals from the Eastern Mediterranean, and given the known harmful effects associated to the prolonged exposure to these substances and the reduced long-term expectations of species recovery, regular monitoring is advocated.

The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome-a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men.

BACKGROUND: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) accumulates in marine mammals and fish. DDT and p,p'-DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. OBJECTIVES: The objective of this study was to assess the sperm epigenome in relation to p,p'-DDE serum levels between geographically diverse populations. METHODS: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p,p'-DDE serum levels (mean=870.734±134.030 ng/mL). We assessed the sperm epigenome in relation to serum p,p'-DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. RESULTS: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. DISCUSSION: These findings suggest that DDT and p,p'-DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Selected pesticidal POPs and metabolites in the soil of five Vietnamese cities: Sources, fate, and health risk implications.

Large quantities of organochlorine pesticides (OCPs) have been used in tropical regions. The fate processes and risks of these legacy contaminants in the tropics are poorly understood. Herein, we investigated the occurrence of three classes of widely used OCPs and their metabolites in surface and core soil from five cities across Vietnam with a prevalent tropical monsoon climate and a long history of OCP application. We aimed to elucidate migration potentials, degradation conditions, and transformation pathways and assess current health risks of these contaminants. Generally, the concentrations of OCPs and metabolites in the soil core were slightly lower than those in surface soil except for hexachlorocyclohexane (HCH) isomers. 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), the sum of dicofol and 4,4'-dichlorobenzophenone (p,p'-DBP), and 2,2-bis(4-chlorophenyl)-1,1-dichloroethane (p,p'-DDD) were the most abundant compounds in both surface and core soils. A uniform distribution of HCHs (the sum of α-, ß-, γ-, and δ-HCH) at trace levels was found in almost all soils, serving as evidence of the lack of recent use of HCH pesticides. Higher concentrations of DDTs (the sum of DDT, DDD, and DDE) were observed in north-central Vietnamese soil, whereas appreciable concentrations of ENDs (the sum of α- and ß-endosulfan and endosulfan sulfate) were only found in southern Vietnamese soils. Empirical diagnostic ratios indicated residuals of DDTs were mainly from technical DDT rather than dicofol, whereas aged HCHs could be explained by the mixture of lindane and technical HCH. Both historical applications and recent input explain DDTs and ENDs in Vietnamese soil. Total organic carbon performs well in preventing vertical migration of more hydrophobic DDTs and ENDs. The dominant transformation pathway of DDT in surface soil followed p,p'-DDE→2,2-bis(4-chlorophenyl)-1-chloroethylene or p,p'-DDMU→1,1-bis(4-chlorophenyl)ethylene or p,p'-DDNU→p,p'-DBP, whereas the amount of p,p'-DDMU converted from p,p'-DDD and p,p'-DDE is similar in soil core. Non-cancer risks of OCPs and metabolites in all soils and cancer risks of those chemicals in core soils were below the safety threshold, whereas a small proportion of surface soil exhibited potential cancer risk after considering the exposure pathway of vegetable intake. This study implied that organic matter in non-rainforest tropical deep soils still could hinder the leaching of hydrophobic organic contaminants as in subtropical and temperate soils. When lands with a history of OCP application are used for agricultural purposes, dietary-related risks need to be carefully assessed.

In ovo o,p'-DDT exposure induces malformation of reproductive organs and alters the expression of genes controlling sexual differentiation in Japanese quail embryo.

In ovo exposure to o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p'-DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p'-DDT-containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 µg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti-Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p'-DDT dose-dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p'-DDT dose-dependently decreased estrogen receptor (ER) α, ERß, and AMHR2 mRNA expression. o,p'-DDT dose-dependently induced left-biased asymmetry of testis size, and ovary-like tissue was found in the left testis after exposure to 8,000 µg per egg o,p'-DDT, although asymmetric gene expression did not occur. o,p'-DDT did not affect ovarian tissue but did decrease 17α-hydroxylase/C17-20 lyase mRNA expression and dose-dependently increased ERß mRNA expression. o,p'-DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p'-DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals.

Organochlorine pesticides disrupt T helper cell regulation and reduce IL-2 and IFN-γ favoring infection and production of autoantibodies among pemphigus patients.

The list of environmental factors that trigger autoimmune diseases in genetically susceptible individuals has grown in the recent years and is far from complete. The possible intervention of the environment in triggering these diseases is ever more perceived by the clinicians. This study investigated the effect of environmental factors like organochlorine pesticides (OCPs) on proportions of different T lymphocyte subsets and their cytokine secretion in-vitro among pemphigus patients, before and after specific immunosuppressive therapy. Higher levels of OCPs like ß-HCH (isoform of hexachlorohexane), α-endosulfan (a form of endosulfan) and p,p΄-DDE (a metabolite of o,p'-dichlorodiphenyltrichloroethane) were observed in the blood of pemphigus patients as compared to healthy controls. HCH and DDT exposure caused specific reduction in CD8+CD45RA+ and CD4+CD25+ T lymphocyte subpopulations in these patient PBMCs. A strong reduction in Th1 (IL-2 and IFN-γ) cytokines upon exposure to these OCPs in-vitro was also observed. These findings indicate that HCH and DDT have a significant impact on Th1 lymphocytes. Impaired production of these cytokines might favor infections and production of autoantibodies. We therefore speculate that the systemic absorption of the pesticide after the topical contact may be one of the factors triggering the immunological mechanism among pemphigus patients.

Water quality, human health risk, and pesticides accumulation in African catfish and Nile tilapia from the Kitchener Drain-Egypt.

Pesticides are toxic and could negatively impact humans and the ecosystem. The Kitchener Drain is among the longest drains in Egypt and carries a wide range of wastewater from the agriculture sector, which contains pesticides and may pollute the ecosystem. Thus, water quality, human health risk, and pesticide accumulation in African catfish and Nile tilapia from the Kitchener Drain-Egypt. The water and fish samples were collected from Kitchener Drain in Kafr Elsheikh Governorate, Egypt, during the four seasons. The results indicated that heptachlor and diazinon were undetected during the four seasons. However, endosulfan, chlorpyrifos, and dicofol were detected in winter and autumn. Only p,p'-DDT was detected during spring. Endosulfan, heptachlor, and aldrin were detected in Nile tilapia during winter. Only heptachlor and aldrin were detected during spring. Endosulfan, heptachlor, dicofol, p,p'-DDT, chlorpyrifos, and diazinon were detected in the autumn season. In summer, dicofol and p,p'-DDT were detected, while endosulfan, heptachlor p,p'-DDT, aldrin, chlorpyrifos, and diazinon were not detected. In African catfish, endosulfan, heptachlor, dicofol, and p,p'-DDT were detected during winter, while chlorpyrifos, aldrin, and chlorpyrifos, aldrin, and diazinon were not detected. In the spring season, endosulfan, heptachlor, and aldrin were detected. Endosulfan, heptachlor, dicofol, p,p'-DDT, aldrin, chlorpyrifos, and diazinon were detected in the autumn season. Similarly, in the summer season, endosulfan, heptachlor, dicofol, p,p'-DDT, aldrin, chlorpyrifos, and diazinon were detected. The sequence of estimated daily intake (EDI) in Nile tilapia during the four seasons is heptachlor > endosulfan > dicofol > p,p'-DDT > aldrin > diazinon > chlorpyrifos. The sequence of EDI in African catfish during the four seasons is endosulfan > p,p'-DDT > heptachlor > aldrin > dicofol > diazinon > chlorpyrifos. In conclusion, the results confirmed the absence of a hazard index for consuming Nile tilapia and African catfish collected from the Kitchener drain.

Cross-sectional and longitudinal associations of dichlorodiphenyltrichloroethane (DDT) metabolites exposure with lung function alternation in the Chinese general adults.

Exposure of dichlorodiphenyltrichloroethane (DDT) pesticide was suggested to be associated with adverse effects on the respiratory system. However, the effects of DDT exposure on lung function remain unclear. Our objectives were to investigate the potential associations of internal levels of DDT and its metabolites including dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) with lung function. Serum DDT, DDE, and DDD concentrations and lung function were measured among 3968 general adults from the Wuhan-Zhuhai cohort. The cross-sectional and longitudinal associations of serum DDT and its metabolites with lung function were assessed using linear mixed models. The results showed negative dose-response relationships of serum DDT, DDE, and DDD levels with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). In the cross-sectional analyses, each 1-unit increase in natural log-transformed values of p,p'-DDE, o,p'-DDT, o,p'-DDE, or p,p'-DDD was significantly associated with a 25.77-, 44.84-, 51.13-, or 43.44-mL decrease in FVC, respectively. Each 1-unit increase in natural log-transformed values of o,p'-DDT, o,p'-DDE, o,p'-DDD, or p,p'-DDD was significantly associated with a 35.72-, 31.87-, 29.54-, or 36.80-mL decrease in FEV1, respectively. In the three-year longitudinal analyses, each 1-unit increase in natural log-transformed serum p,p'-DDT and p,p'-DDE was significantly associated with a 35.10 mL and 36.38 mL decrease in FVC, and a 26.32 mL and 32.37 mL decrease in FEV1, respectively. In conclusion, DDT and its metabolites exposure were associated with lung function decline in the general Chinese adult population.

Mutual interference between 3,6-dichlorinated carbazole and p,p'-dichlorodiphenyltrichloroethane in gas chromatography mass spectrometry analysis.

The widespread contamination of the environment by polyhalogenated carbazoles (PHCZs) has been increasingly observed during the past decade. Among numerous PHCZ congeners, 3,6-dichlorocarbazole (36-CCZ) is often among the most frequently detected at higher concentrations. Although the environmental level of the legacy pesticide p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) has been declining, it continues to be ubiquitously detected. These two compounds were found to interfere with each other during analyses using gas chromatography (GC) coupled with single- or triple-quadrupole low-resolution mass spectrometry (MS or MS/MS). The base peak in the mass spectra was that of m/z 235 for both compounds. In MS/MS with multiple reaction monitoring (MRM), the same transitions (235 → 200 and 235 → 165) were often used. Under the same GC operating conditions, the SH-I-5MS capillary column used in this work did not resolve the two compounds at baseline. Pre-treatment using cleanup column chromatography can fractionate the sample extract, with the two compounds separated in different fractions before instrumental analyses. Reversed-phase HPLC columns also work for resolving 36-CCZ and p,p'-DDT. Possible overlaps in GC retention and similarity in MS spectra might have caused data inaccuracy for 36-CCZ as well as p,p'-DDT in some studies published to date, and steps to avoid the interference should be taken into quality control protocols in future research and environmental monitoring.

Pesticides in sediments from Magdalena River, Colombia, are linked to reproductive toxicity on Caenorhabditis elegans.

Pesticides are prevalent pollutants found in river sediments in agricultural regions worldwide, leading to environmental pollution and toxic effects on biota. In this study, twenty sediment samples were collected from the Magdalena River in Colombia and analyzed for forty pesticides. Methanolic extracts of the sediments were used to expose Caenorhabditis elegans for 24 h, evaluating the effects on its reproduction. The most abundant pesticides found in Magdalena River sediments were atrazine, bromacil, DDE, and chlorpyrifos. The concentrations of DDE and the sum of DDD, DDE, and DDT were above the Threshold Effect Concentration (TEC) values for freshwater sediments, indicating potential effects on aquatic organisms. The ratios of DDT/(DDE + DDD) and DDD/DDE suggest historical contributions of DDT and degradation under aerobic conditions. Several sampling sites displayed a moderate toxicity risk to biota, as calculated by the sediment quality guideline quotient (SQGQ). Nematode brood size was reduced by up to 37% after sediment extract exposure. The presence of chlordane, DDT-related compounds, and chlorpyrifos in Magdalena River sediments was associated with reproductive toxicity among C. elegans.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in adipose tissue of women from Grand Tunis and their association with demographic factors and dietary habits.

Dichlorodiphenyl trichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and polychloronated biphenyls (PCBs) were measured in 25 woman adipose tissues collected in 2016 from Grand Tunis, Tunisia. p,p'-DDE, p,p'-DDT, HCB and ß-HCH were the dominant organochlorine pesticides (OCPs) in decreasing order in all samples. The total OCP levels varied from 79 to 343 ng g-1 lipid with a median value of 189 ng g-1 lipid and DDTs contributed approximately 88% to sum OCP. The ratio of p,p'-DDT/p,p'-DDE across all samples is below one, which suggests mainly historic exposure but may indicate some recent exposure to the banned pesticide. The median concentration of PCBs was 109 ng g-1 lipid and ranged between 27 and 204 ng g-1 lipid. PCB-153, PCB-180, PCB-138 and PCB-170 were the most abundant congeners, which contributed about 78% of the total PCBs. Spearman analysis showed that dominant organochlorine compounds (OCs) are highly positive correlated except for PCB-28/31, indicating that women from Tunis are exposed via similar routes. Inhalation exposure could be a possible pathway for the uptake of the less chlorinated congeners. We found positive and statistically significant association with subjects age for HCB (r = 0.517; p = 0.009) and PCBs (r = 0.65; p = 0.001) levels and a weak age-dependent accumulation was found for HCHs (r = 0.375; p = 0.065) and DDTs (r = 0.388; p = 0.056). The concentrations of OC subgroups were not associated with BMI, parity and residence. No association was observed between fish, red/white meat, milk and dairy products consumption and levels of HCB, HCHs and PCBs. DDTs levels were significantly correlated only with milk (p = 0.048) and milk products (p = 0.047) intake.

Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.

Replication fork arrest-induced DNA double strand breaks (DSBs) caused by lesions are effectively suppressed in cells due to the presence of a specialized mechanism, commonly referred to as DNA damage tolerance (DDT). In eukaryotic cells, DDT is facilitated through translesion DNA synthesis (TLS) carried out by a set of DNA polymerases known as TLS polymerases. Another parallel mechanism, referred to as homology-directed DDT, is error-free and involves either template switching or fork reversal. The significance of the DDT pathway is well established. Several diseases have been attributed to defects in the TLS pathway, caused either by mutations in the TLS polymerase genes or dysregulation. In the event of a replication fork encountering a DNA lesion, cells switch from high-fidelity replicative polymerases to low-fidelity TLS polymerases, which are associated with genomic instability linked with several human diseases including, cancer. The role of TLS polymerases in chemoresistance has been recognized in recent years. In addition to their roles in the DDT pathway, understanding noncanonical functions of TLS polymerases is also a key to unraveling their importance in maintaining genomic stability. Here we summarize the current understanding of TLS pathway in DDT and its implication for human health.

Spatio-temporal distribution of organochlorine pesticides in agricultural soils of southeast China during 2014-2019.

Organochlorine pesticides (OCPs) are organic pollutants that are persistent and undegradable in the environment. To investigate their residual concentrations, spatial and temporal distributions, and the relationship with the crops planted, 12 individual OCPs in 687 soil samples from Jiangsu, Zhejiang and Jiangxi provinces of southeast China were examined. The detection frequencies of OCPs in the studied areas were 1.89%-64.9%. The concentrations of dichloro-diphenyl-trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and endosulfans ranged from 0.01 to 5659 µg/kg, 0.03-3.58 µg/kg, and 0.05-3235 µg/kg, respectively. Jiangsu was mainly contaminated by p,p'-DDT, p,p'-DDD and endosulfan sulfate, Zhejiang was more polluted by OCPs except δ-HCH, and Jiangxi was more vulnerable to the contamination of OCPs except o,p'-DDE. The partial least-squares discrimination analysis (PLS-DA) model with RX2 36.3-36.8% revealed that compounds with similar chemical properties tended to appear in the same year and month. All crop lands were polluted by DDTs and Endosulfans. The highest concentrations of DDTs and Endosulfans were found in citrus and vegetable fields, respectively. This study offers new insight into the layout and partitioning of OCPs in agricultural land and into insecticide management on public health and ecological safety.

Pesticides in the hydrogeo-environment: a review of contaminant prevalence, source and mobilisation in India.

Chemical pesticides in the hydrogeological system are a global concern as they pose a severe threat to humans and other organisms. In agriculture, around 4.12 million tonnes of pesticides were used globally in 2018, which is 50% more than in the 1990s. Various pesticides detected in the hydrogeological system of India since the 1990s have been documented and reviewed to understand the prevalence, source, history and degradation pathways. This review contributes to a better understanding of existing pesticide pollution and the state of hydrogeological resource deterioration. Small to excess levels of pesticide residues were detected in groundwater, surface water, soil, and sediments. Pesticides that were most commonly and predominantly found in the hydrogeological system were HCHs, DDTs, endosulfan, heptachlor, drins (aldrin, dieldrin, endrin), chlordane etc. ß and γ-HCH isomers among HCHs, whereas p,p'-DDT and p,p'-DDE among the DDTs were detected most prevalently. In many regions, pesticide residue levels in water have exceeded the maximum residue limits of WHO and BIS, while those in soils and sediments have exceeded the threshold effect level and probable effect level. Higher pesticide residues were detected in the water resources of rural agricultural areas compared to peri-urban or urban areas. A positive correlation of pesticide residues between water resources and soil has been observed in some regions, suggesting a similar contamination source. Diagnostic ratios of pesticides reveal their source, history and degradation pathways. Diagnostic ratios observed in various studies conducted in India suggest historical as well as recent use of banned pesticides. Strengthening current policies and regulations, monitoring pesticide use, changes in pesticide application practices, awareness among farmers, and the use of prominent removal techniques are necessary to tackle pesticide contamination in India.

The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.

DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1ß secretion, but increasing cellular ROS and mitochondrial O2•-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-ß1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1ß secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1ß secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1ß secretion process, as the NLRP3 activation, deserves further study.

Occurrence and environmental risk assessment of 22 pesticides in Brazilian freshwaters.

Pesticide contamination in water resources is a global threat. Although usually found at low concentrations, pesticides raise considerable toxicological concerns, mainly when mixtures are considered. The occurrence of 22 pesticides (2,4 D, alachlor, aldicarb, aldrin, atrazine, carbendazim, carbofuran, chlordane, chlorpyrifos, DDT, diuron, glyphosate, lindane, mancozeb, methamidophos, metolachlor, molinate, profenofos, simazine, tebuconazole, terbufos, and trifluralin) was investigated, through consolidated database information, in surface freshwaters of Brazil. Moreover, scenarios of environmental risk assessment considering isolated compounds and mixtures were performed, as well as a meta-analytic approach for toxicity purposes. Pesticides in freshwater have been reported from 719 cities (12.9% of Brazilian cities), where 179 (3.2%) showed pesticide occurrence above the limit of detection or quantification. Considering cities with more than five quantified, 16 cities were prone to environmental risks considering individual risks. However, the number increased to 117 cities when the pesticide mixture was considered. The mixture risk was driven by atrazine, chlorpyrifos, and DDT. The national maximum acceptable concentrations (MAC) for nearly all pesticides are higher than the predicted no-effect concentration (PNEC) for the species evaluated, except aldrin. Our results show the need to consider mixtures in the environmental risk assessment to avoid underestimation and review MAC to protect aquatic ecosystems. The results presented here may guide the revision of the national environmental legislation to ensure the protection of Brazilian aquatic ecosystems.