Transcriptome analysis of human cholangiocytes exposed to carcinogenic 1,2-dichloropropane in the presence of macrophages in vitro.

1,2-Dichloropropane (1,2-DCP), a synthetic organic solvent, has been implicated in causality of cholangiocarcinoma (bile duct cancer). 1,2-DCP-induced occupational cholangiocarcinoma show a different carcinogenic process compared to common cholangiocarcinoma, but its mechanism remains elusive. We reported previously that exposure of MMNK-1 cholangiocytes co-cultured with THP-1 macrophages, but not monocultured MMNK-1 cholangiocytes, to 1,2-DCP induced activation-induced cytidine deaminase (AID) expression, DNA damage and ROS production. The aim of this study was to identify relevant biological processes or target genes expressed in response to 1,2-DCP, using an in vitro system where cholangiocytes are co-cultured with macrophages. The co-cultured cells were exposed to 1,2-DCP at 0, 0.1 or 0.4 mM for 24 h, and then the cell lysates were assessed by transcriptome analysis. 1,2-DCP upregulated the expression of base excision repair genes in MMNK-1 cholangiocytes in the co-cultures, whereas it upregulated the expression of cell cycle-related genes in THP-1 macrophages. Activation of the base excision repair pathway might result from the previously observed DNA damage in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages, although involvement of other mechanisms such as DNA replication, cell death or other types of DNA repair was not disproved. Cross talk interactions between cholangiocytes and macrophages leading to DNA damage in the cholangiocytes should be explored.

Exploring the association of organochlorine pesticides exposure and hearing impairment in United States adults.

Hearing loss (HL) is a highly prevalent public health concern. Organochlorine pesticides (OCPs) are widely used environmental pollutants harmful to human health. Studies investigating the effects of OCPs exposure on the auditory system in the general population are rare. To explore the association between OCPs exposure and HL in adults, 366 adults aged 20-69 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2003-2004) were investigated. HL was defined as a pure-tone average (PTA) ≥ 20 dB in the better ear. Multivariate linear and logistic regression analyses were conducted to evaluate the association of four selected serum OCPs with PTAs and the risk of HL. In participants aged < 60 years, hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (p, p'-DDE) exposure was positively associated with low- and speech-frequency PTAs, and with low-frequency HL, respectively. Risk of HL increased in the highest tertile compared with the lowest tertile of serum HCB and p, p'-DDE (odds ratio [OR]: 4.38, 95% confidence interval [CI]: 0.97-19.80; OR: 16.66, 95% CI: 2.64-105.09, respectively). In this study of US adults aged < 60 years, HCB and p, p'-DDE exposure was positively associated with HL. HCB and p, p'-DDE may be potential risk factors for HL.

Effects of Organochlorine Pesticide Residues in Maternal Body on Infants.

There are many organochlorine pollutants in the environment, which can be directly or indirectly exposed to by mothers, and as estrogen endocrine disruptors can cause damage to the lactation capacity of the mammary gland. In addition, because breast milk contains a lot of nutrients, it is the most important food source for new-born babies. If mothers are exposed to organochlorine pesticides (OCPs), the lipophilic organochlorine contaminants can accumulate in breast milk fat and be passed to the infant through breast milk. Therefore, it is necessary to investigate organochlorine contaminants in human milk to estimate the health risks of these contaminants to breastfed infants. In addition, toxic substances in the mother can also be passed to the fetus through the placenta, which is also something we need to pay attention to. This article introduces several types of OCPs, such as dichlorodiphenyltrichloroethane (DDT), methoxychlor (MXC), hexachlorocyclohexane (HCH), endosulfan, chlordane, heptachlorand and hexachlorobenzene (HCB), mainly expounds their effects on women's lactation ability and infant health, and provides reference for maternal and infant health. In addition, some measures and methods for the control of organochlorine pollutants are also described here.

Exposure of infants to organochlorine pesticides from breast milk consumption in southwestern Ethiopia.

Breast milk is often used as an environmental bioindicator since it serves as an important medium to accumulate organochlorine pesticides. The main aim of this study is to determine the level of organochlorine pesticides in human breast milk collected from three districts of southwestern Ethiopia (Asendabo, Deneba, and Serbo) at three times points baselines (1st month), midline ( six months), and end line (12 months) and risk of infants' exposure. A longitudinal study was conducted to assess pesticide residues in human breast milk samples and evaluate the risk-exposure of infants to these pesticides from consumption of mother's milk in Ethiopia. Breast milk samples were collected from 168 mothers at three time points and pesticides were extracted using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. The level of pesticide residues in human milk samples and exposure of infants to the pesticides was evaluated by calculating the estimated daily intake and compared with the provisional tolerable daily intake of the pesticides under study. The results indicated that, from the eight organochlorine pesticides analyzed in 447 breast milk samples at three sampling times, DDT and its metabolites were detected. p,p'-DDE and p,p'-DDT were detected in all (100%) of the breast milk samples while, p,p-DDD, and o,p-DDT were detected in 53.9%, and 42.7%, respectively. The mean concentration of total DDT at three time points(baseline, midline and endline) were 2.25, 1.68 and 1.32 µg/g milk fat, respectively. The mean concentration of total DDT from the three districts was 1.85 µg/g milk fat which is above the maximum residue limit (MRL = 0.02 µg/g milk fat set by FAO/WHO). The mean ratio of DDT/DDE for the three areas was calculated less than five (< 5) indicates historical DDT use in the study area. The estimated daily intake of infants at the first month of breastfeeding was 11.24 µg/kg-BW/day, above the provisional tolerable daily intake (PTDI) for total DDT set by FAO/WHO, which is 10 µg/kg body weight. An intake of OCPs is a big concern for infants' health in Ethiopia and countries with a similar condition, particularly at the first month of lactation. Strict regulations of the health-threatening pesticide by the regulatory body (Environment, Forest and Climate Change Commission) at the country and regional levels is advocated.

Exposure to organochlorine pesticides as a predictor to breast cancer: A case-control study among Ethiopian women.

Breast cancer (BC) is becoming one of the most prevalent non-infectious disease in low and middle income countries. The steady rise of BC incidence may be related to the different risk factors. Among many, rampant presence of environmental pollutants might be one of the risk factors. Therefore, the aim of this study is to investigate exposure to organochlorine pesticides as a risk factor to breast cancer. A case-control study design was employed among breast cancer patients and non-breast cancer individuals (controls). Blood samples were collected from 100 study participants (50 cases and 50 controls) followed by serum separation, extraction and cleanup using standard analytical procdures. The findings revealed that ten organochlorine pesticides were detected in the serum of the study participants. From the detected organochlorine pesticides, heptachlor was observed at higher concentration for breast cancer patients (6.90±4.37 µg/L) and controls (9.15±3.84 µg/L). Mean serum level of p,p'-DDE, p,p'-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in the serum of breast cancer patients than the controls. From the studied pesticides, p,p'-DDT and gamma-chlordane are significant predictors for BC, while, others are equivocal. A unit increment of the concentration of p,p'-DDT (AOR; 2.03, 95% CI: 1.041-3.969) increased the odds of developing breast cancer by two, while for gamma-chlordane (AOR;3.12, 95% CI; 1.186-8.203) by three. Our study results suggesting that, organochlorines are a risk factors for breast cancer in Ethiopia. Decreasing exposure to such organochlorines might have a significant public health relevance in reducing non-communicable chronic illnesses. Besides, continues monitoring of persistent organic pollutants using body biomarkers is important for disease prevention and device mitigation measures.

Risk Assessment of Organochlorine Pesticide Residue in Phaseolus vulgaris Purchased in Igbara-oke, Ondo State, Nigeria.

<b>Background and Objective:</b> Preservation of agricultural products remains a hallmark of all farmers as a result, both pesticides and herbicides are being applied during planting and after harvesting with the sole aim of maximizing profits. Research had shown the various degree of toxicity of organochlorine pesticides residues, the objective of the research was to identify the organochlorine pesticide residues, analyze their risk assessment vis-a-vis, Hazard Index (HI), Estimate Dietary Intake (EDI), Target Hazard Quotient (THQ) and compare the results with Acceptable Dietary Intake (ADI), Reference dose standard (Rfd) and Maximum Residue Limit (MRL) and characterized the identified organochlorine pesticides residue for their toxicological properties. <b>Materials and Methods:</b> <i>Phaseolus vulgaris</i> were purchased in a local market in Igbara -Oke, Ondo state Nigeria, the sample was powdered using a grinder (Sumeet CM/L 2128945) and solid phase extraction techniques were employed, the extract was subjected to fractionation into two fractions of aliphatic hydrocarbons and the pesticides. The pesticide extract was subjected to characterization using gas chromatography-mass spectrophotometer. <b>Results:</b> Total 4 organochlorine pesticide residues were identified and the contaminant rates (mg kg¹) were less than 1. Furthermore, EDI values were lower than the ADI, MRL, also, the THQ values were less than 1, an indication that the <i>Phaseolus vulgaris</i> was safe for consumption. <b>Conclusion:</b> The research had shown no toxicity of the <i>Phaseolus vulgaris</i> purchased from the local market and it shows compliance by the local farmers on the application of pesticides to the food crop by obeying the recommended dose.

Pesticide exposure and related health problems among farmworkers' children: a case-control study in southeast Iran.

Pesticides are potentially hazardous chemicals that can cause injury to human health and the environment. The purpose of this study was to evaluate organophosphate pesticides (OPPs) and organochlorine pesticides (OCPs) exposure in farmworkers' children aged 6 to 11 years in Jiroft city in southeastern Iran. One hundred twenty farmworkers' children as case and 53 non-farmworkers' children aged 6 to 11 years as control were selected and the serum levels of OCPs were measured by using gas chromatography in all participants. In addition, erythrocyte acetylcholinesterase (AChE) and arylesterase activity of paraoxonase-1 (PON-1) were measured to evaluate OPPs effects. Catalase (CAT), superoxide dismutase3 (SOD3), glutathione peroxidase (GPx3) activities, and the levels of serum malondialdehyde (MDA), total antioxidant capacity (TAC), nitric oxide (NO), and protein carbonyl (PC) were measured to investigate OCPs and OPPs effects on oxidative stress (OS). The serum levels of beta-HCH, 4,4 DDE, and 4,4 DDT in the case group were significantly higher than the control group. In addition, in the case group, AChE, PON-1, CAT, SOD3, and GPx3 activities and the levels TAC were significantly lower, while MDA, PC, and NO levels were significantly higher than the control group. OCPs as illegal pesticides are present in southeast Iran and children are exposed to OCPs and OPPs in the studied area. In addition, higher serum levels of pesticides may be a major contributor in OS development, as a cause of many diseases.

Pesticide exposure and gender discrepancy in breast cancer.

OBJECTIVE: It is biologically plausible that occupational and environmental pesticide exposure may contribute to breast cancer risk. Persistent chemical compounds, such as pesticides, tend to be lipophilic and are detected in human breast milk and adipose tissue. Therefore, the present systematic review aims to clarify the gender difference in breast cancer concerning pesticide exposure. MATERIALS AND METHODS: A total of 70 studies satisfied the inclusion criteria and were included in the systematic review. RESULTS: From the studies analyzed, it was observed that exposure to pesticides could be a risk factor for breast cancer in women, in particular in young women and in women who experienced menarche at a young age. In contrast, no association was found for breast cancer in men. Female breast cancer is correlated with estrogen receptor-negative tumor characteristics. Breast cancer in men was no correlated with pesticide exposure. CONCLUSIONS: Breast cancer in women has been linked to estrogen receptor positivity, but this positivity appears to be inversely related to fertility. The estrogen-like effects of organochlorine pesticides could be the cause of the observed gender differences.

Risk of genotoxic damage in schoolchildren exposed to organochloride pesticides.

This study identified and determined organochloride pesticide (OCs) concentrations in hair samples from children at two elementary schools: one exposed to fumigations in agricultural fields, the other unexposed. Three concentrations of OCs levels in the hair were compared (high, medium, low), and total nuclear abnormalities in buccal cells were determined: micronuclei (MNi), condensed chromatin, karyorrhexis, pyknosis, binucleate cells, karyolysis, lobed nuclei, and apoptosis. No significant differences were found for the presence of MNi between the schoolchildren from the exposed and unexposed schools, but the prevalence of OCs in both schools was over 50%, as well as the frequencies of MNi in the children were over 58%. Findings show a significant difference between the frequency of MNi in the total sample of schoolchildren (exposed school + unexposed school) in relation to the concentration of OCs detected in their hair. The children from exposed school that showed the higher concentrations of OCs in hair had higher levels of genotoxic damage in the buccal cells; compared against children with lower concentrations of OCs. The most frequent nuclear abnormalities in the exposed children were lobed nuclei (79.4%), binucleate cells (66.66%), apoptosis (65.07), and MNi (58.7%). We determined the prevalence ratio (PR) and prevalence odds ratio (POR) for the presence of MNi in buccal cells in relation to the OCs concentrations in the hair samples. Both ratios were high for MNi [PR 3.93, 95% confidence interval (CI) 1.97-7.84, p = 0.0003; and POR 7.97, 95% CI 2.62-24.28, p = 0.0003], indicating a 7.97 times greater risk that the exposed children will present > 0.2% of MNi when OCs concentrations exceed 0.447 µg/g. These indicators may be useful biomarkers of genotoxic damage in children exposed to persistent, highly-toxic compounds. Results suggest the potential risk to which those schoolchildren are exposed on a daily basis due to fumigations in nearby agricultural fields.

Co-exposure risks of pesticides residues and bacterial contamination in fresh fruits and vegetables under smallholder horticultural production systems in Tanzania.

This study was carried out to investigate the risks of simultaneous exposure to pesticide residues and bacteria contaminants in locally produced fresh vegetables and vegetables in Tanzania. A total of 613 samples were analyzed for pesticide residues, out of which 250 were also analyzed for bacterial contamination. Overall, 47.5% had pesticide residues, 74.2% exceeded Maximum Residue Levels (MRLs). Organophosphorus (95.2%), organochlorines (24.0%), pyrethroids (17.3%), and carbamates (9.2%) residues dominated. MRL values were mostly exceeded in tomatoes, onions, watermelons, cucumbers, Chinese cabbage, and sweet paper. Tetramethrin (0.0329-1.3733 mg/kg), pirimiphos-methyl (0.0003-1.4093 mg/kg), permethrin (0.0009-2.4537 mg/kg), endosulfan (beta) (0.0008-2.3416 mg/kg), carbaryl (0.0215-1.5068 mg/kg), profenofos (0.0176-2.1377 mg/kg), chlorpyrifos (0.0004-1.2549 mg/kg) and dieldrin (0.0011-0.5271 mg/kg) exceeded MRLs. The prevalence of bacteria contamination was high (63.2%). Enterobacter (55.6%) Pseudomonas aeruginosa (32.4%), E. coli (28.2%), Citrobacter (26.8%), Klebsiella oxytoca (14.8%), and Salmonella (7.7%) were isolated. Furthermore, 46.4% tested positive for both pesticide residues and bacterial contaminants. Vegetables from farms (60.7%) contained more dual contaminants than market-based vegetables (41.8%). This may have resulted from excessive pesticide use and unhygienic handling of fresh fruits and vegetables at production level. Binary logistic regression showed that fresh fruits and vegetables with pesticide residues were 2.231 times more likely to have bacteria contaminants (OR: 2.231; 95% CI: 0.501, 8.802). The contamination levels of pesticide residues and bacterial contaminants could be perceived as a serious problem as most fresh fruits and vegetables recorded values of pesticide residues far above the MRLs with pathogenic bacteria isolated in higher proportions. MRLs was higher in most vegetables consumed raw or semi-cooked such as watermelons, carrots, cucumber, tomatoes, onion and sweet paper. There is an urgent need to develop pesticide monitoring and surveillance systems at farmer level, educating farmers and promoting the use of greener pesticides to mitigate the health effects of pesticides and bacterial contaminants.

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus.

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

A Systematic Review on Organophosphate Pesticide and Type II Diabetes Mellitus.

Organophosphate (OP) pesticides are extremely poisonous and they affect the glucose breakdown in numerous and mechanism. There are higher evidence of stimulating diabetes mellitus through OP pesticides especially the type II diabetes. The upsurge in the level of glucose (hyperglycemia), and insulin resistance along with their related outcomes are discussed in this review. The data related to investigational and clinical techniques endorse a connection amid such molecular mechanism and compounds of OPs. Numerous studies conducted till March 2018 have reported OP' exposures and diabetes-related outcomes. The acute and chronic exposure in case of these insecticides and diabetesrelated outcomes are defined in this study. Initially, it was declared that OPs prompt to hyperglycemia. Then, a high association of glucose in blood beside insulin was found out. The affirmation from some clinical as well as investigational studies supported a connection amid exposure to OP and diabetes, yet in maximum number of instances, non-specific diabetes occurs.

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

The association between prenatal exposure to organochlorine compounds and neonatal thyroid hormone levels: a systematic review.

In this systematic review, the association between prenatal exposure to organochlorine pesticides (OCPs) and neonatal thyroid hormone levels was studied. A systematic search of scientific literature was performed from the PubMed, SCOPUS and ISI web of science electronic bibliographic databases. The search strategy for the review was [(organochlorine OR "organochlorine pesticides" OR "organochlorine pollutants" OR "organochlorine pollutant") AND ("thyroid hormone" OR triiodothyronine OR Thyroxine OR "fetal thyroid function" OR "thyroid function" OR "Thyroid Stimulating Hormone" AND "prenatal" AND "maternal exposure")] in English sources. In this review, 305 papers (PubMed: 30; Scopus: 29; ISI: 246) were identified through an electronic database search. Twenty-seven articles were assessed for eligibility, from which 16 qualified articles were selected for the final evaluation. The most common OCP metabolites which were evaluated in order were hexachlorobenzene (HCB) (13 studies), pp-dichlorodiphenyldichloroethylene (pp-DDE) (13 studies), hexachlorocyclohexane (HCH) (10 studies) and dichlorodiphenyltrichlorethane (DDT) (eight studies). A review of the documents related to the association of prenatal exposure of OCPs with fetal or neonatal thyroid function tests provides us with heterogeneous data in this field. Factors such as differences in the studied populations and their area, ethnic and genetic background, time and rate of exposure, possible interaction of other thyroid-disrupting environmental factors and dietary intake of micronutrients such as iodine and/or selenium are considered the main limitations for making an accurate conclusion. For some OCPs including DDT, DDE, HCH and HCB, there are supporting evidences, and it is suggested that their exposure could potentially alter the fetal thyroid function and consequently impair the neurodevelopment process of the infants.

Concentrations of and risks posed by short-chain and medium-chain chlorinated paraffins in soil at a chemical industrial park on the southeast coast of China.

The concentrations, spatial distributions, and sources of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in soil at a chemical industrial park were determined. The samples were analyzed by two-dimensional gas chromatography coupled with electron capture-negative ion mass spectrometry. The risks posed by SCCPs and MCCPs to soil biota were assessed. The SCCP and MCCP concentrations were 37.5-995.7 and 15.1-739.6 ng/g dry weight, respectively, and the chlorine contents were 60.5%-63.0% and 56.7%-58.3%, respectively. The CP concentrations in soil were at medium levels relative to concentrations at other areas. The median CP concentration in soil from the sewage treatment plant was higher than the median concentration in road soil, and this was attributed to wastewater being treated centrally. No significant correlations were found between the total organic carbon content and CP concentrations (p > 0.05), so the total organic carbon content did not strongly affect the CP concentrations in the study area. Hierarchical cluster analysis divided the soil samples into three groups. C10Cl6-7, C11Cl7-8, and C14Cl7-9 were the main congeners in most soil samples. Principal component analysis and correlation analysis indicated that the relative abundances of MCCP and SCCP were correlated and that the SCCPs may have been derived from the CP-42 and CP-52 commercial products. A preliminary risk assessment indicated that CPs in soil at the industrial park do not pose clear risks to the environmental organisms.

Investigating the risk of breast cancer among women exposed to chemicals: a nested case-control study using improved exposure estimates.

PURPOSE: The aim of this study was to examine if exposures to chemicals at the workplace were associated with an increased risk of postmenopausal breast cancer, using improved exposure estimates. METHODS: The design is a case-control study, nested within a cohort of women from the Malmö Diet and Cancer Study. The study comprised 2400 women, 731 cases and 1669 matched controls, born 1923-1950 and living in Malmö, Sweden between 1991 and 1996. An occupational hygienist reclassified the probability for exposure given by a job-exposure matrix, using individual data on work tasks. First-time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry. RESULTS: Women exposed to chemicals in their occupational environment had a statistically significantly increased risk (OR 1.59, 95% CI 1.11-2.29) of breast cancer, and the risk correlated positively with duration of exposure but not with exposure intensity. Women exposed to chlorinated hydrocarbon solvents for more than 10 years had a significant higher risk of breast cancer (OR 3.06, 95% CI 1.18-7.96) as well as women exposed to oil mist for more than 10 years (OR 3.08, 95% CI 1.12-8.49). CONCLUSIONS: This study gives some support to the hypothesis that exposure to organic solvents as well as oil mist is associated with increased risk of breast cancer.

Exposure to polychlorinated biphenyls and organochlorine pesticides and risk of dementia, Alzheimer's disease and cognitive decline in an older population: a prospective analysis from the Canadian Study of Health and Aging.

BACKGROUND: Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is suspected to have adverse cognitive effects in older populations. OBJECTIVE: To assess whether plasma concentrations of PCBs and OC pesticides are associated with the risk of cognitive decline, Alzheimer's disease (AD) and of all-cause dementia in the Canadian older population. METHODS: Analyses were based on data from the Canadian Study of Health and Aging, a 3-phase, 10-year population-based study of individuals aged 65+ years. Analyses included 669 clinically assessed subjects, of which 156 developed dementia including 108 incident cases of AD. Subjects were screened at each phase with the 100-point Modified Mini-Mental State Examination (3MS), a measurement of global cognitive function. Statistical analyses included Cox proportional hazards model when the outcome was dementia or AD, and a repeated-measure mixed model when the outcome was the 3MS score. RESULTS: No association of PCB and OC pesticides with the risk of dementia and AD was observed. Elevated concentrations of PCB congeners nos 118, 153, 156, 163, and OC pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) were significantly associated with cognitive decline as assessed with the 3MS. A posteriori analyses suggested that only p,p'-DDE was significantly related to a higher cognitive decline in time based on the 3MS among incident cases of dementia compared to subjects remaining nondemented. CONCLUSION: PCB and OC pesticide plasma concentrations were not related to the incident diagnosis of neither dementia, nor AD. Using the 3MS scores as the outcome, higher concentrations of four PCB congeners and two OC pesticides were associated with lower cognitive performances in subjects. The association of p,p'-DDE with cognitive decline in time in incident cases of dementia merits further investigation.

Are the civilization diseases the result of organohalogen environmental pollution?

The notion of 'civilization diseases' is used to describe certain ailments whose aetiology is difficult to explain based on the knowledge about the functioning of the body and its metabolism. Only studies at the cellular level, on biochemical changes shed light on the causes of some diseases described as civilization diseases (cancers, cardiovascular and respiratory diseases, obesity, psychomotor disorders in children and an increase in the frequency of malformations). The factors whose incontestable influence on the increase in the frequency of occurrence of various 'civilization diseases' has been proved are persistent organic pollutants, among others belonging to the group of organohalogen compounds. Among organohalogen pollutants one needs to distinguish organochlorine compounds, which have been used as pesticides, and pollution emitted by various industries such as dioxins and furans, polychlorinated biphenyls, and polybrominated organic compounds used as flame retardants and perfluoroalkylated substances, which are characterized by high chemical and thermal stability as well as high surface activity due to which they may be widely used as oleophobic and hydrophobic factors.

Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month.

BACKGROUND: Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. RESULTS: PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (> 80th percentile) vs. "low" (< 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (- 24% [95% CI - 35% to - 14%] relative to the mean), and PCB-209 with less acetic acid (- 15% [95% CI - 29% to - 0.4%]). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively. CONCLUSIONS: Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health.

Effects of cross-fostering and developmental exposure to mixtures of environmental contaminants on hepatic gene expression in prepubertal 21 days old and adult male Sprague-Dawley rats.

The notion that adverse health effects produced by exposure to environmental contaminants (EC) may be modulated by the presence of non-chemical stressors is gaining attention. Previously, our lab demonstrated that cross-fostering (adoption of a litter at birth) acted as a non-chemical stressor that amplified the influence of developmental exposure to EC on the glucocorticoid stress-response in adult rats. Using liver from the same rats, the aim of the current study was to investigate whether cross-fostering might also modulate EC-induced alterations in hepatic gene expression profiles. During pregnancy and nursing, Sprague-Dawley dams were fed cookies laced with corn oil (control, C) or a chemical mixture (M) composed of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP), and methylmercury (MeHg), at 1 mg/kg/day. This mixture simulated the contaminant profile reported in maternal human blood. At birth, some control and M treated litters were cross-fostered to form two additional groups with different biological/nursing mothers (CC and MM). The hepatic transcriptome was analyzed by DNA microarray in male offspring at postnatal days 21 and 78-86. Mixture exposure altered the expression of detoxification and energy metabolism genes in both age groups, but with different sets of genes affected at day 21 and 78-86. Cross-fostering modulated the effects of M on gene expression pattern (MM vs M), as well as expression of energy metabolism genes between control groups (CC vs C). In conclusion, while describing short and long-term effects of developmental exposure to EC on hepatic transcriptomes, these cross-fostering results further support the consideration of non-chemical stressors in EC risk assessments.