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Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood., Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk., Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer., Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk., Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Swimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic., Objectives: We evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers., Methods: Non-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism., Results: Median level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, μg/L, respectively, and trichloramine in air was 472.6 μg/m 3 . Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, μg/m 3 , respectively. Creatinine-adjusted urinary TCAA increased by 3.1 μmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure., Conclusions: The unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions., Objectives: We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children., Methods: 154 pregnant women and 152 children from six European countries were enrolled in 2014-2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80., Results: All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40-0.59) to good (0.60-0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15-20 urines each would be necessary to obtain an ICC above 0.80., Conclusions: This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: In 2011, the International Agency for Research on Cancer classified radiofrequency (RF) electromagnetic fields (EMF) as possibly carcinogenic to humans (group 2B), although the epidemiological evidence for the association between occupational exposure to RF-EMF and cancer was judged to be inadequate, due in part to limitations in exposure assessment. This study examines the relation between occupational RF and intermediate frequency (IF) EMF exposure and brain tumor (glioma and meningioma) risk in the INTEROCC multinational population-based case-control study (with nearly 4000 cases and over 5000 controls), using a novel exposure assessment approach., Methods: Individual indices of cumulative exposure to RF and IF-EMF (overall and in specific exposure time windows) were assigned to study participants using a source-exposure matrix and detailed interview data on work with or nearby EMF sources. Conditional logistic regression was used to investigate associations with glioma and meningioma risk., Results: Overall, around 10% of study participants were exposed to RF while only 1% were exposed to IF-EMF. There was no clear evidence for a positive association between RF or IF-EMF and the brain tumors studied, with most results showing either no association or odds ratios (ORs) below 1.0. The largest adjusted ORs were obtained for cumulative exposure to RF magnetic fields (as A/m-years) in the highest exposed category (≥90th percentile) for the most recent exposure time window (1-4 years before the diagnosis or reference date) for both glioma, OR = 1.62 (95% confidence interval (CI): 0.86, 3.01) and meningioma (OR = 1.52, 95% CI: 0.65, 3.55)., Conclusion: Despite the improved exposure assessment approach used in this study, no clear associations were identified. However, the results obtained for recent exposure to RF electric and magnetic fields are suggestive of a potential role in brain tumor promotion/progression and should be further investigated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them., Objectives: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4-5years of age., Methods: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003-2008). Neuropsychological development was measured at 1year of age using the Bayley Scales of Infant Development and at 4-5years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (μg/day) and crude levels (μg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables., Results: The median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3μg/L, 9.4μg/L, 11.6μg/L, 10.5μg/L, 2.7μg/L, and 3.1μg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4-5years, with a decrease in -0.54 points (95%CI -1.03, -0.05) and -0.64 (95%CI -1.16, -0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1year did not persist at 4-5years., Conclusions: Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1year disappeared at 4-5years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4-5years, chance cannot be ruled out., (Copyright © 2017 Elsevier Ltd. All rights reserved.)