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Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay.

ABSTRACT: Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500×, 1,000×, or 2,000× of the U.S. Environmental Protection Agency's maximum contaminant levels (MCLs).Maternal water consumption was reduced at ? 1,000×; body weights were reduced at 2,000×. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000× on PND6 and at ? 1,000× on PND21. Postweaning F1 body weights were reduced at 2,000×, and water consumption was reduced at ? 500×. Males at 2,000× had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000× and 2,000×. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, P0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000×.A mixture of regulated DBPs at up to 2,000× the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ? 1,000× may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000× may have been secondary to reduced body weights.

SUBMITTER: Narotsky MG

PROVIDER: S-EPMC4455591 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay.

Narotsky Michael G MG Klinefelter Gary R GR Goldman Jerome M JM DeAngelo Anthony B AB Best Deborah S DS McDonald Anthony A Strader Lillian F LF Murr Ashley S AS Suarez Juan D JD George Michael H MH Hunter E Sidney ES Simmons Jane Ellen JE

Environmental health perspectives 20150219 6

<h4>Background</h4>Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.<h4>Objective</h4>We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.<h4>Methods</h4>Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (P ...[more]

PMID: 25695961

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Project description:BackgroundKnowledge about human exposure and health effects associated with non-routinely monitored disinfection by-products (DBPs) in drinking water is sparse.ObjectiveTo provide insights to estimate exposure to regulated and non-regulated DBPs in drinking water.MethodsWe collected tap water from homes (N = 42), bottled water (N = 10), filtered tap water with domestic activated carbon jars (N = 6) and reverse osmosis (N = 5), and urine (N = 39) samples of participants from Barcelona, Spain. We analyzed 11 haloacetic acids (HAAs), 4 trihalomethanes (THMs), 4 haloacetonitriles (HANs), 2 haloketones, chlorate, chlorite, and trichloronitromethane in water and HAAs in urine samples. Personal information on water intake and socio-demographics was ascertained in the study population (N = 39) through questionnaires. Statistical models were developed based on THMs as explanatory variables using multivariate linear regression and machine learning techniques to predict non-regulated DBPs.ResultsChlorate, THMs, HAAs, and HANs were quantified in 98-100% tap water samples with median concentration of 214, 42, 18, and 3.2 μg/L, respectively. Multivariate linear regression models had similar or higher goodness of fit (R2) compared to machine learning models. Multivariate linear models for dichloro-, trichloro-, and bromodichloroacetic acid, dichloroacetonitrile, bromochloroacetonitrile, dibromoacetonitrile, trichloropropnanone, and chlorite showed good predictive ability (R 2 = 0.8-0.9) as 80-90% of total variance could be explained by THM concentrations. Activated carbon filters reduced DBP concentrations to a variable extent (27-80%), and reverse osmosis reduced DBP concentrations ≥98%. Only chlorate was detected in bottled water samples (N = 3), with median = 13.0 µg/L. Creatinine-adjusted trichloroacetic acid was the most frequently detected HAA in urine samples (69.2%), and moderately correlated with estimated drinking water intake (r = 0.48).SignificanceFindings provide valuable insights for DBP exposure assessment in epidemiological studies. Validation of predictive models in a larger number of samples and replication in different settings is warranted.Impact statementOur study focused on assessing and describing the occurrence of several classes of DBPs in drinking water and developing exposure models of good predictive ability for non-regulated DBPs.

Project description:BackgroundDrinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive.ObjectiveWe conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns.MethodsWe included all births during 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and <5, 5-15, and >15μg TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.ResultsBased on 623,468 births and a prevalence of congenital malformation of ∼2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (OR=1.82; 95% CI: 1.07, 3.12), urinary system (OR=2.06; 95% CI: 1.53, 2.78), genitals (OR=1.77; 95% CI: 1.38, 2.26), and limbs (OR=1.34; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite.DiscussionTTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122.

Dataset Information

Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay.

Publications

Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay.

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