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Identifying Vulnerable Periods of Neurotoxicity to Triclosan Exposure in Children.

ABSTRACT: BACKGROUND:Exposure to triclosan, an endocrine disrupting chemical, may affect thyroid hormone homeostasis and adversely affect neurodevelopment. OBJECTIVE:Using a longitudinal pregnancy and birth cohort, we investigated associations between triclosan exposures during different time windows, and cognitive test scores at 8 y of age in 198 children from the HOME Study. METHODS:We quantified triclosan in urine samples from mother-child pairs up to nine times between the second trimester of gestation and 8 y of age. The Wechsler Intelligence Scale for Children-IV [i.e., Full-Scale Intelligence Quotient (IQ)] assessment was administered to HOME Study children at 8 y of age. We estimated covariate-adjusted triclosan-IQ associations at each visit. We also tested whether associations between triclosan concentrations and cognitive test scores varied among exposure at different time periods. RESULTS:Full-Scale IQ was not significantly associated with urinary triclosan concentrations during gestation or childhood but was significantly associated with a 10-fold increase in maternal urinary triclosan concentration at delivery [-4.5?points (95% CI: -7.0, -2.0)]. Perceptual Reasoning Index (PRI) scores were significantly decreased in association with urinary triclosan concentrations at delivery and at 2 y of age. Associations between repeated triclosan concentrations and cognitive test scores significantly varied among exposure at different time periods for Full-Scale IQ, PRI, Verbal Comprehension Index, and Working Memory (triclosan-visit interaction p?0.04). CONCLUSION:Urinary triclosan concentrations at delivery, but not during mid to late pregnancy and childhood, were associated with significantly lower children's cognitive test scores at 8 y of age in this cohort of U.S. children. https://doi.org/10.1289/EHP2777.

SUBMITTER: Jackson-Browne MS

PROVIDER: S-EPMC6072011 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Identifying Vulnerable Periods of Neurotoxicity to Triclosan Exposure in Children.

Jackson-Browne Medina S MS Papandonatos George D GD Chen Aimin A Calafat Antonia M AM Yolton Kimberly K Lanphear Bruce P BP Braun Joseph M JM

Environmental health perspectives 20180502 5

<h4>Background</h4>Exposure to triclosan, an endocrine disrupting chemical, may affect thyroid hormone homeostasis and adversely affect neurodevelopment.<h4>Objective</h4>Using a longitudinal pregnancy and birth cohort, we investigated associations between triclosan exposures during different time windows, and cognitive test scores at 8 y of age in 198 children from the HOME Study.<h4>Methods</h4>We quantified triclosan in urine samples from mother-child pairs up to nine times between the second ...[more]

PMID: 29727133

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Project description:BACKGROUND:Triclosan exposure may decrease circulating thyroxine levels or cause neuron apoptosis, which in turn may adversely affect neurodevelopment. However, few studies have examined the association of early life triclosan exposure with child behavior. OBJECTIVE:To quantify the association between early-life triclosan exposure and child behavior at age 8-years in 202 mother-child pairs from the HOME study (Cincinnati, OH; enrolled: 2003-2006). METHODS:We quantified urinary triclosan concentrations up to 3 times in mothers (16-weeks, 26-weeks, and delivery) and up to 6 times in children (1, 2, 3, 4, 5, and 8?years). Parents rated children's problem behaviors at age 8-years using the Behavioral Assessment System for Children-2 (BASC-2). Adjusting for covariates and accounting for exposure measurement error, we estimated changes in behavior problem scores per 10-fold increase in mean gestational and childhood triclosan concentrations. In addition, we estimated sex-specific associations. RESULTS:Child sex modified the association of gestational and childhood triclosan with several BASC-2 scales (sex?×?triclosan p-values?<?0.2). In boys, increasing gestational triclosan was associated with higher behavioral symptom index (?: 4.5; 95% CI: 1.0, 8.1), externalizing problems (?: 5.0; 95% CI: 1.2, 9.0), attention problem (?: 6.6; 95% CI: 2.4, 11), hyperactivity (?: 6.4; 95% CI: 2.1, 11), and somatization (?: 3.8; 95% CI: 0.3, 7.3) scores. In contrast, triclosan-BASC-2 associations in girls were generally null and not statistically significant. We observed similar patterns of associations between childhood triclosan and these same behavioral scores; however, their magnitude decreased substantially after adjusting for gestational triclosan and associations were not statistically significant. CONCLUSION:In this cohort, increasing gestational and childhood urinary triclosan concentrations were associated with higher behavior problem scores in 8-year old boys, but not girls.

Project description:ContextDiisocyanates have been associated with respiratory and dermal sensitization. Limited number of case reports, and a few case studies, media, and other references suggest potential neurotoxic effects from exposures to toluene diisocyanate (TDI), 1,6 hexamethylene diisocyanate (HDI), and methylene diisocyanate (MDI). However, a systematic review of the literature evaluating the causal association on humans does not exist to support this alleged association.ObjectiveTo perform systematic review examining the body of epidemiologic evidence and provide assessment of causal association based on principles of the Sir Austin Bradford Hill criteria or considerations for causal analysis.MethodsA comprehensive search of public databases for published abstracts, case reports, cross-sectional surveys, and cohort studies using key search terms was conducted. Additional searches included regulatory reviews, EU IUCLID and EU Risk Assessment databases, and unpublished reports in the International Isocyanate Institute database. An expert panel consisting of physicians, toxicologists, and an epidemiologist critically reviewed accepted papers, providing examination of epidemiologic evidence of each report. Finally, the Hill criteria for causation were applied to the summative analysis of identified reports to estimate probability of causal association.ResultsTwelve papers reporting exposed populations with a variety of neurological symptoms or findings suitable for analysis were identified, including eleven case or case series reports, and one cross-sectional study. Three papers reported on the same population. Each of the papers was limited by paucity of diisocyanate exposure estimates, the presence of confounding exposures to known or suspected neurotoxicants, a lack of objective biological measures of exposure or neurotoxic effects, and lack of relative strength of association measures. Additionally, reported health symptoms and syndromes lacked consistency or specificity. No plausible mechanism of toxicity was found. Application of a predictive mathematical model for determining probability of causal association for neurotoxicity was calculated to be 21%.ConclusionThere is insufficient evidence for a causal association of neurotoxic effects and diisocyanate exposure based on lack of evidence in all categories of the Hill criteria for causality except for temporal association of reported symptoms and alleged exposure. Future reports should attempt to address more rigorous exposure assessment and control for confounding exposures.

Project description:Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitising products. A number of studies have shown the presence of TCS in different human tissues such as blood, adipose tissue, the liver, brain as well as in breast milk and urine. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system and which play key roles in excitatory synaptic transmission. There is, however, no data on the involvement of NMDAR subunits in the apoptotic and neurotoxic effects of TCS. Our experiments are the first to show that TCS used at environmentally relevant concentrations evoked NMDA-dependent effects in neocortical neurons in primary cultures, as MK-801, an uncompetitive NMDA receptor antagonist, reduced the levels of TCS-induced ROS production as well as caspase-3 activity and LDH release. TCS caused a decrease in protein expression of all the studied NMDA receptor subunits (GluN1, GluN2A, GluN2B) that were measured at 3, 6 and 24 h post-treatment. However, at 48 h of the experiment, the level of the GluN1 subunit returned to the control level, and the levels of the other subunits showed a tendency to increase. In TCS-treated neocortical cells, protein profiles of NMDAR subunits measured up to 24 h were similar to mRNA expression of GluN1 and GluN2A, but not to GluN2B mRNA. In this study, cells transiently transfected with GluN1, GluN2A or GluN2B siRNA exhibited reduced levels of LDH release, which suggests the involvement of all of the studied NMDAR subunits in the neurotoxic action of TCS. According to our data, GluN1 and GluN2A were mainly responsible for neuronal cell death as evidenced by neutral red uptake, whereas GluN2A was involved in TCS-induced caspase-3-dependent apoptosis. We suggest that TCS-evoked apoptosis and neurotoxicity could be related to transient degradation of NMDAR subunits in mouse neurons. Furthermore, recycling of NMDAR subunits in response to TCS is possible. Because transfections with specific siRNA did not completely abolish the effects of TCS as compared to cells transfected with negative siRNA in this study, other NMDAR-independent mechanisms of TCS action are also possible.

Dataset Information

Identifying Vulnerable Periods of Neurotoxicity to Triclosan Exposure in Children.

Publications

Identifying Vulnerable Periods of Neurotoxicity to Triclosan Exposure in Children.

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