The relationship between water concentrations and individual uptake of chloroform: a simulation study.

Whitaker, Heather; Nieuwenhuijsen, Mark; Best, Nicola

doi:10.1289/ehp.5963

Cited by 81 publications

(39 citation statements)

References 31 publications

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“…Our simulations were based on a correlation of 0.62 between town mean and true maternal TTHM exposure. Although this relationship is typically unknown in observational epidemiologic studies, it is comparable to that observed in previous DBP studies (Whitaker et al, 2003b;King et al, 2004). Whitaker et al (2003b) and King et al (2004) used individual level water usage data to estimate DBP exposure during pregnancy and reported exposure misclassification rates in excess of 40% for town average trihalomethane classification.…”

Section: Discussionsupporting

confidence: 65%

“…Although this relationship is typically unknown in observational epidemiologic studies, it is comparable to that observed in previous DBP studies (Whitaker et al, 2003b;King et al, 2004). Whitaker et al (2003b) and King et al (2004) used individual level water usage data to estimate DBP exposure during pregnancy and reported exposure misclassification rates in excess of 40% for town average trihalomethane classification. The impact of this exposure misclassification on previously reported association is unknown, but additional research is needed to better understand the relative contribution of various sources of measurement error in epidemiologic studies.…”

Section: Discussionsupporting

confidence: 65%

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A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

Wright

Bateson²

2004

J Expo Sci Environ Epidemiol

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We conducted a sensitivity analysis of relative risk estimates using local area mean disinfection by-product exposures. We used Monte Carlo simulations to generate data representing 100 towns, each with 100 births (n ¼ 10,000). Each town was assigned a mean total trihalomethane (TTHM) exposure value (mean ¼ 45, SD ¼ 28) based on a variable number of sampling locations (range 2-10). True maternal TTHM exposure was randomly assigned from a lognormal distribution using that town's true mean value. We compared the effect of a 20 mg/l increase in TTHM exposure on the risk of small-forgestational age infancy using the true maternal exposure compared to various weighting measures of the town mean exposures. The exposure metrics included: (1) unweighted town mean, (2) town mean weighted by the inverse variance of the town mean, (3) town mean weighted by the inverse standard deviation of the town mean, (4) town mean weighted by 1À(standard deviation of sites per town/mean across all towns), and (5) a randomly selected value from one of the sites within the town of residence. To estimate the magnitude of misclassification bias from using the town mean concentrations, we compared the true exposure odds ratios (1.00, 1.20, 1.50, and 2.00) to the mean exposure odds ratios from the five exposure scenarios. Misclassification bias from the use of unweighted town mean exposures ranged from 19 to 39%, increasing in proportion to the size of the true effect estimates. Weighted town mean TTHM exposures were less biased than the unweighted estimates of maternal exposure, with bias ranging from 0 to 23%. The weighted town mean analyses showed that attenuation of the true effect of DBP exposure was diminished when town mean concentrations with large variability were downweighted. We observed a trade-off between bias and precision in the weighted exposure analyses, with the least biased effects estimates having the widest confidence intervals. Effect attenuation due to intrasystem variability was most evident in absolute and relative terms for larger odds ratios.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 65%

A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

Wright

Bateson²

2004

J Expo Sci Environ Epidemiol

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“…However, no data were available to account for these sources of measurement error in our study. In a simulation study, we showed that there is a moderate positive correlation between chloroform in drinking water and uptake of chloroform (Whitaker et al, 2003b).…”

Section: Discussionmentioning

confidence: 92%

Modelling exposure to disinfection by-products in drinking water for an epidemiological study of adverse birth outcomes

Whitaker

Best

Nieuwenhuijsen

et al. 2004

J Expo Sci Environ Epidemiol

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We are conducting an epidemiological study on the association between disinfection by-product concentrations in drinking water and adverse birth outcomes in the UK, using trihalomethane (THM) concentrations over defined water zones as an exposure index. Here we construct statistical models using sparse routinely collected THMs measurements to obtain quarterly estimates of mean THM concentrations for each water zone. We modelled the THM measurements using a Bayesian hierarchical mixture model, taking into account heterogeneity in THM concentrations between water originating from different source types, quarterly variation in THM concentrations and uncertainty in the true value of undetected and rounded measurements. Quarterly estimates of mean THM concentrations plus estimates of the water source type (ground, lowland surface or upland surface) were obtained for each water zone. THM concentration estimates were typically highest from July to September (third quarter), and varied considerably between water sources. Our exposure estimates were categorized into 'low', 'medium' and 'high' THM classes. Our modelled quarterly exposure estimates were compared to a simple alternative: annual means of the raw data for each water zone. In all, 15-25% of exposure estimates were classified differently. The modelled THM estimates led to slightly stronger and more precise estimates of association with risk of still birth and low birth weight than did the raw annual means. We conclude that our modelling approach enabled us to provide robust quarterly estimates of ecological exposure to THMs in a situation where the raw data were too sparse to base exposure assessment on empirical summaries alone.

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“…A modelling study indicated that swimming had a large impact on an individual's level of chloroform uptake, compared to bathing, showering, or drinking water. 11 The ingestion route likely dominates for non-volatile DBP (for example, haloacetic acids, MX). However, since the putative agent(s) for the increased cancer risk is unknown, the evaluation of different exposure pathways can provide clues for the identification of the relevant chemicals and possible mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

Assessment of lifetime exposure to trihalomethanes through different routes

Villanueva

2006

Occup Environ Med

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Objectives: To evaluate lifetime exposure to trihalomethanes (THM) through ingestion, inhalation, and dermal absorption in a hospital based case-control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. Methods: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person-years of exposure. Results: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mg/l. THM exposure through ingestion was 23.7 mg/day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5-10% were exposed through swimming in pools. Conclusion: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route.D isinfection by-products (DBP) have been associated with elevated risk of several types of cancer, with evidence most consistent for the urinary bladder. This is particularly true among studies that incorporated a detailed evaluation of exposure to trihalomethanes (THM, the most prevalent group of chlorination by-products) as an index of exposure to DBP. [1][2][3][4] Relative risks in these studies were generally below 2.0, and despite the consistency of the evidence, concerns remain about the validity of these findings, particularly regarding the evaluation of exposure.DBP constitute a complex mixture of hundreds of compounds with heterogeneous physical and chemical properties, different mutagenic and carcinogenic potential, and with temporal and spatial variability. 5 6 Different exposure pathways (ingestion, inhalation, dermal absorption) depend on the type of DBP and the exposure setting, such as drinking the water or beverage made up with water, showering, bathing, swimming in pools, and to a lesser extent other water related activities such as washing dishes, cooking, and washing children. [7][8][9][10] Recent studies show that inhalation ...

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The relationship between water concentrations and individual uptake of chloroform: a simulation study.

Cited by 81 publications

References 31 publications

A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

Modelling exposure to disinfection by-products in drinking water for an epidemiological study of adverse birth outcomes

Assessment of lifetime exposure to trihalomethanes through different routes

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