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Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 μg/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 μg/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 μg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available.

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 mug/l. THM exposure through ingestion was 23.7 mug/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.

Trihalomethanes (THM) and haloacetic acids (HAA) are the most frequent chlorination by-products (CBP) in finished drinking waters. Traditionally, THM have been used as surrogates for CBP although the quantitative association between THM and other CBP is not well established. This problem is addressed in the present study from the analysis of THM and HAA in drinking water samples from four Spanish regions, representing areas with very different CBP composition, e.g. between 86 and 8.0 microg/l of THM and 50-3.0 microg/l of HAA. The resulting dataset exhibit a statistically significant correlation between total THM and HAA (Pearson's correlation coefficient, r(p)=0.815,p<0.0005). Furthermore, specific HAA are highly correlated with specific THM or their combinations. Accordingly, multivariate linear regression analysis of the concentrations observed show that the levels in total and specific HAA can be predicted from the THM content. These results are relevant for epidemiological studies on health effects from CBP exposure since they usually involve comparison of populations consuming waters of very distinct quality.

Objectives: Drinking water chlorination generates trihalomethanes and other by-products with mutagenic and carcinogenic properties in animal experiments. Epidemiological studies have associated trihalomethanes to an increased risk of bladder cancer. We evaluate trihalomethane levels in four Spanish areas and calculate the bladder cancer risk attributable to this exposure., Methods: Trihalomethanes have been analysed in 111 drinking water samples from four Spanish areas using gas chromatography. Water utilities were contacted and information on drinking water consumption in Spain has been collected. We reviewed the epidemiological studies that assess the association between bladder cancer risk and exposure to chlorination by-products. Attributable risk was calculated on the basis of these levels, mortality data per area and risk estimates obtained from the literature., Results: Mediterranean areas present the highest levels of trihalomethanes with 81, 80, 61 and 52 µg/l in Sabadell, Alicante, Barcelona and Manresa respectively. Lower levels are found in Tenerife and Asturias with 7 and 20 µg/l respectively. The bladder cancer attributable risk in high trihalomethane exposure areas may be, on average, around 20%., Conclusions: The trihalomethane levels found are high compared to those of other European Union countries. In the high exposure areas, drinking water chlorination may generate a considerable number of bladder cancer cases. These estimations have to be carefully interpreted and verified with more extensive studies.