BBC Horizon programme on the effect of alcohol consumption : This recognition of the toxic effects of Alcohol might open eyes to the need for research into the toxic effects of Chlorine - the other regularly ingested toxin in the West

Yesterday a BBC Horizon programme looked at the effects of binge drinking on health where a 'binge' is a lot less than most people think: 6U in a day for a woman, 8U in a day for a man.

They presented evidence that high levels of alcohol causes
- inflammation of the gut (leading to bacterial toxins in the bloodstream - endotoxins)
- inflammation of the brain causing headache (largely due to breakdown product of alcohol acetaldehyde + shrinkage of an important area, the hippocampus
- inflammation of blood vessels so they become clogged up (the main cause of strokes and heart attacks)
- inflammation of the liver of course

The reason for the inflammation is the toxicity of alcohol on cells.

Perhaps the recognition that ingestion of alcohol causes inflammation throughout the body might lead to more research into whether ingestion and inhalation of chlorine could be just as damaging. They are both toxic to cells.

BBC Horizon : the next step ?

There needs to be an open debate on whether we should use an alternative to chlorine for domestic water supplies and swimming pools in the UK. I feel a programme like BBC's Horizon could offer a balanced discussion seeking the opinions from a wide range of experts such as : 1.Clinicians who have published studies looking at the effect of chlorine on health such as bowel/bladder cancer, asthma. 2.Toxicologist with a special interest in the effect of chlorine on human cells 3.Research pathologists with a special interest in environmental carcinogens. 4.Residents who have switched from Chlorination to Ozonation of domestic water supplies - have they noticed any changes to their health/ water quality. Do we have enough data yet to compare disease rates in areas with ozonation compared to chlorination? 5. A water company regarding the efficacy, cost, and difficulty of switching to ozone. 6. Epidemiologist with an interest in environmental carcinogens : It would be interesting to see a world map of asthma v chlorine use. Unfortunately there are many infectious causes of bowel and bladder cancer that might occur in un-chlorinated water eg.schistosomiasis in Africa which might give confusing results such as the study in India (see list of links) 7. Public health clinician : Are there any practical messages that should be delivered to the public ? Should we be boiling drinking water, or using water filters ? How effective are water filters ? 8. An expert on THM's and other carcinogenic compounds. Is the World Health Organization correct to give a safe concentration for chlorine in drinking water. Assuming levels just below the safe level, what volume of drinking water is considered 'safe' to consume on a daily basis. 9. Expert on bowel flora, and the cleanliness hypothesis with skewing to an allergic type of immune system with reduced exposure to bacteria. There also needs to be more research done, and the potential risks taken more seriously until answers are known. It will be important to deliver any messages in a way to prevent any panic. We do not want people to drink less water, and become dehydrated. However, one of the government's active health messages is to drink frequent glasses of water. Perhaps the type of water should added to the same public health campaign message. 10. Measurement of levels of Chlorine and THMs etc in drinking water in the UK , India etc. Does a hot climate eg.India, help protect from the adverse effects of chlorine by leading to more rapid evaporation, whilst requiring chlorination more to protect from infectious diseases. Do ordinary water filters remove THMs ?

Ozone is a cheap, safe, effective alternative to chlorine.

Apparently Severn Trent use Ozonation for some of their water supplies - it would be interesting to learn more about this but haven't received a reply regarding more information from Severn Trent. The Health Protection Agency pointed me towards contacting water companies such as Severn Trent. US environmental protection agency information. Information for residents where ozone is used in drinking water : Massachusetts, San Diego . From the above info : Ozone may not kill large cysts and some other large organisms, so these should be eliminated by filtration or other procedures prior to ozone treatment. Ozone treatment can produce harmful by-products in drinking water. For example, if bromide is present in the raw water, ozone reacts with it to form bromate, shown to cause cancer in rats. "e U.S. Environmental Protection Agency (EPA) has set a drinking water standard for bromate in water at 0.010 mg/L. The disinfection process does not occur beyond the treatment unit. "is contrasts with chlorination treatment where the residual chlorine remains in the water and continues the disinfection process for some time. Ozone has an active residual time measured in minutes, whereas the active residual time for chlorine is measured in hours. Info from commercial companies eg. Lenntech, McClain, Earth Safe Zone, EnvronOzone

Aging (Senescence) , Telomeres, Hayflick limit and Cancer risk

http://en.wikipedia.org/wiki/Replicative_senescence The Hayflick limit[Note 1] (or Hayflick phenomenon) is the number of times a normal human cell population will divide until cell division stops. Leonard Hayflick demonstrated that a population of normal human fetal cells in a cell culture will divide between 40 and 60 times. Telomeres associated with each cell's DNA will get slightly shorter with each new cell division until they shorten to a critical length and can no longer divide, entering a senescence phase. Postulation : Cancer cells must all have a way of exceeding the Hayflick limit. Many will produce an enzyme called telomerase to allow lengthening of telomeric DNA. In an aging cell population there may be a high proportion of cells already capable to producing telomerase as a way of allowing a tissue to produce new cells. Logical deduction : Any substance such as chlorine, which kills human cells, will cause aging of an exposed tissue by causing increased cell division.

Carcinogenicity

Every time a cell is killed and others have to replicate to replace it, there is a chance of a genetic mistake leading to cancer. In this respect you could say that any substance which kills large numbers of human cells is a carcinogen. Chlorine forms THM compounds when it reacts with organic substances which appear to be particularly carcinogenic.

Where does chlorine go when you drink it ?

Like any gas, chlorine will be less soluble in water as the water warms up in your stomach, so some chlorine gas will be released. Chlorine kills bacteria rapidly, and so we can expect chlorine to kill commensal bacteria in our gut which help keep our bowel healthy. The cells lining our stomach and bowel will also be attacked by chlorine and there is no reason to expect them to be more immune to its effects than bacteria. It is possible that some chlorine gas might be passed out as flatus, however those with long bowel transit times will have bowel mucosa exposed to chlorine for longer periods. We know that individual with long bowel transit times have an increased risk of bowel cancer. I have not been able to find out whether chlorine could be absorbed into the bloodstream, nor whether this might have any detrimental effect on the lining of blood vessels. I believe this is worth some research as atherosclerosis of arteries is the main cause of heart attacks and strokes.

I can smell chlorine ?

I can frequently smell chlorine when I allow water to run out of our domestic tap, or shower. Information from wikipedia : Chlorine is detectable with measuring devices in concentrations of as low as 0.2 parts per million (ppm), and by smell at 3 ppm. Coughing and vomiting may occur at 30 ppm and lung damage at 60 ppm. Q.Could inhaled chlorine be a major cause of asthma (inflamed airways) and cause of aggravations by increasing pre-existing inflammation?

Heavier than air.

Because it is heavier than air, it tends to accumulate at the bottom of poorly ventilated spaces. http://en.wikipedia.org/wiki/Chlorine Q. Does this mean the concentration of chlorine gas will be at highest levels immediately above the surface of swimming pool water, and be highest in swimming pools with poor ventilation?

A compendium of causative agents of occupational asthma.

Med Toxicol. 2013 May 24;8(1):15. doi: 10.1186/1745-6673-8-15. A compendium of causative agents of occupational asthma. Baur X. SourceInstitute for Occupational Medicine, Charité University Medicine Berlin and EOM Society, Berlin, Germany. xaver.baur@charite.de. Abstract OBJECTIVE: The objective is to provide an evidence-based compendium of allergenic and irritant agents that are known to cause occupational asthma in order to improve diagnostics and disease management. METHODS: Two previously published reviews from our group utilized database searches to identify studies which were then rated according to the Scottish Intercollegiate Guideline Network (SIGN) grading system. The evidence level for each causative agent or worksite was graded using the Royal College of General Practitioners (RCGP) three-star system. RESULTS: Approximately 3,000 relevant papers were identified, which covered 372 different causes of allergic and 184 different causes of irritant occupational asthma. The highest level achieved using the SIGN grading system was 2++, indicating a high quality study with a very low risk of confounding or bias and a high probability of a causal relationship. Using the modified RCGP three-star grading system, the strongest evidence of association with an individual agent or worksite ('***') was found for exposure to laboratory animals. Associations with moderate evidence level ('**') were obtained for a) the allergenic agents or worksites: alpha-amylase from Aspergillus oryzae, various enzymes from Bacillus subtilis, papain, bakeries, western red cedar, latex, psyllium, storage mites, rat, carmine, egg proteins, Atlantic salmon, fishmeal, Norway lobster, prawn, snow crab, seafood, trout and turbot, reactive dyes, b) the irritant agents or worksites: benzene-1,2,4-tricarboxylic acid, 1,2- anhydride [trimellitic anhydride], chlorine, cobalt, cement, environmental tobacco smoke, grain, welding fumes, construction work, swine confinement, World Trade Center disaster 2001, and c) agents or worksites causing allergic as well as irritant occupational asthma, included farming, poultry confinement, various isocyanates and platinum salts. A low evidence level (RCGP) was obtained for 84 agents or worksites (42 from each group), providing a total of 141 conditions with a low, moderate or strong evidence level. CONCLUSION: This work comprises the largest compendium and evaluation of agents and worksites causing allergic or irritant occupational asthma from the literature assessed in an evidence-based manner.

Is there a potential link between indoor chlorinated pool environment and airway remodeling/inflammation in swimmers?

Expert Rev Respir Med. 2012 Nov;6(5):469-71. doi: 10.1586/ers.12.51. Is there a potential link between indoor chlorinated pool environment and airway remodeling/inflammation in swimmers? Bougault V, Boulet LP.

Occurrence and formation of chloro- and bromo-benzoquinones during drinking water disinfection.

Water Res. 2012 Sep 15;46(14):4351-60. doi: 10.1016/j.watres.2012.05.032. Epub 2012 Jun 2. Occurrence and formation of chloro- and bromo-benzoquinones during drinking water disinfection. Zhao Y, Anichina J, Lu X, Bull RJ, Krasner SW, Hrudey SE, Li XF. SourceDivision of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. Abstract Consumption of chlorinated drinking water has shown somewhat consistent association with increased risk of bladder cancer in a series of epidemiological studies, but plausible causative agents have not been identified. Halobenzoquinones (HBQs) have been recently predicted as putative disinfection byproducts (DBPs) that might be of toxicological relevance. This study reports the occurrence frequencies and concentrations of HBQs in plant effluents from nine drinking water treatment plants in the USA and Canada, where four common disinfection methods, chlorination, chloramination, chlorination with chloramination, and ozonation with chloramination, are used. In total, 16 water samples were collected and analyzed for eight HBQs: 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DC-3-MBQ), 2,3,6-trichloro-1,4-benzoquinone (2,3,6-TriCBQ), 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), 2,3-dibromo-5,6-dimethyl-1,4-benzoquinone (2,3-DB-5,6-DM-BQ), tetrabromo-1,4-benzoquinone (TetraB-1,4-BQ), and tetrabromo-1,2-benzoquinone (TetraB-1,2-BQ). Of these, 2,6-DCBQ, 2,6-DBBQ, 2,6-DC-3-MBQ and 2,3,6-TriCBQ were detected in 16, 11, 6, and 3 of the 16 samples with the method detection limit (DL) of 1.0, 0.5, 0.9 and 1.5 ng/L, respectively, using a solid phase extraction and high performance liquid chromatography-tandem mass spectrometry method. The concentrations were in the ranges of 4.5-274.5 ng/L for 2,6-DCBQ, below DL to 37.9 ng/L for 2,6-DBBQ, below DL to 6.5 ng/L for 2,6-DC-3-MBQ, and below DL to 9.1 ng/L for 2,3,6-TriCBQ. These authentic samples show DCBQ and DBBQ as the most abundant and frequently detectable HBQs. In addition, laboratory controlled experiments were performed to examine the formation of HBQs and their subsequent stability toward hydrolysis when the disinfectants, chlorine, chloramine, or ozone followed by chloramines, reacted with phenol (a known precursor) under various conditions. The controlled reactions demonstrate that chlorination produces the highest amounts of DCBQ, while pre-ozonation increases the formation of DBBQ in the presence of bromide. At pH < 6.8, 2,6-DCBQ was observed to be stable, but it was easily hydrolyzed to form mostly 3-hydroxyl-2,6-DCBQ at pH 7.6 in drinking water.

DrsNet expert panel response regarding the potential link between chlorine and bowel cancer risk : Group 3 'Not classifiable as to its carcinogenicity to humans'.

Question sent to Cancer Research UK and the expert panel + Response. questionsfromtheaudience@doctors.org.uk Question : Could a simple health message reduce the incidence of bowel cancer ? Until chlorine in tap water is proven NOT to increase the risk of bowel cancer, should the government advise the public to either boil, or leave their tap water to stand overnight, to allow evaporation of chlorine before consumption. At least one study has suggested a link between consumption of chlorine in tap water and bowel cancer : http://www.ncbi.nlm.nih.gov/pubmed/10952098 Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):813-8. Case-control study of colon and rectal cancers and chlorination by-products in treated water. King WD, Marrett LD, Woolcott CG. 'Males exposed to an estimated THM level of 75 microg/liter for > or = 35 years had double the risk of those exposed for < 10 years (odds ratio, 2.10; 95% confidence interval, 1.21-3.66)' Chlorinated water and bowel cancer are both largely western phenomena providing an interesting epidemiological association. From a logical point of view, chlorine kills bacteria very effectively, and probably many mucosal cells in the gut as it comes out of solution as tap water warms up inside our gut. These dead mucosal cells need to be replaced by other dividing cells. I've always felt that anything that increases mitotic rates increases the risk of cancer. It would be interesting if chlorinated tap water was a major aggravating factor in inflammatory bowel disease, a condition already known to be associated with bowel cancer. Of course should a link be proven, then alternatives such as ozonation of tap water might be a more permanent solution and reduce any risk from inhalation of chlorine from showers and swimming pools as well . It could be a significant aggravating factor in asthmatics, and may increase the risk of lung cancer via the mechanism described above. RESPONSE Professor Sir Mike Richards, 23/03/2012 12:16 This is an interesting hypothesis – and like so many hypotheses it is difficult to prove or disprove. The International Association for Research on Cancer (IARC) classifies agents into one of the following categories: Group 1 - carcinogenic to humans (107 agents) Group 2A - Probably carcinogenic to humans (61) Group 2B - possibly carcinogenic to humans (269) Group 3 - Not classifiable as to its carcinogenicity to humans (508) Group 4 - Probably not carcinogenic to humans (1) Chlorinated drinking water is classified as Group 3. I am also very grateful to you for drawing my attention to the case control study from Ontario Canada undertaken between 1992 and 1994. I note that although higher exposure to Chlorinated water appeared to increase the risk of colon cancer in males, the same effect was not observed in females. No relationship was observed for rectal cancer. The authors themselves state that the results of the study should be interpreted with caution because they are only partially congruent with the limited amount of literature addressing this issue. Based on these findings I think it is very unlikely that any government would wish to give advice such as you have suggested, which at the very least would cause inconvenience. There are several other approaches to reducing the risk of colorectal cancer (e.g. related to lifestyle factors) for which there is strong evidence and for which the government does provide advice to the public.

Human health risk assessment from exposure to trihalomethanes in Canadian cities.Cancer incidents were estimated highest for Montreal (94/year) followed by Toronto (53/year)

Environ Int. 2010 Jul;36(5):453-60. doi: 10.1016/j.envint.2010.04.001. Human health risk assessment from exposure to trihalomethanes in Canadian cities. Chowdhury S, Hall K. SourceEcole supérieure d'aménagement du territoire, Université Laval, Québec City, QC, Canada G1V 0A6. Shakhawat.Chowdhury.1@ulaval.ca Retraction in Environ Int. 2012 Feb;39(1):1. Abstract Lifetime exposure to trihalomethanes (THMs) through ingestion, inhalation and dermal contacts may pose risks to human health. Current approaches may under predict THMs exposure by using THMs in cold water during showering and bathing. Warming of chlorinated water during showering may increase THMs formation through reactions between organics and residual chlorine, which can increase human health risks. In this study, THMs concentrations in shower water were estimated using THMs rate increase model. Using cold water THMs, exposure through ingestion was estimated, while THMs exposure during showering was estimated using THMs in warm water. Human health cancer risks and additional expenses for 20 most populated Canadian cities from exposure to THMs were estimated. Inhalation and dermal contact during showering contributed 30% to 50% of total cancer risks, while risks from inhalation and dermal contacts were comparable for all cities. Overall cancer risks were estimated between 7.2 x 10(-6) and 6.4 x 10(-5) for these cities. Cancer incidents were estimated highest for Montreal (94/year) followed by Toronto (53/year), which may require additional medical expenses of 18.8 and 10.7 million dollars/year for Montreal and Toronto respectively. Cancer risks from exposure to THMs can be controlled by reducing THMs in water supply and varying shower stall volume, shower duration and air exchange rate in shower stall.

Health effects of disinfection by-products in chlorinated swimming pools.

http://www.ncbi.nlm.nih.gov/pubmed/21885333 Int J Hyg Environ Health. 2011 Nov;214(6):461-9. doi: 10.1016/j.ijheh.2011.07.012. Epub 2011 Sep 1. Health effects of disinfection by-products in chlorinated swimming pools. Florentin A, Hautemanière A, Hartemann P. SourceDESP, Nancy Université - Faculté de Médecine de Nancy, 9 Avenue de la forêt de Haye BP 184, 54 505 Vandœuvre-lès-Nancy Cedex, France. arnaud.florentin@medecine.uhp-nancy.fr Abstract Increased attendance at swimming pools is correlated with higher input of organic and minerals pollutants introduced by swimmers in the swimming pool water. In most swimming pools, microbiological control is performed by disinfection with the addition of chlorine. Chlorine is now well-known to lead to the formation of many disinfection by-products (DBPs) including trihalomethanes and chloramines. The hypothesis of a link between the presence of eye and skin irritation syndromes in swimmers and contact with swimming pool water treated with chlorine was initially proposed by Mood (1953). During recent decades many epidemiological studies have described the importance of DBPs generated with natural or imported organic matter present in water. Many of these DBPs are suspected to be toxic or even carcinogenic. Trihalomethanes and haloacetic acid families are the most studied but others DBPs, like chloral hydrate, haloacetonitriles, N-nitrosodimethylamine and the bromate ion, are emerging compounds of interest. Epidemiological data about the risk of cancer are still controversial. However, numerous publications highlight a toxic risk especially the risk of allergy and respiratory symptoms for babies and elite swimmers. The few publications dedicated to risk assessment do not suggest increased risk, other than for elite swimmers. These publications are likely to underestimate the risk associated with DBPs because of the lack of data in the literature precludes the calculation of risk associated with certain compounds or certain pathways. Thus for regulations, the need to take into account the risks associated with disinfection by-products is now important without forgetting the need of the control of microbiological hazards in swimming pools.

New onset asthma 11 times more common amongst regular compared to infrequent swimmers.

http://www.ncbi.nlm.nih.gov/pubmed/21257346 J Sci Med Sport. 2011 May;14(3):184-9. doi: 10.1016/j.jsams.2010.12.006. Epub 2011 Jan 22. Attendance at chlorinated indoor pools and risk of asthma in adult recreational swimmers. Ferrari M, Schenk K, Mantovani W, Papadopoulou C, Posenato C, Ferrari P, Poli A, Tardivo S. SourceDepartment of Medicine, School of Sports Medicine, University of Verona, Italy. Abstract To study a potential correlation between attendance at chlorinated indoor pools and the onset of asthma in adult leisure swimmers. 1136 adult swimmers attending indoor pools in the city of Verona completed a modified ECRHS questionnaire. The cumulative time spent in the pools was calculated on the basis of the mean frequency and duration of weekly swim activity for every year of attendance. The median value (320 h) was used to divide participants into 2 groups. Other questions concerned the family history of allergies, the medical diagnosis and the onset of asthma. The prevalence of respiratory symptoms in the study group was compared with that of a general population sample. New-onset asthma, first identified at least 12 months after the start of regular pool attendance, was more prevalent among swimmers characterized by a higher cumulative pool attendance (23/514, 4.5%) than in swimmers who were attending indoor pools less frequently (2/508, 0.4%; ratio 11.1, 95% CI 2.6-47.4). The statistical analysis revealed an independent association between the cumulative lifetime hours spent in indoor swimming pools and new onset asthma (relative risk 1.05, 95% CI 1.02-1.07). Respiratory symptoms were less frequent in the study population versus a general population sample (prevalence ratio 0.26-0.68). Attendance at chlorinated indoor pools may constitute a risk factor for developing asthma in leisure adult swimmers. Future research and efforts should aim at improving disinfection techniques, hygiene and ventilation in indoor swimming pools in order to provide an unobjectionable ambient for salubrious swim activities.

Spatial variations of human health risk associated with exposure to chlorination by-products occurring in drinking water.

J Environ Manage. 2011 Mar;92(3):892-901. doi: 10.1016/j.jenvman.2010.10.056. Epub 2010 Nov 19. Spatial variations of human health risk associated with exposure to chlorination by-products occurring in drinking water. Legay C, Rodriguez MJ, Sadiq R, Sérodes JB, Levallois P, Proulx F. SourceÉcole supérieure d'aménagement du territoire, Université Laval, Pavillon Antoine Savard, Québec City, QC., Canada. Abstract During disinfection, chlorine reacts with organic matter present in drinking water and forms various undesirable chlorinated by-products (CBPs). This paper describes a study of the spatial variability of human health risk (i.e., cancer effects) from CBP exposure through drinking water in a specific region. The region under study involves nine drinking water distribution systems divided into several zones based on their characteristics. The spatial distribution of cancer risk (CR) was estimated using two years of data (2006-2008) on various CBP species. In this analysis, trihalomethanes (THMs) and haloacetic acids (HAAs) served as surrogates for CBPs. Three possible routes of exposure (i.e., via ingestion, inhalation and dermal contact) were considered for each selected compound. The cancer risk assessment involved estimating a unit risk (R(T)) in each zone of the selected distribution systems. A probabilistic analysis based on Monte Carlo simulations was employed. Risk assessment results showed that cancer risk varied between systems, but also within individual systems. As a result, the population of the same region was not exposed to the same risk associated with CBPs in drinking water. Unacceptable levels (i.e., R(T) > 10(-4)) for the estimated CR were determined for several zones in the studied region. This study demonstrates that a spatial-based analysis performed to represent the spatial distribution of risk estimates can be helpful in identifying suitable risk management strategies. Suggestions for improving the risk analysis procedure are also presented.

Update on asthma and cleaners.

Curr Opin Allergy Clin Immunol. 2010 Apr;10(2):114-20. doi: 10.1097/ACI.0b013e32833733fe. Update on asthma and cleaners. Zock JP, Vizcaya D, Le Moual N. SourceCentre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. jpzock@creal.cat Abstract PURPOSE OF REVIEW: The present study summarizes the recent literature on the relation between cleaning exposures and respiratory health, in particular asthma, including reviews, epidemiological surveys, surveillance programmes and exposure studies. The authors also aimed to identify gaps in the current knowledge and to recommend future research on the topic. RECENT FINDINGS: A large international general population study showed an increased risk of new-onset asthma associated with cleaning work, with professional use of cleaning products and with domestic use of cleaning sprays. Three surveillance studies confirm the recognition of occupational asthma cases among cleaners and among others who use cleaning products at work. Six workforce-based studies show that respiratory symptoms are partly work-related, and are associated with certain specific exposures including sprays, chlorine bleach and other disinfectants. SUMMARY: Recent studies have strengthened the evidence of asthma and other adverse respiratory effects in cleaning workers. Similar effects are seen in other settings in which cleaning products are used such as healthcare professionals and homemakers. Both new-onset asthma and work-exacerbated asthma due to cleaning exposures may play a role. Exposure to cleaning sprays, chlorine bleach and other disinfectants may be particularly relevant. The predominant effect mechanisms remain largely unclear and may include both specific sensitization and irritant-related features.

DNA damage induction by two halogenated acetaldehydes, byproducts of water disinfection. High levels of DNA breaks.

Water Res. 2010 Apr;44(8):2638-46. doi: 10.1016/j.watres.2010.01.026. Epub 2010 Feb 10. DNA damage induction by two halogenated acetaldehydes, byproducts of water disinfection. Liviac D, Creus A, Marcos R. SourceGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain. Abstract Drinking water contains disinfection byproducts, generated by the interaction of chlorine (or other disinfecting chemicals) with organic matter, anthropogenic contaminants, and bromide/iodide naturally present in most source waters. One class of these chemicals is the halogenated acetaldehydes (HAs), identified in high quantities when ozone is used as primary or secondary disinfectant. In this study, an analysis of the genotoxic potential of two HAs, namely tribromoacetaldehyde (TBA) and chloral hydrate (CH) has been conducted in human cells (TK6 cultured cells and peripheral blood lymphocytes). The comet assay was used to 1) measure the induction of single and double-strand DNA breaks, 2) evaluate the capacity of inducing oxidative DNA damage, and 3) determine the DNA repair kinetics of the induced primary genetic damage. In addition, chromosome damage, as a measure of fixed damage, was evaluated by means of the micronucleus test. The results of the comet assay show that both compounds are clearly genotoxic, inducing high levels of DNA breaks, TBA being more effective than CH. According to the comet results, both HAs produce high levels of oxidized bases, and the induced DNA damage is rapidly repaired over time. Contrarily, the results obtained in the micronucleus test, which measures the capacity of genotoxic agents to induce clastogenic and aneugenic effects, are negative for the two HAs tested, either using TK6 cells or human peripheral blood lymphocytes. This would indicate that the primary damage induced by the two HAs is not fixed as chromosome damage, possibly due to an efficient repair or the death of damaged cells, which is an important point in terms of risk assessment of DBPs exposure.

Infant swimming in chlorinated pools and the risks of bronchiolitis, asthma and allergy. More than 4 times the risk in infants with no other risk factors.

Eur Respir J. 2010 Jul;36(1):41-7. doi: 10.1183/09031936.00118009. Epub 2010 Jan 14. Infant swimming in chlorinated pools and the risks of bronchiolitis, asthma and allergy. Voisin C, Sardella A, Marcucci F, Bernard A. SourceDept of Public Health, Catholic University of Louvain, Louvain, Belgium. Abstract Recent studies suggest that swimming in chlorinated pools during infancy may increase the risks of lower respiratory tract infection. The aim of the present study was to assess the influence of swimming in chlorinated pools on the risks of bronchiolitis and its late consequences. A total of 430 children (47% female; mean age 5.7 yrs) in 30 kindergartens were examined. Parents completed a questionnaire regarding the child's health history, swimming practice and potential confounders. Attendance at indoor or outdoor chlorinated pools ever before the age of 2 yrs was associated with an increased risk of bronchiolitis (OR 1.68; 95% CI 1.08-2.68; p = 0.03), which was exposure-dependent for both types of pool (p-value for trend <0.01). Associations persisted, and were even strengthened, by the exclusion of other risk factors. Among children with no parental antecedents of atopic disease or no day-care attendance, odds ratios for bronchiolitis amounted to 4.45 (1.82-10.9; p = 0.001) and 4.44 (1.88-10.5; p = 0.007) after >20 h spent in chlorinated pools during infancy. Infant swimmers who developed bronchiolitis also showed higher risks of asthma and respiratory allergies later in childhood. Swimming pool attendance during infancy is associated with a higher risk of bronchiolitis, with ensuing increased risks of asthma and allergic sensitisation.

Carcinogens in drinking water: the epidemiologic evidence.

Carcinogens in drinking water: the epidemiologic evidence. Cantor KP. Rev Environ Health. 2010 Jan-Mar;25(1):9-16. Review. No abstract available. PMID:20429153[PubMed - indexed for MEDLINE]

The epidemiology and possible mechanisms of disinfection by-products in drinking water.Major limitations in exposure assessment, small sample sizes and potential biases may account for the inconclusive and inconsistent results in epidemiological studies.

Philos Trans A Math Phys Eng Sci. 2009 Oct 13;367(1904):4043-76. doi: 10.1098/rsta.2009.0116. The epidemiology and possible mechanisms of disinfection by-products in drinking water. Nieuwenhuijsen MJ, Grellier J, Smith R, Iszatt N, Bennett J, Best N, Toledano M. SourceCentre for Research in Environmental Epidemiology (CREAL), Parc de Recerca Biomèdica de Barcelona-PRBB (Office 183.05), , C. Doctor Aiguader, 88, 08003 Barcelona, Spain. mnieuwenhuijsen@creal.cat Abstract This paper summarizes the epidemiological evidence for adverse health effects associated with disinfection by-products (DBPs) in drinking water and describes the potential mechanism of action. There appears to be good epidemiological evidence for a relationship between exposure to DBPs, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers including colorectal cancer is inconclusive and inconsistent. There appears to be some evidence for an association between exposure to DBPs, specifically THMs, and little for gestational age/intrauterine growth retardation and, to a lesser extent, pre-term delivery, but evidence for relationships with other outcomes such as low birth weight, stillbirth, congenital anomalies and semen quality is inconclusive and inconsistent. Major limitations in exposure assessment, small sample sizes and potential biases may account for the inconclusive and inconsistent results in epidemiological studies. Moreover, most studies have focused on total THMs as the exposure metric, whereas other DBPs appear to be more toxic than the THMs, albeit generally occurring at lower levels in the water. The mechanisms through which DBPs may cause adverse health effects including cancer and adverse reproductive effects have not been well investigated. Several mechanisms have been suggested, including genotoxicity, oxidative stress, disruption of folate metabolism, disruption of the synthesis and/or secretion of placental syncytiotrophoblast-derived chorionic gonadotropin and lowering of testosterone levels, but further work is required in this area.

Impact of chlorinated swimming pool attendance on the respiratory health of adolescents. 7-14 times the risk of developing asthma amongst atopic students.

Pediatrics. 2009 Oct;124(4):1110-8. doi: 10.1542/peds.2009-0032. Epub 2009 Sep 14. Impact of chlorinated swimming pool attendance on the respiratory health of adolescents. Bernard A, Nickmilder M, Voisin C, Sardella A. SourceDepartment of Public Health, Catholic University of Louvain, Brussels, Belgium. alfred.bernard@uclouvain.be Abstract OBJECTIVE: The goal was to estimate the burden of allergic diseases associated with chlorinated pool exposure among adolescents. METHODS: We examined 847 students, 13 to 18 years of age, who had attended outdoor or indoor chlorinated pools at various rates. Of them, 114 had attended mainly a copper-silver pool and served as a reference group. We measured total and aeroallergen-specific immunoglobulin E (IgE) levels in serum and screened for exercise-induced bronchoconstriction. Outcomes were respiratory symptoms, hay fever, allergic rhinitis, and asthma that had been diagnosed at any time (ever asthma) or was being treated with medication and/or was associated with exercise-induced bronchoconstriction (current asthma). RESULTS: Among adolescents with atopy with serum IgE levels of>30 kIU/L or aeroallergen-specific IgE, the odds ratios (ORs) for asthma symptoms and for ever or current asthma increased with the lifetime number of hours spent in chlorinated pools, reaching values of 7.1 to 14.9 when chlorinated pool attendance exceeded 1000 hours. Adolescents with atopy with chlorinated pool attendance of >100 hours had greater risk of hay fever (OR: 3.3-6.6), and those with attendance of >1000 hours had greater risk of allergic rhinitis (OR: 2.2-3.5). Such associations were not found among adolescents without atopy or with copper-silver pool attendance. The population attributable risks for chlorinated pool-related ever-diagnosed asthma, hay fever, and allergic rhinitis were 63.4%, 62.1%, and 35.0%, respectively. CONCLUSION: Chlorinated pool exposure exerts an adjuvant effect on atopy that seems to contribute significantly to the burden of asthma and respiratory allergies among adolescents.

Chlorinated drinking water, cancers and adverse health outcomes in Gangtok, Sikkim, India.

J Environ Sci Eng. 2007 Oct;49(4):247-54. Chlorinated drinking water, cancers and adverse health outcomes in Gangtok, Sikkim, India. Sharma RN, Goel S. Source Department of Civil Engineering (Environmental Engineering and Management), Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India. Erratum in J Environ Sci Eng. 2009 Jul;51(3):3 p following 232. Abstract Long-term impacts of drinking chlorinated water on the incidence of cancers and other adverse health outcomes were assessed in a population-based cross-sectional study. The study was conducted by comparing a group exposed to chlorinated drinking water for more than thirty years with control groups with less or no exposure to chlorine. A house-to-house survey was completed to gather information on residential history, age, education, income, source and extent of treatment of water and health characteristics. All residents below thirty years of age were excluded from the database used for analyses to ensure that the groups were comparable. Fourteen cancer cases were found in the long-term exposed groups of 1085 persons and 9 cancer cases in the two control populations of 725 persons. The odds ratio for cancers (OR) was 1.05 (95% CI = 0.43-2.65) and is not statistically significant. Reciprocal or inverse odds [corrected] ratios for gastrointestinal disorders, kidney problems and skin infections were statistically significant ranging from 2.06 (95% CI = 1.01-4.17) to 2.2 (95% CI = 1.45-3.33). These OR values indicate that there is no significant association between the incidence of cancer and exposure to chlorinated water while chlorinating drinking water significantly reduced the incidence of non-carcinogenic adverse health effects like gastrointestinal diseases, skin infections, and kidney diseases.

Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE.

J Water Health. 2009 Jun;7(2):185-207. doi: 10.2166/wh.2009.073. Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE. Nieuwenhuijsen MJ, Smith R, Golfinopoulos S, Best N, Bennett J, Aggazzotti G, Righi E, Fantuzzi G, Bucchini L, Cordier S, Villanueva CM, Moreno V, La Vecchia C, Bosetti C, Vartiainen T, Rautiu R, Toledano M, Iszatt N, Grazuleviciene R, Kogevinas M. SourceCentre for research in Environmental, Epidemiology (CREAL), Parc de Recerca Biomédical de Barcelona-PRBB, Barcelona, Spain. mnieuwenhuijsen@imim.es Abstract There appears to be very good epidemiological evidence for a relationship between chlorination by-products, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers, including colorectal cancer appears to be inconclusive and inconsistent. There appears to be some evidence for a relationship between chlorination by-products, as measured by THMs, and small for gestational age (SGA)/intrauterine growth retardation (IUGR) and preterm delivery, but evidence for other outcomes such as low birth weight (LBW), stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent.The overall aim of the HIWATE study is to investigate potential human health risks (e.g. bladder and colorectal cancer, premature births, SGA, semen quality, stillbirth, congenital anomalies) associated with long-term exposure to low levels of disinfectants (such as chlorine) and DBPs occurring in water for human consumption and use in the food industry. The study will comprise risk-benefit analyses including quantitative assessments of risk associated with microbial contamination of drinking water versus chemical risk and will compare alternative treatment options. The outcome will be improved risk assessment and better information for risk management. The work is divided into different topics (exposure assessment, epidemiology, risk assessment and management) and studies.

Step aside tobacco, chlorine could be man's next great carcinogen.

Med Hypotheses. 2009 Jun;72(6):759. doi: 10.1016/j.mehy.2009.01.010. Epub 2009 Mar 12. Step aside tobacco, chlorine could be man's next great carcinogen. Katona S. Step aside tobacco, chlorine could be manﾒs next great carcinogen. Is it a coincidence that the Western world disinfects its drinking water with chlorine, and a high proportion of the population develop bowel cancer and inflammatory bowel disease ? Perhaps we should start to question the health risks due to a chemical capable of killing most organisms in our water supply. Consider what many carcinogens have in common, namely that they are toxic to cells. Any chemical which damages cells makes them divide more often. During each cell division there is a chance a mistake may result in a cancer cell being formed. Any gas is most soluble in a cold liquid. When chlorinated water is ingested, the water warms up, and chlorine will come out of the water, and be trapped in the bowel. Most gas ends up in the large intestine which is most affected by bowel cancel and inflammatory bowel disease. Patients who have a long bowel transmit time, a known association with bowel cancer, would be expected to have chlorine trapped in the bowel for the longest period of time. The caecum and splenic flexure are sites where gas might be expected to collect, and are also common places to find bowel cancer. Persistent exposure to chlorine could be expected to kill mucosal cells, and both initiate, and perpetuate the kind of inflammation seen in inflammatory bowel disease, whose presence is already known to increase the risk of bowel cancer. A case control study in Ontario compared 767 patients with colon cancer, and 661 with rectal cancer, with 1545 controls with exposure information to chlorination bi-products (trihalomethanes or THMs) for at least 30 years. Males exposed to the highest levels of THMs had double the risk of colon cancer [1], although no association was found in a study in Iowa [2]. Interestingly there was no increased risk of rectal cancer in the Ontario study [1] but those with a low fibre intake had over twice the relative risk in Iowa [2]. A meta-analysis concluded there was a positive association between chlorination by-products in drinking water and bladder and rectal cancer in humans [3]. There may be health risks caused by consumption of chlorinated water, such as bladder cancer [4]. More studies are needed, but in the meantime the public should be warned to boil tap water, or let it stand overnight before consumption, to allow chlorine to evaporate. Even these measures may not remove THMs sufficiently. Cutaneous, mucosal and inhalation exposure may also be sufficient to cause a significant risk to health [5-6]. It took decades to establish, and publicise the link between tobacco and cancer. Lets not make the same mistake twice. [1] Case-control study of colon and rectal cancers and chlorination by-products in treated water. Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):813-8. King WD, Marrett LD, Woolcott CG. [2] Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. Epidemiology. 1998 Jan;9(1):29-35. Hildesheim ME, Cantor KP, Lynch CF, Dosemeci M, Lubin J, Alavanja M, Craun G. [3] Chlorination, chlorination by-products, and cancer: a meta-analysis. Am J Public Health. 1992 Jul;82(7):955-63. Morris RD, Audet AM, Angelillo IF, Chalmers TC, Mosteller F. [4] Drinking water source and chlorination byproducts. I. Risk of bladder cancer. Epidemiology. 1998 Jan;9(1):21-8. Cantor KP, Lynch CF, Hildesheim ME, Dosemeci M, Lubin J, Alavanja M, Craun G. [5] Risk from exposure to trihalomethanes during shower: Probabilistic assessment and control. Sci Total Environ. 2009 Jan 6. [Epub ahead of print] Chowdhury S, Champagne P. [6] Cancer risk assessment from exposure to trihalomethanes in tap water and swimming pool water. J Environ Sci (China). 2008;20(3):372-8. Panyakapo M, Soontornchai S, Paopuree P.

Characteristics of trihalomethane (THM) production and associated health risk assessment in swimming pool waters treated with different disinfection methods.

Sci Total Environ. 2009 Mar 1;407(6):1990-7. doi: 10.1016/j.scitotenv.2008.11.021. Epub 2008 Dec 20. Characteristics of trihalomethane (THM) production and associated health risk assessment in swimming pool waters treated with different disinfection methods. Lee J, Ha KT, Zoh KD. Source Institute of Health and Environment, School of Public Health, Seoul National University, Seoul 110-799, South Korea. Abstract Swimming pool water must be treated to prevent infections caused by microbial pathogens. In Korea, the most commonly used disinfection methods include the application of chlorine, ozone/chlorine, and a technique that uses electrochemically generated mixed oxidants (EGMOs). The purpose of this study was to estimate the concentrations of total trihalomethanes (TTHMs) in indoor swimming pools adopting these disinfection methods, and to examine the correlations between the concentrations of THMs and TTHMs and other factors affecting the production of THMs. We also estimated the lifetime cancer risks associated with various exposure pathways by THMs in swimming pools. Water samples were collected from 183 indoor swimming pools in Seoul, Korea, and were analyzed for concentrations of each THM, TOC, and the amount of KMnO(4) consumption. The free chlorine residual and the pH of the pool water samples were also measured. The geometric mean concentrations of TTHMs in the swimming pool waters were 32.9+/-2.4 microg/L for chlorine, 23.3+/-2.2 microg/L for ozone/chlorine, and 58.2+/-1.7 microg/L for EGMO. The concentrations of THMs differed significantly among the three treatment methods, and the correlation between THMs and TTHMs and the other factors influencing THMs varied. The lifetime cancer risk estimation showed that, while risks from oral ingestion and dermal exposure to THMs are mostly less than 10(-6), which is the negligible risk level defined by the US EPA, however swimmers can be at the greater risk from inhalation exposure (7.77x10(-4)-1.36x10(-3)).

Impact of chlorination on the incidence of cancers and miscarriages in two different campus communities in India. In India Chlorinated water may halve the risk of cancer compared to untreated water. ?Demonstrates importance of pathogens or reassurance regarding safety of chlorine.

J Environ Sci Eng. 2008 Jul;50(3):175-8. Impact of chlorination on the incidence of cancers and miscarriages in two different campus communities in India. Goel S. SourceDepartment of Civil Engineering, Indian Institute of Technology, Kharagpur, West Bengal, India. sudhagoel@civil.iitkgp.ernet.in Abstract Long-term impacts of drinking chlorinated water on the incidence of cancers and miscarriages were assessed in a population-based cross-sectional study conducted in the two campus communities of IIT Kanpur (IITK) and IIT Kharagpur (IITKgp). IITK has been using untreated groundwater since the community was established in 1963, while IITKgp has been using chlorinated water for more than 30 years. A house-to-house survey was carried out to gather information on residential history, i.e age, education, income, source and extent of treatment of water and health characteristics. Only adults above 20 years of age were included for data analyses. Odds ratios were calculated based on the hypothesis that exposure to chlorinated drinking water may result in a higher incidence of cancers and miscarriages as found in many studies. The odds ratios (OR) in this study were found to be 0.56 (95% CI = 0.16 to 1.62) for cancers and 0.33 (95% CI = 0.19-0.56) for miscarriages. These OR values are not statistically significant indicating the lack of association between cancers or miscarriages and exposure to chlorinated drinking water, and are in agreement with some published epidemiological studies as well. Reciprocal OR values were calculated based on an alternative hypothesis that chlorination actually decreases the risk of cancers and miscarriages. Based on this, the OR values for cancers are 1.77 (95% CI = 0.55 to 5.66) and for miscarriages are 3.07 (95% CI = 1.78 to 5.29). These results show that there is no association between exposure to chlorinated drinking water and cancers while there is significant decrease in the incidence of miscarriages for those exposed to chlorinated drinking water.

Removal of trihalomethanes from drinking water by nanofiltration membranes. (But does an ordinary carbon filter that 'Jo Blogs' can buy in the high street also work ?)

J Hazard Mater. 2008 Apr 1;152(2):789-94. Epub 2007 Jul 28. Removal of trihalomethanes from drinking water by nanofiltration membranes. Uyak V, Koyuncu I, Oktem I, Cakmakci M, Toroz I. Source Department of Environmental Engineering, Faculty of Engineering, Pamukkale University, 20020 Kinikli, Denizli, Turkey. vuyak@pau.edu.tr Abstract Chlorine reacts with the natural organic matter (NOM) in waters and forms disinfection by-products (DBP). Major of these by-products are trihalomethanes (THM) and haloacetic acids (HAA). They have been known to cause cancer and other toxic effects to human beings. This study determined the removal efficiencies of THM by nanofiltration (NF) techniques with NF200 and DS5 membrane. The rejection of this chlorination by-products was studied at various feed concentration by changing transmembrane pressure. Experimental results indicated that in general increasing operating pressure produces a higher flux but does not have a significant effect on THM rejection. On the other hand, increasing the feed concentration produces a little change in the overall flux and rejection capacity. NF200 membrane removed more THM than DS5 membrane. The higher removal efficiency of dibromochloromethane (DBCM) was attributed to brominating characteristics (higher molecular weight (MW) and molecular size). As a consequence, the results of this study suggest that the NF membrane process is one of the best available technologies for removing THM compounds.

Reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers.

Drowning in disinfection byproducts? Assessing swimming pool water. Zwiener C, Richardson SD, DeMarini DM, Grummt T, Glauner T, Frimmel FH. Source Engler-Bunte-Institute, Universitaet Karlsruhe, Karlsruhe, Germany. christian.zwiener@ciw.uni-karlsruhe.de Erratum in Environ Sci Technol. 2008 Mar 1;42(5):1812. De Marini, David M [corrected to DeMarini, David M]. Abstract Disinfection is mandatory for swimming pools: public pools are usually disinfected by gaseous chlorine or sodium hypochlorite and cartridge filters; home pools typically use stabilized chlorine. These methods produce a variety of disinfection byproducts (DBPs), such as trihalomethanes (THMs), which are regulated carcinogenic DBPs in drinking water that have been detected in the blood and breath of swimmers and of nonswimmers at indoor pools. Also produced are halogenated acetic acids (HAAs) and haloketones, which irritate the eyes, skin, and mucous membranes; trichloramine, which is linked with swimming-pool-associated asthma; and halogenated derivatives of UV sun screens, some of which show endocrine effects. Precursors of DBPs include human body substances, chemicals used in cosmetics and sun screens, and natural organic matter. Analytical research has focused also on the identification of an additional portion of unknown DBPs using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS/MS with derivatization. Children swimmers have an increased risk of developing asthma and infections of the respiratory tract and ear. A 1.6-2.0-fold increased risk for bladder cancer has been associated with swimming or showering/bathing with chlorinated water. Bladder cancer risk from THM exposure (all routes combined) was greatest among those with the GSTT1-1 gene. This suggests a mechanism involving distribution of THMs to the bladder by dermal/inhalation exposure and activation there by GSTT1-1 to mutagens. DBPs may be reduced by engineering and behavioral means, such as applying new oxidation and filtration methods, reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers. The positive health effects gained by swimming can be increased by reducing the potential adverse health risks.

Shame they don't tell us how much DBA is normally found in chlorinated tap water. Do levels get high enough to deliver 4mg/kg to a human.

Toxicology. 2007 Feb 12;230(2-3):126-36. Epub 2006 Dec 8. Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice. Melnick RL, Nyska A, Foster PM, Roycroft JH, Kissling GE. Source Environmental Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. melnickr@niehs.nih.gov Abstract Dibromoacetic acid (DBA) is a water disinfection byproduct formed by the reaction of chlorine oxidizing compounds with natural organic matter in water containing bromide. Male and female F344/N rats and B6C3F(1) mice were exposed to DBA in drinking water for 2 weeks (N=5), 3 months (N=10), or 2 years (N=50). Concentrations of DBA in drinking water were 0, 125, 250, 500, 1000, and 2000mg/L in the 2-week and 3-month studies, and 0, 50, 500, and 1000mg/L in the 2-year studies. Toxic effects of DBA in the prechronic studies were detected in the liver (hepatocellular cytoplasmic vacuolization in rats and mice) and testes (delayed spermiation and atypical residual bodies in male rats and mice, and atrophy of the germinal epithelium in rats). In the 2-year studies, neoplasms were induced at multiple sites in rats and mice exposed to DBA; these included mononuclear cell leukemia and abdominal cavity mesothliomas in rats, and neoplasms of the liver (hepatocellular adenoma or carcinoma and hepatoblastoma) and lung (alveolar adenoma or carcinoma) in mice. The increase in incidence of hepatocellular neoplasms in male mice was significant even at the lowest exposure concentration of 50mg/L, which is equivalent to an average daily dose of approximately 4mg/kg. These studies provide critical information for future re-evaluations of health-based drinking water standards for haloacetic acids.

Chromosomal aberation test : perhaps a useful method to evaluate safety of water supplies.

J Water Health. 2006 Dec;4(4):523-31. Reevaluation of the toxicity of chlorinated water and the usefulness of MX as an index. Itoh S, Nakano A, Araki T. Source Department of Urban Management, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. itoh@urban.env.kyoto-u.ac.jp Abstract Changes in the toxicity in chlorinated water after chlorine addition were examined. For toxicity evaluation, the chromosomal aberration test and the transformation test were conducted as indexes of initiation activity and promotion activity, respectively, in the carcinogenesis process. Activity inducing chromosomal aberrations in chlorinated Lake Biwa water gradually decreased over time after chlorination. In contrast, activity inducing transformations determined by the two-stage assay gradually increased. Thus, toxicity that decreases or increases is present in chlorinated water. Furthermore, activity inducing transformations determined by the non-two-stage assay gradually decreased over time. This direction of change is opposite to that of activity inducing transformations determined by the two-stage assay and is consistent with that of activity inducing chromosomal aberrations. The drastic decrease in initiation activity detected as activity inducing chromosomal aberrations could be the main cause for the decrease in activity inducing transformations determined by the non-two-stage assay (an index of the sum of initiation and promotion activity). MX change was quantitatively consistent with those of activity inducing chromosomal aberrations and transformations determined by the non-two-stage assay. On the other hand, directions of changes in concentrations of typical by-products such as chloroform were consistent only with that of activity inducing transformations determined by the two-stage assay. Findings of this study suggest that MX is appropriate as an index for comparing the carcinogenicity of tap water near and far from a water purification plant.

NTP Toxicology and carcinogenesis studies of bromodichloromethane (CAS No. 75-27-4) in male F344/N rats and female B6C3F1 mice (Drinking Water Studies).

Natl Toxicol Program Tech Rep Ser. 2006 Feb;(532):1-248. NTP Toxicology and carcinogenesis studies of bromodichloromethane (CAS No. 75-27-4) in male F344/N rats and female B6C3F1 mice (Drinking Water Studies). National Toxicology Program. Abstract Bromodichloromethane is a by-product of the chlorination of drinking water. It is formed by the halogen substitution and oxidation reactions of chlorine with naturally occurring organic matter (e.g., humic or fulvic acids) in water containing bromide. Bromodichloromethane has been shown to be carcinogenic at multiple sites in rats (large intestine and kidney) and in mice (liver and kidney) after administration by gavage in corn oil. To further characterize its dose-response relationships for evaluations of human risk, bromodichloromethane was nominated to the NTP by the United States Environmental Protection Agency for toxicity and carcinogenicity studies in rats and mice by drinking water exposure. Male F344/N rats and female B6C3F1 mice were exposed to bromodichloromethane (greater than 98% pure) in drinking water for 3 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, mouse bone marrow cells, and mouse peripheral blood erythrocytes. 3-WEEK STUDY IN RATS: Groups of 10 male F344/N rats were exposed to target concentrations of 0, 43.7, 87.5, 175, 350, or 700 mg/L bromodichloromethane (equivalent to average daily doses of approximately 0, 6, 12, 20, 38, or 71 mg bromodichloromethane/kg body weight) in drinking water for 3 weeks. All rats survived to the end of the study. The mean body weight gains of 350 and 700 mg/L rats were significantly less than that of the controls. Concentration-related decreases in water consumption were evident during the first week on study. Relative kidney weights of rats in the 175, 350, and 700 mg/L groups were significantly greater than that of the controls. There were no significant chemical-related histopathological changes. 3-WEEK STUDY IN MICE: Groups of 10 female B6C3F1 mice were exposed to target concentrations of 0, 43.7, 87.5, 175, 350, or 700 mg/L bromodichloromethane (equivalent to average daily doses of approximately 0, 6, 10, 16, 29 or 51 mg/kg) in drinking water for 3 weeks. All mice survived to the end of the study. Final mean body weights of the 175, 350, and 700 mg/L mice and mean body weight gains of 350 and 700 mg/L mice were significantly less than those of the controls. These decreases were attributed to decreased water consumption. There were significant concentration-related decreases in water consumption by groups exposed to 87.5 mg/L or greater throughout the study; these decreases were attributed to poor palatability of the dosed water. Relative liver, kidney, and thymus weights of mice in the 350 and 700 mg/L groups were significantly greater than those of the controls. Absolute lung weights of mice in the 350 and 750 mg/L groups were significantly less than that of the controls. There were no significant chemical-related histopathological changes. 2-YEAR STUDY IN RATS: Groups of 50 male F344/N rats were exposed to target concentrations of 0, 175, 350, or 700 mg/L bromodichloromethane (equivalent to average daily doses of approximately 0, 6, 12, or 25 mg/kg) in drinking water for 2 years. Survival of exposed groups was similar to that of the controls. Mean body weights of all exposed groups were generally similar to those of the controls throughout the study. Water consumption by exposed rats was less than that by the controls throughout the study; the decreases were attributed to poor palatability of the dosed water. There were no increased incidences of neoplasms that were attributed to bromodichloromethane. The incidences of chronic inflammation in the liver of the 350 and 700 mg/L groups were significantly greater than that in the controls; however, the biological significance of these increases is uncertain. 2-YEAR STUDY IN MICE: Groups of 50 female B6C3F1 mice were exposed to target concentrations of 0, 175, 350, 700 mg/L bromodichloromethane (equivalent to average daily doses of approximately 9, 18, or 36 mg/kg) in drinking water for 2 years. Survival of exposed groups was similar to that of the controls. Mean body weights of all exposed groups were generally less than those of the controls from week 4 through the end of the study. Water consumption by exposed mice was less than that by the controls throughout the study; the decreases were attributed to poor palatability of the dosed water. The incidences of hepatocellular adenoma or carcinoma (combined) occurred with a negative trend, and the incidence in the 700 mg/L group was significantly decreased relative to the control group. The incidence of hemangiosarcoma in all organs was significantly decreased in the 350 mg/L group. GENETIC TOXICOLOGY: The results of in vitro mutagenicity tests with bromodichloromethane were mixed. Bromodichloromethane did not induce mutations in any of several tester strains of Salmonella typhimurium, with or without exogenous metabolic activation (S9 liver enzymes). In contrast to the negative results in Salmonella, tests for mutation induction in mouse lymphoma L5178Y/tk(+/-)cells were positive in the presence of induced rat liver S9; no mutagenic activity occurred in tests conducted without S9. In cytogenetic tests with cultured Chinese hamster ovary cells, bromodichloromethane induced a small increase in sister chromatid exchanges (SCEs) in one of four trials conducted in the presence of induced rat liver S9 enzymes; no significant increase in SCEs occurred without S9, and no induction of chromosomal aberrations occurred in bromodichloromethane-treated Chinese hamster ovary cells with or without S9. Results of in vivo tests for chromosomal damage were negative. No increases in the frequency of micronucleated erythrocytes were seen in bone marrow of male B6C3F1 mice administered bromodichloromethane by intraperitoneal injection for 3 days. In addition, no induction of micronuclei was observed in circulating erythrocytes of female B6C3F1 mice administered up to 700 mg/L bromodichloromethane in drinking water for 3 weeks. CONCLUSIONS: Under the conditions of this 2-year drinking water study, there was no evidence of carcinogenic activity of bromodichloromethane in male F344/N rats exposed to target concentrations of 175, 350, or 700 mg/L. There was no evidence of carcinogenic activity of bromodichloromethane in female B6C3F1 mice exposed to target concentrations of 175, 350, or 700 mg/L.

Leukaemia risk : increased for CML, and decreased for CLL

Am J Epidemiol. 2006 Jan 15;163(2):116-26. Epub 2005 Nov 30. Chlorination disinfection by-products in drinking water and the risk of adult leukemia in Canada. Kasim K, Levallois P, Johnson KC, Abdous B, Auger P; Canadian Cancer Registries Epidemiology Research Group. Source Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, Québec, Canada. Abstract The authors conducted a population-based case-control study of 1,068 incident leukemia cases and 5,039 controls aged 20-74 years during 1994-1997 to examine the association between exposure to drinking water chlorination disinfection by-products and adult leukemia risk in Canada. Residence and drinking water source histories and data from municipal water supplies were used to estimate individual chlorination disinfection by-product exposure according to water source, chlorination status, and chlorination disinfection by-product levels during the 40-year period before the interview. The analysis included 686 cases and 3,420 controls for whom water quality information was available for at least 30 of these years. Increased risk of chronic myeloid leukemia was associated with increasing years of exposure to different chlorination disinfection by-product indexes, with an adjusted odds ratio of 1.72 (95% confidence interval: 1.01, 3.08) for the highest exposure duration to total trihalomethanes of more than 40 microg/liter. In contrast, the risk of the other studied leukemia subtypes was found to decrease with increasing years of exposure to chlorination disinfection by-products. A protective effect was noted for chronic lymphoid leukemia (odds ratio = 0.60, 95 percent confidence interval: 0.41, 0.87) associated with the highest exposure duration to total trihalomethanes of more than 40 microg/liter. More studies with long-term exposure measures and large enough to evaluate leukemia subtypes are needed to further understanding of the issue.

Pancreatic cancer : no increased risk

Environ Health Perspect. 2005 Apr;113(4):418-24. Chlorination disinfection by-products and pancreatic cancer risk. Do MT, Birkett NJ, Johnson KC, Krewski D, Villeneuve P; Canadian Cancer Registries Epidemiology Research Group. Source Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada. Erratum in Environ Health Perspect. 2005 Aug;113(8):A511. Abstract Chlorination disinfection by-products (CDBPs) are produced during the treatment of water with chlorine to remove bacterial contamination. CDBPs have been associated with an increased risk of bladder cancer. There is also some evidence that they may increase the risk of pancreatic cancer. We report results from a population-based case-control study of 486 incident cases of pancreatic cancer and 3,596 age- and sex-matched controls. Exposure to chlorination by-products was estimated by linking lifetime residential histories to two different databases containing information on CDBP levels in municipal water supplies. Logistic regression analysis found no evidence of increased pancreatic cancer risk at higher CDBP concentrations (all odds ratios < 1.3). Null findings were also obtained assuming a latency period for pancreatic cancer induction of 3, 8, or 13 years.

Meta-analysis (all studies grouped) : Consumption of chlorinated drinking water associated with 1.4x risk of bladder cancer in men.

J Epidemiol Community Health. 2003 Mar;57(3):166-73. Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer. Villanueva CM, Fernández F, Malats N, Grimalt JO, Kogevinas M. Source Respiratory and Environmental Health Research Unit, Municipal Institute of Medical Research (IMIM), Barcelona, Spain. Erratum in J Epidemiol Community Health. 2005 Jan;59(1):87. Abstract STUDY OBJECTIVE: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer. DESIGN: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. SETTING: Populations in Europe and North America. PARTICIPANTS: Those included in six case-control studies (6084 incident bladder cancer cases, 10,816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. MAIN RESULTS: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. CONCLUSIONS: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods.

Estimation of potential lifetime cancer risks for trihalomethanes from consuming chlorinated drinking water in Taiwan. (This abstract doesn't tell us much)

Environ Res. 2001 Feb;85(2):77-82. Estimation of potential lifetime cancer risks for trihalomethanes from consuming chlorinated drinking water in Taiwan. Hsu CH, Jeng WL, Chang RM, Chien LC, Han BC. Source School of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, Republic of China. Abstract Data on concentrations of trihalomethanes (THMs) in raw and chlorinated water collected from three water treatment plants in Taiwan and estimates of the lifetime cancer risk for THMs from drinking water, using age-adjusted factors and volatilization terms, are presented. Data on THM levels in drinking water were obtained from the annual reports of the Environmental Protection Administration (EPA) of Taiwan. The methodology for estimation of lifetime cancer risks was taken from the USEPA. Chloroform was the major species of THMs, especially in the water plant of south Taiwan. Chloroform contributed the majority of the lifetime cancer risks (range: 87.5-92.5%) of total risks from the three water supply areas. All lifetime cancer risks for CHCl(3), CHBrCl(2), CHBr2Cl, and CHBr3 from consuming tap water in the three water supply areas were higher than 10(-6). The sum of lifetime cancer risks for CHCl(3), CHBrCl(3), CHBr2Cl, and CHBr3 was highest (total risk for total THMs<1.94x10(-4)) for tap water from south Taiwan. Copyright 2000 Academic Press.

Case-control study of colon and rectal cancers and chlorination by-products in treated water. (x2 risk in men with high compared to low exposure but not in women ?!)

Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):813-8. Case-control study of colon and rectal cancers and chlorination by-products in treated water. King WD, Marrett LD, Woolcott CG. Source Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada. kingw@post.queensu.ca Abstract This population-based case-control study was conducted in southern Ontario, Canada from 1992 to 1994 to assess the relationship between chlorination by-products in public water supplies and cancers of the colon and rectum. Interviews providing residence and water source histories were completed by 76% of eligible cancer cases and 72% of eligible controls. Supplemental data from municipal water supplies were used to estimate individual exposure to water source, chlorination status, and by-product levels as represented by trihalomethanes (THMs) during the 40-year period before the interview. The analyses included 767 colon cases, 661 rectal cases, and 1545 controls with exposure information for at least 30 of these years (75% of subjects with completed interviews). Among males, colon cancer risk was associated with cumulative exposure to THMs, duration of exposure to chlorinated surface water, and duration of exposure to a THM level > or = 50 microg/liter and 75 microg/liter. Males exposed to chlorinated surface water for 35-40 years had an increased risk of colon cancer compared with those exposed for < 10 years (odds ratio, 1.53; 95% confidence interval, 1.13-2.09). Males exposed to an estimated THM level of 75 microg/liter for > or = 35 years had double the risk of those exposed for < 10 years (odds ratio, 2.10; 95% confidence interval, 1.21-3.66). In contrast, these relationships were not observed among females. No relationship was observed between rectal cancer risk and any of the measures of exposure to chlorination by-products. The results of this study should be interpreted with caution because they are only partially congruent with the limited amount of literature addressing this issue.

A call for more research.

N Z Med J. 1999 Oct 22;112(1098):404-7. Something in the water? A health impact assessment of disinfection by-products in New Zealand. Malcolm MS, Weinstein P, Woodward AJ. Source Department of Public Health, Wellington School of Medicine. Abstract Disinfection by-products (DBP) are a large group of halogenated chemicals formed by the reaction of disinfectant agents with naturally-occurring organic substances in water. Numerous studies have found associations between DBP and some cancers and adverse reproductive outcomes. For both cancer and birth defects the relative risk associated with exposure to DBP is about 1.5. About 66% of New Zealanders, or 2.4 million people, use chlorinated water supplies and are exposed to DBP. New Zealand's unique combination of flora, climate and geology will create unique mixtures of DBP but little detailed information is available on the level or composition of DBP in New Zealand. The population attributable risk per cent, for cancers and birth defects in New Zealand, is about 25%. In other words, a quarter of all bladder, colon and rectal cancers and birth defects may be preventable by reducing DBP exposure. This is equal to 329 preventable cancer deaths in 1995 and 94 preventable birth defects in 1996. DBP exposure can be reduced without compromising microbiological safety of water supplies. The health effects of DBPs must be weighed against the cost of DBP reduction and not against the potential water borne disease prevented by disinfection. Some aspects of New Zealand's water supplies and population provide a unique opportunity to undertake research. Further research is needed on the occurrence of DBPs and their health consequences in order to undertake a properly informed risk assessment.

An urgent need to know more....1998....still waiting

Chronic Dis Can. 1998;19(3):103-7. Safe drinking water: a public health challenge. Wigle DT. Source Bureau of Operations, Planning and Policy, Laboratory Centre for Disease Control, Health Canada, Tunney's Pasture, AL: 0602E2, Ottawa, Ontario, K1A 0L2, Canada. Don_T_Wigle@hc-sc.gc.ca Abstract Disinfection of drinking water through processes including filtration and chlorination was one of the major achievements of public health, beginning in the late 1800s and the early 1900s. Chloroform and other chlorination disinfection by-products (CBPs) in drinking water were first reported in 1974. Chloroform and several other CBPs are known to cause cancer in experimental animals, and there is growing epidemiologic evidence of a causal role for CBPs in human cancer, particularly for bladder cancer. It has been estimated that 14 16% of bladder cancers in Ontario may be attributable to drinking water containing relatively high levels of CBPs; the US Environmental Protection Agency has estimated the attributable risk to be 2 17%. These estimates are based on the assumption that the associations observed between bladder cancer and CBP exposure reflect a cause-effect relation. An expert working group (see Workshop Report in this issue) concluded that it was possible (60% of the group) to probable (40% of the group) that CBPs pose a significant cancer risk, particularly of bladder cancer. The group concluded that the risk of bladder and possibly other types of cancer is a moderately important public health problem. There is an urgent need to resolve this and to consider actions based on the body of evidence which, at a minimum, suggests that lowering of CBP levels would prevent a significant fraction of bladder cancers. In fact, given the widespread and prolonged exposure to CBPs and the epidemiologic evidence of associations with several cancer sites, future research may establish CBPs as the most important environmental carcinogens in terms of the number of attributable cancers per year.

Drinking water source and chlorination byproducts. II. Risk of colon (no increased risk) and rectal cancers (2.4x risk in those with a low fibre intake).

Epidemiology. 1998 Jan;9(1):29-35. Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. Hildesheim ME, Cantor KP, Lynch CF, Dosemeci M, Lubin J, Alavanja M, Craun G. Source Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Abstract We evaluated the association between chlorination byproducts and colon and rectal cancer risk in a population-based case-control study conducted in Iowa in 1986-1989. Data were gathered from 685 colon cancer cases, 655 rectal cancer cases, and 2,434 controls. We calculated odds ratios for the 560 colon cancer cases, 537 rectal cancer cases, and 1,983 controls for whom water exposure information was available for at least 70% of their lifetime. We estimated exposure to chlorination byproducts with two types of measures: duration of lifetime at residences served by chlorinated water and estimated lifetime trihalomethane exposure. For rectal cancer, we observed an association with duration of chlorinated surface water use, with adjusted odds ratios of 1.1, 1.6, 1.6, and 2.6 for 1-19, 20-39, 40-59, and > or =60 years of exposure, compared with no exposure. Rectal cancer risk was also associated with several different measures of estimated lifetime trihalomethane exposure. For colon cancer and subsites, we detected no important increase in risk associated with duration of chlorinated surface water, nor with trihalomethane estimates. When we evaluated chlorination byproducts jointly with other factors, we found larger relative risk estimates for rectal cancer among subjects with low dietary fiber intake. The risk related to > or =40 years of exposure to a chlorinated surface water source was 2.4 (95% confidence interval = 1.5-4.0) for persons with low fiber intake and 0.9 (95% confidence interval = 0.4-1.8) for persons with high fiber intake, relative to the risk of persons with high-fiber diets and no exposure to chlorinated surface water. We observed a similar risk differential for low and high levels of physical activity.

Results of long-term carcinogenicity studies of chlorine in rats. A call for more research...

Ann N Y Acad Sci. 1997 Dec 26;837:189-208. Results of long-term carcinogenicity studies of chlorine in rats. Soffritti M, Belpoggi F, Lenzi A, Maltoni C. Source Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Bentivoglio Castle, Italy. Abstract Four groups, each of 50 male and 50 female Sprague-Dawley rats, of the colony used in the Cancer Research Center of Bentivoglio of the Ramazzini Foundation, 12 weeks old at the start of the study, received drinking water containing sodium hypochlorite, resulting in concentrations of active chlorine of 750, 500, and 100 mg/l (treated groups), and tap water (active chlorine < 0.2 mg/l) (control group), respectively, for 104 weeks. Among the female rats of the treated groups, an increased incidence of lymphomas and leukemias has been observed, although this is not clearly dose related. Moreover, sporadic cases of some tumors, the occurrence of which is extremely unusual among the untreated rats of the colony used (historical controls), were detected in chlorine-exposed animals. The results of this study confirm the results of the experiment of the United States National Toxicology Program (1991), which showed an increase of leukemia among female Fischer 344/N rats following the administration of chlorine (in the form of sodium hypochlorite and chloramine) in their drinking water. The data here presented call for further research aimed at quantifying the oncogenic risks related to the chlorination of drinking water, to be used as a basis for consequent public health measures.

The association of drinking water source and chlorination by-products with cancer incidence among postmenopausal women in Iowa: a prospective cohort study. A dose response relation

Am J Public Health. 1997 Jul;87(7):1168-76. The association of drinking water source and chlorination by-products with cancer incidence among postmenopausal women in Iowa: a prospective cohort study. Doyle TJ, Zheng W, Cerhan JR, Hong CP, Sellers TA, Kushi LH, Folsom AR. Source Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015, USA. Abstract OBJECTIVES: This study assessed the association of drinking water source and chlorination by-product exposure with cancer incidence. METHODS: A cohort of 28,237 Iowa women reported their drinking water source. Exposure to chlorination by-products was determined from statewide water quality data. RESULTS: In comparison with women who used municipal ground-water sources, women with municipal surface water sources were at an increased risk of colon cancer and all cancers combined. A clear dose-response relation was observed between four categories of increasing chloroform levels in finished drinking water and the risk of colon cancer and all cancers combined. The relative risks were 1.00, 1.06, 1.39, and 1.68 for colon cancer and 1.00, 1.04, 1.24, and 1.25 for total cancers. No consistent association with either water source or chloroform concentration was observed for other cancer sites. CONCLUSIONS: These results suggest that exposure to chlorination by-products in drinking water is associated with increased risk of colon cancer.

Drinking water chlorination and cancer-a historical cohort study in Finland.(A large study - increased risk only observed in women)

Cancer Causes Control. 1997 Mar;8(2):192-200. Drinking water chlorination and cancer-a historical cohort study in Finland. Koivusalo M, Pukkala E, Vartiainen T, Jaakkola JJ, Hakulinen T. Source Finnish Cancer Registry, Helsinki, Finland. Abstract Chlorination of water rich in organic material is known to produce a complex mixture of organochlorine compounds, including mutagenic and carcinogenic substances. A historical cohort study of 621,431 persons living in 56 towns in Finland was conducted in order to assess the relation between historical exposure to drinking water mutagenicity and cancer. Exposure to quantity of mutagenicity was calculated on the basis of historical information of raw water quality and water treatment practices using an empirical equation relating mutagenicity and raw water pH, KMnO4 value and chlorine dose. Cancer cases were derived from the population-based Finnish Cancer Registry and follow-up time in the study started in 1970. Age, gender, time period, social class, and urban residence were taken into account in Poisson regression analysis of the observed numbers of cases using expected numbers of cases standardized for age and gender as a basis. Excess risks were calculated using a continuous variable for mutagenicity for 3,000 net rev/l exposure representing an average exposure in a town using chlorinated surface water. After adjustment for confounding, a statistically significant excess risk was observed for women in cancers of the bladder (relative risk [RR] = 1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI = 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11, CI = 1.01-1.22). These results support the magnitude of excess risks for rectal and bladder cancers found in earlier epidemiologic studies on chlorination by-products and give additional information on exposure-response concerning the mutagenic compounds. Nevertheless, due to the public health importance of water chlorination, uncertainty related to the magnitude of observed risks, and the fact that excess risks were observed only for women, the results of the study should be interpreted with caution.