Effect of Genetic Differences on Levels of Water Disinfection Byproducts in Blood After Showering

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00340535
Recruitment Status : Completed
First Posted : June 21, 2006
Last Update Posted : August 9, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

This study will examine whether genetic differences among individuals affect blood levels of certain chemicals called DBPs after showering. Chemicals such as chlorine and ozone are used to kill germs in water. These chemicals may react with organic matter in the water and form other chemicals called disinfection byproducts, or DBPs. Although people are usually exposed to DBPs by drinking tap water, these chemicals may also penetrate the body during showering. This study will see whether the levels of DBPs after showering vary among individuals depending on differences in genes that code for enzymes called GSTT1, CYP2D6, and CYP2E1, which break down DBPs. This study, sponsored by the Centers for Disease Control and Prevention and the National Institutes of Health, is conducted at the University of Pittsburgh's Center for Clinical Pharmacology.

Healthy adults between 18 and 45 years of age who do not smoke cigarettes and are not taking any medicines may be eligible for this study. Candidates are screened with a medical history and blood and urine tests. Participants are given a diary to record the foods they eat and how much water they drink during the 2 days before their study appointment. The following activities are scheduled on the appointment day:

  • Measurements of blood pressure, height, and weight, and pregnancy test for women
  • Questions about alcohol consumed and medications taken in the last 48 hours
  • Review of food and water diary
  • Interview for demographic information (name, address, date of birth, etc.) and other information, such as sex, height, weight. Subjects are also asked about anything, such as exercise, that might affect their breathing, since breathing problems are a rare side effect of chlorzoxazone, a drug used in this study.
  • Urine sample collection
  • Blood draw and insertion of a small catheter (plastic tube) to allow for additional blood draws during the test procedure without having repeated needle sticks
  • 10-minute shower in a private bathroom
  • Blood sample collection 10 minutes after the shower and again at 30 minutes after the shower
  • Dose of chlorzoxazone (a drug used to treat muscle pain)
  • Interview about subject's exposure to water
  • Light breakfast
  • Blood and urine collections 2 hours after the chlorzoxazone dose
  • Lunch
  • Observation for drug side effects for 2 hours, or longer if needed

Seven blood samples totaling 75 milliliters (about 5 tablespoonfuls) of blood are collected during this study. The blood is tested for chemicals called trihalomethanes to see how they are broken down. The urine samples are tested for chemicals called haloacetic acids, which are found in tap water after it has been treated with chlorine.

Condition or disease
Normal Physiology

Detailed Description:

Disinfection byproducts in drinking water (DBP) are inadvertently created when chlorine interacts with organic compounds in the untreated water. DBP have been implicated in elevated risk of several types of cancer. Until recently, ingestion was considered to be the major route of exposure. However, an NCI collaborative study in Spain is now showing a link between bladder cancer and exposure to DBP in water during showering or bathing. However, little is known of the mechanisms of action. Almost all drinking water disinfected with chlorine contains measurable levels of DBP. The DBP found in greatest concentration are the trihalomethanes [(THM); chloroform, bromoform, bromodichloromethane, and dibromochloromethane]. Previously, our collaborators from the CDC measured changes in blood THM levels after showering and bathing, and ingesting water. Showering resulted in the largest increases, with a wide range in the increase among subjects with similar exposures. Enzyme variants due to genetic polymorphisms may be responsible for these differences.

We plan to assess the association between the presence of enzyme variants (genetic polymorphisms) and the increase of trihalomethanes in the blood of people exposed to DBP while showering. The study will be conducted at the General Clinical Research Center (GCRC), Center for Clinical Pharmacology (CCP), University of Pittsburgh, Dr. Robert Branch, Director. Approximately 250 volunteers will be identified from Dr. Branch's ongoing research program. These subjects will have been pre-screened with a normal standard blood panel and for genetic polymorphisms of interest. From this pool of pre-screened individuals, we will recruit approximately 100 people who have enzyme variants of differing activity.

We will ask the 100 volunteers to provide seven 10-mL blood samples and two urine samples, and take a 10-minute shower at the study site (the CCP in Pittsburgh, PA). Blood samples will be analyzed for trihalomethane concentrations, and red blood cell enzyme activities. To study the activity of the enzyme CYP2E1, we will administer a single dose of chlorzoxazone, a muscle relaxant metabolized by this enzyme. We will measure enzyme activity by analyzing blood samples collected 2 hours post-administration. We will conduct a brief interview with each volunteer to obtain demographic and other information that might impact the dose of THM. We will collect ambient air samples before, during and after showering for each participant and analyze them for levels of THMs. A water sample will be collected during showering and analyzed for levels of THM and haloacetic acids. We will ask 10 randomly selected study subjects to repeat study activities for quality control purposes.

Levels of THM in blood before and after showering, and the rate of decrease in blood concentration, will be analyzed with respect to the presence of genetic polymorphisms for selected enzymes, or their phenotypic activity. Blood THM levels will also be compared with various demographic and physiologic measurements. To test intra-individual variation in several measures, ten randomly selected participants (stratified by sex, i.e. 5 males and 5 females) will be asked to conduct the study twice, with the two study appointments separated by at least a week.

Study Type : Observational
Actual Enrollment : 100 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: Levels of Selected Potentially Carcinogenic Drinking Water Disinfection Byproducts in Whole Blood After Showering
Study Start Date : June 23, 2004

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Blood trihalomethane levels [ Time Frame: Before and after showering ]
    Levels of triahlomethane levels in the blood

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
convenience sample of individuals recruited at the University of Pittsburgh.

The study population will be comprised of non-smoking males and females in the age range 18-45 years. The age range was selected to limit variability in activity of important enzyme systems.


Persons with lung conditions will be excluded because inhalation is a major route of exposure for trihalomethanes.

Liver conditions will be excluded because of the potential risks possibly associated with chlorzoxazone administration.

Pregnant and lactating women will be excluded from participation in the study, for multiple reasons, the major one being possible (but unknown) adverse health risks from chlorzoxazone exposure.

In addition, we will exclude persons with chronic conditions such as diabetes who chronically use medication, such as Orinase or others. These persons will be excluded due to unknown effects of such disease on the enzyme systems under investigation and to avoid any possible adverse effects of the study, including chlorzoxazone administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00340535

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Laura Beane-Freeman National Cancer Institute (NCI)

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00340535     History of Changes
Obsolete Identifiers: NCT00559793, NCT01338272
Other Study ID Numbers: 999904228
First Posted: June 21, 2006    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: March 9, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Disinfection byproducts
Genetic Variation