• Association between the presence of enzyme variants (genetic polymorphisms) and the increase of trihalomethanes in the blood of participants exposed to disinfection byproducts while showering [ Designated as safety issue: No ]
  
• Levels of trihalomethanes (THM) in blood before and after showering [ Designated as safety issue: No ]
  
• Rate of decrease in concentration with respect to presence of genetic polymorphisms for selected enzymes or their phenotypic activity [ Designated as safety issue: No ]
  
• Comparison of blood THM levels with various demographic and physiologic measurements [ Designated as safety issue: No ]
  
• Intra-individual variation in several measures in ten participants [ Designated as safety issue: No ]
  
• Levels of THM in ambient air samples before, during, and after showering [ Designated as safety issue: No ]
  
• Levels of THM and haloacetic acids in water samples [ Designated as safety issue: No ]
  
• Measurement of enzyme activity in blood [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To assess the association between the presence of enzyme variants (genetic polymorphisms) and the increase of trihalomethanes in the blood of participants exposed to drinking water disinfection byproducts while showering.

OUTLINE: Participants are pre-screened with a normal standard blood panel and for genetic polymorphisms of interest. Participants with enzymes variants of differing activity continue in the study.

During the study appointment, participants' blood pressure, height, and weight are measured. Participants also complete a Food and Water Consumption Diary and a Study Check List detailing how much water and food was consumed within the last 48 hours. Participants complete an interview to obtain demographic information (name, address, date of birth, etc.) and information such as sex, height, and weight. Participants are asked about factors, such as exercise, that might affect their breathing. Participants also undergo baseline blood sample collection and provide a urine sample. They will then take a 10-minute shower in a private bathroom at the study site (with water temperature between 104 and 105 degrees) without using soap or shampoo. Blood is collected 10 minutes after the shower and again at 30 minutes after the shower. In order to study the activity of the enzyme, CYP2E1, participants receive a single dose of chlorzoxazone, a muscle relaxant metabolized by the enzyme. Blood is collected 2 hours after chlorzoxazone administration for measurement of enzyme activity. Participants also provide a second urine sample 2 hours after chlorzoxazone administration. Blood is also analyzed for trihalomethanes (THMs). Urine samples are tested for haloacetic acids. Ambient air samples are collected before, during, and after showering (for each participant) and analyzed for THMs. A water sample is collected during the shower and analyzed for levels of THM and haloacetic acids.

Levels of THM in blood before and after showering and the rate of decrease in blood concentration is analyzed with respect to the presence of genetic polymorphisms for selected enzymes or their phenotypic activity. Blood THM levels are compared with various demographic and physiologic measurements. In order to test intra-individual variation in several measures, 10 randomly selected participants (stratified by sex [i.e., 5 males and 5 females]) are asked to conduct the study twice. The 2 study appointments are separated by at least 1 week.

Left over samples of DNA from previous screening tests at the Center for Clinical Pharmacology are stored for future genetic testing at the National Cancer Institute.