The Healthy Men Study: An Evaluation of Exposure to Disinfection By-Products in Tap Water and Sperm Quality
Luben, Thomas J., Olshan, Andrew F., Herring, Amy H., Jeffay, Susan, Strader, Lillian, Buus, Rebecca M., Chan, Ronna L., Savitz, David A., Singer, Philip C., Weinberg, Howard S., Perreault, Sally D., Environmental Health Perspectives
Disinfection by-products (DBPs) form when chlorine or other disinfectants react with organic matter during preparation of drinking water. There are many classes of DBPs, including trihalomethanes (THMs) and haloacetic acids (HAAs). The relative concentrations of these DBPs, as well as the proportional distributions of individual chemicals within these classes, vary based on source water characteristics and treatment methods and on distribution system characteristics. The U.S. Environmental Protection Agency (EPA) and others have evaluated the potential adverse health effects of DBPs in both toxicologic and epidemiologic research. Several epidemiologic studies have suggested a possible association between DBPs and adverse pregnancy outcomes (Klotz and Pyrch 1999; Savitz et al. 1995, 2005, 2006; Toledano et al. 2005; Waller et al. 1998; Wright et al. 2003). To date, only one study has addressed DBPs and male reproductive health wherein exposure to DBPs was associated with decrements in sperm motility (Fenster et al. 2003).
Animal studies have consistently demonstrated an association between oral exposure to HAAs and adverse effects in the male reproductive system (Christian et al. 2002; Linder et al. 1994a, 1994b, 1995, 1997a, 1997b; Veeramachaneni et al. 2000). Testicular toxicity, including acute spermatotoxicity (Linder et al. 1994b), impaired reproductive competence and sperm quality (Linder et al. 1995), delayed spermiation and distorted sperm motility and morphology (Linder et al. 1997a), histopathologic changes in testis and epididymis (Linder et al. 1997b), transient subfertility (Luft et al. 2000), and altered sperm production and epididymal tubule changes (Christian et al. 2002), has been demonstrated when rodents were exposed to high doses (in the milligrams per kilogram range) of selected individual HAA species, with dibromoacetic acid being the most studied.
These rodent toxicology studies suggest that HAAs in drinking water, especially the brominated species, could pose a risk to the male reproductive system in humans, and that an evaluation of similar outcomes in human semen (sperm numbers, morphology, and motility) would be appropriate. Continued or intermittent exposure of men to DBPs in drinking water, even at levels below those that are acutely toxic to rodents, may have the potential to produce testicular toxicity as evidenced by altered semen quality.
We conducted a cohort study to address this possibility by evaluating semen quality in men with well-characterized exposures to DBPs. We were able to integrate this study with a cohort study of drinking-water DBPs and pregnancy loss (Savitz et al. 2006). Recruitment for both studies involved couples in three geographic locations in the United States, with our study adding home semen collection in a subcohort. We examined exposure to THMs and HAAs based on the concentration of these two classes of DBPs (as well as the four individual species of THMs and nine individual species of HAAs) and to TOX (total organic halides) measured weekly in the tap water from distribution systems serving the three study sites. These study sites were selected specifically to provide a reference site with low overall DBPs and two sites with relatively high levels of DPBs but differing with respect to brominated versus chlorinated species. Based on the concentrations of four regulated THMs (THM4), nine HAAs (HAA9), and total organic halides (TOX) measured weekly in tap water sampled from the distribution systems (Savitz et al. 2006), we calculated mean levels of DBPs over the 90 days preceding semen sampling. We then used questionnaire data to estimate the daily volume of tap water ingested and the frequency and duration of bathing and showering for each participant; we used these data to create exposure indices estimating exposure to DBPs via the ingestion, inhalation, and dermal routes of exposure. In the statistical analyses, we considered exposure to combined DBPs in accordance with current regulations [i. …