title: Preliminary screening for the potential of drinking water disinfection byproducts to alter male reproduction.
abstract: There is increasing epidemiologic interest in the role drinking water disinfection byproducts (DBPs) may play in adverse reproductive outcomes such as inability to conceive, spontaneous abortion, and low birth weight. Although dozens of DBPs already have been identified, only a few studies have attempted to determine whether DBPs alter male reproductive parameters such as testicular and epididymal histology, testicular and epididymal sperm numbers, and epididymal sperm morphology and motility in laboratory animals. In these studies, alterations in epididymal sperm motility seemed to be predictive of more generalized toxicity of the male reproductive system. Because there is a need to prioritize DBPs for thorough reproductive and developmental toxicity testing, preliminary screening for the potential of DBPs to alter reproductive function seems warranted. Here, we elected to examine only cauda epididymal sperm motion parameters and testicular and epididymal histopathology. The effects of exposure to two commonly occurring DBPs, bromodichloromethane (BDCM) and chloral hydrate (CH), via drinking water were evaluated in F344 rats at an interim (52 week) necropsy during cancer bioassay studies. Exposure to 22 and 39 mg/kg BDCM and 55 and 188 mg/kg CH did not produce any systemic toxicity. Histopathologic evaluation revealed no gross lesions in the reproductive organs, and no tumors were detected in any tissues. In contrast, exposure to 39 mg/kg BDCM significantly decreased the mean straight-line, average path, and curvilinear velocities of sperm recovered from the cauda epididymidis. This BDCM exposure shifted the average path velocity distribution to a lower modal velocity range. Exposure to 188 mg/kg CH significantly decreased both the percentage of motile and progressively motile sperm. This CH exposure shifted the straight-line velocity distribution to a lower modal velocity range. These are the first reproductive toxicity data from exposure to BDCM and CH. The observed effects on sperm motion occurred in the absence of carcinogenesis. Because the effects of BDCM on sperm motility occurred at a lower exposure than that of other DBPs that compromise sperm motility, a thorough reproductive evaluation now is underway.
authors.affiliation: Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Klinefelter
authors.forename: J D
authors.initials: JD
authors.lastname: Suarez
authors.forename: N L
authors.initials: NL
authors.lastname: Roberts
authors.forename: A B
authors.initials: AB
authors.lastname: DeAngelo
mesh_terms: D000818:Animals; D002697:Chloral Hydrate / Q000633:toxicity*; D004202:Disinfectants / Q000633:toxicity*; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013081:Sperm Motility / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*; D022882:Trihalomethanes; D014881:Water Supply / Q000592:standards*
chemical_list: D004202:Disinfectants; D006846:Hydrocarbons, Halogenated; D022882:Trihalomethanes; D002697:Chloral Hydrate; C025191:bromodichloromethane