Neurotoxicological evaluation of two disinfection by-products, bromodichloromethane and dibromoacetonitrile, in rats.
The Safe Drinking Water Act requires that the U.S. EPA consider noncancer endpoints for the assessment of adverse human health effects of disinfection by-products (DBPs). As an extension of our studies in which we demonstrated neurotoxicity at relatively low levels of dibromo- and dichloroacetic acids, we examined the potential neurotoxicity of other classes of DBPs. Bromodichloromethane (BDCM) and dibromoacetonitrile (DBAN) were administered to male and female F-344 rats via drinking water for 6 months. During exposure, rats were tested for neurobehavioral effects using a functional observational battery and motor activity, followed by perfusion fixation for neuropathological evaluation at the end of exposure. Calculating for chemical loss, fluid consumption, and body weight, average intakes were approximately: 9, 27, and 72mg/(kgday) BDCM, and 5, 12, and 29mg/(kgday) DBAN. Fluid consumption was decreased in most treatment groups, but body weight gain was altered only at the high concentrations. There were few neurobehavioral changes, and these were not considered toxicologically relevant. Of the general observations, there was only minimally decreased body tone in DBAN-treated high-dose males. Treatment-related neuropathological findings were not observed. Lowered fluid consumption was the most sensitive and consistent endpoint in the present studies. Thus, unlike the haloacetic acids, neurotoxicity may not be a concern for toxicity of halomethanes or haloacetonitriles.
Moser
Virginia C
VC
Neurotoxicology Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. moser.ginger@epa.gov
Phillips
Pamela M
PM
McDaniel
Katherine L
KL
Sills
Robert C
RC
D000097:Acetonitriles / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D005260:Female; D006651:Histocytochemistry; D016014:Linear Models; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D022882:Trihalomethanes / Q000008:administration & dosage / Q000633:toxicity
D000097:Acetonitriles; D002273:Carcinogens; D022882:Trihalomethanes; C025191:bromodichloromethane; C051715:dibromoacetonitrile