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Cumulative toxicity of an environmentally relevant mixture of nine regulated disinfection by-products in a multigenerational rat reproductive bioassay
Simmons, J., G. Klinefelter, J. Goldman, A. Deangelo, D. Best, T. Mcdonald, L. Strader, A. Murr, J. Suarez, M. George, S. Hunter, AND M. Narotsky. Cumulative toxicity of an environmentally relevant mixture of nine regulated disinfection by-products in a multigenerational rat reproductive bioassay. Presented at Society of Toxicology Meeting, PHOENIX, AZ, March 23 - 27, 2014.
CUMULATIVE TOXICITY OF AN ENVIRONMENTALLY RELEVANT MIXTURE OF NINE REGULATED DISINFECTION BY-PRODUCTS IN A MULTIGENERATIONAL RAT REPRODUCTIVE BIOASSAY J E Simmons, GR. Klinefelter, JM Goldman, AB DeAngelo, DS Best, A McDonald, LF Strader, AS Murr, JD Suarez, MH George, ES Hunter III, MG Narotsky, NHEERL/ORD, U.S. EPA, RTP, NC Disinfection of water has advanced public health by greatly decreasing waterborne disease. Oxidizing disinfectants react with organic materials in the water, forming complex disinfection by-product (DBP) mixtures. While a large unknown fraction remains, >600 DBPs have been identified. Most prevalent in chlorinated water are trihalomethanes (THMs) and haloacetic acids (HAAs); 4 THMs (chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and 5 HAAs (chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, dibromoacetic acid) are regulated by EPA as a group at 80 and 60 μg/L, respectively. This study is the first multigenerational reproductive toxicity bioassay in animals with a drinking water mixture of the regulated THMs and HAAs. At realistic chemical proportions, a mixture was prepared at 0, 500×, 1000×, and 2000× of EPA's maximum contaminant levels (MCLs). Timed-pregnant Sprague-Dawley rats (P0 generation) were exposed from gestation day 0 until weaning of the F1 offspring. Weanlings continued exposure in their respective treatment groups, were examined for reproductive endpoints, and bred to produce F2 litters. Pre- and postnatal survival was unaffected. F1 pup weights were unaffected at birth but reduced at 2000× on postnatal day (PND) 6 and at ≥1000× on PND 21. Males at 2000× had a small but significantly increased incidence of retained nipples and effects on sperm motility. Onset of puberty showed dose-related delays at 1000× and 2000×. F1 estrous cycles, breeding, and fertility were unaffected and F2 litters showed no effects on pup weight, or prenatal or neonatal survival. Histologically, P0 dams had nephropathy and adrenal cortical pathology at 2000×. In sum, while puberty was delayed at DBP concentrations ≥1000× and males at 2000× had retained nipples and altered sperm motility, exposure at these concentrations to the 9 DBP mixture did not affect F1 animals' ability to reproduce. (This abstract does not reflect EPA policy.)
This study is the first multigenerational reproductive toxicity bioassay in animals with a drinking water mixture of regulated THMs and HAAs. At realistic chemical proportions, a mixture as prepared at 0,SOO x, 1000x, and 2000x of EPA's maximum contaminant levels (MCLs).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
INTEGRATED SYSTEMS TOXICOLOGY DIVISION