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Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids
Citation:
NAROTSKY, M. G., D. S. BEST, A. Mc Donald, E. A. Godin, E. S. HUNTER, AND J. E. SIMMONS. Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 31(1):59-65, (2011).
Impact/Purpose:
This report describes research evaluating the effects of mixtures of regulated disinfection by-products (DBPs), administered by gavage, in pregnant F344 rats. Although many of the DBPs have been evaluated individually, tap water contains DBPs as a mixture. Thus, this research evaluated mixtures of the four regulated trihalomethanes (THMs), the five regulated haloacetic acids (HAAs), and all nine of these DBPs using chemical proportions seen in chlorinated tap water. Mixtures were evaluated in F344 rats, a strain shown to be sensitive to toxicantinduced pregnancy loss as well as toxicant-induced eye malformations. HAAs, evaluated for the first time in this sensitive research model, caused pregnancy loss; this is the first report of this effect for HAAs. Furthermore, HAAs contributed to the potency of THMs in causing pregnancy loss. In contrast, THMs reduced the potency of HAAs in causing eye malformations. This report gives insights into the combined effects of the HAAs and THMs and will aid in the risk assessment of these DBPs in drinking water.
Description:
Chlorination of drinking water results in the formation of hundreds of disinfection byproducts (DBPs), the most prevalent are trihalomethanes (THMs) and haloacetic acids (HAAs). Four THMs (chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five HAAs (chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibrornoacetic acid) are regulated in drinking water. In rats, THMs have been shown to cause pregnancy loss (i.e., full-litter resorption, an all-or-none effect) but teratogenicity has not been observed. HAAs produce terata and cause partial- and full-litter, resorption (i.e., not all-or-none). Here, we assessed the combined toxicity of these DBPs. Rats were treated with mixtures of four THMs (THM4), five HAAs (HAA5), or nine DBPs (DBP9; THM4+HAA5). Chemical proportions reflected those in chlorinated tap water. Mixtures, in 10% AlkamulsB EL-620, were administered daily to F344 rats by gavage on gestation days 6-20. For THM4, pregnancy loss was seen in 0114, 0126, 11114 (79%), and 12113 (92%) of the dams at 0, 307, 613, and 920 pmollkglday, respectively. For HAA5, pregnancy loss was seen in 019, 0115, 3117 (18%), and 1011 1 (91%) of the dams at 0, 308, 615, and 1231 prnollkglday, respectively. Eye malformations (anophthalmia, microphthalmia) were seen in 0, 53%, and 79% of the live litters at 0, 308, and 615 pmollkglday. Prenatal loss was unaffected in live litters. For DBP9, pregnancy loss was seen in 0118, 011 9, 611 7 (35%), and 718 (88%) of the dams at 0, 307, 615, and 1228 prnollkglday, respectively. In live litters, prenatal survival and eye development were unaffected by treatment. Thus, THM4, HAAS, and DBP9 each caused pregnancy loss at 2613 pmollkglday; i.e., both HAAs and THMs contributed to DBP9-induced pregnancy loss. The presence of THMs in the full mixture, however, reduced the incidence of HAA-induced eye defects. September 20,2008 Key words: disinfection by-products, trihalomethanes, haloacetic acids, mixtures, developmental toxicity, pregnancy loss, anophthalmia
