Citation:

NAROTSKY, M. G., D. S. BEST, T. A. MCDONALD, E. MYERS, E. S. HUNTER, AND J. E. SIMMONS. EFFECTS OF DEFINED MIXTURES OF TRIHALOMETHANES AND HALOACETIC ACIDS ON PREGNANCY MAINTENANCE AND EYE DEVELOPMENT IN F 344 RATS. Presented at Gordon Conference on Drinking Water Disinfection By-products, S. Hadley, MA, August 13 - 19, 2006.

Description:

Although disinfection of drinking water is important for control of microbial contamination, it results in the formation of hundreds of disinfection by-products (DBPs). The most prevalent DBPs are trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acid). THMs and HAAs are regulated in drinking water at 80 and 60 ¿g/L, respectively. In rats, THMs have been shown to cause pregnancy loss (i.e., full-litter resorption, an all-or-none effect). HAAs have been shown to cause eye defects and partial-litter, as well as full-litter, resorption (i.e., not an all-or-none effect). 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 tap water; e.g., in DBP9, molar percentages of the respective chemicals were 30.0, 11.9, 7.0, 1.0, 1.7, 22.7, 15.9, 8.2, and 1.5. Mixtures, prepared in 10% Alkamuls® EL-620, were administered daily to F344 rats by gavage on gestation days 6-20. Litters were examined on postnatal days 1 and 6. For the THM4 mixture, pregnancy loss was seen in 0/14, 0/25, 11/14 (79%), and 12/13 (92%) of the dams at 0, 307, 613, and 920 ¿mol/kg, respectively. Pup weights were reduced at 613 and 920 ¿mol/kg. Postnatal loss was increased at 920 ¿mol/kg. For the HAA5 mixture, pregnancy loss was seen in 0/9, 0/15, 3/17 (18%), and 11/11 (100%) of the dams at 0, 308, 615, and 1231 ¿mol/kg, respectively. Eye malformations (anophthalmia or microphthalmia) were seen in 0, 53%, and 79% of the live litters at 0, 308, and 615 ¿mol/kg. Prenatal loss was unaffected in live litters. For the DBP9 mixture, pregnancy loss was seen in 0/18, 0/19, 6/17 (35%), and 7/8 (88%) of the dams at 0, 307, 615, and 1228 ¿mol/kg, respectively. In live litters, prenatal loss was unaffected. Thus, THM4, HAA5, and DBP9 each caused pregnancy loss at ¿613 ¿mol/kg; 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. [This abstract does not necessarily reflect EPA policy.]

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