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Assessment of Diiodoacetic Effects on Eye Malformations in a Developmental Toxicity Screen with F344 Rats
Fuentes, L. AND M. Narotsky. Assessment of Diiodoacetic Effects on Eye Malformations in a Developmental Toxicity Screen with F344 Rats. Triangle Consortium of Reproductive Biology, Research Triangle Park, NC, February 10, 2018.
This abstract will be presented at the Triangle Consortium of Reproductive Biology. It describes the findings of a dose-response study of a developmental toxicity screen with Diiodoacetic acid, a drinking water contaminant and disinfection by-product.
Diiodoacetic acid (DIA) is an iodinated haloacetic acid and a drinking water disinfection by-product (DBP) formed in drinking water treated by chloramination (chlorine plus ammonia) to prevent microbial contamination and regrowth. Although disinfection of drinking water has proven to be successful in decreasing disease, the interaction between the disinfectant and organic materials in the source water produces hundreds of DBPs. In order to protect public health, the Environmental Protection Agency (EPA) has implemented regulatory limits for the amount of certain contaminants in public water systems. Disinfection by chlorination has been typically preferred by US water utilities, however, chloramination is an alternative method that is being used with increasing frequency because it forms smaller amounts of the EPA-regulated DBPs. On the other hand, chloramination has produced new, non-regulated, DBPs, many of which with little, if any, toxicological data available. A dose-response developmental toxicity study was conducted by administering DIA via gavage to timed-pregnant F344 rats daily on gestation days (GD) 6-10 at 0, 25, 50, 75, 100, 150, and 200 mg/kg. The study was conducted in two blocks; DIA treated groups had four to seven pregnant dams per group. F344 rats are used as the preferred research model due to its sensitivity to toxicant-induced pregnancy loss and eye malformation. DIA was administered during GD 6-10, as this time frame encompasses the critical period when eye development occurs. Dams were allowed to deliver and on postnatal day (PD) 1, all pups were weighed, sexed, and examined for any abnormalities. Pups were subsequently examined on PD 6 and then euthanized. Maternal uterine implantation sites were counted to determine prenatal loss. There was significant maternal weight loss after 2 days of dosing at 150 and 200 mg/kg. There were no effects on prenatal or postnatal survival and no effects on pup weight. Pups with micro- or anophthalmia (confirmed at necropsy) were present in two of five litters at 150 mg/kg and one of four litters at 200 mg/kg. Thus, these preliminary findings indicate that DIA causes maternal toxicity and eye malformations at the two highest dose levels. Further work will be pursued that may provide insights toward characterizing the effects of DIA on developmental toxicity in F344 rats. [This abstract does not necessarily reflect EPA policy.]
Record Details:Record Type: DOCUMENT (PRESENTATION/POSTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
REPRODUCTIVE TOXICOLOGY BRANCH