Article

Integrated disinfection by-products mixtures research: assessment of developmental toxicity in Sprague-Dawley rats exposed to concentrates of water disinfected by chlorination and ozonation/postchlorination.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Journal of Toxicology and Environmental Health Part A (impact factor: 1.83). 01/2008; 71(17):1216-21. DOI:10.1080/15287390802182623
Source: PubMed

ABSTRACT Epidemiological and animal toxicity studies have raised concerns regarding possible adverse health effects of disinfection by-products (DBPs) found in drinking water. The classes and concentrations of DBPs are influenced by the choice of disinfection process (e.g., chlorination, ozonation) as well as source water characteristics (e.g., pH, total organic carbon, bromide content). Disinfected waters were found to contain more than 500 compounds, many of which remain unidentified. Therefore, a "whole-mixture" approach was used to evaluate the toxic potential of alternative disinfection scenarios. An in vivo developmental toxicity screen was used to evaluate the adverse developmental effects of the complex mixtures produced by two different disinfection processes. Water was obtained from East Fork Lake, Ohio; spiked with iodide and bromide; and disinfected either by chlorination or by ozonation/postchlorination, producing finished drinking water suitable for human consumption. These waters were concentrated approximately 130-fold by reverse osmosis membrane techniques. To the extent possible, volatile DBPs lost in the concentration process were spiked back into the concentrates. These concentrates were then provided as drinking water to Sprague-Dawley rats on gestation days 6-16; controls received boiled, distilled, deionized water. The dams (19-20 per group) were allowed to deliver and their litters were examined on postnatal days (PD) 1 and 6. All dams delivered normally, with parturition occurring significantly earlier in the ozonation/postchlorination group. However, no effects on prenatal survival, postnatal survival, or pup weight were evident. Skeletal examination of the PD-6 pups also revealed no treatment effects. Thus, approximately 130-fold higher concentrates of both ozonated/postchlorinated and chlorinated water appeared to exert no adverse developmental effects in this study.

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    Article: Prospective power calculations for the Four Lab study of a multigenerational reproductive/developmental toxicity rodent bioassay using a complex mixture of disinfection by-products in the low-response region.
    Cheryl A Dingus, Linda K Teuschler, Glenn E Rice, Jane Ellen Simmons, Michael G Narotsky
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    ABSTRACT: In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non-independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA's Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by-products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss.
    International Journal of Environmental Research and Public Health 10/2011; 8(10):4082-101. · 1.61 Impact Factor
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Keywords

130-fold higher concentrates
 
500 compounds
 
adverse developmental effects
 
alternative disinfection scenarios
 
animal toxicity studies
 
chlorinated water
 
deionized water
 
drinking water
 
drinking water suitable
 
East Fork Lake
 
gestation days 6-16
 
PD-6 pups
 
postnatal days
 
reverse osmosis membrane techniques
 
source water characteristics
 
Sprague-Dawley rats
 
total organic carbon
 
toxic potential
 
vivo developmental toxicity screen
 
volatile DBPs