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Abstract for RACB90062

Reproductive Toxicity of a Mixture of Ground Water Contaminants in Sprague-Dawley Rats

Report Date: March 1991


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

A chemical mixture of 25 ground water contaminants (MIX) was tested for its effects on fertility and reproduction in Sprague-Dawley (CD) rats using the continuous breeding protocol. The dose levels of 1, 5, and 10% of the maximum technically achievable stock (l0X, 50X, and 100X) were administered via drinking water. Male and female rats (F0) were continuously exposed for a 7-day pre cohabitation and a 16 week cohabitation period (Task 2).

MIX treatment had no effect on F0 fertility. Male and female body weights in Task 2 were within 10% of control values. Reproduction endpoints adversely affected in the F0 generation were male live pups per litter, live pup weight (absolute and adjusted), cumulative days to deliver 1st, 2nd, and 3rd litter, and dam weights at delivery. The water consumption values in all three treated groups were significantly decreased.

The F1 pups from the final litter in control and 10% groups were weaned for second generation studies. Male and female pup weights ( F1) were significantly lower on postnatal days 0, 4, 7, 14, and 21 in the treated group. F1 body weights in the 10% group continued to be lower until terminal necropsy. As anticipated, water consumption was significantly lower in the 10% group. The fertility index was not affected by Complex Mixture treatment in the F1 generation, but live F2 pup weights, both absolute and adjusted, were significantly decreased. At F1 necropsy, all organ weight values were lower than the control values and differences for a number of organs were significant even when expressed as organ-to-body weight ratios.

Sperm motility, sperm count, incidence of abnormal sperm, estrous cycle length, and the relative frequencies of different estrous stages in F1 rats were not affected. Based on the present study it is concluded that MIX at 1, 5, and 10% levels is unpalatable, primarily causes weight changes that appear secondary to decreased fluid intake, and is not a selective reproductive toxicant.

NTIS # PB91184739