||K S Crump Group, Inc., Research Triangle Park, NC.; Dow Corning Corp., Midland, MI.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
A series of reproductive studies has provided consistent evidence that OMCTS caused decreases in mean litter size, numbers of pups born, and numbers of uterine implantation sites in the Sprague-Dawley rat. The smallest lower statistical confidence bound on the benchmark dose (BMDL) estimated from these data was 51 mg/kg/day (323 ppm). Human exposures either in the workplace, through consumer products, or in the general environment that result in estimates of intake of at least 100-fold lower than the BMDL, i.e., a margin of exposure (MOE) of 100 or greater, are not expected to cause any adverse reproductive effects in those populations. All MOEs calculated for the selected receptors were greater than 100 and with few exceptions were greater than 1000. When the impact of assumptions regarding dermal absorption and route equivalence is considered, all MOEs for consumer use products are greater than 1000 and, for many products, greater than 10,000. MOEs of even greater magnitude are tissue rather than estimates of intake across the biological barrier. MOE's may be further increased when the species- and strain-specific modes of action can be considered. This risk assessment is preliminary and will be refined when an ongoing two generation reproductive study is completed. However, given the several major assumptions that result in overestimates of intake and the assumptions with regard to route and species extrapolation, these preliminary MOEs are more likely to increase than to decrease. Conclusions with regard to the lack of potential for risk to reproduction in populations exposed, as described in the exposure assessment, are likely to remain unchanged in the final risk assessment.