Development of an inhalation unit risk factor for ethylene dibromide.

The Texas Commission on Environmental Quality (TCEQ) follows standard scientific methods to develop up-to-date toxicity factors for chemicals emitted in the state of Texas. An inhalation unit risk factor (URF) was developed for ethylene dibromide (EDB, CAS 106-93-4) based on an increased incidence of nasal cavity adenocarcinomas observed in female rats in a 2-year inhalation cancer bioassay conducted by the National Toxicology Program (NTP). The NTP study provided evidence of several EDB-induced tumors in male and female rats and in female mice. Tumor incidences that were statistically increased at the low dose and that showed a statistically significant increasing trend were considered in identifying the critical effect. Following benchmark concentration (BMC) modeling and animal-to-human dosimetric adjustments, the increased incidence of nasal cavity adenocarcinomas observed in female rats was determined to be the most sensitive tumorigenic effect in the most sensitive species and sex and was utilized as the carcinogenic endpoint for the development of the URF. The 95% lower confidence limit of the BMC at the 10% excess risk level (BMCL10 of 292.8 ppb) was determined for calculation of the URF. The resulting URF based on increased nasal cavity adenocarcinomas observed in female rats is 3.4E-04 per ppb (4.4E-05 per µg/m3). The lifetime air concentration corresponding to a no significant excess risk level of one in 100,000 is 0.029 ppb (0.22 µg/m3), which is considered sufficiently health-protective for use in protecting the general public against the potential carcinogenic effects of chronic exposure to EDB in ambient air.

Regulation and the use of "negative" results from human reproductive studies: the case of ethylene dibromide.

This paper examines the regulatory usefulness of five studies of the reproductive effects of occupational exposure to ethylene dibromide. None of the studies found a statistically significant adverse effect. Results from an epidemiologic study can find no adverse effect either because there is in fact no association between the outcome and the exposure being studied or because the study was not powerful enough to detect an association between the two. This distinction is especially important when "negative" studies are offered as evidence that a chemical is not harmful to workers. General reasons for low power in reproductive studies are discussed, and each of the studies is examined to see if the results were in fact negative and what factors were operating to affect the power of each study. Four of the studies showed potential reproductive impairments that were not large enough to be judged statistically significant by the authors. The power of all of these studies was then examined and found to be low for a number of reasons. These studies therefore do not represent evidence that ethylene dibromide is harmless; on the contrary, they may indicate the opposite. In general, when regulating potentially harmful chemicals in a low-power situation, power should be raised by raising the alpha level of the study, especially when animal data show a strong positive effect.