Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
SUMMARY 4 HFC-236FA On the basis of the available data on HFC-236fa, the subcommittee recommends a 1-hr EEGL of 10,000 ppm, a 24-hr EEGL of 2,000 ppm, and a 90-day CEGL of 350 ppm. The 1-hr EEGL is based on a cardiac sensitization study in which the no-observed-adverse-effect level (NOAEL) for HFC-236fa in dogs was 100,000 ppm for a 5-min exposure. The NOAEL was divided by an uncertainty factor of 10 to account for interspecies variability, yielding a value of 10,000 ppm for exposures up to 1 hr. A 14-week toxicity study in rats was used to determine the 24-hr EEGL for HFC-236fa. In the study, a NOAEL of 20,000 ppm was identified on the basis of decrements in âalerting responseâ (the response to a sudden auditory stimulus). The subcommittee had reservations about using alerting response as a toxicity end point, because effects were transient, responses were subjectively evaluated (and are known to vary among strains and individual animals), and it is unclear whether such effects are applicable to humans. However, in the absence of other data regarding effects caused by HFC-236fa, alerting response was considered to be the most appropriate available end point. A 24-hr EEGL of 2,000 ppm was determined by dividing the NOAEL of 20,000 ppm by an uncertainty factor of 10 to account for interspecies variability. The 14-week toxicity study in rats was also considered to be the most relevant study for calculating the 90-day CEGL. The NOAEL of 20,000 ppm was divided by an uncertainty factor of 10 to extrapolate from animals to humans to yield a value of 2,000 ppm. That value was adjusted to account for the discontinuous exposure regimen used in the study by multiplying 2,000 ppm by 1/4 (to account for exposure for 6 hr per day) and by 5/7 (to account for exposure five times per week), which yielded a 90-day CEGL of 350 ppm. If HFC-236fa is considered for use on vessels with female crew members, the 24-hr EEGL and 90-day CEGL might have to be reconsidered on the basis of maternal toxicity. A developmental toxicity study in rats reported reduced weight gain and decrements in alerting response in pregnant animals exposed at 20,000 ppm. That is the same concentration as the NOAEL in the 14-week toxicity study used to calculate the 24-hr EEGL and the 90-day CEGL. Uncertainties exist with regard to the effects that HFC-236fa might have on human performance. End points of narcosis and decrements in alerting response have been observed in laboratory animals, but it is unclear whether human performance would be similarly affected. Because HFC-236fa was
