Because mice do not have susceptibility alleles equivalent to those found in humans, new knock-in mouse models with human alleles associated with a range of BeS/CBD risk are being developed that may be useful in experimental study of beryllium dose-response, beryllium type and characteristics conferring risk, dose rate, and therapeutic approaches to beryllium disease.
Historically, CBD is the noncancer health end point on which occupational exposure limits are based. The epidemiologic evidence shows that the long-standing limit of 2 μg/m3 is inadequate for preventing CBD. The studies have also shown that the risk of CBD in workers depends on the industry, process, and physicochemical form of beryllium being handled. In general, BeS should be regarded as an early marker of disease that is likely to progress to CBD, although the timing and probability of progression are not well-defined. There is growing evidence that skin exposure may be an important contributor to sensitization and development of CBD.
The use of the BeLPT and worker surveillance programs now allow earlier identification of people who are sensitized and who are at risk of CBD. It is clear from animal and human data that susceptibility to CBD has a genetic component and, as noted in Chapter 2, the physiochemical properties of the beryllium and the route of exposure also play a role.
There are currently no adequate animal models of CBD. However, efforts are under way to create mouse models with human alleles associated with a range of BeS and CBD risk that may be useful in experimental study of beryllium dose-response, beryllium type and characteristics conferring risk, dose rate, and therapeutic approaches to beryllium diseases.
In its second report, the committee will evaluate critical health end points on which to base chronic inhalation exposure levels, and consider how susceptibility to CBD should be factored into a risk assessment. The committee will also discuss aspects of the use of the BeLPT in routine surveillance and medical monitoring, including the value of the BeLPT in predicting CBD, protocols for further followup tests after a positive BeLPT result, the likelihood of developing CBD after a true positive test, and a standardized method for achieving consistent test results in different laboratories.