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TENTH INTERIM REPORT OF THE SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS 10 It appears that PO may cause cancer by mixed modes of action (i.e., genotoxicity and cellular proliferation would both be required), as is the case for formaldehyde. The current document should address (1) the weight of scientific evidence for this versus other mechanisms; and (2) what type of biologically-based cancer risk assessment would be most appropriate in each instance. This discussion would include the present description of the linearized multistage model, though so much detail about the default EPA (1987) risk assessment paradigm is probably not necessary. Four more references (in addition to Rios-Blanco et al. 2003a & b) are included under Additional References, and those data may be of use in the document. AEGL-1 Values The total set of human data (13.2â15.20 ppm) should be presented to justify the identification of the NOAEL for AEGL-1 derivation. The n value should be 1, rather than 1.2, for irritant effect. The supporting data and corroborative studies should be presented in the text and not in tables along with an alternative set of AEGLs. AEGL-2 Values The derivation of alternative sets of AEGL values need not be done, since this will cause confusion (e.g., Tables 21 vs 22). The data and studies, supportive of the derived AEGL, can simply be presented and referenced in the text. Why was 15.20 ppm not used, even though it was associated with the same effect as 380â525 ppm (i.e., âirritation was not intolerableâ)? AEGL-3 Values The end point selected for derivation of the AEGL-3 is the same as that for AEGL-2. More appropriate animal studies could be used to derive the AEGL-3 values, and those can be supported with the human data. In any case, the use of a single, free-standing human number (as presented in the text) is not convincing. Cancer Risk Assessment The potency of PO as a rodent carcinogen needs to be clearly documented. There are large populations of human veterinary pathologists, embalmers, and workers in biology museums, who were exposed to formaldehyde vapors for 30 to 40 years. This was before mandated air quality standards were applied only 30 years ago. Are there any epidemiologic data that demonstrate that formaldehyde is a human carcinogen? Since PO is compared with formaldehyde, what kinds of effects are expected? This section should put primary emphasis on the key short-term studies (8 days and 30 days). These studies should be presented in greater detail. The total cumulative dose associated with the observed outcome may be used to support the AEGL-3 values based on other effects.
