The NRC convened the Committee on Acute Exposure Guideline Levels to review the AEGL documents approved by NAC. The committee members were selected for their expertise in toxicology; medicine, including pharmacology and pathology; industrial hygiene; biostatistics; and risk assessment.
The charge to the committee is to (1) review the proposed AEGLs for scientific validity, completeness, internal consistency, and conformance to the NRC (1993) guidelines report; (2) review research recommendations and—when appropriate—identify additional priorities for research to fill data gaps; and (3) review periodically the recommended standard procedures for developing AEGLs.
This interim report presents the committee’s conclusions and recommendations for improving the following AEGL technical support documents (TSDs): aliphatic nitriles (acetonitrile, isobutyronitrile, propionitrile, chloroacetonitrile, and malononitrile), benzonitrile, and methacrylonitrile. These documents were reviewed by the committee at a meeting on May 2-4, 2012.
The committee reviewed the AEGL TSD on five aliphatic nitriles (acetonitrile, isobutyronitrile, propionitrile, chloroacetonitrile, and malononitrile) that was presented by Julie Klotzbach of SRC, Inc. Table 1 presents a summary of the proposed AEGL values for the aliphatic nitriles and their basis. The committee agreed that its previous comments (NRC 2011a) on the TSD have been adequately addressed, and that the document can be finalized for publication after a few clarifications and editorial changes are made.
A statement of caution should be given for the cumulative effects of concomitant exposure to multiple aliphatic nitriles that share a common mechanism of toxicity through their biotransformation to cyanide.
For each of the aliphatic nitriles with extant standards and guidelines, more substantive discussion should be added about the basis for the differences between the AEGL values and other relevant guidelines. Simply presenting the other values without discussion is not sufficiently informative. See section on Comments Relevant to All AEGL TSDs in Part A of this report (NRC 2012) for guidance.
AEGL Specific Comments
The context for selecting the point-of-departure for AEGL-3 values should include the following data:
• Maternal deaths were observed after exposure to acetonitrile at 400 and 1,200 ppm in the NTP (1994) study
• Deaths of male rats exposed at 800 and 1,600 ppm and female rats at 1,600 ppm in the NTP (1996) study; the deaths that occurred during week 1 of the 13-week segment of the study are especially pertinent.
Because the number of days of exposure preceding death of these adult rats was not reported, the rationale for selecting a higher point-of-departure can be strengthened by emphasizing embryonic and fetal end points that could occur after a single exposure. Moreover, a no-effect level of 1,200 ppm for fetal effects in the NTP (1994) study also lends support for the 6-h point-of-departure of 1,500 ppm from the Saillenfait et al. (1993) study.