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 NAC’s 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 NAC’s AEGL documents for 29 chemicals: chloroacetyl chloride, dichloroacetyl chloride, methanesulfonyl chloride, trimethylacetyl chloride, bromoacetone, butane, BZ (3-quinuclidinyl benzilate), chloroacetone, epichlorohydrin, ethyl phosphorodichloridate, ethylene chlorohydrin (2-chloroethanol), isocyanates (cyclohexyl, ethyl, and phenyl isocyanates), mercaptans (ethyl, methyl, phenyl, and tert-octyl mercaptans), methacrylonitrile, methyl bromide, methyl chloride, methyl isothiocyanate, nitrogen mustards (HN-1, HN-2, and HN-3), perchloryl fluoride, piperidine, tetramethoxysilane, and trimethoxysilane.
At its meeting held on April 5-7, 2011 the committee review the technical support documents (TSDs) on chloroacetyl and dichloroacetyl chloride (CAC and DCAC, respectively), methanesulfonyl chloride, and trimethylacetyl chloride. Presentations of the CAC and DCAC and trimethylacetyl chloride TSDs were made by Lisa Ingerman of Syracuse Research Corporation. A presentation of methanesulfonyl chloride was made by Julie Klotzbach of Syracuse Research Corporation. Although CAC and DCAC are combined into a single TSD, AEGL-specific comments below are separated.
The following is excerpted from the Executive Summary of the TSD:
Because the database for DCAC was very limited, and the available data indicated that DCAC was less toxic than CAC, all AEGL values developed for CAC were adopted for DCAC…. AEGL-1 values were derived from a multiple-exposure study in which rats, mice, and hamsters received 18-20 exposures for 6 hours/day to nominal concentrations of 0.5, 1, 2.5 or 5 ppm CAC (Dow 1982)…. The AEGL-2 values were derived using a study in which rats inhaled 32, 208, 522, or 747 ppm CAC for 1 hour (Dow 1986)…. The AEGL-3 values were also based on the Dow (1986) 1-hour inhalation rat study in which exposure was to 32, 208, 522, or 747 ppm CAC.
A revised document should be submitted to the committee for review.
AEGL-Specific Comments for Chloroacetyl Chloride
Page 26, lines 26-28: “AEGL-1 values were derived using a single 6-hour exposure to ~1 ppm (0.84 ± 0.51 ppm) because this is the highest concentration that caused conjunctival redness but no other more serious effects after one exposure.” The authors should revisit the point of departure (POD) for the