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) periodically review the recommended Standing Operating Procedures for developing AEGLs.
This interim report presents the committee’s conclusions and recommendations for improving NAC’s AEGL documents for 25 chemicals: allyl alcohol, bis-chloromethyl ether, chloromethyl methyl ether, bromine pentafluoride, bromine trifluoride, chlorine pentafluoride, carbon tetrachloride, chloroform, chlorosilanes (26 selected compounds), epichlorohydrin, formaldehyde, hydrogen bromide, hydrogen iodide, methyl bromide, methyl chloride, nitric acid, nitric oxide, nitrogen dioxide, nitrogen tetroxide, piperidine, titanium tetrachloride, toluene, trimethylbenzenes (1,2,4-; 1,2,5-;and 1,3,5-TMB), vinyl acetate monomer, and vinyl chloride.
At its meeting held on June 15-18, 2010, the committee reviewed the technical support document (TSD) on allyl alcohol. A presentation on the TSD was made by Julie Klotzbach, of Syracuse Research Corporation. The following is excerpted from the Executive Summary of the TSD:
Allyl alcohol is a colorless liquid that is a potent sensory irritant. Signs of intoxication following inhalation exposure to allyl alcohol vapor include lacrimation, pulmonary edema and congestion, and inflammation, hemorrhage, and degeneration of the liver and kidney…. The AEGL-1 values are based upon nasal irritation as indicated by reversible nasal inflammation observed histologically in rats 14 days after exposure to 51 ppm allyl alcohol for 1 hour; 22 ppm for 4 hours, or 10 ppm for 8 hours…. The AEGL-2 was obtained by dividing the AEGL-3 by 3…. The AEGL-3 values are based on the calculated LC01 value in rats of 2600 ppm for 10 minutes, 820 ppm for 30 minutes, 400 ppm for 1 hour, 93 ppm for 4 hours, and 45 ppm for 8 hours.
Page vii, lines 15-18: The TSD notes, “An intraspecies uncertainty factor of 3 and interspecies uncertainty factor of 3 were applied because allyl alcohol is highly irritating and corrosive, and much of the toxicity is likely caused by a direct chemical effect on the tissues; this type of port-of-entry effect is not expected to vary greatly among individuals or among species.” Because effects other than direct-acting effects appear to be occurring, these uncertainty factors should be reviewed and additional justification provided.
Better justification is needed for using the Kirkpatrick (2008) study rather than the Dunlap et al. (1958) study for AEGL-1 values. Although the Kirkpatrick study is newer, it is in rats, and results are reported 14 days postexposure. Were any observations reported during or immediately post exposure? The Dunlap study used human volunteers, and the end points are relevant to deriving AEGL-1 values. Dunlap’s results are supported by Torkelson et al. (1959) and McCord (1932).
Page 11, lines 4-6: “The incidences of alcohol flushing and material around the mouth exhibited a concentration-related increase at 220 and 403 ppm.” Clarification is needed on whether alcohol flushing is a direct-acting irritant effect. In humans, alcohol flushing results from excess aldehyde in the blood from buildup of this metabolite, most commonly in individuals with the slow variant of the aldehdye dehydrogenase gene.