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 n-butyl isocyanate.

n-Butyl Isocyanate

At its meeting held on April 5-7, 2011, the committee reviewed the AEGL technical support document (TSD) on n-butyl isocyanate. Presentation on the TSD was made by Heather Carlson-Lynch, of Syracuse Research Corporation.

The following is excerpted from the Executive Summary of the TSD:

The basis for derivation of AEGL-1 values for n-butyl isocyanate was industrial hygiene reports indicating that occupational exposure to 40 ppb (0.040 ppm) n-butyl isocyanate was without ocular irritation (DuPont, 1986; DuPont, 2008).… The 50 ppb (0.050 ppm) exposure from the DuPont (1986) report was actually 70 ppb (0.070 ppm). This was considered a protective POD for AEGL-2 derivation because the ocular irritation was neither escape impairing nor irreversible…. The 4-hour BMCL05 of 3.35 ppm from the DuPont (1968) rat study was used as the POD for AEGL-3 derivation

AEGL-Specific Comments

The use of the industrial hygiene data (DuPont 1986, 2008) needs to be reconsidered. At least the data needs further delineation of its limitations in the TSD text. The first “experiment” involved five individuals with one measurement each. All individuals, presumably workers, acclimated to the isocyanate irritant effects. The second experiment involved voluntary reports by supervisors. The document suggests that there were no reports on a clipboard, from which they deduced that the air levels monitored did not cause problems. The latter information, or lack of data, should not be interpreted to mean that there were no effects. The most that can be said is that no effects were reported. These limitations have an impact on the scientific credibility of the AEGL-1 and AEGL-2 values.


Page 9, lines 23-35: “An industrial hygiene survey (DuPont, 1986) reported that exposure to nbutyl isocyanate at a concentration of 5 to 10 ppb (0.005 to 0.01 ppm) resulted in ocular irritation. At exposure levels of 50 ppb (0.05 ppm), normal work operations were not possible but exposure at this level was not expected to impair escape ability. A more recent communication (DuPont, 2008) reported that analytical techniques (impinger/gas chromatograph method) used in sampling analysis in the earlier DuPont report were underestimating n-butyl isocyanate levels. For levels less than 20 ppb, use of the more advanced XAD7 tube/HPLC method gave n-butyl isocyanate levels that were 2 to 4 fold greater than the previous method. At higher concentrations, measurements using the newer method resulted in n-

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