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 (SOP) 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.

ACRYLONITRILE

At its meeting held on October 26-29, 2010, the committee reviewed the technical support document (TSD) on acrylonitrile. 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:

Nonlethal effects of occupational exposure to AN [acrylonitrile] include headache, nasal and ocular irritation, thoracic discomfort, nervousness and irritability.… The AEGL-1 values were based on the absence of effects in informed human volunteer subjects (6 males) exposed for 8 hours to 4.6 ppm AN.… The 4.6 ppm value is recommended for all AEGL-1 exposure durations…. The AEGL-2 values were based upon slight transient effects in rats exposed to 305 ppm AN for 2 hours…. The AEGL-3 values were derived using 30-minute, 1-, 4-, and 8-hour BMCL05 estimates of lethality threshold.

A revised document should be submitted to the committee for review.

AEGL-Specific Comments

AEGL-1

The point of departure (POD) of 4.6 ppm is based on six male toxicologist volunteers 28-45 years old (Jakubowski et al. 1987). A discussion of the uncertainty associated with the POD should include considerations that the focus of this study was for the metabolism of arylonitrile, not for identifying acute toxicity. In additions, considerations should be given for the small sample size, and the male-only adult subjects.

Further, it should be clearly stated that the volunteers for the Jakubowski study were toxicologists working in the same laboratory as the lead authors, as this raises some ethical concerns. Yet, as three studies (Jakubowski, Sakurai, and personal communication) indicate a similar effect level, the committee agrees with the choice of the Jakubowski study for AEGL-1. Also see “Other Comments” regarding Page 10, lines 10-12, regarding the use of “personal communication” as supporting evidence.

Page 6, lines 13-14 (also see page 15, line 11): Since children may be more sensitive to acute inhalation, given that the POD was based on observations in adult males, the decision for not applying an intraspecies uncertainty factor (UF) to derive the AEGL-1 needs either adequate justification or revision.

Page 30, Section 5.1, Human Data Relevant to AEGL-1 (also see page 31, lines 14-35): The TSD also enlisted three ranges of occupational exposure as lending support to the proposed AEGL-1



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