COMMENTS ON CHLOROMETHYL METHYL ETHER

At its January 28–30, 2004, meeting, the subcommittee reviewed the AEGL document on chloromethyl methyl ether (CMME). The presentation was made by Sylvia Milanez of Oak Ridge National Laboratory. The subcommittee recommends a number of revisions. A revised draft would be reviewed by the subcommittee at its next meeting.

Overall Comments

The subcommittee recommends that comments on the AEGL values that would be derived on the basis of the toxicity for bis-chloromethyl ether (BCME) be added to the document. The AEGLs for BCME are expected to be similar to those calculated for CMME, after adjusting for the level of contamination. The explanations for not deriving an AEGL-1 need to be consistent throughout the document. Because CMME is classified as a human carcinogen, more detail on the cancer risk assessment and how it impacts on the AEGL values should be included in the main text of the document. The subcommittee recommends that data from single dose studies, including those involving BCME, be examined in more detail prior to AEGL-2. The use of single exposure studies might lead to AEGL-2 values exceeding those calculated on the basis of carcinogenicity. The sensitivity of the cancer risk assessment to different BCME contamination levels should also be examined. It should also be noted that the International Agency for Research on Cancer (IARC) classifies CMME as a “possible human carcinogen,” category 2B.

General Comments

The subcommittee was concerned about the use of a repeat exposure study (Drew et al. 1975) to derive the AEGL-2 values and suggests recalculating the AEGL-2 values using the single 7-hour exposure study in which exposures to CMME ranged from 0.7 to 9.5 ppm (Drew et al. 1975) and the single exposure studies with BCME. There was concern that the repeat exposure study might be inappropriate for the derivation of AEGL-2 values. At the concentration used to derive AEGL-2 values, 2 of 25 rats died, and death is an AEGL-3 effect. Three possible solutions were discussed:

  1. The easiest solution, but perhaps not the best, is to make a clear statement of why the repeat exposure study was used as the basis for AEGL-2 despite the occurrence of this AEGL-3 effect (e.g., by arguing that in the view of the author there is no good single exposure study, so, this multiple exposure study was chosen). Because of the repeated exposures, 2 of 25 rats died at 1 ppm, but that can be disregarded because a single exposure study acceptable for deriving AEGL-3 showed a LC01 (lethal concentration in one percent of the exposed animals) of 15 ppm (Drew et al. 1975).

  2. An alternative solution is to use the lung edema (lung-to-body weight change) from the single exposure study (Drew et al. 1975) to derive AEGL-2 values if that effect can be



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