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TENTH INTERIM REPORT OF THE SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS 20 Page 8, line 21. The factor of 3 is not a modifying factor but an adjustment for molar equivalency. This needs to be revised to be consistent with pages A-2 and C-2. The AEGL-2 and AEGL-3 were derived using the HCl data for time scaling but in each case a different approach was taken with the same data. This is inconsistent because the AEGL document on HCl may soon be finalized with a similar issue, it will be necessary to make these two documents consistent. If the AEGL document for HCl is not finalized, then it is recommended that time scaling approaches using the same data should be consistently applied. COMMENTS ON ETHYLENIMINE At its July 21â23, 2003 meeting, the subcommittee reviewed the revised AEGL document on ethylenimine. The document was presented by Kowetha Davidson of Oak Ridge National Laboratory. The subcommittee recommends a number of revisions. General Comment There are relatively few publications available from which to derive AEGLs, but derivation of the AEGL-1 (page vi, line 4â5) is problematic. Upon what basis was an AEGL-2 value divided by one half to obtain an AEGL-1? Since no data were available for deriving AEGL-1 values (page vi, line 11), ethylenimine has poor warning properties (page vi, line d16) and death and other signs of poisoning can be delayed some 3 to 7-hr after exposure. Therefore, consideration should be given for not recommending an AEGL-1 for this material. In order to simply divide an AEGL-2 based on âextreme respiratory difficulty in guinea pigsâ by two or any other value to obtain an AEGL-1 (notable discomfort and irritation), some indication of the slope of the concentration- response relation must be given. As written, derivation of the AEGL-1 does not appear founded in rigorous science. Specific Comments Page vi, lines 28â29. The NAC suggests that the âdirect alkylating activity of ethylenimine is not expected to vary markedly among individuals in the population.â No empirical evidence or citations to peer-reviewed literature were supplied to support that contention. Even if the alkylating events proceed in a similar fashion and the time course at the nucleic acid and protein level between different people was identical, it is the repair of such molecular lesions that seems to account for different outcomesâunless of course the damage is so extensive that normal repair is overwhelmed. More extensive discussion of the basis for the NAC conclusion is needed here. Page 3, lines 40â43 and page 4, lines 1â28. The Weightman and Hoyle (1964) report does not add much to the TSD for ethylenimine. Exposure was to several chemicals, one of which is
TENTH INTERIM REPORT OF THE SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS 21 ethylenimine. It needs to be explicitly stated that one cannot attribute the observed effects directly to ethylenimine. Page 3, line 40; page 19, line 24. Indicate whether these subjects were volunteers. Page 5, line 41. What is an âairlineâ respirator? Does this sentence mean to convey that these workers were equipped with personal protective clothing and an air-supplied respirator (as indicated on line 37)? Page 5, line 25. In what cells or tissues were the chromosome aberrations measured? Page 6, line 7. As written, the text suggests the odor of ethylenimine could be confused with that of ammonia? How does âbecause its odor is similar to that of ammoniaâ indicate poor warning properties for ethylenimine? Page 8, line 10. Note nasal irritation also occurred at 100 ppm or higher. Page 8, Carpenter et al. (1948) study. There is no discussion of effects at 10 ppm; presumably none were observed. Page 9, table 3. The 10 ppm group should be included. Page 11, line 11. State at what concentrations the kidney effects occurred. Page 12, lines 15â16. State the duration of administration of the compound in the diet. Page 15, line 23. The delayed onset of the inflammatory responses should be noted. Page 16, line 16. It should be clarified that based on lethality data, ethylenimine is more acutely toxic. Page 16, lines 15â16. The paragraph deals with the comparative potency of propylenimine compared to ethylenimine and states, âEthylenimine is more toxic than either of the latter substances.â However, no indication of the magnitude of that difference was given. Presumably, this potency difference is restricted to lethality? Page 17, lines 3â4. Delete. The statement is speculationâparticularly in light of the page 16, line 41 observations. Page 19, lines 24â33. It is not clear how specific substances in the Weightman and Hoyle (1964) study were ruled-out as causative. This section needs to acknowledge that the effects may not be attributed solely to ethylenimine due to the mixed exposure. Page 20, lines 16â21. Clarification is needed for the uncertainty factor of 3 for interspecies differences. Why would there be pharmacokinetic differences across species for an