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TENTH INTERIM REPORT OF THE SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS 2 COMMENTS ON HYDRAZINE At its July 21â23, 2003 meeting, the subcommittee reviewed the AEGL document on hydrazine. The presentation was made by Robert Young of Oak Ridge National Laboratory. The subcommittee recommends a number of revisions. A revised draft should be reviewed by the subcommittee at its next meeting. Major Issues The uncertainty factors (UFs) are not applied consistently. For irritants and direct acting chemicals (and the case is made for irritation as the primary effect for AEGL-1 and AEGL-2 values), interspecies and intraspecies UFs generally applied were 3 each. This was done for the hydrazine AEGL-1. However, for AEGL-2 values, the statement is made, âAn uncertainty factor of 10 for interspecies variability was applied to account for the high degree of variability in the data due to the extreme reactivity of hydrazine that compromised exposure concentration measurements.â There is no explanation of how the deposition of hydrazine on chamber surfaces and difficulties in concentration measurements relate to interspecies variability, especially when hydrazine appears to be direct acting agent. The study by Latendresse et al. (1995) does not appear to suffer from compromised exposure concentration measurements. If the NAC believes the overall uncertainty factor of 30 is appropriate, the subcommittee recommends using inter- and intraspecies UFs of 3 and 3, with a possible modifying factor of 10 for the compromised exposure concentration measurements, which will make the magnitude of all factors to be 100. However, that adjustment cannot apply to the Latendresse study. The subcommittee recommends using a smaller UF based upon the quality of the study and a possible modifying factor to account for the small database and numbers of animals. The section on level of distinct odor awareness (LOA) is misplaced in the Executive Summary after AEGL-1 and before the AEGL-2 values. The 10-min AEGL-3 is proposed by the NAC to be 63 ppm. How does the NAC explain this level compared with the odor threshold level of 3â4 ppm cited on page 30? From an emergency response perspective, the odor threshold is very important because this is the level at which people will start detecting exposure to hydrazine. A general statement regarding exposure concentrations should be included. In addition to being highly reactive, the subcommittee understands that hydrazine also adsorbs to most materials, including Teflon. Therefore, the subcommittee recommends that the NAC focus on the more recent studies that have presumably solved the technical problems with concentration measurements and use other studies as supporting information. In Section 2.2.2, the Morgenstern and Ritz study (it is only one) seems to have been added without considering what influence those data have on the rest of this section. For example, in the first paragraph, reference is made to a more recent study (1987) when the Morgenstern study was reported in 2001. Does the Morgenstern study follow up or include individuals from the previous studies? How are these studies linked, if at all? Delete the last paragraph. With the Morgenstern (2001) study, the information presented in the last paragraph does not seem to apply.
TENTH INTERIM REPORT OF THE SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS 3 Section 2.5. See comment above. Are there one or more studies and how do they apply here? Section 4.4.1. As written, the text is unclear as to whether species variability or exposure concentration is the issue. The authors seem to be equally confused. Section 5.2. If hydrazine is a direct-acting toxicant and irritation is the primary adverse effect, then why is hydrazine discussed as a cumulative exposure? Why did the NAC use cumulative exposure and derive AEGL-1 values that are constant across time? At the end of this paragraph, add the human exposure level (not stated other than below the TLV of 0.1 at the time). Section 6.3. If the effect is irritation or a direct-acting effect, why not use a UF of 3 rather than 10? Derivation of an AEGL for irritants should be consistent, as has been the case for other chemicals. The use of the modifying factor appears inconsistent with the SOP, as the UF should be 10 with a modifying factor of 2, only because of the lack of data and the small study size of Latendresse study. Section 7.1. No mention has been made of human exposure levels. Section 7.3. The statement is made that the lethal effects of hydrazine appear to be more dependent on concentration than duration; therefore, exponential scaling was used. If the adverse health effects are more dependent on concentration than duration of exposure, then there is no basis for exponential scaling. Section 7.3, 5th paragraph. The subcommittee does not believe that the highly reactive nature of hydrazine that results in a compromised exposure-concentration measurement is a proper rationale for using an uncertainty factor of 10. This seems to be better addressed with a modifying factor. Section 8.1, 5th paragraph. Why was the HRC data set not included in the benchmark dose evaluation? Pages 10, 11, and 34. Rewrite the description of the paper by Sotaniemi et al. (1971). If the concentrations derived from the simulation of the fatal episode were likely to be 0.05 ppm as estimated, then the AEGL derivations could be incorrect. Since this study is not relied upon for the AEGL calculations, the reasons need to be fully stated. The actual dose received from a once-a-week, 6-month exposure is not known. This is a major variable and this should be acknowledged. Can dermal exposure in this case report be ruled out, or is it a possible route of systemic uptake? Pages 22â23. Delete tables and summarize the parenteral studies in a sentence or two at Section 3.3.1. Note the inability to scale the intraperitoneal doses to inhalation exposures with the information at hand. Page 32. Support the AEGL-1 value by brief discussion of the Koizumi results for the 12 workers exposed repeatedly at up to 0.12 ppm as these 8-hr TWA values were confirmed by personal sampling.
