Eleventh Interim Report of the Subcommittee on Acute Exposure Guideline Levels (2004) / Chapter Skim
Currently Skimming:
Eleventh Interim Report of the Subcommittee on Acute Exposure Guideline Levels
Eleventh Interim Report of the Subcommittee on Acute Exposure Guideline Levels
Pages 1-40
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
This interim report presents the subcommittee's comments concerning the NAC's draft AEGL documents for ~ ~ chemicals: chioromethy! methyl ether, jet-propulsion fuel 8, tetranitromethane, carbon monoxide, acetone cyanohydrin, monochIoroacetic acid, phosphorus trichior~de, phosphorus oxychioride, fluorine, cis-l, 2-dichIoroethylene, trans-l, 2dichioroethylene, and acrylic acid.
|
From page 2... ...
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.
|
From page 3... ...
The reason given in the text is that "there were no inhalation exposure studies with technical grade CMME that produced end points consistent with the definition of AEGL-~" (page 23~. This description differs from the statements in the Executive Summary, in the summary table in the Executive Summary (page vii)
|
From page 4... ...
(1975) study (30-clay exposure study)
|
From page 5... ...
The axis values below ~ should not be zeros. COMMENTS ON JET-PROPULSION FUEL At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on jet-propulsion fuel 8 (JP-8)
|
From page 6... ...
Using an interspecies UF of ~ when relying on animal data is a major departure from past decisions as well as from the SOP. The subcommittee floes not agree with the argument.
|
From page 7... ...
("Olsen compared the health of ~ ~ Air Force personnel exposed to jet fuels with IS non-exposed subjects.") There are no health effects data in this table.
|
From page 8... ...
not produce eye irritation, because MacEwen and Vernot (1985) reported eye irritation in mice and rats exposed for ~ hour to JP-5 at 625 ppm.
|
From page 9... ...
Was consideration given to using the immune studies to derive the AEGL values (Robledo and Whitten 1998 or Harris 20011? Could those studies be used to derive AEGL values?
|
From page 10... ...
Page 46, lines 24-25 It would be worthwhile to point out that doses of volatile organic hydrocarbons (VOCs) absorbed systemically are considerably greater in mice and rats than in humans subjected to equivalent inhalation exposures.
|
From page 11... ...
This explanation is not convincing. Using an interspecies UF of ~ when relying on animal data is a major departure from past decisions as weld as from the SOP.
|
From page 12... ...
71:144-149. COMMENTS ON TETRANITROMETHANE At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on tetranitromethane.
|
From page 13... ...
that the multiple exposure study, which shows the same "threshold" for two species and two genders appears more appropriate might be secondary to the merits of a single versus multiple exposure study. The male rat appears to be most sensitive and hence an AEGL derived on the basis of the single exposure in male rats appears to be sufficiently protective for human.
|
From page 14... ...
Repetitive. COMMENTS ON CARBON MONOXIDE At its January 28-30, 2004, meeting, the subcommittee reviewed the revised AEGL document on carbon monoxide.
|
From page 15... ...
do not match the units used to derive the AEGL values, which makes it difficult to compare the effects presented in the table with the AEGL values. Can the values in the table be converted to ppm or mglm3 so that the data in the table are useful for comparisons?
|
From page 16... ...
and EPA (2000) show that the derived AEGL values are protective of these risk groups.
|
From page 17... ...
COMMENTS ON ACETONE CYANOHYDRIN At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on acetone cyanohydrin. The document was presented by Peter Grief of FOBIG GmbH, Germany.
|
From page 18... ...
58~10~:704-712, 1997) contributes to the reduced AEGE-l or that a combined acetone and nitrite exposure contributes to headache or systemic toxicity as a result of cyanohydrin contact, the AEGL values at each level and duration of exposure should be equivalent to those for HCN (NRC, 2002~.
|
From page 19... ...
The reliance on HCN toxicity is appropriate. Some notation should be made by the AEGL values that the total of both acetone cyanohydrin and hydrogen cyanide concentrations should be measured and considered.
|
From page 20... ...
The sentence should be rewritten to indicate that, once absorbed, a dose of acetone cyanohydrin behaves in a manner identical to that of its molar equivalent in absorbed free cyanide. Page vii, lines 158-IS9 ant]
|
From page 21... ...
1914. The interaction between hydrogen cyanide and aldehydes and ketones in dilute solutions.
|
From page 22... ...
19~:225-238. COMMENTS ON MONOCHLOROACETIC ACID At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on monochioroacetic acid (MCA)
|
From page 23... ...
It is remarkable that ammonia neutralization decreased signs of irritation but did not decrease the mortality rate. That might suggest a systemic effect of PC13, in addition to a local irritating effect on the pulmonary epithelium.
|
From page 24... ...
The subcommittee recommends changing the wording "and, therefore, results in a lack of confidence in the reported results." Page 4, line 37. Who was the source of the personal communication?
|
From page 25... ...
Replace "for may irritant" with "for many irritant." Fix typo throughout report. COMMENTS ON PHOSPHORUS OXYCHLORIDE At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on phosphorus oxychioride (POCK.
|
From page 26... ...
affect the proposed AEGL values. COMMENTS ON FLUORINE At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on fluorine.
|
From page 27... ...
Unless data can be cited to show that systemic fluonde toxicity results from inhaled fluorine gas, the value of references to systemic uptake is not clear. in this context, it might be worthwhile to review the Biological Exposure Indices (BEN)
|
From page 28... ...
If the NAC insists that chronic ingestion of fluoride ion in food or water is relevant to AEGL development for fluorine gas, it is incumbent upon the NAC to cite data concerning systemic uptake of fluoride after fluorine gas exposure in relation to the circulating and or target-tissue (e.g., bone, teeth) fluoride concentrations associated with systemic fluorine toxicity.
|
From page 29... ...
Delete the editorialization. AEGL-l Values The subcommittee recommends that the NAC use the 25-ppm concentration that elicited slight to moderate discomfort.
|
From page 30... ...
COMMENTS ON ACRYLIC ACID At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on acrylic acid. The document was presented by Peter Griem of FOBTG GmbH, Germany.
|
From page 31... ...
Because AEGL values apply only to once-in-a-lifetime exposures, the many details from subchronic studies can only be used as supporting evidence, at best. As written, it is not clear whether these changes in rabbit, mouse, and nonhuman primates were seen after the first 6 hours (the first encounter)
|
From page 32... ...
What is the justification for applying an ~ derived from acrylic acid aerosol studies of mortality in rats to the vapor study results collected in primates by Harkema and coworkers? Page xiii, line 263.
|
From page 33... ...
1993. Efficacy of volatile organic compounds in evoking nasal pungency and odor.
|
From page 34... ...
· . ; , ~ COMMENTS ON C AND TRANS-I ,2-DICHI,OROETHYLENE At its January 28-30, 2004, meeting, the subcommittee reviewed the AEGL document on cis- ~ ,2-dichloroethylene (cis- ~ ,2-DCE)
|
From page 35... ...
are of very questionable toxicological significance and are probably undeserving of the extent of coverage they are given on page ~ 5, line 24, and on page ~ 6, line 5. It should be noted here that morphological changes were seen in just one of six rats (16%)
|
From page 36... ...
~ he apparent morphological changes they clescrlneo te.g., ~yperem~a, alveolar septum distension, fibrous swelling, poorly maintained cardiac muscle striations) , with the exception of fatty liver change, are vague, nonspecific, and of questionable toxicological significance.
|
From page 37... ...
The authors felt that this supporter! the hypothesis that I,2-DCE and other lipophilic anesthetics act by specific receptor interactions as opposed to simple partitioning into neuronal membrane lipids.
|
From page 38... ...
As described earlier in this critique, mice and rats should absorb more I,2-DCE and attain higher brain levels than humans after equivalent inhalation exposures. The toxicodynamic component of the UF should be close to I, because there is well-documented evidence (see ecotoxicology literature by Lynn McCarty and others)
|
From page 39... ...
program: Applications of physiologically based pharmacokinetic modeling.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.