Fourteenth Interim Report of the Committee on Acute Exposure Guideline Levels (2006) / Chapter Skim
Currently Skimming:
Fourteenth Interim Report of the Committee on Acute Exposure Guideline Levels
Fourteenth Interim Report of the Committee on Acute Exposure Guideline Levels
Pages 1-42
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 committee's comments concerning the NAC's draft AEGL documents for 16 chemicals: xylenes (mixtures of ortho, para, and meta xylenes; meta-xylene predominates the mixture constituting 40-70% of the commercial mixture) ; acetone; acetone cyanohydrin; carbon disulfide; allyl alcohol; acrolein; chloroform; peracetic acid; n,n-dimethylformamide; carbon tetrachloride; 1,2-dichloroethylene; sulfur dioxide; hydrazine; ethylenimine; propylenimine; and trichloroethylene.
|
From page 2... ...
Add NRC 2001 (SOP manual) as a reference either at the end of the first or second paragraphs.
|
From page 3... ...
COMMENTS ON ACETONE At its previous meeting, the committee reviewed the AEGL document on acetone. The document was presented by Jens-Uwe Voss of Germany.
|
From page 4... ...
The highest acetone exposure concentration (50,600 ppm) was lethal to some, but not all rats.
|
From page 5... ...
(1944) clearly show lower metabolic efficiency at higher blood acetone concentrations.
|
From page 6... ...
of inhaled acetone vapor concentrations in rats. Metabolic rate constants were determined for a wide range of inhaled acetone concentrations from 5,000 to 45,000 ppm.
|
From page 7... ...
and therefore experiencing more-pronounced CNS depression. An interspecies factor would not be necessary if PBPK modeling were utilized.
|
From page 8... ...
Summary The proposed AEGL values appear appropriate. Time scaling for derivation of the AEGL values appears appropriate.
|
From page 9... ...
Time scaling for derivation of the AEGL values appears appropriate. The use of UFs for AEGL-2 and -3 appears appropriate.
|
From page 10... ...
These four references place the first initial of the last-cited author in front of the author's last name; all the other references place the initial after the last name (compare, for example, page viii, lines 11 and 14)
|
From page 11... ...
Reduce quotation of Lehman and expend neurotoxicity data. Page 19, line 36.
|
From page 12... ...
and add the citation on page 57, line 2. COMMENTS ON ALLYL ALCOHOL At its previous meeting, the committee reviewed the AEGL document on allyl alcohol.
|
From page 13... ...
. Further, the SOP manual states that UFs are derived based on the supporting data from human or animal studies (2.5.3.4.6)
|
From page 14... ...
The revised document can be finalized if the committee's recommended revisions are made appropriately. Scientific Comments Page 2, line 14; page 9, lines 33-34; page 10, lines 19-20; page 21, lines 44-45.
|
From page 15... ...
The derivation of n = 1.2 needs to be presented in an appendix as indicated in the SOP manual (see §2.7.5, §3.1, and Appendix G)
|
From page 16... ...
Data Analysis for Proposed AEGL-3 Use of 3 for the interspecies UF is appropriate, but the rationale should be changed to be science based. It is more appropriate to base the value on the fact that the toxicity data is fairly consistent across five species of animals (SOP manual section 2.5.3.2.3)
|
From page 17... ...
Page 23, lines 10-11. Cite the SOP manual, page 90, §2.5.3.4.4, for this conclusion.
|
From page 18... ...
Page A-2, line 12. It might be easier to simply say "for all exposure durations" rather than listing each of the exposure times for the AEGL-1 values.
|
From page 19... ...
COMMENTS ON CHLOROFORM At its previous meeting, the committee reviewed the AEGL document on chloroform. The document was presented by Robert Young, of Oak Ridge National Laboratory.
|
From page 20... ...
COMMENTS ON PERACETIC ACID At its previous meeting, the committee reviewed the AEGL document on peracetic acid. The revised document was presented by Kowetha Davidson, of Oak Ridge National Laboratory.
|
From page 21... ...
While it appears that peracetic acid is more toxic, how likely is it that exposure will occur in the absence of the other significant components of most commercial mixtures (acetic acid and hydrogen peroxide)
|
From page 22... ...
This would be a good place to refer to any data or the specific section in the SOP manual that supports the assertion that effects of exposure to corrosive and irritant materials like peracetic acid are expected to be similar across species and within populations, the justification used to support the selection of UFs of 3 in the derivation of all proposed AEGLs. Page 15, Section 4.4.3.
|
From page 23... ...
The summary table of proposed AEGL values on page 6 of the Preface is listed first; confusion engendered by listing this table on page 6 before Table 1 on page 2 would be avoided by having the Preface page numbers shown in Roman numerals. Throughout the document, concentrations are referred to as "x.xx mg peracetic acid/m3." In a document on peracetic acid, it is acceptable (and easier to read)
|
From page 24... ...
The revised document can be finalized if the committee's recommended revisions are made appropriately. Summary The proposed AEGL values appear appropriate given the limited data base for their derivations.
|
From page 25... ...
While the older terms should be used because they are in the source documents, in accordance with the spirit of the SOP manual, the current terminology should be appended in parentheses for the sake of clarity. For example, on page 5, the old abbreviations SGOT and SGPT are used (lines 9-10)
|
From page 26... ...
The total uncertainty factor of 30, in conjunction with the available human experimental data and the supporting animal data (both cited below) , should protect against all but hypersensitive human hepatotoxic effects." Page 28, line 23.
|
From page 27... ...
Page 14, line 3. Change to read "at 2 and 4 weeks" (changed word underlined)
|
From page 28... ...
. COMMENTS ON CARBON TETRACHLORIDE At its previous meeting, the committee reviewed the AEGL document on carbon tetrachloride (CCl4)
|
From page 29... ...
The three risk values required by the SOP manual have still not been derived. They should be added to the document.
|
From page 30... ...
(1986) approach frequently results in underestimation of 4- and 8-h AEGLs for VOCs when extrapolating from shorter to longer exposure periods.
|
From page 31... ...
The authors might point out that a PBPK model could have been used for interspecies extrapolations and time scaling in the AEGL derivations, but the decision was made to use reported model simulations to support adoption of an interspecies UF of 1. The NAC provided a white paper on utilization of PBPK modeling for establishing AEGLs, but there was little opportunity for it to be reviewed by the committee.
|
From page 32... ...
Thus, the AEGLs should progressively decrease, as is the case with AEGL-2s and -3s in the current document. COMMENTS ON SULFUR DIOXIDE At its previous meeting, the committee reviewed the AEGL document on sulfur dioxide (SO2)
|
From page 33... ...
Change sentence to "The excess deaths were attributed to bronchitis or to other impairments of the respiratory tract." Response: Text revised as suggested. Page 7, lines 8-9.
|
From page 34... ...
Insert "ambient" before "air pollution." Response: Text revised as suggested Section 3.1. Do we really need all these animal data when there are so many human data available?
|
From page 35... ...
Response: The AEGL-2 values have been revised to 0.75 ppm for all time points. The justification in the appropriate text and tables in the TSD have been revised as follows: "AEGL-2 values were based on the weight of evidence from human asthmatic data suggesting that 1.0 0.75 ppm induces moderate, but reversible, respiratory response in exercising asthmatics for exposure durations of 10 min to 3 h 5- to 75-minutes.
|
From page 36... ...
and utilization of animal data for AEGL-3 values. (AEGL-3 values were derived using a lower 95% confidence limit, per the SOP manual.)
|
From page 37... ...
COMMENTS ON HYDRAZINE At its previous meeting, the committee reviewed the AEGL document on hydrazine. The revised document was presented by Robert Young, of Oak Ridge National Laboratories.
|
From page 38... ...
Although the uncertainties regarding species variability may be indirectly the result of uncertainties inherent in exposure measurements of early studies, such deficiencies are more appropriately data-quality issues. Therefore, the AEGL-2 and -3 values are now derived using an interspecies UF of 3 and an MF of 3 for data inadequacies resulting from difficulties in accurately measuring exposure concentrations in older studies.
|
From page 39... ...
Recommend restating the following paragraph as follows: "Because there were no data to empirically derive the chemical-specific exponent, the default values of n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points were used in the Cn × t = k equation in accordance with the SOP manual." This is better than the following: "To obtain AEGL values in the absence of an empirically derived chemical-specific scaling exponent, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the Cn × t = k equation." COMMENTS ON ETHYLENIMINE At its previous meeting, the committee reviewed the AEGL document on ethylenimine. The revised document was presented by Kowetha Davidson, of Oak Ridge National Laboratory.
|
From page 40... ...
This shorthand is not appropriate in this instance. COMMENTS ON PROPYLENIMINE At its previous meeting, the committee reviewed the AEGL document on propylenimine.
|
From page 41... ...
. Perhaps show an example of calculated AEGL values with a PBPK model and, using Cn × T = k, point out which physiologic processes are accounted for in the PBPK model that were not accounted for in the air-concentration-extrapolation methodology.
|
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.