Eighteenth Interim Report of the Committee on Acute Exposure Guideline Levels (2010) / Chapter Skim
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Eighteenth Interim Report of the Committee on Acute Exposure Guideline Levels
Eighteenth Interim Report of the Committee on Acute Exposure Guideline Levels
Pages 1-40
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Subsequently, Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Substances was published in 2001; it provided updated procedures, methods, and other guidelines used by the National Advisory Committee (NAC) on Acute Exposure Guideline Levels for Hazardous Substances for assessing acute adverse health effects.
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, epichlorohydrin, formaldehyde, hydrogen bromide, hydrogen iodide, methyl bromide, methyl chloride, nitric acid, nitric oxide, nitrogen dioxide, nitrogen tetroxide, piperidine, titanium tetrachloride, toluene, trimethylbenzenes (1,2,4-; 1,2,5-;and 1,3,5-TMB) , vinyl acetate monomer, and vinyl chloride.
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AEGL -3 Page 28, lines 1-4: "An intraspecies uncertainty factor of 3 and interspecies uncertainty factor of 3 were applied because allyl alcohol is highly irritating and corrosive, and much of the toxicity is likely caused by a direct chemical effect on the tissues; this type of port-of-entry effect is not expected to vary greatly among individuals or among species." Since there appear to be other than direct-acting effects occurring, the values of the uncertainty factors should be reviewed and better justified. If some of the tissue irritation and systemic effects are caused by metabolism of the alcohol to an aldehyde, the amount of irritation to the tissues might be affected by whether individuals have the slow or fast form of genetic polymorphisms for aldehyde dehydrogenase.
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2008. Acute Inhalation Study of Allyl Alcohol in Albino Rats (with 1-, 4-, and 8-hour Exposure Durations)
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CHLOROMETHYL METHYL ETHER At its meeting held on June 15-18, 2010, the committee reviewed the TSD on chloromethyl methyl ether. A presentation on the TSD was made by Mark Follansbee, of Syracuse Research Corporation.
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, and excerpted analyses below on related compounds, the committee strongly recommends publication of the halogen fluorides as a single document with chlorine trifluoride, chlorine dioxide, and hydrogen fluoride as appendixes or possibly republishing chlorine trifluoride and chlorine dioxide from Volume 5 of Acute Exposure Guideline Levels for Selected Airborne Chemicals and hydrogen fluoride from Volume 4 as chapters, as well as chapters on chlorine pentafluoride, bromine pentafluoride, and bromine trifluoride. Alternatively, it should be ensured that references are made throughout the document to hydrogen fluoride, chlorine trifluoride, and chlorine dioxide.
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The relative toxicities indicate that ClO2, an intermediate in the dissociation of ClFx, plays a role in the toxicity of these agents. (In the moist respiratory tract, ClF3 is predicted to hydrolyze to ClOF, which further degrades to ClO2F and ClF [Dost et al.
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belongs in Section 4 with the discussion on relative toxicities and mechanisms described above. Page 18, lines 4-6: "These observations suggest that the effects of ClF5 exposure may be more likely to be due to the direct irritation of the respiratory tract than to fluoride poisoning." This is a weak statement.
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, which should only consider values for ClF5. Page 25, Section 8.3: This section on data adequacy and research needs should be rewritten according to guidance in the Standing Operating Procedures (NRC 2001)
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Page 17, Section 8.3: The Section states that there were no BrF3 data. The inference is that structure-activity relationships are adequate to derive AEGL values using data from ClF3 and other halogen fluorides and HF and that no further research is needed.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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In addition, the AEGL-3 is only 2-fold lower than 2,382 ppm, at which dizziness, nausea, sleepiness, and severe headache were observed within 3-7 min of exposure. Additional comparisons to human data further illustrate the need for ensuring that the proposed AEGL-3 values for carbon tetrachloride provide adequate protection against death.
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The committee found that the revised TSD appropriately addressed its comment from a previous meeting and is ready to be finalized. CHLOROSILANES At its meeting held on June 15-18, 2010, the committee reviewed the TSD on 26 selected chlorosilanes.
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Other Comments Document Publication and Aggregation Because the toxic effects of acute exposure to chlorosilanes seem adequately explained by the generation of and exposure to hydrogen chloride, consideration should be given to rewriting the chlorosilane TSD as an appendix or attachment to the hydrogen chloride TSD when the AEGL documents are reviewed for updating (the hydrogen chloride TSD was published in 2004)
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The assumption made in the draft TSD is that the acute toxicity is due to hydrogen chloride formed as a hydrolysis product, and the animal data support this assumption. The data were generated using 11 of the 26 chlorosilanes covered by the draft TSD, including two of the three that have alkene substituent groups.
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Page 23, lines 41-43, and page 49: No sensitive subpopulations were identified, nor are any such identified in Section 4.4 of the hydrogen chloride TSD. However, the derivation of the AEGL-1 values for hydrogen chloride describes people who have asthma as being part of a sensitive subpopulation.
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in which the lethality studies used in the draft TSD as the basis of the AEGL-3 values for epichlorohydrin are considered more "uncertain" and "not qualitatively superior" to data from an unpublished study by Kimmerle (1967) , which was cited in the RIVM report but not included in AEGL TSD.
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The relevant AEGL values for noncancer effects should be presented in the table reporting the values associated with cancer risks of 10-4, 10-5, and 10-6 to facilitate comparisons. It would be preferable to structure the table in the traditional format of presenting AEGL values: The exposure durations should be the column headings, and the AEGL values and cancer risk levels should constitute the row designations; entries should be sorted by ascending level of risk using the 1-h values.
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The AEGL Standing Operating Procedures appear to support the use of such data. For example, the procedures state, "Therefore, no dosimetry adjustments have been made to date by the NAC-AEGL Committee for attaining human-equivalent doses in the development of AEGLs for gases, vapors, and aerosols" (p.
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2008. Acute Exposure Guideline Levels for selected Airborne Chemicals, Vol.
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In addition, there are substantial species differences in the anatomy and physiology of the nasal passages between rodents and humans, and their effects on the dosimetry of formaldehyde should be elaborated in more details. It is also unknown whether tissue saturation could occur in human nasal passages, particularly at high concentrations and long exposure durations.
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:1908-1913. HYDROGEN BROMIDE AND HYDROGEN IODIDE At its meeting held on June 15-18, 2010, the committee reviewed the TSD on hydrogen bromide and hydrogen iodide.
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The need for this protracted observation period is important because delayed death after acute exposure was noted in Section 3.1.1 (page 12, line 37)
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1989. Relative acute toxicities in the respiratory tract of inhaled hydrogen fluoride, hydrogen bromide, and hydrogen chloride.
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METHYL CHLORIDE At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on methyl chloride. A presentation on the TSD was made by Julie Klotzbach, of Syracuse Research Corporation.
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:A142-A151. NITRIC ACID At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on nitric acid.
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Nitric acid may exist in the following airborne forms: gas, vapor, mist, fume, and aerosol. The TSD should point out that mist will probably be scrubbed in the mouth or nasal passages, gas and vapor in the upper respiratory tract, and fume and aerosol in the alveolar region.
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PIPERIDINE At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on piperidine. A presentation on the TSD was made by Julie Klotzbach, of Syracuse Research Corporation.
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. TITANIUM TETRACHLORIDE At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on titanium tetrachloride.
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(The only citations from this century are three older AIHA references for the emergency response planning guideline [ERPG] and WEEL values, and the 2004 NRC AEGL volume that contains a report on hydrogen chloride.)
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For example, beyond increased hydrogen chloride formation under conditions of high relative humidity, exposure to water following an airborne release notably includes contact with perspiration and tears. It would also be helpful if the discussion of TiCl4 transformation products could focus on air more specifically, as the TSD seems to blur this context a bit in having only provided sequential reactions in water (page 1, lines 11-14)
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. Although no quantitative exposure data were found in news reports for these recent incidents, a more structured pursuit of such information might be fruitful, and additional injury and mortality information could be reflected in an updated section on human data.
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noted that the rat pulmonary response suggests chronic exposure might result in upper respiratory tract irritation and possibly acute or chronic bronchitis. Compared with the other primary fate product, TiCl4 is considered more toxic than hydrogen chloride because it can penetrate to the deep lung where it can then hydrolyze to hydrogen chloride and cause further damage (as reflected in the TSD in other cited papers)
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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. TOLUENE At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on toluene.
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TRIMETHYLBENZENES At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on 1,3,5trimethylbenzene, 1,2,4-trimethylbenzene, and 1,2,3-trimethylbenzene. A presentation on the TSD was made by Julie Klotzbach, of Syracuse Research Corporation.
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This factor is followed by a decision to lower it to 3 because, if a value of 10 is used, the resulting AEGL-2 values would be lower than concentrations of vinyl acetate that did not result in serious adverse health effects in human volunteer studies. Better justification is needed for lowering the uncertainty factor for intraspecies differences from 10 to 3.
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Revisions are needed to reconcile the following statements: The text on page 35, lines 18-19, states, "Human exposure to 20 ppm resulted in one of three individuals reporting persistent slight throat irritation." However, the text on page 35, line 23, states that 20 ppm was used to derive AEGL-1 values because "exposure to 20 ppm represents a no-effect level for notable discomfort." The text on page 35, lines 27-28, states, "Because irritation is considered a threshold effect and therefore should not vary over time, the AEGL-1 value is not scaled across time .
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88-920010328. VINYL CHLORIDE At its meeting held on June 15-18, 2010, the committee reviewed the AEGL TSD on vinyl chloride.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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