Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 5 (2007) / Chapter Skim
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Appendix 4 Ethylenediamine Acute Exposure Guideline Levels
Appendix 4 Ethylenediamine Acute Exposure Guideline Levels
Pages 145-192
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From page 145... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Subcommittee on Acute Exposure Guideline Levels.
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With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to unique or idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.
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From page 147... ...
An uncertainty factor of 3 was used for interspecies variability because a similar response was seen in two species, and a modifying factor of 3 was used because the key study did not specify the severity of the bronchiolar edema. An intraspecies uncertainty factor of 10 was applied because the data were insufficient to determine the mode of lung and kidney lesions (or which was the more
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Data were not available to determine the concentration-time relationship, and scaling across time was performed using the equation Cn × t = k and n = 3, as was done for AEGL-2. A total uncertainty factor of 100 was applied: 10 for interspecies variability (cause of death was undefined and there were no studies using other species)
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. The exposure concentration was not determined.
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In many cases there was incomplete information about the actual EDA exposure concentration or time that elicited the human responses. Studies in which quantitative data were provided for air EDA concentration and/or exposure duration are summarized in Table 4-3.
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Ethylenediamine 151 TABLE 4-3 Summary of Quantitative Human Ethylenediamine (EDA) Inhalation Studies Exposure Concentration Exposure Time End Point Reference 1.0-11 ppm Unknown Odor threshold Hellman and Small 1974a 100 ppm 5-10 sec Inoffensive Pozzani and 200 ppm 5-10 sec Slight tingling of Carpenter 1954 face and nasal mucosa 400 ppm 5-10 sec Intolerably irritating to nasal mucosa 0.4 ppm Not specified (≤8 h)
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(1999) conclude that there is insufficient data to define the dose-response for an EDA-induced asthmatic response or an exposure level "without adverse effect." 2.2.1.
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Nakazawa and Matsui (1990) described two cases of occupational exposure to EDA in a Japanese chemical factory.
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. The EDA air concentration and exposure duration that elicited the stated symptoms were not specified.
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had bronchoconstriction immediately following a 5-min challenge with nebulized EDA. The EDA exposure concentration was 2 to 10-fold below concentrations that were non-irritating to control (non-sensitized)
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No experimental details or other results were given in the study report, but subsequent publications by the same laboratory indicated that the observation period was two weeks, that the exposure concentrations were nominal and not ana
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; lower body weights; liver and kidney lesions; alopecia 484 27/30 toxic deaths (mean 11.4 days) ; liver, kidney, lung, adrenal effects; alopecia a Study provided nominal concentrations, which are in brackets.
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. The four surviving rats had a significantly lower weight gain and increased liver and kidney weights after 30 days than the controls, some hair loss, and most rats had cloudy swelling of the liver and kidney convoluted tubules.
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Rats inhaling 2.43 mg/m3 EDA for ≥4 months had lowered body weight gains, altered CNS activity, increased eosinophil counts, catalase activity, and liver, lung, and kidney lesions; rats inhaling
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, as described for rats in Section 3.2.1. High-dose animals had lower total body weight gain, increased relative lung and kidney weights, and microscopic lesions in the liver, lungs, and kidneys.
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Both sexes of the high dose F0 and F1 parents, however, had toxic effects (lowered weight gain, decreased liver weight, increased kidney weight, and hepatocellular pleiomorphism)
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classifies EDA as carcinogenicity weight-ofevidence group D: not classifiable as to human carcinogenicity, based on no human data and inadequate animal data (EPA 2005)
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, whereas most or all rats exposed to 225 or 484 ppm died and had liver, kidney, and lung lesions. Dubinina et al.
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were initially given a single per os dose of 50 mg [14C] EDA-2HCl per kg body weight on day 0, prior to EDA dietary treatment.
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Repeated exposure of rabbits to 100 ppm ethylamine (C2H7N) caused lung, liver, and kidney damage, lung irritation, and corneal injury (Benya and Harbison 1994)
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Species Variability EDA toxicity in a species other than the rat was examined in only one inhalation study, in which rats and guinea pigs exposed for 8 h to 1,000 ppm EDA (nominal; analytical approximately 484 ppm) did not die but had lung edema and kidney swelling (Carpenter et al.
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The derived AEGL values are for a once-in-a-lifetime exposure and do not consider previous sensitization.
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RATIONALE FOR AEGL-1 5.1. Summary of Human Data Relevant to AEGL-1 No human studies were located with end points consistent with the definition of AEGL-1.
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RATIONALE FOR AEGL-2 6.1. Summary of Human Data Relevant to AEGL-2 The only human study for which both the exposure concentration and duration were defined was the bronchial provocation test in which a 31-year-old male EDA-sensitized chemical worker exposed to 30 ppm EDA for 15 min had a delayed asthmatic response (Ng et al.
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An uncertainty factor of 3 was used for interspecies variability because a similar response was seen in two species, and a modifying factor of 3 because the key study did not specify the severity of the bronchiolar edema. An intraspecies uncertainty factor of 10 was applied because the data were insufficient to determine the mode of lung and kidney lesions (or which was the more sensitive end point)
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A total uncertainty factor of 100 was applied: 10 for interspecies variability (cause of death was undefined and there were no studies using other species) and 10 for intraspecies variability (lack of toxicity data in key study precludes definition of the mode or variability of the toxic response in humans)
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in the key study and consequently the potential variability of the human response to EDA. The AEGL-3 was based on a range-finding study in which 0/6 rats died after an 8-h exposure to ~1,000 ppm (2,000 ppm nominal)
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A total uncertainty factor of 100 was applied: 10 for interspecies variability (cause of death was undefined and there were no studies using other species) and 10 for intraspecies variability (lack of toxicity data in key study precludes definition of the mode or variability of the toxic response in humans)
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15 a OSHA PEL-TWA (Occupational Safety and Health Administration, Permissible Exposure Limits - Time Weighted Average)
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8.3. Data Quality and Research Needs Although EDA is a high production volume chemical, very few inhalation toxicity studies were available for deriving AEGL values, and data were insufficient to determine the mode of EDA toxicity.
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, which will ideally include exposure times of ≤1 h. The small database, lack of mechanistic information, and shortcomings of the available studies led to the use of large uncertainty factors in developing AEGL values for EDA.
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In: Threshold Limit Values and Biological Exposure Indices for Chemical Substances and Physical Agents, p.
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2005. Hazardous Substances Data Bank.
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2005. Occupational Safety and Health Administration.
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, Adopted 28th July, 2000 by Ordinance of the Swedish National Board of Occupational Safety and Health. ten Berge, W.F., A
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2. Results of 20 coded compounds tested for the National Toxicology Program.
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Total uncertainty factor: 30 Interspecies: 3: A similar response was seen in two species in the key study. Intraspecies: 10: Data were insufficient to determine the mode of lung and kidney lesions (or which was the more sensitive end point)
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. Derivation of AEGL-3 Key study: Smyth et al.
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Total uncertainty factor: 100 Interspecies: 10: The cause of death was not defined in the key study, and there were no supporting data with AEGL-3 end points from other species. Intraspecies: 10: Lack of toxicity data in key study precludes defi nition of the mode or variability of the toxic response in humans.
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. The same citation listed an OT50 of 0.30 for n-butanol, as compared to the reference value of 0.04 ppm as the odor threshold provided by van Doorn et al (2002)
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186 Acute Exposure Guideline Levels tion, it takes into account that odor perception is very fast (about 5 sec) which leads to the perception of concentration peaks.
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End point/Concentration/Rationale: Not applicable. Uncertainty Factors/Rationale: Total uncertainty factor: Not applicable.
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Uncertainty Factors/Rationale: Total uncertainty factor: 30 Interspecies: 3: A similar response was seen in two species in the key study. Intraspecies: 10: Data were insufficient to determine the mode of lung and kidney lesions and consequently the potential variability of the human response to EDA.
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Note that EDA-sensitized persons may experience more severe and/or different effects at a given exposure concentration and/or duration. Uncertainty Factors/Rationale: Total uncertainty factor: 100 Interspecies: 10: The cause of death was not defined in the key study, and there were no supporting data with AEGL-3 end points from other species.
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APPENDIX D Category Plot for Ethylenediamine
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Chemical Toxicity - TSD All Data 192 Ethylenediamine 10000.0 Human - No Effect Human - Discomfort 1000.0 Human - Disabling Animal - No Effect Animal - Discomfort 100.0 ppm Animal - Disabling AEGL-3 Animal - Some Lethality 10.0 AEGL-2 Animal - Lethal AEGL 1.0 0 60 120 180 240 300 360 420 480 Minutes FIGURE D-1 Chemical toxicity -- TSD all data, ethylenediamine.
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