Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 8 (2010) / Chapter Skim
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4 Ethylenimine
4 Ethylenimine
Pages 186-229
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From page 186... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 187... ...
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 idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Ethylenimine is a volatile, clear, colorless, flammable explosive liquid that has an odor similar to that of ammonia and an odor threshold reported as 2 ppm in air; however an odor detection (OD50)
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From page 188... ...
In all studies, the time to death and other signs of toxicity were delayed depending on exposure concentration. Signs of toxicity in these animals included eye irritation, respiratory tract irritation, respiratory difficulty, prostration, complete loss of muscular coordination (mouse only)
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From page 189... ...
Humans and animals exhibit delays between the time of exposure and the onset of symptoms, and the eyes and respiratory tract were the most sensitive targets in rat, guinea pigs, and humans. An uncertainty factor of 3 was applied for intraspecies variability because the effects appear to involve direct contact of the eyes or respiratory epithelium with a very reactive alkylating agent and the alkylating activity is not expected to vary appreciably among individuals in the population.
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From page 190... ...
1948) a AEGL-2 and -3 values do not account for the potential cancer risk associated with exposure to ethylenimine, because quantitative data were not available for deriving a unit risk value.
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From page 191... ...
. The database on inhalation exposure to ethylenimine is limited to only a few human case reports and acute inhalation studies in animals.
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From page 192... ...
Granulomatous polyps were found in the smaller bronchi along with emphysema and bronchopneumonia. There was some debate whether tracheal destruction was a direct effect of inhaling ethylenimine or if it was caused by the extensive delay in granulation resulting from the aggressive steroid therapy in the early stages of treatment.
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From page 193... ...
However, some symptoms (lacrimation, eye inflammation, photophobia, nausea, vomiting and extreme respiratory tract irritation) are similar to those described after exposure to sulfur mustard, another alkylating agent (ATSDR 2003, NRC 2003)
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From page 194... ...
The other workers who wore protective clothing and respirators experienced no signs or symptoms suggestive of exposure to the eyes or respiratory tract. Exposure to the scrotal area was believed to have occurred via the bottom opening of the pant legs of the rubber suits, which conducted the vapors like a chimney.
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From page 195... ...
. No other information on the potential carcinogenicity of ethylenimine in humans was located in the available literature.
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From page 196... ...
Nonlethal effects due to inhalation exposure to ethylenimine are characterized by irritation or damage to contact organs; the effects are delayed in onset depending on exposure concentration. Severe eye and respiratory tract inflammation, photophobia, nausea, vomiting, and coughing may develop several hours after exposure to ammonia, isopentane, ethylenimine, and N-ethylethylenimine in succession.
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From page 197... ...
; no evidence to the eyes and respiratory tract; delayed of testicular effects onset (~12-24 h) Unknown Unknown Skin sensitization Occurred in a laboratory worker Carpenter et al.
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From page 198... ...
TABLE 4-3 Continued 198 Concentration (ppm) Exposure Time Effects Comments Reference <0.5 ppm 8 yr No chromosome aberrations This is an occupational exposure study Gaeth and Thiess 1972 detected 10-5 to 10-4 M 8h Chromosome aberrations in human In vitro study Chang and Elequin 1967 leukocytes and embryonic lung fibroblast cells
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From page 199... ...
Extreme respiratory difficulty was evident at all concentrations ≥25 ppm, but was not observed in less than 3 h at 25 ppm. No other details were presented concerning respiratory difficulty.
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From page 200... ...
(1948) conducted acute toxicity studies in guinea pigs exposed to ethylenimine at concentrations ranging from 10 to 4000 ppm for durations ranging from 5 to 480 min (8 h)
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From page 201... ...
Respiratory difficulty was not observed in guinea pigs exposed to 10 ppm for any duration. Prostration was observed 3 h after exposure to 250 ppm and 2 h after exposure to 500 ppm.
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From page 202... ...
Controls were injected with similar volumes of arachis oil or water alone. Sarcomas developed at the injection site in 6/12 rats receiving ethylenimine in arachis oil compared with 0/24 receiving a comparable volume of arachis oil alone and in 2/12 rats injected with ethylenimine in water.
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From page 203... ...
3.5. Genotoxicity Ethylenimine is a very reactive monofunctional alkylating agent; the formation of an ethylenimonium ion accounts for its alkylating activity (Verschaeve and Kirsch-Volders 1990)
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From page 204... ...
No inhalation studies specifically designed to examine effects of inhaling nonlethal concentrations of ethylenimine were located in the available literature. One study showed that dermal only exposure to ethylenimine vapor at a concentration of 4000 ppm for 4 h failed to elicit any signs of toxicity in guinea pigs (Carpenter et al.
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From page 205... ...
Rat 35 63 480 1/6 Died at lowest concentration tested, 25 ppm Guinea pig 27 48 480 Lowest lethal concentration, 25 ppm (2/6 died) a LC50 values of lowest tested concentration causing death.
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From page 206... ...
SPECIAL CONSIDERATIONS 4.1. Metabolism, Disposition, and Kinetics Data on absorption, distribution, and metabolism after inhalation exposure to ethylenimine were not located in the available literature.
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From page 207... ...
The effects are delayed relative to the time of exposure. Ethylenimine is a very reactive alkylating agent and its toxicity may be related to its alkylating properties.
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From page 208... ...
Eye and respiratory tract irritation and characteristic delayed response also have been observed in humans exposed to ethylenimine.
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From page 209... ...
are presented below. The calculated values of n are 1.1 for the rat data and 0.91 for the guinea pig data.
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210 FIGURE 4-1 Rat data: Concentration–time curve for LC50 values for ethylenimine.
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From page 211... ...
FIGURE 4-2 Guinea pig data: Concentration–time curve LC values for ethylenimine.
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From page 212... ...
An acute lethality study showed that exposure to 10 ppm for 240 or 480 min was not lethal and did not affect the eyes or respiratory tract of guinea pigs. A concentration of 25 ppm did not cause death or respiratory difficulty in guinea pigs exposed for 60 min, but caused death after exposure for 240 min.
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From page 213... ...
An uncertainty factor of 3 was applied for intraspecies variability because the effects appear to involve direct contact of the eyes or respiratory epithelium with a very reactive alkylating agent, and the alkylating activity is not expected to vary considerably among individuals in the population. Five male students responded similarly to an exposure to ethylenimine with respect to the time of onset of symptoms and the intensity of effects.
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From page 214... ...
A total uncertainty factor of 10 was applied to the LC01. An uncertainty factor of 3 was applied for interspecies differences, because ethylenimine is a very reactive direct-acting alkylating agent, and the AEGL-2 effects would most likely be confined to the respiratory tract.
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From page 215... ...
An uncertainty factor of 3 was applied for intraspecies variability because the effects appear to involve direct contact of the eyes or respiratory epithelium with a very reactive alkylating agent, and the alkylating activity is not expected to vary considerably among individuals in the population. Five male students responded similarly to an exposure to ethylenimine with respect to the time of onset of symptoms and the intensity of effects.
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From page 216... ...
The absence of AEGL-1 values does not imply that exposures below the AEGL-2 are without adverse health effects. AEGL-2 values were based on a NOEL for extreme respiratory difficulty in guinea pigs exposed to ethylenimine for 240 min.
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From page 217... ...
The AEGL-2 values were, therefore, derived from a no-effect-level for extreme respiratory difficulty determined from the guinea pig
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From page 218... ...
no-effect-level for extreme respiratory difficulty determined from the guinea pig study. Guinea pigs but not rats were exposed to the lowest concentration not associated with a very serious effect.
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From page 219... ...
Pp. 109-138 in Comparative Chemical Mutagenesis, F.J.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 221... ...
Pp. 175-256 in Comparative Chemical Mutagenesis, F.J.
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From page 222... ...
3 for intraspecies variability, because the effects appear to involve direct contact of the eyes or respiratory epithelium with a very reactive alkylating agent. Studies have shown that DNA damage is probably the initiating step in a cascade of events leading to cell damage and DNA damage is persistent in respiratory and systemic organs following inhalation exposure to alkylating agents.
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From page 223... ...
Studies have shown that DNA damage is probably the initiating step in a cascade of events leading to cell damage and DNA damage is persistent in respiratory and systemic organs following inhalation exposure to alkylating agents. Alkylating activity of ethylenimine is not expected to vary appreciably among individuals in the population Calculations: C = (k/t)
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From page 224... ...
. Although this is a single exposure study, it cannot be used to derive risk values for inhalation exposure, because the test material was administered subcutaneously.
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From page 225... ...
represents the concentration above which it is predicted that more than one-half of the exposed population will experience at least a distinct odor intensity and about 10% of the population will experience a strong odor intensity. The LOA should help chemical emergency responders in assessing the public awareness of the exposure due to odor perception.
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From page 226... ...
Clinical signs: eye and respiratory irritation, and extreme respiratory difficulty at 25-250 ppm; prostration at 250 ppm; no effects at 10 ppm Gross pathologic effects: congestion and hemorrhage in the lungs, congestion in all internal organs at 25-250 ppm; no effects at 10 ppm Microscopic effects: lung congestion leakage of fluid and red blood cells into bronchioles, tubular necrosis and cloudy swelling in the kidneys at 25-250 ppm; no effects at 10 ppm Mortality: 10 ppm, (0/6)
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From page 227... ...
Intraspecies: 3 - The effects appear to involve direct contact of the eyes or respiratory epithelium with a very reactive alkylating agent, and the alkylating activity of ethylenimine is not expected to vary appreciably among individuals in the population. Studies have shown that DNA damage is probably the initiating step in a cascade of events leading to cell damage and DNA damage is persistent in respiratory and systemic organs following inhalation exposure to alkylating agents.
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From page 228... ...
Respiratory tract damage appears to be due to direct effect of an alkylating agent on the respiratory epithelium, and this mechanism is not expected to be different among species. Humans and animals exhibit delays between the time of exposure and the onset of symptoms and the eyes and respiratory tract are the most sensitive targets in both species.
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From page 229... ...
APPENDIX E Category Plot for Ethylenimine Chemical Toxicity - TSD All Data Ethylenimine 10000.0 Human - No Effect Human - Discomfort 1000.0 Human - Disabling Animal - No Effect 100.0 Animal - Discomfort ppm 10.0 Animal - Disabling AEGL-3 Animal - Some Lethality AEGL-2 1.0 Animal - Lethal AEGL 0.1 0 60 120 180 240 300 360 420 480 Minutes FIGURE E-1 Category plot for ethylenimine.
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