Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 6 (2008) / Chapter Skim
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. All treated rats showed signs of eye and respiratory tract irritation, and some had lacrimation and red nasal discharge.
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. 12 Prepublication Copy
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. The subjects graded their sensory responses for eye irritation, nose irritation, pulmonary discomfort, CNS effects, and olfactory cognition on a five-point scale, ranging from "absent" to "extreme" (intolerable)
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10 ppm (n = 10) Parameter 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 Olfactory cognition 3 9 1 4 9 2 5 3 Eye irritation 11 1 2 11 2 5 4 1 Nose irritation 7 5 2 6 6 1 5 5 Pulmonary discomfort 10 2 2 7 6 5 4 1 CNS effects 11 2 1 13 9 1 a Data from Hine et al.
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. No effects were seen in rats exposed to 5 Prepublication Copy 15
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3 at 7 days + 8 40 1 Died at 8 hour + Fibrinoid degenerative thrombus, one decisive vessel change, diffuse cellular infiltrate 14 60 4 1 at 18 hour + Scattered myofibril fragments with loss of striation 1 at 2 days + Scattered myofibril fragments with loss of striation 2 at 8 days + Perivascular edema, cellular infiltration 16 40 20 11 at 8-17 hour 0 Occasional suggestive areas of round-cell infiltration, edema of some small vessel walls 4 at 7 days 0 5 at 14 days 0 20 50 3 1 at <20 hour + Scattered myofibril fragments with loss of striation 2 at 8 days + Widespread endothelial lesion 100/60b 24 3 2 at <24 hour + Scattered myofibril fragments with loss of striation, suggested perivascular lymphocytic cuffing (6 hour/18 hour) Same, more pronounced 1 at 2 days + +c 32 40 5 All at 3 days Well-established heart lesions in 2/5 rats 48 20 18 2 at 2 days + Several small areas of typical "infarcted cardiopathy" 6 at 4 days + Several small areas of typical "infarcted cardiopathy" 6 at 7 days + Several small areas of typical "infarcted cardiopathy" 4 at 13 days 0 a Calculated from the beginning of the exposure period.
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. Mice exposed to 1.10 or 1.00 mM/L Prepublication Copy 17
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7-hour exposures to 5-40 ppm allylamine. Since mortality occurred at 18 Prepublication Copy
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In an inhalation exposure study for which there were incomplete experimental data (e.g., number of animals exposed, exposure duration labeled as "variable," individual animal results; Research Pathology Associates 1984) , F-344 rats exposed to 100 or 150 ppm of allylamine for 5 or 10 days (hours/day not specified)
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3.5. Genotoxicity Allylamine was not mutagenic in the Salmonella/microsome preincubation assay when tested at concentrations of 0, 1, 3, 10, 33, 100, 333, 1,000, or 3,333 µg/plate using strains TA98, TA100, TA1535, 20 Prepublication Copy
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. About 60% of the given radioactivity was excreted in the urine by 24 hour, after which time there was little additional excretion, Prepublication Copy 21
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by acrolein and possibly the other metabolites, which causes its hypercontraction and vasospasm and results in ischemia and subendocardial 22 Prepublication Copy
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, LC50 values were determined only for rats. Prepublication Copy 23
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The 10, 30, and 60-minute AEGL-2 values were based on human exposure to 10 ppm for 5 minute, which caused slight or moderate eye and nose irritation, pulmonary discomfort, and severe olfactory cognition and which was the NOAEL for "extreme or intolerable" irritation (Hine et al.
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(1960) a study in which 35 young adult human volunteers were exposed for 5 minute to 2.5, 5, or 10 ppm of allylamine, which caused dose-related increases in the incidence of slight or moderate eye irritation, nose irritation, and pulmonary discomfort Prepublication Copy 25
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Human volunteers exposed for 5 minute to 2.5-10 ppm allylamine had slight to moderate eye and nose irritation and pulmonary discomfort, whereas at the next higher concentration tested, ~14 ppm, exposure was "intolerable" (extreme pulmonary discomfort and irritation of the eyes, nose, and throat) and was almost immediately terminated.
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exposed to 100 or 150 ppm of allylamine for 6 hour/day for 10 days all survived exposure to 100 ppm, but 3/5 males and 3/5 females died at 150 ppm. Both dose groups had increased heart weights and heart lesions, Prepublication Copy 27
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An intraspecies uncertainty factor of 3 was applied because allylamine acts as a contact irritant, and the severity of its effects is not expected to vary greatly among humans. Also, use of a greater uncertainty 28 Prepublication Copy
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. All treated rats showed signs of eye and respiratory tract irritation, and some had lacrimation and red nasal discharge.
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a LLV (Level Limit Value) , Swedish Occupational Exposure Limit Values, by Ordinance of the Swedish National 30 Prepublication Copy
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, Swedish Occupational Exposure Limit Values, by Ordinance of the Swedish National Board of Occupational Safety and Health, adopted July 28, 2000; defined as a recommended value consisting of a time-weighed average for exposure during a reference period of 15 minute.
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1995. Histopathological changes in the respiratory tract of mice exposed to ten families of airborne chemicals.
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All subjects detected the odor of allylamine, and there were dose-related increases in the incidence of slight or moderate eye irritation (21%, 15%, 50%) , nose irritation (50%, 54%, 100%)
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, but rats exposed to 60 ppm for 14 hour had cardiovascular lesions consisting of scattered myofibril fragments with loss of striation, perivascular edema, and cellular infiltration (LOAEL)
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8-hour AEGL-2: C1.7 × 8 hours = 10.95 ppm1.7−hour 8-hour AEGL-2 = C = 1.2 ppm (2.8 mg/m3) Prepublication Copy 35
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All treated rats showed signs of eye and respiratory tract irritation, and some had lacrimation and red nasal discharge. Rats dying from exposure had stomachs distended with air, fluid-filled lungs, alveolar hemorrhage, and pulmonary edema.
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Log Time Intercept 3.2567 −1.1823 1,933 3.2862 1 0.0000 Slope 286 2.4564 4 0.6021 R Squared 0.9798 −0.9898 177 2.2480 8 0.9031 Correlation n = 0.8457765 Degrees of Freedom 1 k = 568.14929 Observations 3 38 Prepublication Copy
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Allylamine Best Fit Concentration x Time Curve 3.4 3.2 3 2.8 Log Concentration 2.6 2.4 2.2 2 0 0.2 0.4 0.6 0.8 1 Log Time FIGURE 1-2 Prepublication Copy 39
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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 6 APPENDIX D Category Plot for Allylamine Chemical Toxicity - TSD All Data Allylamine 100000.0 Human - No Effect Human - Discomfort 10000.0 Human - Disabling 1000.0 Animal - No Effect ppm 100.0 Animal - Discomfort Animal - Disabling AEGL-3 10.0 Animal - Some Lethality AEGL-2 1.0 Animal - Lethal AEGL-1 0.1 AEGL 0 60 120 180 240 300 360 420 480 Minutes FIGURE 1-3 40 Prepublication Copy
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Health 1:343-352. Test Species/Strain/Sex/Number: Long-Evans rats, five/dose group Exposure Route/Concentrations/Durations: Inhalation for 1, 4, or 8 hour; see below: Effects: All treated rats showed signs of eye and respiratory tract irritation, and some had lacrimation and red nasal discharge.
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Nonlethal, irreversible, or long-term effects occurred when damage progressed to the tracheobronchial region, manifested by reduced performance on pulmonary function tests, bronchitis, bronchiolitis, emphysema, and bronchiectasis. Nondisabling reversible effects were manifested by irritation to the eyes, throat, and nasopharyngeal region of the respiratory tract.
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Atopic subjects, including asthmatics, responded similarly to nonatopics to brief nasal exposure to ammonia, and exercising subjects experienced only non-significant clinical changes in pulmonary function after exposure to ammonia. Asthmatic and exercising individuals are not expected to respond differently from nonasthmatic or resting individuals.
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TABLE 2-2 Physical and Chemical Data Parameter Value/Description Reference Chemical name Ammonia Synonym Anhydrous ammonia, ammonia gas, AM-Fol, Nitro-sil, R 717, spirit of hartshorn, UN1005 (DOT) CAS registry no.
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No deaths occurred among the nine mildly affected patients. Three of 27 moderately affected patients showed signs and symptoms similar to pulmonary edema and died within 36 h.
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used the HGSYSTEM gas dispersion model to estimate atmospheric ammonia concentrations generated at the time of the ammonia accident in Potchefstroom, South Africa. They provided upper bound (wind speed = 1 m/sec)
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Experimental Studies, Case Reports, and Anecdotal Data The available literature detailing the disabling, long-term, or irreversible effects of inhaling ammonia gas or vapor is quite extensive. However, none of the studies contain quantitative exposure data.
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reported that based on observations of human responses to ammonia, the lowest concentration (or threshold) of ammonia to cause coughing is 1720 ppm, the lowest concentration to cause eye irritation is 698 ppm, and the lowest concentration to cause throat irritation is 408 ppm.
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No coughing was reported; the authors noted that 1000 ppm causes immediate coughing. This study showed that irritation of upper respiratory tract and throat occurred in subjects inhaling 500 ppm of anhydrous ammonia for 15 to 30 minutes.
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Each group was exposed to ammonia at concentrations of 50, 80, 110, and 140 ppm for up to 2 hours. Subjective responses (smell, eye irritation, throat irritation, cough, etc.)
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2.5 (1-3) WD Throat irritation 2h 0.4 (0-2)
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Exposure periods ranged from 2 to 6 hours/day for 5 weeks. There was no adverse effect on respiratory function and no increase in the frequency of eye, nose, and throat irritation with increasing ammonia concentrations.
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high level exposures, decreased sensitivity of reflex glottis closure in elderly people implies a loss of protective reflexes, which could increase the risk of damage to the lower respiratory tract to the effects from inhaled ammonia in the elderly. Ammonia causes severe irritation and burning to the skin, eyes, oral cavity, and respiratory tract, particularly mucous surfaces immediately upon contact due to the rapid conversion of ammonia to the very caustic ammonium hydroxide.
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80 ppm 2h Highly intense odor; highly intense eye, nose, throat, and Verberk, 1977 chest irritation, highly intense urge to cough, and moderate general discomfort. 100 ppm 5-30 seconds Significant increase in nasal airway resistance, but atopic McLean 1979 subjects including asthmatics, responded similarly to the non atopic subjects.
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