Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 6 (2008) / Chapter Skim
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Pages 58-114
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1993 1000 ppm Single breath Threshold for reflex glottis closure, 60-year old subjects. Erskine et al.
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Animals surviving the low and intermediate concentrations lost weight during the 14-day observation period. Gross examination of surviving mice showed mild congestion of the liver at Prepublication Copy 59
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was assessed in three male Long-Evans rats exposed sequentially to the following concentrations of ammonia: 100, 300, 300, or 100 ppm for 6 hours for each 60 Prepublication Copy
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Groups of F344/N rats infected with Mycoplasma pulmonis or uninfected were exposed continuously to 100 ppm of ammonia for 3, 5, 7, and 9 days after inoculation to assess the histopathologic effect on the respiratory tract. Ammonia caused hyperplasia and degenerative lesions in the respiratory epithelium of the anterior nasal cavity.
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The entire respiratory tract was examined microscopically. No clinical signs of toxicity were noted for mice exposed to ammonia.
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resulted in slight to moderate exfoliation, erosion, ulceration, and necrosis of the respiratory epithelium of the nasal cavity; no lower respiratory tract lesions were produced (Zissu Prepublication Copy 63
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Repeated exposures to 1101 ppm for 6 weeks (8 hours/day) produced transient dyspnea and lacrimation in dogs and rabbits, whereas continuous exposure to 672 ppm for 90 days resulted in signs of irritation to the eyes and nose and pathologic lesions in the lungs of dogs and rabbits and pneumonitis in several species (dog, rabbit, guinea pig, and monkey)
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Ventilatory rate and tidal volume had no effect on retention. Other experiments showed 78 to 80% retention in the lower respiratory tract and 88% retention in the upper respiratory tract when mechanical devices were used to bypass the upper and lower respiratory tract, respectively.
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Ammonia is water soluble and efficiently scrubbed in the nasopharyngeal regions; ammonia would not reach the tracheobronchial and pulmonary regions of the respiratory tract until the scrubbing action has been saturated. It is unlikely that concentrations detected only by odor or irritation to the nasal cavity or eyes would reach the tracheobronchial and pulmonary regions and have a differential effect on asthmatic individuals.
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An interspecies uncertainty factor is not applied to these data because the AEGL-value is based on human data. An intraspecies uncertainty factor of 1 was selected because ammonia is efficiently scrubbed in the upper respiratory tract, and if irritation is occurs, it would be confined to the nasal cavity (and possibly the eyes)
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Further, exposure concentrations were not measured for the cases in which severe but reversible damage occurred in the respiratory tract. Therefore, AEGL-2 levels for ammonia can be determined from studies reporting Aunbearable@ upper respiratory tract irritation, which could potentially impair the ability to escape, rather than the threshold for irreversible or long-term effects.
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An intraspecies uncertainty factor of 1 was selected because ammonia is a contact irritant, it is efficiently scrubbed in the upper respiratory tract, and any perceived irritation is not expected to be greater than that of the most sensitive non-expert subject. The range of responses for this group is considered comparable to the range of responses that would be encountered in the population including asthmatics.
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Therefore, atmospheric ammonia concentrations generated by the HGSYSTEM model cannot serve as a surrogate for exposure and should not be used to derive AEGL values. Because of the inability to estimate the response variable, the inability to estimate concentrations to individuals sheltered inside buildings, and the uncertainties associated with accident dose reconstruction as surrogates for exposure, animal data are preferred for deriving AEGL-3 values.
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, but tracheobranchial and pulmonary effects may occur at a lower concentration in the elderly. Investigations showed that reflex glottis closure (protective mechanism)
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Reflex glottis closure and nasopharyngeal scrubbing may protect the lower respiratory tract from potential injury during brief exposures. When the scrubbing capacity of the nasopharyngeal region is exceeded, the potential for damage to the lower regions of the respiratory tract increases.
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(Continued on next page) Prepublication Copy 73
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At the ERPG-2 level, ammonia will likely have a strong odor and cause some eye and upper respiratory irritation in susceptible populations, but serious effects are unlikely. The ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to one hour without experiencing or developing life-threatening health effects.
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The studies on lethal or irreversible effects in humans did not have quantitative exposure estimates. However, human studies on upper respiratory tract irritation with quantitative exposure were available.
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1972. Bronchiectasis following ammonia burns of the respiratory tract.
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1996. Acute Inhalation Risk Potentially Posed by Anhydrous Ammonia.
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1995. Histopathological changes in the respiratory tract of mice exposed to ten families of airborne chemicals.
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Time Scaling: None Uncertainty Factors: Interspecies: NA Intraspecies: 1 Calculations: AEGL-1, 10 minutes: 30 ppm/UF = 30 ppm/1 = 30 ppm AEGL-1, 30 minute, 1, 4, & 8 hours: Same as AEGL-1: 30 ppm Prepublication Copy 79
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1/2 = (1.45 H 106 ppm minutes/30 min) 1/2 1-hour AEGL-2 C = 160 ppm 4-hour AEGL-2 C = 110 ppm, same as the POD 8-hour AEGL-2 C = 110 ppm, same as the POD 80 Prepublication Copy
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1/2 C = 398 ppm = 400 ppm Prepublication Copy 81
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The responses by all subjects exposed to 30 ppm of ammonia were consistent with the definition of AEGL1 or below the definition of AEGL-1. Uncertainty Factors/Rationale: Total uncertainty factor: 1 Interspecies: Not applicable Intraspecies: 1; Ammonia is a contact irritant and is efficiently scrubbed in the upper respiratory tract, particularly at the low AEGL-1 concentration; therefore, members of the population are not expected to respond differently to effects confined to the upper respiratory tract.
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Atopics, including asthmatics, and nonatopics responded similarly to a brief nasal exposure to ammonia; a child experienced less severe effects than that of an adult exposed to high concentrations of ammonia; and exercising subjects showed only a nonclinically significant decrease in pulmonary function after exposure to ammonia. Modifying Factor: 1; POD was from a controlled exposure study on human subjects Animal to Human Dosimetric Adjustment: Not applicable.
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is threefold less sensitive in the elderly than in young subjects; this mechanism may only be applicable when concentrations of ammonia exceed 570 ppm. Modifying Factor: 1 Animal to Human Dosimetric Adjustment: 1 Time Scaling: Cn x t = k where n = 2 based upon an empirical analysis of mouse and rat lethality data in which the durations of exposure ranged from 10 to 60 minutes (ten Berge et al.
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Ammonia APPENDIX C CATEGORY PLOT FOR AMMONIA Chemical Toxicity - TSD All Data Ammonia Human - No Effect 100000.0 Human - Discomfort Human - Disabling 10000.0 Animal - No Effect Animal - Discomfort ppm 1000.0 Animal - Disabling AEGL-3 Animal - Some Lethality 100.0 AEGL-2 Animal - Lethal AEGL-1 AEGL 10.0 0 60 120 180 240 300 360 420 480 Mi FIGURE 2-1 Chemical Toxicity TSD All Data -- Ammonia. Prepublication Copy 85
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800-806. 88 Prepublication Copy
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NRa NRa AEGL-1 NR NR NR Not recommended due to steep dose-response relationship, mechanism of toxicity, and because toxicity occurs at or below the odor threshold AEGL-2 0.30 ppm 0.21 ppm 0.17 ppm 0.04 ppm 0.020 ppm Absence of significant 0.9 mg/m3 0.7 mg/m3 0.5 mg/m3 0.1 mg/m3 0.06 mg/m3 hematological alterations in mice consistent with the known continuum of arsine toxicity (Peterson and Bhattacharyya 1985) 90 Prepublication Copy
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Washington, DC: National Academy Press. Prepublication Copy 91
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A total uncertainty factor of 10 was applied: 3 for interspecies uncertainty because interspecies variability was small (LC50 values for rats, mice, and guinea pigs were within a factor of 2.5, and these studies yield similar or higher AEGL-3 values) , and 3 for intraspecies uncertainty because great human variability is unlikely given the homogeneity of the animal data, and a larger uncertainty factor yields 8-hour AEGL-3 concentrations that caused only mild irritation in workers exposed for up to 8 hours (Fannick 1982)
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Exposures to sufficiently high concentrations has produced choking, coughing, a burning sensation on the face, in the nasal and oral passages, and in the upper respiratory tract as well as bronchoconstriction and pulmonary edema (HSDB 2005)
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1996 Flammability/explosion limits 2.1-15.5% NIOSH 2002 1 mg/m3 = 0.349 ppm; 1 ppm = 2.87 mg/m3 Conversion factors Verschueren 1996, IARC 1995 Prepublication Copy 95
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The men reported the crotonaldehyde vapor to be highly irritating to all mucosal surfaces, particularly the nose and upper respiratory tract (Sim and Pattle 1957)
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Values reported for the odor detection and irritation thresholds in humans were quite variable, ranging from Prepublication Copy 97
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The available studies are summarized in Table 5-4. 98 Prepublication Copy
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The surviving animals breathed with a "snuffling" sound for 4-5 days after cessation of exposure. Prepublication Copy 99
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1380 3/12 4/12 4/12 4/12 6/12 1820 6/12 7/12 7/12 7/12 7/12 2050 8/12 8/12 9/12 9/12 9/12 15 550 0/10 0/10 0/10 0/10 0/10 809 ppm 680 0/10 2/10 2/10 2/10 2/10 (750 ppm) 750 2/10 4/10 4/10 4/10 5/10 850 2/10 3/10 5/10 5/10 7/10 980 3/10 6/10 6/10 7/10 7/10 1090 3/10 5/10 7/10 8/10 8/10 1290 5/10 7/10 10/10 10/10 10/10 100 Prepublication Copy
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reported that the animals rubbed their faces with their paws and displayed respiratory distress, and that microscopic examination showed lung hemorrhage, edema in the lungs and brain, and disintegration of renal glomerular capillaries. Prepublication Copy 101
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of 8-week old female F344 rats 20 hours after receiving 300 mg/kg 104 Prepublication Copy
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In a pulmonary function study, animals treated with >16,000 ppm-min died and some had lung edema, and rats exposed to >8000 ppm-min developed proliferative lesions of the respiratory bronchioles. The respiration rate was reduced by 50% (i.e., RD50)
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and crotonaldehyde, were more acutely toxic than their saturated analogs propionaldehyde and butyraldehyde and were the most acutely toxic of the aldehydes tested. Crotonaldehyde, formaldehyde, and acrolein primarily caused lung and respiratory tract irritation and lung injury and had a mild narcotic effect, whereas the narcotic effect was the primary sign resulting from acetaldehyde, propionaldehyde, and butyraldehyde exposure.
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DATA ANALYSIS FOR AEGL-1 5.1. Summary of Human Data Relevant to AEGL-1 Two human studies were located in which concentrations of crotonaldehyde were measured and 108 Prepublication Copy
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in a 100 m3 chamber. The men found it to be highly irritating to the nose and upper respiratory tract and lacrimated after about 30 seconds (Sim and Pattle 1957)
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(1.6 mg/m3) 110 Prepublication Copy
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A total uncertainty factor of 10 was applied: 3 for interspecies uncertainty because interspecies variability was small (LC50 values for rats, mice, and guinea pigs were within a factor of 2.5, and these studies yield similar or higher AEGL-3 values) , and 3 for intraspecies uncertainty because great human variability in unlikely given the homogeneity of the animal data, and a larger uncertainty factor yields 8-hour AEGL-3 concentrations that caused only mild irritation in workers exposed for up to 8 hours (Fannick 1982)
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A total uncertainty factor of 10 was applied: 3 for interspecies uncertainty because interspecies variability was small (LC50 values for rats, mice, and guinea pigs were within a factor of 2.5, and these studies yield similar or higher AEGL-3 values) , and 3 for intraspecies uncertainty because great human variability in unlikely given the homogeneity of the animal data, and a larger uncertainty factor yields 8hour AEGL-3 concentrations that caused only mild irritation in workers exposed for up to 8 hours (Fannick 1982)
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The ERPG-2 for crotonaldehyde is based on human acute exposure studies (Sim and Pattle 1957; Rinehart 1967) and the rat pulmonary function study of Rinehart (1967)
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A possible confounding factor was the simultaneous exposure of the workers to several other airborne chemicals, although it is likely that crotonaldehyde was the most acutely irritating of all of the airborne chemicals used in the plant. 114 Prepublication Copy
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