Assessment of Exposure-Response Functions for Rocket-Emission Toxicants (1998) / Chapter Skim
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Appendix E: Acute Toxicity of Nitrogen Dioxide
Appendix E: Acute Toxicity of Nitrogen Dioxide
Pages 147-196
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From page 147... ...
Because NO2 is a gas, the primary route of exposure is via inhalation, making the lung the primary target organ; however, extrapulmonary effects also have been reported. There have been numerous reviews on the toxicity of NO2 (NRC 1977; WHO 1977; EPA 1982, 1993~.
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From page 148... ...
In the workplace, exposures to NO2 have been reported In such occupations as electroplating, acetylene welding, agriculture, space exploration, detonation of explosives, certain military activities, and bunting of n~trogen-containing propellants (Mohsen~n 1994~. In such situations, exposure concentrations can be very high.
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From page 149... ...
Such acciclental-exposure data, together with relevant animal studies, are most useful in establishing emergency short-term exposure limits.
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From page 150... ...
At lower exposure concentrations, a variety of nonlethal effects have been observed (see Table E-1 B)
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From page 152... ...
Because the safety of volunteer subjects is of paramount importance, high exposure concentrations cannot be used, and only a few nonevasive end points usually are measured. Norma/ Subjects Some significant responses, which could be attain uted to inhalation of NO2, have been reported at concentrations of more than 1.0 ppm In normal subjects, as described below.
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From page 153... ...
153 In a, Cat a)
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From page 154... ...
(1979) reported that healthy subjects exposed to NO2 for 2 hr at a concentration of 5.0 ppm exhibited increased airway resistance and impaired oxygen exchange in me lung.
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From page 155... ...
(1990) exposed exercising individuals to NO2 at 4.0 ppm for 20 men on alternate days for 12 days and found enhanced phagocytic activity, a reduction in total cell count, and a decrease in number of mast cells, T and B lymphocytes, and natural killer cells in BAL fluid 24 hr post-exposure.
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From page 157... ...
157 CO Ids ~ _ ' a' ~ ~ ~ ~ -O .
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From page 159... ...
found significant increases in airway responsiveness to methacholine in asthmatic subjects following a 1-fur exposure to NO2 at 0.5 ppm. Orehek et al.
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1990~. Even at higher exposure concentrations and longer durations, subjects with mild asthma exposed at 3.0 ppm, with exercise, for 60 min or at 0.3 ppm for 3.75 hr failed to exhibit changes In pulmonary function, symptoms, or increased airway responsiveness to carbacho]
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From page 162... ...
A similar conclusion has been drawn from those epidem~olog~cal studies examining the effects of NO2 on puhnonary function (EPA 1993~. Because of the low exposure concentrations of NO2, the extended exposure durations, and the presence of other tonic chemicals in the air, evidence from epidem~olog~cal studies is of little value for establishing short-term exposure limits for accidental releases of NO2 EFFECTS IN ANIMALS Numerous health effects from exposure to NO2 have been confirmed in several species of animals.
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From page 163... ...
163 cn a)
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1994~. Rats exposed for 2 min at 1,000 ppm exhibited 100% mortality following exercise (Lehnert et al.
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~ ~n co ~ CI ~ x o c~ o z o =' cn m c o .m c a)
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From page 166... ...
the level of type IT hyperplasia correlated with increased exposure concentration, and alveolar fibrin appeared at concentrations of 25, 50, 75 and 100 ppm. The fibrin response increased with increasing exposure concentration (Lehnert et al.
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From page 167... ...
Effects on Lung Function Both short-term and long-term exposures to NO2 produce changes in puhnonary function. Exposures of rats to various concentrations of NO2 for durations of ~ to 20 man produced changes in minute ventilation, tidal volumes, and breading frequencies (Lehnert et al.
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From page 168... ...
168 In C' a, 3 a, o In Cal CO .
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From page 169... ...
o <~' ~<~, 3 ~cat _ ~)
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From page 170... ...
About 6 hr later, airway resistance and hypoxemia ~ncreasec! and lung compliance decreased aanuszkiewicz and Mayorga 1994~.
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171 cn a, a, tr CO ._ o °D a ~ct5 CD , ,, c = 03 ~-~ ~ E E = a)
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From page 172... ...
at 500 ppm for 15 to 20 min. they had significant increases in protein, albumin, and number of epithelial cells in BAL fluid and a significant decrease in the number of alveolar macrophages in BAL fluid Januszkiewicz and Mayorga 1994; Mayorga et al.
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1969~. Also, a 2-fur exposure at ~ ppm increased the number of PMNs in the BAL fluid of those animals compared with controls (Gardner et al.
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1979~. In general, exposure to high concentrations of NO2 for brief periods resulted in more severe pulmonary infections and greater mortality than exposure to lower concentrations for longer periods that producer} similar C x T products.
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From page 177... ...
177 ~ ° _ CtS Co C~ C CO C ~ - , cO cn co a~ a~ ~ ° CO ~^, .c ~(> ~ Q ~o 5 ~ ~Cl5 o C Q _ E - a)
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From page 178... ...
ESTABLISHED INHALATION EXPOSURE LIMITS Table E-3 lists existing exposure limits for civilian and military populations. Table E-4 lists Army incapacitation criteria for NO2.
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From page 180... ...
Army Acceptable Human Criteria in Armored Vehicle During Live Fire Testing AIHA 1964 AIHA 1964 AIHA 1964 AIHA 1964 15 min 50 Mayorga 1994 5 min 100 Mayorga 1994 Abbreviations: EPA, U.S. Environmental Protection Agency; NMQS, National Ambient Air Quality Standard; LOC, level of concern; ACGIH, American Conference of Governmental Industrial Hygienists; TLV, Threshold Limit Value; TWA, time-weighted average; STEL, short-term exposure limit; NIOSH, National Institute for Occupational Safety and Health; IDLH, immediately dangerous to life and health; REL, recommended exposure limit; OSHA, Occupational Safety and Health Administration; PEL, permissible exposure level; NRC, National Research Council; SPEGL, short-term public emergency guidance level; AIHA, American Industrial Hygiene Association; EEL, emergency exposure limits.
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From page 181... ...
APPENDIX E: ACUTE TOXICITY OF NITROGEN DIOXIDE 1 81 ppm 50 35 25 20 10 5 3 0.5 0.25 0.12 0.06 0.053 0.04 Amid NRC Maximum Exposure Level | Amid AIHA 30-min Al HA N I OS H I DLH ANGIE STEL ~ ANGIE TLV | EPA LOO H~SHA PEL l 1-hrSPEGL H NIOSH REL | 2-fur SPEGL l 4-fur SPEGL 8-fur SPEGL ~ 1 6-fur SPEGL ~ EPA Air Quality Standard - 24-hr SPEGL | FIGURE E-1 Currently recommended exposure limits for Truman exposure to NO2 (see Table E-3 for sources)
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From page 182... ...
Although the severity of effects increases with increasing exposure concentration and duration, concentration has the more pronounced influence. Using data from accidental exposures, controlled human studies, and experimental animal studies, the goal of this chapter is to identify exposure levels associated with a threshold for effects in sensitive and normal populations and exposure levels that might result in moderate and severe effects.
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From page 183... ...
By comparison, exposure of healthy humans at concentrations up to 4 ppm usually failed to affect pulmonary function (ATS 1996~. However, In another study, no significant lung-function alterations could be found in asthmatic subjects exposed at 0.3 ppm NO2 for ~ hr (Morrow and Utell 1989~.
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From page 184... ...
Mild effects are reversible with 48 hr and do not interfere with normal activity or require medical attention. Moderate effects are irreversible effects that do not alter organ function or interfere with normal activity, or they are reversible effects that alter organ function or interfere with normal activity.
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From page 185... ...
Serious effects requiring medical treatment or hospitalization; progressive respiratory injury, including edema, permanent pulmonary injury, loss of consciousness, and possible death aThe concentrations listed are the lowest estimated concentrations at which effects in the specified severity category might occur in some members of the healthy population. As exposure concentration increases, more individuals are expected to be affected, and the severity of response within an individual is expected to increase.
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From page 186... ...
To be safe, the tests could be limited to exposure concentrations expected to produce mild effects only. Controlled human exposures at high NO2 exposure concentrations to determine the sensitivity of individuals with cardiopulmonary impairments and that of healthy individuals are not possible.
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From page 187... ...
1983b. Effect of 0.1 ppm NO2 on Pulmonary Functions and Non-specific Bronchial Reactivity of Normals and Asthmatics.
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From page 188... ...
1987. Effect of Nitrogen Dioxide, Ozone, and Peroxyacetyl Nitrate on Metabolic and Pulmonary Function.
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From page 189... ...
1983. Effects of 0.1 ppm nitrogen dioxide on airways of normal and asthmatic subjects.
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From page 190... ...
1991. Acute pulmonary effects of nitrogen dioxide exposure during exercise in competitive athletes.
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From page 191... ...
1982. Effects of nitrogen dioxide on pulmonary function in normal healthy humans and subjects with asthma and chronic bronchitis.
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From page 192... ...
1987. Acu~ e~ct of ~bogen dioxide exposure on ~e ~ncdonal ac~i~ of alpha-l-pro~ase ^~itor ~ bro~ho~eolar 1~ ~id of normal su~ec~.
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From page 193... ...
1990. Short-term exposure to 0.3 ppm nitrogen dioxide does not potentials airway responsiveness to sulfur dioxide in asthmatic subjects.
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From page 194... ...
1989. Inflammatory cell response in bronchoal~reolar fluid after nitrogen dioxide exposure of healthy subjects [abstract]
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From page 195... ...
1977. Experimental studies on the shortterm effect of air pollutants on pulmonary function in man: Two-hour exposure to NO2, O3, and SO2 alone and in combination.
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From page 196... ...
1972. The respiratory effects of exposure to SO2-NO2 mixtures on healthy subjects [in Japanese]
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