Guides for Short-Term Exposures of the Public to Air Pollutants

Page 1

Guides for Short - Term Exposures of the Public toAir Pollutants I. Guide f o r Oxides of Nitrogen The Committee on Toxicology National Academy of Sciences - National Research Council

Page 2

Prepared under Contract No. CPA 70-57 between the National Academy of Sciences, Advisory Center on Toxicology and the A i r Pollution Control Office of the Environmental Protection Agency. Division of Health Effects Research A i r Pollution Control Office Environmental Protection Agency The in form ti - on contained in thi.3 pub lii distribution or at tri but io q tothe Natio::al Academy of Sciences with ol it prior written approval.

Page 3

The A i r Pollution Control Office (APCO) has focused its initial concern on long - term exposures of the public to air pollutants. It is also concerned with occasional circumstances in which the public maybe exposed briefly to relatively high concentrations of air pollutants. For example, steam boilers usually have short bursts of high emissions when the tubes are blown o r when the fires are started up. Similarly, batch processes in the metallurgical industry produce pulses of effluent. testing and launching of rockets result in intermittent releases of exhaust short periods of high concentration of stack effluents in localized areas. Accidental release of chemicals sometimes occur' in industry a r during transport, and may lead to public exposure. Rapidly changing meteorological conditions may result in Recognizing these occasional peak additions tothe ambient exposure of the public, APCO has requested the assistance of the Committee on Toxicology of t h e National Academy of Sciences -National Research Council in providing Guides for Short - Term Exposure Limits for Air Pollutants. In preparing these guides, the Committee utilized the principles described in the NAS-NRC document entitled " Basis for Establishing Short - Term Inhalation Exposure Limits of the Public to Atmospheric In studying the literature sources for this document, primary consideration was given to material dealing with brief, intermittent exposure to the nitrogen oxides. In this Guide the effects of oxides of nitrogen on domestic animals, fish and wildlife, vegetation, and materials are not included. Analytical and air-monitoring procedures are also excluded. discussed thoroughly in " Air Quality Criteria for Nitrogen Oxides, " to be published early in 1971 by APCO. These subjects are

Page 4

The nitrogen oxides of possible concern for air pollution purposes Other oxides are known t o exist but a red no concern because of are nitric oxide (NO), nitrogen dioxide (NOz), and nitrogen pentoxide their relatively low toxicity o r absence from ambient air. Nitric oxide i s found to b e of little concern asan air pollutant since.it is not an irritant gas (69) and is one-fifth as acutely toxic as described by the equation: In the presence of oxygen, NO is converted t o NO2 at a rate gases in moles / cc,t is time, and kisa rate constant for temperature having a value at 20° C of 14. 8 x 10-3 m6 m o l e s - 2 sec-l (69). Westberg, e,t &,(78) have reported that the conversion of NO t o NO2 is influenced by the presence of other pollutants, such as carbon monoxide and ozone, which might also be present in the air. Conflicting reports on the toxicity of N205are present in the t o be qualitatively similar to those of ozone (03) although N2O5 is about three times as active as a pulmonary irritant as the latter. classify N2O5 asa lung irritant with a potency of the same order as that of phosgene, and claim that the increase in the toxicity of an03 atmosphere brought about by the presence of oxides of nitrogen can b e attributed to N2O5 present. Diggle and Gage (1-2) report the toxic Effects of N2O5 On the other hand, Byers and Saltzman, as reported in Stern(5), found Nz05to possess an LC50 for albino mice of approximately 75 ppm (-- 1OX that of 03). No t i m e of exposure w a s given. Stokinger (6) in preliminary studies showed that no deaths occurred in rodents upon exposure to at least 42 ppm of N2O5. Stokinger expresses the opinion that the claims of Diggle and Gage are not supported by their data. Byers and Saltzman (in 5)attribute the greater apparent toxicity found by Diggle and Gage to their method of administering N2O5 as a solution

Page 5

The kinetics of the decomposition a s well as the synthesis of N2O5 have been extensively studied under various conditions of tempera - contaminants (72-76). It becomes evident that N2O5 a s well as NO react in air to form a variety of products, the principal one being NO2. Because of its relative prevalence, stability, and toxicity, NO2 is the oxide of nitrogen of primary concern as a n air pollutant. From the available scientific literature on the physiologic and toxicologic effects of gaseous nitrogen dioxide (NOz), it is apparent that NO2 as a freely diffusible gas has the potential of causing adverse effects on human health and well-being. Appendix 11. It should b e noted that the data in the literature from which Table C was derived were based on exposures of "normal" healthy human volunteers. Similarly,most of the ancillary information on animals given in the Sm mary, and in Tables A and B of Appendix I, is from healthy animals. The population t o which this Guide is tobe applied hasa wide range of states of health and well-being. These are summarized in Table C - Factors Affecting Human Response t o NO2 Among the most critical items t o be recognized i n deriving limiting exposure values for the Guides are the factors and conditions that can modify and significantly alter human response to NO2. five most important(temperature, predisposing disease, heredity, age, and interactions with other environmental pollutants) are discussed below. A commonly overlooked and disregarded condition that greatly modifies the response to NO2 is temperature. Experimental animals exposed tothe additional stress of a hot o r cold environment were more susceptible t o the effects of NO2. A minimum toxic effect was observed at 15O C, with an increased effect above and below this temperature Individuals who have asthma, chronic bronchitis, emphysema, and other forms of chronic obstructive pulmonary disease form the groups which will be most severely affected by short - term exposure to high levels of nitrogen oxides. Current evidence indicates that normal healthy individuals will not be adversely affected by short - term exposures that produce effects among these more susceptible groups (62)

Page 6

Her edit arv Pr ed i s DO s it i on In addition tothe well-known hypersusceptibility of the hereditary asthmatic,a recently discovered association between the hereditary defect, serum antitrypsin deficiency, and familial pulmonary emphysema indicates the presence of another group of individuals with increased susceptibility to the irritant gas NO2 (59). defect get along without respiratory difficulties until coming in contact with respiratory irritants. Excessive exposures of those persons could initiate early pulmonary emphysema. Although the frequency of hemizygotes is not known nationwide i n the U. S. A., pedigrees obtained on small groups in a few states indicate a hemizygote frequency between 2. 3 and 5 percent, a not insignificant frequency (59). Individuals hemizygous f o r the It isa recognized medical fact that responses to environmental influences among the very young and the very old are frequently different from those inthe in-between age groups - both in degree of sensitivity and in the character of the response. Moreover,the bases for these differing responses among the very young are not the same as those among the very old. In the very young, increased susceptibility results from either as yet undeveloped metabolizing enzyme systems or from incompletely developed cellular structures.The age - sus ceptibility factor for the young might be estimated to be between 5 and 10, on the basis of increased neonatal deaths in mice exposed to ozone (37) (66). Factors associated with old age, such a s differences in physical activity and pre-existing car dio - respiratory disabilities, will tend to modify the susceptibility of various age groups t o pollutants such as NO2. Extremely little information exists from which to estimate these factors. Interactions Affecting Response t o Exposure The information on NO2 interactions i s incomplete and therefore must be considered only suggestive for the purposes of Short - Term Guide development. Each instance must be evaluated individually in this respect, as t o whether extrapolation of interactions t o ambient pollutant levels is. scientifically sound. a ) Physicochemical Interaction. It would appear from two independently derived sets of data that the acute toxic response to NO2 may be considerably reduced when NO2 is inhaled for short periods (20 minutes to an hour),either concomitantly with o r subsequent to, solid o r liquid particulates (65)(66). It proved to be immaterial whether the concomitant aerosol was a solid o r liquid particulate (clays, siliceous

Page 7

materials,or oils) ; the mice survived longer when exposed t o the NO2particulate mixture than to NO2 alone, indicating an interaction with reduced toxic effect. Similarly, oil mists of res pir able particle size greatly reduced the toxicity of NO2 inhaled by rats, provided exposure to the oils preceded exposure to NO2 by a few hours (66). On the other hand, Boren (77) has reported that inhalation of carbon particles followed by in term it ted NO2 exposure resulted in lung de st ruc - tion not observed with NO2 exposure alone. Exposure t o NO2 followed by inhalation of carbon particles resulted in a decreased macrophage response contrary to the response normally observed after exposure to carbon particles alone. b ) Physiologic Interactions. Almost complete protection from the lethal effects of inhaled NO2 was afforded mice exposed to mixtures of NO2 and either hydrogen sulfide ormer capt an s in four-hour exposures (5). Although the l e v e l at which the different sulfur compounds negated the effects of NO2 varied with the compound, some of them, including hydrogen sulfide, counteracted the NO2 effects at molar ratios far below equivalency (1. 5 ppm H2S p r e s e n t with 82 ppm NO2). This suggests that relatively minute concentrations of these sulfur compounds, if coexisting in the air, can negate the physiologic effects of relatively m u c h higher concentrations Mi c r obial Interactions In contrast to the beneficial physicochemical and physiologic inter - actions tobe expected from certain air pollutants coexisting with NO2, bacterial infection of the lung after NO2 exposure would appear to have a distinctly adverse effect (23)(27)(68). A two-hour exposure to NO2 at 3.5 ppm increased the mortality of mice infected with Klebsiella the same increase in mortality at 0. 5 ppm. In considering the relevance of these results to human responses, it i s important t o note that both the exposed and control mice had overwhelming bacterial exposures.Forty - seven percent of the infected controls not exposed t o NO2 died in the first instance, the 3.5 ppm level, and 68 percent of the controls in the second instance, the 0. 5 ppm level. work of-Ehrlich and Coffin with the observations of Wagner and his copulmonary infections f o r 18 months at 5 ppm NO2. difference between the exposed and control groups in d e g r e e of pulmonary infection, body weight gain, o r oxygen consumption. Daily exposures for two months was required to produce It i s difficult t o reconcile the preceding The latter exposed rats from a colony having spontaneous They found no

Page 8

Summary of NO2 Toxicity Nitrogen dioxide has been reported to produce the following 1) It acts as a deep-lung irritant at high concentrations (several hundred pprn for a few minutes), which may result in pulmonary edema o r lead to bronchiolitis fib rosa obliterans (53). 2)At levels of 10 ppm or more, the acute effects of NO2 are additive with the effects of 0 3 . At levels below 10 ppm, NO2 mixed exposures with ozone had less than additive effects (6). The effects of NO2 with other gaseous irritants (S02, aldehydes, etc. )are reported to for four hours. The maximum effect was observed 24-48 hours postLipoperoxidation was observed in rats exposed t o NO2 at1 ppm 4) Alterations in mast - cell morphology were observed in rat lung tissue after exposure at 1 pprn for one hour or0.5 pprn for four hours. These alterations were reversible within 24-27 hours (47). 5 ) NO2 may increase the retention of particulates including microbial s by its ciliostatic effect. mu co ciliary activity within five minutes (161. A concentration of 100 ppm inhibited 6 ) Chronic exposure of experimental animals to NO2 at a concent ration of 0. 5 ppm followed by a pulmonary challenge with high levels of infectious organisms (K.- pneumoniae) resulted in an increased mortality (24). However, no such interaction of NO2 and bacteria was observed in "naturally" infected rat lungs, suggesting synergism only at extreme levels of bacterial challenge (21). 7 ) It was observed that the rate of tumor induction in mice having spontanebus pulmonary tumors might have been accelerated from daily Final tumor size and mortality were not

Page 9

From knowledge of the irritant action of NO2 on the respiratory tract it i s predictable that the individuals most susceptible to NO2 action are not the healthy,but those predisposed by age, heredity, and preexisting respiratory disease.These are the persons that predictably will respond most sensitively at concentrations t o which healthy individuals would be The effects of NO2 are, within limits, reversible. The extent of .- ~ recovery seems to be a function of a) the degree of exposure, b)the length of the interval between exposures, and c)the health and / orage of the exposed individual. Most experimental studies have been done with healthy animals. The effects of NO2 exposure on animals with anemia or preexisting pulmonary disease(emphysema, chronic bronchitis, asthma, etc. ) should b e evaluated t o provide a firmer basis for establishing short - term guides. Asa consequence of the lack of this critical information, this Guide, which has been developed for the protection of human health and well-being from short - term exposure t o oxides of nitrogen, is only a "best-judgment" estimate. Hence, the following limiting values proposed should b e regarded as highly tentative and subject to revision as more appropriate and pertinent information is developed.

Page 10

Guide Values for Short - Term Exposure of the Public t o Oxides of Nitrogen Short - term Public Limits of 1 ppm for 10 minor less, 30 rnin o r _ _ 60 min represent "ceiling" values not tobe exceeded. Any fluctuations in concentration must not exceed a maximum allowable concentration of value f o r the 5-hr period as long as the "ceiling" limit of 1 pprn is not The limit of 0.5 ppm for5 hr/da.y, 3-4 days / more present an average These limits are suggested in order to protect asthmatics, believed tobe the most susceptible segment of …