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Chapter 4 ENVIRONMENTAL HEALTH EFFECTS This chapter provides some commentary on the health aspects of NOX in relation to the regulation of exhaust emissions from heavy-duty vehicles. The intent is to place emissions control technology in the context of the health consider- ations. This chapter is not an original review of research in this field. Instead, the material is drawn largely from a number of published reviews of the health impacts of NOX and diesel exhaust (National Research Council, l977, l98l; U.S. Environmental Protection Agency, l97l; World Health Organization l977). The discussion concentrates on the extent to which dose-response relation- ships can be defined at low levels of NOX exposure and on the health trade-offs that may be involved in applying current control technologies (particularly the increased emissions of carcinogenic particulates with reductions in NOX emissions). BIOMEDICAL EFFECTS OF NOX The most toxic of nitrogen oxides is nitrogen dioxide (NO2), and much of the concern with NOX relates to the toxicity of NO2. The effects depend on both concentration and duration of exposure (Gardner et al., l979). The chemical reactions of NOX leading to the toxic responses are essentially instantaneous and involve the formation of nitrous acid (HNO2) and nitric acid (HNO3). Both acids may be neutralized at rapid rates in the lung. NOÂ£ is only moderately water soluble and thus penetrates the the deep portions of the lung. The region of the terminal respiratory bronchials and adjacent alveoli are most affected (Coffin and Stokinger, l977). Damage from NO2 exposure is almost completely limited to the lung, since the chemical reactions occur very rapidly. A major toxic effect is the death of respiratory tract cells. These cells are replaced, so that the net effect is a stimulation of cell turnover and some shift in cell types; for example, ciliated cells can be replaced by mucous-secreting cells. Biochemical indicators of injury in terms of, for example, increased cell permeability are observed with exposures as low as 0.4 ppm NO2 (Menzel et al., l977). Pulmonary defenses against exogenous bacteria and viruses are dimin- ished by even short-term exposures to NO2. Single three-hour exposures at a concentration of l ppm NO2 result in a small excess mortality in mice 73
74 after challenge with infectious agents; recovery from this effect occurs in 24-36 hours (Coffin, Gardner, and Blommer, l976). Chronic exposure is also characterized by cell death and replacement of pulmonary cells. Biochemical and functional indicators of damage occur relatively rapidly and reach a steady state within about two weeks. The development of irreversible structural damage of the lung requires a long time and involves increased thickness of alveolar walls, loss of ciliated cells, narrowing of small airways, alterations in the morphology of clara cells, transformation of alveolar cells from Type II to Type I, and the appearance of altered alveolar collagen (Coffin and Stokinger, l977). In rodents, the development of frank emphysema with extensive destruction of air spaces requires relatively high exposure (e.g., l5 ppm NO2). The suppression of mortality from continuous exposures to high concentrations of NO2 by anti-oxidants such as vitamin E and other free radical scavengers supports the possibility that the toxic effects of N(>2 are largely due to membrane damage by chemical oxidation of unsaturated fatty acids (Menzel, l970). While there is some evidence for the development of tolerance from a biochemical standpoint, the possibility of adaptation to exposure to NOÂ£ is questionable at present. Additive toxicity with other air pollutants and NO2 is most likely, but no evidence for potentiation has been found. The kinds of pulmonary damage caused by NO2 and ozone are similar. In summary, the most sensitive toxicologic response to NO2 in experimental animals appears to be a decrease in resistance to infection, and this has been observed at concentrations down to 0.5 ppm NO2 for exposure times of 4 hours or more. Direct evidence for the effects of NO2 on humans comes from controlled exposure studies and from epidemiologic studies (National Research Council, l977). Controlled exposure studies provide information on the effects of single short-term exposures. The most frequently observed effect of NO2 exposure includes increases in airway resistance and changes in susceptibility to the effects of bronchial constricting drugs. There is reasonably clear-cut evidence for these effects at exposure concentrations above 2 ppm in healthy individuals with 5-l5 minute exposures. A substantial series of studies fails to show any clear-cut evidence for effects on pulmonary function at exposures of l ppm or below. The functional significance of the induction of bronchial constriction or increased susceptibility to bronchial constricting drugs is not clear. There is some unconfirmed evidence for a greater than normal sensitivity to NO2 in bronchitics, but the results of different studies are not consistent. The extent of hypersusceptibility in children, the elderly, and individuals with cardiovascular disease has not been studied. Epidemiologic studies are complicated because there are usually com- plex mixtures of pollutants in the air. Epidemiologic studies of NO2 effects made before l973 are of questionable validity due to the use of the unreliable Jacobs-Hocheiser technique for measuring NO2. With few exceptions, epidemiologic studies fail to show any significant effects on lung function in populations exposed to ambient levels of urban NO2 pollution. There was evidence of an increased incidence of bronchitis
75 in children in the Chattanooga, Tennessee, area who lived near a plant that emitted N(>2, but no reliable NOÂ£ estimates were associated with the several studies made of this population. A number of epidemiologic studies have shown increased respiratory illness rates among young children living in homes using gas cooking stoves (Florey et al., l979; Keller et al., l979; Speizer et al., l980). The annual average levels in these houses were on the order of 0.03-0.07 ppm, with peak levels during the operation of the stoves in the domain of 0.5-l.0 ppm. No such effect of indoor NOÂ£ pollution has been observed in adults. HEALTH ASPECTS OF POLLUTANT TRADE-OFFS Current methods of controlling NOX emissions from heavy-duty diesel engines can increase emissions of carbon monoxide, hydrocarbons, and particulates. Heavy-duty diesels emit relatively small amounts of carbon monoxide, so that modest increases in emissions of this pollutant are not of special concern. Hydrocarbons interact with sunlight and NO2 to form oxidants, which in general produce the same kinds of lung damage as NO2. Hence, a rise in hydrocarbon emissions tends to vitiate the health benefits of reduced NOX emissions. The rise in particulate emissions with decreased NOX emission is of special concern because diesel exhaust particles might constitute a carci- nogenic risk to humans. Like the combustion of most organic materials, the combustion of diesel fuel produces polycyclic aromatic hydrocarbons (PAH), which are well-known carcinogens, as part of the output of particulates. These particulates have been shown to be mutagenic in a variety of assay systems and are capable of initiating skin cancer in mice (Pepelko, Danner, and Clarke, l980). Diesel exhaust has not been found, so far, to be carcinogenic when inhaled by laboratory animals; nor have epidemiological studies of various occupational groups revealed a convincing connection between diesel exhaust and human cancer (National Research Council, l98l). However, the available evidence, although negative, is consistent with a level of carcinogenic risk that is of serious concern. The scientific evidence clearly demonstrates the carcinogenic!ty of diesel exhaust constituents in laboratory animals. Further work, such as the Environmental Protection Agency's current research program to characterize the carcinogenic potential of diesel exhaust for humans, is needed. For purposes of risk assessment, the dose-response relationships for carcinogens are generally assumed to be linear, and without thresholds of activity (Interagency Regulatory Liaison Group, l979). The implication of this dose-response characteristic is that there is no such thing as a safe dose of a carcinogen; in other words, excess risks are induced by even minute exposures. This stems from the facts that mutagenicity and carcinogenicity
76 both represent manifestations of genotoxicity and that there is ample evidence for the linear, nonthreshold character of mutagenesis. The initiation stage of carcinogenesis in mouse skin also shows a linear, nonthreshold pattern (Albert, l98l). Limited epidemiologic evidence also support the linear, non- threshold character of carcinogenic action. The dose-response relationships at low levels of exposure for NOX are uncertain, but the rapid neutralization of nitric and nitrous acids by lung fluids would tend to make very low levels of NOX exposure relatively nontoxic. Hence, there are grounds for believing, given the present state of knowledge, that the carcinogenic particulates in diesel exhaust may represent a more serious health risk than NOX at low levels of exposure. SUMMARY AND CONCLUSIONS NOX, and particularly NO2, is toxic to the lung. The most important effect at concentrations below l ppm appears to be increased susceptibility to pulmonary infection. Recent epidemiologic evidence indicates that young children are susceptible at average levels not far from the current national air quality standard of 0.05 ppm, although this effect may in fact be due to transient spikes in indoor N02 concentrations, which can approach 0.5-l.0 ppm. There are no dose-response data for heightened susceptibility to pulmonary infection in animals at NO2 concentrations below 0.5 ppm, and there is no dose-response data for this effect in humans. We have no knowlege of the mechanism of the effect in humans. For that reason, there is no basis for postulating the shape of the dose-response relationship. Consequently, considering NOX in isolation, it appears to be a good idea to reduce atmospheric concentrations to the extent feasible. However, there is no basis for an accurate prediction of the health impacts of increased NOX levels on the order of 25-50 percent over l976 urban levels, which have been projected to occur given a high-growth scenario for the use of heavy-duty vehicles without more stringent NOX emission controls. In heavy-duty diesel engines, reducing NOX emissions according to current control strategies may increase emissions of particulates. This represents a trade-off of very different kinds of health effects between the two classes of pollutants. The principal hazard from increasing diesel exhaust particulates is the possible excess risk of lung cancer; here, there is wide acceptance of a linear, nonthreshold dose-response relationship for the effects of low-level exposures to environmental carcinogens. By contrast, the effect of NOX in heightening susceptibility to respiratory infection is probably a less serious toxic effect than lung cancer and, although the dose-response relationships for NOX are highly uncertain, the likelihood that there is a threshold for NOX is greater than that for the action of carcinogens. From a health standpoint, it might be imprudent to suppress NOX emissions from heavy-duty engines at the expense of a substantial increase in the emission of particulates. The extent to which these two species affect human health requires further study, especially to assess the carcinogenic risk of diesel particulates.
77 REFERENCES Albert, R. E. l98l. "A Biological Basis for the Linear Non-Threshold Dose- Response Relationship for Low-Level Carcinogen Exposure." In Measure- ment of Risks (G. Berg and H. David Maillie, eds.). New York! Plenum Publishing Corp. Coffin, D. L., and H. E. Stokinger. l978. "Biological Effects of Air Pollutants." In Air Pollution, 3d ed., vol. 2 (A. C. Stern, ed.), p. 264-35l. New York: Academic Press, Inc. Coffin, D. L., D. E. Gardner, and E. J. Blommer. l976. "Time-Dose Response for Nitrogen Dioxide Exposure in an Infectivity Model System." Environmental Health Perspectives l3:ll-l5. Florey, C. du V., R. J. W. Melia, S. Chinn, B. D. Goldstein, A. G. F. Brooks, H. H. John, I. B. Craighead, and X. Webster. l979. "The Relation Between Respiratory Illness in Primary School Children Gardner, D. E., F. J. Miller, E. J. Blommer, and D. L. Coffin. l979. "Influence of Exposure Mode on the Toxicity of Environmental Health Perspectives 30:23-29. Interagency Regulatory Liaison Group, Work Group on Risk Assessment. l979. "Scientific Bases for Identification of Potential Carcinogens and Estimation of Risks." Journal of the National Cancer Institute 63:24l-268. ~ Keller, M. D. , R. R. Lanese, R. I. Mitchell, and R. W. Cote. l979. "Respiratory Illness in Households Using Gas and Electricity for Cooking." Environmental Research l9:495-503. Menzel, D. B. l970. "Toxicity of Ozone, Oxygen, and Radiation." Annual Review of Pharmacology l0:379-394. Menzel, D. B., M. D. Abou-Donia, C. R. Roe, R. Ehrlich, D. E. Gardner, and D. L. Coffin. l977. "Biochemical Indices of Nitrogen Dioxide Intoxication of Guinea Pigs Following Low-Level Long-Term Exposure." In Proceedings of the International Conference on Photochemical Oxidant Pollution and Its Control, September l973 (B. Dimitriades, ed.). Research Triangle Park, N.C.: U.S. Environmental Protection Agency. (EPA 600/3/-77-00lb)
78 l98l. Health Effects of Exposure to Diesel Exhaust. Diesel Impacts Study Committee, Health Effects Panel. Washington, D.C.:- National Academy Press. Pepelko, W. E., R. M. Danner, and N. A. Clarke, eds. l980. Health Effects of Diesel Engine Emissions: Proceedings of an International Symposium, vol. 2. Cincinnati, Ohio: Health Effects Research Laboratory. (EPA 600/9-80-057b) Speizer, F. E., B. Ferris, Jr., Y. M. M. Bishop, and J. Spengler. l980. "Respiratory Disease Rates and Pulmonary Function in Children Associated with NOX Exposure." American Review of Respiratory Diseases l2l:3-l0. U.S. Environmental Protection Agency. l97l. Air Quality Criteria for Nitrogen Oxides. Air Pollution Control Office. Washington, D.C.: U.S. Environmental Protection Agency. World Health Organization and U.N. Environment Program. l977. Oxides of Nitrogen. Geneva: World Health Organization.