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Sackner et al. (1979) studied a diverse group of normal and asthmatic subjects exposed
n
to concentrations reaching 1,000 /*g/m of NaNO3 for 10 min at rest.., There were no
significant effects on an extensive battery of pulmonary function tests.
Utell et al. (1979) studied both normal and asthmatic volunteers exposed to
7,000 jitg/m3 of 0.46 pm NaNO3 aerosol for 16 min via mouthpiece. The major health effect
end points measured in their study included Raw, both full and PEFV curves, airway
reactivity to carbachol, and aerosol deposition. Aerosol deposition as a percentage of inhaled
aerosol averaged about 50% for normals and about 56% for asthmatics; the group differences
were not significant. The exposure to NaNO3 aerosol was indistinguishable from the control
NaCl exposure in normals. Similarly, there were no effects of NaNO3 exposure in
asthmatics.
Utell et al. (1980) subsequently studied 11 subjects with influenza exposed to the same
NaNO3 regimen as above. The subjects were initially exposed at the time of illness and then
re-exposed 1,3, and 6 weeks later. Aerosol deposition ranged from 45 to 50% over the,four
exposure sessions. All subjects had cough and fever, and 10 of 11 had viral or immunologic
evidence of acute influenza. Baseline measurements of FVC and FEVj were within normal
limits and did not change throughout the 6-week period. There were small but significant
decreases in Gaw following NaNO3 inhalation but not after NaCl exposure. This difference
was present during,acute illness and 1 week later, but was not seen at 3 and 6 weeks after
illness. The decrease in SGaw seen on the initial exposure was accompanied by a decrease in
partial expiratory flow at 40%TLC; this was also observed at the 1 week follow-up exposure.
This study suggests that the presence of an acute viral respiratory tract infection may render
humans more susceptible to the acute effects of nitrate aerosols. Nevertheless, the
concentration of nitrates used in this exposure study exceed maximum ambient levels by more
than 100-fold.
In addition to NaNO3 aerosols, ammonium nitrate (NH4NO3) exposure has been studied
by Kleinman and associates (1980). Twenty normal and 19 asthmatic subjects were exposed
to a nominal 200 jwg/m3 of 1.1 /*m NH4NO3 aerosol. The 2-h exposures included mild, -
intermittent exercise and were conducted under warm conditions (31 °C, 40% RH). There
were no significant physiologically meaningful effects of the NH4NO3 exposure in either
subject group.
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1 Stacy et al. (1983) also studied the effects of 80 jug/m3 of NH4NO3 in a group of
2 healthy male adults. As in the Kleinman et al. (1980) study, there were no changes in lung
3 function or symptoms.
4
5
6 15.8 CONCLUSIONS AND DISCUSSION
7 At the beginning of this chapter, a series of questions were posed concerning the
8 potential biological responses to NO2 exposure in humans. Some of these questions can be
9 answered in part using the data presented in this section, others will clearly require additional
10 research.
11 NO2 exposure at sufficiently high concentrations produces changes in lung function in
12 healthy subjects. A number of investigators have reported increased airway resistance after
13 exposure to NO2 concentrations exceeding 1 ppm (Beil and Ulmer, 1976; von Nieding et al.,
14 1979; von Nieding and Wagner, 1977; von Nieding et al., 1980). However, at
15 concentrations of NO2 between 2 and 4 ppm, some investigators have not observed any NO2-
16 induced changes in airway resistance or spirometry (Linn et al., 1985b; Mohsenin, 1987b;
17 Mohsenin, 1988; Sandstrom et al., 1990a). At NO2 exposure concentrations below 1.0 ppm,
18 there is little if any convincing evidence of change in lung volumes, flow-volume
19 characteristics of the lung, or airways resistance in healthy subjects. Nitrogen dioxide is
20 believed to have its primary effect on small airways. However, routine spirometry and
21 airway resistance measurements are not sensitive indicators of small airways function. Thus,
22 the absence of change in these physiological indicators of large airways function at low NO2
23 concentrations should not be viewed as evidence that NO2 has no effects on lung function.
24 Further developments will be necessary to permit sensitive, reproducible, noninvasive
25 evaluation of small airways, the primary site of NO2 deposition in the lung.
26 Symptoms associated with NO2 exposure in healthy subjects have been limited to
27 detection of the odor of NO2, in some cases at surprisingly low concentrations, less than
28 0.1 ppm (Bylin et al., 1985). Few of the studies examined in this review noted a significant
29 increase in respiratory symptoms. Sandstrom et al. (1990a) noted mild nasopharyngeal
30 irritation after exposure to 4 ppm for 20 min.
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1 Nitrogen dioxide exposure does result in increased airway responsiveness in normal
2 subjects exposed to concentrations in excess of 1.0 ppm. Mohsenin (1987b) and Frampton
3 et al. (1991) reported an increase in airway responsiveness after exposure to 2.0 and 1.5 ppm
4 respectively. Increased airway responsiveness may be associated with airway inflammation.
5 Repeated bouts of airway inflammation could promote deleterious long-term changes in the
6 lung such as loss of elasticity and acceleration of age-related changes in lung function.
7 However, the development of such responses is only speculative, given the present level of
8 scientific evidence.
9 Potentially sensitive subjects in the population include children, older adults, patients
10 with asthma or COPD, or individuals who may be unusually sensitive to NO2 for other
11 reasons. There are insufficient data on children, adolescents or older adults, either healthy or
12 with asthma, to determine their NO2 responsiveness relative to healthy young adults.
13 At the concentrations that may fall within the ambient range (e.g., < 1.0 ppm), the
14 effects of NO2 on lung function (i.e., spirometry, airway resistance) in asthmatics have
15 tended to be small. For example, Bauer et al. (1986a) observed a 4 to 6% decline in FEVj
16 in asthmatics exposed to 0.3 ppm NO2 for 30 min. Koenig et al. (1988) reported a 4%
17 decrease in FVC, but no significant change in other spirometry variables, after exposure of
18 adolescent asthmatics to 0.30 ppm NO2. On the other hand, several other investigators (Avol
19 et al., 1988; Bylin et al., 1985; Hazucha et al., 1982, 1983; Kleinman et al., 1983; Koenig
20 et al., 1985; Linn et al., 1985b, 1986; Mohsenin, 1987a; Roger et al,, 1990) have not found
21 any significant changes in spirometry or airway resistance of asthmatics exposed to
22 concentrations < 1.0 ppm. Again, spirometry and airway resistance are not sensitive
23 measures of small airways function, where NO2 is known to be primarily deposited.
24 A second important category of sensitive subjects includes patients with COPD who
25 have shown increased airway resistance after brief exposures to greater than 1.6 ppm NO2
26 (von Nieding et al., 1970, 1971, 1973a) (see Table 4.3-54). In addition, during a longer
27 (4-h) exposure, Morrow and Utell (1989) reported decreased (approx. 5%) FVC in COPD
28 patients exposed to 0.30 ppm. Other investigators (Linn et al., 1985a; Kerr et al., 1979) did
29 not find responses in COPD patients even with exposures to levels as high as 2.0 ppm. It
30 appears that brief acute exposure to relatively high concentrations of NO2 (> 2 ppm) will
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1 cause bronchoconstriction in some COPD patients and that these responses may also be
2 observed with longer exposures to lower concentrations.
3 An unresolved issue with the current data base is the existence of NO2-induced
4 pulmonary responses in asthmatics that have been reported at low but not at high
5 NO2 exposures. Although small functional responses have been observed in studies from
6 various laboratories, effects are not consistently present and demonstrating reproducibility of
7 responses has been difficult, even within the same laboratory. Furthermore, all responses to
8 NO2 that have been observed in asthmatics have occurred at concentrations between 0.2 and
9 0.5 ppm. Changes in lung function or airway reactivity have not been seen even at much
10 higher concentrations (i.e., up to 4 ppm). There is, at present, no plausible explanation for
11 this apparent lack of a concentration-response relationship. There is a possibility that a
12 portion of the variability in response to NO2 may be attributed to differences in the severity
13 of asthma. This is a complex issue and is discussed in Appendix A. In patients with chronic
14 obstructive lung disease, Bauer et al. (1987) and Morrow and Utell (1989) have observed
15 decreased lung function (FVC, FEVj) after exposure to 0.30 ppm for 4 h but Linn et al.
16 (1985a) and von Nieding and Wagner (1979) found no effects in COPD patients below 2.0
17 ppm for short duration exposures. It appears that further work will be necessary to provide
18 enough information to estimate the concentration-response relationships for NO2 exposure of
19 asthmatics and COPD patients, who appear to be the sensitive subpopulations.
20 Li several studies of asthmatics exposed to NO2,. airway responsiveness to a variety of
21 agents has been demonstrated. However, in many other studies using similar experimental
22 exposures, there was no significant change in airway responsiveness. In order to evaluate
23 this apparent dilemma, a meta-analysis was utilized; the approach is described in
24 Section 15.4. Without regard to the type of airway challenge, NO2 concentration, exposure
25 duration, or other variables, the overall trend was for airway responsiveness to increase (59%
26 of 354 subjects increased). This trend was somewhat more convincing for exposures
27 conducted under nonexercising conditions (69% of 154 subjects increased); indeed the excess
28 positive responses were almost entirely accounted for by exposures conducted under resting
29 conditions. The implications of this overall trend are unclear and will require further
30 investigations to verify if there is an interaction with exercise-induced changes in lung
31 function that may possibly obscure changes in airway responsiveness due to NO2 exposure.
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1 Increased airway responsiveness could potentially lead to temporary exacerbation of asthma
2 leading possibly to increased medication usage or even increased hospital admissions. The
3 lowest observed effect level for this response appears to be in the 0.2- to 0.3-ppm range.
4 Several recent studies have examined the possibility that NO2 could induce a pulmonary
5 , inflammatory response and/or alter immune system host defenses. These studies typically
6 , include collection of cells and airways fluids washing from the lung using BAL. In contrast
7 to O3 exposure, NO2 does not, at the concentrations studied, induce an increase in
8 neutrophils or eosinophils, the typical markers of inflammation following O3 exposure.
9 However, Sandstrom et al. (1990a) have observed an increase in mast cells and lymphocytes
10 in BAL fluid, which they attribute to an unspecific inflammatory response. Boushey et al.
11 (1988) have reported an increase in natural killer lymphocytes in BAL fluid.: Macrophage
12 numbers have not been increased by NO2 exposure nor did their ability to,kill virus appear to
13 have been altered by exposure, although Frampton et al. (1989a) suggested that, in some
14 subjects, macrophage responses may have been impaired. At present there is no evidence of
15 increased pulmonary epithelial permeability, although this possibility has not been examined
16 ; systematically. Mucociliary clearance was not altered after NO2 exposure in the one study in
17 which it was measured (Rehn et al., 1982), Nitrogen dioxide was found to cause a reduction
18 in alpha-1-antiprotease activity in one study (Mohsem'n and Gee, 1987) but not in another
19 (Johnson et al., 1990). Following NO2 exposure, Frampton et al. (1989b) found an increase
20 in alpha-2-macroglobulin, a molecule that has immunoregulatory as well as antiprotease
21 activity. Immunological responses to NO2 exposure are just beginning to be elucidated and
22 additional research will be required to determine whether these responses have any
23 implications for epidemiologically determined associations between NO2 exposure and
24, • increased respiratory tract infections. -
25 The effects of repeated NO2 exposure have been examined in two studies (Sandstrom
26 et al., 1990b; Boushey et al., 1988). Boushey et al. (1988) reported only a slight increase
27 (12%) in circulating lymphocytes and a possible increase in natural killer lymphocytes after
28 four 2-h exposures to 0.60 ppm. There were no detectable changes in inflammatory
29 mediators. Sandstrom et al. (1990b), on the other hand, found decreased numbers of mast
30 cells, macrophages, and lymphocytes in the BAL fluid. Despite the decreased numbers, the
31 phagocytic activity of alveolar macrophages was enhanced. These observations suggest that
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1 host defense responses are different after repeated exposure than after a single acute exposure.
2 More research appears to be necessary to confirm and expand these observations because of
3 the important potential connection between altered host defense responses and increased
4 respiratory infectivity.
5 In healthy adults, a variety of mixtures of other pollutants with NO2 have been
6 examined, primarily using spirometry and airway resistance measurements as end points.
7 In general, NO2 does not cause responses to other pollutants, such as O3, SO2, or particulate
8 matter, to be increased significantly. In other words, there is no more than an additive
9 response when NO2 is included in the pollutant mixture. However, further investigation of
10 N02 mixtures appears warranted using other biological markers, including measures of
11 epithelial permeability, clearance, airway responsiveness, airway inflammation, 'and measures
12 that are sensitive to changes in small airways function. In asthmatics, there is a tendency for
13 increased responsiveness to cold air, methacholine, carbachol, and histamine after NO2
14 exposure (see previous discussion). In one study, asthmatics were also more responsive to
15 SO2 after a previous exposure to NO2 (Torres and Magnussen, 1990). In addition to other
16 pollutants, NO2 exposure could potentially enhance (or inhibit) responses to other substances,
17 particularly airborne antigens. In two studies (Ahmed et al., 1983a; Orehek et al., 1981) the
18 response to grass pollen inhalation was examined in sensitive subjects after exposure to
19 0.1 ppm NO2 but no significant difference in the response after air and NO2 exposures was
20 observed. Given the increase in responsiveness to nonantigenic substances such as
21 methacholine, histamine, SO2, or cold air discussed previously, it may be worthwhile to
22 re-examine this hypothesis using higher NO2 concentrations or more prolonged exposures.
23 Responses to other NOX species have also been studied. Nitric oxide does not appear to
24 cause any lung function effects at low concentrations (< 1.0 ppm) either alone (Kagawa,
25 1982) or combined with NO2 (Kagawa, 1990). von Nieding et al., (1973b) reported
26 increased airways resistance in subjects exposed to excessively high concentrations
27 (>20 ppm). Responses to HNO3 vapor have been studied in adolescent asthmatics (Koenig
28 et al., 1989a,b). The results are suggestive of small changes in lung function but further
29 investigation is needed to confirm these apparent responses to HNO3 vapor. Nitrates (e.g.,
30 sodium nitrate) have not been found to cause any deleterious effects (Utell et al., 1979, 1980;
31 Kleinman et al., 1980; Stacy et al., 1983) at levels that might be expected in the atmosphere.
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31
Conclusions:
1. Nitrogen dioxide causes decrements in lung function, particularly increased airway
resistance in healthy subjects at concentrations exceeding 1.0 ppm.
2.
3.
4.
5.
Nitrogen dioxide exposure results in increased airway responsiveness in healthy subjects
exposed to concentrations exceeding 1.0 ppm for exposure durations of 1 h or longer.
Nitrogen dioxide exposure is associated with cellular inflammatory responses in the
airways that may include increased levels of mast cells and lymphocytes but not
neutrophils and eosinophils. Changes in some biochemical mediators of inflammation
or enzymes may be altered by NO2 exposure.
Nitrogen dioxide exposure of asthmatics causes in some subjects increased airway
responsiveness to a variety of provocative mediators, including cholinergic and
histaminergic chemicals, SO2, and cold air. However, the presence of these responses
appears to be influenced by the exposure protocol, particularly whether or not the
exposure includes exercise. However, NO2 concentration-response relationships are not
evident.
Modest decrements in spirometric measures of lung function (3 to 8%) may occur in
asthmatics and COPD patients exposed to NO2 concentrations (0.30 ppm).
Nitric acid exposure may cause some pulmonary function responses in asthmatics but
other commonly occurring nitrogen oxide species do not appear to cause any function
responses at concentrations expected, even at higher levels than in worst-case scenarios,
in the ambient environment.
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abstracts of the American Thoracic Society; May; Anaheim, CA. Am. Rev. Respir. Dis. 131(suppl.):
A171.
Stacy, R. W.; Seal, E., Jr.; House, D. E.; Green, J.; Roger, L. J.; Raggio, L. (1983) A survey of effects of
gasepus and aerosol pollutants on pulmonary function of normal males. Arch. Environ. Health 38:
104-115, .-,...-.-
Stearns, D. R.; McFadden, E. R., Jr.; Breslin, F. J.; Ingram, R. H., Jr. (1981) Reanalysis of the refractory
period in exertional .asthma. J. Appl. Physiol.: Respir. Environ. Exercise Physiol. 50: 503-508.
Suzuki, T.; Ishikawa, K. (1965) [Research on the effects of smog on the human body: report of the specialized
study on prevention of air pollution, no. 2]. Tokyo, Japan: Research Coordination Bureau of the Science
and Technology Agency, JG; pp. 199-221.
Toyama, T.; Tsunoda, T.; Nakaza, M.; Higashi, T.; Nakadate, T. (1981) [Airway response to short-term
inhalation of NO2, O3 and their mixture in healthy men]. Sangyo Igaku 23: 285-293.
U. S. Environmental Protection Agency. (1982a) Air quality criteria for oxides of nitrogen. Research Triangle
, Park, NG: Office of Health and Environmental Assessment, Environmental Criteria and Assessment
Office; EPA report no. EPA-600/8-82-026. Available from: NTIS, Springfield, VA; PB83-131011.
U. S. Environmental Protection Agency. (1982b) Review of the national ambient air quality standards for
nitrogen oxides: assessment of scientific and technical information; OAQPS staff paper. Research
Triangle Park, NC: Office of Air Quality Planning and Standards; EPA report no. EPA-450/5-82-002.
Available from: NTIS, Springfield, VA; PB83-132829.
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1 U. S. Environmental Protection Agency. (1986) Second addendum to air quality criteria for particulate matter and
2 sulfur oxides (1982): assessment of newly available health effects information. Research Triangle Park,
3 NC: Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office;
4 EPA report no. EPA-600/8-86-020F. Available from: NTIS, Springfield, VA; PB86-221249.
6 U. S. Environmental Protection Agency. (1989) An acid aerosols issue paper: health effects and aerometrics.
7 Research Triangle Park, NC: Office of Health and Environmental Assessment, Environmental Criteria
8 and Assessment Office; EPA report no. EPA-600/8-88-005F.
9
10 Utell, M. L; Swinburne, A. J.; Hyde, R. W.; Speers, D. M.; Gibb, F. R.; Morrow, P. E. (1979) Airway
H reactivity to nitrates in normal and mild asthmatic subjects. J. Appl. Physiol.: Respir. Environ. Exercise
12 Physiol. 46: 189-196.
13
14 Utell, M. J.; Aquilina, A. T.; Hall, W. J.; Speers, D. M.; Douglas, R. G., Jr.; Gibb, F. R.; Morrow, P, E.;
15 Hyde, R. W. (1980) Development of airway reactivity to nitrates in subjects with influenza. Am. Rev.
16 Respir. Dis. 121: 233-241.
17
18 von Nieding, G.; Wagner, H. M. (1977) Experimental studies on the short-term effect of air pollutants on
19 pulmonary function in man: two-hour exposure to NO2, O3 and SO2 alone and in combination. In:
20 Kasuga, S.; Suzuki, N.; Yamada, T.; Kimura, G.; Ihagaki, K.; Onoe, K., eds. Proceedings of the fourth
21 international clean air congress; May; Tokyo, Japan. Tokyo, Japan: Japanese Union of Air Pollution
22 Prevention Associations; pp. 5-8.
23
24 von Nieding, G.; Wagner, H. M. (1979) Effects of NO2 on chronic bronchitics. Environ. Health Perspect. 29:
25 137-142.
26
27 von Nieding, G.; Wagner, H. M.; Krekeler, H.; Smidt, U.; Muysers, K. (1970) Absorption of NO2 in low
28 concentrations in the respiratory tract and its acute effects on lung function and circulation. Presented at:
29 the second international clean'air congress; December; Washington, DC; paper no. MB-15G.
31 von Nieding, G.; Wagner, M.; Krekeler, H.; Smidt, U.; Muysers, K. (1971) Grenzwertbestimmung der akuten
32 NO2-Wirkung auf den respiratorischen Gasaustausch und die Atemwegswiderstaende des chronisch
33 lungenkranken Menschen (Minimum concentrations of NO2 causing acute effects on the respiratory gas
34 exchange and airway resistance in patients with chronic bronchitis]. Int. Arch. Arbeitsmed. 27: 338-348.
J*J
36 von Nieding, G.; Krekeler, H.; Fuchs, R.; Wagner, M.; Koppenhagen, K. (1973a) Studies of the acute effects of
37 NO2 on lung function: influence on diffusion, perfusion and ventilation in the lungs. Int. Arch.
38 Arbeitsmed. 31: 61-72.
39
40 von Nieding, G.; Wagner, H. M.; Krekeler, H. (1973b) Investigation of the acute effects of nitrogen monoxide
41 on lung function in man. In: Proceedings of the third international clean air congress; October;
42 Duesseldorf, Federal Republic of Germany. Duesseldorf, Federal Republic of Germany: Verein Deutscher
43 Ingenieure; pp. A14-A16.
44
45 von Nieding, G.; Wagner, M.; Loellgen, H.; Krekeler, H. (1977) Zur akuten Wirkung von Ozon auf die
46 Lungenfunktion des Menschen [The acute effect of ozone on the pulmonary function of man]. VDI Ber
47 (270): 123-129.
48
49 von Nieding, G.; Wagner, H. M.; Krekeler, H.; Loellgen, H.; Fries, W.; Beuthan, A. (1979) Controlled studies
50 of human exposure to single and combined action of NO2, O3, and SO2. Int. Arch. Occup. Environ.
51 Health 43: 195-210.
52
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1
2
3
4
5
von Nieding, G.; Wagner, H. M.; Casper, H.; Beuthan, A.; Smidt, U. (1980) Effect of experimental and
occupational exposure to NO2 in sensitive and normal subjects. In: Lee, S. D., ed. Nitrogen oxides and
their effects on health. Ann Arbor, MI: Ann Arbor Science Publishers, Inc.; pp. 315-331.
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APPENDIX ISA. SEVERITY OF ASTHMA
A major issue in the evaluation of human clinical studies involving asthmatics is the
variability in response between, and even within, laboratories. In the absence of significant
differences in exposure protocol or exposure dose, the explanation most often invoked to
explain differences in response is that the severity of disease and/or disease characteristics in
one subject group may have been different than the other. There are a large number of
physiological tests which may be used to characterize the severity of asthma, although no
single test appears to be definitive. There are also numerous clinical distinctions between the
various categories of asthma that are discussed below. The premise presented here suggests
that since asthma is a clinically defined disease, the factors used to characterize subjects
should be based on clinical and physiological information.
Asthma is a disease "characterized by increased responsiveness of the tracheobronchial
tree to a variety of stimuli" (American Thoracic Society, 1987; McFadden, 1988, 1991).
A characteristic feature of asthma is widespread narrowing of the airways that changes in
severity either spontaneously or with treatment. There is a broad range of severity, from
"mild and almost undetectable to severe and unremitting", and considerable heterogeneity of
clinical features that include, most commonly, wheezing, dyspnea, and cough. Fatal asthma
is also characterized by mucosal edema, inflammation of the airways, and mucus plugging of
the peripheral airways. Even mild asthma is associated with eosinophilic inflammation,
epithelial damage, degranulation of mast cells, and thickening of the subepithelial basement
membrane (Beasley et al., 1989; Laitinen et al., 1985; Wardlaw et al., 1988). Although
there have been numerous attempts to precisely define asthma, Bates (1990) suggests that
"endless attempts to refine linguistic definition are misplaced."
Prevalence: The prevalence of asthma in the U.S. adult population ranges from 2 to
4% (McWhorter et al., 1989); a point prevalence rate of 2.6% was estimated from the
National Health and Nutrition Examination Survey I (NHANES) survey. Based on data from
National Health and Nutrition Examination Survey II, Schwartz et al. (1990) reported a
prevalence rate for asthma in children less than 12 years of age at 4%; 3% among whites and
7.2% among blacks. Prevalence was higher among males, older children (age 8-11), and
urban residents.
15A-1
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Categorization: Scadding (1985) discussed extensively the categorization and degree of
severity of asthma. He defined two basic classes of asthmatics which he referred to as
extrinsic and cryptogenic. The term extrinsic, or allergic, implies that an external agent (such
as ragweed pollen) is responsible for the antigen-antibody reaction which triggers the cascade
of events responsible for airway narrowing. The term cryptogenic, or intrinsic, implies .there
is no known environmental or antigen-antibody reaction that has been identified to have
precipitated the disease. Scadding (1985) proposed further subdivision of these two basic
qualitative classifications into extrinsic atopic (the largest category), extrinsic nonatopic,
cryptogenic intrinsic, and cryptogenic unspecified. Diagnostic features of the various
categories of asthma suggested by Scadding (1985) are presented in Table 15A-1.
Classes of asthmatics:
a. Extrinsic
i. Atopic (IgE)
ii. Nonatopic (non-IgE)
b. Cryptogenic
i. Intrinsic
ii. Unspecified
Severity of Disease: Each qualitative class is then graded in severity (Table 15A-2)
according to the clinical course of the disease: mild (controlled by bronchodilators and
avoidance of precipitating factors, does not interfere with normal activities); moderate
(requires steroids, occasionally interferes with activities); and severe (history of life-
threatening episodes, seriously interferes with activities). The temporal course of the asthma
is also described (Table 15A-3) as episodic (episodes of asthma interspersed with symptom-
free periods) or persistent (persistent symptoms with periodic exacerbations).
There is a group of mild extrinsic atopic asthmatics (often participants in clinical
exposure studies) who rarely use medication; have infrequent episodes of mild bronchospasm
that usually do not require medical intervention or medication, although they may
occasionally use a bronchodilator; and have normal lung function. Perhaps these individuals
with near normal function should be classified as minimal asthmatics. There appears also to
be some difference of opinion as to what precise criteria are required before an individual is
classified as asthmatic. For example, many (about 40%) individuals with allergic rhinitis
15A-2
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August 1991
15A-3
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TABLE 15A-2. CLINICAL SEVERITY OF ASTHMA
Mild Controlled by bronchodilators and
avoidance of known precipitating
factors; does not interfere with
normal activities
Moderate Occasionally interferes with normal
activities; requires use of systemic
corticosteroids in treatment
Severe Seriously interferes with normal
activities; life-threatening episodes
(status asthmaticus)
TABLE 15A-3. TEMPORAL COURSE OF ASTHMA
Episodic Episodes of wheezy dyspnea with
symptom-free intervals; frequency
and severity of episodes may be
indicated
Persistent Persistent symptoms with episodic
exacerbations; severity both of
persistent symptoms and of episodes
may be indicated
Other forms of chronic bronchopulmonary disease may be present, notably bronchial
hypersecretion, persistent airways obstruction, and emphysema and may be partly
responsible for persistent symptoms; if so, additional diagnostic terms, as appropriate,
should be added
may experience exercise-induced bronchospasm (Voy, 1986). Furthermore, allergic subjects
may be more sensitive than normal subjects to SO2-induced bronchoconstriction (Koenig
et al., 1987). However, the nonspecific airway reactivity of these individuals may be within
the normal range (McDonnell et al., 1987). (Note, however, that McDonnell et al. [1987]
screened their subjects so that only subjects with allergic rhinitis were selected; none of the
subjects had exercise-induced bronchospasm.)
15A-4
-------
In general, the asthmatics who participate in human clinical studies come from the
group of asthmatics who would fall into the category of mild extrinsic atopic asthma with an
episodic time course. In most cases the disease is sufficiently mild or outside the normal
allergy season that the patient may go without medication altogether or can discontinue it for
brief periods.
Two clinical features which can easily be ascertained are the temporal nature of the
disease (i.e., frequency of episodes of bronchospasm) and the type, dosage and frequency of
medication use (i.e., frequency of use of inhaled or oral bronchodilators or steroids). These
could be documented by a diary and intermittent measurement of peak flow. In order to
differentiate between the minimal and mild severity group, several criteria could be used
including frequency of episodes (bronchospasm and/or medication) and normality of function
(FEVj/FVC ratio, SRaw, Peak Flow). An alternative solution may be to provide a detailed
clinical and physiological characterization of individual subjects and allow the reader to
judge.
From the standpoint of interpreting responses to a specific pollutant, it may be useful
to work with a more homogeneous group of asthmatics, defined as indicated above. Though
this might result in increased sensitivity to detection of adverse responses, it would, of
course, reduce the size of the population to which the findings could be extrapolated.
Nevertheless, more precise definition of study populations would facilitate comparisons
between different studies.
Certain basic anthropomorphic information is necessary to characterize any subject
population, minimally including height, weight, age, and gender. However, in the case of
asthmatics, other useful quantitative information can be valuable in comparing subjects in
various studies.
In addition to evaluation of baseline lung function and frequency of episodes (as
medication use, frequency of attacks, age at onset of disease, family history of atopy,
frequency of emergency treatment, hospitalization, or all of the above, possibly using a diary
and peak flow meter), the following information may be useful in evaluating studies of
asthmatics exposed to inhaled materials:
15A-5
-------
1. Nonspecific bronchial reactivity (methacholine or histamine)
2. Evaluation of reversibility of obstruction with beta agonist
3. General classes of medication and frequency of use
4. Levels of serum Immunoglobulin E (IgE)
5. Number of positive skin tests to regionally/seasonally common allergens
6. Known precipitating factors; seasonal variability
7. Response to standard exercise challenge
8. Duration of disease
Many of these factors and suggested categories to quantitate them are included in a
questionnaire and survey (Table 15A-4) developed by Howard Kehrl, M.D., of the Clinical
Research Branch, Health Effects Research Laboratory of the U.S. Environmental Protection
Agency. It is recognized that it may, at times, be difficult to persuade journal editors to
include an extensive list of subject (patient) characteristics; but that does not preclude
obtaining the information and making it available to interested parties or submitting the data
to a data repository.
Many of the more recently published studies have carefully evaluated the clinical and
physiological characteristics of asthmatics (and others) used as subjects. However, the
subjects have not been adequately characterized in some studies and the basis of the patient
classifications is unclear. Table 15-A-4 provides a format for collecting some of the
important clinical information. The absence of adequate subject characterization significantly
inhibits cross-study comparisons that are needed to evaluate differences between studies.
15A-6
-------
TABLE 15A-4.
ASTHMA SYMPTOMS
1. Spontaneous Wheezing or Chest Tightness or Shortness of Breath
a. never - none in last year
b. rare - less than once a month
infrequent - less than 5 times a month
c.
d. frequent - more than once a week but not every day
e. daily
f. nocturnal or early a.m.
2. Cough - frequency
a. never
b. with chest infections
usually only with wheezing or chest tightness
occasional, usually upon awakening
frequent, often nocturnal and interferes with sleep
daily, interferes with sleep and activities of everyday living
c.
d.
e.
f.
Cough - productive of sputum
a. never
b. only with chest infection
rare - 1 to 5 times per month
occasionally - 6 to 15 times per month
frequently or almost daily
c.
d.
e.
FACTOR PROVOKED ASTHMA
1. Exercise-induced Wheezing or Chest Tightness
a. all seasons with
1. mild exercise
2. moderate exercise
3. heavy exercise
b. only with cold air
1. mild exercise
2. modest exercise
3. rigorous exercise
c. abates with sustained exercise
yes no
15A-7
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TABLE 15A-4. (cont'd)
2. Avoidance of
a. aspirin - (i) rhinitis
(ii) facial flushing
(iii) wheezing
b. NSAID's
c. sulfites
d. pets
e. environmental tobacco smoke
f. other (foods, perfumes, odors, etc.)
3. Seasonal or Allergen Provoked Asthma
yes no
a. concommittant allergen-induced hay fever
yes no
b. percent component of symptoms due to allergen exposure
1. 100%
2. 50 to 100%
3. 20 to 49%
4. <20%
c. allergen exposure increases asthma activity
yes no
d. allergen exposure increases susceptibility to chest colds
yes no
4. Infection Induced Asthma Flare
a. colds/URI - nasal congestion or discharge, sore throat sinusitis
1. cause wheezing
2. frequency
a. almost never; less than once a year
b. infrequent; no more than twice a year
c. occasional; 3-6 times per year
d. frequent; more than 6 times a year
b. LRI - chest cold, bronchitis, pneumonia
1. usually preceded by URI
yes no
2. cause wheezing
yes no
3. frequency
a. none in last 5 years
b. almost never; less than once a year
c. infrequent; no more than twice a year
d. occasional; 3 to 6 times per year
e. frequent; more than 6 times a year
15A-8
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TABLE 15A-4. (cont'd)
MEDICATION
1. Steroid Burst and Taper within Past 3 Years (oral corticosteroids)
a. short, tapering course
b. chronic use
2. Theophyline Usage
a. daily
b. intermittent
3. Beta Agonist Inhaler
a. routine daily usage
b. usage more than 5 times per week
c. from 1 to 5 times per week
d. occasional usage
e. only for EIB (exercise-induced bronchoconstriction)
4. Inhaled Corticosteroids
a. intermittent use
b. chronic use
5. Other Medications (e.g., chromolyn sodium)
PHYSICIAN DIRECTED TREATMENT
1. Insured or Student Health
yes no
2. Hospitalization within Last 2 Years
3. Emergency Treatments (ER or doctor's office)
a. more than once a month
b. more than once a year but less than once a month
c. less than once a year
d. none in last 3 years
4. Routine physician contacts (doctor's office)
a. visits more than once a month
b. more than once a year but less than once a month
c. less than once a year
d. none in last 3 years
15A-9
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1
TABLE 15A-4. (cont'd)
IMMUNOLOGY PARAMETERS
1. Eosinophil Count (cells x 104/nl)
a. less than 200
b. 200-400
c. 401-600
d. 600-900
e. more than 900
f. Note: Allergy season? (Y/N) Recent steroid use? (Y/N)
2. Serum IgE (lU/ml)
a. less than 10
b. 10-100
c. 101-400
d. 401-800
e. more than 800
3. Skin Tests (number positive)
a. less than 3
b. 3-5
c. 6-10
d. more than 10
PULMONARY FUNCTION
1. Spirometry - FEV^FVC
a. more than 80%
b. 72-79%
c. 64-71%
d. 55-63%
e. less than 55%
-i.
Plethysmography - SRaw (cm H2O»L
Male Female
a. <4.0 <5.0
b. 4.0 to 7.5 5.0 to 8.0
c. 7.5 to 12.0 8.0 to 12.0
d. >12.0 >12.0
15A-10
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TABLE 15A-4. (cont'd)
AIRWAY RESPONSIVENESS
1. Airway Narrowing Triggered by (Note provocative dose, if known)
a. Methacholine
b. Histamine
c. Cold/Dry Air
d. Exercise
e. Sulfur Dioxide
2. Nonspecific Airway Reactivity
a. Normal range
b. < 10th percentile of normal range
c. 75th-100th percentile for asthmatic range
d. 25th-50th percentile for asthmatic range
e. < 25th percentile for asthmatic range
NSAID = Non-steroidal anti-inflammatory drugs.
URI = Upper respiratory infection.
LRI = Lower respiratory infection.
ISA-11
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REFERENCES
American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary
disease and asthma. Chapter 2. Asthma. Am. Rev. Respir. Dis. 136:228.
Bates, D. V. Workshop Summary. Chest 98(#5, Suppl): 251S, 1990.
Koenig, J. Q.; Marshall, S. G.; Horike, M.; Shapiro, G. G.; Furukawa, C. T.; Bierman, C. W.; Pierson,
W. E. (1987) The effects of albuterol on sulfur dioxide-induced bronchoconstriction in allergic
adolescents. J. Allergy Clin. Immunol. 79: 54-58.
Koenig, J. Q.; Morgan, M. S.; Horike, M.; Pierson, W. E. (1985) The effects of sulfur oxides on nasal and
lung function in adolescents with extrinsic asthma. J. Allergy Clin. Immunol. 76: 813-818.
McDonnell, W. F.; Horstman, D. H.; Abdul-Salaam, S.; Raggio, L. J.; Green, J. A. (1987) The respiratory
responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway
reactivity. Toxicol. Ind. Health 3: 507-517.
McFadden, E. R. Asthma: General features, pathogenesis and pathophysiology. Chap 79 in Fishman, A. P.
Pulmonary Diseases and Disorders, New York: McGraw-Hill, 19,88. p. 1295.
McFadden, E. R. Airway responsivity and chronic obstructive lung disease. Chap 10 in Cherniack, N.S.'
Chronic Obstructive Pulmonary Disease, Philadelphia: Saunders, 1991. pp. 90-96.
McWhorter, W. P.; Polis, M. A.; Kaslow, R. A. (1989) Occurrence, predictors, and consequences of adult
asthma in NHANESI and follow-up survey. Am. Rev. Respir. Dis. 139: 721-724.
Scadding, J. G. (1985) Definition and clinical categorization. In: Weiss, E. B.; Segal, M. S.; Stein, M., eds.
Bronchial asthma: mechanisms and therapeutics. 2nd ed. Boston, MA: Little, Brown and Company;
pp. 3-13. ,
Schwartz, J.; Gold, D.; Dockery, D. W.; Weiss, S. T.; Speizer, F. E. (1990) Predictors of asthma and
persistent wheeze in a national sample of children in the United States: association with social class,
perinatal events, and race. Am. Rev. Respir. Dis. 142: 555-562.
Voy, R. O. (1986) The U. S. Olympic committee experience with exercise-induced bronchospasm, 1984. Med.
Sci. Sports Exercise 18: 328-330.
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16. HEALTH EFFECTS ASSOCIATED
WITH EXPOSURE TO NITROGEN DIOXIDE
16.1 INTRODUCTION
This chapter concisely summarizes and integrates key information and conclusions from
preceding chapters into a coherent framework or perspective upon which to base
interpretations concerning human health risks posed by ambient or near-ambient levels of
NO2 in the United States. Toward this end, the chapter is organized into several sections,
each of which discusses one or more major components of an overall health risk evaluation:
(1) ambient and indoor NO2 levels and related exposure aspects; (2) qualitative and
quantitative characterization of key health effects of NO2 and their biological bases; and
(3) identification of population groups potentially at enhanced risk for health effects
associated with NO2 exposure.
16.2 AMBIENT AND INDOOR NITROGEN DIOXIDE LEVELS
In urban areas, hourly NO2 patterns at fixed-site, ambient air monitors often show a
bimodal pattern of morning and evening peaks, related to motor vehicular traffic patterns,
superimposed on a lower baseline level. Sites affected by large stationary sources of NO2
(or NO that rapidly converts to NO2) are often characterized by short episodes at relatively
high concentrations.
The highest hourly and annual ambient NO2 levels are reported from stations in
California. The seasonal patterns at California stations are usually quite marked and reach
their highest levels through the fall and winter months, whereas stations elsewhere in the
U.S. usually have less prominent seasonal patterns and may peak in the winter, in the
summer, or contain little discernable variation. One-hour NO2 values can exceed 0.2 ppm;
but, in 1988, only 16 stations (12 in California) reported an apparently credible second high
1-h value greater than 0.2 ppm. Since at least 98% of 1-h values at most stations are below
0.1 ppm, such values above 0.2 ppm are quite rare excursions.
August 1991
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1 Since 1980, the U.S. nationwide mean annual-average level among reporting NO2
2 stations has been consistently below 0.03 ppm, with no significant trend evident. For
3 103 Metropolitan Statistical Areas reporting a valid year's data for at least one station in 1988
4 and/or 1989, annual averages ranged from 0.007 to 0.061 ppm. The only recently measured
5 exceedances of the current annual standard, 0.053 ppm, have occurred at stations in southern
6 California.
7 Most people, however, spend a significant portion of their time indoors. This can result
8 in increased exposure, depending on the presence and use of indoor sources (e;g., gas stoves,
9 kerosene heaters, and unvented gas space heaters) or reduced exposure, depending on the
10 absence of such sources and on the tightness of home construction and the use of air
11 conditioning and other building features which affect the degree of penetration of outdoor
12 NO2 into buildings. Although the data base on peak hourly concentrations in homes With and
13 without indoor sources is much smaller than for 24-h and weekly averages, several studies
14 (Wade et al., 1975; Hollowell and Traynor, 1978; Hollowell et al., 1980) report peak hourly
15 NO2 values in gas stove kitchens in the range of 0.1 to 1.2 ppm. Modeling efforts suggest
16 that 1-h NO2 concentrations are commonly 0.15 ppm or greater during cooking periods in gas
17 stove homes (Sexton etal., 1983).
18 Several studies have examined the issue of human exposure to NO2 and the relationship
19 of indoor/outdoor air quality for occupants of homes with and without significant indoor
20 sources of NO2 (Quackenboss et al., 1986; Sexton et al., 1983; Colome et al., 1987; and
21 Leaderer et al., 1987). Quackenboss et al. (1986) found that in the winter in Portage, WI,
22 indoor weekly average NO2 concentrations were 3.2 times higher that outdoor NO2 levels in
23 gas stove homes, while indoor levels were 0.6 times outdoor NO2 levels in electric stove
24 homes during the same period. The fact that indoor NO2 levels in electric stove homes were
25 below measured outdoor levels may be due to chemical reactions of NO2 with indoor
26 surfaces. Given the large amount of time spent at home by most subjects, Quackenboss et al.
27 found relatively high correlations between measurements of indoor NO2 concentrations and
28 total personal exposure in gas stove homes (r = 0.85 summer and 0.87 winter) and to a
29 lesser extent in electric stove homes (r = 0.68 summer and 0.61 winter). Correlation
30 between outdoor NO2 levels and total personal exposure is less in the summer (r = 0.55 for
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
gas stove homes and r = 0.68 for electric stove homes) and much lower in the winter
(r = 0.20 and 0.28, respectively).
In contrast, Colome et al. (1987), in a study of over 600 randomly sampled residences
in southern, California, report that outdoor concentrations of NO2 .are found to be the single
most important determinant of average indoor levels of NO2 in southern California. Outdoor
NO2 levels account for between 15 to 40% of the variation in indoor concentrations in this
study. Based on the regression analysis of data from multiple homes, indoor/outdoor ratios
varied from 0.46 to 1.00, depending on the season of the year.
In most regions of the country, except southern California, total personal exposure to
elevated NO2 concentrations appears to be dominated by the existence of indoor sources of
NO2 (i.e., gas stoves, kerosene heaters, etc.). Total personal exposure for residents of
electric stove homes (approximately 50% of the U.S. population) is expected to be
significantly lower than levels observed at outdoor fixed monitoring stations (Sexton et al.,
1983).
16.3 KEY HEALTH EFFECTS OF NO2
This section concisely discusses below two key types of health effects that are of most
concern at ambient or near-ambient concentrations of NO2: (1) increases in airway
responsiveness in response to acute, short-term exposures of asthmatic individuals; and
(2) increased occurrence of respiratory illness among children associated with longer-term
exposures to NO2. A third category of NO2 effects, emphysema, is also noted below but
appears to be of major concern with exposures to much higher than ambient levels of NO2.
16.3.1 Airway Reactivity in Asthmatics and Short-Term (1-3 h) Exposure to
N03
. Subjects with asthma who as a group have airway hyperresponsiveness to a variety of
chemical and physical stimuli are considered one of the potentially most NO2-responsive
groups in the population. The physiological end point which, to date, appears to be the most
sensitive indicator of response to NO2 in asthmatics is a change in airway responsiveness or
reactivity. Airway inhalation challenge tests are used to evaluate the "responsiveness" of a
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1 subject's airways to inhaled materials. To test for the degree of airway responsiveness, a
2 pharmacologically active chemical (such as histamine, methachloine, or carbachol) that causes
3 constriction of the airways is used. Responses are usually measured by evaluating changes in
4 airway resistance or spirometry after each dose of the challenge is administered. Airway
5 hyperresponsiveness is an abnormal degree of airway narrowing, caused primarily by airway
6 smooth muscle shortening in response to nonspecific stimuli. An extensive discussion of such
7 responses is presented in Chapter 15.
8 Asthma is defined as a disease "characterized by increased responsiveness of the
9 tracheobronchial tree to a variety of stimuli" (American Thoracic Society, 1987; McFadden,
10 1988). A characteristic feature of asthma is widespread narrowing of the airways that
11 changes in severity either spontaneously or with treatment. There is a broad range of
12 severity, from "mild and almost undetectable to severe and unremitting," and considerable
13 heterogeneity of clinical features that most commonly include wheezing, dyspnea, and cough.
14 Even rnUd asthma is associated with eosinophilic inflammation, epithelial damage,
15 degranulation of mast cells, and thickening of the subepithelial basement membrane (Beasley
16 et al., 1989; LaMnen et al., 1985; Wardlaw et al., 1988). Asthmatics as a group are
17 significantly more responsive than healthy normal subjects to a variety of airway challenges.
18 The differences in airway responsiveness may span several orders of magnitude (at least
19 100 fold) between normal and asthmatic individuals (O'Connor et al., 1987). Despite the
20 absence of airway hyperresponsiveness in some asthmatics and the presence of airway
21 hyperresponsiveness in some non-asthmatics (Pattemore et al., 1990), there is a correlation
22 between increased asthma symptoms or increased medication usage and increased airways
23 responsiveness (Britton et al., 1988).
24 The prevalence of asthma in the U.S. adult population ranges from 2 to 4%
25 (McWhorter et al., 1989); a point prevalence rate of 2.6% was estimated from the
26 NHANES I survey. Based on data from the more recent NHANES II survey, Schwartz et al.
27 (1990) reported a prevalence rate for asthma in children less than 12 years of age at 4%; 3%
28 among whites and 7.2% among blacks. Prevalence was higher among males, older children
29 (age 8-11), and urban residents.
30 At concentrations below 1.0 ppm NO2, there is little (if any) convincing evidence of
31 lung function decrements or changes in airway responsiveness in healthy individuals. There
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1
2
3
4
5 -
6
7
8
9 .-
10
11
12
13
14
15 .
16
17.
18
19
20
21
22
23
24
25
26,
27
28
29
30
31
is some evidence that acute exposure to NO2 may cause an increase in airway responsiveness
in asthmatics. This response has been observed only at relatively low NO2 concentrations,
mostly within the range of 0.20 to 0.30 ppm NO2, the concentration range of concern within
the ambient environment. A meta-analysis of data on more than 300 asthmatics
experimentally exposed to NO2 indicates a slight excess increase of airway responsiveness
following NO2 exposure (see Chapter 15). In the concentration range between 0.20 and 0.30
ppm, the excess increase in airway responsiveness was attributable to subjects exposed to
NO2 ,at rest. The change in nonspecific (i.e., not to specific allergens) airway responsiveness
may reflect increased NO2-induced permeability of the airway epithelium leading to increased
access of the provocative agent to airway receptors, release of local mediators of
inflammation, or alterations in airway smooth muscle tone. Since NO2 does not appear to
cause airway inflammation at these levels and the increase in airway responsiveness appears
to be fully reversible, the implications of the observed increase in responsiveness are unclear.
Although it is conceivable that increased nonspecific airway responsiveness caused by NO2
could lead to increased responses to a specific antigen, there is presently no plausible
evidence to support this hypothesis. It is also possible that persistence of airway
hyperresponsiveness may be associated with ah accelerated rate of decline in pulmonary
function with age (O'Connor et al., 1987).
An unresolved issue with the current data base is the existence of NO2-induced
pulmonary responses in asthmatics that have been reported at low, but not at high, NO2
concentrations. Although small changes in spirometry or airway resistance have been
observed in studies from various laboratories, effects are not consistently present and
demonstrating reproducibility of responses has been difficult, even within the same
laboratory. Furthermore, most responses to NO2 that have been observed in asthmatics have
occurred at concentrations between 0.2 and 0.5 ppm. Changes in lung function or airway
responsiveness have not been seen even at much higher concentrations (i.e., up to 4 ppm).
There is, at present, no plausible explanation for this apparent lack of a concentration-
response relationship for both airway responsiveness and pulmonary function changes.
Controlled human exposure studies are limited to acute fully reversible functional and/or
symptomatic responses. This may in many cases limit the magnitude of expected responses
and hence the statistical significance of responses in studies with small numbers of subjects.
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1 Exposures seldom last longer than one to two weeks and rarely longer than 8 h/day. These
2 data, therefore, are primarily useful in evaluation of short-term NO2-induced. health, effects.
3 .,-.•,..',-•
4 16.3.2 Respiratory Morbidity in Children Associated with Exposure to NO2
5 The effects of NO2 on respiratory illness and the factors determining occurrence and
6 severity are important public health concerns because of the potential for exposure to NO2
7 and because childhood respiratory illness is common (Samet et al., 1983; Samet and Utell,
8 1990). This takes on added importance since recurrent childhood respiratory illness may be a
9 risk factor for later susceptibility to lung damage (Glezen, 1989; Samet et al., 1983; Gold
10 etal., 1989).
11 The discussion of epidemiological findings in Chapter 14 indicates that the combined
12 evidence is supportive for the effects of exposure to NO2 on respiratory disease in children
13 under 12 years of age. The studies were evaluated for several key factors, including:
14 (1) measurement error in exposure, (2) misclassification of the health outcome, (3) selection
15 bias, (4) adjustment for covariates, (5) publication bias, (6) internal consistency, and
16 (7) plausibility of the effect based on other evidence. The health outcome should be an
17 outcome for which there is good reason to suspect that NO2 exposure has an effect. The
18 health outcome measure considered was lower respiratory illness, which is typically attributed
19 to infectious disease, probably of viral origin. Symptoms evaluated commonly consisted of
20 cough, wheeze, colds going to chest, chronic phlegm and bronchitis. Each study was
21 reviewed with special attention given to the factors just discussed. Those studies which most
22 appropriately address these factors provide stronger bases for conclusions to be drawn.
23 Consistency between studies indicates the level of the strength of the total data base.
24 The epidemiological studies generally provide some evidence that repeated NO2
25 exposure increases respiratory illness in children, although many reported non-statistically
26 significant results. Melia et al. (1977) first reported on a survey of children in randomly
27 selected areas of England and Scotland, using the presence of a gas stove as a measure of
28 NO2 exposure. An EPA reanalysis of that data yields an estimated odds ratio of 1.31 for the
29 presence of symptoms of respiratory illness. The cross-sectional study of Melia et al. (1979)
30 also found that the presence of a gas stove was associated with increased risk of respiratory
31 disease. The odds ratio was 1.24 with 95% confidence limits of 1.09 to 1.42. Melia et al.
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1 '--• (1980) described the results of a third study of respiratory symptoms in children aged six to
2 seven in northern England. Multiple logistic regression analysis of the data presented by
3 Melia et al. (1980) showed a significant increase in symptoms as a function of bedroom NO2
4 levels. Melia et al. (1982), reporting on a fourth study of children in England, found that a
5 multiple logistic regression analysis of these data was not statistically significant, although the
6 . symptoms were positively related to NO2 exposure. However, an EPA reanalysis of the
7 Melia et al. (1982) results suggest that an increase of 30 /xg/m3 (0.016 ppm) in bedroom NO2
8 levels yields an 11 % increase in the odds of respiratory illness. In a final Melia et al. (1983)
9 study, infants under 1 year of age were examined, but no relationship was found between
10 type of fuel used for cooking and the prevalence of respiratory symptoms.
11 An analysis of the Six City studies reported by Ware et al. (1984) estimated an
12 unadjusted odds ratio of 1.08 (95% confidence limits of 0.97 to 1.19) for an index of lower
13 respiratory illness associated with gas stove use. Other indicators such as bronchitis, cough,
14 and wheeze did not show any increased incidence. Neas et al. (1990, 1991) analyzed a
15 different cohort enrolled later in the Six City studies, used a different symptom questionnaire,
16 and made indoor NO2 measurements for all subjects. They found evidence for increased
17 respiratory disease, with an estimated odds ratio of 1.47 (95% confidence limits of 1.17 to
18 1,86) at an exposure of 31 jug/m3 (0.016 ppm).
19 Ogston et al. (1985) studied respiratory disease in 1-year-olds in the Tayside region of
20 northern Scotland. The presence of a gas stove yielded an odds ratio of 1.14, with 95%
21 confidence limits of 0.86 to 1.50. Ekwo et al. (1983) studied respiratory symptoms in
22 relation to gas stove use in Iowa City, I A. Gas stove use provided an odds ratio of 2.4 for
23 hospitalization for chest illness before age 2, and 1.1 for chest congestion and phlegm with
24 colds. Dijkstra et al. (1990) studied the effects of indoor factors on respiratory health of
25 children in The Netherlands. A logistic regression analysis yielded an odds ratio of 0.94 with
26 95%, confidence limits of 0.66 to 1.33, thus showing no evidence of an increase in
27 respiratory disease with increasing NO2 exposure. Keller et al. (1979) also did not find any
28 , statistically significant changes in respiratory disease associated with gas stove use, but the
29 unadjusted estimated odds ratio for lower respiratory illness was 1.10, with 95% confidence
30 limits of 0.74 to 1.54.
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1 Many of the above studies suggest an increase in respiratory symptoms in children from
2 exposure to levels of NO2 occurring in homes with gas stoves as compared to homes with
3 electric stoves, but the reported associations in the majority of the studies did not reach
4 statistical significance. The overall consistency of these studies was examined and the
5 evidence synthesized in a quantitative meta-analysis carried out be EPA (Hasselblad and
6 Kotchmar, submitted).
7 The studies used in the EPA meta-analysis employed different health end point
8 indicators. In order to compare these studies, a standard end point was defined, and then
9 each study was compared with this standard end point. For purposes of discussion, the end
10 point chosen was the presence of lower respiratory illness in children aged 12 or under. It
11 was assumed that the relative odds of developing lower respiratory illness is similar across
12 this age range as a function of NO2 exposure, even though the actual rates may not be
13 (a common assumption in many analyses). The goal was to estimate the odds ratio
14 corresponding to an increase of 30 jug/m3 (0.016 ppm) in NO2 exposure. This is
15 approximately the increase seen as a result of gas stove use as compared with electric stove
16 use in both the United States and England.
17 An attempt was made to include as many studies as possible. The criteria for inclusion
18 were: (1) the health end point measured must be reasonably close to the standard end point;
19 (2) exposure differences must exist and some estimate of exposure must be available; and
20 (3) an odds ratio for a specified exposure must have been calculated, or data presented so that
21 it can be calculated.
22 Graphs of the odds ratio from each study are presented in Figure 16-1. Each curve can
23 be given one of three interpretations: (1) the normal approximation to the likelihood of the
24 logarithm of the odds ratio; (2) a distribution such that the 0.025 percentile and the
25 0.975 percentile points of the distribution are the 95% confidence limits of the estimated odds
26 ratio; and (3) the posterior for the odds ratio for a particular study given a flat prior on the
27 log-odds ratio.
28 Two methods of combining evidence were employed in the EPA meta-analysis, one
29 being the Bayesian method described by Eddy (1989) and Eddy et al. (1990a,b). The result
30 of the analysis is a distribution for estimates of the location of the true value of the odds
31 ratio. This can be done separately for each study or for the combination of all studies, and
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li
s-1
§.4
COMBINED (fixed)
COMBINED (random)
Mefiaetal. (1979)
Meaaetal.fl977)
Ware etal. (1984)
EkwoetaI.(19S3)
Keller etal. (1979)
Ogsstonetal. (19S5)
Mela etal. (1982)
D)jkstraetal.(1990)
Uellaetal.(1983)
Mala et si. (1960)
Odds Radio
Figure 16-1. U.S. Environmental Protection Agency meta-analysis of epidemiologic
studies of NO2 exposure effects on respiratory disease in children
<12 years old. Each curve can be treated as a likelihood function or
posterior probability distribution. K treated as a likelihood function, the
95% confidence limits for the odds ratio can be calculated as those two
points on the horizontal axis for which 95% of the area under the curve is
contained between the two points. If treated as a posterior probability
distribution, then the area under the curve between any two points is the
probability that the odds ratio lies between those two points.
1 the results are shown in Figure 16-1. The second basic model assumed that the parameter of
2 interest is not fixed, but is itself a random variable from a distribution. Such models are
3 designated by several names including random effects models or hierarchical models. The
4 purpose of a random effects model is to relax the assumption that each study is estimating
5 exactly the same parameter. DerSimonian and Laird (1986) discuss the random effects
6 model. The results from using the different models were basically the same, namely that the
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1 odds ratio is estimated to be about 1.2 with 95% confidence limits ranging from about 1.1 to
2 1.3. The studies in which NO2 was actually measured gave an estimated odds ratio of 1.27,
3 whereas the others yielded an estimate of 1.18 (which is consistent with a measurement error
4 effect).
5 The individual evidence for an effect of NO2 on respiratory disease is somewhat mixed.
6 All but one of the studies used in the synthesis showed increased respiratory disease rates
7 associated with increased exposure. A few of the individual studies were statistically
8 significant. Combining the eleven studies giving quantitative estimates of effects tend to
9 show increases of respiratory illness in children associated with exposure to NO2. The EPA
10 meta-analysis indicates that, when combined, the studies collectively provide evidence for an
11 increase of 30 /*g/m3 (0.016 ppm) in NO2 exposure being associated with an increase of
12 about 20% in the odds of respiratory illness, subject to the assumptions made for the
13 synthesis. Although several assumptions were made to combine the studies, the consistency
14 between the individual studies is demonstrated, indicating greater collective strength in the
15 data base and suggesting that the effect is real.
16 The exposure estimates used in these studies are either a surrogate (gas vs. electric) or a
17 2-week integrated NO2 average measured by Palmes tubes. The effects studied may be
18 related to peak exposures, average exposures, or a combination of the two. To the extent
19 that the observed health effects depend on peak exposures rather than average exposures, the
20 above exposure estimates introduce measurement error. These studies can not distinguish
21 between the relative contributions of short-term peak exposures and longer-term average
22 exposures to the observed health effects. However, the estimated effect is almost surely an
23 underestimate, given the problems of misclassification of exposures and outcomes. The effect
24 was not dependent on any one or two studies. The results of this analysis are not sensitive to
25 the inclusion (or exclusion) of any one study. In fact, any two studies can be eliminated, and
26 the 95% confidence limits will exclude the no effect odds ratio of 1.0. Thus, the combined
27 evidence is supportive for the effects of exposure to NO2 on respiratory disease in children
28 under 12 years of age.
29 Several of the epidemiology studies in the quantitative analysis in Chapter 14 used a
30 single 2-week NO2 average or used two 2-week NO2 averages to characterize chronic
31 exposure. The representativeness of such estimates of chronic exposure (e.g., 1 year) is a
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1 consideration in generalizing the results of these studies to the long-term ambient situation.
2 To roughly estimate the possible divergence from an actual annual ambient mean resulting
3 from selecting one or two 2-week averages, data from the U.S. Environmental Protection
4 Agency's Aerometric Information and Retrieval System data bank (AIRS, 1991) for ten
5 stations, selected from among those having fairly complete records for 1988 or 1989 (see
6 Chapter 7), have been analyzed for the variability in their 2-week averages (Table 16-1).
7 These stations represent various regions of the United States but emphasize California where
8 high levels most frequently occur. For each station, 2-week averages were calculated week
9 by week; these were then ranked and the 10th and 90th percentiles determined. These two
10 percentiles were then divided by the station's annual mean to provide a common frame of
11 reference. For example, the 10th and 90th percentile fractions for a single 2-week average
12 for Los Angeles in 1988 were 0.77 and 1.27 times the annual mean, respectively. This
13 would indicate that 80% of the 2-week averages were between 77 and 127% of the annual
14 average of 0.061 ppm ( 0.047 to 0.078 ppm respectively). In a similar manner, percentiles
15 were calculated from two 2-week averages, using the means of 2-week averages that were
16 26 weeks apart, thus providing data for two opposite seasons such as winter and summer.
17 The 26 possible averages were ranked as before. Since these averages represent more weeks
18 of data taken at two different times, it is expected that they would come closer to the true
19 annual average; this is generally the case.
20 The results suggest that most (80%) of the single 2-week averages are within 80 and
21 125% of the mean, except for possibly cities with very low means such as Dallas. The two
22 2-week averages produce a better estimate, with most lying between 85 and 120% of the
23 mean. The reader is cautioned that these numbers and analysis may not be representative of
24 actual exposure situations. These selected data and analyses are offered only to describe
25 potential relationships between ambient NO2 annual averages and 2-week data periods.
26 The plausibility of respiratory illness in children being increased by NO2 exposure (as
27 demonstrated by the epidemiologic studies and EPA meta-analysis discussed above) is
28 supported by findings from numerous animal studies evaluating NO2 impacts on host defense
29 mechanisms. Key findings from such studies are summarized next.
30
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TABLE 16-1. U.S. ENVIRONMENTAL PROTECTION AGENCY ANALYSIS
OF VARIABILITY IN 2-WEEK AMBIENT AVERAGES OF 1-H NO2
DATA AT TEN SELECTED LOCATIONS
Fraction of Annual Average
Two 2-week
City
Los Angeles, CA
Azusa, CA
Upland, CA
Anaheim, CA
New York, NY
Chicago, IL
Cincinnati, OH
Worchester, MA
Miami, FL
Dallas, TX
Year
1988
1989
1988
1988
1988
1989
1989
1988
1989
1989
Annual
Average
(ppm)
0.061
0.051
0.047
0.046
0.041
0.034
0.030
0.029
0.018
0.011
2-week Average
10th
Percentile
0.77
0.81
0.79
0.71
0.84
0.86
0.84
0.81
0.77
0.45
90th
1.27 •
1.27
1.38
1.23
1.19
1.18
1.23
1.19
1.26
1.46
10th
0.87
0.83
0.87
0.86
0.91
0.93
0.88
0.83
0.90
0.75
Average
90th
Percentile
1.20
1.17
1.22
1.10
1.16
1.10
1.11
1.23
1.18
1.31
1 16.3.3 Biological Bases Relating NO2 Exposure to Respiratory Morbidity:
2 Effects of NO2 on the Respiratory Host Defense System
3 The lung is one of the common sites of attack of microorganisms. While many types of
4 microorganisms are implicated in respiratory infection, viruses represent a major cause,
5 particularly for infants and children. In a viral respiratory infection, viral replication and
6 altered immune responses to viral infections produce signs and symptoms of respiratory
7 illness (Douglas, 1986). The respiratory system has several defense mechanisms against
8 inhaled infectious and chemical agents. Host defense mechanisms comprise a complex,
9 cooperative response system of several cell types, cell products, tissues, and organs in, the
10 body. Two major approaches have been used to demonstrate the effects of NO2 on host
11 defenses: (1) evaluation of effects on selected mechanisms of host defenses; and (2) use of
12 infectivity models, which reflect the overall functioning of all host defense mechanisms
13 against the infectious agent used. These two approaches are discussed below.
14 Nitrogen dioxide exposure can impair one or more components of this important defense
15 system, resulting in the host being more susceptible to respiratory infection. Epidemiological
16 studies have reported an association between an increase in symptoms of respiratory disease
17 of infectious origin and NO2 exposure (Chapter 14). Animal studies provide important
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1 evidence indicating that several defense systems are a target organ for inhaled NO2. Nitrogen
2 dioxide affects all of the host defenses studied (e.g., mucociliary clearance, alveolar
3 macrophages, and the humoral and cell-mediated immune system.) The biological basis
4 relating NO2 exposure to respiratory symptoms and infection shown in epidemiological
5 studies (Chapter 14) are presented in extensive discussions in Chapter 13 (animal toxicology).
6 Studies on the effects of NO2 exposure on mucociliary transport in the conducting
7 airways show a reduction in the number and activity of the cilia, morphological changes in
8 the cilia, and decreased mucociliary velocity at concentrations as low as 0.5 ppm for 7 mo of
9 exposure (Yamamoto and Takahashi, 1984). Others have observed similar effects at higher
10 levels for shorter exposure durations. Several short-term (days to weeks) studies with
11 concentrations at or above 2 ppm demonstrated structural changes in cilia and ciliated cells,
12 decreases in numbers of ciliated cells, and decreases in ciliary beating. As a foreign agent
13 deposits below the mucociliary region, in the gaseous exchange region of the lung, host
14 defenses are provided by the alveolar macrophage which acts to remove or kill viable
15 particles, to remove nonviable particles, and to process and present antigens to lymphocytes
16 for antibody production. Exposure to NO2 has produced a variety of effects on alveolar
17 macrophages in several animal species after several weeks of exposure to levels as low as
18 0.3 ppm; however, most effects were observed at higher levels. These effects included
19 decreased phagocytosis and bactericidal activity, altered metabolism, increases in numbers of
20 macrophages and morphological changes (Rombout et al., 1986; Aranyi et al., 1976;
21 Goldstein et al., 1974; Suzuki et al., 1986; Chang et al., 1986; Suzuki et al., 1986;
22 Schlesinger et al., 1987; Mochitate et al., 1986). Decreases in the ability of alveolar
23 macrophages to engulf foreign particles (phagocytosis) and bactericidal activity are likely
24 highly related to increased susceptibility to pulmonary infections. Controlled human exposure
25 studies have also examined macrophage function and show that these cells, when exposed to
26 NO2, tended to inactivate influenza virus in vitro less effectively than cells collected after air
27 exposure (Frampton etal., 1989a).
28 An example of the alteration of host defenses against tumor cells following exposure to
29 NO0 is seen in studies examining the colonization of the lung by B16 melanoma tumor cells.
Zj
30 Richters and Kuraitis (1981, 1983) and Richters et al. (1985) reported that when mice were
31 exposed to 0.4 or 0.8 ppm NO2 for 10-12 weeks and then injected with transplantable tumor
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1 cells, colonization of these cells increased in the lung, indicating decreased resistance to such
2 challenge. Questions have been raised regarding the appropriateness of the statistical analysis
3 used in evaluating these data and the interpretation of the model used. Although the authors
4 attribute effects to increased metastases, an alternative interpretation is an NO2-induced
5 change in lung permeability to cells. Another study reported that NO2 inhibits formation of
6 B16F10 tumors in the lung (Weinbaum etal., 1987).
7 The humoral and cell-mediated immune systems together are essential for antibody
8 production and the secretion of cellular products that are lethal to certain invading organisms
9 and also regulate the normal host's defense response. There is some indication that exposure
10 to NO2 suppresses some of these specific immune responses and that the effect is both
11 concentration- and time-dependent. For example, a significant suppression of antibody
12 production by spleen cells has been reported in experimental animals exposed for 1 week to
13 1 mo to NO2 concentrations as low as 0.4 - 0.5 ppm (Lefkowitz et al., 1986; Fujimaki et al.,
14 1982). Subchronic exposure to NO2 also resulted in decreased numbers of circulating
15 T lymphocytes, T-helper/inducer lymphocytes, and T-cytotoxic/suppressor lymphocytes in
16 mice (Damji and Richters, 1989). The cause of this suppression is not clear.
17 Animal infectivity studies present key data relating exposure to NO2 and effects on the
18 overall functioning of host defense mechanisms. In these studies, animals were exposed to
19 varying concentrations and durations of NO2 followed by exposure to an aerosol of an
20 infectious agent. Microbial-induced mortality was used as the end point. Exposure to NO2
21 increased both bacterial- and influenza-induced mortality after subchronic exposures to levels
22 as low as 0.5 - 1.0 ppm NO2 (Ehrlich and Henry, 1968; Ito, 1971; Ehrlich et al., 1977).
23 After acute (2 h) exposure, 2.0 ppm NO2 is the lowest effective concentration measured
24 (Ehrlich et al., 1977). Nitrogen dioxide increases microbial-induced mortality by impairing
25 the host's ability to defend the respiratory tract from infectious agents, thereby increasing
26 susceptibility to viral, mycoplasma, and bacterial infections (Ehrlich and Henry, 1968; Ito,
27 1971; Ehrlich et al., 1977; Parker et al., 1989; Gardner et al., 1977a,b, 1979, 1980, 1982;
28 Graham et al., 1987; Jakab, 1987; Motomiya et al., 1973; Miller et al., 1987). Using an
29 animal model designed to evaluate the effects of NO2 on non-fatal respiratory infection, NO2
30 decreased the intrapulmonary bactericidal activity in mice in a concentration-related manner,
31 without a decrease in the number of alveolar macrophages (Goldstein et al., 1973). Exposure
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1 to NO2 was found to increase the severity of mycoplasma-induced lesions within the lung,
2 but did not increase the susceptibility of the mice to the infection (Parker et al., 1989).
3 Animal studies have also shown that influenza infection is exacerbated with NO2 exposure
4 (Ito, 1971). In studies with cytomegalovirus and paramyxovirus (Jacob, 1987; Rose et al.,
5 1988), the pathogenesis of these infections are enhanced.
6 The toxicology literature also provides evidence that the host's response to inhaled NO2
7 can be significantly influenced by the exposure duration, concentration, and temporal pattern
8 of exposure. The relationship of concentration (C) times duration (T, time) to susceptibility
9 to respiratory infections indicates that when the product of C XT is held constant and the
10 individual C's and T's are varied, a difference in response occurs. The incidence of
11 mortality was significantly more influenced by the concentration of NO2 than by the duration
12 of the exposure (Gardner et al., 1977a,b). The exposure pattern of NO2 is also important
13 when comparing and determining the effects of continuous versus intermittent exposure.
14 When such data were adjusted for differences in C XT, the incidence of respiratory infection
15 was essentially the same for both groups (Gardner et al., 1979). When animal studies were
16 designed to mimic a typical urban outdoor exposure environment having periodic spikes of
17 NO2 superimposed on a lower continuous background level of NO2, the evidence indicates
18 that the animals exposed to the baseline plus short-term spikes were significantly more
19 susceptible to a laboratory-induced infection than either the control or the background-NO2-
20 exposed mice (Miller et al., 1987; Gardner et al., 1982; Graham et al., 1987). It should be
21 noted that the exposure patterns tested in animals are likely to be different from indoor NO2
22 exposure patters. This body of work for host defenses in mice shows that an average
23 exposure value (CxT) is not an exact index or predictor of effects; rather, actual patterns of
24 exposure represent the causative exposure.
25 It is of interest that morphological studies have also indicated that the NO2
26 concentration played a more important role in inducing lung lesions than did exposure
27 duration when the product of CXT was constant. The measured effect of concentration was
28 greater with intermittent exposure than with continuous (Chapter 13).
29 Recent controlled human exposure studies examining the effects of NO2 on pulmonary
30 host defense systems report a trend (not statistically significant) toward an elevated rate of
31 infection to a laboratory-induced live attenuated influenza, A/Korea/reassortment virus
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1 (Goings et al., 1989). Frampton et al. (1989a) report a trend (p<0.07) for less effective
2 inactivation of virus by macrophages obtained from subjects exposed continuously to
3 0.60 ppm NO2, but no effects of virus inactivation were seen in subjects exposed to 2.0 ppm
4 spikes. Exposure to NO2 may transiently increase levels of antiprotease alpha-2-
5 macroglobulin (a2M) in lavaged fluids isolated from the respiratory system' through local
6 release. While serving as an indicator of changes in protease-antiprotease balance, alterations
7 in a2M in alveoli may have significance for local immunoregulation and may alter alveolar
8 macrophage defenses against infection (Frampton et al., 1989b). These findings suggest, but
9 do not prove, that NO2 may play a role in increasing the susceptibility of adults to respiratory
10 virus infections.
11 The strength of the animal lexicological, human clinical, and epidemiological studies on
12 host defenses provides the rationale and plausible biological basis to explain the relationship
13 seen in population studies showing increased frequency and severity of respiratory symptoms
14 and/or infections in humans exposed to NO2. The human body must be able to defend itself
15 against a wide variety of inhaled foreign substances. When these defenses are overcome,
16 serious consequences can occur. The significance of the observations from relevant animal
17 models is clear. With minor variations, the mammalian species, including humans, share in
18 common an array of defensive mechanisms that are anatomically, functionally, and
19 physiologically integrated in the respiratory tract to prevent and control infectious disease.
20 All information available to date would indicate that qualitative extrapolation of data observed
21 in animals to humans is valid. The accumulated evidence that NO2 causes dysfunction in
22 several defenses provides the plausible biological mechanism necessary to link NO2 exposure
23 to increased morbidity and respiratory symptomatology in children indicative of respiratory
24 infection.
25 -...-...,
26 16.3.4 Emphysema and Exposure to NO2 -
27 Studies in several species of animals have shown that chronic exposure to high levels of
28 NO2 (relative to ambient) can cause emphysema. Since emphysema is an irreversible disease,
29 representing important public health concerns, whether NO2 creates a risk for this disease in
30 humans is a major question. Although this question cannot be definitely answered yet, the
31 potential for risk requires discussion. The definition of emphysema as used in the United
August 1991 16.16 DRAFT-DO NOT QUOTE OR CITE
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1 States is an anatomic one best characterized by National Institutes of Health (NIH) (1985)
2 criteria. These criteria are: "An animal model of emphysema is defined as an abnormal state
3 of the lungs in which there is enlargement of the airspace distal to the terminal bronchiole.
4 Airspace enlargement should be determined qualitatively in appropriate specimens and
5 quantitatively by stereologic methods." An additional essential criterion for human
6 emphysema is the destruction of alveolar walls.
7 Several studies (Haydon et al., 1967; Freeman et al.-, 1977; Port et al., 1977) relate
8 long-term (1 to over 30 months) exposure of rats and rabbits to high concentrations of
9 . NO2 (> 8 ppm, much greater than ambient levels) with morphologic lung lesions which
10 meet the 1985 NIH workshop criteria for a human model of emphysema (i.e., alveolar wall
11 destruction occurred in addition to other characteristic changes), One study (Hyde et al.,
12 1978) reported on dogs exposed to a mixture of 0.64 ppm NO2 and 0.25 ppm NO for
13 68 months. Upon examination 32 to 36 months after exposure ceased, the dogs had
14 morphologic lesions that meet the 1985 NIH workshop criteria for human emphysema. In the
15 same dogs, pulmonary function was also measured. Pulmonary function decrements observed
16 at the end of exposure progressed post-exposure. This suggests that the morphological effects
17 may also have been progressive. Another group of dogs in the same study was exposed to a
18 mixture of "low" NO2 (0.14 ppm) and "high" NO (1.1 ppm), but emphysema was not
19 observed. Since the study did not include an NO2-only group, it is not possible to discern
20 , the effects of NO2 in the mixture. However, the presence of emphysema in the "high"
21 NO2-"low" NO group and its absence in the "low" NO2 - "high" NO group implies that NO2
22 was a significant etiologic factor.
23 Emphysema was reportedly observed in numerous other NO2 studies with several
24 species of animals, but either the reports lacked sufficient detail for independent conclusions
25 or only the criteria for animal (not human) emphysema were met. Several other studies
26 discussed in Chapter 13 were negative for emphysema. Various factors such as the exposure
27 protocol may also play a role in the outcome of studies. Potential differences may relate to
28 age of the animals during exposure, concentration and duration of exposure, and the duration
29 after exposure ceases before the animals are evaluated for emphysematous pathology.
30 In spite of the fact that there is a fairly extensive toxicologic data base concerning
31 morphologic effects of NO2, it is still not possible to establish a reasonably accurate
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1 "no-observed-effect" level for emphysema. This is likely due to a combination of factors:
2 the complexity of changes occurring with NO2 exposure, the lack of published papers
3 utilizing highly sensitive morphometric techniques, interspecies difference in response, and
4 inadequate description of methods and findings in some published reports. Qualitatively, it is
5 clear that NO2 can cause emphysema in animals. While the lowest NO2 concentration for the
6 shortest exposure duration that will result in emphysematous lung lesions pan not be reliably
7 determined from the published studies, the exposures that did cause emphysema, according to
8 the NIH criteria, are far higher than those currently reported in ambient air. .
9 '••;.,
10 16.3.5 Subpopulations Potentially Susceptible to NO2 Exposure
11 Certain groups within the population may be more susceptible to the effects of NO2
12 exposure, including persons with preexisting respiratory disease, children, -and the elderly.
13 The reasons for paying special attention.to these groups is that they may be.affected by lower
14 levels of NO2 than other subpopulations or the impact of a given response may be greater.
15 Some causes of heightened susceptibility are better understood than others. Subpopulations
16 that already have reduced lung functions and reserves (e.g., the elderly, asthmatics,
17 emphysemics, chronic bronchitics) will be more impacted than other groups by decrements in
18 pulmonary function. For example, a young healthy person may not even nqtice a small
19 percentage change in pulmonary function, but a person whose activities are already limited by
20 reduced lung function may not have the reserve to compensate for the same percentage
21 change.
22 The airways of asthmatics may be hyperresponsive to a variety of inhaled materials
23 including pollens, cold-dry air, allergens, and air pollutants. Asthmatics have the potential to
24 be among the most susceptible members of the population with regard to respiratory
25 responses to NO2 (Section 15.3.1). On the average, asthmatics are much more sensitive to
26 inhaled bronchoconstrictors such as histamine, methacholine, or carbachol. The potential
27 addition of an NO2-induced increase in airway response to the already heightened
28 responsiveness to other substances raises the possibility of exacerbation of this pulmonary
29 disease by N02. This is discussed in Section 15.4.
30 Other potentially susceptible groups include patients with chronic obstructive pulmonary
31 disease (COPD), such as emphysema and chronic bronchitis. Many of these patients have
t
August 1991 , , , 16-18 DRAFT-DO NOT QUOTE OR CITE
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1 airway hyperresponsiveness to physical and chemical stimuli. A major concern with COPD
2 patients is the absence of an adequate pulmonary reserve, a susceptibility factor described
3 , above.; The poor distribution of ventilation in COPD may lead to a greater delivery of NO2
4 -to the segment of the lung that is well ventilated, thus resulting in a greater regional tissue
5 ' • dose. : , ,-'••''
6 Since over 2 million Americans have emphysema, it would be important to know
7 whether NO2 has the potential to excaberate the disease. Lafuma et al. (1987) exposed both
8 normal hamsters and hamsters with laboratory-induced (with elastase) emphysema to
9 3,760 /ig/m3 (2 ppm) NO2 for 8 h/day, 5 days/week for 8 weeks. The emphysematous
10 lesions produced by elastase and NO2 showed increases in mean linear intercepts and
11 pulmonary volumes and a decrease in internal alveolar surface areas, compared to those
12 treated with elastase and exposed to clean air. The NO2-exposed animals developed a
13 -•-. different type of emphysematous lesions than those caused by elastase. The investigators
14 . suggested that the results may imply a role for NO2 in enhancing preexisting emphysema.
15 Stavert et al. (1986) state that whereas NO2 inhalation alone may not cause emphysema, it is
16 conceivable that this oxidant gas may act as a co-determinant to allow the progression or
17 amplification of emphysema caused by other means. However, it is not clear what the
18 potential would be for exacaberation of emphysema in humans at ambient concentrations.
19 . Based upon epidemiology studies, children 12 years or younger constitute a
20 subpopulation potentially susceptible to an increase in respiratory morbidity associated with
21 NO2 exposure (Section 14.5). Children may be more susceptible due to an immature host
22 defense system. Data on the resident population of the United States provides information on
23, the numbers of children in various age ranges (Table 16-2). Approximately 37 million
24 children are in the age group 9 years and younger, while around 54 million children are in
25 the age group 14 years and younger. ,It is also possible that the increase in respiratory
26 morbidity may be more detectible in this age group compared to adults due to the greater
27 frequency of lower respiratory illness in this age group of children (Glezen and Denny,
28 1973). '
29
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TABLE 16-2. ESTIMATES OF THE RESIDENT POPULATION OF CHILDREN AND
YOUNG ADULTS OF THE UNITED STATES, BY AGE AND SEX, JULY 1, 1989
Age
All Ages
<1
1-4
5-9
10-14
15-19
Total
248,239,000
3,945,000
14,808,000
18,212,000
16,950,000
17,812,000
Population
Male
120,982,000
2,020,000
7,578,000
9,321,000
8,689,000
9,091,000
Female
127,258,000,
1,925,000
7,229,000
8,891,000
.8,260,000
8,721,000
Source: Centers for Disease Control (1990).
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9
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13
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16
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APPENDIX A:
GLOSSARY OF TERMS AND SYMBOLS
ABBREVIATIONS, ACRONYMS, AND SYMBOLS
A Angstrom (10~10 meter)
"A" strain A particular type of influenza virus
AaDO2 Difference between alveolar and arterialized partial pressure of oxygen
AAS Atomic absorption spectroscopy
AATCC American Association of Textile Chemists and Colorists
Ad A particular strain of laboratory mouse
AICHE American Institute of Chemical Engineers
AM Alveolar macrophage
AMP Adenosine monophosphate; adenosine 5' phosphate
ANSA 8-anilino-l-naphthalene-sulfonic acid
APCD Air Pollution Control District
APHA American Public Health Association
A/PR/8 A particular strain of influenza virus
A/PR/8/34 A particular strain of influenza virus
AQCR Air Quality Control Region
AQSM Air Quality Simulation Model
ASTM American Society for Testing and Materials
atm One atmosphere, a unit of pressure
ATP Adenosine triphosphate
avg Average
BAKI Potassium iodide solution acidified with boric acid
BHA Butylated hydroxyanisole
BHT Butylated hydroxytoluene
BP Blood pressure
A-l
-------
"scat
C3H
C57BL
C57BL/6
cAMP
CAMP
CD-I
cGMP
°C
14C
CHE
CL
CLdyn
cm
CNS
CO
C02
CoA
COH
CPK
CR-1
CRD
CV
CxT
d
DEN
DIFKIN
DLCO
DMN
DNA
Extinction coefficient due to scatter by aerosols
A particular strain of laboratory mouse
A particular strain of laboratory mouse
A particular strain of laboratory mouse
Cyclic adenosine monophosphate; adenosine 5'-phosphate
Community Air Monitoring Program
A particular strain of laboratory mouse
Cyclic guanosine monophosphate; guanosine 5'-phosphate
Degrees Celsius (Centigrade)
A radioactive form of carbon
Cholinesterase
Lung compliance
Dynamic lung compliance
Static lung compliance ,
Centimeter
Central nervous system; the brain and spinal cord
Carbon monoxide
Carbon dioxide
Coenzyme A
Coefficient of haze
Creatine phosphokinase
A particular strain of laboratory mouse
Chronic respiratory disease
Closing volume
Exposure concentration in ppm multiplied by time of exposure in hours or
other time measurement
Day
Diethylnitrosamine (also DENA)
Diffusion Kinetics Model
Diffusion capacity of the lung for carbon monoxide
Dimethylnitrosamine
Deoxyribonucleic acid
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D = CT
DPPD
EC
EKG
EPA
°F
FEF
FET
FEV
FEV,
FEV,
1.0
0.75
FRM
ft
FT
FVC
g
G6P
GC
GL
GC-MS
GM
GMP
GSH
GSSG
H*
3H
ha
HbO2
HNO2
HNO3
HO*
Dose equals concentration multiplied by time
N,N diphenylphenylenediamine
Prefix of International Commission on Enzymes' identification numbers
Electrocardiogram
U.S. Environmental Protection Agency
Degrees Fahrenheit
Forced expiratory flow
First-edge time
Forced expiratory volume
One-second forced expiratory volume
0.75-second forced expiratory volume
Federal Reference Method for air quality measurement
Foot
Fourier transform spectroscopy (also FS)
Forced vital capacity
Gram
Glucose-6-phosphate
Guanylate cyclase
Gas chromatography
Gas chromatograph in combination with mass spectrometry
General Motors Corporation
Guanosine 5'-phosphate; guanosine monophosphate
A tripeptide, glutathione (reduced form)
The disulfide (oxidized) form of GSH
Hydrogen (free radical)
Tritium; a radioactive form of hydrogen
Hectare
Oxyhemoglobin
Nitrous acid (also HONO)
Nitric acid (also HONO^
Hydroxyl free radical (also OH)
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H02* Hydroperoxyl free radical
HO2NO2 Pernitrous acid
HO2NO2 Pernitric acid (also
hr Hour ......
HR Heart rate . .
hv Planck's constant (h) times the frequency of radiated energy (v) = Quanta of
energy (E)
H2O2 Hydrogen peroxide
H2S Hydrogen sulfide
H2SO4 Sulfuricacid
IARC International Agency for Research on Cancer
Ig Immunoglobulins
IgA Imniunoglobulin A fraction
IgG Imniunoglobulin G fraction
IgGj Imniunoglobulin Gj fraction
IgG2 Imniunoglobulin G2 fraction
IgM Imniunoglobulin M fraction
in Inch
IR Infrared
k Rate constant or dissociation constants
kg Kilograms
km Kilometer
1 Liter (also £)
LC50 Lethal concentration 50%; that concentration which is lethal to 50% of test
subjects ' .','••.
LD50 Lethal dose 50%; dose which is lethal to 50% of the subjects
LT50 The time required for 50% of the test animals to die when given a lethal dose,
LDH Lactic acid (lactate) dehydrogenase
LPS Bacterial lipopolysaccharide , -,•••, .
m Meter • ..
M Molar
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M
MAK
max
MFR
•
mg/m
Mg
ml
mM
MMD
MMFR
mo
MFC
MT
N
N
1 "%
N
N-6-MI
NA
NAAQS
NaCl
NAD+
NADB
NADH
NADPH
NaOH
NAS
NASN
NDIR
NEDA
NEDS
Third body (in a reaction)
Maximum permissible concentration (in Germany)
Maximum
Maximal flow rate
Micrograms per cubic meter
Milligrams per cubic meter
Magnesium
Milliliter
Millimoles
Mass median diameter
Mid-maximal flow rate
Month
Maximum permissible concentration (in the U.S.S.R.)
Metric Ton
Nitrogen
Normal
A radioactive form of nitrogen
N-nitrosoheptamethyleneimine
Not applicable
National Ambient Air Quality Standard
Sodium chloride; common table salt
Nicotinamide-adenine dinucleotide (+ indicates oxidized form)
National Air Data Bank
Nicotinamide-adenine dinucleotide (reduced form)
Nicotinamide-adenine dinucleotide phosphate (reduced form)
Sodium hydroxide
National Academy of Sciences
National Air Surveillance Network
Nondispersive infrared
N-(l-Naphthyl)-ethylenediamine dihydrochloride
National Emissions Data System
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NEIC
ng
NH4
nm
NO
NOHb
NOX
N20
NO2
N203
N204
NSF
O
O^D)
03
OH
0(3P)
32P
PaCO2
PaCO2
PAH
PAN
Pa02
PA02
pH
PHA
PO2
ppb
pphm
ppm
ppt
National Enforcement Investigations Center
Nanogram
Ammonium ion or radial
Nanometer
Nitric oxide
Nitrosylhemoglobin
Nitrogen oxides
Nitrous oxide
Nitrogen dioxide
Dinitrogen trioxide
Dinitrogen tetroxide
National Science Foundation
Atomic oxygen
Excited atomic oxygen
Ozone
Hydroxyl group
Ground state atomic oxygen
A radioactive form of phosphorus
Alveolar partial pressure of carbon dioxide
Arterial partial pressure of carbon dioxide
p-Ammiohippuric acid
Peroxyacetyl nitrate
Arterial partial pressure of oxygen
Alveolar partial pressure of oxygen
Log of the reciprocal of the hydrogen ion concentration
Phytohemagglutinin
Partial oxygen pressure
Parts per billion
Parts per hundred million
Parts per million
Parts per trillion
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Q
QRS
RAMS
RAPS
Raw
RBC
RM
RNA
RV
SAI
SD
SCOT
SGPT
SH-
SMSA
SN
S02
SPF
SRaw
SRM
ss
STP
TEA
Tg
TGS-ANSA
TLC
TPTT
TSP
USEPA
UV
vc
Cardiac output
A complex of three distinct electrocardiogram waves which represent the
beginning of ventricular contraction
Regional Air Monitoring System
Regional Air Pollution Study
Airway resistance
Red blood cell; erythrocyte
Reference method for air quality measurement
Ribonucleic acid
Residual volume
Science Applications, Inc.
Standard deviation
Serum glutamic-oxaloacetic transaminase
Serum glutamic-pyruvic transaminase
Sulfhydryl group
Standard Metropolitan Statistical Area
Suspended nitrates
Sulfur dioxide
Specific pathogen free
Specific airway resistance
Standard reference material
Suspended sulfates
Standard temperature and pressure
Triethanolamine
Terragram; 106 metric tons or 1012 grams
A 24-hour method for the detection of analysis of NO2 in ambient air
Total lung capacity
20% transport time
Total suspended particulate
U.S. Environmental Protection Agency
Ultraviolet radiation
Vital capacity
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VE
VEE
Vmax
VT
V/V
WBC
wk
yr
Zn
>
<
Ventilatory volume
Venezuelan equine encephalomyelitis (virus)
Maximum expiratory flow rate
Total volume
Volume per volume
White blood ceUs
Week
Year
Zinc
Microgram
Microliter
Micrometer
Greater than
Less than
Approximately
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GLOSSARY
AaDO2: Alveolar-arterial difference or gradient of the partial pressure of oxygen. An overall
measure of the efficiency of the lung as a gas exchanger. In healthy subjects, the
gradient is 5 to 15 mm Hg (torr).
A/PR/8 virus: A type of virus capable of causing influenza in laboratory animals; also,
A/PR/8/34.
Abscission: The process whereby leaves, leaflets, fruits, or other plant parts become detached
from the plant.
Absorption coefficient: A quantity which characterizes the attenuation with distance of a beam
of electromagnetic radiation (like light) in a substance.
Absorption spectrum: The spectrum that results after any radiation has passed through an
absorbing substance.
Abstraction: Removal of some constituent of a substance or molecule.
Acetaldehyde: CH3CHO; an intermediate in yeast fermentation of carbohydrate and in alcohol
metabolism; also called acetic aldehyde, ethaldehyde, ethanal.
Acetate rayon: A staple or filament fiber made by extrusion of cellulose acetate. It is
saponified by dilute alkali whereas viscose rayon remains unchanged.
Acetylcholine: A naturally-occurring substance in the body which can cause constriction of
the bronchi in the lungs.
Acid: A substance that can donate hydrogen ions.
Acid dyes: A large group of synthetic coal tar-derived dyes which produce bright shades in a
wide color range. Low cost and ease of application are features which make them the
most widely used dyes for wool. Also used on nylon. The term acid dye is derived
from their precipitation in an acid bath.
Acid mucopolysaccharide: A class of compounds composed of protein and polysaccharide.
Mucopolysaccharides comprise much of the substance of connective tissue.
Acid phosphatase: An enzyme (EC 3.1.3.2) which catalyzes the disassociation of phosphate
(PO4) from a wide range of monoesters of orthophosphoric acid. Acid phosphatase is
active in an acidic pH range.
Acid rain: Rain having a pH less than 5.6, the minimum expected from atmospheric CO2.
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Acrolein: CH2=CHCHO; a volatile, flammable, oily liquid giving off irritant vapor. Strong
irritant of skin and mucuous membranes. Also called acrylic aldehyde, 2-propenal..
Acrylics (plastics): Plastics which are made from acrylic acid and are light in weight, have • ••••
great breakage resistance, and a lack of odor and taste. Not resistant to scratching,
burns, hot water, alcohol or cleaning fluids. Examples include Lucite and Plexiglass. ;
Acrylics are thermoplastics and are softened by heat and hardened into, definite shapes
by cooling.
Acrylic fiber: The generic name of man-made fibers derived from acrylic resins (minimum of
85% acrylonitrite units).
Actinic: A term applied to wavelengths of light too small to affect one's sense of sight, such
as ultraviolet. ., <,
Actinomycetes: Members of the genus Actinomyces; nonmotile, nonsporeforming, anaerobic
bacteria, including both soil-dwelling saprophytes and disease-producing parasites.
Activation energy: The energy required to bring about a chemical reaction.
Acute respiratory disease: Respiratory infection, usually with rapid onset and of short
duration.
Acute toxicity: Any poisonous effect produced by a single short-term exposure, that results in
severe biological harm or death.
Acyl: Any organic radical or group that remains intact when an organic acid forms an ester.
Adenoma: An ordinarily benign neoplasm (tumor) of epithelial tissue; usually well
circumscribed, tending to compress adjacent tissue rather than infiltrating or invading.
Adenosine monophosphate (AMP): A nucleotide found among the hydrolysis products of all
nucleic acids; also called adenylic acid.
Adenosine triphosphatase (ATPase): An enzyme (EC 3.6.1.3) in muscle and elsewhere that
catalyzes the release of the high-energy, terminal phosphate group of adenosine
triphosphate.
Adrenalectomy: Removal of an adrenal gland. This gland is located near or upon the kidney
and is the site of origin of a number of hormones. . \
Adsorption: Adhesion of a thin layer of molecules to a liquid or solid surface.
Advection: Horizontal flow of air at the surface or aloft; one of the means by which heat is
transferred from one region of the earth to another.
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Aerodynamic diameter: The diameter of a unit density sphere having the same settling speed
(under gravity) as the particle in question of whatever shape and density.
Aerosol: Solid particles or liquid droplets which are dispersed or suspended in a gas.
Agglutination: The process by which suspended bacteria, cells or similar particles adhere and
form into clamps.
Airborne pathogen: A disease-causing microorganism which travels in the air or on particles
iri the air. '
Air pollutant: A substance present in the ambient atmosphere, resulting from the activity of
man or from natural processes, which may cause damage to human health or welfare,
the natural environment, or materials or objects.
Air spaces: All alveolar ducts, alveolar sacs, and alveoli. To be contrasted with airways.
Airway conductance (Gaw): Reciprocal of airway resistance. Gaw = (l/Raw).
Airway resistance (Raw): The (frictional) resistance to airflow afforded by the airways
between the airway opening at the mouth and the alveoli.
Airways: All passageways of the respiratory tract from mouth or nares down to and including
respiratory bronchioles. To be contrasted with air spaces.
Alanine aminotransferase: An enzyme (EC 2.6.1.2) transferring amino groups from L-alanine
to 2-ketoglutarate. Also known as alanine transaminase.
Albumin: A type of simple, water-soluble protein widely distributed throughout animal tissues
and fluids, particularly serum.
9
Aldehyde: An organic compound characterized by the group -C-H.
Aldolase: An enzyme (EC 4.1.2.7) involved in metabolism of fructose which catalyzes the
formation of two 3-carbon intermediates in the major pathway of carbohydrate
metabolism.
Algal bloom: Sudden spurt in growth of algae which can affect water quality adversely.
Alkali: A salt of sodium or potassium capable of neutralizing acids.
Alkaline phosphatase: A phosphatase (EC 3.1.3.1) with an optimum pH of 8.6, present
ubiquitously.
Allergen: A material that, as a result of coming into contact with appropriate tissues of an
animal body, induces a state of sensitivity resulting in various reactions; generally
associated with idiosyncratic hypersensitivities.
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Alpha-hydroxybutyrate dehydrogenase: An enzyme (EC 1.1.1.30), present mainly in
mitochondria, which catalyzes the conversion of hydroxybutyrate to acetoacetate
intermediate biochemical pathways.
Alpha rhythm: A rhythmic pulsation obtained in brain waves exhibited in the sleeping state of
an individual.
Alveolar capillary membrane: Finest portion of alveolar capillaries, where gas transfer to and
from blood takes place.
, - . . 'i
Alveolar macrophage (AM): A large, mononuclear, phagocytic cell found on the alveolar
surface, responsible for particle clearance from the deep lung and for viral and bacterial
killing.
Alveolar oxygen partial pressure (PAO2): Partial pressure of oxygen in the air contained in -<
the air sacs of the lungs.
Alveolar septa: The tissue between two adjacent pulmonary alveoli, consisting of a
close-meshed capillary network covered on both surfaces by thin alveolar epithelial
cells.
Alveolus: An air cell; a terminal, sac-like dilation in the lung. Gas exchange
occurs here.
Ambient: The atmosphere to which the general population may be exposed. Construed here
not to include atmospheric conditions indoors, or in the workplace.
Amine: A substance that may be derived from ammonia (NH3) by the replacement of one,
two or three of the hydrogen (H) atoms by hydrocarbons or other radicals (primary,
secondary or tertiary amines, respectively).
Amino acids: Molecules consisting of a carboxyl group, a basic amino group, and a residue
group attached to a central carbon atom. Serve as the building blocks of proteins.
p-Aminohippuric acid (PAH): A compound used to determine renal plasma flow.
Aminotriazole: A systemic herbicide, C2H4N4, used in areas other than croplands, that also
possesses some antithyroid activity; also called amitrole.
Ammonification: Decomposition with production of ammonia or ammonium compounds, esp.
by the action of bacteria on nitrogenous organic matter.
Ammonium: Anion (NH4+) or radical (NH4) derived from ammonia by combination with
hydrogen. Present in rainwater, soils and many commercial fertilizers.
Amnestic: Pertains to immunologic memory: upon receiving a second dose of antigen, the
host "remembers" the first dose and responds faster to the challenge.
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Anaerobic: Living, active or occurring in the absence of free oxygen.
Anaerobic bacteria: A type of microscopic organism which can live in an environment not
containing free oxygen.
Anaphylactic dyspneic attack: Difficulty in breathing associated with a systemic allergic
response.
Anaphylaxis: A term commonly used to denote the immediate, transient kind of
immunological (allergic) reaction characterized by contraction of smooth muscle and
dilation of capillaries due to release of pharmacologically active substances.
Angiosperm: A plant having seeds enclosed in an ovary; a flowering plant.
Angina pectoris: Severe constricting pain in the chest which may be caused by depletion of
oxygen delivery to the heart muscle; usually caused by coronary disease.
Angstrom (A): A unit (10~8 cm) used in the measurement of the wavelength of light.
Anhydride: A compound resulting from removal of water from two molecules of a carboxylic
(-COOH) acid. Also, may refer to those substances (anhydrous) which do not contain
water in chemical combination. . ,
Anion: A negatively charged atom, radical, or ion.
Anorexia: Diminished appetite; aversion to food.
Anoxic: Without or deprived of oxygen. ,
Antagonism: When the effects of a mixture are less than the sum of the effects of each
individual chemical.
Anthraquinone: A yellow crystalline ketbne, C14H8O2 derived from anthracene and used in
the manufacture of dyes.
Anthropogenic: Of, relating to or influenced by man. An anthropogenic source of pollution
is one caused by man's actions.
Antibody: Any body or substance evoked by the stimulus of an antigen and which reacts
specifically with antigen in some demonstrable way.
Antigen: A material such as a foreign protein that, as a result of coming in contact with
appropriate tissues of an animal, after a latent period, induces a state of sensitivity
and/or the production of antibody.
Antistatic agent: A chemical compound applied to fabrics to reduce or eliminate accumulation
of static electricity.
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Arachidonic acid: Long-chain fatty-acid which serves as a precursor of prostaglandins.
Area source: In air pollution, any small individual fuel combustion or other pollutant source;
also, all such sources grouped over a specific area.
Aromatic: Belonging to that series of carbon-hydrogen compounds in which the carbon atoms
form closed rings containing unsaturated bonds (as in benzene).
Arterial partial pressure of oxygen (PaO2): Portion of total pressure of dissolved gases in
arterial blood as measured directly from arterial blood.
Arterialized partial pressure of oxygen: The portion of total pressure of dissolved gases in
arterial blood attributed to oxygen, as measured from non-arterial (e.g., ear-prick)
blood.
Arteriosclerosis: Commonly called hardening of the arteries. A condition that exists when the
walls of the blood vessels thicken and become infiltrated with excessive amounts of
minerals and fatty materials.
Artifact: A spurious measurement produced by the sampling or analysis process.
Ascorbic acid: Vitamin C, a strong reducing agent with antioxidant properties.
Aspartate transaminase: Also known as aspartate aminotransferase (EC 2.6.1.1). An enzyme
catalyzing the transfer of an amine group from glutamic acid to oxaloacetic, forming
aspartic acid in the process. Serum level of the enzyme is increased in myocardial
infarction and in diseases involving destruction of liver cells.
Asphyxia: Impaired exchange of oxygen and carbon dioxide, excess of carbon dioxide and/or
lack of oxygen, usually caused by ventilatory problems.
Asthma: A disease characterized by an increased responsiveness of the airways to various
stimuli and manifested by slowing of forced expiration which changes in severity either
spontaneously or as a result of therapy. The term asthma may be modified by words or
phrases indicating its etiology, factors provoking attacks, or duration.
Asymptomatic: Presenting no subjective evidence of disease.
Atmosphere: The body of air surrounding the earth. Also, a measure of pressure (atm.) equal
to the pressure of air at sea level, 14.7 pounds per square inch.
Atmospheric deposition: Removal of pollutants from the atmosphere onto land, vegetation,
water bodies or other objects, by absorption, sedimentation, Brownian diffusion,
impaction, or precipitation in rain.
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Atomic absorption spectrometry: A measurement method based on the absorption of radiant
energy by gaseous ground-state atoms. The amount of absorption depends on the
population of the ground state which is related to the concentration of the sample being
analyzed.
Atopic: Clinical hyperreactivity of the airways associated with asthma and allergies.
Atropine: A poisonous, white crystalline alkaloid (C17H23NO3) derived from belladonna and
related plants, used to relieve spasms of smooth muscles. It is an anticholinergic agent
that blocks the parasympathetic actions of acetylcholine and other cholinergic agents.
Autocorrelation: Statistical interdependence of variables being analyzed; produces problems,
for example, when observations may be related to previous measurements or other
conditions.
Autoimmune disease: A condition in which antibodies are produced against the subject's own
tissues.
Autologous: A term referring to cellular elements, such as red blood cells and alveolar
macrophage, from title same organism; also, something natually and normally occurring
in some part of the body.
Autotrophic: A term applied to those microorganisms which are able to maintain life without
an exogenous organic supply of energy, or which only need carbon dioxide or
carbonates and simple inorganic nitrogen.
Autotrophic bacteria: A class of microorganisms which require only carbon dioxide or
carbonates and a simple inorganic nitrogen compound for carrying on life processes.
Auxin: An organic substance that causes lengthening of the stem when applied in low
concentrations to shoots of growing plants.
Awn: One of the slender bristles that terminate the glumes of the spikelet in some cereals and
other grasses.
Azo dye: Dyes in which the azo group is the chromophore and joins benzene or naphthalene
rings.
Background measurement: A measurement of pollutants in ambient air due to natural sources;
usually taken in remote areas.
Bactericidal activity: The process of killing bacteria.
Barre: Bars or stripes in a fabric, caused by uneven weaving, irregular yarn or uneven dye
distribution.
Basal cell: One of the innermost cells of the deeper epidermis of the skin.
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Base cation: CA2+, Mg2+, K+, orNa+.
Base saturation: The degree to which soil cation exchange capacity is occupied by base
cations. This expressed as a percent, use charge-equivalents.
Benzenethiol: A compound of benzene and a hydrosulfide group.
Beta (j8)-lipoprotein: A biochemical complex or compound containing both lipid and protein
and characterized by having a large molecular weight, rich in cholesterol. Found in
certain fractions of human plasma.
Bilateral renal sclerosis: A hardening of both kidneys of chronic inflammatory origin.
Biomass: That part of a given habitat consisting of living matter.
Biosphere: The part of the earth's crust, waters and atmosphere where living organisms can
subsist.
Biphasic: Having two distinct successive stages.
Bleb: A collection of fluid beneath the skin; usually smaller than bullae or blisters.
Blood urea: The chief end product of nitrogen metabolism in mammals, excreted in human
urine in the amount of about 32 grams (1 oz.) a day.
Bloom: A greenish-gray appearance imparted to silk and pile fabrics either by nature of the
weave or by the finish; also, the creamy white color observed on some good cottons.
Blue-green algae: A group of simple plants which are the only N2-fixing organisms which
photosynthesize as do higher plants.
Brightener: A compound such as a dye, which adheres to fabrics in order to provide better
brightness or whiteness by converting ultraviolet radiation to visible light. Sometimes
called optical bleach or whitening agent. The dyes used are of the florescent type.
Broad bean: The large flat edible seed of an Old World upright vetch (Vicia faba), or the
plant itself, widely grown for its seeds and for fodder.
Bronchi: The first subdivisions of the trachea which conduct air to and from the bronchioles
of the lungs.
Bronchiole: One of the finer subdivisions of the bronchial (trachea) tubes, less than 1 mm in
diameter, and having no cartilage in its wall.
Bronchiolitis: Inflammation of the bronchioles, which may be acute or chronic. If the
etiology is known, it should be stated. If permanent occlusion of the lumens is present,
the term bronchiolitis obliterans may be used.
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Bronchiolitis fibrosa obliterans syndrome: Obstruction of the bronchioles by fibrous
granulation arising from an ulcerated mucosa; the condition may follow inhalation of
irritant gases.
Bronchitis: A non-neoplastic disorder of structure or function of the bronchi resulting from
infectious or noninfectious irritation. The term bronchitis should be modified by
appropriate words or phrases to indicate its etiology, its chronicity, the presence of
' associated airways dysfunction, or the type of anatomic change. The term chronic
bronchitis, when unqualified, refers to a condition associated with prolonged exposure
to nonspecific bronchial irritants and accompanied by mucus hypersecretion and certain
structural alterations in the bronchi. Anatomic changes may include hypertrophy of the
mucous-secreting apparatus and epithelial metaplasia, as well as more classic evidences
of inflammation. In epidemiologic studies, the presence of cough or sputum production
on most days for at least three months of the year for at least two consecutive years has
sometimes been accepted as a criterion for the diagnosis.
Bronchoconstrictor: An agent that causes a reduction in the caliber (diameter) of a bronchial
tube.
Bronchodilator: An agent which causes an increase in the caliber (diameter) of a bronchus or
bronchial tube.
Bronchopneumonia: Acute inflammation of the walls of the smaller bronchial tubes, with
irregular area of consolidation due to spread of the inflammation into peribronchiolar
alveoli and the alveolar ducts.
Bronchospasm: Temporary narrowing of the bronchi due to a violent, involuntary contraction
of the smooth muscle of the bronchi.
Bronchus: One of the subdivisions of the trachea serving to convey air to and from the lungs.
The trachea divides into right and left main bronchi which in turn form lobar,
segmental, and subsegmental bronchi.
Brownian diffusion: Diffusion by random movement of particles suspended in liquid or gas,
resulting from the impact of molecules of the fluid surrounding the particles.
BTPS conditions (BTPS): Body temperature, barometric pressure, and saturated with water
vapor. These are the conditions existing in the gas phase of the lungs. For humans the
normal temperature is 37°C, the pressure is based on the barometric pressure, and the
partial pressure of water vapor is 47 torr.
Buffer: A substance in solution capable of neutralizing both acids and bases and thereby
maintaining the original pH of the solution.
Buffering: In reference to soil acidification, this is resistance to change resulting from
reserves of acid or base cations on the soil cation exchange sites.
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Buffering capacity: Ability of a body of water and its watershed to neutralize introduced acid.
Butanol: A four-carbon, straight-chain alcohol, C4H9OH, also known as butyl alcohol.
Butylated hydroxytoluene (BHT): A crystalline phenolic antioxidant.
Butylated hydroxyanisol (BHA): An antioxidant.
14C labeling: Use of a radioactive form of carbon as a tracer, often in metabolic studies.
C-proline: An amino acid which has been labeled with radioactive carbon.
Calcareous: Resembling or consisting of calcium carbonate (lime), or growing on limestone or,
lime-containing soils.
Calorie: Amount of heat required to raise temperature of 1 gram of water at 15°C by
1 degree.
Cannula: A tube that is inserted into a body cavity, or other tube or vessel, usually to remove
fluid.
Capillary: The smallest type of vessel; resembles a hair. Usually in reference to a blood or
lymphatic capillary vessel. <
Carbachol: A cholinergic parasympathetic stimulant, carbamoylcholine chloride
(^6H15CIN2O2)' mat produces constriction of the bronchial smooth muscles similar to
acetylcholine.
Carbon monoxide: An odorless, colorless, toxic gas with a strong affinity for hemoglobin and
cytochrome; it reduces oxygen absorption capacity, transport and utilization.
Carboxyhemoglobin: A fairly stable union of carbon monoxide with hemoglobin which
interferes with the normal transfer of carbon dioxide and oxygen during circulation of
blood. Increasing levels of carboxyhemoglobin result in various degrees of
asphyxiation, including death.
Carcinogen: Any agent producing or playing a stimulatory role in the formation of a
malignancy.
Carcinoma: Malignant new growth made up of epithelial cells tending to infiltrate the
surrounding tissues and giving rise to metastases.
Cardiac output: The volume of blood passing through the heart per unit time:
Cardiovascular: Relating to the heart and the blood vessels or the circulation.
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Carotene: Lipid-soluble yellow-to-orange-red pigments universally present the photosynthetic
tissues of higher plants, algae, and the photosynthetic bacteria.
Cascade impactor: A device for measuring the size distribution-of particulates and/or aerosols,
consisting of a series of plates with orifices of graduated size which separate the sample
into a number of fractions of decreasing aerodynamic diameter.
Catabolism: Destructive metabolism involving the release of energy and resulting in
breakdown of complex materials in the organism.
Catalase: An enzyme (EC 1.11.1.6) catalyzing the decomposition of hydrogen peroxide to
water and oxygen.
Catalysis: A modification of the rate of a chemical reaction by some material which is
unchanged at the end of the reaction.
Catalytic converter: An air pollution abatement device that removes organic contaminants by
oxidizing them into carbon dioxide and water.
Catecholamine: A pyrocatechol with an alkalamine side chain, functioning as a hormone or
neurotransmitter, such as epinephrine, morepinephrine, or dopamine.
Cathepsins: Enzymes which have the ability to hydrolyze certain proteins and peptides; occur
in cellular structures known as lysosomes.
Cation: A positively charged ion.
Cation exchange capacity: The ability of a soil to absorb positively-charged ions by
electostatic forces. This absorption occurs on negatively-charged sites on clays and
organic matter in soils.
Cellular permeability: Ability of gases to enter and leave cells; a sensitive indicator of injury
to deep-lung cells.
Cellulose: The basic substance which is contained in all vegetable fibers and in certain
man-made fibers. It is a carbohydrate and constitutes the major substance in plant life.
Used to make cellulose acetate and rayon.
Cellulose acetate: Commonly refers to fibers or fabrics in which the cellulose is only partially
acetylated with acetate groups. An ester made by reacting cellulose with acetic
anhydride with SO4 as a catalyst.
Cellulose rayon: A regenerated cellulose which is chemically the same as cellulose except for
physical differences in molecular weight and crystallinity.
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Cellulose triacetate: A cellulose fiber which is completely acetylated. Fabrics of triacetate
have higher heat resistance than acetate and may be safely ironed at higher temperature.
Such fabrics have improved ease-of-care characteristics because after heat treatment
during manufacture, a change in the crystalline structure of the fiber occurs. •
Cellulosics: Cotton, viscose rayon and other fibers made of natural fiber raw materials.
Celsius scale: The thermometric scale in which freezing point of water is ,0 and boiling point
is 100.
Central hepatic necrosis: The pathologic death of one or more cells, or of a portion of the
liver, involving the cells adjacent to the central veins.
Central nervous system (CNS): The brain and the spinal cord.
Centroacinar area: The center portion of a grape-shaped gland.
Cerebellum: The large posterior brain-mass lying above the pons and medulla and beneath the
posterior portion of the cerebrum. ,
Cerebral cortex: The layer of gray matter covering the entire surface of the cerebral
hemisphere of mammals.
Chain reaction: A reaction that stimulates its own repetition.
Challenge: Exposure of a test organism to a virus, bacteria, or other stress-causing agent,
used in conjunction with exposure to a pollutant of interest, to explore possible
susceptibility brought on by the pollutant. :
Chamber study: Research conducted using a closed vessel in which pollutants are reacted or
substances exposed to pollutants.
Chemiluminescence: A measurement technique in which radiation is produced as a result of
chemical reaction.
Chemotactic: Relating to attraction or repulsion of living protoplasm by chemical stimuli.
Chlorophyll: A group of closely related green photosynthetic pigments occurring in leaves,
bacteria, and organisms. '
Chloroplast: A plant cell inclusion body containing chlorophyll.
Chlorosis: Discoloration of normally green plant parts that can be caused by disease, lack of
nutrients, or various air pollutants, resulting in the failure of chlorophyll to develop.
Cholesterol: A steroid alcohol C2H45OH; the most abundant steroid in animal cells and body
j-» • i ** ^^ - J
fluids.
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Cholinesterase (CHE): One (EC 3.1.1.8) of a family of enzymes capable of catalyzing the
' hydrolysis of acylcholines.
Chondrosarcoma: A malignant neoplasm derived from cartilage cells, occurring most
frequently near the ends of long bones.
Chromatid: Each of the two strands formed by longitudinal duplication of a chromosome that
becomes visible during an early stage of cell division.
Chromophore: A chemical group that produces color in a molecule by absorbing near
ultraviolet or visible radiation when bonded to a nonabsorbing, saturated residue which
possesses no unshared, nonbonding valence electrons.
Chromosome: One of the bodies (46 in man) in the cell nucleus that is the bearer and carrier
of genetic information.
Chronic obstructive pulmonary disease (COPD): This term refers to diseases of uncertain
etiology characterized by persistent slowing of airflow during forced expiration. It is
recommended that a more specific term, such as chronic obstructive bronchitis or
chronic obstructive emphysema, be used whenever possible. Synonymous with chronic
obstructive lung disease (COLD). "• '
Cilia: Motile, often hairlike extensions of a cell surface.
Ciliary action: Movements of cilia in the upper respiratory tract, which move mucus and
foreign material upward.
Ciliogenesis: The formation of cilia.
Citric acid (Krebs) cycle: A major biochemical pathway in cells, involving terminal oxidation
of fatty acids and carbohydrates. It yields a major portion of energy needed for essential
body functions and is the major source of CO2. It couples the glycolytic breakdown of
sugar in the cytoplasm with those reactions producing ATP in the mitochondria. It also
serves to regulate the synthesis of a number of compounds required by a cell.
Clara cell: A nonciliated cell in the epithelium of the respiratory tract.
Closing capacity (CC): Closing volume plus residual volume, often expressed as a ratio of
TLC (i.e., CC/TLC%).
Closing volume (CV): The volume exhaled after the expired gas concentration is inflected
from an alveolar plateau during a controlled breathing maneuver. (Most commonly
obtained during a single-breath nitrogen washout test.) Since the value obtained is
dependent on the specific test technique, the method used must be designated in the
text, and when necessary, specified by a qualifying symbol. Closing volume is often
expressed as a ratio of the vital capacity (i.e., CV/VC%).
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Codon: A sequence of three nucleotides which encodes information required to direct the
synthesis of one or more amino acids. .,...,"
Coefficient of haze (COH): A measurement of visibility interference in the atmosphere.
Cohort: A group of individuals or vital statistics about them having a statistical factor in
common in a demographic study (e.g., year of birth, sex, level of exposure to a'
pollutant, etc.). . .-,.•..,
Collagen: The major protein of the white fibers of connective tissue, cartilage, and bond^
Comprises over half the protein of the mammal.
Collisional deactivation: Reduction in energy of excited molecules caused by collision with
other molecules or other objects such as the walls of a container.
Colorimetric: A chemical analysis method relying on measurement of the degree of color
produced in a solution by reaction with the pollutant of interest.
Community exposure: A situation in which people in a sizeable area are subjected to ambient
pollutant concentrations.
Compliance (CL,Cst): A measure of distensibility. Pulmonary compliance is given by the
slope of a static volume-pressure curve at a point, or the linear approximation of a
nearly straight portion of such a curve, expressed as the change in volume per unit
change in distending pressure in L/cm H2O or mL/cm H2O. Since the static volume- '
pressure characteristics of lungs are nonlinear (static compliance decreases as lung
volume increases) and vary according to the previous volume history (static compliance
at a given volume increases immediately after full inflation and decreases following '
deflation), careful specification of the conditions of measurement are necessary.
Absolute values also depend on organ size. See also Dynamic compliance.
Complement: Thermolabile substance present in serum that is destructive to certain bacteria
and other cells which have been sensitized by specific complement-fixing antibody-.
Compound: A substance with its own distinct properties, formed by the chemical combination
of two or more elements in fixed proportion.
Concanavalin-A: One of two crystalline globulins occurring in the jack bean; a potent
hemagglutinin.
Conductance (G): The reciprocal of resistance. See Airway conductance.
Conifer: A plant, generally evergreen, needle-leafed, bearing naked seeds singly or in cones.
Converter: See catalytic converter.
Coordination number: The number of bonds formed by the central atom in a complex.
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Copolymer: The product of the process of polymerization in which two or more monomeric
substances are mixed prior to polymerization. Nylon is a copolymer.
Coproporphyrin: 'One of two porphyrin compounds found normally in feces as a
decomposition product of bilirubin (a bile pigment). Porphyrin is a widely-distributed
pigment consisting of four pyrrole nuclei joined in a ring.
Cordage: A general term which includes banding, cable, cord, rope, string, and twine made
from fibers. Synthetic fibers used in making cordage include nylon and dacron.
Corrosion: -Destruction or deterioration of a material because of reaction with its environment.
Corticosterone: A steroid obtained from the adrenal cortex. It induces some deposition of
glycogen in the liver, sodium conservation, and potassium excretion.
Cosmopolitan: In the biological sciences, a term denoting worldwide distribution.
Coulometric: Chemical analysis performed by determining the amount of a substance released
in electrolysis by measuring the number of coulombs used.
Coumarin: A toxic white crystalline lactone (C9H6O2) found in plants.
Coupler: A chemical used to combine two others in a reaction (e.g., to produce the azo dye
in the Griess-Saltzman method for NO2).
Crevice corrosion: Localized corrosion occurring within crevices on metal 'surfaces exposed to
corrosives. '
Critical Load: A quantitative estimate of an exposure to one or more pollutants below which
significant harmful effects on specified sensitive elements of the ecosystem do not occur
according to present knowledge.
Crosslink: To connect, by an atom or molecule, parallel chains in a complex chemical
molecule, such as a polymer.
Cryogenic trap: A pollutant sampling method in which a gaseous pollutant is condensed out of
sampled air by cooling (e.g., traps in'one method for nitrosamines are maintained below
-79°C, usirig solvents maintained at their freezing points).
Cuboidal: Resembling a cube in shape.
Cultivar: An organism produced by parents belonging to different species or to different
strains of the same species, originating and persisting under cultivation.'
Cuticle: A thin outer layer, such as the thin continuous fatty film on the surface of many
higher plants.
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Cyanosis: A dark bluish or purplish coloration of the skin and mucous membrane due to
deficient oxygenation of the blood.
Cyclic GMP: Guanoshie 5'-phosphoric acid.
Cytochrome: A class of hemoprotein whose principal biological function is electron and/or
hydrogen transport. ;
Cytology: The anatomy, physiology, pathology and chemistry of the cell.
Cytoplasm: The substance of a cell exclusive of the nucleus.
Dacron: The trade name for polyester fibers made by E.I. du Pont de Nemours and Co.,
Inc., made from dimethyl terephthalate and ethylene glycol.
Dark adaptation: The process by which the eye adjusts under reduced illumination and the
sensitivity of the eye to light is' greatly increased. . .
Dark respiration: Metabolic activity of plants at night; consuming oxygen to use stored sugars
and releasing carbon dioxide.
Deciduous plants: Plants which drop their leaves at the end of the growing season.
Degradation (textiles): The decomposition of fabric or its components or characteristics
(color, strength, elasticity) by means of light, heat, or air pollution.
Denitrification: A bacterial process occurring in soils, or water, in which nitrate is used as the
terminal electron acceptor and is reduced primarily to N2. It is essentially an anaerobic
process, it can occur in the presence of low levels of oxygen only 'if the microorganisms
are metabolizing in an anoxic microzone.
De novo: Over again.
Deoxyribonucleic acid (DMA): A nucleic acid considered to be the carrier of genetic
information coded in the sequence of purine and pyrimidine bases (organic bases).
It has the form of a double-stranded helix of a linear polymer.
Depauperate: Falling short of natural development or size.
Deposition:
Acidic: Removal of acidic pollutants from the atmosphere by dry and wet deposition.
Dry: Removal of pollutants from the atmosphere through interactions with various
surfaces of plants, land, and water.
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Respiratory tract: . The depositing of inhaled pollutants within the respiratory tract-which
depends on breathing patterns, airway geometry, and the physical and chemical
properties of the inhaled pollutants.
Wet: Removal of pollutants from the atmosphere by precipitation (e.g., rain or snow).
Derivative spectrophotometer: An instrument with an increased capability for detecting
overlapping spectral lines and bands and also for suppressing instrumentally scattered
light. .,.'.."..•-.•
Desorb: To release a substance which has been taken into another substance or held on its
surface; the opposite of absorption or adsorption.
Desquamation: The sheading of the outer layer of any surface.
Detection limit: A level below which an element or chemical compound cannot be reliably
detected by the method or measurement being used for analysis. :
Detritus: Loose material that results directly from disintegration.
DeVarda alloy: An alloy of 50 percent Cu, 45 percent Al, 5 percent Zn.
Diastolic blood pressure: The blood pressure as measured during the period of filling the
cavities of the heart with blood. , :
Diazonium salt: A chemical compound (usually colored) of the general structure ArN2+Cl",
where Ar refers to an aromatic group.
Diazotizer: A chemical which, when reacted with amines (RNH2, for example), produces a
diazonium salt (usually a colored compound). , , ;
Dichotomous sampler: A device used to collect separately fine and coarse particles from an
aerosol and to measure gravimetrically the concentration of such different-sized particles
in the ambient air.
Differentiation: The process by which a cell, such as a fertilized egg, divides into specialized
cells, such as the embryonic types that eventually develop into an entire organism.
Diffusion: The process by which molecules or other particles intermingle as a result of their
random thermal motion. , ,
f
Diffusing capacity of the lung (DL, DLO2, DLCO2, DLCO): Amount of gas (O2, CO, CO2)
commonly expressed as milliliters of gas (STPD) diffusing between alveolar gas and
pulmonary capillary blood per torr mean gas pressure difference per minute, such as
mL O2/(min-torr). Synonymous with transfer factor and diffusion factor.
Dimer: A compound formed by the union of two like radicals or molecules.
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Dimerize: Formation of dimers. • ,
1,6-diphosphofructose aldolase: An enzyme (EC 4.1.1.13) cleaving fructose 1,6-bisphosphate
to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate;
D-2,3-diphosphoglycerate: A salt or ester of 2,3-diphosphoglyceric acid, a major component
of certain mammalian erythrocytes involved in the release of O2 from HbO2. Also a
postulated intermediate in the biochemical pathway involving the conversion of 3- to
2-phosphoglyceric acid.
Diplococcus pneumonias: A species of spherical-shaped bacteria belonging to the genus
Streptococcus. May be a causal agent in pneumonia.
Direct dye: A dye with an affinity for most fibers; used mainly when color resistance to
washing is not important.
Disperse dyes: Also known as acetate dyes; these dyes were developed for use on acetate
fabrics, and are now also used on synthetic fibers.
Distal: Far from some reference point such as median line of the body, point of attachment or
origin.
Diurnal: Having a repeating pattern or cycle 24 hours long.
DLCO: The diffusing capacity of the lungs for carbon monoxide. The ability of the lungs to
transfer carbon monoxide from the alveolar air into the pulmonary capillary blood.
Dorsal hyphosis: Abnormal curvative of the spine; hunch-back.
Dose: The quantity of a substance to betaken all at one time or in fractional amounts within a
given period; also the total amount of a pollutant delivered or concentration per unit
time times time.
Dose-response curve: A curve on a graph based on responses occurring in a system as a result
of a series of stimuli intensities or doses.
Dry deposition: The processes by which.matter is transferred to ground from the atmosphere,
other than precipitation; includes surface absorption of gases and sedimentation, "
Brownian diffusion and impaction of particles.
Dyeing: A process of coloring fibers, yarns, or fabrics with either natural or synthetic dyes.
Dynamic calibration: Testing of a monitoring system using a continuous sample stream of
known concentration. '
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Dynamic compliance (Cd ): the ratio of the tidal volume to the change in intrapleural
pressure between the points of zero flow at the extremes of tidal volume in L/cm H2O
or mL/cm H2O. Since at the points of zero airflow at the extremes of tidal volume,
volume acceleration is usually other than zero, and since, particularly in abnormal
states, flow may still be taking place within lungs between regions which are
exchanging volume. Dynamic compliance may differ from static compliance, the latter
pertaining to condition of zero volume acceleration and zero gas flow throughout the
lungs. In normal lungs at ordinary volumes and respiratory frequencies, static and
dynamic compliance are the same.
Dynel: A trademark for a modacrylic staple fiber spun from a copolymer of acrylonitrile and
vinyl chloride. It has high strength, quick-drying properties, and resistance to alkalies
and acids.
Dyspepsia: Indigestion, upset stomach.
Dyspnea: Shortness of breath; difficulty or distress in breathing; rapid breathing.
Ecosystem: The interacting system of a biological community and its environment.
Eddy: A current of water or air running contrary to the main current.
Edema: Pressure of excess fluid in cells, intercellular tissue or cavities of the body.
Elastance (E): The reciprocal of compliance; expressed in cm H2O/L or cm H2O/mL.
Elastomer: A synthetic rubber product which has the physical properties of natural rubber.
Electrocardiogram: The graphic record of the electrical currents that initiate the heart's
; contraction. .
Electrode: One of the two extremities of an electric circuit.
.Electrolyte: A non-metallic electric conductor in which-current is carried by the movement of
ions; also a substance which displays these qualities when dissolved in water or another
solvent.
Electronegativity: Measure of affinity for negative charges or electrons.
Electron microscopy: A technique which utilizes a focused beam of electrons to produce a
high-resolution image of minute objects such as paniculate matter, bacteria, viruses, and
DNA.
Electronic excitation energy: Energy associated in the transition of electrons from their normal
low-energy orbitals or orbitals of higher energy.
Electrophilic: Having an affinity for electrons.
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Electrophoresis: A technique by which compounds can be separated from a complex, .mixture
by their attraction to the positive or negative pole of an applied electric potential.
Eluant: A liquid used in the process of elution.
Elute: To perform an elution.
Elution: Separation of one material from another by washing or by dissolving one in a solvent
in which the other is not soluble.
Elutriate: To separate a coarse, insoluble powder from a finer one by suspending them
in water and pouring off the finer powder from the upper part of the fluid.
Emission spectrometry: A rapid analytical technique based on measurement of the .
characteristic radiation emitted by thermally or electrically excited atoms or ions.
Emphysema: A condition of the lung characterized by abnormal, permanent enlargement
of airspaces distal to the terminal bronchiole, accompanied by the destruction of
their walls, and without obvious fibrosis.
Emphysematous lesions: A wound or injury to the lung as a result of emphysema.
Empirical modeling: Characterization and description of a phenomena based on experience or
observation.
Encephalitis: Inflammation of the brain.
Endoplasmic reticulum: An elaborate membrane structure extending from the nuclear
membrane or eucaryotic cells to the cytoplasmic membrane.
Endothelium: A layer of flat cells lining especially blood and lymphatic vessels.
Entropy: A measure of disorder or randomness in a system. Low entropy is associated with
highly ordered systems. , .
Enzyme: Any of numerous proteins produced by living cells which catalyze biological
reactions. , ,
Enzyme Commission (EC): The International Commission on Enzymes, established in 1956,
developed a scheme of classification and nomenclature under which each enzyme is
assigned an EC number which identifies it by function.
Eosinophils: Leukocytes (white blood cells) which stain readily with the dye, eosin.
Epidemiology: A study of the distribution and determinants of disease in human population
groups.
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Epidermis: The outermost living layer of cells of any organism. '
Epididymal fat pads: The fatty tissue located near the epididymis. The epididymis is the first
convoluted portion of the excretory duct of the testis. ;
Epiphyte: A plant growing on another plant but obtaining food from the atmosphere.
Epithelial: Relating to epithelium, the membranous cellular layer which covers free surfaces
or lines tubes or cavities of an animal body, which encloses, protects, secretes, excretes
and/or assimilates.
Erosion corrosion: Acceleration or increase in rate of deterioration or attack on a metal
because of relative movement between a corrosive fluid and the metal surface.
Characterized by grooves, gullies, or waves in the metal surface.
Erythrocyte: A mature red blood cell.
Escherichia coll: A short, gram-negative, rod-shaped bacteria common to the human intestinal
tract. A frequent cause of infections in the urogenital tract.
Esophageal: Relating to the portion of the digestive tract between the pharynx and the
stomach.
Estrus: That portion or phase of the sexual cycle of female animals characterized by
willingness to permit coitus.
Estrus cycle: The series of physiologic uterine, ovarian and other changes that occur in higher
animals. •
Etiolation: Paleness and/or altered development resulting from the absence of light.
Etiology: The causes of a disease or condition; also, the study of causes.
Eucaryotic: Pertaining to those cells having a well-defined nucleus surrounded by a
double-layered membrane.
Euthrophication: Elevation of the level of nutrients in a body of water, which can contribute
to accelerated plant growth and filling.
Excited state: A state of higher electronic energy than the ground state, usually a less stable
one.
Expiratory (maximum) flow rate: The maximum rate at which air can be expelled from the
lungs.
Exposure level: Concentration of a contaminant to which an individual or a population is
exposed.
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Extinction coefficient: A measure of the space rate of diminution, or extinction, of any
transmitted light, thus, it is the attenuation coefficient applied to visible radiation.
ExtrameduUary hematopoiesis: The process of formation and development of the various types
of blood cells and other formed elements not including that occurring in bone marrow.
Extravasate: To exclude from or pass out of a vessel into the tissues; applies to urine, lymph,
blood and similar fluids.
Far ultraviolet: Radiation in the range of wavelengths from 100 to 190 nanometers.
Federal Reference Method (FRM): For NO2, the EPA-approved analyzers based on the gas-
phase chemiluminescent measurement principle and associated calibration procedures;
regulatory specifications prescribed in Title 40, Code of Federal Regulations, Part 50,
Appendix F.
Fenestrae: Anatomical aperatures often closed by a membrane.
FEVt/FVC: A ratio of timed (t = 0.5, 1, 2, 3 s) forced expiratory volume (FEVt) to forced
vital capacity (FVC). The ratio is often expressed in percent 100 x FEVt/FVC. It is an
index of airway obstruction.
Fiber: A fine, threadlike piece, as of cotton, jute, or asbestos.
Fiber-reactive dye: A water-soluble dyestuff which reacts chemically with the cellulose in
fibers under alkaline conditions; the dye contains two chlorine atoms which combine
with the hydroxyl groups of the cellulose.
Fibrin: A white insoluble elastic filamentous protein derived from fibrihogen by the action of
thrombin, especially in the clotting of blood.
Fibroadenoma: A benign neoplasm derived from glandular epithelium, involving proliferating
fibroblasts, cells found in connective tissue.
Fibroblast: An elongated cell with cytoplasmic processes present in connective tissue, capable
of forming collagen fibers.
Fibrosis: The formation of fibrous tissue, usually as a reparative or reactive process and not
as a normal constituent of an organ or tissue.
Fine particles: Airborne particles smaller than 2 to 3 ^m in aerodynamic diameter.
Flocculation: Separation of material from a solution or suspension by reaction with a
flocculant to create fluffy masses containing the material to be removed.
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Flow volume curve: Graph of instantaneous forced expiratory flow recorded at the mouth,
against corresponding lung volume. When recorded over the full vital capacity, the
curve includes maximum expiratory flow rates at all lung volumes in the vital capacity
range and is called a maximum expiratory flow-volume curve (MEFV). A partial
expiratory flow-volume curve (PEFV) is one which describes maximum expiratory flow
rate over a portion of the vital capacity only.
Fly ash: Fine, solid particles of noncqmbustible ash carried out of a bed of solid fuel by a
draft.
Fogs: Suspension of liquid droplets formed by condensation of vapor or atomization; the
concentration of particles is sufficiently high to obscure visibility.
Folded-path optical system: A long (e.g., 8-22 m) chamber with multiple mirrors at the ends
which can be used to reflect an infrared beam through an ambient air sample many
times; a spectrometer can be used with such a system to detect trace pollutants at very
low levels.
Forced expiratory flow (FEF): Related to some portion of the forced vital capacity (FVC)
curve. Modifiers refer to the amount of the FVC already exhaled when the
measurement is made. For example:
FEF75% = Instantaneous forced exhaled flow after 75% of the forced vital capacity has
been exhaled.
FEF200-1200 = Mean forced expiratory flow between 200 mL and 1200 mL of the
forced vital capacity (formerly called the maximum expiratory flow rate [MEFR]).
FEF25-75% = Mean forced expiratory flow during the middle half of the forced vital
capacity (formerly called the maximum mid-expiratory flow rate [MMFR]).
FEF
capacity.
max = The maximal forced expiratory flow achieved during an forced vital
Forced expiratory volume (FEV): Denotes the volume of gas which is exhaled in a given time
interval from the beginning of the execution of a forced vital capacity. Conventionally,
the times used are 0.5, 0.75, or 1 sec, symbolized FEV0 5, FEV0 75, FEVj 0. These '
values are often expressed as a percent of the forced vital capacity; for example
(FEVj o/FVC) X 100.
Forced inspiratory vital capacity (FIVC): The maximal volume of air inspired with a
maximally forced effort from a position of maximal expiration.
Forced vital capacity (FVC): The maximum volume of air that can be forcibly expelled from
the lungs after the deepest inspiration.
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Fractional threshold concentration: The portion of the concentration at which an event or a
response begins to occur, expressed as a fraction.
Free radical: Any of a variety of highly-reactive atoms or molecules characterized by having
an unpaired electron.
Fritted bubbler: A porous glass device used in air pollutant sampling systems to introduce
small bubbles into solution.
Functional residual capacity (FRC): The volume of gas remaining in the lungs at the end of a
normal expiration. It is the sum of expiratory reserve volume and residual volume (see
Pulmonary measurements).
Gas chromatography (GC): A method of separating and analyzing mixtures of chemical
substances. A flow of gas causes the components of a mixture to migrate differentially
from a narrow starting zone in a special porous, insoluble sorptive medium. The
pattern formed by zones of separated pigments and of colorless substances in this
process is called a chromatogram, and can be analyzed to obtain the concentration of
identified pollutants.
Gas exchange: Movement of oxygen from the alveoli into the pulmonary capillary blood as
carbon dioxide enters the alveoli from the blood. In broader terms, the exchange of
gases between alveoli and lung capillaries.
Gas-liquid chromatography: A method of separating and analyzing volatile organic
compounds, in which a sample is vaporized and swept through a column filled with
solid support material covered with a nonvolatile liquid. Components of the sample can
be identified and their concentrations determined by analysis of the characteristics of
their retention in the column, since compounds have varying degrees of solubility in the
liquid medium.
Gas trapping: Trapping of gas behind small airways that were opened during inspiration but
closed during forceful expiration. It is a volume difference between forced vital
capacity and vital capacity.
Gastric juice: A thin watery digestive fluid secreted by glands in the mucous membrane of the
stomach.
Gastroenteritis: Inflammation of the mucous membrane of stomach and intestine.
Genotype: The type of genes possessed by an organism.
Geometric mean: An estimate of the average of a distribution. Specifically, the nth root of
the product of n observations.
Geometric standard deviation: A measure of variability of a distribution. It is the
antilogarithm of the standard deviation of the logarithms of the observations.
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Globulins (a, b, q): A family of proteins precipitated from plasma (or serum) by
half-saturation with ammonium sulfate, or separable by electrophoresis. The main
groups are the a, b, q fractions, differing with respect to associated lipids and
carbohydrates and in their content of antibodies (immunoglobulins).
Glomular nephrotic syndrome: Dysfunction of the kidneys characterized by excessive protein
loss in the urine, accumulation of body fluids and alteration in albumin/globulin ratio.
Glucose: A sugar which is a principal source of energy for man and other organisms.
Glucose-6-phosphatedehydrogenase: An enzyme (EC 1.1.1.49) catalyzing the
dehydrogenation of glucose-6-phosphate to 6-phospnogluconolactone.
Glutamic-oxaloacetic transaminase (SGOT): An enzyme (EC 2.6.1.1) whose serum level
increases in myocardial infarction and in diseases involving destruction of liver cells.
Also known as aspartate aminotransferase.
Glutamic-pyruvic transaminase (SGPT): Now known as alanine aminotransferase
(EC 2.6.1.2), the serum levels of this enzyme are used in liver function tests.
Glutathione (GSH): A tripeptide composed of glycine, cystine, and glutamic acid.
Glutathione peroxidase: An enzyme (EC 1.11.1) which catalyzes the destruction of
hydroperoxides formed from fatty acids and other substances. Protects tissues from
oxidative damage. It is a selenium-containing protein. ,
Glutathione reductase: The enzyme (EC 1.6.4.2) which reduces the oxidized form of
glutathione.
Glycolytic pathway: The biochemical pathway by which glucose is converted to lactic acid in
various tissues, yielding energy as a result.
Glycoside: A type of chemical compound formed from the condensation of a sugar with
another chemical radical via a hemiacetal linkage.
Goblet cells: Epithelial cells that have been distended with mucin and when this is discharged
as mucus, a goblet-shaped shell remains.
Golgi apparatus: A membrane system involved with secretory functions and transport in a
cell. Also known as a dictyosome.
Grana: The lamellar stacks of chlorophyll-containing material in plant chloroplasts.
Griege carpet: A carpet in its unfinished state (i.e., before it has been scoured and dyed).
The term also is used for woven fabrics in the unbleached and unfinished state.
Ground state: The state of minimum electronic energy of a molecule or atom.
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Guanylate cyclase (GC): An enzyme (EC 4.6.2.1) catalyzing the transformation of guanosine
triphosphate to guanosine 3':5'-cyclic phosphate.
H-Thymidine: Thymine deoxyribonucleoside: One of the four major nucleosides in DNA.
3H-thyrnidine has been uniformly labeled with tritium, a radioactive form of hydrogen.
Haze: Fine dust, smoke or fine vapor reducing transparency of air.
Hemagglutination: The agglutination of red blood cells. Can be used as a measurement of
antibody concentration. ^
Hematocrit: The percentage of the volume of a blood sample occupied by cells.
Hematology: The medical specialty that pertains to the blood and blood-forming tissues.
Hemochromatosis: A disease characterized by pigmentation of the skin possibly due to
inherited excessive absorption of iron.
Hemoglobin (Hb): The red, respiratory protein of the red blood cells, hemoglobin transports
oxygen from the lungs to the tissues as oxyhemoglobin (HbO^ and returns carbon
dioxide to the lungs as hemoglobin carbamate, completing the respiratory cycle.
Hemolysis: Alteration or destruction of red blood cells, causing hemoglobin to be released
into the medium in which the cells are suspended.
Hepatectomy: Complete removal of the liver in an experimental animal. ......
Hepatic: Relating to the liver.
Hepatocyte: A liver cell.
Heterogeneous process: A chemical reaction involving reactants of more than one phase or
state, such as one in which gases are absorbed into aerosol droplets, where the reaction
takes place.
Heterologous: A term referring to donor and recipient cellular elements from different
organisms, such as red blood cells from sheep and alveolar macrophage from rabbits.
Heterotrophs: Fungi and bacteria that rely on organic matter for their energy source.
Hexose monophosphate shunt: Also called the phosphogluconate oxidative pathway of glucose
metabolism which affords a total combustion of glucose independent of the citric acid
cycle. It is the important generator of NADPH necessary for synthesis of fatty acids
and the operation of various enzymes. It serves as a source of ribose and 4- and
7-carbon sugars.
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High volume (hi-vol) sampler: A high flow-rate device used to collect particles from the
atmosphere and to measure gravimetrically the concentration of particles across a broad
range of sizes in ambient air.
Histamine: A depressor amine derived from the amino acid histidine and found in all body
tissues, with the highest concentration in the lung; a powerful stimulant of gastric
secretion, a constrictor of bronchial smooth muscle, and a vasodilator that causes a fall
in blood pressure.
Homogenate: Commonly refers to tissue ground into a creamy consistency in which the cell
structure is disintegrated.
Host defense mechanism: Inherent means by which a biologic organism protects itself against
infection, such as antibody formation, macrophage action, ciliary action, etc.
Host resistance: The resistance exhibited by an organism, such as man, to an infecting agent,
such as a virus or bacteria.
Humoral: Relating to the extracellular fluids of the body, blood and lymph.
Hybrid: An organism descended from parents belonging to different varieties or species.
Hydrocarbons: A vast family of compounds containing carbon and hydrogen in various
combinations; found especially in fossil fuels. Some contribute to photochemical smog.
Hydrolysis: Decomposition involving splitting of a bond and addition of the H and OH parts
of water to the two sides of the split bond.
Hydrometeor: A product of the condensation of atmospheric water vapor (e.g., fog, rain,
hail, snow).
Hydroxyproline: An amino acid found among the hydrolysis products of collagen.
Hygroscopic: Pertaining to a marked ability to accelerate the condensation of water vapor.
Hygroscopic growth: Growth induced by moisture; often applied in reference to the growth in
size of inhaled particles within the respiratory tract in combination with resident
moisture.
Hyperplasia: Increase in the number of cells in a tissue or organ excluding tumor formation.
Hyperplastic: Relating to hyperplasia; an increase in the number of cells.
Hypertrophy: Increase in the size of a tissue element, excluding tumor formation.
Hypertension: Abnormally elevated blood pressure.
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Hypolimnia: Portions of a lake below the thermocline, in which water is stagnant and uniform
in temperature.
Hypoxia: A lower than normal amount of oxygen in the air, blood or tissues.
Immunoglobulin (Ig): A class of structurally related proteins consisting of two pairs of
polypeptide chains. Antibodies are Ig's and all Is's probably function as antibodies.
Immunoglobulin A (IgA): A type of antibody which comprises approximately 10 to 15% of
the total amount of antibodies present in normal serum.
Immunoglobulin G (IgG): A type of antibody which comprises approximately 80% of the
total amount of antibodies present in normal serum. Subtractions of IgG are fractions
Gi, and G2- ...-..,
Immunoglobulin M (IgM): A type of antibody which comprises approximately 5 to 10% of
the total amount of antibodies present in normal serum.
Impaction: An impinging or striking of one object against another; also, the force transmitted
by this act.
Impactor: An instrument which collects samples of suspended particulates by directing a
stream of the suspension against a surface, or into a liquid or a void.
Index of proliferation: Ratio of promonocytes to polymorphic monocytes in the blood.
Infarction: Sudden insufficiency of arterial or venous blood supply due to emboli, thrombi, or
pressure.
Infectivity model: A testing system in which the susceptibility of animals to airborne
infectious agents with and without exposure to air pollutants is investigated to produce
information related to the possible effects of the pollutant on man.
Inflorescence: The arrangement and development of flowers on an axis; also, a flower cluster
or a single flower.
Influenza A2/Taiwan Virus: An infectious-viral disease, believed to have originated in
Taiwan, characterized by sudden onset, chills, fevers, headache, and cough.
1 *3
Infrared: Light invisible to the human eye, between the wavelengths of 7 x 10"' and 10" m
(7,000 and 10,000,000 A).
Infrared laser: A device that utilizes the natural oscillations of atoms or molecules to generate
coherent electromagnetic radiation in the infrared region of the spectrum.
Infrared spectrometer: An instrument for measuring the relative amounts of radiant energy in
the infrared region of the spectrum as a function of wavelength.
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Ingestion: To take in for digestion.
In situ: In the natural or original position.
Instrumental averaging time: The time over which a single example or measurement is taken,
resulting in a measurement which is an average of the actual concentrations over that
period.
Insult: An injury or trauma.
Intercostal: Between the ribs, especially of a leaf.
Interferant: A substance which a measurement method cannot distinguish completely from the
one being measured, which therefore can cause some degree of false response or error.
Interferon: A macromolecular substance produced in response to infection with active or
inactivated virus, capable of inducing a state of resistance.
Intergranular corrosion: A type of corrosion which takes place at and adjacent to grain
boundaries, with relatively little corrosion of the grains.
Interstitial edema: An accumulation of an excessive amount of fluids in a space within tissues.
Interstitial pneumonia: A chronic inflammation of the interstitial tissue of the lung, resulting
in compression of air cells.
Intraluminal mucus: Mucus that collects within any tubule.
Intraperitoneal injection: An injection of material into the serous sac that lines the abdominal
cavity.
In utero: Within the womb; not yet born.
In vitro: Refers to experiments conducted outside the living organism.
In vivo: Refers to experiments conducted within the living organism.
Irradiation: Exposure to any form of radiation.
Ischemia: Local anemia due to mechanical obstruction (mainly arterial narrowing) of the
blood supply.
Isoenzymes: Also called isozymes. One of a group of enzymes that are very similar in
catalytic properties, but may be differentiated by variations in physical properties, such
as isoelectric point or electrophoretic mobility. Lactic acid dehydrogenase is an
example of an enzyme having many isomeric forms.
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Isopleth: A line on a map or chart connecting points of equal value.
Jacobs-Hochheiser method: The original Federal Reference Method for NO2 currently
unacceptable for air pollution work.
Klebsiella pneumoniae: A species of rod-shaped bacteria found in soil, water, and in the
intestinal tract or man and other animals. Certain types may be causative agents in
pneumonia. '
Kyphosis: An abnormal curvature of the spine, with convexity backward. . ..,, ,
Lactate: A salt or ester of lactic acid.
Lactic acid (lactate) dehydrogenase (LDH): An enzyme (EC 1.1.1.27) with many isomeric
forms which catalyzes the oxidation of lactate to pyruvate via transfer of H to NAD.
Isomeric forms of LDH in the blood are indicators of heart damage.
Lamellar bodies: Arranged in plates or scales. One of the characteristics of Type II alveolar
cells. :
Lavage fluid: Any fluid used to wash out hollow organs, such as the lung.
Leaching: The removal of elements from soil, litter, or plant foliage by water.
Lecithin: Any of several waxy hygroscopic phosphatides that are widely distributed in animals
and plants; they form colloidal solutions in water and have emulsifying, wetting and
hygroscopic properties.
Legume: A plant with root nodules containing nitrogen fixing bacteria.
Lesion: A wound, injury or other more or less circumscribed pathologic change in the tissues.
Leukocyte: Any of the white blood cells.
Lewis base: A base, defined hi the Lewis acid-base concept, is a substance that can donate an
electron pair.
Lichens: Perennial plants which are a combination of two plants, an alga and a fungus,
growing together in an association so intimate that they appear as one.
Ligand: Those molecules or anions attached to the central atom in a complex.
Light-fastness: The ability of a dye to maintain its original color under natural or indoor light.
Linolenic acid: An unsaturated fatty acid essential in nutrition.
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Lipase: An enzyme that accelerates the hydrolysis or synthesis of fats or the breakdown of
lipoproteins.
Lipids: A heterogeneous group of substances which occur widely in biological materials. They
are characterized as a group by their extractability in nonpolar organic solvents.
Lipofuscin: Brown pigment granules representing lipid-containing residues of lysosomal
digestion. Proposed to be an end product of lipid oxidation which accumulates in
tissue.
Lipoprotein: Complex or protein Containing lipid and protein.
Loading rate: The amount of a nutrient available to a unit area of body of water over a given
period of time.
Locomotor activity: Movement of an organism from one place to another of its own volition.
Long-pathlength infrared absorption: A measurement technique in which a system of mirrors
in a chamber is used to direct an infrared beam through a sample of air for a long
distance (up to 2 km); the amount of infrared absorbed is measured to obtain the
concentrations of pollutants present.
Lung compliance (CI): The volume change produced by an increase in a unit change in
pressure across the lung (i.e., between the pleura! surface and the mouth).
Lycra: A spandex textile fiber created by E. I. du Pont de Nemours & Co., Inc., with
excellent tensile strength, a long flex life and high resistance to abrasion and heat
degradation. Used in brassieres, foundation garments, surgical hosiery, swim suits, and
military and industrial uses.
Lymphocytes: White blood cells formed in lymphoid tissue throughout the body, they
comprise about 22 to 28% of the total number of leukocytes in the circulating blood and
function in immunity.
Lymphocytogram: The ratio, in the blood, of lymphocyte with narrow cytoplasm to those
with broad cytoplasm.
Lysosomes: Organelles found in cells of higher organisms that contain high concentrations of
degradative enzymes and are known to destroy foreign substances that cells engulf by
pinocytosis and phyocytosis. Believed to be a major site where proteins are broken
down.
Lysozymes: Lytic enzymes destructive to cell walls of certain bacteria. Present in some body
fluids, including tears and serum.
Macaca speciosa: A species of monkeys used in research.
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Macrophage: Any large, ameboid, phagocytic cell having a nucleus without many lobes,
regardless of origin.
Malaise: A feeling of general discomfort or uneasiness, often the first indication of an
infection or disease.
Malate dehydrogenase: An enzyme (EC 1.1.1.37) with at least six isomeric forms that
catalyze the dehydrogenation of malate to oxaloacetate or its decarboxylation (removal
of a CO2, group) to pyruvate. Malate, oxaloacetate, and pyruvate are intermediate
components of biochemical pathways.
Mannitol: An alcohol derived from reduction of the sugar, fructose. Used in renal function
testing to measure glomerular (capillary) filtration.
Manometer: An instrument for the measurement of pressure of gases or vapors.
Mass median diameter (MMD): Geometric median size of a distribution of particles based on
weight.
Mass spectrometry (MS): A procedure for identifying the various kinds of particles present in
a given substance, by ionizing the particles and subjecting a beam of the ionized
particles to an electric or magnetic field such that the field deflects the particles in
angles directly proportional to the masses of the particles.
Maximal expiratory flow Cv^^ x): Forced expiratory flow, related to the total lung capacity
or the actual volume of the lung at which the measurement is made. Modifiers refer to
the amount of lung volume remaining when the measurement is made. For example:
^max75% = Instantaneous forced expiratory flow when the lung is at 75% of its total
lung capacity.
'v'maxS 0 = Instantaneous forced expiratory flow when the lung volume is 3.0 L
Maximal expiratory flow rate (MEFR): Obsolete terminology. See FEF200_i2oo under
Forced expiratory flow.
Maximal mid-expiratory flow rate (MMFR or MMEF): Synonymous with FEF25_75%.
Maximal ventilation (max Vg): The volume of air breathed in 1 min during repetitive
maximal respiratory effort. Synonymous with maximum ventilatory minute volume.
Maximal voluntary ventilation (MW): The volume (L/min, DTPS) of air breathed by a
subject during voluntary maximum hyperventilation (rapid deep breathing) lasting a
specific period of time. Replaces maximal breathing capacity.
Mean (arithmetic): The sum of observations divided by sample size.
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Mechanical clearance: See Mucociliary action.
Median: A value in a collection of data values which is exceeded in magnitude by one-half
the entries in the collection.
MEFR: See FEF2oo-i200 under Forced.expiratory flow.
Mesoscale: Of or relating to meteorological phenomena from 1 to 100 kilometers in
horizontal extent.
Messenger RNA: A type of RNA which conveys genetic information encoded in the DNA to
'direct protein synthesis. :
Metaplasia: The abnormal transformation of an adult, fully differentiated tissue of one kind
into a differentiated tissue of another kind.
Metaproterenol: A bronchodilator used for the treatment of bronchial asthma. :
Metastases: The shifting of a disease from one part of the body to another; the appearance of
neoplasms in parts of the body remote from the seat of the primary tumor.'
Meteorology: The science that deals with the atmosphere and its phenomena. '
Methacholine: A parasympathomimetic bronchoconstrictor drug with similarities to carbachol
and acetylcholine. •"' "' , • •
Methemoglobin: A form of hemoglobin in which the normal reduced state of iron (Fe2+) has
been oxidized to Fe3+. It contains oxygen in firm union with ferric (Fe3+) iron and is
not capable of exchanging oxygen in normal respiratory processes.
Methimazole: An anti-thyroid drug similar in action to propylthiouracil.
Methyltransferase: Any enzyme transferring methyl groups from one compound to another.
Microcoulometric: Capable of measuring millionths of coulombs used in electrolysis of a
substance, to determine the amount of a substance in a sample.
Microflora: A small or strictly localized plant.
Micron: One-millionth of a meter.
Microphage: A small phagocyte; a polymorphonuclear leukocyte that is phagocytic.
Millimolar: One-thousandth of a molar solution. A solution of one^thousandth of a mole (in
grams) per liter.
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Mineral acid anion: An anion associated with strong, or mineral acids such as sulfuric, nitric,
or hydrochloric. These anions include NO3", SO42", and Cl1.
Minute ventilation C^E): See Pulmonary measurements.
Minute volume: The minute volume of breathing; a product of tidal volume times .the
respiratory frequency in one minute; synonymous with minute ventilation.
Mitochondria: Organelles of the cell cytoplasm which contain enzymes active in the
conservation of energy obtained in the aerobic part of the breakdown of carbohydrates
and fats, in a process called respiration. ,
MMFR: Maximal midexpiratory flow. See FEF25.75% under Forced expiratory flow.
Mobile sources: Automobiles, trucks and other pollution sources which are not fixed in one
location.
Modacrylic fiber: A manufactured fiber in which the fiber-forming substance is any long
chain synthetic polymer composed of less than 85% but at least 35% by weight of
acrylonitrite units.
Moeity: One of two or more parts into which something is divided.
Mole: The mass, in grams, numerically equal to the molecular weight of a substance.
Molecular correlation spectrometry: A spectrophotometric technique which is used to identify
unknown absorbing materials and measure their concentrations by using preset
wavelengths.
Molecular weight: The weight of one molecule of a substance obtained by adding the
gram-atomic weights of each of the individual atoms in the substance.
Monocyte: A relatively large mononuclear leukocyte, normally constituting 3 to 7% of the
leukocytes of the circulating blood.
Morbidity: The quantity or state of being diseased; also, used in reference to the ratio of the
number of sick individuals to the total population of a community (i.e., morbidity rate).
Mordant: A substance which acts to bind dyes to a textile fiber of fabric.
Morphological: Relating to the form and structure of an organism or any of its parts.
Morphology: Structure and form of an organism at any stage of its life history.
Morphometry: The quantitative measurement of structure (morphology).
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Mortality rate: For a given period of time, the ratio of the number of deaths occurring per
1,000 population. Also known as death rate.
Moving average: A procedure involving taking averages over a specific period prior to and
including a year in question, so that successive averaging periods overlap (e.g., a
three-year moving average would include data from 1967 through 1969 for the 1969
average and from 1968 through 1970 for 1970).
MSA: Metropolitan statistical area. .
Mucociliary action: Ciliary action of the mucous membranes lining respiratory tract airways
that aids in removing particles from the lungs.
Mucociliary clearance: Removal of materials from the upper respiratory tract via ciliary
action.
Mucociliary transport: The process by which mucus is transported, by ciliary action, from the
lungs.
Mucosa: The mucous membrane; it consists of epithelium, lamina propria and, in the
digestive tract, a layer of smooth muscle.
Mucous membrane: A membrane secreting mucus which lines passages and cavities
communicating with the exterior of the body.
i. . . -
Mucus: The clear, viscid secretion of mucous membranes, consisting of rrtucin, epithelial
cells, leukocytes, and various inorganic salts suspended in water.
Murine: Relating to mice.
Mutagen: A substance capable of causing, within an organism, biological changes that affect
potential offspring through genetic mutation.
Mutagenic: Having the power to cause mutations. A mutation is a change in the character of
a gene (a sequence of base pairs in DNA) that is perpetuated in subsequent divisions of
the cell in which it occurs.
Myocardial infarction: Infarction of any area of the heart muscle usually as a result of
occlusion of a coronary artery.
Mycorrhizae: Fungi that live in association with plant roots and assist in the uptake of water
and nutrients in exchange for carbohydrates.
Nares: The nostrils.
Nasopharyngeal: Relating to the nasal cavity and the pharynx (throat).
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National Air Surveillance Network (NASN): Network of monitoring stations for sampling air
to determine extent of air pollution; established jointly by federal and state
governments. ..
Near ultraviolet: Radiation of the wavelengths 2,000-4,000 Angstroms.
Necrosis: Death of cells that can discolor areas of a plant or kill the entire plant.
Necrotic: Pertaining to the pathologic death of one or more cells, or of a portion of tissue or
organ, resulting from irreversible damage.
Neonate: A newborn.
Neoplasm: An abnormal tissue that grows more rapidly than normal; synonymous with tumor.
Neoplasia: The pathologic process that results in the formation and growth of a tumor.
Neutrophil: A mature white blood cell formed in bone marrow and released into the
circulating blood, where it normally accounts for 54 to 65 % of the total number of
leukocytes.
Ninhydrin: An organic reagent used to identify amino acids.
Nitramine: A compound consisting of a nitrogen attached to the nitrogen of amine.
' ' . ;)
Nitrate: A salt or ester of nitric acid (NO3~).
Nitrification: The principal natural source of nitrate in which ammonium (NH4+) ions are
oxidized to nitrites by specialized microorganisms. Other organisms oxidize nitrites to
nitrates.
Nitrifiers: Soil microorganisms that convert NH4+ or organic N to NO3", a process referred
to as nitrification. Organisms that convert NH4+ to NO3" are referred to as autotrophic
nitrifiers, and organisms that convert organic N to NO3" are referred to as heterotrophic
nitrifiers.
Nitrite: A salt or ester of nitrous acid (NO2=).
Nitrocellulose: Any of several esters of nitric acid formed by its action on cellulose, used in
explosives, plastics, varnishes and rayon; also called cellulose nitrate.
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Nitrogen cycle: Refers to the complex pathways by which nitrogen-containing compounds are
moved from the atmosphere into organic life, into the soil, and back to the atmosphere.
Nitrogen fixation: The metabolic assimilation of atmospheric nitrogen by soil microorganisms,
which becomes available for plant use when the microorganisms die; also, industrial
conversion of free nitrogen into combined forms used in production of fertilizers and
other products.
Nitrogen oxide: A compound composed of only nitrogen and oxygen. Components of
photochemical smog.
Nitrogen saturation: A condition in which ecosystems are unable to accumulate anymore
nitrogen.
Nitrogen washout: The multiple breath curve obtained by plotting the fractional concentration
of nitrogen in expired alveolar gas vs. time, for a subject switched from breathing
ambient air to an inspired mixture of pure oxygen. A progressive decrease of nitrogen
concentration ensues which may be analyzed into two or more exponential components.
Nitrosamine: A compound consisting of a nitrosyl group connected to the nitrogen of an
amine.
Nitrosation: Addition of a nitrosyl group.
N-Nitroso compounds: Compounds carrying the functional nitrosyl group.
Nitrosyl: A group composed of one oxygen and one nitrogen atom (~N=0).
Nitrosylhemoglobin (NOHb): The red, respiratory protein of erythrocytes to which a nitrosyl
group is attached.
N/P Ratio: Ratio of nitrogen to phosphorous dissolved in lake water, important due to its
effect on plant growth.
Nucleolus: A small spherical mass of material within the substance of the nucleus of a cell.
Nucleophilic: Having an affinity for atomic nuclei; electron-donating.
Nucleoside: A compound that consists of a purine or pyrimidine base combined with
deoxyribose or ribose and found in RNA and DNA.
5'-Nucleotidase: An enzyme (EC 3.1.3.5) which hydrolyzes nucleoside 5'-phosphates into
phosphoric acid (H3PO4) and nucleosides.
Nucleotide: A compound consisting of a sugar (ribose or deoxyribose), a base (a purine or a
pyrimidine), and a phosphate; a basic structural unit of RNA and DNA.
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Nylon: A generic name chosen by E. I. du Pont de Nemours & Co., Inc. for a group of
protein-like chemical products classed as synthetic linear polymers; two main types are
Nylon 6 and Nylon 66.
Occlusion: A point which an opening is closed or obstructed.
Olefin: An open-chain hydrocarbon having at least one double bond.
Olfactory: Relating to the sense of smell.
Olfactory epithelium: The inner lining of the nose and mouth which contains neural tissue
sensitive to smell.
Oligotrophic: A body of water deficient in plant nutrients; also generally having abundant
dissolved oxygen and no marked stratification.
Oribitals: Areas of high electron density in an atom or molecule.
Orion: An acrylic fiber produced by E. I. du Pont de Nemours and Co., Inc., based on a
polymer of acrylonitrite;.used extensively for outdoor uses, it is resistant to chemicals
and withstands high temperatures.
Oronasal breathing: Breathing through the nose and mouth simultaneously; typical human
breathing pattern at moderate to high levels of exercise versus normally predominant
nasal breathing while at rest.
Osteogenic osteosarcoma: The most common and malignant of bone sarcomas (tumors). It
arises from bone-forming cells and affects chiefly the ends of long bones.
Ovarian primordial follicle: A spheroidal cell aggregation in the ovary in which the
primordial oocyte (immature female sex cell) is surrounded by a single layer of flattened
follicular cells.
Oxidant: A chemical compound which has the ability to remove electrons from another
chemical species, thereby oxidizing it; also, a substance containing oxygen which reacts
in air to produce a new substance, or one formed by the action of sunlight on oxides of
nitrogen and hydrocarbons.
Oxidation: An ion or molecule undergoes oxidation by donating electrons.
Oxidative deamination: Removal of the NH2 group from an amino compound by reaction
with oxygen.
Oxidative phosphorylation: The mitochondrial process by which "high-energy" phosphate
bonds form from the energy released as a result of the oxidation of various substrates.
Principally occurs in the tricarboxylic acid pathway.
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Oxyhemoglobin: Hemoglobin in combination with oxygen. It is the form of hemoglobin
present in arterial blood.
Ozone layer: A layer of the stratosphere from 20 to 50 km above the earth's surface
characterized by high ozone content produced by ultraviolet radiation.
Ozone scavenging: Removal of O3 from ambient air or plumes by reaction with NO,
producing NO2 and O2.
Paired electrons: Electrons having opposite intrinsic spins about their own axes.
Parenchyma: The essential and distinctive tissue of an organ or an abnormal growth, as
distinguished from its supportive framework.
Parenchymal: Referring to the distinguishing or specific cells of a gland or organ.
Partial pressure: The pressure exerted by a single component in a mixture of gases.
Particle: Any object, solid or liquid, having definite physical boundaries in all directions;
includes, for example, fine solid particles such as dust, smoke, fumes, or smog, found
in the air or in emissions.
Particulate matter (PMX): Matter in the form of small airborne liquid or solid particles,
subscript "x" indicates the particulate mean aerodynamic diameter.
Particulates: Fine liquid or solid particles such as dust, smoke, mist, fumes or smog, found in
the air or in emissions.
Pascal: A unit of pressure in the International System of Units. One pascal is equal to
7.4 x 10"3 torr. The pascal is equivalent to one newton per square meter.
Pathogen: Any virus, microorganism, or other substance causing disease.
Pathophysiological: Derangement of function seen in disease; alteration in function as
distinguished from structural defects.
Peak expiratory flow (PEF): The highest forced expiratory flow measured with a peak flow
meter.
Peptide bond: The bond formed when two amino acids react with each other.
Percentiles: The percentage of all observations exceeding or preceding some point; thus, 90th
percentile is a level below which will fall 90% of the observations.
Perennial: Trees and other plants that live more than one year are called perennials.
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Perfusate: A liquid, solution or colloidal suspension that has been passed over a special
surface or through an appropriate structure.
Perfusion: Artificial passage of fluid through blood vessels.
Permanent-press fabrics: Fabrics in which applied resins contribute to the easy care and
appearance of the fabric and to the crease and seam flatness by reacting with the
cellulose on pressing after garment manufacture.
Permeation tube: A tube which is selectively porous to specific gases.
Peroxidation: Refers to the process by which certain organic compounds are converted to '
peroxides.
Peroxyacetyl nitrate (PAN): Pollutant created by action of sunlight on hydrocarbons and NOX
in the air; an ingredient of photochemical smog.
pH: A measure of the effective acidity or alkalinity of a solution. It is expressed as the
negative logarithm of the hydrogen-ion concentration. Pure water has a hydrogen ion
concentration equal to 10~' M/L at standard conditions (25°C). The negative
logarithm of this quantity is 7. Thus, pure water has a pH value of 7 (neutral). The
pH scale is usually considered as extending from 0 to 14. A pH less than 7 denotes
acidity; more than 7 denotes alkalinity.
Phagocytosis: A mechanism by which alveolar macrophages and polymorphonuclear
leukocytes engulf particles; one of several lung defense mechanisms by which foreign
agents (biological and nonbiological) are removed from the respiratory tract.
Phenotype: The observable characteristics of an organism, resulting from the interaction
between an individual genetic structure and the environment in which development takes
place.
Phenylthiourea: A crystalline compound, C7H8N2S, that is bitter or tasteless depending on a
single dominant gene in the tester.
Phlegm: Viscid mucus secreted in abnormal quantity in the respiratory passages.
Phosphatase: Any of a group of enzymes that liberate inorganic phosphate from phosphoric
esters (E.G. sub-subclass 3.1.3).
Phosphocreatine Mnase: An enzyme (EC 2.7.3.2) catalyzing the formation of creatine and
ATP, its breakdown is a source of energy in the contraction of muscle; also called
creatine phosphate.
Phospholipid: A molecule consisting of lipid and phosphoric acid group(s). An example is
lecithin. Serves as an important structural factor in biological membranes.
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Photochemical oxidants: Primary ozone, NO2, PAN with lesser amounts of, other compounds
formed as products of atmospheric reactions involving organic pollutants, nitrogen
oxides, oxygen, and sunlight.
Photochemical smog: Air pollution caused by chemical reaction of various airborne chemicals
in sunlight, ,
Photodissociation: The process by which a chemical compound breaks down into simpler
components under the influence of sunlight or other radiant energy.
Photolysis: Decomposition upon irradiation by sunlight.
Photomultiplier tube: An electron multiplier in which electrons released by photoelectric
emission are multiplied in successive stages by dynodes that produce secondary
emissions.
Photon: A quantum of electromagnetic energy.
Photostationary: A substance or reaction which reaches and maintains a steady state in the
presence of light. , . , .
Photosynthesis: The process in which green parts of plants, when exposed to light under
suitable conditions of temperature and water supply, produce carbohydrates using
atmospheric carbon dioxide and releasing oxygen.
: > v .- > •
Phyllosphere: Usually refers to the leaf surface of plants.
Phytotoxic: Poisonous to plants.
Phytoplankton: Minute aquatic plant life.
P,i (II) bonds: Bonds in which electron density is not symmetrical about a line joining the
bonded atoms.
Pinocytotic: Refers to the cellular process (pinocytosis) in which the cytoplasmic membrane '
forms imaginations in the form of narrow channels leading into the cell. Liquids can
flow into these channels and the membrane pinches off pockets that are incorporated
into the cytoplasm and digested.
Pitting: A form of extremely localized corrosion that results in holes in the metal. One of the
most destructive forms of corrosion.
Pituary: A stalk-like gland near the base of the brain which is attached to the hypothalmus.
The anterior portion is a major repository for hormones that control growth, stimulate
other glands, and regulate the reproductive cycle.
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Placenta: The organ in the uterus that provides metabolic interchange between the fetus and
mother.
Plasmid: Replicating unit, other than a nucleus gene, that contains nucieoprotein and is
involved in various aspects of metabolism in organisms; also called paragenes.
Plasmolysis: The dissolution of cellular components, or the shrinking of plant cells by osmotic
loss of cytoplasmic water.
Plastic: A plastic is one of a large group of organic compounds synthesized from cellulose,
hydrocarbons, proteins or resins and capable of being cast, extruded, or molded into ;
various shapes.
Plasticizer: A chemical added to plastics to soften, increase malleability or to make more
readily deformable.
Platelet (blood): An irregularly-shaped disk with no definite nucleus; about one-third to one-
half the size of an erythrocyte and containing no hemoglobin. Platelets are more
numerous than leukocytes, numbering from 200,000 to 300,000 per cu. mm. of blood.
Plethysmograph: A device for measuring and recording changes in volume of a part, organ or
the whole body; a body plethysmograph is a chamber apparatus surrounding the entire
body.
Pleura: The serous membrane enveloping the lungs an lining the walls of the chest cavity.
Plume: Emission from a flue or chimney, usually distributed stream-like downwind of the
source, which can be distinguished from the surrounding air by appearance or chemical
characteristics.
Pneumonia (interstitial): A chronic inflammation of the interstitial tissue of the lung, resulting
in compression of the air cells. An acute, infectious disease.
Pneumonocytes: A nonspecific term sometimes used in referring to types of cells
characteristic of the respiratory part of the lung.
Podzol: Any of a group of zonal soils that develop in a moist climate, especially under
coniferous or mixed forest.
Point source: A single stationary location of pollutant discharge.
Polarography: A method of quantitative or qualitative analysis based on current-voltage curves
obtained by electrolysis of a solution with steadily increasing voltage.
Pollution gradient: A series of exposure situations in which pollutant concentrations range
from high to low.
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Polyacrylonitrile: A polymer made by reacting ethylene oxide and hydrocyanic acid. Dynel
and Orion are examples.
Polyamides: Polymerization products of chemical compounds which contain amino (-NH2)
and carboxyl (-COOH) groups. Condensation reactions between the groups form
amides (-CONH2). Nylon is an example of a polyamide.
Polycarbonate: Any of various tough transparent thermoplastics characterized by high impact
strength and high softening temperature.
Polycythemia: An increase above the normal in the number of red cells in the blood.
Polyester fiber: A man-made or manufactured fiber in which the fiber-forming substance is
any long-chain,synthetic polymer composed of at least 85% by weight of an ester of a
dihydric alcohol and terephthalic acid. Dacron is an example.
Polymer: A large molecule produced by linking together many like molecules.
Polymerization: In fiber manufacture, converting a chemical monomer (simple molecule) into
a fiber-forming material by joining many like molecules into a stable, long-chain
structure. • . - . .
Polymorphic monocyte: Type of leukocyte with a multi-lobed nucleus.
Polymorphonuclear leukocytes: Cells which represent a secondary nonspecific cellular defense
mechanism. They are transported to the lungs from the bloodstream when the burden
handled by the alveolar macrophages is too large.
Polysaccharides: Polymers made up of sugars. An example is glycogen which consists of
repeating units of glucose.
Polystyrene: A thermoplastic plastic which may be transparent, opaque, or translucent. It is
light in weight, tasteless and odorless, it also is resistant to ordinary chemicals.
Polyurethane: Any of various polymers that contain NHCOO linkages and are used especially
in flexible and rigid foams, elastomers and resins.
Pores of Kohn: Also known as interalveolar pores; pores between air cells. Assumed to be
pathways for collateral ventilation.
Precipitation: Any of the various forms of water particles that fall from the atmosphere to the
ground, rain, snow, etc.
Precursor: A substance from which another substance is formed; specifically, one of the
anthropogenic or natural emissions or atmospheric constituents which reacts under
sunlight to form secondary pollutants comprising photochemical smog.
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Probe: In air pollution sampling, the tube or other conduit extending into the atmosphere to
be sampled, through which the sample passes to treatment, storage and/or analytical
equipment.
Proline: An amino acid, C5H9NO2, that can be synthesized from glutamate by animals.
Promonocyte: An immature monocyte not normally seen in the circulating blood.
Proteinuria: The presence of more than 0.3 gm of urinary protein in a 24-hour urine
collection.
Pulmonary: Relating to the lungs.
Pulmonary edema: An accumulation of excessive amounts of fluid in the lungs.
Pulmonary lumen: The spaces in the interior of the tubular elements of the lung (bronchioles
and alveolar ducts).
Pulmonary measurements: Measurements of the volume of air moved during a normal or
forced inspiration or expiration. Specific lung volume measurements are defined
independently.
Lung volume measurements = Tidal volume, inspiratory reserve volume, expiratory
reserve volume, residual volume (four basic independent volumes).
Capacities = Combinations of basic volumes.
Total lung capacity (TLC) = Tidal volume + inspiratory reserve volume + expiratory
reserve volume + residual volume; the volume of gas in the lungs at the time of
maximal inspiration or the sum of all volume compartments. The method of
measurement should be indicated, as with residual volume.
Vital capacity (VC) = Tidal volume + inspiratory reserve volume + expiratory reserve
volume; the greatest volume of gas that can be expelled by voluntary effort after
maximal inspiration. Also forced vital capacity and forced inspiratory vital capacity.
Functional residual capacity (FRC) = Residual volume + expiratory reserve volume;
the volume of gas remaining in the lungs at the resting, end-tidal expiratory position.
Equivalent to the sum of residual volume and expiratory reserve volume. The method
of measurement should be indicated as with residual volume.
Inspiratory capacity (1C) = Tidal volume + inspiratory reserve volume.
Inspiratory vital capacity (IVC) = The maximal, volume that can be inspired from the
resting end-expiratory position; also forced inspiratory vital capacity.
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Expiratory reserve volume (ERV) = The maximal that can be exhaled from the resting
end-tidal expiratory position. See also Functional residual capacity.
Residual volume (RV) = That volume of air remaining in the lungs after maximal
exhalation. The method of measurement should be indicated in the text or, when
necessary, by appropriate qualifying symbols.
Residual volume (RV) = Total lung capacity ratio (RV/TLC) = expresses the
percentage of the total lung capacity occupied by residual volume; varies somewhat with
age but ordinarily should be no more than 20 to 30%.
Tidal volume = That volume of air inhaled or exhaled with each breath during quiet
breathing, used only to indicate a subdivision of lung volume. When tidal volume is
used in gas exchange formulations, the symbol VT should be used.
Minute ventilation (MV) = The volume of gas exchanged per minute at rest or during
any stated activity; it is the tidal volume times the number of respirations per minute.
See Ventilation.
Pulmonary resistance: Sum of airway resistance and viscous tissue resistance.
Purine bases: Organic bases which are constituents of DNA and RNA, including adenine and
guanine. ,
Purulent: Containing or forming pus.
Pyrimidine bases: Organic bases found in DNA and RNA. Cytosine and thymine occur in
DNA and cytosine and uracil are found in RNA.
QRS: Graphical representation on the electrocardiogram of a complex of three distinct waves
which represent the beginning of ventricular contraction.
Quasistatic compliance: Time dependent component of elasticity; compliance is the reciprocal
of elasticity. - :
Rainout: Removal of particles and/or gases from the atmosphere by their involvement in
cloud formation (particles act as condensation nuclei, gases are absorbed by cloud
droplets), with subsequent precipitation.
Rayleigh scattering: Coherent scattering in which the intensity of the light of wavelength X,
scattered in any direction making an angle with the incident direction, is directly
proportional to 1 + cos2 and inversely proportional to X4.
Reactive dyes: Dyes which react chemically with cellulose in fibers under alkaline conditions.
Also called fiber reactive or chemically reactive dyes.
Reduction: Acceptance of electrons by an ion or molecule.
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Reference method (RM): For NO2, an EPA-approved gas-phase chemiluminescent analyzer
and associated calibration techniques; regulatory specifications are described in Title 40,
Code of Federal Regulations, Part 50, Appendix F. Formerly, Federal Reference
Method. ...-.-
Residual capacity: The volume of air remaining in the lungs after a maximum expiratory
effort; same as residual volume. -, •...-.•
Residual volume (RV): The volume of air remaining in the lungs after a maximal expiration.
RV = TLC-VC
Resin: Any of various solid or semi-solid amorphous natural organic substances, usually
derived from plant secretions, which are soluble in organic solvents but not in water;
also any of many synthetic substances with similar properties used in finishing fabrics,
for permanent press shrinkage control or water repellency.
Resistance flow (R): The ratio of the flow-resistive components of pressure to simultaneous
flow, in centimeters of H^O/L per sec. Flow-resistive components of pressure are
obtained by subtracting any elastic or inertial components, proportional respectively to
volume and volume acceleration. Most flow resistances in the respiratory system are
nonlinear, varying with the magnitude and direction of flow, with lung volume and lung
volume history, and possibly with volume acceleration. Accordingly, careful ,
specification of the conditions of measurement is necessary; see Airway resistance and
Total pulmonary resistance.
Ribosomal RNA: The most abundant RNA in a cell and an integral constituent of ribosomes.,
Ribosomes: Discrete units of RNA and protein which are instrumental in the synthesis of
proteins in a cell. Aggregates are called polysomes.
Runoff: Water from precipitation, irrigation or other sources that flows over the ground
surface to streams.
Sclerosis: Pathological hardening of tissue, especially from overgrowth of fibrous tissue or
increase in interstitial tissue.
Secondary particles (or secondary aerosols): Dispersion aerosols that form in the atmosphere
as a result of chemical reactions, often involving gases.
Selective leaching: The removal of one element from a solid alloy by corrosion processes.
Septa: A thin wall dividing two cavities or masses of softer tissue.
Seromucoid: Pertaining to a mixture of watery and mucinous material such as that of certain
glands.
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Serum antiprotease: A substance, present in serum, that inhibits the activity of prbteinases
(enzymes which' destroy proteins).
Sigma (s) bonds: Bonds in which electron density is symmetrical about a line joining the
bonded atoms.
Silo-filler's disease: Pulmonary lesion produced by oxides of nitrogen produced by fresh
silage.
Single breath nitrogen elimination rate: Percentage rise in nitrogen fraction per unit of volume
expired.
Single breath nitrogen technique: A procedure in which a vital capacity inspiration, of
' 100% oxygen is followed by examination of nitrogen in the vital capacity expired.
Singlet state: The highly-reactive energy state of an atom in which certain electrons have
unpaired spins. .
Sink: A reactant with or absorber of a substance. •
Sodium'arsenite: Na3AsO3, used with sodium hydroxide in the absorbing solution of a
24-hour integrated manual method for NO2.
Sodium dithionite: A strong reducing agent (a supplier of electrons).
Sodium metabisulfite: Na2S2O5, used in absorbing solutions of NO2 analysis methods.
Sorb: To take up and hold by absorption or adsorption.
' ' .
Sorbent: A substance that takes up and holds another by absorption or adsorption.
Sorbitol dehydrogenase: An enzyme that interconverts the sugars, sorbitol and fructose.
Sorption: The process of being sorbed.
Spandex: A manufactured fiber in which the fiber forming substance is a long chain synthetic
elastomer composed of at least 85% of a segmented polyurethane.
Specific airway conductance (SGaw): Airway conductance divided by the lung volume at
which it was measured; that is, normalized airway conductance. Airway conductance
(Gaw)/thoracic gas volume (TGV).
I • ' L
Specific airway resistance (SRaw): Airway resistance multiplied by the volume at which it was
measured. SRaw = airway conductance (Raw) x thoracic gas volume (TGV); liter (L) x
centimeter of water per liter per. second (cm H2O/L/S).
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Spectrometer: An instrument used to measure radiation spectra or to determine wavelengths of
the various radiations.
Spectrophotometry: A technique in which visible, UV, or infrared radiation is passed through
a substance or solution and the intensity of light transmitted at various wavelengths is
measured to determine the spectrum of light absorbed.
Spectroscopy: Use of the spectrometer to determine concentrations of an air pollutant.
Spermatocytes: A cell destined to give rise to spermatozoa (sperm).
Sphingomyelins: A group of phospholipids found in brain, spinal cord, kidney and egg yolk.
Sphygomenometer: An apparatus, consisting of a cuff and a pressure gauge, which is used to
measure blood pressure.
Spirometer: A mechanical device, including bellows or other sealed, moving parts, which
collects and stores gases and provides a graphical record of lung volume changes over
time. See Breathing pattern and Respiratory cycle.
Spirometry: The measurement, by a form of gas meter (spirometer), of volumes of air that
can be moved in and out of the lungs. •
Spleen: A large vascular organ located on the upper left side of the abdominal cavity. It is a
blood-forming organ in early life. It is a storage organ for red corpuscles and because
of the large number of macrophages, acts as a blood filter. '
Sputum: Expectorated matter, especially mucus or mucopurulent matter expectorated in
diseases of the air passages. '
Squamous: Scale-like, scaly.
Standard deviation: Measure of the dispersion of values about a mean value. It is calculated
as the positive square root of the average of the squares of the individual deviations
from the mean.
Standard temperature and pressure: 0°C, 760 mm mercury.
Staphylococcus aureus: A spherically-shaped, infectious species of bacteria found especially
on nasal mucous membrane and skin.
Static lung compliance (0^^): Measure of lung's elastic recoil (volume change resulting
from change in pressure) with no or insignificant airflow.
Steady state exposure: Exposure to air pollutants whose concentration remains constant for a
period of time. 'IT'*•
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Steroids: A large family of chemical substances comprising many hormones .and vitamins and
having large ring structures.
Stilbene: An aromatic hydrocarbon C14H12 used as a phosphor and in making dyes.
Stoichiometric factor: Used to express the conversion efficiency of a nonquantitative reaction,
such as the reaction of NO2 with azo dyes in air monitoring methods.
Stoma: A minute opening or pore (plural is stomata).
STPD conditions: Standard temperature and pressure, dry. These are the conditions of a
volume of gas at 0°C, at 760 torr, without water vapor. A STPD volume of a given
gas contains a known number of moles of that gas.
Stratosphere: That region of the atmosphere extending from 11 km above the surface of the
earth to 50 km. At 50 km above the earth temperature rises to a maximum of 0°C.
Streptococcus pyogenes: A species of bacteria found.in the human mouth, throat and-
respiratory tract and in inflammatory exudates, blood stream, and lesions in human
diseases. It causes formation of pus or even fatal septicemias.
Stress corrosion cracking: Cracking caused by simultaneous presence of tensile stress and a
specific corrosive medium. The metal or alloy is virtually unattached over most of its
surface, while fine cracks progress through it. •'.•..
Strong interactions: Forces or bond energies holding molecules together. Thermal energy will
not disrupt the formed bonds.
Sublobular hepatic necrosis: The pathologic death of one or more cells, or of a portion of the
liver, beneath one or more lobes.
Succession: The progressive natural development of vegetation towards a climax, during
which one community is gradually replaced by others. , .
Succinate: A salt of succinic acid involved in energy production in the citric acid cycle.
Sulfadiazine: One of a group of sulfa drugs. Highly effective against pneumococcal,
staphlococcal, and streptococcal infections.
Sulfamethazine: An antibacterial agent of the sulfonamide group, active against homolytic
streptococci, staphytococci, pneumococci and meningococci.
Sulfanilimide: A crystalline sulfonamide (C6H8N2O2S), the amide of sulfanilic acid and
parent compound of most sulfa drugs.
Sulfhydryl group: A chemical radical consisting of sulfur and hydrogen which confers
reducing potential to the chemical compound to which it is attached (-SH).
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Sulfur dioxide (SO^: Colorless gas with pungent odor released primarily from burning of
fossil fuels, such as coal, containing sulfur.
Sulfur dyes: Used only on vegetable fibers, such as cottons. They are insoluble in water and
must be converted chemically in order to be soluble. They are resistant (fast) to alkalies
and washing and fairly fast to sunlight.
Supernatant: The clear or partially clear liquid layer which separates from the homogenate
upon centrifugation or standing.
Surfactant: A substance capable of altering the physiochemical nature of surfaces, such as one
used to reduce surface tension of a liquid.
Symbiotic: A close association between two organisms of different species in which at least
one of the two benefits.
Synergistic: A relationship in which the combined action or effect of two or more components
is greater than that of the components acting separately.
Systolic: Relating to the rhythmical contraction of the heart.
Tachypnea: Very rapid breathing.
Terragram (Tg): One million metric tons, 1012 grams.
Teratogenesis: The disturbed growth processes resulting in a deformed fetus.
Teratogenic: Causing or relating to abnormal development of the fetus.
Threshold: The level at which a physiological or psychological effect begins to be produced.
Thylakoid: A membranous lamella of protein and lipid in plant chloroplasts where the
photochemical reactions of photosynthesis take place. :
Thymidine: A nucleoside (CjQHj^^C^) that is composed of thy mine and deoxyribose; occurs
as a structural part of DNA. :..-.'-.>,
Tidal volume (VT): The volume of air that is inspired or expired in a single breath during
regular breathing.
Titer: The standard of strength of a volumetric test solution. For example, the titration of a
volume of antibody-containing serum with another volume containing virus.
Tocopherol: a-d-Tocopherol is one form of Vitamin E prepared synthetically. The a form
exhibits the most biological activity. It is an antioxidant and retards rancidity of fats.
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Torn A unit of pressure sufficient to support a 1 mm column of mercury; 760 torr =
1 atmosphere. -
Total lung capacity (TLC): The sum of all the compartments of the lung, or the volume of air
in the lungs at maximum inspiration.
Total pulmonary resistance (RL): Resistance measured by relating flow-dependent
transpulmonary pressure to airflow at the mouth. Represents the total (factional)
resistance of the lung tissue (R^) and the airways (Raw). RL = R +
a\v
Total suspended particulates (TSP): Solid and liquid particles present in the atmosphere.
Trachea: Commonly known as the windpipe, a cartilaginous air tube extending from the
larnyx (voice box) into the thorax (chest) where it divides, serving as the entrance to
each of the lungs.
Tracheobronchial region: The area encompassed by the trachea to the gas exchange region of
the lung; the conducting airways. ..'-•..
Transaminase: Aminotransferase; an enzyme transferring an amino,group from an a-amino
acid to the carbonyl carbon atom of an a-keto acid.
Transmissivity (UV): The percent of ultraviolet radiation passing through a medium.
Transmittance: The fraction of the radiant energy entering an absorbing layer which reaches
the layer's further boundary.
Transpiration: The process of the loss of water vapor from plants.
Triethanolamine: An amine, (HOCH2CH2)3N, used in the absorbing solution of one analytical
method for NO2.
Troposphere: That portion of the atmosphere in which temperature decreases rapidly with
altitude, clouds form, and mixing of air masses by convection takes place. Generally
extends to about 7 to 10 miles above the earth's surface.
Type 1 cells: Thin, alveolar surface, epithelial cells across which gas exchange occurs.
Type 2 cells: Thicker, alveolar surface, epithelial cells that produce surfactant and serve as
progenitor cells for Type 1 cell replacement.
Ultraviolet: Light invisible to the human eye of wavelengths between 4 x 1(T7 and 5 x 10~9 m
(4,000 to '50A).
Urea-formaldehyde resin: A compound composed of urea and formaldehyde in an '
arrangement that conveys thermosetting properties. ;
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Urobilinogen: One of the products of destruction of blood cells; found in the liver, intestines
and urine. .
Uterus: The womb; the hollow muscular organ in which the impregnated ovum (egg)
develops into the fetus.
Vacuole: A minute space in any tissue.
Vagal: Refers to the vagus nerve. This mixed nerve arises near the medulla oblongata and
passes down from the cranial cavity to supply the larynx, lungs, heart, esophagus,
stomach, and most of the abdominal viscera.
Valence: The number of electrons capable of being bonded or donated by an atom during
bonding.
Van Slyke reactions: Reaction of primary amines, including amino acids, with nitrous acid,
yielding molecular nitrogen.
Variance: A measure of dispersion or variation of a sample from its expected value; it is
usually calculated as the square root a sum of squared deviations about a mean divided
by the sample size.
Vat dyes: Dyes which have a high degree of resistance to fading by light, NOX and washing.
Widely used on cotton and viscose rayon. Colors are brilliant and of almost any shade.
The name was originally derived from their application in a vat.
Venezuelan equine encephalomyelitis: A form of equine encephalomyelitis found in parts of
South America, Panama, Trinidad, and the United States, and caused by a virus.
Fever, diarrhea, and depression are common. In man, there is fever and severe
headache after an incubation period of 2 to 5 days.
Ventilation: Physiological process by which gas is exchanged between the outside air and the
lungs. The word ventilation sometimes designates ventilatory flow rate (or ventilatory
minute volume), which is the product of the tidal volume by the ventilatory frequency.
Conditions are usually indicated as modifiers; for example: ,
VE = Expired volume per minute (L/min, BTPS),
Vj = Inspired volume per minute (L/min, BTPS).
Ventilation is often referred to as "total ventilation" to distinguish it from "alveolar
ventilation" (see Ventilation, alveolar). : .
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Ventilation, alveolar (V^)1 The portion of the total ventilation that is involved in gas
exchange with the blood; alveolar ventilation is less than total ventilation because when
a tidal volume of gas leaves the alveolar spaces, the last part does not get expelled from
the body but occupies the dead space, to be reinspired with the next inspiration. Thus
the volume of alveolar gas actually expelled completely is equal to the tidal volume
minus the volume of the dead space. This truly complete expiration volume times the
ventilatory frequency constitutes the alveolar ventilation.
Ventilation, dead-space (VD): Ventilation per minute of the physiologic dead space (volume
of gas not involved in gas exchange with the blood), BTPS, defined by the following
equation: :
VD = VE(PaCO2 - PECO2)/(PaCO2 - PTCO2)
Ventilation/perfusion ratio (^A/Q): Ratio of the alveolar ventilation to the blood perfusion
volume flow through the pulmonary parenchyma, such as, pulmonary blood flow or
right heart cardia output; this ratio is a fundamental determinant of the oxygen and
carbon dioxide pressure of the alveolar gas and of the end-capillary blood. Throughout
the lungs the local ventilation/perfusion ratios vary, and, consequently, the local
alveolar gas and end-capillary blood compositions also vary. ,
Villus: A projection from the surface, especially of a mucous membrane.
Vinyl chloride: A gaseous chemical suspected of causing at least one type of cancer. It is
used primarily in the manufacture of polyvinyl chloride, a plastic.
Viscose ,rayon: Filaments of regenerated cellulose coagulated from a solution of cellulose
xanthate. Raw materials can be cotton linters or chips of spruce, pine, or hemlock.
Visible region: Light between the wavelengths of 4,000-8,000 A.
Visual range: The distance at which an object can be distinguished from background.
Vital capacity (VC): The greatest volume of air that can be exhaled from the lungs after a
maximum inspiration (see Pulmonary measurements).
Vitamin E: Any of several fat-soluble vitamins (tocopherols), essential in nutrition of various
vertebrates.
Washout: The capture of gases and particles by falling raindrops.
Weak interactions: Forces, electrostatic in nature, which bind atoms and/or molecules to each
other. Thermal energy will disrupt the interaction. Also called van der Waal's forces.
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Weathering: In this context, weathering refers to the releases of base cations from soil
minerals to cationic forms which can be taken up by plants, leached, or absorbed to
cation exchange sites.
Wet deposition: The process by which atmospheric substances are returned to earth in the
form of rain or other precipitation.
Wheat germ lipase: An enzyme, obtained from wheat germ, which is capable of cleaving a
fatty acid from a neutral fat; a lipolytic enzyme.
X-ray fluorescence spectrometry: A nondestructive technique which utilizes the principle that
every element emits characteristic x-ray emissions when excited by high-energy
radiation.
Zeolites: Hydrous silicates analogous to feldspars, occurring in lavas and various soils.
Zooplankton: Minute animal life floating or swimming weakly in a body of water.
*U.S. GOVERNMENT PRINTING OFFICE: 1W2-64S-003/40672
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