-------
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cr
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centratic
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averaging
time
O 0
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odd
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ro 01 <
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ss =
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ro 01 < o
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_C T3 C >>
00 -H « <
6-28
-------
CM CM
0 0
d d
en *
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d d
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o o
d d
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d d
3- -*
CM CM
d d
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m
d
so en
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in "tf1
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CM
f-
i
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en
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lyr
Pasadena 64
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£ $ CM ~ 0
ooooo
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Tt" CM -H O O
OOOOO
« oo oo ON in
3- CM i O O
OOOOO
7
CO
Determined by continuous Grie
6-29
-------
8-
w \0
v-i o\
a -
d S
w
O
O
O
c«
z2
ii O\
f) ~*
15
H Z
< W
Z W I
w otf -S
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is
u %
1/5 ,
w w
§1
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B|
z^
2"
s
o
Os
O
0 ^
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% °
0
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a- f
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C2
^O
2 o
e
H
o
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1
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^^ o
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d
c-
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3 \0
03
^
en
Place, site No.,
averaging
time
ooop
dddd
en sfr "^ ^O
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o o o o o
o o o o o
oo oo oo t^
o p o p
d d d o
fS i-i O 00
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odd
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10
d
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p o o o
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p o -^ i oooo oooo
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c.go^oc, -«^;^- SSSSS
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SSSPi?3 SS3£8:S ££££2
-^ o o
6-30
-------
Sin
0
d d
OO 00
O 0
d d
CN ro
O 0
ON ON
d d
r- m
ro ro
d d
r- ON
NO in
d d
ro oo
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d d
ON
> 0 c
Sis;.]
i-H * 1 » 1 C
C
a
ro ^f m
O O O
odd
NO r oo
o o o
odd
00 ON O
0 0 -H
o o o
CN CN ro
odd
CN ON 00
CN -H -!
odd
m f- oo
>§
~H ^H g
£
Sm NO
O O
odd
P- 00 ON
o o o
odd
- ~CN
O O O
NO in NO
odd
NO ro ro
CN CN CN
odd
ro NO oo
* ro CN
odd
f- ro
m ^1-
d d
NO
d
t~- T)- ro
NO ^ ro
0 O 0
ON ro ON
in ^ CN
000
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in ro CN
O O O
V. H &
X X T3
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ON
O
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d
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in
d
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CN
d
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in
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NO
o ^
ro m NO
000
d d o'
P- oo ON
O O O
odd
i CN ro
O O O
O CN CN
CN CN CN
odd
NO CN O
"fr rj- *
o o o
§ro ON
00 t-;
^ d d
c- r-
m CN
ON
00
O NO ro
H \O -H
CN -H -H
in -H ro
ON CN oo
, . o
-H oo r--
CN f- NO
< o o
X X -S
i 00 -*
00
o
d
d
m oo
o o
CN
d
r-
ro
O
CN ro
0 0
O 00
0 0
ro i
O O
O
o.l
SfcH C^
>> *&
~~!
o q
d d
0 0
d d
0 0
0 0
» 1 r 1
d d
d d
ON OO
in rf
d d
ro m
00 NO
o d
o
q
O m
0
NO O
00 NO
o o
rt ON
-H 0
X X
< 00
S 0
d d
0 0
d d
8 g 2
o o o
d d
d d
ON
ro
d
r- CN ro
0 0 O
O ON CN
^" r-H i*
o o o
CN r-c O
000
>, ^
§ G x1^
|
o o o o
d d d d
o o q q
dddd
o o 2 « 2
ooooo
dddd
-H oo r- ro
ro CN CN CN
dddd
m O NO
NO m rl-
odd
in ^H
ON r-
d d
00
ro ^H ro oo ro
-H 0 0 O 0
oo NO ro CN ro
i p- in CN ~H
' O O O O
in oo ro r-- ^J-
^H oo in CN '~H
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in oo NO ro CN
O m TJ- CN i
-H 0 0 O 0
oo ~H in ON ro
i oo m CN -H
-H 0 0 0 0
X X 13 B >>
-H 00 «-l " 1 ^H
.
^*
2
H
c
«^
^
A
Determined by continuous Grie
6-31
-------
X
O
z
1.0
0.8
0.6
0.4
0.2
0.1
0.08
0.06
0.04
0.02
0.01
0.1 0.5 1 5 10 50
% OF TIME CONCENTRATION IS EXCEEDED
90
Figure 6-12. Frequency distribution of 3-hour-average concentrations
of NOX at Los Angeles CAMP Station, December 1, 1963,
to December 1, 1964.
a 17 percent increase in NOX emissions during E.
the winter months. NOX values are also
affected by ambient temperatures and by
photochemical reactions. Comparison of the
NO and NOX values by season clearly demon-
strates the influence of the photochemical
reactions that convert NO to NO2- The NO
median value in the summer season (Figure
6-12) represents 50 percent of the NOX
median, whereas in the winter season the NO
median represents 80 percent of the NOX
median. This comparison of seasonal NO and
NOX values demonstrates the increased con-
version of NO to NO2 during the summer due
to the presence of increased sunlight.
EFFECTS OF MEASUREMENT
SYSTEMS ON DATA
In addition to the continuous monitoring
of pollutants at CAMP stations, the Air
Pollution Control Office of EPA obtains
data from its Gas-Sampling Network in the
National Air Surveillance Networks (NASN).
This latter network, a cooperative effort
with local health and air pollution agen-
cies, determines 24-hour concentrations of
certain pollutants on a biweekly schedule at
approximately 150 sites. The yearly average
24-hour NO2 concentrations are shown in
Table 6-10 for the NASN network for the
years 1967, 1968, and 1969.
6-32
-------
Table 6-10. AVERAGE 24-HOUR NO2 CONCENTRATION3 AT NATIONAL AIR SAMPLING
NETWORK SITES, 1967 THROUGH 1969
(ppm)
State
Alabama
Alaska
Arizona
Arkansas
California
Colorado
Connecticut
Delaware
District of Columbia
Florida
Georgia
Illinois
City
Birmingham
Mobile
Montgomery
Fairbanks
Grand Canyon Park
Phoenix
Tucson
El Dorado
Little Rock
Anaheim
Berkeley
Fresno
Glendale
Humboldt County
Long Beach
Oakland
Sacramento
San Bernardino
San Diego
San Francisco
San Jose
Santa Ana
Denver
Denver CAMP
Bridgeport
Hartford
New Haven
Waterbury
Kent County
Newark
Wilmington
Washington
Washington CAMP
Washington CAMP
Jacksonville
Miami
St. Petersburg
Tampa
Atlanta
Columbus
Savannah
Chicago
Chicago CAMP
Peoria
Rockford
Station
number
3
1
1
1
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
1
1
2
1
1
1
1
1
1
1
3
2
2
2
2
2
1
1
1
1
2
1
1967
0.046
0.070
0.109
0.094
0.045
0.096
0.132
0.144
1968
0.052
0.1 17b
0.057
0.159
0.2 16b
0.131
0.113
0.110
0.123
0.092b
0.112
0.071
0.107
0.047b
0.075
0.104
0.101
0.072
0.080
0.118
0.155
1969
0.093b
0.025
0.016
0.045
0.0 12b
0.089
0.028b
0.047
0.012
0.148
0.027b
0.042
0.08 lb
0.012
0.1 82b
0.053b
0.0 19b
0.106
0.106
0.095
0.116
0.059
0.032
0.076b
0.1 06b
0.077
0.072
0.037
0.042
0.054b
0.07 lb
0.040
0.069
0.038
0.061
0.020
0.079b
0.096
0.025b
0.031
0.054
0.160
0.050b
0.036
6-33
-------
Table 6-10 (continued). AVERAGE 24-HOUR NO2 CONCENTRATION3 AT NATIONAL AIR
SAMPLING NETWORK SITES, 1967 THROUGH 1969
(ppm)
State
Indiana
Iowa
Kansas
Kentucky
Louisiana
Maine
Maryland
Massachusetts
Michigan
Minnesota
Missouri
Montana
Nebraska
New Jersey
New Mexico
New York
City
East Chicago
Evansville
Gary
Hammond
Indianapolis
Monroe
New Albany
New Albany
South Bend
Des Moines
Dubuque
Topeka
Wichita
Covington
Lexington
Louisville
Carville
New Orleans
Acadia National Park
Baltimore
Boston
Springfield
Worcester
Detroit
Flint
Grand Rapids
Lansing
Saginaw
Minneapolis
Kansas City
St. Louis
St. Louis CAMP
Glacier National Park
Omaha
Burlington County
Camden
Glassboro
Jersey City
Newark
Patterson
Albuquerque
Albany
Buffalo
Buffalo
New York City
Station
number
1
2
2
1
1
1
1
1
1
1
1
2
1
1
1
2
1
1
1
2
1
1
2
1
1
1
1
1
1
1
1
3
1
1967
0.081
0.044
0.051
0.028b
0.086b
0.051
0.030
0.088
0.063b
0.100
0.071
0.076
0.094
0.116
0.076
0.097
0.106
0.071
0.131
0.116
0.082b
0.179
1968
0.081
0.032
0.099
0.032
0.08 lb
0.070
0.091
0.057
0.110
0.077
0.115
0.053
0.080b
0.024b
0.095b
0.055b
0.1 15b
0.090b
0.130
0.093
0.093
0.076
0.08 lb
0.1 16b
0.115
0.072
0.091
0.121
0.059
0.066b
0.137
0.129
0.060
0.084b
0.079
0.1 48b
1969
0.086
0.031
0.045
0.054
0.079
0.034
0.072b
0.031
0.033
0.072
0.023
0.064
0.096
0.062b
0.096
0.043
0.061
0.020
0.099
0.040b
0.086
0.087
0.119
0.085
0.090
0.038
0.031
0.076
0.045
0.135
0.108
0.0 12b
0.075
0.062
0.128
0.020
0.065
0.092
0.099
0.048
0.071
0.029
0.1 42b
6-34
-------
Table 6-10 (continued). AVERAGE 24-HOUR NO2 CONCENTRATION3 AT NATIONAL AIR
SAMPLING NETWORK SITES, 1967 THROUGH 1969
(ppm)
State
North Carolina
Ohio
Oklahoma
Oregon
Pennsylvania
Puerto Rico
Rhode Island
South Dakota
Tennessee
Texas
City
Rochester
Syracuse
Utica
Durham
Greensboro
Greensboro
Akron
Canton
Cincinnati
Cincinnati CAMP
Cleveland
Columbus
Dayton
Toledo
Youngstown
Oklahoma City
Tulsa
Portland
Allentown
Clearfield County
Indiana County
Johnstown
Lancaster
Philadelphia
Philadelphia
Pittsburgh
Reading
Warminster
West Chester
York
Bayamon
Bayamon
Guayanilla
Guayanilla
Providence
Custer
Chattanooga
Memphis
Nashville
Austin
Beaumont
Corpus Christi
Dallas
El Paso
Station
number
1
1
1
1
1
2
1
1
1
3
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
1
1
1
1
2
2
1
1
2
1
1
1
1
1
2
1
1
2
1
1967
0.087
0.072
0.032
0.088
0.074
0.039
0.027b
0.125
0.079
0.075
0.049
0.040b
0.029
0.051
0.076
0.084
0.043
1968
0.096b
0.093b
0.062
0.102
0.099
0.107
0.103
0.102
0.096
0.119
0.105
0.043
0.093
0.096
0.090
0.056
0.074
0.077
0.101b
0.088b
0.132
0.112
0.066
0.066
0.096
0.047
0.03 lb
0.100
0.025
0.089b
0.090b
0.101
0.100
0.071
1969
0.086
0.074
0.070
0.076b
0.076
0.038
0.092
0.099
0.091
0.099
0.087
0.057
0.096b
0.083b
0.048b
0.033
0.056b
0.090
0.033
0.040
0.080
0.024
0.113
0.081
0.054
0.042
0.076
0.041
0.034
0.087
0.015b
0.042
0.078
0.068b
0.030
0.042b
0.026b
0.074
6-35
-------
Table 6-10 (continued). AVERAGE 24-HOUR N02 CONCENTRATION3 AT NATIONAL AIR
SAMPLING NETWORK SITES, 1967 THROUGH 1969
(ppm)
State
Utah
Virginia
Washington
West Virginia
Wisconsin
Wyoming
City
El Paso
Fort Worth
Houston
Lubbock
Pasadena
Pasadena
San Antonio
Tom Green County
Salt Lake City
Norfolk
Page
Shenandoah National
Park
Richmond
Seattle
Tacoma
Charleston
Milwaukee
Casper
Station
number
2
1
1
1
1
2
1
1
1
1
1
1
2
1967
0.035
0.048
0.052
0.076
0.093
0.035
1968
0.083
0.1 16b
0.074b
0.068
0.084
0.087
0.035
0.102
0.096
0.109
0.109
0.032
1969
0.048b
0.071
0.105
0.02 lb
0.050
0.065
0.015
0.060
0.077
0.015
0.088
0.095b
0.023
0.092
0.090
0.025
Determined by integrated Jacobs-Hochheiser method.
bThe number and distribution of individual values making up this average do not meet the NASN criteria
for calculating a yearly average. Nevertheless, it is felt that the average is adequate for drawing the general
relationships reported in this chapter.
Since there is an NASN station at each of
the CAMP stations, the NO2 values deter-
mined by the CAMP continuous instrument
with the Griess-Saltzman method of analysis
can be readily compared with the NASN
24-hour-integrated-value based on the Jacobs-
Hochheiser method.
Table 6-11 presents the ratios of NASN to
CAMP NO2 values for the years 1967, 1968,
and 1969. The table shows that NASN NC>2
values are three times greater, on the average,
than the corresponding CAMP values. There is
no satisfactory explanation for the discrep-
ancy at this time. Both methods have been
carefully checked under laboratory conditions
and are internally consistent. In the field,
however, it is possible that other factors, such
as difference in type and age of sampling-line
particulate filters, may be affecting the meas-
urements.
Limited laboratory testing suggests that the
specific particulate filter employed in the
sampling line and the age of the filter may
exert a major influence on measurement
values. Frequent in-field calibration and
servicing of the instruments is, therefore,
essential.
The results are further complicated by the
fact that the CAMP continuous instruments
cannot be expected to give accurate or precise
results for 1-hour NO2 concentrations below
190 Mg/m3 (0.10 ppm). CAMP instruments
6-36
-------
Table 6-11. RATIO OF AVERAGE
YEARLY NASNaTOCAMPb
NO2 MEASUREMENTS
City
Chicago
Cincinnati
Denver
Philadelphia
St. Louis
Washington
Median
Minimum
Maximum
N02 ratio: NASN/CAMP
1967
3.2
3.3
2.0
3.2
5.5
3.0
3.2
2.0
5.5
1968
3.0
3.2
2.7
4.3
2.9
3.0
2.7
4.3
1969
3.0
2.3
-
4.5
1.5
2.7
1.5
4.5
aNational Air Sampling Network.
Continuous Air Monitoring Program.
are designed to measure NC>2 concentrations
from 0 to 1.9 mg/m3 (0 to 1 ppm), but are
calibrated by the use of NC>2 mixtures in the
range of 0.2 to 1.9 mg/m3 (0.1 to 1 ppm).
Many of the days during which comparisons
in Table 6-11 were made, had 24-hour CAMP
values of 20 to 130 jug/m3 (0.01 to 0.07
ppm), however; and since these 24-hour
values are established by a process involving
summation of the hourly values, a large pro-
portion of the included hourly values were in
the 20- to 60- Mg/m3 (0.01 to 0.03 ppm) con-
centration range. Under these circumstances
large errors (100 to 200%) would not be
uncommon. By contrast, the NASN technique
has been calibrated in the 0- to 190- Mg/m3 (0
to 0.1 ppm) range, as well as at higher concen-
trations, hence should be more trustworthy.
F. SUMMARY
Continuous measurement of the oxides of
nitrogen by various monitoring networks has
made it possible to compile selected-time-
averages of mean concentrations for selected
time periods. From these values, various
temporal patterns have been analyzed and
related to photochemical and meteorological
parameters.
Both NO and NC>2 concentrations display
distinct diurnal variations dependent on the
intensity of the solar ultraviolet energy and
the amount of atmospheric mixing. These
concentrations also vary with the traffic
patterns in the sampling area.
Nitric oxide concentration shows a seasonal
variation, with higher values occurring during
the late fall and winter months. Nitrogen
dioxide, however, does not display such
distinct seasonal patterns. An analysis of
limited air-quality data for total NOX concen-
trations has not clearly indicated any yearly
trends.
The effect of meteorological factors on NO
and NO2 concentrations has been well
documented. Periods of stagnation in urban
areas have resulted in high peak levels of NOX
and resultant high-oxidant levels.
Continuous measurement has indicated
that peak values of NO above 1.23 mg/m3 (1
ppm) are common, but NO2 concentrations
have rarely been measured at this level. Most
NO 2 concentrations measured in urban areas
have been under 0.94 mg/m3 (0.5 ppm).
Methods for measuring atmospheric con-
centrations of NOX are still in need of im-
provement. In one instance, measurements of
NO2 taken at the same site by different
methods were found to differ by a factor of
3, but there is no satisfactory explanation for
the discrepancy at this time.
G. REFERENCES
1. The Automobile and Air Pollution, A Program
for Progress Part II. U.S. Department of Com-
merce. Washington, D.C. December 1967.
2. Nitrogen Oxides and Air Pollution, California Air
Resources Board. Sacramento. January 1966.
3. Brier, G.W. Some Statistical Aspects of Long-
Term Fluctuations in Solar and Atmospheric
Phenomena. Ann. N.Y. Acad. Sci. 95: 173-187,
1961.
4. Ingels, R.M., et al. Trends in Atmospheric Con-
centrations of Oxides of Nitrogen, 1957-1961.
Los Angeles County Air Pollution Control
District. August 1962.
6-37
-------
5. Green, M.H. New Jersey Air Monitoring Systems
and Air Quality Data, October 1965 through
December 1968. N.J. Department of Health,
Division of Clean Air and Water. Trenton. Tech-
nical Bulletin No. A-69-1. July 1969. 216 p.
6. Larsen, R.I. A New Mathematical Model of Air
Pollutant Concentration Averaging Tjme and
Frequency. J. Air Pollut. Contr. Ass. 19: 24-30.
January 1969.
7. Air Quality Criteria for Hydrocarbons. National
Air Pollution Control Administration. Wash-
ington, D.C. Publication No. AP-64. March 1970.
p. 5-1 to 5-13.
Comprehensive Technical Report on All Atmos-
pheric Contaminants Associated with Photo-
chemical Air Pollution. System Development
Corporation. Santa Monica, California. Report
No. TM-(L)-4411/002/01. June 1970.
Schuck E. A., J.N. Pitts, Jr., J.K.S. Wan. Rela-
tionships Between Certain Meteorological
Factors and Photochemical Smog. Air and Water
Pollut. 10: 689-711, 1966.
6-38
-------
CHAPTER 7.
EFFECTS OF NITROGEN OXIDES ON MATERIALS
A. INTRODUCTION
Field studies and laboratory research have
successfully linked nitrogen oxides (NOX) to
problems regarding effects on textile dyes and
additives, natural and synthetic textile fibers,
and metals. While not as well known as those
caused by sulfur dioxide or ozone, these ef-
fects, nevertheless, are important and re-
present a significant economic burden.
Nitric oxide (NO) and its principal reaction
product, nitrogen dioxide (NC^), participate
in a number of complex atmospheric reac-
tions. Eventually, atmospheric processes bring
the NOX to the nitric acid stage where it
rapidly reacts to produce various particulate
nitrates. This chapter discusses only the mate-
rial effects that are attributed to NOX and
particulate nitrates, but does not preclude the
possibility that other reactants such as nitric
acid (HNC>3) can cause damage. One must
not, however, lose sight of the role of NOX in
the photochemical formation and buildup of
ozone and other oxidants, as well as in the
photo-oxidation of sulfur dioxide in the pres-
ence of reactive hydrocarbons to produce sul-
furic acid aerosols. The photochemical reac-
tion products are believed to cause more
damage than NOX directly; thus, control and
reduction of NOX should also be valuable in
reducing damage from these products. AP-63,
Air Quality Criteria for Photochemical
Oxidants, discusses the effects of photo-
chemical pollutants on materials.
B. EFFECTS ON TEXTILE DYES
1. Acetate Rayon Fading
a. Historical Background
Just prior to World War I, a German dye
manufacturer investigated some unusual cases
of dye fading on stored wool goods.1 Fading
was most noticeable on the edges of the
goods, and the primary cause was traced to
NOX in the air. Open electric-arc lamps and
incandescent gas mantles were major sources
of these pollutants by virtue of a process of
high-temperature fixation. The investigators
found that all the susceptible dyes contained
free or substituted amino groups, and they
suggested that these might become either
diazotized or nitrosated by the NOX,
During and following the war years,
increased replacement of older forms of light-
ing with electric filament lamps led to a
general decline of the wool-fading problem. In
the mid-1920's, however, researchers de-
veloped and introduced a new fiber, cellu-
lose acetate rayon. Traditional dyes were of
little use on this fiber, but chemists soon
developed disperse dyes that were effective.
Some of these dyes, however, contained
amino-groups that the Germans had pre-
viously found susceptible to NOX fading.
Shortly thereafter a puzzling type of fading
began to occur increasingly on dyed acetate.
Blue, green, and violet shades of fabrics,
either stored or in use, faded mysteriously.
Because this fading was frequently observed
in rooms heated by gas heaters, it was called
"gas-fume fading" or "gas fading."
During the 1930's, acetate fading became a
serious problem. Dye and fiber chemists, ap-
parently unaware of the earlier German work,
devoted considerable efforts toward a
solution. These efforts culminated in 1937
when Rowe and Chamberlain2 systematically
investigated the fundamental chemistry of
dye degradation and independently reached
the same conclusions as the earlier German
team. Since then, much research has been
7-1
-------
carried out in an effort to understand gas
fading and to develop ways of preventing
it.3-5
b. Gas-Fading Characteristics
Gas fading is marked by a definite and
characteristic reddening of the fabric. This
reddening effect took on special importance
in the mid-1950's when investigators dis-
covered that ozone also fades many of the
same dyes found to be sensitive to NOX. In
many cases the characteristic reddening
enables scientists to discriminate between gas
fading and the bleached, washed-out fading
that ozone produces.
c. Test for Sensitivity
Recognizing the importance of fading by
NOX, the American Association of Textile
Chemists and Colorists (AATCC) developed a
fading-test procedure that they tentatively
adopted in 1941 and formally approved in
1957. It is presently designated as Standard
Test Method 23-1962, Colorfastness to
Oxides of Nitrogen in the Atmosphere.6 This
method calls for suspending test specimens
along with a control sample in a chamber, and
exposing them to combustion gases from a gas
burner that has been adjusted so that the
chamber temperature does not exceed 60° C.
The resulting concentration of NOX is about
38 mg/rrP (20 ppm).7 Specimens remain in
the chamber until the control sample shows a
change in shade corresponding to a fading
standard. When this happens, the specimens
are said to have had a treatment equivalent to
6 months of actual exposure to average air, as
represented by three separate locations in
southern New Jersey. If the test specimens do
not fade appreciably after one exposure
period, the procedure is repeated (using a
fresh control sample) as many times as neces-
sary to make an evaluation. Dyed fabrics are
classified and rated according to the number
of exposures necessary to produce appreciable
changes in shade.
Despite an earlier research report that pure
NO slightly fades some dyes,4 current
opinion1 >7 favors N©2 as the fading agent.
This is largely because (1) photochemical
interactions convert NO to NO2 and (2)
controlled environment studies using con-
centrations of NO2 below 188 mg/m3 (<100
ppm) produce color changes similar to those
found in field exposures. Since the test con-
centrations were so far above normal ambient
levels, the validity of these controlled-
environment studies is open to questions.
Cellulose acetate fibers are excellent absorbers
of NO2,^ and this property undoubtedly also
plays an important role in dye-fading
mechanisms.
The disperse dyes sensitive to gas fading
have an amino anthraquinone structure. The
reactions that cause fading include nitro-
sation, diazotization, and oxidation.1 Blue
dyes are especially susceptible; some violets
and reds also fade. Even blends of the
susceptible colors with resistant dyes are
subject to gas fading. Nevertheless, these
sensitive dyes are economically valuable
because they are moderately priced and have
desirable dyeing properties.
d. Attempts at Protection
To alleviate the fading problem, researchers
have developed a number of chemical in-
hibitors that can be added to the dyed fabric
and selectively react with the nitrogen
oxides.7-8 Inhibitors, however, are only
effective temporarily, since they are eventual-
ly used up and the dye again becomes
vulnerable to fading. Subsequently, re-
searchers developed dyes that were resistant
to fading; but those dyes had poor light-
fastness. In the 1950's, chemists synthesized
new dyes that resisted the fading effects of
both NOX and light.7'9'10 These dyes
however, are more expensive and have poor
dyeing properties, which result in slower
processing rates and require greater care
during application. Other means to cir-
cumvent the fading problem include using
alternative fibers, or fibers with colored
pigments incorporated in them.
Notwithstanding, costly gas-fading inci-
dents still persist.1l~13 Many incidents of fad-
ing have occurred in warehouses, and caused
7-2
-------
whole truckloads of materials to be returned
to manufacturers. Fading of acetate linings in
men's suits has been a particularly vexing
problem. Some fiber manufacturers do not
allow labelling with their brand names unless
the resulting fabrics meet established color-
fastness standards against both pollutants and
light.13 Even though dyers are aware of this
fading problem, many still use the sensitive
dyes for economic reasons. Nevertheless, use
of fibers vulnerable to fading is decreasing as
both fabric producers and retailers become
more sensitive to the public's demand for
products of higher quality.
2. Cotton and Viscose Rayon Fading
(Cellulosics)
While NOX fading of certain disperse dyes
on cellulose acetate fabrics is now well docu-
mented, the textile industry has paid little
attention to the fading, caused by pollutants,
on cotton and viscose rayon (collectively re-
ferred to as cellulosics). Consumers and re-
tailers have registered color-change com-
plaints, but textile people generally attribute
this fading to light.
An early indication of the cotton problem
occurred in the mid-1950's. Dye chemists in-
vestigated a series of complaints that some
colored cotton fabrics were fading during the
drying cycle in home gas-fired dryers.14 The
investigators traced the fading to oxides of
nitrogen formed during the combustion of
natural gas used to heat the dryers. Fading
occurred only while the textile materials were
moist. Subsequent research about 10 years
later confirmed the gas-dryer fading problem
and found that NOX levels (expressed as NC>2)
in such dryers ranged from 1.1 to 3.7 mg/m^
(0.6to2ppm).ls
Within the last decade, additional evidence
of this type of fading has emerged. When
exposed to a number of different field en-
vironments in the absence of light, some dyed
cellulosic fabrics showed fading after 2 to 3
months.16 >l 7 Fading occurred in certain blue
and green shades, representing dyes from four
major classes: direct, sulfur, vat, and reactive
dyes. Laboratory exposure of these shades to
the standard gas-fading test pro-
cedure did not produce fading. The test
procedure, was designed to evaluate dyed
acetate fabrics, and has no provisions for
controlling relative humidity, because humid-
ity is not a critical factor in acetate
fading. The field exposures, however, in-
dicated that relative humidity might be an
important controlling factor in cellulosics
fading. Subsequent laboratory exposures to
the gas-fading test procedure were therefore
conducted under high-humidity conditions
(probably greater than 50 percent). The
results were dramatic; the same concentra-
tions of NOX produced color changes that
generally agreed with the field results.
Presently, the textile-dye industry is con-
sidering modifying the gas-fading test pro-
cedure to call for humidity-controlled con-
ditions.1 8-20
3. Yellowing of Whites
A new problem that has received little
publicity, but is of considerable concern to
the textile industry is the yellow discoloration
of undyed-white or pastel-colored fab-
rics.15-20 These fabrics may be woven from
any number of common fibers, but most of
the discoloration has occurred on Nylon,
acetate, and permanent-press materials. Dis-
coloration has usually occurred on items
stored or on display, including dresses, shirts.
curtains, and lingerie. Returned items have
represented major losses to some textile
companies.
Since most discoloration occurs on whites,
dyes were ruled out as a source of the
problem. Investigators turned to various ad-
ditives, including optical brighteners; cationic,
antistatic, and soil-release finishers; softeners;
and resinous processing agents, which are ap-
plied to fibers and fabrics to enhance certain
properties. When tested by standard labora-
tory procedures, including the gas-fading
procedure, many of these additives yellowed
on exposure to NOX. Washing the fabrics
sometimes removed the yellow discoloration,
but this is impractical for items that yellow in
warehouses or on display. Today, the problem
7-3
-------
is best solved by selecting resistant additives.
Such selection may result in diseconomies,
but the textile industry and retailers recognize
that some action must be taken to avoid an
increasing number of complaints about the
discoloration of whites.
C. EFFECTS ON TEXTILE FIBERS
1. Cellulosic Fibers
Researchers have not studied the direct
effect of NOX on cellulosic fibers, but Morris
et al.21 did conduct a field study of cellu-
losics from which they attributed damage to
ambient levels of NOX in Berkeley, California.
They exposed combed cotton yarn samples at
a 45-degree angle in cabinets facing south.
Poly vinyl fluoride film, rather than glass, was
used to cover the cabinets in order to allow a
greater amount of sunlight to enter. One
chamber in each cabinet was set up as a
control, in which entering air was filtered
through carbon canisters. Ambient air was
circulated through the other chamber. (The
investigators did not note the rate of air
change.) Some samples were exposed directly
to daylight, while others were shaded.
Samples were exposed for three separate
28-day periods (December through February),
as well as for consecutive combinations of
these three periods, as is shown in Table 7-1.
During exposure, both air pollution and
weather measurements were made (Table
7-2).
Table 7-1. BREAKING-STRENGTH OF COTTON YARN SAMPLES EXPOSED TO AIR
AND SUNLIGHT IN BERKELEY, CALIFORNIA21
Exposure
Number of
days
28
28
28
56
56
84
Period3
I
II
III
I, II
II, III
I, II, III
Breaking-strength,
%loss
Filtered air
11
15
15
20
19
26
Unfiltered air
15
18
16
24
29
32
Pollution effect,
increase in % loss
breaking-strength
4
3
1
4
10
6
al - December, II - January, III - February.
Table 7-2. AIR POLLUTANT LEVELS3 AND WEATHER MEASUREMENTS21
Exposure
period
I
II
HI
Total oxidant,
ppm
0.03
0.03
0.03
;ug/m3
60
60
60
Nitric oxide ,
ppm
0.19
0.23
0.07
Mg/ni3
230
280
90
Nitrogen
dioxide,
ppm
0.08
0.08
0.05
jug/m3
150
150
90
Temp,
°F
50
50
50
Total
sunshine,
%days
100
100
72
Rain,
in.
0.5
6
10
aFor clock hour with highest average value.
7-4
-------
At least 20 yarn specimens were evaluated
for each exposure period. The investigators
assessed deterioration by measuring loss of
breaking strength. Table 7-1 shows the mean-
breaking-strength in percent losses, for un-
shaded samples, exposed to filtered and un-
filtered ambient air, for the various exposure
periods. An analysis of variance of these
mean-loss values revealed that unfiltered air
deteriorates cotton yarn to a significantly
greater extent than filtered air. The shaded
samples did not develop a corresponding dif-
ference between filtered and unfiltered air.
While textile investigators are well aware of
the pronounced deteriorating action of direct
sunlight, the results of this study serve to em-
phasize the importance of sunlight in stimu-
lating reactions between some air pollutants
and materials. It is noteworthy that the small-
est difference between breaking-strength losses
for filtered and unfiltered air occurred during
Period IIIthe period having the most rain
(which cleans the air), the lowest levels of
NOX, and the lowest total hours of sunshine.
While it is impossible to designate the ag-
gressive pollutant in this study, the investiga-
tors proposed that NOX, either directly or
indirectly, were instrumental in causing
damage. Sulfur dioxide was not measured,
since levels were known to be low.
The investigators did not mention the fact
that, although the filter material, activated
carbon, absorbs NC>2 effectively, it absorbs
NO poorly. Levels of NO in the filtered air
chamber could, conceivably, have contributed
to the decrease in breaking strength. If this
were the case, cotton specimens exposed to
clean air would show a smaller loss in
breaking strength, and the relative pollution
effect would increase.
2. Synthetic Fibers
Ambient levels of NOX do not appear to
cause noticeable damage to synthetic fibers.
Several items, however, are worthy of mention
In March 1964, New York City news-
papers22 reported an episode of runs in Nylon
stockings worn by women in the vicinity of a
demolition project. Investigators identified
the guilty agent as NO2 gas released during
dynamite blasting operations. Local weather
conditions at that time were unfavorablea
temperature inversion existed along with wind
stagnation and high humidity. The in-
vestigators proposed that the combination of
these conditions in the presence of ab-
normally high levels of released NO2 and dust
had produced nitric acid aerosols that
damaged the Nylon stockings.
Travnicek,23 noting the New York City
episode, suggested that "the corrosive effect
of NOX is rather strong, not only for Nylons,
but for practically all other fiber-forming
polymers, because it combines acid corrosion
and oxidation."
Spandex is a synthetic, elastomeric
material. On exposure to the standard gas-
fading test procedure, it develops a yellow
cast.2 ° This is not a dye-fading problem, since
the oxides of nitrogen react directly with the
polymeric material.
D. EFFECTS ON NICKEL-BRASS
ALLOYS
1. Stress-Corrosion
In 1959 the Pacific Telephone and Tele-
graph Company noticed considerable
breakage of their nickel-brass (65 Cu-23
Zn-Ni) wire springs in some relays located in
Los Angeles area central offices.24'26
Failures often occurred within 2 years after
installation. These failures were totally un-
expected, since the wire springs had been used
with excellent results for years, throughout
the nation. Investigators found that breakage
occurred on wires that were under moderate
stress and a positive electrical potential, and it
was concluded that the failure mechanism was
a form of stress-corrosion-cracking. Bell
Laboratories subsequently showed that high-
nitrate concentrations in airborne dust, which
had accumulated on surfaces adjacent to
cracked areas, produced the failures. The
nitrate content of dust from Los Angeles is
from 5 to 15 times greater than from most
eastern and midwestern cities. Furthermore,
Los Angeles dust consists of light-colored,
very fine, claylike materials and considerable
7-5
-------
organic matter in a highly oxidized, polar con-
dition. This combination results in dust that is
more sensitive and reactive to moisture than
the carbonaceous, oily, siliceous, high-sulfate
content of most eastern dusts. Nitrates are
also more hygroscopic than sulfate salts. Ad-
ditional tests have shown that failures take
place only when surface nitrate concentra-
tions are above 2.4 jug/cm^ and when the
relative humidity, a very important control-
ling factor, is above 50 percent. Other salts
will cause stress corrosion, but only when the
relative humidity is greater than 75 percent;
for sulfate salts it must exceed 95 percent.
Sometime after this stress-corrosion prob-
lem was first observed in Los Angeles, scat-
tered failures were reported, not only in wire
springs, but in other nickel-brass components
elsewhere in California, and in New York
City, and Philadelphia. Westinghouse25 has
reported failures in Texas and New Jersey.
Bell Laboratories26 also reported a totally
different type of corrosion problem that has
been observed in such widely scattered loca-
tions as Cincinnati, Cleveland, Detroit, Los
Angeles, New York, and Philadelphia. The
nickel bases of palladium-topped contacts of
crossbar switches corroded forming bright-
greenish corrosion products that gradually
crept up over the palladium cap of the contact,
resulting in electrically open circuits. Investiga-
tors concluded that the "creeping green" corro-
sion was promoted by the presence of anions,
principally nitrates, in accumulated dust.
Nitrates in urban atmospheres have been
identified as one of the end products of the
photochemical reactions between oxides of
nitrogen and hydrocarbons (see chapter 4). In
Cincinnati and Philadelphia, the cities for
which data are available, the 1965 average
airborne nitrate particulate concentrations
were 3.4 and 3.0 jug/m3 respectively. The
corresponding average gaseous NOX levels
were 124 and 158 Mg/m3 (0.066 and 0.084
ppm).
2. Protection
The telephone company took several meas-
ures to correct the stress-corrosion problem.
7-6
Researchers found that when zinc is left out
of the nickel-brass alloy, stress-corrosion no
longer occurs. To prevent future problems, a
copper-nickel material was specified for sub-
sequently manufactured wire-spring relays. In
high-nitrate areas, local central offices pro-
tected existing nickel-brass relays by installing
high-efficiency filters in outside-air intakes of
ventilating systems, and by redesigning their
cooling systems to keep relative humidity
below 50 percent.
E. FUTURE RESEARCH NEEDS
At present, the accepted procedure for
evaluating the fading characteristics of dyed
fabrics uses NOX generated from a natural-gas
flame. This produces levels of NOX that, while
of low magnitude, vary considerably. In addi-
tion, since temperature and relative humidity
are not controlled, experimental results do
not correspond, absolutely, to practical envi-
ronmental conditions.
Although dye chemists use this procedure
to assess the vulnerability of dyes and addi-
tives to NOX, they have no sound idea of the
dose-response relationships. Reported com-
plaints and field studies have been the princi-
pal means for establishing the actual existence
of atmospheric fading problems.
To estimate costs resulting from NOX
damage, investigators must determine reliable
dose-response relationships for vulnerable
materials. Such research would also delineate
the influence of temperature, relative humid-
ity, sunlight, and other possible parameters,
including interaction with other pollutants.
F. SUMMARY
Investigators have found that oxides of
nitrogen and their corresponding reaction
products cause certain textile dyes to fade,
cause some textile additives to yellow, deteri-
orate cotton fabrics, and accelerate corrosion
of certain metals. The most serious problems
concern textile dyes and additives.
Many years ago, complaints by retailers
lead to the discovery that NOX fades a number
of sensitive, disperse dyes used on cellulose
acetate fibers. The sensitive colors were
-------
mainly shades of blue. To correct this fading
problem, dye chemists developed both dye-
additive inhibitors that provide temporary
protection and fade-resistant dyes. In both
cases, especially in the latter, the end result is
a more expensive fabric.
During the last decade or so, investigators
found that certain blue and green shades of
dyed cellulosics faded under high-humidity
conditions. They first encountered this prob-
lem when investigating complaints that cotton
fabrics faded during the drying cycle in home
gas-fired dryers. They found that oxides of
nitrogen, which are among the products of
combustion of natural gas, readily reacted
with some dyes under moist conditions.
NC>2 levels in the dryers ranged from 1.1 to
3.7 mg/m3 (0.6 to 2 ppm). Later, field ex-
posures, in the absence of light, showed fad-
ing occurred in certain dyed cellulosic fabrics.
Previous laboratory exposures to NOX had
not faded these fabrics. Subsequent labora-
tory exposure to NOX, under conditions of
high humidity did produce fading in these
fabrics and confirmed the importance of
atmospheric moisture in the fading reactions.
A more recent problem concerns the yel-
low discoloration of undyed-white and
pastel-colored fabrics. Chemists have traced
this yellowing to the action of NOX on certain
additives applied to fabrics to enhance their
marketing properties. These additives include
optical brighteners, softeners, antistatic and
soil-release finishes, and resinous processing
agents. To prevent this yellow discoloration,
textile processors must be critical in selecting
NOx-resistant additives, which are generally
more costly.
Information concerning the damaging ef-
fects of NOX on textile fibers is meager. One
study has been reviewed here in which investi-
gators exposed cotton fabrics to ambient air
containing above-average levels of NOX. The
exposed yarns showed increased losses in fiber
strength.
New York City scientists who investigated
an episode of runs in Nylon stockings traced
the problem to abnormal levels of NC<2 re-
leased during dynamite blasting operations.
The combination of unfavorable weather con-
ditions and NC>2 produced acid aerosols that
damaged the Nylon.
Nitrogen oxides react with spandex, a
synthetic elastomeric fiber, producing a yel-
low discoloration. This is an inherent prop-
erty of the fiber rather than a dye-fading
phenomenon.
High-particulate-nitrate levels have caused
stress-corrosion failures of nickel-brass wire
springs on relays used by telephone com-
panys. Failures take place when surface ni-
trate concentrations exceed 2.4 jug/cm2 and
the relative humidity is above 50 percent.
This problem was first noticed in the Los
Angeles area, where airborne nitrate levels are
5 to 15 times greater than in most eastern and
midwestern cities.
Another type of this corrosion has been
associated with annual average particulate
nitrate concentrations of 3.0 and 3.4 jug/m.3
with corresponding NOX levels of 124 and
158 jug/m3 (0.066 and 0.084 ppm).
The apparent lack of dose-response rela-
tionships for the various materials sensitive to
NOX points the way for future research. Until
these relationships can be developed, eco-
nomic estimates will be, at the very best, gross
projections.
G. REFERENCES
1. Giles, C. H. The Fading of Colouring Matter. J.
Ap'pl. Chem., 15: 541-550, December 1965.
2. Rowe, F. M. and K. A. J. Chamberlain. The
"Fading" of Dyeings on Cellulose Acetate Rayon
- The Action of "Burnt Gas Fumes" (Oxides of
Nitrogen, etc. in the Atmosphere) on Cellulose
Acetate Rayon Dyes. J. Soc. Dyers Colour., 53:
268-278, July 1937.
3. Seibert, C. A. Atmospheric (Gas) Fading of
Colored Cellulose Acetate. Amer. Dyest. Rep.,
29: 363-374, July 1940.
4. Greenspan, F. P. and P. E. Spoerri. A Study of
Gas Fading of Acetate Rayon Dyes. Amer.
Dyest. Rep.,30: 645-665, November 1941.
5. Ray, T. K., et al. A Comparison of the Effect on
Rayon Fabrics of Various Gases Under Con-
trolled Conditions. Amer. Dyest. Rep., 37:
391-396, June 1948.
7-7
-------
6. 1969 Technical Manual of the American Associa-
tion of Textile Chemists and Colorist, Volume
45.391-396, June 1948.
7. Salvin, V. S., W. D. Paist and W. J. Myles. Ad-
vances in Theoretical and Practical Studies of Gas
Fading. Amer. Dyest. Rep., 14: 297-304. May
1952.
8. Mousalli, F. S. and W. J. Myles. Gas Fading of
Acetate and Triacetate Prints. Amer. Dyest.
Rep.,54: 1136-1140. December 1965.
9. Salvin, V. S. and R. A. Walker. Relation of Dye
Structure to Properties of Disperse Dyes - Part I
Anthraquinone Blues. Amer. Dyest. Rep., 48:
35-37, July 1959.
10. Salvin, V. S. and R. A. Walker. Correlation Be-
tween Colorfastness and Structure of Anthra-
quinone Blue Disperse Dyes. Text. Res., 30:
381-388, May 1960.
11. Gas Fume Fading. Dyer, Text. Printer, 128:
89-90, July 1962.
12. Fume Fading. National Institute of Drycleaning,
Silver Spring, Maryland, FF-141, 2 pgs., June
1966.
13. Moreley, D. J. Upholstery Fabric Fading by
Impurities Present in the Air. Bull. Furniture Ind.
Res. Assoc., 2-3, March 1967.
14. A Study of the Destructive Action of Home Gas
Fired Dryers on Certain Dyestuffs. Amer. Dyest.
Rep., 45: 471, July 1956.
15. McLendon, V. and F. Richardson. Oxides of
Nitrogen as a Factor in Color Changes of Used
and Laundered Cotton Articles. Amer. Dyest.
Rep.,54: 305-311, April 1965.
16. Salvin, V. S. Effect of Atmospheric Contami-
nants on Light-Fastness Testing. Amer. Dyest.
Rep., 47: 450-451, June 1958.
17. Salvin, V. S. Relation of Atmospheric Contami-
nants and Ozone to Lightfastness. Amer. Dyest.
Rep.,5J: 12-20, January 1964.
18. Rabe, P., and R. Dietrich. A Comparison of
Methods for Testing the Fastness to Gas Fading
of Dyes on Acetate. Amer. Dyest. Rep., 45:
737-740, September 1956.
19. Salvin, V. S. Testing Atmospheric Fading of
Dyed Cotton and Rayon Amer. Dyest. Rep., 58:
28-29, October 1969.
20. Salvin, V. S. Effect of Atmospheric Contami-
nants on Fabrics - Dyed and Undyed. Test. Qual.
Contr. Pzp.,14: 56-64, 1969.
21. Morris, M. A., M. A. Young and T. Molvig. The
Effect of Air Pollutants on Cotton. Text. Res.,
34: 563-564, June 1964.
22. City Finds Nylon Culprit: Blasting Gas. The New
York Times, March 11,1964.
23. Travnicek, Z. Effects of Air Pollution on Tex-
tiles, Especially Synthetic Fibers. Int. Clean Air
Congr. Proc., I: 224-226, London, Eng., October
1966.
24. Hermance, H. W. Combatting the Effects of
Smog on Wire-Spring Relays. Bell Lab. Rec.,
48-52 .February 1966,
25. McKinney, N. and H. W. Hermance. Stress Corro-
sion Cracking Rates of a Nickel-Brass Alloy
Under Applied Potential, Stress Corrosion Test-
ing. ASTM STP 452: 274-291, 1967.
26. Hermance, H. W., C. A. Russell, E. J. Bauer, T. F.
Egan and H. V. Wadlow. Relation of Air-Borne
Nitrate to Telephone Equipment Damage. For
publication in "Environmental Science and
Technology", 1970.
7-8
-------
CHAPTER 8.
EFFECTS OF NITROGEN
OXIDES ON VEGETATION
A. INTRODUCTION
The primary importance of nitrogen oxides
(NOX) as phytotoxicants was first inferred 20
years ago in California when photochemical
oxidants were shown to have adverse effects
on vegetation. The essential role of NOX in
the production of atmospheric oxidants, in-
cluding peroxyacyl nitrates (PAN) and re-
search activities in vegetative effects of these
pollutants are thoroughly reviewed in A P C O
Publication AP-63, Air Quality Criteria for
Photochemical Oxidants. Although the
importance of NOX in photochemical re-
actions is well recognized, the separate effects
on vegetation attributable to the oxides of
nitrogen per se are difficult to assess. Never-
theless, plant scientists agree that indirect
exposure of sensitive plants to NOX, through
the photochemical reactions producing
oxidants, constitutes the most significant and
widespread mechanism for NOx phyto-
toxicity. These effects, however, have yet to
be thoroughly examined.
Evidence of damage to plants resulting
from direct exposures of NOX in the atmos-
phere is usually confined to the proximity of
specific industrial sources. For example,
damage from high ambient levels of nitrogen
dioxide (NC>2) has been observed near nitric
acid plants. Direct effects due to nitric oxide
(NO) and other NOX components or
derivitives have not been delineated in the
field.
In view of the foregoing, this chapter is
limited to a discussion of the direct effects of
NOX on vegetation determined principally
from the results of laboratory studies. The
bulk of discussion is focused on the effects of
NO2, but very recent, limited evidence of NO
effects are also treated.
Evidence of plant response to phytotoxic
levels of NOX can be divided into three major
categories: (1) acute injury, (2) chronic
injury, and (3) physiological effects. Acute
injury is manifested by collapse of cells with
subsequent development of identifiable
necrotic patterns. Symptoms usually result
from short exposures (hours) to varying levels
of NO2, and appear within 2 to 48 hours after
exposure.
Chronic injury is caused by intermittent
exposure, over long periods, to low concentra-
tions of gas. It results in chlorotic or other
pigmented patterns in leaf tissue and may be
accompanied by loss of leaves (leaf-drop).
Growth alterations, reduced yields, and
changes in quality of plant products are
among the physiological effects frequently
associated with pollutant exposure. At
present atmospheric NOX exposure has not
been associated with any of these effects. In
the laboratory physiological effects are often
measured in terms of more subtle responses
such as reduced photosynthesis or changes in
rates of transpiration and enzymatic pro-
cesses. Although most research concerning the
physiological effects of NOX has dealt with
laboratory exposures to NO2, recently the
effect of NO exposure has been measured in
terms of the reduction in apparent photo-
synthesis. Apparent photosynthesis is
measured by the amount of carbon dioxide
(CO2) absorbed by the plant.
Descriptions of plant injury from NO2 are
found in two recent publications containing
color plates.4 ! 8
8-1
-------
B. ACUTE INJURY
Historically, vegetation in the vicinity of
nitric acid plants has been injured by gases
that escape during plant operations.1 Leaves
develop brown or black spots, especially on
the margins. The levels of exposure at which
these effects become apparent are unknown,
but probably vary widely. Experimental
studies have not revealed any direct acute
effect of NO exposure on vegetation.
Benedict and Breen2 exposed ten selected
annual and perennial weeds to a mixture of
NO and NO2 for 4 hours. These plants were
chosen as indicators of plant injury from air
pollutants. Two types of markings developed:
(1) a discoloration associated with collapse of
cells and necrosis and (2) a general, overall
waxy appearance of the leaf. With broad-
leaved plants the collapsed, irregular-shaped
neerotic markings were intercostal, but
nearer the margins of the leaf. Middle-aged
leaves usually developed the most markings;
but with sunflower, annual bluegrass, and
nettleleaf goosefoot, the middle-aged and old
leaves were equally sensitive. On mustard
plants, the oldest leaves were the most sensi-
tive. In all species, the young leaves were
injured least. Mustard was the most sensitive
indicator tested, but all plants were somewhat
resistant.
Heck3 fumigated cotton, pinto bean, and
endive plants with 1.9 mg/m^ (1.0 ppm) NO2
for 48 hours and observed slight, but definite,
spotting on the leaves. When concentrations
of 6.6 mg/m^ (3.5 ppm) were used for 21
hours, mild necrotic spots appeared on cotton
and bean, but endive leaves were completely
necrotic.
Van Haut and Stratmann4 grouped plants
in relation to their sensitivity or resistance to
injury by NO2 and NO. When 60 species of
plants were fumigated with a 1:1 mixture of
NO and NO2, they developed gray-green or
brownish spots on the leaves, which later
became necrotic. Leaf injury reported was
similar to that caused by SO2, except that the
NOX were 2 to 5 times less toxic. Very young
and mature leaves were less sensitive than
rapidly growing ones. The authors made no
mention of duration or concentration of ex-
posures.
MacLean et al.5 exposed 14 ornamental
species and 6 citrus varieties to high con-
centrations of NO2 for short periods and clas-
sified them according to their susceptibility to
injury. The fumigations caused marginal and
intercostal necrosis, which was often visible
within 1 hour. Collapsed tissues on the upper
leaf surface suggested an initial injury to
palisade cells. The necrosis later spread
throughout the leaf. Citrus responded with
the wilting of young leaves and leaf-drop.
Older leaves developed marginal and inter-
costal necrosis. The varieties, listed in the
order of decreasing sensitivity, were Marsh
seedless grapefruit, pineapple orange, Valencia
orange, Tangelo orange, Hamlin orange, and
Temple orange. Ornamentals represented a
wide range of susceptibility. Tissue collapse
and subsequent leaf-drop occurred rapidly in
azaleas. Croton plants exposed to 282 mg/m^
(150 ppm) for 4 hours showed slight inter-
costal necrosis, but Carissa given a like treat-
ment showed no observable effects. Although
defoliation and/or necrosis were complete in
several instances, all species survived and
axillary buds developed within 2 to 6 weeks.
C. CHRONIC INJURY
Evidence of chronic NOX injury is limited.
No evidence is available that would indicate a
chronic effect of NO on plants. Leaf-drop and
chlorosis were observed in navel orange trees
after 35 days of fumigation with 940 Mg/m^
(0.5 ppm) NO2 and leaf-drop after 8 months
exposure to 470 /zg/ni^ (Q.25 ppm).6 Similar
effects were found on tobacco, tomato,
spinach, and soybean plants exposed to the
Los Angeles Basin smog; on the same plants
raised in greenhouses equipped with car-
bon filters; and in irradiation chambers sup-
plied with automobile exhaust from motors
equipped with afterburners. Since leaf le-
sions typical of ozone injury were not ob-
served, Glater postulated that low, constant
levels of NOX were the cause of injury.7
8-2
-------
D. PHYSIOLOGICAL EFFECTS
1. Observed Responses
All of the evidence of physiological effects
is based on controlled experiments. Heck, et
al.8 recently fumigated bean and tomato
plants with 12.3 mg/m3 (10.0 ppm) NO and
observed an immediate 60 to 70 percent
reduction in apparent photosynthesis. An im-
mediate reduction in photosynthesis also
occurred with concentrations above 5.6
mg/m3 (>3 ppm). The rate of CO2 ab-
sorption returned to normal as soon as the
fumigations were discontinued. No visible
injury developed after exposure.
Hill and Bennett9 have compared the effect
of NO with the effect of NO2 on the rate of
apparent photosynthesis of alfalfa and oats. A
threshold concentration of about 0.7 mg/m3
(0.6 ppm) NO or 1.1 mg/m3 (0.6 ppm) NO2
was required to reduce CO2 assimulation.
Combining the two gases gave an additive
physiological effect. Nitric oxide produced a
more rapid reduction in apparent photo-
synthesis than NO2, and recovery was more
rapid when the fumigation was stopped. Con-
centrations causing up to 50 percent
reduction in apparent photosynthesis after 1
to 2 hours did not induce leaf injury.
Yields of the navel oranges exposed to 470
Mg/m3 (0.25 ppm) for 8 months were
reduced.6
Taylor and Eaton10 exposed pinto bean
plants to 560 Mg/m3 (0.3 ppm) NO2 for 10 to
19 days and reported a decrease in dry weight
and an increase in unit-weight chlorophyll
content. Similar studies with tomato plants
exposed to concentrations ranging from 280
to 490 Mg/m3 (0.15 to 0.26 ppm) showed a
decrease in dry weight and leaf area, a darker
green color, and a strong tendency for the
leaves to curl downward.
2. Biochemical Mechanisms
Little work has been done on the
biochemical mechanism(s) by which oxides of
nitrogen cause direct injury to plants. When
NO2 reacts with water, it forms a
stoichiometric mixture of nitrous and nitric
acids. This reaction probably occurs as the gas
reaches the wet surfaces of the spongy
parenchyma in the leaves of plants. In vitro
studies by Weill and Caldwell11 on the effect
of 1 molar nitrous acid on beta-amylase from
barley showed the enzyme to be slowly in-
activated. They concluded that easily
oxidized groups such as sulfhydryls could be
affected. DiCarlo and Redfern12 conducted
more detailed studies with alpha-amylase
obtained from Bacillus subtilis and concluded
that the nitrite was reacting with an essential
amino group in proteins. It reacts with two
oxidation states of catalase, a hemoprotein
from mammalian tissues, and with a perox-
idase obtained from horseradish.13 To date,
all enzymatic studies have used one molar
nitrate. The low concentrations of nitrate that
would occur in plant tissues after exposure to
a few parts per million of NO2 in air have yet
to be examined.
E. FACTORS AFFECTING RESPONSE TO
NITROGEN DIOXIDE
Several factors such as species of plant,
stage of plant development, plant environ-
ment (temperature, light, humidity, soil
moisture, mineral nutrition), and variable
susceptibility within species (variety or clone)
influence the degree of injury to vegetation
by air pollutants. Depending upon the kind of
plant and its environment, one factor may be
of much greater importance than another.
Benedict and Breen2 reported that moist
soil conditions caused several times as much
injury to their ten test species as did dry
conditions.
Taylor and MacLean14 recognized the
increased sensitivity of plants to NO2 caused
by low light intensity and reported that 5.6
mg/m3 (3.0 ppm) NO2 in darkness caused as
much injury as 11.3 mg/m3 (6.0 ppm) in
light. Czech and Nothdurft,15 and Van Haut
and Stratmann4 also reported that night
fumigations may cause more injury than day-
time exposures. Van Haut and Stratmann,4
reporting on the effect of time of day, found
that NO2 caused more leaf injury during
8-3
-------
certain periods than at others. Rye plants were
most sensitive from noon to 4 p.m. Oats had a
bimodal sensitivity, with more injury oc-
curring from midnight to 2 a.m. than from
noon to 2 p.m.
Of special interest is the study by Dunning,
et al., which showed that leaf injury occurred
on tobacco after a 4-hour exposure to a
mixture of 188 Mg/m3 (0.10 ppm) NO2 + 260
/ug/m3 (0.10 ppm) SO2.17 If these pollutants
act synergistically, perhaps very low con-
centrations of each in combination with the
other will cause plant injury.
influence of time and concentration and
permits the development of a three-
dimensional injury -response surface:
C = A0 + Ail + A2/T
C = Concentration, ppm
2 = Constants (partial regression co-
efficients) specific for pollutant
plant species, and environmental
conditions.
I = Percent injury
T = Time, hours
F. DOSE INJURY RELATIONSHIP BE
TWEEN NITROGEN DIOXIDE AIR
POLLUTION AND VEGETATION
Dosage is a measure of the combination of
duration of exposure and pollutant concentra-
tion; therefore, it is an essential element of air
quality criteria. The general types of in-
formation needed and problems involved have
been thoroughly discussed in a preceding air
quality criteria document.16
Presently, it is possible to cite only cursory
results concerning the effects of variable
dosages of NOX on the physiology of plants.
Results available are summarized in Table 8-1.
The acute effects of NO2 have not been
widely studied. Threshold levels of injury
reported are tabulated in Table 8-2. The thresh-
old injury level is defined as the exposure
necessary to injure 5 percent of the area of
the leaf (upper surface). Preliminary time-
concentration curves for several sensitivity
groupings have been developed. Based on
these curves, Table 8-3 suggests exposure
durations and concentrations necessary to
produce injury in sensitive, low-sensitive, and
resistant plants at the threshold-injury level.
Table 8-4 gives a complete list of plants that
have been studied, and places them in three
NO2-susceptibility classes on the basis of the
projections in Table 8-3.
Heck, et al.6 present a modified model for
reporting injury to vegetation from a group of
common air pollutants, including nitrogen
dioxide. The model recognizes the separate
Constants developed for selected test species
are shown in Table 8-5. These species are
classed in susceptibility groupings based on
Table 8-3 projections. The values of the
constants are dependent upon the prevailing
environmental conditions. The experimental
design suggests that these equations can be
used by control agencies to predict injury to
vegetation under environmental conditions
when vegetation would be most sensitive
(high humidity and temperatures between 75°
and 90° F). These equations are preliminary
attempts to place usable tools in the hands of
control agencies. They should not be applied
to time periods less than 30 minutes or over 8
hours, or for concentration averages below
0.5 or above 25.0 ppm.
G. NEED FOR FUTURE RESEARCH
Plants vary in sensitivity to NOX. Further
testing in the high concentration range [28
to 47 mg/m3 (15 to 25 ppm)] for more than 1
hour will yield little more information, except
to show the exact kind of leaf lesions that will
occur on a given species. This information
would only be worthwhile for evaluating
injury caused by spills, rocket fuels, acci-
dental release of concentrated gas, or elevated
atmospheric levels in the vicinity of poorly
controlled, industrial use or production of
NO2.
8-4
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8-6
-------
Table 8-3. PROJECTED N02 EXPOSURES FOR 5 PERCENT INJURY
LEVELS ON SELECTED VEGETATION3
Time,
hr
0.5
J.O
2.0
4.0
8.0
Concentrations producing injury
Sensitive ,b
ppm
6-10
4-8
3-7
2-6
2-5
mg/m^
11.3-18.8
7.5-15.0
5.6-13.2
3.8-11.3
3.8-9.4
Low-sensitive,
ppm
9-17
7-14
6-12
5-10
4-9
mg/m-'
16.9-32.0
13.1-26.3
11.3-22.6
9.4-18.8
7.5-16.9
Resistant,
ppm
>16
>13
>11
>9
>8
mg/irr
^30.1
>24.4
>20.7
>16.9
^15.0
aReference 6.
bPlant type.
Table 8-4. RELATIVE PLANT SENSITIVITY TO N02 INJURY
Species
Variety
Reference
Sensitive plants
Apocynaceae
Periwinkle (Vinca minor, L.)
Balsaminaceae
Sultana (Impatiens sultani, Hook.)
Begoniaceae
Begonia (Begonia Rex, Putz.)
Chenopodiaceae
Spinach (Spinacia oleracea, L.)
Compositae
Chrysanthemum (Chrysanthemum, sp.)
Lettuce (Lactuca saliva, L.)
Cruciferae
Broccoli (Brassica oleracea botrytis, L.)
Radish (Raphanus sativus, L.)
Radish (Raphanus sativus, L.)
Bright Eyes
White Impatiens
Thousand Wonders White
Bloomsdale Long Standing
Oregon
Ruby
Early Prize Head
Iceberg
Grand Rapids
Great Lakes
Romaine
Burpee Bibb
Black Seeded Simpson
Butter King
Big Boston
Butter Crunch
Calabrese
Cherry Belle
8
8
8
8
8-7
-------
Table 8-4 (continued). RELATIVE PLANT SENSITIVITY TO NO2 INJURY
Species
Variety
Reference
Gramineae
Bromegrass (Bromus inermis, L.)
Oats (Avena Sativa, L.)
Wheat (Triticum vulgare, V.I 1.)
Solanaceae
Pepper (Capsicum fnttescens, L.)
Low-sensitive plants
Chenopodiaceae
Spinach (Spinacia oleracea, L.)
Compositae
Dahlia (Dahlia variabilis)
Cruciferae
Mustard (Brassica arvensis, Rabenh)
Cucurbitaceae
Cucumber (Cucumis sativus, L.)
Musk melon (Cucumis melo, L.)
Squash (Cucurbita, sp.)
Gramineae
Barley (Hordeum vulgare, L.)
Leguminosae
Bean (Phaseolus vulgaris, L.)
Lima Bean (Phaseolus lunatus, L.)
Soybean (Glycine max, merr.)
Malvaceae
Cotton (Gossypium, sp.)
Cotton (Gossypium hirsutim, L.)
Solanaceae
Tobacco (Nicotiana tabacum, L.)
Sac Smooth
Clintland 64
329-80
Pendek
Wells
Cal Chili 505
Noble
Early Hybrid # 7
American
Heinz Pickling
Black Diamond
London
Early White Bush
Golden Summer Crookneck
Pinto
Henderson
BF
Thaxter
Scott
Bonsei
Kanrich
Acala 4-42
White Gold
Bel-B
Beltsville W3
Beltsville C
10
8-8
-------
Table 8-4 (continued). RELATIVE PLANT SENSITIVITY TO N02 INJURY
Species
Variety
Reference
Tomato (Lycopersicon esculentum, Mill.)
Resistant plants
Amaranthaceae
Pigweed (Amaranthus retroflexus)
Caryophyllaceae
Chickweed (Stellaria media, cyrill)
Chenopodiaceae
Beet (Beta vulgaris, L.)
Lamb's - quarters (Chenopodium album, L.)
Nettle-leaf goosefoot (Chenopodium murale)
Compositae
Dandelion (Taraxacum officinale, Weber)
Sunflower (Helianthus annuus, C.)
Cucurbitacea
Cucumber (Cucymis salivus, L.)
Ericaceae
Azalea (Rhododendron, sp.)
Euphorbiaceae
Croton (Codiaeum, Juss)
Gramineae
Annual bluegrass (Poa annua, L.)
Coin (Zea mays, L.)
Kentucky blue grass (Poa pratensis)
Orchard grass (Dactylis glomerata, L.)
Sorghum (sorghum, sp.)
Malvaceae
Cheeseweed (Malva parviflora, L.)
Solanaceae
Tobacco (Nicotiana tabacum, L.)
Roma
A
B
C
D
Pearson Improved
Perfected Detroit
Long Marketeer
Alaska
2
2
2
2
2
2
Pioneer and Golden Cross
Potomac
Martin
Beltsville B
W3
Burley 21
8-9
-------
Table 8-5. NO2 TIME-CONCENTRATION RESPONSE EQUATIONS (0.5 to 7 hours)3
c = AO + A!I + A2/T
Species
Sensitive plants
Oats (Clintland 64)
Radish (Cherry Belle)
Oats (329-80)
Bromeglass (Sac Smooth)
Begonia
Chrysanthemum
Oats (Pendek)
Wheat (wells)
Sultana
Broccoli
Periwinkle
Low-sensitive plants
Cotton (Paymaster)
Cotton (Acala 4-42)
Tobacco (Bel B)
Tobacco (Bel W3)
Tobacco (White Gold)
Resistant plants
Azalea
Corn (Pioneer)
AO
1.45
2.40
1.75
2.49
2.45
3.16
2.79
2.80
3.93
3.07
2.92
3.97
3.68
3.62
3.65
4.03
3.79
2.60
A]
0.13
0.14
0.15
0.16
0.15
0.16
0.14
0.13
0.13
0.20
0.23
0.23
0.22
0.21
0.18
0.30
1.90
2.70
A2
24
1.02
3.24
1.9
2.99
2.14
2.88
2.94
1.73
2.94
3.02
1.94
3.15
3.98
4.40
3.56
3.39
4.10
R2
0.76
0.83
0.56
0.71
0.63
0.72
0.50
0.52
0.67
0.53
0.55
0.58
0.50
0.38
0.31
0.40
0.33
0.37
D
4.5
4.1
5.7
5.2
6.2
6.1
6.4
6.4
6.3
7.0
7.1
7.1
7.9
8.7
9.0
9.1
16.7
20.3
E
2.3
3.2
2.9
3.5
3.5
3.7
3.8
3.8
4.8
4.5
4.5
5.3
5.2
5.2
5.2
6.0
13.8
16.5
D+E
6.8
7.3
8.6
8.7
9.7
9.8
10.2
10.2
11.1
11.5
11.6
12.4
13.1
13.9
14.2
15.1
30.5
36.8
aSee text for explanation of equation.
R2 = coefficients of determination; represent percent variation in model.
D = concentrations that will cause 5 percent injury in 1 hour.
E = concentrations that will cause 5 percent injury in 8 hours.
D+E= Basis for placing the plant in a specific susceptibility category; exact cut-off sums
not yet established.
To determine in detail how lower levels of
NOX affect vegetation will require much time
and effort. Representative species must be
grown under a variety of carefully controlled,
reproducible, environmental conditions. The
plants selected as standards would then have
to be fumigated with specific concentrations
of NC>2 and/or NO for specified times.
Evaluation would require preliminary in
vitro work to determine the effect of NOX
gases on enzymes, growth regulators, plant
pigments, and other metabolic systems. The
same reactions could then be looked for in
selected fractions of the treated plants and in
the untreated, but similarly grown, controls.
Enzymatic effects should be pursued
intensively, so that the way in which the
particular pollutant affects plant metabolism
could be defined. As biochemical effects were
understood, correlations could be made with
reactions known to occur in other organisms
such as mammals, insects, and birds.
The tentative findings by Heck involving
synergism show that studies should be broad-
ened to explore more fully the interactions
between NOX and other air pollutants.
8-10
-------
H. SUMMARY
Many kinds of plants develop severe acute
leaf injury (lesions) when exposed to con-
centrations of NC>2 greater than 47 mg/m3
(25 ppm) for a 1-hour period. Though
characteristic for each plant, the lesions are
difficult to distinguish from similar injury
caused by SO2- The fact that very young and
mature leaves are more resistent to NC>2 than
those that are expanding rapidly may provide
aid in identifying NC>2 injury.
Under controlled growth conditions, the
injury-threshold value for NC>2 (level that
injures 5 percent of the leaf area) for certain
sensitive plants is 7.5 to 15.0 mg/m3 (4 to 8
ppm) for 1 hour. Increasing the exposure-
duration decreases this threshold concentra-
tion; with a rough time-concentration rela-
tionship in which 4.3 to 6.6 mg/m3 (2.3 to
3.5 ppm) NO2 administered to sensitive plant
species for 8 to 21 hours, or 1.9 mg/m3 (1
ppm) NC>2 for 48 hours, causes leaf injury.
Continuous fumigation with 940 Mg/m3 (0.5
ppm) NC>2 for 35 days resulted in leaf drop
and chlorosis in citrus, but no actual necrotic
lesions developed.
The effects of exposure to low levels of
NC>2 for extended periods are less evident.
Recently completed studies suggest that 470
Mg/m3 (0.25 ppm) or less of NC>2 supplied
continuously for 8 months increased leaf-drop
and reduced yield of navel oranges. The
degree of injury from lower, atmospheric con-
centrations of NO2 remains to be determined.
Very mild chronic effects, resulting from
fumigation of pinto bean plants with 560
Atg/m3 (0.3 ppm) and of tomato plants with
280 to 490 jug/m3 (0.15 to 0.26 ppm) NO2,
approximate the possible effects of persist-
ently high ambient concentrations.
The limited information on the effective-
ness of NO in reducing apparent photo-
synthesis indicates that it would reduce the
growth of plants if concentrations in the
range of 3.8 to 7.5 mg/m3 (2 to 4 ppm)
persisted continuously.
I. REFERENCES
1. Thomas M. D. Gas Damage to Plants. Ann. Rev.
Plant Physiol.2:293-322, 1951.
2. Benedict, H. M. and W. H. Breen. The Use of
Weeds as a Means of Evaluating Vegetation
Damage Caused by Air Pollution. Proc. 3rd Nat.
Air Pollut. Symp., Pasadena, Calif., April 18-20,
1955. 177-190
3. Heck, W. W. Plant Injury Induced by Photo-
chemical Reaction Products of Propylene-
Nitrogen Dioxide Mixtures. J. Air Pollut. Contr.
Ass. 74:255-261, July 1964.
4. Van Haut, H. and H. Stratmann. Experimental
Investigations of the Effect of Nitrogen Dioxide
on Plants. (Experimentelle untersuchungen uber
die Winkunge von Stuckstoff dioxid auf
Pflanzen). Transactions of the Land Inst. of
Pollution Control and Soil Conservation of the
Land of North Rhine-Westphalia, (Essen). No.
7:50-70, 1967.
5. MacLean, D. C., et al., Effects of Acute
Hydrogen Fluoride and Nitrogen Dioxide
Exposures on Citrus and Ornamental Plants of
Central Florida. Environ. Sci. Technol.
2:444-449, June 1968.
6. Thompson, C. R., et al., Effects of Continuous
Exposure of Navel Oranges to NO2- Atmos.
Environ. In Press, 1970.
7. Glater, R. A. B. Smog and Plant Structure in Los
Angeles County, March 1970. Reports Group,
School of Engineering and Applied Science.
University of California at Los Angeles, p. 1-39,
Report No. 70-17.
8. Heck, W. W., O. C. Taylor, and D. T. Tingey,
Response of Plants to Acute Doses of Nitrogen
Dioxide. BioScience, 21 (In Press, 1971).
9. Hill, A. C. and J. H. Bennett. Inhibition of
Apparent Photosynthesis by Nitrogen Oxides.
Atmos. Environ. (In Press, 1970).
10. Taylor, O. C. and F. M. Eaton. Suppression of
Plant Growth by Nitrogen Dioxide. Plant
Physiol. 47:132-135, January 1966.
11. Weill, E. C. and M. L. Caldwell. A Study of the
Essential Groups of B-amylase. J. Amer. Chem.
Soc. 67:212-214, February 1945.
12. DiCarlo, F. J. and S. Redfern. a-Amylase from B.
subtilis II. Essential Groups. Arch. Biochem.
75:343-350, 1947.
13. Nicholls. P. and G. R. Schonbaum "Catalases"
In: Enzymes 8, Boyer, P. D. et al (eds.)
Academic Press. 1963, 180-181.
14. Taylor, O. C., and D. C. MacLean. Nitrogen
Oxides and the Peroxyacyl Nitrates. In: "Recog-
nition of Air Pollution Safety to Vegetation: A
Pictorial Atlas." J. S. Jacobson and A. C. Hill,
eds. Air Pollution Control Association, Pittsburg,
Pennsylvania, pp. E1-E14, 1970.
8-11
-------
15. Czeck, M. and W. Nothdurft. Investigation of the
Damage to Field and Horticultural Crops by
Chlorine, Nitrous and Sulfur Dioxide Gases.
(Untersuchungen uber Schadigungen land-
wirtschaftlicher und gartnerischer Kulturpflanzen
durch Chlor-Nitrose-und Schwefeldioxydgase).
Landwirtshaftliche Forschung. Darmstadt,, 4:
No. 1, 1-36, 1952.
16. Air Quality Criteria for Photochemical Oxidants.
Nat. Air Pollut. Contr. Admin., Government
Printing Office, Washington, D. C. AP-63, 6-1 to
6-23, March, 1970.
17. Dunning, J. A., D. T. Tingey, and R. A. Reinert.
Nitrogen Dioxides and Sulfur Dioxide Interact to
Injure Horticultural and Agronomic Crops. Hort.
Sci. 5:333, 1970.
18. Recognition of Air Pollution Injury to Vegeta-
tion: A Picturial Atlas. Jacobson, J. S. and A. C.
Hill 1, Ed. Air Pollution Control Association, Publ.
1970.
8-12
-------
CHAPTER 9.
TOXICOLOGICAL EFFECTS OF NITROGEN OXIDES
A. INTRODUCTION
Data from human and animal studies
indicate that both nitric oxide (NO) and
nitrogen dioxide (NO 2) have untoward effects
on health. Animal mortality studies indicate
that NO2 is about four times more toxic than
NO.1 This chapter represents an attempt to
evaluate health studies and to identify the
probable hazardous doses of both pollutants.
The potential role of nitrogen oxides
(NOX) in atmospheric reactions that result in
photochemical smog is discussed in chapter 4.
Although considerable information is
available regarding the toxicology of some of
these photochemical products, they are not
discussed in this chapter. Many are treated in
AP-63, Air Quality Criteria for Photochemical
Oxidants, and AP-64, Air Quality Criteria for
Hydrocarbons.
B. NITRIC OXIDE
No cases of human poisoning due to NO
have been reported in the scientific literature,
although NO is undoubtedly included in oc-
cupational exposures to NOX. When present
in high concentrations, NO is rapidly con-
verted to NO2, a property that makes it diffi-
cult to control NO concentrations in labora-
tory experiments.
In animals, extremely high concentrations
of NO produced central nervous system
paralysis and convulsions.2 Mice exposed to
3,075 mg/m3 (2,500 ppm) were narcotized in
6 to 7 minutes and died within 12 minutes,
but when the narcotized animals were re-
turned to fresh air after 4 to 6 minutes of
exposure, they recovered rapidly.
D,ata from limited experiments on guinea
pigs indicate no effect on pulmonary function
from 4-hour exposures to concentrations of
19.7 to 94.0 mg/m3 (16 to 50 ppm) NO.3
1. Methemoglobin Increase
Methemoglobin (MeHb) does not bind
oxygen; hence, it reduces the oxygen-carrying
capacity of blood when it replaces normal
hemoglobin. Low concentrations of MeHb
ranging from 0.01 to 0.5 gram MeHb per 100
milliliters (g/100 cc) are usually present in
normal human blood,4 although the range in
normal subjects has been reported to vary
between 0 and 8 percent of total hemo-
globin5 (i.e., up to 1.2 g MeHb/100 cc, as-
suming a hemoglobin value of 15 g/100 cc).
The earliest clinical evidence of MeHb in
human blood is cyanosis, which begins when
the concentration reaches 10 to 15 percent of
the total hemoglobin, a concentration not
likely to result from exposure to ambient con-
centrations of NOX. Symptoms such as
exertional dyspnea (labored breathing),which
reflects hypoxia (low oxygen supply) are not
likely to appear until blood levels of MeHb
reach 30 to 45 percent of total hemoglobin.4
High quantities of MeHb and cyanosis were
detected in the blood of animals that died as a
result of poisoning from exposures to 1,500
mg/m3 (1,200 ppm) NO.6'7 Evidence con-
cerning MeHb formation following exposure
to lower concentrations of NO is conflicting.
The significance of low blood levels of
MeHb is not well understood. In chapter 10,
the use of blood levels of MeHb as an index of
exposure to ambient NOX is discussed,8 but
few epidemiological investigators actually use
this parameter in their experimental design.
In vitro, NO combines with hemoglobin to
form NO-hemoglobin (NO-Hb) and with
9-1
-------
MeHb to form NO-methemoglobin (NO-
MeHb), both of which have biological half-
lives of about 2 days. A preliminary examina-
tion of the blood of rats exposed for 1 and 9
days to 12.3 mg/m3 (10 ppm) NO in air by
electron-spin resonance revealed neither NO-
Hb nor NO-MeHb.9
2. Enzyme Inhibition
A concentration of about 24.6 mg/m3 (20
ppm) NO inhibited hydrogenase activity of
the bacteria Proteus vulgaris, both in vivo and
in vitro.1 ° This activity could be restored by
the addition of ^28204, which reduces NO
to nitrous oxide (N2O), except at concentra-
tions of 12.3 x 103 mg/m3 (10,000 ppm) NO
and above where inhibition was irreversible.
Although ambient levels of NO are not
inherently toxic, toxicological potential lies in
its relationship to NO2 which is discussed in
AP-63, Air Quality Criteria for Photochemical
Oxidants.11
C. NITROGEN DIOXIDE
1. Effects in Animals
a. Mortality
Many early studies produced negative
evidence of NO2 toxicity in animals. This
may have been due to the presence of large
amounts of NO in the experimental mixtures,
for recent studies have produced more reliable
and positive evidence of toxicity. Several
factors affecting the mortality due to NO2 are
discussed in the following section.
(1) Length of exposure and concentration
(ct). Short exposures of rats to high concen-
trations are more toxic than equivalent
exposures to low concentrations for longer
times. This is illustrated in Table 9-1.12
Most investigations involving inhalation of
high concentrations of NO2 have implicated
pulmonary edema as the major cause of
death. When 112 animals of various species
were exposed to 56.4 to 1,880 mg/m3 (30 to
1,000 ppm) NO2, 84 animals died, 74 from
pulmonary edema, 5 from asphyxia, and 5
from pneumonitis (inflammation of lung
tissues) (Table 9-2). Exposure to 56.4 mg/m3
(30 ppm) NO2 for 3 hours produced no
apparent immediate or delayed harmful
effects in guinea pigs. The harmful effects of
2- to 3-hour exposures of 103.4 mg/m3 (55
ppm) NO2 were questionable in experiments
with rats and mice. None were found at the
Table 9-1. COMPARISON OF LETHAL LEVELS OF ACUTE
EXPOSURE OF MALE RATS TO NO2'2
Number
of
experiments
3
2
6
10
10
7
Exposure
time,
min
2
5
15
30
60
240
LCSO,a'b
ppm
l,445d
833d
420 (362-487)
174 (154-197)
168 (153-185)
88 (79-99)
mg/m^
2,715
1,566
790(680-916)
325 (290-370)
315 (290-350)
165 (140-185)
LCtso,b'c
ppm x min
2,890
4,165
6,300 (5,430-7,305)
5,220 (4,620-5,910)
10,080 (9,180-11,100)
21,120(18,960-23,760)
aLC5Q represents the concentration lethal to 50 percent of the animals.
"95 percent confidence limits in parenthesis.
cLCt5Q represents the exposure (concentration x time) lethal to 50 percent of the animals.
dNo confidence limits.
9-2
-------
Table 9-2. TIME NECESSARY TO PRODUCE
DEATH IN ANIMALS3 EXPOSED TO
HIGH CONCENTRATIONS OF NO2'3
Concentration,
ppm
30
100
150
400
600
800
1,000
mg/rrp
56.4
188.0
282.0
752.0
1,128.0
1,524.0
1,880.0
Time until death,
min
318
90
58
32
29
19
% deaths
0
74
70
92
93
100
100
aAnimals included the following species: cats, guinea
pigs, mice, rats, and rabbits. Death occurred in 84 of
112 animals.
same concentration with rabbits, cats, and
guinea pigs.1 3
It is rare that any species can withstand
exposure to NC>2 concentrations of 188 to
1,880 mg/m3 (100 to 1,000 ppm). In
experiments with these concentrations, death
occurred after 10 minutes to 21 hours of
exposure, depending on the animal.12 Four-
hour exposure to 99.6 mg/m3 (53 ppm) NC>2
was fatal to rats and 122.2 to 141 mg/m3 (65
to 75 ppm) NC>2, to dogs.
(2) Temperature. An ambient temperature
increase of about 11° C (20° F) increases the
toxicity of NC>2 for rats by about 25
percent.
14
(3) Presence of other irritants. The survival
time for rabbits was increased from 60 to 140
minutes when nonlethal amounts of sulfur
dioxide (862) were added to the NC>2 dose
that caused 50 percent mortality.14
b. Respiratory tract effects
(1) Changes in pulmonary function. Short-
term (less than 4 hours) exposure to
NC>2 produced reversible changes in
pulmonary function.3'15 In general, both
short-term and continuous exposures caused
respiratory rates to increase and tidal volumes
(the volume of air inhaled in an average single
breath) to decrease during exposures to con-
centrations ranging from 1.5 (0.8 ppm) to 94
mg/m3 (50 ppm). The degree of response
varied with the exposure and the animal
(Table 9-3 and Figure 9-1).
Other pulmonary functions have been
examined, but show no evidence of N(>2
effects. Guinea pigs exposed to 9.4 mg/m3 (5
ppm) NC>2 for either 4 or 7.5 hours a day, 5
days a week, for periods up to 5.5 months
had no changes in expiratory flow resist-
ance.16 Four rabbits exposed to 47.0 mg/m3
(25 ppm) NC>2 continuously for 18 months
had a transient increase in the rate of oxygen
consumption. The rate reverted to normal
within 48 to 72 hours after exposure. In 16
rabbits exposed to 1.9 and 9.4 mg/m3 (1 and
5 ppm) NC>2 for the same length of time, no
change in oxygen consumption occurred.17
Beagles exposed to 0.9 to 1.9 mg/m3 (0.5
to 1.0 ppm) NO2 plus 245 Mg/m3 (0.2 ppm)
NO, and to 2.8 to 3.8 mg/m3 (1.5 to 2.0
ppm) NO2 plus 245 jug/m3 (0.2 ppm) NO for
16 hours a day for 18 months, showed no
changes in body weight, or in carbon
monoxide (CO)-diffusing capacity, com-
pliance, or total expiratory resistance of the
lungs when compared with a control group of
20 breathing filtered air.18
(2) Chemical effects.
(a) Structural proteinsNO2 can alter the
configuration of the lung tissue structural pro-
teins, collagen and elastin.19 One animal from
each of five sets of four litter-mate female
rabbits served as a control; one breathed 1.9
mg/m3 (1 ppm) NO2 for 1 hour; and the re-
maining two were exposed to 9.4 mg/m3 (5
ppm) NO2 for 1 hour. All the animals were
sacrificed immediately after exposure, except
one in the last group, which was sacrificed 24
hours after exposure. The lungs were excised
and converted to a lipid-free powder from
which collagen and elastin were isolated by a
combination of solvent-extraction and
enzymatic-hydrolysis methods. Differential
ultraviolet spectrophotometry indicated that
9-3
-------
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LRETURN TO AIR
2345
N02, ppm | EXPOSURE, hr | SUBJECTS
13
6.5
5.2
10
10
10
180
160
140
120
100
80
RETURN TO AIR
TIME, hours
Figure 9-1. Effect of N02 on tidal volume and respiratory rate of
guinea pigs.10
the molecular structures of both collagen and
elastin were altered in both exposure groups.
Similarity between the spectra of collagen and
elastin from the animal sacrificed 24 hours
after exposure and those from the control
animal indicated that the changes were
reversible under the conditions of the ex-
periment. The authors suggested that meta-
bolic activity of the lung tissue was reduced in
the highly acidic environment produced by
exposure to NC>2 and speculated that re-
peated exposure to NC>2 with concurrent
repeated denaturation of collagen and elastin
may be a factor in the etiology of pulmonary
emphysema.
Rabbits exposed on a schedule of 470
Mg/m3 (0.25 ppm) NO2, 4 hours a day for 6
days; and sacrificed immediately, developed
structural changes in the lung collagen, as
determined by electron microscopy. These
changes were not reversible and were apparent
in animals sacrificed 7 days after the final
exposure.2 °
(b) Lipid peroxidationShort-term low-
level exposures [4 hours at 1.9 mg/m3 (1
ppm)] produced evident peroxidation in
extracts of lipids from rat lungs.21 Peroxida-
tion was maximum 24 hours after exposure,
and lasted for at least 24 hours more. In six
daily 4-hour exposures to 1.9 mg/m3 (Ippm),
the lipid peroxidation increased, possibly as a
cumulative effect. The significance of this
peroxidation is not yet established; however,
rats fed a vitamin-E-deficient diet and ex-
posed to NC>2 had more peroxidation in
both surfactant and tissue lipids than did
9-5
-------
those on vitamin-E-supplemented diets.22
Vitamin E is an antioxidant.
(3) General Pathological Effects. Patho-
logically, all animal lungs demonstrate the
same general pattern of response to NC>2, ir-
respective of the duration of exposure, but
the severity tends to increase as the con-
centration increases. An inflammatory re-
action characterized by macrophage infiltra-
tion and epithelial degeneration occurs during
the 24-hour period immediately following
exposure and can develop into pulmonary
edema at sufficiently high concentrations.
Subsequent regeneration follows. Such
changes were described in rabbits exposed to
188 mg/m3 (100 ppm) and in rats and guinea
pigs exposed to 141 to 150 mg/m3 (75 to 80
ppm) NC>2 for 2 hours.2 3 In experiments in
which rats and guinea pigs were exposed to
28.2 to 37.6 mg/m3 (15 to 20 ppm) and
rabbits to 47.0 mg/m3 (25 ppm) NC>2 for 2
hours a day for 5 successive days, initial
edema and inflammation were not as severe as
they were in the single-dose experiments; but
chronic peribronchial and perivascular in-
flammation followed later. On the fourth day
after epithelium was destroyed by a solitary
high dose, lung tissue did repair itself in both
rabbits and guinea pigs. Regeneration became
intense and appeared to be complete in 2
weeks; after a series of high intermittent doses
repair was slower. Animals exposed inter-
mittently during a period of 21 months
required up to 3 weeks after the last exposure
to recover.2 3>24
(4) Cellular Changes.
(a) Structural damageshort-term ex-
posureIn short-term exposures to low con-
centrations (0.5 ppm for 4 hours or 1 ppm, 1
hour) rats sustained reversible lung-tissue
change.25 In tissues from animals sacrificed
immediately after exposure, the mast cells
were ruptured and disoriented, and showed
loss of cytoplasmic granules. This occurred
primarily in the pleura, bronchi, and sur-
rounding tissues, but most markedly in the
mediastinum. This response seemed reversible,
since animals sacrificed 24 to 27 hours after
exposure appeared to have only a few rup-
9-6
tured mast cells. The investigators considered
that the release of granular material from the
lung mast cells in response to NC>2 inhalation
signified the potential onset of an acute in-
flammatory reaction.
After 4 hours exposure to 32.0 mg/m3 (17
ppm) NC>2, the appearance of bits of free
fibrin in both alveolar spaces and tissue in-
dicated transient leakage of plasma from rat
alveolar capillaries. With continued exposure
in the same experiment, researchers noted
that focal injury to type I alveolar epithelial
cells was exaggerated within 48 hours, as bits
of amorphous cellular debris appeared in
ductal alveoli. The facts that fibrin and debris
tended to disappear and that injured cells
healed as exposure continued suggests the
development of tolerance.26
Primary lesions appeared in lung alveoli of
squirrel monkeys exposed for 2 hours to 18.8
to 94.0 mg/m3 (10 to 50 ppm) NO2- Progres-
sive alveolar expansion occurred with in-
creasing concentrations of NO2- At 18.8
mg/m3 (10 ppm) NC>2, many septal breaks
appeared and the alveoli expanded markedly.
In some areas, large air vesicles with extreme-
ly thin septal walls were seen. Other tissues
appeared to be normal. At 28.2 mg/m3 (15
ppm) NO2 alveolar tissue was expanded with
minimal wall thinning and patchy interstitial
infiltration with lymphocytes. The bron-
chioles were normal. At 65.8 mg/m3 (35
ppm) NO2 areas of lung were collapsed and
alveolar septa became very basophilic. In
other areas, the alveoli were expanded and
haa thin septal walls. The bronchi were
moderately inflamed; some showed epithelial
proliferation.15 Exposure to 94.0 mg/m3 (50
ppm) NO2 resulted in extreme vesicular
dilatation or total collapse of alveoli, along
with extensive edema and lymphocyte in-
filtration. The bronchi showed epithelial
surface erosion and absence of cilia.
(b) Orientation changescontinuous ex-
posureAfter 3 days of continuous exposure
to 3.8 mg/m3 (2 ppm) NO2, the terminal
bronchiolar epithelium of rats changed from
an active, inhomogeneous, lining layer, to a
-------
uniform layer of enlarged cells. This subtle
biochemical effect on epithelial cell metabo-
lism was further documented by the demon-
stration of abnormal ciliogenesis. Although
ciliary basal bodies developed normally, they
failed to orient appropriately at the apical sur-
faces of the cells. They either formed no cilia
or directed them intracytoplasmically into
vacuoles. Intracytoplasmic, crystalloid in-
clusion bodies also developed in time.2 6'2 8
(c) Hy perplasiaIn another case, con-
tinuous exposure to 32.0 mg/m3 (17 ppm)
NO2 precipitated a wave of accelerated cel-
lular replication (hyperplasia) of terminal-
bronchiolar and type-II epithelial cells and
macrophages in rat lungs. This response was
measured both by nuclear autoradiography
with tritiated thymidine incorporation and by
mitotic-figure counts.29 The activity peaked
at 24 hours and returned to baseline values
within a week, despite the continued
exposure and without apparent vital injury to
the epithelial cells involved.
In hamsters continuously exposed to higher
NC>2 concentrations [84.6 to 103.4 mg/m3
(45 to 55 ppm)] for 2.5 months, researchers
noted transitory hyperplasia (increased cell
production) of the respiratory bronchiolar
epithelium. The lung volumes increased
during exposure and reverted toward normal
after a 2-week recovery.30 In hamsters
exposed to 188 mg/m3 (100 ppm) NC>2 for 6
hours, tritiated thymidine uptake indicated an
intense epithelial proliferation in the major
bronchi, that was maximal 24 hours after
exposure and normal again within 4 days. In
the periphery, the response was delayed and
less intense.31
(d) Emphysematous lesionsWith
exposures of 3 months or longer, 0.9 to 47.0
mg/m3 (0.5 to 25 ppm) NC>2 caused changes
in animal lung tissue similar to those seen in
human emphysema. Pre-emphysematous
lesions indicative of the development of early
focal emphysema were observed in the lungs
of mice exposed to 940 Mg/m3 (0.5 ppm)
N(>2 for 6, 18, and 24 hours a day for periods
from 3 to 12 months.32 The data are given in
Table 9-4. Alveoli, consistently increased in
size by cell-distension rather than by septal
breakage. The investigators also noted in-
flammation of the bronchiolar epithelium and
reduction in distal airway size.
Continuous exposure of young rats to 18.8
to 47.0 mg/m3 (10 to 25 ppm) NO2 pro-
duced voluminous, heavy, dry, air-retaining
lungs in expanded, kyphotic thoracesa con-
dition grossly resembling emphysema (see
Table 9-5).33-36 Such animals died of
respiratory complications after several months
of exposure. Pathological findings included
narrow, occasionally fibrotic and occluded
terminal bronchioles with no cilia; distended,
ruptured peripheral alveoli; and alterations in
the staining characteristics of both collagen
and elastic tissue, particularly in tissue from
the alveolar ducts.37 Terminal bronchiolar,
ductal, and adjacent alveolar epithelium was
hypertrophic (enlarged).
When such lungs were allowed to recover,
the hypertrophic epithelium receded and cilia
reappeared. With the recession, the lung
weights returned to normal. Additional
pulmonary connective tissue usually appears
in rats as a part of aging; however, the
previously exposed, healing rats developed
excessive lung weight, compared to controls
of the same age. This suggested an "anam-
nestic" connective-tissue response in old
age.38 Abnormally huge collagen fibrils and
overtly thick basement laminae were revealed
by electron microscopy of the lungs from
such rats, including those exposed to as little
as 3.8 mg/m3 (2 ppm) NO2.39
Early, emphysema-like lesions could also be
produced in larger animals by exposure to
NO 2- Twelve pure-bred beagle dogs, divided
into two equal groups, were exposed con-
tinuously for 6 months to either filtered air,
or filtered air and approximately 47.0 mg/m3
(25 ppm) NO2- Autopsies on the NC>2-
exposed dogs revealed bullous emphysema in
the lungs of one animal and increased
firmness with scattered, small bullae in each
of the remaining five animals. A diffuse in-
crease in collagen was noted in the lungs of all
9-7
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six animals, but no such changes were ob-
served in the controls.40 Further studies
suggested that adding 1 Mg/m3 ferric oxide
dust to air containing 48.9 mg/m3 (26 ppm)
NC>2 may protect dogs against the develop-
ment of pathological changes. This was the
case in a subsequent 6-month experiment.41
(5) Combined Effects of NO2 With Tobacco
Smoke. Exposure either for 2 hours to 28.2
mg/m3 (15 ppm) NC>2 or for 1 hour to 3
percent (v/v) tobacco smoke had only a slight
effect on the surface structure of hamster
lungs. When hamsters were exposed to the
same concentrations for the same times, but
sequentially (NC>2 followed by tobacco
smoke), the combination of exposures pro-
duced marked alterations in surface morphol-
ogy. The structure of mucus-secreting cells
was not typical, and a marked loss of cilia was
noted 2 days after exposure. These changes
were not reversible. Seven days after expo-
sure, the surface structure of the main
bronchi and secondary airways appeared to be
even more disrupted; small patches of cilia
and deep holes appeared in the bronchial
mucosa. The authors concluded that NC>2 and
tobacco smoke act synergistically on the
bronchial epithelium, producing pathological
changes much greater than those caused by
either pollutant alone.42
c. Systemic Effects
(1) Tissue Changes. Kidney, liver, and heart
tissues of squirrel monkeys given 2-hour expo-
sures to NO2 were damaged in proportion to
the dosage. At 28.2 mg/m3 (15 ppm) some
tubular erosion appeared in the kidneys; liver
cells ballooned and developed clear cytoplasm
with displaced nuclei and congested intersti-
tial spaces. At 65.8 mg/m3 (35 ppm) renal
glomerular tufts were swollen and heart tissue
showed areas of interstitial fibrosis. At 94
mg/m3 (50 ppm) the hearts developed inter-
stitial edema and lymphocytes infiltrated
kidney and liver tissue. Centrolobular necrosis
also appeared in the liver.l s
(2) Weight Loss. Studies on the effects of
long-term exposure to NC>2 have produced
conflicting results with respect to weight loss.
No significant reduction in the rate of weight
gain was noticed in rabbits, guinea pigs, rats,
or hamsters exposed to 1.9, 9.4, or 47 mg/m3
(1, 5, and 25 ppm) NC>2 and dogs to 1.9 and
9.4 mg/m3 (1 and 5 ppm) NC>2, for 6 hours a
day for 18 months.17 Furthermore, no sig-
nificant differences in weight gains appeared
in mice exposed to 940 Mg/rn3 (0.5 ppm)
NC>2 for 6, 18, or 24 hours a day, 5 days a
week, for up to 12 months.43 Combined NOX
exposures of 940 to 1,880 Mg/m3 (0.5 to 1.0
ppm) NC>2 plus 245 Mg/m3 (0.2 ppm) NO or
2.8 to 3.8 mg/m3 (1.5 to 2.0 ppm) NO2 plus
245 Mg/m^ (0-2 ppm) NO 16 hours a day for
18 months did not change weight gain in the
12 beagles in either experiment.1 8
In contrast, rats exposed continuously to
22.6 mg/m3 (12 ppm) NO2 for 9 months con-
tinued to grow, but their body weights re-
mained 20 percent below those of control
animals.31'34 One observer44 reported a 10
percent weight loss in rabbits exposed to 5.6
Mg/m3 (3 ppm) NO2 for 15 weeks, while
controls added 11 percent to their weight.
The effect was apparently dose dependent,
for rabbits exposed to 2.5 mg/m3 (1.3 ppm)
NO2 for 17 weeks increased their weight 2
percent compared to an 8 percent increase by
controls.
(3) Voluntary Behavior. Six-hour exposures
of 6.9 to 39.3 mg/m3 (3.7 to 20.9 ppm) NO2
depressed the voluntary running activity of
male mice, when the concentration was 14.5
mg/m3 (7.7 ppm) or greater. Although the
threshold was not identified, it could be
narrowed to between 6.9 and 14.5 mg/m3. In
all cases, activity returned to normal on the
first post-exposure day.9
(4) Hematologic Effects. Studies of the
effect of NO2 on the circulating blood have
included both short- and long-term exposures.
In one short-term study, a group45 exposed
dogs to 73.3 and 99.6 mg/m3 (39 and 53
ppm) for 60 minutes, 97.8 and 160 mg/m3
9-10
-------
(52 and 85 ppm) for 15 minutes, and 235 and
308 mg/m3 (125 and 164 ppm) for 5
minutes, and found no changes in the hema-
tocrits and blood platelet counts determined
4, 24, 48, and 72 hours after exposure. The
same was true in dogs exposed to 1.9 and
47.0 mg/m3 (1 and 25 ppm) NC>2 6 hours a
day for 18 months.'7
Freeman, et al.37 found polycythemia in
rats allowed to breathe 3.8 mg/m3 (2 ppm)
N(>2 or more, continuously. The concentra-
tion of erythrocytes rose within 2 to 3 weeks
and achieved levels of about 40 to 100
percent above baseline values. After some
delay, both hematocrit and hemoglobin
levels rose, but to a lesser degree, so that the
fully developed polycythemia was charac-
terized by a reduction in mean corpuscular
volume, mean corpuscular hemoglobin, and
mean corpuscular hemoglobin concentration.
Cellular diameters measured on the flat sur-
face of stained smears were normal. The
blood of monkeys (M. speciosa) exposed to
3.8 and 16.9 mg/m3 (2 and 9 ppm) NC>2
followed a similar course.37
Leukocytosis occurred in the peripheral
blood of rabbits exposed to both 2.5 and 5.6
mg/m3 (1.3 and 3.0 ppm) NO2 for 15 to 17
weeks but it receded with cessation of
exposure. The leukocytic response was ac-
celerated by the presence of SO2- Phagocytic
activity was depressed by NO2 and both
leukocytic and phagocytic alterations were
greater at the higher NC>2 exposure.44
Methemoglobin (MeHb) has been detected
in the blood of animals exposed to NC>2 as
well as to NO. Cats, rabbits, guinea pigs, mice,
and rats were exposed to 56.4 to 1,880
mg/m3 (30 to 1,000 ppm) NC>2 for un-
specified periods of time. MeHb was not
detected in animals receiving up to 103
mg/m3 (55 ppm) NC^. Cats exposed to 188
mg/m3 (100 ppm) showed detectable
amounts of MeHb after approximately 1 hour
of exposure, however. At concentrations of
282 mg/m3 (150 ppm) NO2 and above, the
blood of all animals tested contained MeHb
after 1 hour of exposure, but the MeHb was
no longer measurable 1 to 2 hours after
animals were returned to clean air. In these
experiments the NC<2 values reflected the
total oxides of nitrogen present in the ex-
posure chamber; the concentration of NO was
not evaluated separately.46
In other experiments, MeHb appeared in
the blood of rabbits and rats exposed to
fumes produced in the electric-arc welding
process.47 Rats exposed for 6 hours a day, 5
days a week, for 43 days, to fumes containing
45.1 mg/m3 (24 ppm) NO2 developed 4.5 to
21.7 percent MeHb (mean of 13.6 percent).
Detectable levels were still present on the
eleventh day of the post-exposure period.
Rabbits similarly exposed for 45 days, formed
an average of 2.8 percent MeHb (range 0.9 to
4.5 percent). On the sixth day of the post-
exposure period, detectable amounts re-
mained in male rabbits only. Male rats
exposed to 132 mg/m3 (70 ppm) NO2 for 6
hours a day formed 2.6 percent MeHb after
the first day of exposure and 3 percent by the
third day. Three days after exposure, the
levels were within the control range. In these
experiments, it was estimated that between
12 and 17 percent of the nitrous fumes
existed as NO.47
A mixture of 180 ppm NO2 plus
caused death in 12 dogs within 55 to 285
minutes. MeHb concentrations increased
significantly (p < 0.01), with an average of
325 mg per 100 g of blood before, and 700
mg per 1 00 g after, exposure.4 8
(5) Immunologic Effects. A circulating
substance with properties similar to a lung
antibody appeared in the serum of guinea pigs
exposed to 9.4 mg/m3 (5 ppm) NO2 either 4
hours a day 5 days a week, or 7.5 hours a day
5 days a week, for up to 5.5 months. In a
second group, exposed to 28.2 mg/m3 (15
ppm) NO2 continuously for 1 year, the
antibody reacted in vitro with proteins
extracted from the lung tissue of control
animals. The titers of reactive substances in-
creased with the intensity and duration of
exposure, but no absolute values were
9-11
-------
ascribed to the data because the latex ag-
glutination method employed is not quanti-
tative.16
(6) Effects on Enzyme Systems. The effect
of exposure to 28.2 mg/m3 (15 ppm) NO2
continuously for 10 weeks; on oxygen con-
sumption, lactic dehydrogenase, and aldolase;
in guinea pig lung, liver, spleen, and serum
was determined.49 The following significant
changes occurred: oxygen consumption in-
creased in spleen and kidney; lactic dehydro-
genase activity increased in lung, liver, and
kidney; and aldolase activity increased in
tissues. Short-term exposures also caused a
significant increase in the activities of the
same enzymes in some tissues. Exposure of
guinea pigs to 75.2 mg/m3 (40 ppm) for 30
minutes at 2-hour intervals for a total of 4.5
hours revealed the following significant
changes: oxygen consumption increased in
liver, spleen, and kidney; lactic dehydrogenase
activity increased in liver, kidney, and serum;
and aldolase activity increased in liver, spleen,
kidney, and serum. The mechanism that
causes these enzymatic changes is not known,
but it might reflect a general response to
stress.
Following a 2-hour exposure to 65.8 and
94.0 mg/m3 (35 and 50 ppm) NO2, lactic
dehydrogenase isoenzymes from lung tissue of
squirrel monkeys shifted to predominantly
anaerobic band 5 when chromatographed, and
after a 2-hour exposure to 18.8 mg/m3 (10
ppm) NC>2, a similar increase in band 5 was
noted in serum lactic dehydrogenase
isoenzymes. This change in isoenzyme pattern
was present at 2 days, but returned to normal
8 days after termination of the NO2 expo-
sure. A similar shift to anaerobic isoenzyme
was observed in the heart tissue of hamsters
exposed for 2 hours to 9.4 and 65.8 mg/m3
(5 and 35 ppm) N02-15'50
d. Susceptibility to Respiratory Infection
(1) Bacteria and Influenza. Study of rabbits
exposed to concentrations of NO2 ranging
from ambient Cincinnati levels to 113 mg/m3
(60 ppm) revealed increased numbers of
polymorphonuclear leukocytes (heterophiles)
in lung washings; this condition persisted for
more than 72 hours after a single 3-hour ex-
posure. When streptococci were instilled into
lungs of NC>2-exposed, anesthetized rabbits
30 minutes before lavage, a pronounced in-
hibition of phagocytic activity was observed,
in comparison to controls.51
Exposure of mice, hamsters, and squirrel
monkeys to NO2 increases susceptibility to
bacterial pneumonia and influenza infection.
This susceptibility, observed in both short-
and long-term exposures, is based on three
parameters: (1) increased mortality rates, (2)
reduced survival times, and (3) reduced ability
to clear inhaled infectious agents from the
lungs, as determined by the number of viable
organisms that can be cultured. Mice in these
experiments were exposed for 2 hours to NC>2
in concentrations ranging from 2.8 to 47.0
mg/m3 (1.5 to 25 ppm), then challenged with
an aerosol of Klebsietta pneumonia within 1,
6, and 27 hours after the NC>2 exposure.5 2<53
The minimum NC>2 concentrations required
to produce a statistically significant rise in
subsequent mortality was 6.6 mg/m3 (3.5
ppm) for 2 hours when the infectious
challenge took place 1 hour after the NC>2
exposure. When the infectious challenge was
delayed,- a statistically significant effect was
noted at 6, but not at 27 hours, at NO2 con-
centrations of 9.4 mg/m3 (5 ppm) and above.
Exposure to 47.0 mg/m3 (25 ppm) NO2, 6
and 14 days prior to the challenge with K.
pneumoniae did not increase mortality. The
same authors reported that when mice were
infected with K. pneumoniae first, and then
exposed for 2 hours to 47.0 mg/m3 (25 ppm)
NO2, within 1, 6, 27, 48, and 72 hours after
the infectious challenge, the mortality in-
crease was statistically significant. This effect
was not observed at 4.7 mg/m3 (2.5 ppm)
NO2.
A 2-hour exposure to 9.4 mg/m3 (5 ppm)
NO2 in various inbred strains of mice (BDFj,
BALB/c, C57BL, and LA?!) either before or
after infectious challenge with an aerosol of
K. pneumoniae favored increased mortalities.
A similar enhancement in mortality was
9-12
-------
observed in hamsters exposed for 2 hours to
65.8 mg/m3 (35 ppm) N(>) and above, and
challenged with K. pneumoniae.5 °
The rate of clearance of inhaled bacteria
from the lungs of mice and hamsters was
reduced upon short-term exposure to NC^-5 °
The animals were exposed to 9.4 mg/m3 (5
ppm) NC>2 for 2 hours, and within 1 hour
challenged with K. pneumoniae aerosols. Im-
mediately, and at 1, 3, 5, 6, 7, and 8 hours
after the infectious challenge, the animals
were sacrificed and K. pneumoniae in lungs
was quantitatively assayed. In control animals
the bacterial population was markedly
reduced during the 6 hours following the
challenge. Thereafter, the population in-
creased, reaching its initial concentration after
approximately 8 hours. In mice and hamsters
exposed to 9.4 mg/m3 (5 ppm) NC«2, the
period of initial clearance was reduced to 4.5
and 5 hours, respectively, and the original
concentration was re-established in less than 7
hours.4 8
In a long-term study, Ehrlich and
Henry43-54 exposed four groups of mice to
940 Mg/m3 (0.5 ppm) NO2 for 6, 18, and 24
hours a day, 7 days a week, for up to 12
months. Challenge with an aerosol of K.
pneumoniae took place after 1, 3, 6, 9, and
12 months of exposure. Statistically sig-
nificant increases in mortality were observed
after continuous exposure to 940 Mg/m3 (0.5
ppm) for 3 months, and after 6- and 18-hour-
a-day exposures for 6 months. After 12
months exposure, mortality could only be
increased significantly when the NC>2 ex-
posure was continuous. The clearance rate of
viable bacteria from the lungs of mice was
also affected by long-term exposure to 940
Mg/m3 (0.5 ppm) NO2- In mice exposed to
NC>2 for 6 and 18 hours a day for 9 months
some reduced capacity to clear bacteria from
lungs was observed, and after 12 months ex-
posure a significant inhibition of bacterial
clearance was apparent. Mice exposed to NO2
fot 24 hours a day showed significantly
reduced capacity to clear viable bacteria after
6, 9, and 12 months of exposure.
Henry et al.15 exposed squirrel monkeys to
18.8 to 94.0 mg/m3 (10 to 50 ppm) NC«2 for
2 hours and challenged them by the intra-
tracheal route with K. pneumoniae. Exposure
to 94.0 mg/m3 (50 ppm) NC>2 for 2 hours
was not fatal, whereas the same exposure
followed by challenge with K. pneumoniae
was fatal to three out of three monkeys.
Squirrel monkeys exposed to 18.8 mg/m3 (10
ppm) NC>2 for 2 hours and then challenged
with K. pneumoniae had bacteria present in
their lungs 19 to 51 days after challenge. In
many bronchioles, epithelial cilia were
missing; cells had proliferated; and lympho-
cytes and polymorphonuclear cells had in-
filtrated the collapsed areas.
The same group5 5 exposed male squirrel
monkeys continuously to NO2 and challenged
them with K, pneumoniae aerosols. Out of
four monkeys exposed to 18.8 mg/m3 (10
ppm) NC>2 for 1 month, one died and two
had the infectious agent present in the lungs
at autopsy. Two out of seven monkeys
exposed to 9.4 mg/m3 (5 ppm) NC>2 for 2
months died, and five had the infectious agent
present in the lungs at autopsy.
Squirrel monkeys were also experimentally
infected with influenza A/PR-8 virus, 24
hours before continuous exposure to 18.8 and
9.4 mg/m3 (10 and 5 ppm) NO2- All six
monkeys exposed to 18.8 mg/m3 (10 ppm)
died within 3 days, while at 9.4 mg/m3 (5
ppm) one out of three succumbed to the
disease. There were no deaths in the control
group challenged with influenza virus.5 3
When the squirrel monkeys were exposed
to 9.4 mg/m3 (5 ppm) NC>2 for 5 months
and, during the exposure, challenged three
times by the intractracheal route with the
influenza A/PR-8 virus, the formation of
protective serum neutralization antibody
appeared to be depressed as evidenced by
serum neutralization antibody titers and
hemagglutination-inhibition titers.5 6
(2) Bacteria and Tobacco Smoke. Combined
exposures to NC>2, tobacco smoke, and K.
pneumoniae were reported for hamsters.42-57
A 2-hour exposure to 28.2 mg/m3 (15 ppm)
9-13
-------
NC>2 followed by 1-hour exposure to 3 per-
cent (v/v) tobacco smoke significantly
decreased the resistance to bacterial pneu-
monia, as evidenced by enhanced mortalities.
Furthermore the combined exposures reduced
the rate of clearance of viable bacteria from
the lungs of hamsters to a greater extent than
exposures to the individual pollutants. The
combined exposure produced irreversible,
marked alterations in surface morphology of
lung tissue. The typical structure of mucus-
secreting cells was not apparent, and a marked
loss of cilia was noted 2 days after exposure.
(3) Interferon Formation. Impairment of
interferon formation by NC>2 exposure has
been demonstrated by challenging rabbit al-
veolar monocytes with parainfluenza-3
virus.58 Rabbits exposed to 49.0 mg/m3 (25
ppm) NC>2 for 3 hours, either immediately
after, or at 0, 3, 6, 12, or 24 hours before
innoculation with rabbit pox virus, failed to
develop the anticipated resistance to
infection. This inhibition of resistance per-
sisted for at least 96 hours after NC>2 ex-
posures. During this period, alveolar mono-
cytes from NC>2exposed animals were un-
able to produce the antiviral substance, inter-
feron, in vitro when innoculated with the
parainfluenza-3 virus.
2. Effects in Man
a. Experimental Exposures
(1) Odor Perception. In a series of experiments
with healthy male volunteers between the
ages of 20 and 35 years, individuals were
exposed to varying concentrations of NC>2 in
a specially designed chamber, and the
olfactory threshold was measured under
various conditions (Table 9-6). At a con-
centration of 225 Mg/m3 (0.12 ppm) NO2,
only a few subjects perceived the odor im-
mediately. Perception was immediate in over
Table 9-6. RECOGNITION OF N02 ODOR BY HEALTHY
YOUNG ADULT MEN AFTER VARIED EXPOSURES IN AN
EXPERIMENTAL CHAMBER59
Concentration,3
mg/m^
0.225
0.415
0.835
8.0
19.9
39.9
56.8
ppm
0.12
(0.1-0.15)
0.22
(0.16-0.28)
0.42
(0.39-0.46)
4.0
(3.0-4.2)
10.6
(10.1-11.2)
19.7
(19.3-20.1)
30.2
(29.1-31.4)
Subjects
9
13
8
12
4
8
3
Odor perception on entry
to chamber
Number of
subjects
3
8
8
12
4
8
3
Duration,3
min
5
(0.5-10)
3
(MO)
2.5
(1-5)
5.5
(3-10)
8
(6-13)
12
(5-24)
32
(25-40)
3The range of actual measured values is included in parentheses.
9-14
-------
half of the subjects exposed to 415
(0.22 ppm) NO2- At higher concentrations,
beginning with 835 Mg/m^ (0.42 ppm) NC>2,
all subjects recognized the odor immediately.
Persistent recognition of the odor varied
considerably, ranging from a few minutes at
the lower exposure levels to over 30 minutes
at some of the higher concentrations.5 9
In another study60 of 14 subjects, the N©2
olfactory threshold was 230 jug/m3 (0.12
ppm). The effect of NC>2 and SC>2 was ad-
ditive, i.e., a lower concentration of each gas
led to odor perception if both gases were
present simultaneously.
Recently diesel exhaust odor has been the
subject of considerable study and it has been
found that NC>2 may contribute to the odor
of diesel exhaust. An assessment of the major
industrial odorants in diesel exhaust revealed
that the mixture with the greatest odor
contained about 940 Mg/m3 (0.5 ppm)
NQ2.61
(2) Pulmonary Function. In one experi-
ment, exposure to NC>2 was controlled in a
special room equipped with an air filter.62
Six normal subjects and four patients with
"moderate to marked" pulmonary disease
were exposed to concentrations of 940 to
5,640 jug/m3 (0.5 to 3 ppm) NC>2 on several
occasions for 2 to 3 hours at a time. Several
physiological parameters were measured
before, during, and after exposure, when the
subjects were either at rest or exercising.
Smokers were not excluded from the study,
but were required to abstain from smoking
for the 8-hour period prior to the chamber
study. The data showed no consistent changes
in airway resistance, pulse rate, respiratory
rate, or subjective complaints that could be
related to the NO2 challenge.
NC>2 and SC>2 produced additive effects on
pulmonary function in five healthy males,
ages 21 to 40, who were judged to be free
from respiratory disease.63 One subject
smoked 5 to 6 cigarettes a day. Each subject
was exposed on separate occasions to 7.5 to
9.4 mg/m3 (4 to 5 ppm) NO2 and 10.5 to
13.1 mg/m3 (4 to 5 ppm) SO2. Each ex-
posure was for 10 minutes, with 2-week
intervals between exposures. The subjects
wore nose clips and inhaled the gas-air
mixtures through a mouthpiece. Inspiratory
and expiratory flow resistance and pulmonary
compliance were measured before, immedi-
ately after, and 10, 20, and 30 minutes after
exposure. Vital capacity, FEV} (1 - second
forced expiratory volume), maximal mid-
expiratory flow rate, and peak flow rate were
measured prior to and 30 minutes after
exposure. Inhalation of NO2 caused an in-
crease in both inspiratory and expiratory flow
resistance, the maximum recorded increase
occurring 30 minutes after the end of ex-
posure. No data were given for the recovery
time. Mean pulmonary compliance was un-
changed, immediately after exposure, but was
slightly decreased 30 minutes after exposure
(significant at p <0.10 but not at <0.05).
Lung volumes and peak flow rates did not
change significantly. Inhalation of SC>2 caused
an increase in both inspiratory and expiratory
flow resistance that was maximal immediately
after inhalation and restored to pre-exposure
levels 30 minutes later.
Exposure to a mixture of 4.7 mg/m3 (2.5
ppm) NX>2 and 6.6 mg/m3 (2.5 ppm) SC>2
produced a bimodal increase in both inspira-
tory and expiratory flow resistance. The first
increase, which corresponded to the effect of
SC>2 alone, occurred immediately after ex-
posure. The second increase in resistance
corresponded to the effect of NC>2 alone, and
was maximal 30 minutes after exposure. SC>2
is known to cause an immediate reflex
increase in airway resistance along para-
sympathetic pathways.64 The mechanism by
which NC>2 induces resistance is unknown,
but the delay suggests that it is different from
that of SO2.6 3
b. Occupational exposures
There are numerous possibilities for oc-
cupational exposure to NOX. Hazardous oc-
cupations include the manufacture of NO,
nitration of cellulose, and other organic
9-15
-------
materials; electric-arc welding; and photo-
engraving. Accidental exposures have resulted
from the combustion of celluloid and nitro-
cellulose films, and from inhalation of silage
gas.
Four clinical types of poisonings due to
occupational exposures65 have been encoun-
tered: (1) irritant gas, (2) reversible, (3) shock,
and (4) combinations of the other three.
Irritant gas exposure is characterized initially
by severe irritation that results in pain, burn-
ing, and choking in the throat and chest;
violent cough; and the expectoration of
yellow-tinged sputum. The reversible type is
characterized by dyspnea, cyanosis, vomiting,
vertigo, somnolence, a feeling of intoxication,
fainting, loss of consciousness, and methe-
moglobinemia. Persons suffering this type of
poisoning do not develop pulmonary edema,
and if removed from the exposure early
enough, may recover completely. Otherwise,
the poisoning may rapidly become fatal.
Shock-type patients immediately show severe
symptoms of asphyxiation, convulsions, and
respiratory arrest; death is presumably due to
stasis in the pulmonary circulation. This form
is exceptional and may result from the sudden
inhalation of high concentrations. In the com-
bined type the patient immediately shows
symptoms referable to the central nervous
system, such as vertigo, somnolence, and a
staggering gait. There may be cyanosis. After
apparent recovery, this stage may be followed
some hours later by progressive dyspnea,
marked cyanosis, and pulmonary edema.
Several accidental exposures to silage
gas,66'67 which may contain very high con-
centrations of NC>2, have been reported. In
several instances the exposure proved fatal.
One man died 20 hours after being exposed to
this type of gas for 5 to 8 minutes.64 One
person exposed at the same time for 2 to 3
minutes survived, although he suffered acute
pneumonitis. Exposure to NO2 has been ex-
plained in six degrees, with corresponding
clinical syndromes: (1) at 940mg/m3 (500
ppm) or higher victims develop acute pulmo-
nary edema and die within 48 hours; (2) at
564 to 752 mg/m3 (300 to 400 ppm) pulmo-
nary edema with broncho-pneumonia devel-
ops and death ensues in 2 to 10 days; (3)
those exposed to 282 to 376 mg/m3 (150 to
200 ppm) develop bronchiolitis fibrosa obli-
terans, which is fatal in 3 to 5 weeks; (4)'
exposure to 94 to 188 mg/m3 (50 to 100
ppm) produces bronchiolitis with focal
pneumonitis lasting 6 to 8 weeks, followed by
spontaneous recovery; (5) individuals exposed
to NO2 in the range of 47 to 141 mg/m3 (25
to 75 ppm) develop varying degrees of bron-
chitis and broncho-pneumonia, but recover
completely; and (6) chronic intermittent
exposure to concentrations of NO2 in the
order of 18.8 to 75.2 mg/m3 (10 to 40 ppm)
may produce chronic pulmonary fibrosis and
emphysema.
Occupational exposure to NO2 is frequent-
ly encountered in a variety of welding
processes. Evaluation of responses to inhala-
tion of such fumes is complicated by the
presence of other contaminants. Predominant
among these are NO, ozone, manganese, ferric
oxide fumes, and particulates of various
types. In a case of acute poisoning from NOX
from an oxyacetylene torch, a welder died
from chemical pneumonitis 10 days later.68
Other, workers present during the exposure
developed coughs and other respiratory
symptoms. Random air samples obtained
under simulated conditions revealed oxides of
nitrogen in the range of 71.4 to 662 mg/m3
(38 to 352 ppm), occurring as NO2- After 3
minutes exposure to fumes containing 395 to
714 mg/m3 (210 to 380 ppm) NO2, welders
developed a dry cough and tightness in their
chests. These symptoms disappeared when
they returned to clean air.
Pulmonary edema developed 18 hours after
a 30-minute accidental exposure to the fumes
of an oxyacetylene torch estimated to have
produced approximately 169 mg/m3 (90
ppm) NO2- In pulmonary function tests con-
ducted at that time the vital capacity was 50
percent of the expected level, but the 0.5-,
1.0-, and 2.0-second FEV's were not dimin-
ished.69
9-16
-------
The effects of electric-arc welding ex-
posures from both bare and coated rods have
also been examined. In an experiment with
bare rods, two men were exposed to the
fumes of the electric-arc welding process for
190 minutes.47 '70 The average concentration
of nitrous fumes, expressed as NC>2, was 158
mg/m^ (84 ppm), with a maximum of 175
mg/m^ (93 ppm) that lasted for 40 minutes
and a peak of 194 mg/m^ (103 ppm) lasting 5
minutes. These concentrations measured by
the total nitrate method actually include an
unspecified mixture of NO-NO2-N2O4- Sub-
jects were also exposed to approximately 785
/ug/m^ (0.4 ppm) ozone throughout the
period. They reported no headache, eye irrita-
tion, throat irritation, or other ill effects,
however.
In welders exposed to the fumes from
electric-arc welding using coated rods47 for
the same length of time, the average MeHb
concentration was 2.5 percent and the maxi-
mum was 3 percent. The concentration of
"nitrous gas" in the working area did not
exceed 25 mg/m^ (13.3 ppm), expressed as
NC>2, of which not more than 20 percent was
estimated to be NO.
The possible long-term effects of occupa-
tional exposure to nitrous fumes was reported
by Becklake et al.71 in a study of seven
miners who were accidentally exposed to
nitrous fumes for periods of 5 to 75 minutes
and who developed pulmonary edema 3 to 27
hours after exposure (see Table 9-7). The
investigators studied pulmonary function at
the time of each patient's discharge from the
hospital and compared yearly follow-up ex-
amination data to the mean values for the
same data from 16 normal persons.
Among the seven patients, the most com-
mon effects were a reduction in maximal
breathing capacity and an increase in expira-
tory resistance; the latter functional impair-
ment was common to all the patients who
complained of exertional dyspnea. In the two
patiejits who felt that their capacity for work
was unaffected by the accident, tests showed
thatf pulmonary function had returned to
normal during the study period. Chest roent-
genograms of those patients with more than 6
years of underground mining service, taken
within a year prior to the exposure, had been
normal. Following the accident, the arterial
oxygen saturation was not affected either at
rest or during exercise. The mixing index, a
measure of efficiency in clearing nitrogen gas
from the lungs, was significantly different
from predicted values in four patients, al-
though it returned to normal in the course of
the study period in the three who could be
followed. The investigators concluded that
the exposed individuals sustained a degree of
bronchial and bronchiolar narrowing due to
fibrosis, secondary to various degrees of bron-
chiolitis obliterans.
A study of the survivors of the Cleveland
Clinic fire in 1967, who also were exposed to
high concentrations of nitrogen oxides, is dis-
cussed in chapter 10, Section C.I.
Multiple clinical symptoms, biochemical,
and hematologic changes were described in
workers engaged in the manufacture of sulfur-
ic acid and hence exposed to an average of 4.9
mg/m^ (2.6 ppm) NC<2 for 3 to 5 years.72
Because the data are not supported by diag-
nostic criteria, this report cannot be evalu-
ated. In contrast, Italian workers employed in
the manufacture of nitric acid and exposed to
an average of 56.4 to 65.8 mg/m^ (30 to 35
ppm) NC»2 for an unspecified number of years
exhibited no signs or symptoms of injury.73
D. OTHER OXIDES OF NITROGEN
Although several other oxides of nitrogen
besides NO and NO2 exist in the atmosphere,
they are generally present in very small quan-
tities and except for nitrous oxide (^O) have
not been of toxicological interest. Informa-
tion concerning their effects is likewise scarce.
Considerable attention has been focused on
N2O for the past century because of its anes-
thetic and analgesic properties. At concentra-
tions of 80 percent (1.44 x 106 mg/m3), N2O
is an effective general anesthetic. Inhalation
of 10 to 20 percent ^O (1.8 x 105 to 3.6 x
10^ mg/m^) provides effective analgesia.74
Although extensive information relevant to
9-17
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E. FUTURE RESEARCH NEEDS
To cope with the problem of NOX pollu-
tion, future research should include:
1. Further delineation of in vivo bio-
chemical and biophysical effects of nitrogen
oxide exposures relative to: (a) oxidation of
fatty acid double bonds in cellular lipids and
in lung surfactants; (b) denaturation or altera-
tion of lung proteins (collagen and elastin,
enzymes, and cellular membranes).
2. A definition of the relationship of
metabolic tissue changes to NC>2 dosage in
terms of a concentration-time response. The
relative importance of low-concentration,
long-term exposures versus short-term peak
concentration should be studied.
3. The determination of interaction of
NOX with particulate pollutants in terms of
biochemical, biophysical, infectious, and
ultrastructural responses.
4. The assessment of the biologic impor-
tance of tolerance and cross tolerance with
other oxidant pollutants.
5. Expanded studies to determine the
effects of NO2 on the infectious defense
mechanisms and immunological processes.
F. SUMMARY
The two oxides of nitrogen present in
ambient air in greatest quantities, nitric oxide
(NO) and nitrogen dioxide (NC>2), are poten-
tial health hazards. Summaries of laboratory
studies of animal exposures are given in
Tables 9-8, 9-9, and 9-10. The toxicology of
nitrous oxide (N2O) and other oxides of
nitrogen does not appear to be relevant to the
problems of ambient air pollution at the
present time. N2O is analgesic at concentra-
tions of about 1.8 x 105 to 3.6 x 105 mg/m3
(1.0 to 2.0 x 10^ ppm) and a general anes-
thetic at concentrations of 1.4 x 10^ mg/m3
(8.0 x 10^ ppm) and above.
Nitric Oxide
At/ concentrations found in the atmos-
phere, NO is not an irritant and is not con-
sidered to have adverse health effects. Its
main toxic potential at ambient concentra-
tions results from its oxidation to NO2- A
12-minute exposure to 3,075 mg/m3 (2,500
ppm) NO was lethal to mice. Lower doses,
from 24.6 mg/m3 (20 ppm) to 1.23 x 104
mg/m3 (104 ppm), of NO produced reversible
inhibition of bacterial hydrogenase activity.
Nitrogen Dioxide
Animal Studies
NO2 exerts its primary toxic effect on the
lungs. Most of the available information
comes from studies with animals. Concentra-
tions greater than 188 mg/m3 (100 ppm) are
lethal to most animal species, and 90 percent
of the deaths are caused by pulmonary
edema. The mortality rate may be modified
by varying the exposure product concentra-
tion x time (Ct), the temperature, and the
presence of other irritants.
Pulmonary function. Short-term exposures to
nonlethal concentrations of NO2 have
produced transient pulmonary-function
changes in the lungs of animals. Guinea pigs
have shown increased respiratory rates and de-
creased tidal volumes after exposure to con-
centrations of 9.8 mg/m3 (5.2 ppm) for 2
hours, and 24.4 mg/m3 (13.0 ppm) for 1
hour. Pulmonary function returned to normal
when animals were returned to clean air.
Similar changes in pulmonary function were
observed in squirrel monkeys exposed for 2
hours to 18.8 to 94.0 mg/m3 (10 to 50 ppm)
NO2 and in other monkeys exposed contin-
uously for 2 months to 9.4 mg/m3 (5 ppm)
NO2- Monkeys (M. speciosa) continuously
breathing 3.8 or 16.9 mg/m3 (2 or 9 ppm)
NO2 developed tachypnea which has persisted
for almost 2 years.
Rats continuously exposed to 1.5 mg/m3
(0.8 ppm) NO2 maintained a 20 percent in-
crease in respiratory frequency throughout
their lifetimes. Dogs exposed to 0.9 to 3.8
mg/m3 (0.5 to 2.0 ppm) NO2 plus 245 jug/m3
(0.2 ppm) NO for 18 months, however,
showed no signs of changes in pulmonary
function.
9-19
-------
Metabolism. The structure of lung collagen
and elastin was altered in rabbits exposed to
1.9 mg/m3 (1 ppm) NC>2 for 1 to 4 hours, but
the alteration appeared to be reversible within
24 hours. Similar changes were observed in
rabbits exposed to 470 jug/m3 (0.25 ppm)
NC>2, 4 hours a day, for 6 days, but recovery
was delayed and some damage persisted after
7 days. It has been suggested that the meta-
bolic activity of the lung tissue is reduced
following exposure to NC>2, and that repeated
exposure, with associated denaturation of
collagen and elastin, may be a factor in the
pathogenesis of pulmonary emphysema.
Lung lipids extracted from rats, exposed to
1.9 mg/m3 (1 ppm) NC>2 for 4 hours were
peroxidated. The process was delayed and sus-
tained, reached a maximum at 24 hours after
exposure, and was maintained for an addi-
tional 24 hours. Rats fed a vitamin E-deficient
diet and exposed to NC>2 had more peroxida-
tion of surfactant and tissue lipids than simi-
larly exposed rats receiving vitamin E supple-
mentation.
Pathology. Pathological lesions have been
observed in the lungs of animals following
both short- and long-term NC>2 exposures. At
exposures to 141 to 188 mg/m3 (75 to 100
ppm) for 2 hours, rabbits, rats, and guinea
pigs developed acute inflammation in bron-
chiolar epithelium, but appeared to recover 2
weeks after exposure. At 1.9 mg/m3 (1 ppm)
for 1 hour, or 940 Mg/m3 (0.5 ppm) for 4
hours, mast cells of rat lungs became degranu-
lated, possibly signifying the onset of an acute
inflammatory reaction. These cells returned
to normal 24 hours after the end of exposure.
More serious damage was found in lungs of
squirrel monkeys exposed for 2 hours to 18.8
to 94.0 mg/m3 (10 to 50 ppm) NO2; the pri-
mary lesions found at low concentrations
became progressive alveolar expansion. Hyper-
plasia of the respiratory bronchiolar epithe-
lium was seen in hamsters exposed to 84.6 to
103 mg/m3 (45 to 55 ppm) for 10 weeks. A
similar response was noted in the major bron-
chi and distal portions of the respiratory tract
in hamsters exposed to 188 mg/m3 (100
ppm) for 6 hours.
Chronic Changes. Since certain pathological
changes seen in animals after experimental
NO2 exposure are similar to changes occur-
ring in the pathogenesis of chronic obstructive
pulmonary disease in man, it is suggested that
long-term, low-level exposures to this pollut-
ant may play a significant role in the develop-
ment of chronic lung disease.
Improved histochemical and electron
microscopic techniques have shown that
long-term exposure of rats to NC>2 at concen-
trations that do not produce acute inflamma-
tory responses have a cumulative and sus-
tained effect. Emphysema-like lesions were
produced in the rat lungs with concentrations
of 18.8 to 47.0 mg/m3 (10 to 25 ppm). Rats
exposed to 3.8 mg/m3 (2 ppm) for their
natural lifetime had less cilia; less-than-normal
bronchiolar, epithelial blebbing; and crystal-
loid, rod-shaped, intracytoplasmic inclusion
bodies in their bronchiolar epithelium. Similar
effects have been seen occasionally in rats
continuously exposed to 1.5 mg/m3 (0.8
ppm). Mice exposed to 940 Mg/m3 (0.5 ppm)
for 3 to 12 months on 6-, 18-, and 24-hour
daily schedules have shown increase in the
size of alveoli, due to alveolar distension
rather than septal breakage. Additionally,
inflammation of the bronchiolar epithelium
with a reduction in distal airway size sug-
gested the development of early focal emphy-
sema. Rats exposed chronically to 18.8 to
47.0 mg/m3 (10 to 25 ppm) NC>2 were
observed to develop compensatory changes
such as polycythemia, thoracic kyphosis, and
a lateral flaring of the ribs. Early evidence of
pulmonary emphysema was observed in dogs
exposed continuously to 47.0 mg/m3 (25
ppm) NC>2 for 6 months.
Susceptibility to Infection. Exposure of
mice, hamsters, and squirrel monkeys to NC>2
causes increased susceptibility to bacterial
pneumonia and influenza infections, demon-
strated by increased mortality, decreased
survival time, and a reduction in ability to
clear infectious agents from the lungs.
9-20
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9-27
-------
In mice, the threshold of increased suscept-
ibility to Klebsiella pneumoniae occurred at
6.6 mg/m3 (3.5 ppm) NC>2 for 2 hours, if the
infectious challenge was given within 1 hour
after the NC>2 exposure. Mice infected with
K. pneumoniae and exposed up to 72 hours
later to 9.4 or 47.0 mg/m3 (5 or 25 ppm)
NC>2 for 2 hours exhibit similarly enhanced
susceptibility to the respiratory infection.
Squirrel monkeys exposed to 18.8 mg/m3 (10
ppm) NC>2 for 2 hours, then challenged with
K. pneumoniae aerosol, retained the infec-
tious agent in the lungs for extended periods
of time. Two-hour exposure to 94.0 mg/m3
(50 ppm) NC>2 followed by infectious chal-
lenge, led to a markedly increased mortality
in squirrel monkeys.
Continuous exposure reduces the NC>2
threshold concentration. In long-term studies
of mice, significantly increased susceptibility
to infection occurred after continuous daily
exposure to 940 jug/m3 (0.5 ppm) NC>2 for 3
months, or 6- or 18-hour daily exposure for 6
months. A significant increase in susceptibil-
ity to influenza virus or K. pneumoniae has
also been found in squirrel monkeys contin-
uously exposed to 18.8 and 9.4 mg/m3 (10
and 5 ppm) NC>2 for 1 and 2 months, respec-
tively.
Impairment of interferon formation and
decreased resistance to viral infection was
demonstrated in rabbits exposed to 47.0
mg/m3 (25 ppm) NO2 for a 3-hour period.
Systemic effects. Inhalation of NC>2 can
produce systemic effects generally secondary
to those on the lungs. Monkeys exposed to
28.2 to 94.0 mg/m3 (15 to 50 ppm) NC>2 for
2 hours exhibited cellular changes in heart,
liver, and kidney tissue. Long-term exposure
of rats to 2.5 to 5.6 mg/m3 (1.3 to 3.0 ppm)
for 15 to 17 months has been associated with
loss of weight and reduced rates of weight
gain.
A circulating substance, possibly a lung
antibody, has been detected in the blood of
guinea pigs exposed to 9.4 mg/m3 (5.0 ppm)
for 4 hours daily, 5 days per week, for 5.5
months. Guinea pigs exposed to 28.2 mg/m3
(15 ppm) NC>2 for 10 weeks showed an altera-
tion in O2 consumption and enzyme activi-
ties (aldolase and lactic dehydrogenase) in the
serum, lung, kidney, liver, and spleen.
Rats and monkeys continuously exposed to
3.8 mg/m3 (2.0 ppm) NC>2 for 3 weeks ex-
hibited marked polycythemia. An increase in
circulating methemoglobin was detected in
the blood of several species exposed to con-
centrations greater than 122 mg/m3 (70 ppm)
NC>2 for 1 hour.
Human Studies
The small amount of information available
concerning the toxicological effects of the
oxides of nitrogen in man pertains to levels of
these compounds higher than those normally
found in ambient air. Experimental exposure
of volunteer subjects to 9.4 mg/m3 (5 ppm)
NC>2 for 10 minutes has produced a substan-
tial, but transient, increase in airway resist-
ance. Other information derived from occupa-
tional exposure to higher concentrations of
NO/NO2 mixtures is complicated by the
presence of other pollutants. Impaired pulmo-
nary function, indicated by reduced maximal
breathing capacity, increased expiratory re-
sistance, and occasional decreased vital capac-
ity, has been observed in patients accidentally
exposed to high concentrations of nitrous
fumes for a few minutes. In some cases, the
impairment has lasted for more than 2 years
after the incident. Occupational exposure to
169 mg/m3 (90 ppm) NO2 for 30 minutes
produced pulmonary edema and decreased
vital capacity 18 hours later. Exposure to
very high concentrations for about 5 minutes
has produced death within 2 days to 5 weeks.
The human threshold for perceiving the
odor of NO2 appears to be about 225 jug/m3
(0.12 ppm).
G. REFERENCES
1. Gray, E. Le B. Oxides of Nitrogen, Their Oc-
currence, Toxicity, Hazard. AMA Arch, of Ind.
Health, 19: 479-586, 1959.
2. Flury, F. and F. Zernik. Schadliche Gas. Berlin,
Sprunger, 1931.
3. Murphy, S. D., et al. Altered Function in
Animals Inhaling Low Concentrations of Ozone
9-28
-------
and Nitrogen Dioxide. Amer. Ind. Hyg. Ass. J.,
25: 246-253, 1964.
4. Paul, W. D. and C. R. Kemp. Methemoglobin: A
Normal Constituent of Blood. Proc. Soc. Exp.
Biol. Med., 56: 144-196, 1951.
5. Bodansky, M. Methemoglobinemia and
Methemoglobin-Producing Compounds. Pharma-
col. Rev, 3: 144-196, 1951.
6. Flury, F. The Role of Nitrogen Monoxide in
Poisoning from Nitrogen Fumes. Arch. Exp.
Pathol. Pharmakol., 157: 104-106, 1930.
7. Pflesser, G. The Importance of Nitrogen Mon-
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1935.
8. Petr,'B. and P. Schmidt. The Influence of an
Atmosphere Contaminated with Sulfur Dioxide
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1967.
9. Sancier, K. M., G. Freeman, and J. S. Mills.
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of Nitrogen Dioxide on Resistance of Squirrel
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halation and Lung Antibodies. Arch. Environ.
Health, 10: 274-277, 1965.
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Threshold Limit of NO2- Arch. Environ. Health,
10: 455-466, 1965.
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Long-Term Exposure to Low Levels of Air Pol-
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Beagle. Arch. Environ. Health, 19: 45-50, 1969.
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20. Mueller, P. K. and M. Hitchcock. Air Quality
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Continuously Exposed to Two Parts per Million
of Nitrogen Dioxide. Arch. Environ. Health, 17:
181-192, 1968.
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the Terminal Bronchiole of the Rat During
Continuous Low-Level Exposure to Nitrogen
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Effects of Subacute Concentrations of NO2 on a
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9-29
-------
31. Kleinerman, J. Effects of NC>2 in Hamsters:
Autoradiographic and Electron Microscopic
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on Histopathology of Lung Tissue. Arch.
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After Low-Level Exposure to NO2- Arch.
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Emphysema and a Model System with NC^. Yale
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Covert Pathogenesis of NC<2 Induced
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Nitrogen Dioxide: I. Effects on Resistance to
Bacterial Pneumonia. Arch. Environ. Health, 17:
860-865, 1968.
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Concentrations of Nitrogen Dioxide and Sulfur
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October 1962.
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Inhaling Nitrogen Dioxide for Single, Short-Term
Exposures. Aeronautical Systems Div., Tech.
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Ass. J. 23: 457-462, 1962.
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Chemical and Physiological Investigation of
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Effect of Nitrogen Dioxide-Nitrogen Tetroxide
on Oxyhemoglobin Dissociation. SAM-TR-67-33.
U. S. A. F. Sch. Aerosp. Med., 1-5, April 1967.
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Chronic Exposures to Nitrogen Dioxide Effects
on Oxygen Consumption and Enzyme Activity
on Guinea Pig Tissues. Arch. Environ. Health,
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604-614, 1966.
51. Gardner, D. E., R. C. Holyman, and D. L. Coffin.
Effects of Nitrogen Dioxide on Pulmonary Cell
Population. J. Bacteriol. 98: 1041-1043, 1969.
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tory Infection. Arch. Environ. Health, 6:
638-742, 1963.
53. Purvis, M. R. and R. Ehrlich. Effect of Atmos-
pheric Pollutants on Susceptibility to Respira-
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Infec. Dis., 113: 72-75, 1963.
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ence of Nitrogen Dioxide on Resistance to
Respiratory Infections. (Inhalation Carcino-
genesis. AEC Symposium Series 18. CONF-
691001. Gatlinburg. October 1969.) 14 pages.
National Technical Information Service. Spring-
field, Virginia. April 1970. 243-257.
55. Henry, M. C., et al. Chronic Toxicity of NO2 in
Squirrel Monkeys III. Effect of Resistance to
Bacterial and Viral Infection. Arch. Environ.
Health, 20: 566-570, 1970.
56. Fenters, J., et al. Chronic Toxicity of Nitrogen
Dioxide. IV. Serologic Response in Squirrel
Monkeys Exposed to 5 ppm NO2 and Influenza
9-30
-------
Virus. Arch. Environ. Health, To Be Published,
1970.
57. Ehrlich, R., et al. Effects of Nitrogen Dioxide
and Tobacco Smoke on Retention of Inhaled
Bacteria. (Third International Symposium on
Inhaled Particles. London. September 16-23,
1970.) pp. 7.6.1-7.6.4.
58. Valand, S. B., J. D. Acton, and Q. N. Myrvik.
Nitrogen Dioxide Inhibition of Viral Induced
Resistance in Alveolar Monocytes. Arch.
Environ. Health, 20: 303-309, 1970.
59. Henschler, D., et al. Olfactory Threshold of
Some Important Irritant Gases and Manifesta-
tions in Man by How Concentrations. Arch.
Gewerbepathol. Gewerbehyg., Berlin, 17:
547-570, 1960.
60. Shalamberidze, O. P. Reflex Effects of Mixtures
of Sulfur and Nitrogen Dioxides. Hyg. Sanit., 32:
10-14, 1967.
61. Vogh, J. W. Nature of Odor Components in
Diesel Exhaust. J. Air Pollut. Contr. Ass., 19:
773-777, 1969.
62. Rokaw, S. N., et al. Human Exposures to Single
Pollutants - NO2 in a Controlled Environment
Facility. (Preprint of presentation at the Ninth
AMA Air Pollution Medical Research Confer-
ence. Denver. July 24, 1968.)
63. Abe, M. Effects of Mixed NO2 - SO2 Gas on
Human Pulmonary Functions. Bull. Tokyo Med.
Dent. Univ., 14: 415-433, 1967.
64. Nadel, J. A., et al. Mechanism of Bronchocon-
striction During Inhalation of Sulfur Dioxide. J.
Appl. Physiol., 20: 164-167, 1965.
65. Von Oettingen, W. F. The Toxicity and Pollution
Dangers of Nitrogen Fumes. U. S. Public Health
Service. Washington, D. C. Public Health Bulletin
No. 272. 1941.34 pages.
66. Grayson, R. R. Silage Gas Poisoning: Nitrogen
Dioxide Penumonia, a New Disease in Agricul-
tural Workers. Ann. Intern. Med., 45: 393-408,
1956.
67. Lowry, T. and L. M. Schuman. Silo-Filler's
Disease. A Syndrome Caused by Nitrogen
Dioxide. J. Amer. Med. Ass., 162: 153-160,
1956.
68. Adley, F. E. Exposures to Oxides of Nitrogen
Accompanying Shrinking Operations. J. Ind.
Hyg. Toxicol., 28: 17-20, 1946.
69. Norwood, W. D., et al. Nitrogen Dioxide Poison-
ing Due to Metal Cutting with Oxyacetylene
Torch. J. Occup. Med., 8: 201-305, 1966.
70. Harrold, G. C., S. F. Meek, and C. P. McCord. A
Chemical and Physiological Investigation of
Electric Arc Welding: Bare, Washed Welding
Rods. J. Ind. Hyg. Toxicol., 22: 347-378, 1940.
71. Becklake, M. R., et al. The Long-Term Effects of
Exposure to Nitrogen Fumes. Amer. Rev.
Tuberc. Pulm. Dis., 76: 398-409, 1957.
72. Vigdortschik, N. A., et al. The Symptomatology
of Chronic Poisoning with Oxides of Nitrogen. J.
Ind. Hyg. Toxicol., 19: 469-473, 1937.
73. Vigliana, B. C. and N. Zurlo. Experiences of the
Clinical del Lavoro with Maximum Allowable
Concentrations of Industrial Poisons. Arch.
Gewerbepathol. Gewerbehyg., 13: 528-535,
1955.
74. Goodman, L. S. and A. Gelman (eds.). The
Pharmacological Basis of Therapeutics. New
York: Macmillan, 1965.
75. Freeman, G., N. J. Furiosi, and G. B. Haydon.
Effects of Continuous Exposure to 0.8 ppm NO2
on Respiration of Rats. Arch. Environ. Health,
13: 454-456, 1966.
9-31
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CHAPTER 10.
EPIDEMIOLOGICAL APPRAISAL
OF NITROGEIN OXIDES
A. INTRODUCTION
In contrast to the large volume of toxico-
logical data, epidemiological data on the
effects of exposure to nitrogen oxides (NOX)
are meager. Epidemiological studies have been
primarily concerned with nitrogen dioxide
(NC>2) because it is the oxide of nitrogen that
has been most closely associated with effects
on health. Generalizations drawn from the
toxicological data in chapter 9 form the basis
for several of the epidemiology studies pre-
sented in this chapter; that is to say, NO2
exerts its primary toxic effect on the lungs
where, in animals, exposure can be associated
with increased susceptibility to respiratory
infection and emphysematous changes.
Exposure to other pollutants, such as
ozone, SC>2, metal fumes, and aerosols, pre-
sents a major problem in the interpretation of
all information collected. The studies re-
ported here have incorporated some measures
to minimize interference by these factors.
B. EPIDEMIOLOGIC EVIDENCE OF
LONG TERM EFFECTS
1. The Cleveland Clinic Study1 -
An Accidental High Exposure
On May 15, 1929, the X-ray room of the
Cleveland Clinic was engulfed in flames;
50,000 nitrocellulose films were ignited; and
three explosions occurred. The air was filled
with concentrations of nitric oxide (NO),
carbon monoxide (CO), and hydrocyanic acid
(HCN) estimated at 63.3 g/m3 (51,500 ppm),
45.9 g/m3 (40,000 ppm), and 6 g/m3 (5,400
ppm), respectively. Ninety-seven individuals
succumbed within 2 hours. Neither CO nor
HCN was considered the primary cause of
death in the 26 additional individuals who
died in less than 1 month, nor were either CO
or HCN implicated in 92 nonfatal cases of
serious physical injury.
Much later, an epidemiological study was
conducted to determine whether survivors of
the disaster incurred a risk of dying sooner
than nonexposed individuals.
Study groups consisted of individuals who:
1. Were present in the building at the
time of the explosion.
2. Entered the building that afternoon.
3. Were exposed to smoke in an adjacent
building.
4. Assisted rescue and first-aid workers.
An estimated 98 to 99 percent of the indi-
viduals present at the fire were enumerated by
searching records and 87 percent of these
were actually studied. Individuals, who were
present at the fire, but who were not in any
of the four exposure groups were used as
controls.
When cumulative observed survival rates
and cumulative expected survival rates were
compared, their ratios, calculated for the
years 1929 to 1965, showed no statistically
significant differences between mortality rates
of exposed and nonexposed groups.
2. The Chattanooga Studies - Ambient
NO£ and Respiratory Illness
a. Community effects
Shy, et al.2'3 studied the effects of com-
munity exposure to nitrogen dioxide in four
residential areas in greater Chattanooga. One
area, in close proximity to a large TNT plant,
had high-NO2 and low-particulate exposure.
Another had high-suspended particulate and
low-NO2 exposure. The two other areas
served as "clean" controls.
10-1
-------
(1.) Pollutant monitoring. Each area con-
tained three elementary schools. In the high-
NC>2 area surrounding the TNT plant,
monitoring sites were selected to represent
the average pollution level near each of the
three schools. Sites for pollution monitoring
stations in the high-particulate and the
control areas were selected to represent
average pollutant exposure on an area-wide
basis. The effects of wind, topography,
vegetation, and local pollution sources were
considered in selecting a site.
Twenty-four-hour total-suspended-particu-
late matter, suspended nitrates, suspended
sulfates, and gaseous nitrogen dioxide concen-
trations were measured daily at each site, in
November 1968 and November 1969. From
December 1968 through February 1969, and
again in April 1969, these 24-hour concentra-
tions were measured once every 4 days on a
systematic sampling schedule (Table 10-1).
Twenty-four-hour sulfur dioxide concentra-
tions were measured once weekly in Novem-
ber 1968, but measurements were discon-
tinued when concentrations were found to be
less than 2.8 jug/m^ (0.015 ppm) at each site.
Integrated 24-hour NC>2 samples were
collected by gas-bubbler techniques and
Table 10-1. ARITHMETIC MEAN AND 90TH PERCENTILE CONCENTRATIONS OF POLLUTANTS SAMPLED
FOR 24 HOURS AT VARIOUS SITES2
Pollutant
NO2, ppm
Suspended
nitrate,
Mg/m3
Suspended
sulfate,
Mg/m3
Total
suspended
particulates,
Mg/m3
Soiling
index,c
Coh/1000
lineal ft
Level
of
exposure
Meana
90 percentile"
Standard deviation
Mean
90 percentile
Standard deviation
Mean
90 percentile
Standard deviation
Mean
90 percentile
Standard deviation
Mean
90 percentile
Standard deviation
High NO2
School
1
0.109
0.242
0.098
7.2
14.8
9.1
13.2
22.6
6.8
96
183
63
0.80
1.46
0.51
School
2
0.078
0.141
0.054
6.3
13.4
5.8
11.4
19.2
6.4
83
138
46
0.89
1.73
0.64
School
3
0.062
0.098
0.040
3.8
8.0
4.6
10.0
19.5
4.9
63
108
42
0.91
1.84
0.68
High
parti-
culate
0.055
0.087
0.024
2.4
4.6
1.7
10.7
17.3
4.6
99
181
58
2.09
4.37
1.67
Control
1
0.063
0.096
0.030
2.6
5.9
2.6
9.8
15.8
4.5
72
128
45
1.39
3.29
1.20
Control
2
0.043
0.069
0.021
1.6
3.1
1.0
10.0
15.6
4.5
62
112
35
1.23
2.53
0.89
aMean = arithmetic mean of all samples collected.
"90 f ercentile = concentration exceeded by only 10 percent of samples.
c4-h9ur measurements.
10-2
-------
analyzed by the Jacobs-Hochheiser method.
Total-suspended-particulate matter, nitrate,
and sulfate were collected with a high-volume
sampler and subsequently, analyzed.
(2.) Health-effect evaluation. Two possible
health effects of NO2 exposure were in-
vestigated in this community during the
1968-69 school year: (1) impaired ventilatory
function in elementary school children and
(2) increased frequency of acute respiratory
illness in family groups. A total of 987
second-grade school children participated in
the ventilatory testing. Weekly ventilatory
function (Forced Expiratory Volume in 0.75
seconds, FEVg 75) of each child was adjusted
for differences in individual standing height,
for boys and girls, separately. These tests were
made during November 1968 and March
1969.
The socioeconomic factors considered
were: house value or rent, education of the
head of the household, and the number of
people in a household (crowding). In each
case, the high-NC^low-particulate exposure
area exibited the highest socioeconomic level,
followed in rank by control areas. The low-
NC>2high-particulate exposure area had a
distinctly lower socioeconomic level. Home
cigarette smoking in the control and high-
NC>2 areas differed only by 1 percent. No
differences in the duration of residence at the
current address were found in any of the
areas.
Four ventilatory tests with Stead-Wells
spirometers were made weekly in November
1968 and again in March 1969. Analysis of
variance was used to determine the statistical
significance of factors such as sex, month of
test, study area, schools within high-NC>2
area, and the concentration of NC>2 on day of
test (see Tables 10-2 and 10-3).
At the beginning of the study, all members
of the household of each participating second-
grade child were asked to volunteer for the
second phase of the study a prospective
study, designed to assess the frequency of
acute respiratory disease. A total of 4,043
individuals in 871 families participated. At
bi-weekly intervals from November 1968
through April 1969, each family was asked to
report the incidence of new colds or sore
throats, in terms of the age and sex of sick
household members and the severity of the
illness. Severity indices included: the presence
of fever, length of home confinement, and
consultation with a doctor for treatment.
Area differences in respiratory illness rates
were analyzed in the following groupings: the
entire 24-week period, the influenza-A inter-
val, the interim interval, and the influenza-B
interval.
(3.) Conclusions. The ventilatory per-
formance of second-grade school children in
the high-NO2 exposure area was significantly
lower than performance of children in the
control areas.
Table 10-2. ANALYSIS OF VARIANCE OF EFFECTS ON HEIGHT-AD JUSTED FEV0 75 OF SEX
OF CHILD, MONTH OF TESTING, AND STUDY AREA 2
Factor
Sex of child
Month of test
Study area
High-NC>2 vs. Controls 1 and 2
High-TSPa vs. Controls 1 and 2
Control 1 vs. Control 2
Mean
square
0.3852
0.0318
0.0098
0.001 1
0.0004
F
value
189.3
15.6
4.8
0.6
0.2
Probability of
significant difference
p<0.01
p<0.01
p<0.05
not significant
not significant
aTotal suspended particulate matter.
10-3
-------
Table 10-3. ANALYSIS OF VARIANCE OF EFFECTS ON HEIGHT-ADJUSTED FEV0 75
OF NO2 CONCENTRATIONS ON DAY OF TEST, SCHOOL WITHIN HIGH-NO2 AREA,
SEX OF CHILD, AND MONTH OF TEST2
Factor
Sex of child
Month of test
NO2 on day of test
Schools within high-N02 area
Schools 1 vs. 2 and 3
School 3 vs. 1 and 2
School 1 vs. 2
Mean
square
0.0952
0.0178
0.0009
0.0019
0.0007
0.0030
F
value
90.3
16.9
0.9
1.8
0.6
2.8
Probability of
significant difference
p<0.01
p<0.01
not significant
not significant
not significant
not significant
Illness-incidence rates for each family
segment in the high-NO2 area were consist-
ently and significantly higher than indicence
rates in the two control areas throughout the
entire study period. This increased incidence
of acute respiratory disease was observed
when the 24-hour NC>2 concentration, meas-
ured over a 6-month period, was between 117
and 205 jug/m3 (0.062 and 0.109 ppm) and
the mean suspended nitrate level was 3.8
Mg/m3 or greater (Tables 10-1 and 10-4).
School 3 in the high-NO2/low-particulate
area had consistently higher incidence rates
than the control areas, even though the
average NC>2 level was the same as in control
1 (Table 10-4). The NC>2 and suspended
Table 10-4. AVERAGE BIWEEKLY RESPIRATORY ILLNESS RATES PER 100 FOR EACH FAMILY
SEGMENT ACCORDING TO EXPOSURE TO OXIDES OF NITROGEN3
Rank of Population
by N02 exposure
Average
24-hour
NO2, ppm
0.109
0.078
0.062
0.063
0.043
Average
24-hour
suspended
nitrate,
Mg/m3
7.2
6.3
3.8
2.6
1.6
Study
population
School 1
(high-N02)
School 2
(high-N02)
School 3
(high-N02)
Control 1
Control 2
Family segment
All family
members
17.7
17.5
16.3
13.9
15.0
Second
graders
23.4
23.4
20.4
18.0
20.1
Siblings
19.9
18.0
19.1
15.6
17.0
Mothers
15.3
14.4
13.4
11.8
12.3
Fathers
11.0
12.8
12.1
8.8
9.6
10-4
-------
nitrate levels at school 3 were, however, more
variable than control area levels. This varia-
bility was associated with higher peak-levels
of these pollutants (Table 10-1).
Illness-incidence rates peaked during the
A2/Hong Kong-influenza epidemic and again
during an influenza-B outbreak. Families
residing in the two polluted areas reported a
consistent excess of respiratory illness over
the control area, particularly during the A2
epidemic and the interim period between
epidemics.
Control-2 area appeared to be hard hit by
the influenza-B epidemic. During this time,
illness rates among second graders and
mothers in the Control-2 area were equal to
rates of comparable family segments in the
high-NO2 area. Rates in Control-1 area, how-
ever, remained well below those of the high-
NC>2 area in all intervals and in all family
segments.
In the high-NO2 area and in the high-partic-
ulate area excess illness rates occurred in all
family segments: second-grade children,
siblings, fathers, and mothers. The relative
excess was 18.3 percent in the high-NO2 area
and 10.4 percent in the high-particulate area
(Table 10-5). Area differences in illness rates
could not be explained by difference in
family composition, economic level, demo-
graphic characteristics, or prevalence of
chronic conditions. Parental smoking habits
did not appear to influence respiratory illness
rates in second-grade school children. Expo-
sure to NC<2 and to suspended particulates
appear to be the most probable explanation
for the observed excess in respiratory illness
rates for the population. Severity of illness
was essentially the same among all the areas;
however, a precise NC>2 dose-response rela-
tionship cannot be established from the data.
b. Acute Lower Respiratory Illness
in Children
Later, Pearlman, et al.4 made a retrospec-
tive study of acute lower respiratory illness
among infant cohorts and first and second
graders living in three of the Chattanooga
neighborhoods previously described, (all,
except the high-particulate area). Pearlman
felt, on the basis of aerometric observations,
that one of the control areas (Control 1) in
the Shy study could properly be designated
an intermediate-NC»2-exposure area. The high-
Table 10-5. PERCENT RELATIVE EXCESS* OF RESPIRATORY
ILLNESS AMONG FAMILY SEGMENTS IN EXPOSED VERSUS
CONTROL AREAS DURING 24 WEEKS OF STUDY3
Family segment
All family members
Second graders
Siblings
Mothers
Fathers
Study areas
High-N02
18.8
16.8
16.0
18.3
31.5
High-particulate
10.4
12.6
-0.06
34.2
22.8
a /-Illness rate of exposed group _ n
Illness rate of control groups
10-5
-------
NC>2 exposure area and the other control area
(Control 2) completed the pollutant-dose
gradient for the Pearlman study.
Parents were asked to complete a question-
naire for the study-children, reporting the
frequency with which a physician had diag-
nosed croup, bronchitis, pneumonia, and
asthma, during the 3-year period from July
1966 through June 1969. Completed ques-
tionnaries were returned by 95 percent of the
1820 school children and 84 percent of the
1311 infants still residing in the study areas.
Questionnaire responses were validated by
physicians' office and hospital records. Sensi-
tivity and specificity exceeded 67 percent for
each clinical diagnosis. Parents could usually
approximate the number of episodes of each
illness but were often unable to date each,
precisely, within the 3-year study period.
About 7 percent of the respondents in each
area had a history of asthma and were ex-
cluded from the main analysis. There were
too few asthmatics in each dose-duration
category to permit firm conclusions about
this subpopulation, but excess bronchitis was
noted among the ones residing in the high-
exposure area.
Exposure to intermediate and high levels of
NC>2 was associated with a significant increase
in acute bronchitis among the infant cohort,
exposed for 3 years, and school children,
exposed for 2 and 3 years. This greater fre-
quency of acute bronchitis was observed
when the mean 24-hour NC<2 concentration,
measured over a 6-month period, was between
118 and 156 Mg/m3 (0.063 and 0.083 ppm)
(Table 10-6).
Pearlman suggested a threshold relationship
for NC>2 exposure and bronchitis since the
morbidity excess followed the pollutant gradi-
ent only among school children exposed for 3
years. Area differences in total acute lower
respiratory illness could be accounted for by
bronchitis excess. Croup, pneumonia, and
hospitalizations for acute lower respiratory ill-
ness did not show significant area differences.
Since the high-NO2 exposure area of this
study included a school with NC<2 levels
about the same as the levels in the intermedi-
ate area, the difference in NC>2 exposure
levels between the high and intermediate areas
was diminished. This may explain why the ill-
ness rates of some intermediate exposure
groups exceeded the rates of high exposure
groups. Groups within each school of the
high-NO2 area were too small, however, to
allow separate analysis of illness rates.
The Pearlman study replicated Shy's obser-
vation that excess acute respiratory illness can
be found among children living in NC>2-pol-
Table 10-6. DISTRIBUTION OF CHILDREN REPORTING ONE OR MORE
EPISODES OF BRONCHITIS BY LENGTH OF EXPOSURE4
6-month mean NC>2
High-N02,
156 Mg/m3 (0.083 ppm)
Intermediate-N02,
118 Mg/m3 (0.063 ppm)
Low-NO2 (control),
81 Mg/m^ (0.043 ppm)
School children
exposure, yr
1
20.9
31.6
25.1
2
34 .7a
45 .5a
20.3
3
32 .2a
31.2a
23.2
Infant exposure,
yr
1
33.3
26.2
21.1
2
37.5
29.5
34.0
3
46.8a
50.5a
36.3
aDiffers significantly from low-N02(control) area.
10-6
-------
luted areas. He suggested that acute lower-
respiratory illness may be a more selective,
sensitive indicator of pollutant effect upon
host response than is acute general respiratory
illness.
3. Czechoslovakia!! Study - Ambient
N(>2 and SC>2 on Peripheral Blood
Studies of Czechoslovakian children5 who
lived near a factory that emits NOX and SC>2
have produced some positive information not
usually sought in the United States. Data are
available from three towns: (1) Ohrazenice,
which experiences air pollution predomi-
nately from SC>2 [concentrations ranging
from 30 to 320 Mg/m3 (0.01 to 0.12 ppm)],
with slight admixtures of NOX [concentra-
tions ranging from 5 to 50 Mg/m3*]; (2)
Rosice, which experiences a larger amount of
pollution by NOX (concentrations ranging
from 20 to 70 /Lig/m3), and only a small
amount of SC>2 pollution [concentrations up
to 12 /zg/m3 (0.005 ppm)]; and (3) Bohda-
nec, which has no nearby air pollution
sources.
Petr and Schmidt5 observed a statistically
significant difference in the configuration of
lymphocytes and monocytes in the smears of
peripheral blood from children in the three
areas. Although they failed to indicate the
size of the study group, they noted that the
children did not differ from one another in
age or socioeconomic grouping. The authors
consider the results to be a sensitive indicator
of the children's reaction to SC>2 and nitrous
gases in the environment.
When they studied the blood of ten 8- to
10-year-old children from each of the three
towns, Petr and Schmidt5 observed relative
increases in resistance to hemolysis and in-
creases in number of immature red blood cells
in children from Rosice (high-NO2/low-SO2)
and Ohrazenice (high-SO2/low-NO2) as
compared to children from Bohdanec (con-
trol). They interpreted this as a compensatory
response of tne children to noxious sub-
*It is not possible to calculate ppm from total oxides of
nitrogen.
stances in the environment. Methemoglobin
levels were determined in these same children,
and the investigators observed an average of
2.5 percent methemoglobin in the blood of
the Rosice (high-NO2/low-SO2) children,
compared to an average of 0.86 percent in the
children from Bohdanec (control). The differ-
ence was statistically significant (p <0.025),
but the possible contribution of large
amounts of nitrates in the drinking water
could not be overlooked. When the study was
repeated in the Rosice (high-NO2/low-SO2)
children at a later date, after the source of
atmospheric nitrous gases had been con-
trolled, they found no abnormal levels of
methemoglobin. The authors implicated the
atmospheric NOX as an etiologic agent in
methemoglobinemia.
It is difficult to interpret the significance of
hematological changes. More experimental
and epidemiological work are needed to con-
firm these data. For example, no information
is given about antecedent viral or bacterial
infections, which are known to infect children
seasonally, and could explain peripheral blood
changes. Controlled studies of red-cell age,
and of lymphocyte and monocyte morphol-
ogy are also needed.
4. Occupational Exposure
While occupational exposures to NOX are
fairly common, either in connection with the
use of rocket fuel (nitrogen tetroxide) or
dynamite, most occupational exposures in-
clude mixed pollutants and many are poorly
documented. Among the frequently cited
studies are those of Vigdortschik,6 who pre-
sented evidence that nitrogen oxide exposure
over many years is capable of producing
pulmonary fibrosis; and of McCord,7 who
suggested that some methemoglobinemias
occur as a result of nitrogen oxide exposure
among welders. Such studies, although sugges-
tive, need further confirmation.
C. IMPLICATIONS OF
CHATTANOOGA STUDIES
The most substantial studies of ambient
exposure to NO2 in the United States, the
10-7
-------
Chattanooga studies, have several implications
in regard to respiratory illness, implications
that can be extended to other cities.
The National Air Surveillance Network
(NASN) has measured NC<2 levels for the
years 1967, 1968, and 1969, by the Jacobs-
Hochheiser 24-hour method (see chapter 6,
Table 6-7), the same method that was em-
ployed in the Chattanooga studies. Although
the Chattanooga analyses were based on a
6-month NC»2 average, the yearly average
would not be substantially different, since
NC»2 does not exhibit marked seasonal varia-
tions (See discussion chapter 6, Section B.2),
and direct comparison of the NASN yearly
averages with the lower limit at which health
effects were noted in the Chattanooga studies
is, therefore, possible. Any site that exhibits a
concentration of 113 pig/m3 (0.06 ppm) or
greater exceeds the Chattanooga health-effect-
related NC<2 value. As might be expected, an
analysis of the NASN data shows that the
yearly NC»2 averages reflect variations accord-
ing to population densities. Ten percent of
cities with populations of less than 50,000
show a yearly average equal to or exceeding
113 jug/m3 (0.06 ppm). In the population
range from 50,000 to 500,000, 54 percent of
the cities equal or exceed a yearly average of
113 Mg/m3 (0.06 ppm). In the over-500,000
population class, 85 percent of the cities
equal or exceed 113 Mg/m3 NC«2 (0.06 ppm)
on a yearly average.
It is important to realize that the relation-
ship to population is a very general one and
that the exact location of the sampling site
within each city or general area plays a domi-
nant role in determining the concentrations
measured. This is illustrated by an examina-
tion of those locations in Table 6-7 (chapter
6) that have more than one station in opera-
tion. The levels reported in 1969 by two
Denver and two Chicago stations show that
within any one city the NC>2 yearly averages
can differ by factors of 2 to 3, depending on
the site.
D. FUTURE RESEARCH NEEDS
The dearth of information relating com-
munity health effects to ambient concentra-
10-8
tion of NOX is apparent, but the following
studies are particularly needed:
1. Studies to determine which segment of
the population is most susceptible to ab-
normal levels of NOX.
2. Studies to precisely delineate the rela-
tionship among methemoglobin levels, periph-
eral blood alterations, and NOX concen-
trations.
3. Replication of studies of the enhanced
susceptibility to respiratory infection at
various NOX levels.
4. Studies to determine the relationship of
other pollutants to the oxides of nitrogen and
their combined effect on human health.
E. SUMMARY
There is a paucity of well-controlled epi-
demiological studies involving exposure of
human populations to ambient levels of nitro-
gen oxides. The Cleveland Clinic Fire of 1929
exposed many employees to extremely high
levels of HCN, CO, and NOX. A follow-up
study of survivors revealed no increase in
mortality between the exposed group of
employees and a control group.
Effects of community exposure to NC>2 in
four residential areas of greater Chattanooga
were studied. In one area, NC>2 concentra-
tions were high and particulate matter was
low; in another, NO2 concentrations were low
and particulate matter was high. Two other
areas served as "clean" controls.
The ventilatory performance (FEVg.vs) of
children in the high-NC>2 area was signifi-
cantly reduced, when compared to the per-
formance of children in the control areas. In
addition, an 18.8 percent relative excess of
respiratory illness occurred among families
living in the elevated-NC>2 area. This increased
incidence of acute respiratory disease in
family groups was observed when the mean
24-hour NC<2 concentration, measured over a
6-month period, was between 117 and 205
f/g/m3 (0.062 and 0.109 ppm) and the mean
suspended-nitrate level was 3.8 jug/m3* or
greater.
*Suspended nitrate is a solid, and solids are not reported in
PPm.
-------
In a retrospective study of the same Chatta-
nooga area, exposure to intermediate and high
levels of NO2 in ambient air was associated
with a significant increase in the frequency of
acute bronchitis. This occurred among infants,
exposed for 3 years, and school children,
exposed for 2 and 3 years. This increased fre-
quency of acute bronchitis was observed
when the mean 24-hour N(>2 concentration,
measured over a 6-month period, was between
118 and 156 Mg/m3 (0.063 and 0.083 ppm)
and the mean suspended nitrate level was 2.6
Mg/m3 or greater.
A report from Czechoslovakia indicates
that NOX produced several alterations in the
peripheral blood. Increased levels of methe-
moglobin were observed in school children
residing in a town that had relatively high
ambient levels of NOX; however, the findings
in this report require further clarifying investi-
gation.
The Chattanooga studies have several impli-
cations in regard to respiratory illnessimplica-
tions that can be extended to other cities.
Since NC>2 does not exhibit marked seasonal
variations, it is possible to make direct com-
parison of the NASN yearly averages with the
lower limit at which health effects were noted
in the Chattanooga studies. Any site where a
concentration of 113 Mg/m-> (0.06 ppm) or
greater is measured exceeds the Chattanooga
health-effect-related NC<2 value. Ten percent
of cities in the United States with populations
of less than 50,000 have a yearly average
equal to or exceeding 113 jug/m3 (0.06 ppm).
In the population range from 50,000 to
500,000, the yearly average NO 2 equals or
exceeds 113 Mg/m3 (0.06 ppm) in 54 percent
of the cities. In the over-500,000 population
class, 85 percent of the cities equal or exceed
113 Mg/m3 (0.06 ppm) yearly average NO2-
F. REFERENCES
1. Gregory, K. L., V. F. Malinoski, and C. R. Sharp.
Cleveland Clinic Fire: Survivorship Study,
1929-1965. Arch. Environ. Health, 18: 508-515,
April 1969.
2. Shy, et al. The Chattanooga School Study:
Effects of Community Exposure to Nitrogen
Dioxide. Methods, Description ot Pollutant
Exposure and Results of Ventilatory Function
Testing. To be Published in J. Air Pollut. Contr.
Ass. (1970).
3. Shy, et al. The Chattanooga School Study:
Effects of Community Exposure to Nitrogen
Dioxide. Incidence of Acute Respiratory Illness.
To be published in J. Air Pollut. Contr. Ass.,
(1970).
4. Pearlman, M. E., et al. Nitrogen Dioxide and
Lower Respiratory Illness. Submitted to
Pedatrics, 1970.
5. Petr, B. and P. Schmidt. The Influence of an
Atmosphere Contaminated with Sulfur Dioxide
and Nitrous Gases on the Health of Children. Z.
Gesamte Hyg. Grenzgeb., 13: 34-48, 1967.
6. Vigdortschik, N. A., et al. The Symptomatology.
of Chronic Poisoning with Oxides of Nitrogen. J.
Ind. Hyg. Toxicol., 19: 469-473, 1937.
7. McCore, C. P., G. C. Harrold, and S. F. Meek. A
Chemical and Physiological Investigation of
Electric Arc Welding. J. Ing. Hyg. Toxicol., 23:
200-215, 1941.
10-9
-------
-------
CHAPTER 11.
SUMMARY AND CONCLUSIONS
A. INTRODUCTION
This document contains a consolidation
and an assessment of the current state of
knowledge regarding the group of air pollut-
ants known as the oxides of nitrogen. This
chapter provides a concise presentation of
that information, including reasonable con-
clusions for evaluating the concentrations of
nitrogen oxides (NOX) and the accompanying
situations that have an effect on either health
or welfare. The studies and data cited com-
prise the best available basis for developing
specific standards for NOX in the ambient air,
aimed at protecting public health and the
environment.
Although the essential role of NOX in the
production of photochemical oxidants is
treated from the physical-chemical standpoint
in this document, little research has been
done to demonstrate the significance of the
indirect effects of NOX on health, vegetation,
and materials through the photochemical
reaction mechanism; thus, only the direct
effects of NOX are treated here. A P C O pub-
lication AP-63, Air Quality Criteria for Photo-
chemical Oxidants, provides a comprehensive
review of photochemical oxidant effects.
Units of pollution concentration used in
this document are expressed as both mass per
unit volume (e.g., micrograms per cubic
meter, jug/m^) and as volume-ratios (e.g.,
parts per million, ppm). Conversion between
these units requires a knowledge of the gas
density, which varies with temperature and
pressure measurement. In this document 25°C
(77° F) has been taken as standard tempera-
ture, and 760 mm Hg (atmospheric pressure
at «ea level) as standard pressure. All refer-
ences to NOX are expressed in terms of NC>2
mass per unit volume on the basis of the con-
version formula: ppm x 1880 = ng/m^ at 25°
C, 760 mm Hg, unless otherwise specified.
Similarly, hydrocarbons and oxidant concen-
trations are expressed as mass of methane and
ozone per unit volume, respectively.
B. PROPERTIES OF NITROGEN OXIDES
AND PHYSICAL EFFECTS ON
LIGHT TRANSMISSION
Of the oxides of nitrogen known to exist,
only two, nitric oxide (NO) and nitrogen
dioxide (NO2) are emitted to the atmosphere
in significant quantities. Nitric oxide is
formed during all atmospheric combustion
processes in a spontaneous chemical reaction
between the nitrogen and oxygen in the air.
The amount formed depends on the combus-
tion temperature, the concentration of both
reactants and products, and the length of time
favorable conditions persist for the reaction.
Both NO and NO2 are formed when com-
bustion temperatures exceed approximately
1093°C (2000° F), but usually less than 0.5
percent is NO2- More NO2 is formed when
atmospheric oxygen (02) reacts with NO, but
at the dilute concentrations of NO charac-
teristically found in ambient atmospheres,this
reaction proceeds very slowly. During the
initial phases of exhaust gas dilution, how-
ever, the concentration of NO is high, and
forces the reaction to proceed more rapidly
until the exhaust has been sufficiently diluted
(to 1 ppm or less). At that time the major
process for converting NO to NO2 reverts to
the photochemical cycle.
Visibility reduction is common in polluted
atmospheres. Scattering and absorption of
light rays by particles and gases reduce the
11-1
-------
brightness and contrast of distant objects. The
degree of reduction depends on the concen-
tration and properties of the pollutants.
Nitrogen dioxide absorbs light energy over the
entire visible spectrum, although primarily in
the shorter, blue-wavelength regions; thus,
NO2 can by itself reduce visibility. At pre-
sent, however, under most ambient condi-
tions, aerosols make the major contributions
to visibility reduction.
C. SOURCES AND CONTROL OF
ATMOSPHERIC NITROGEN OXIDES
On a global basis, the total amount of
nitrogen oxides generated by natural sources
exceeds the amount from man-made, techno-
logical sources. Natural scavenging processes
keep background levels in nonurban areas
low, on the order of 8 ng/m? (4 ppb) NC>2
and 2 Mg/m3 (2 ppb) NO. In urban areas,
however, where 60 percent of the techno-
logical sources are located, the levels are fre-
quently higher because pollutants are added
faster than scavenging processes control them.
Fuel combustion is the major source of
technological NOX air pollution. Chemical
processing is responsible for high, but local-
ized emissions.
Control of NOX emissions has been di-
rected at both combustion sources and chemi-
cal processes. For stationary combustion
sources, the control principle has been based
on reducing either the flame temperature or
the availability of oxygen, to prevent NO
formation. Similar principles of control are
applicable to motor vehicles. Catalytic prin-
ciples, which have been applied to reduce
NOX emissions from chemical processes, are
also being investigated for possible use in
control of NOX in motor-vehicle exhaust.
D. CHEMICAL INTERACTIONS
OF NITROGEN OXIDES
IN THE ATMOSPHERE
The role of NOX in the generation of pho-
tochemical oxidants is a complex function of
the interaction of certain hydrocarbons (HC)
with the NO2 photolytic cycle, which is dis-
cussed here as well as in the document AP-63,
Air Quality Criteria for Photochemical Oxi-
dants and the document AP-64, Air Quality
Criteria for Hydrocarbons.
In order to fully describe the HC-NOX-OX
interrelationship a comprehensive simulation
model that takes into account emission rates,
chemical reactions, and atmospheric disper-
sion factors, is required. In the absence of
such an applicable model an observation-
based model was developed and applied to
ambient aerometric data. This latter model is
restricted to defining the maximum daily oxi-
dant that may be reached from a given early-
morning precursor level and, therefore, the
model results in definition of the upper-level
oxidant curve, as a function of precursor con-
centrations. The model for the NOX-OX rela-
tionship indicates that an NOX 6- to 9-a.m.
value of 80 Mg/m3 (0.04 ppm) is associated
with the reference concentration of 200
Mg/nrP (0.1 ppm) maximum daily 1-hour-
average oxidant.
The reference concentration of 200 /ug/m3
OX used here was selected on the basis of
convenience and does not represent the
lowest health-related value (130 Mg/m3 OX)
expressed in APCO publication AP-63, Air
Quality Criteria for Photochemical Oxidants.
Application of the observation-based model
to ambient NOX, HC, and oxidant interrela-
tionships showed that the peak oxidant level
is dependent on the concentration of both
reactants. Analysis of data from three urban
areas indicates that a reference concentration
of 200 fjig/m3 (0.1 ppm) maximum daily
1-hour-average oxidant is associated with an
HC range of 200 to 930 Mg/m3 (0.3 to 1.4
ppm C) 6- to 9-a.m. nonmethane hydrocar-
bon, when the 6- to 9-a.m. average NOX,
expressed as NO2, was below 80 ng/m^ (0.04
ppm). Similarly, observation of the 200
Mg/m3 (0.3 ppm C) nonmethane HC level
showed NOX in the range of 80 to 320#g/m3
(0.04 to 0.16 ppm), expressed as NO2- These
conclusions are supported by the predomi-
nance of weekend data near the low-concen-
tration end of the upper-limit oxidant curve,
which reflects the lower oxidant values from
lower emissions on weekends.
11-2
-------
E. METHODS FOR MEASURING
NITROGEN OXIDES
Research is still needed to develop and
thoroughly evaluate more sensitive, reliable,
and practical methods for measuring ambient
levels of NO, NO2, and NOX. All of the field
techniques in use at present can measure only
NO2 directly; NO must be oxidized to NO2,
then measured. NOX can be determined either
by summing NO and NO2 concentrations that
have been measured independently or by
oxidizing NO to NO2, then measuring the
total as NO2-
Any method used for measuring NO2 in
the ambient air should be calibrated against
atmospheres containing known amounts of
NO2- The use of permeation tubes to generate
the test atmospheres is recommended.
Two techniques are currently used in
atmospheric monitoring programs. For sam-
pling periods of 30 minutes or less, the most
suitable currently available method for meas-
uring NO2 is the colorimetric Griess-Saltzman
method. This method can also be automated
for continuous measurement. The Jacobs-
Hochheiser method is the most suitable of the
available methods for long-term (up to 24
hours) sampling, or for situations requiring a
delay of the analysis for more than 4 hours
after sampling. The Griess-Saltzman and
Jacobs-Hochheiser methods are not inter-
changeable, can yield different results, and
must be chosen carefully, according to the
purposes of the sampling to be done.
When used in conjunction with an oxidiz-
ing prescrubber to convert NO to NO2, the
continuous Griess-Saltzman method can be
used to measure NO in ambient air in either a
series or parallel mode, with the same or
separate samples of air. Problems exist in
obtaining complete NO to NO2 oxidation,
and researchers disagree as to which of the
two modes is more satisfactory.
F. ATMOSPHERIC LEVELS OF
NITROGEN OXIDES
Continuous measurement of the oxides of
nitrogen by various monitoring networks has
made it possible to compile tables of mean
concentrations averaged over different time
periods and to relate various temporal pat-
terns to photochemical and meteorological
parameters.
Both NO and NO2 concentrations display
distinct diurnal variations dependent on both
the intensity of the solar ultraviolet energy
and the amount of atmospheric mixing. In
many sampling areas, these variations are also
associated with the traffic patterns.
Nitric oxide shows an additional seasonal
variation, with higher values occurring during
the late fall and winter months. Nitrogen
dioxide, however, does not display any
distinct seasonal patterns.
The effect of meteorological parameters on
NO and NO2 concentrations has been reason-
ably well documented. As might be expected,
periods of stagnation and high traffic volume
in urban areas have resulted in high peak
levels of NOX.
Continuous measurement has indicated
that peak values of NO above 1.2 mg/m3 (1
ppm) are widespread, but NO2 concentrations
have rarely been measured at this level. Peak
concentrations of NO2 in urban areas rarely
exceed 0.94 mg/rn3 (0.5 ppm).
Considerable differences were found among
NO2 data collected at the same site, at the
same time, but by different methods. The
methods of NO, NO2, and NOX measurement
are still in need of refining and must be
judged accordingly.
G. EFFECTS OF NITROGEN OXIDES
ON MATERIALS
Significant effects of NOX have been ob-
served and studied on three classes of ma-
terials: textile dyes and additives, natural and
synthetic textile fibers, and metals.
The most pronounced problem is associ-
ated with textile dyes and additives. Fading of
sensitive disperse dyes used on cellulose
acetate fibers has been attributed to NO2
levels below 188 mg/m3 (<100 ppm). Loss of
color, particularly in blue- and green-dyed
cotton and viscose rayon, has occurred in gas
dryers where NOX concentrations range from
1.1 to 3.7 mg/m3 (0.6 to 2 ppm). Yellow dis-
coloration in undyed white and pastel-colored
11-3
-------
fabrics has recently been attributed, to NOX
by controlled laboratory experiments.
Laboratory and field observations have
shown that cotton and Nylon textile fibers
can be deteriorated by the presence of NOX,
but specific reactants and threshold levels are
undetermined at this time.
Failure of nickel-brass wire springs on re-
lays has been related to high particulate
nitrate levels. This type of stress corrosion has
been observed when surface concentrations of
particulate nitrates have exceeded 2.4
Mg/cm^ and relative humidity was greater
than 50 percent. Another type of this corro-
sion has been associated with annual average
particulate nitrate concentrations of 3.0 and
3.4 Mg/m3 with corresponding NOX levels of
124 and 158 Mg/m3 (0.066 and 0.084 ppm).
H. EFFECTS OF NITROGEN OXIDES
ON VEGETATION
The degree of injury occurring with the
lower concentrations of NC>2 present in the
atmosphere remains to be determined. Expo-
sure of many kinds of plants to concentra-
tions of NC>2 above 47 mg/m3 (25 ppm) for
any extended period causes acute necrotic
leaf injury. Such lesions are usually charac-
teristic for each plant, but their nonspecific
character in relation to other toxicants
renders these symptoms of little value in diag-
nosing NC>2 damage in the field.
The 1-hour visible-injury-threshold value
for NC>2 can be achieved by exposing plants
to 18.8 to 28.2 mg/m3 (10 to 15 ppm). In-
creasing the exposure time, however, obviates
the threshold level; 4.3 to 6.6 mg/m3 (2.3 to
3.5 ppm) NC>2 administered for 8 to 21 hours
and 1.9 mg/m3 (1 ppm) NC>2 for 48 hours
cause equivalent leaf injury. Continuous fumi-
gation with 940 Mg/m3 (0.5 ppm) NC>2 for 35
days resulted in leaf drop and chlorosis in
citrus, but no actual necrotic lesions devel-
oped.
The effects of exposure to low levels of
NO2 for extended periods are less evident.
Recently completed studies suggested that
470 Mg/m3 (0.25 ppm) or less of NC>2, sup-
plied continuously for 8 months will cause
increased leaf drop and reduced yield in navel
oranges.
The mechanism(s) by which NOX causes
direct injury to plants can only be postulated
at this time. Evidence of diurnal fluctuation
in sensitivity to NC>2 has been presented, and
could indicate that the pollutant is reacting
with a particular plant metabolite, which only
accumulates at certain periods during the day.
The absence of a protective metabolite within
the plant at certain periods would also cause a
diurnal sensitivity.
Limited information regarding the effect of
nitric oxide on photosynthesis indicates that
NO would reduce the growth of plants if
concentrations in the range of 3.8 to 7.5
mg/m3 (2.0 to 4.0 ppm) persisted contin-
uously.
I. TOXICOLOGICAL EFFECTS OF
NITROGEN OXIDES
Both of the prominent oxides of nitrogen
present in ambient air are potential health
hazards. At ambient concentrations, NO pre-
sents no direct threat to general health; NO2
does, however. Effects of NO2 determined in
extensive studies are summarized in Table
11-1.
The toxicology of nitrous oxide (N2O) and
other oxides of nitrogen does not appear to
be relevant to the problems of ambient air
pollution at the present time.
1. Nitric Oxide
NO is not an irritant and is not considered
to have adverse health effects at concentra-
tions found in the atmosphere. Its greatest
toxic potential at ambient concentrations is
related to its tendency to undergo oxidation
to NO2- A 12-minute exposure to 3,075
mg/m3 (2,500 ppm) NO has proved lethal to
mice. In addition, NO has been observed to
inhibit bacterial hydrogenase activity at lower
concentrations24.6 mg/m3 (20 ppm). This
inhibition was reversible, however, until the
exposure reached about 12,300 mg/m3
(10,000 ppm).
2. Nitrogen Dioxide
NO2 exerts its primary toxic effect on the
lungs. High concentrations, greater than 188
mg/m3 (100 ppm), are lethal to most animal
114
-------
Table 11-1. SUMMARY OF REPRESENTATIVE N02 EFFECTS
Effect
Lowest level associated
with reference oxidant
production of 200 fig/m?
(0.1 ppm)
Increased incidence of
acute respiratory disease
in families
Increased incidence of
acute bronchitis in infants
and school children
Human
olfactory threshold
Rabbits -
structural changes in
lung collagen
Nave] orange -
leaf abscission;
decreased yield
Rats-
morphological changes
in lung mast cells
characterized by
degranulation
Mice -
pneumonitis; alveolar
distension
Mice -
increased susceptibility
to respiratory infection
Navel orange -
leaf abscission,
chlorosis
Rats-
tachypnea, terminal
bronchiolar hypertrophy
NO-? concentration,
ppm
0.04
0.062
to
0.109
0.063
to
0.083
0.12
0.25
0.25
0.5
1.0
0.5
0.5
0.5
0.8
iUg/m-5
80
117 to
205
118 to
156
225
470
470
940
1880
940
940
940
1504
Duration
3hr
(6 to 9 a.m.)
2 to 3 yr
2 to 3 yr
...
4 hr/day
for 6 days
8 mo,
continuously
4hr
Ihr
6 to 24 hr/day
for 3 to 12 mo
6 to 24 hr/day
up to 12 mo
35 days,
continuously
Lifetime,
continuously
Comment
Chattanooga study - 6-mo
mean concentration range
Chattanooga study - 6-mo
mean concentration range
Immediate perception
Still apparent 7 days after
final exposure
Possibly precedes onset of
acute inflammatory reaction
Possibly emphysematous
condition
Based on mortality following
challenge with K. pneumoniae
Reference
1
2
3
4
5
6
7
8
9
6
10
11-5
-------
Table 11-1 (Continued). SUMMARY OF REPRESENTATIVE N02 EFFECTS
Effect
Rats-
bronchiolar epithelial
changes, loss of cilia,
reduced cytoplasmic blebbing
crystalloid inclusion bodies
Rabbits -
structural changes in lung
collagen
Sensitive plants -
visible leaf damage
Rats, monkeys -
polycythemia
Man -
increase in airway
resistance
Monkeys -
tissue changes in lungs,
heart, liver, and kidneys
NO^ concentration,
ppm
0.8
to
2.0
>
1.0
1.0
2.0
5
15
to
50
Mg/m3
1504
to
3760
1880
1880
3760
9,400
28,200
to
94,000
Duration
Lifetime,
continuously
Ihr
21 to 48
hr
3wk,
continuously
10 min
2hr
Comment
Possibly pre-emphysematous
lesion
Denaturation of structural
protein suggested
Approximate doubling of red
cell number with lesser in-
creases in hematocrit and
hemoglobin
Transient
Degree of damage directly
related to concentration
ofN02
Reference
11
12
13
14
15
16
species; 90 percent of the deaths are caused
by pulmonary edema.
The concentration time product determines
nonlethal morbidity effects of NC>2 expo-
sures. At 940 Mg/m3 (0.5 ppm) for 4 hours or
1.9 mg/m3 (1.0 ppm) for 1 hour, mast cells of
rat lungs became degranulated, possibly signi-
fying the onset of an acute inflammatory
reaction. These cells returned to normal 24
hours after exposure was terminated. Lung
proteins, collagen and elastin, were found to
be altered structurally in rabbits exposed to
1.9 mg/m3 (1 ppm) NC>2 for 1 to 4 hours.
The condition was also reversible within 24
hours. Similar changes were observed in rab-
bits exposed to 470 Mg/m3 (0.25 ppm) NC>2,
4 hours a day for 6 days, except that recovery
was delayed and some denaturation was still
apparent 7 days after the final exposure.
Denaturation of collagen and elastin associ-
ated with repeated exposure to NC>2 has been
suggested as a possible factor in the patho-
genesis of pulmonary emphysema.
Early pulmonary emphysema-type lesions
have been observed in dogs exposed contin-
uously to 47.0 mg/m3 (25 ppm) for 6
months. In lung tissue from monkeys exposed
to 18.8 to 94.0 mg/m3 (10 to 50 ppm) NO2
for 2 hours, alveoli were expanded and had thin
septal walls. This response involved increas-
ing numbers of alveoli as the NC>2 concentra-
tion was increased. Hyperplasia has been ob-
served in respiratory bronchiolar epithelium
of hamsters exposed to 94.0 nig/m3 (50 ppm)
for 10 weeks, and a similar response was
noted in major bronchi and distal portions of
11-6
-------
the respiratory tract of hamsters exposed to
18.8 mg/m3 (100 ppm) for 6 hours.
Long-term exposures to NC>2 concentra-
tions that do not produce acute inflammatory
responses have a cumulative, sustained effect,
suggestive of a pre-emphysematous condition.
Examination of lung tissue from rats ex-
posed to 3.8 mg/m3 (2 ppm) for their natural
lifetimes showed loss of cilia; decreased bron-
chiolar blebbing; and intercellular, crystalloid,
rod-shaped, inclusion bodies. Similar effects
have been seen in lungs of rats continuously
exposed to 1.5 mg/m3 (0.8 ppm). Alveoli in
lungs of mice exposed to 940 Mg/ni3 (0.5
ppm) for 3 to 12 months on 6-, 18-, and
24-hour daily schedules have shown increase
in size from distension rather than from septal
breakage. The accompanying inflammation of
the bronchiolar epithelium and reduction in
distal airway size suggested the development
of early focal emphysema.
Rats chronically exposed to 18.8 to 47.0
mg/m3 (10 to 25 ppm) N(>2 developed com-
pensatory changes, such as polycythemia and
thoracic kyphosis, with lateral flaring of the
ribs.
Since certain pathological changes seen in
animals after experimental NC>2 exposure are
similar to changes that occur in the patho-
genesis of chronic obstructive pulmonary
disease in man, it is suggested that long-term,
low-level exposures to NC>2 may play a signifi-
cant role in the development of chronic lung
disease.
Exposure of mice, hamsters, and squirrel
monkeys to NC>2 increased susceptibility to
bacterial pneumonia and influenza infection.
The susceptibility has been demonstrated by a
significantly increased mortality, decreased
survival time, and a reduction in ability to
clear infectious agents from the lungs. In
mice, threshold for increased susceptibility to
Klebsiella pneumoniae occurred after expo-
sure to 6.6 mg/m3 (3.5 ppm) NC>2 for 2
hours, if the infectious challenge was given
within 1 hour after the NC>2 exposure. Squir-
rel monkeys exposed to 18.8 mg/m3 (10
ppm) NC>2 for 2 hours and then challenged
with K. pneumonia aerosol retained the in-
fectious agent in their lungs for extended
periods of time.
In long-term studies of mice, significantly
increased susceptibility to infection occurred
after continuous daily exposure to 940 Mg/m3
(0.5 ppm) NC>2 for 3 months, and after 6- and
18-hour daily exposures for 6 months. A
significant increase in susceptibility to influ-
enza virus or K. pneumoniae was also seen in
squirrel monkeys continuously exposed to
18.8 and 9.4 mg/m3 (10 and 5 ppm) NC>2 for
1 and 2 months, respectively. In addition,
interferon formation has been impaired and
resistance to viral infection has decreased
following exposure of rabbits to 47.0 mg/m3
(25 ppm) NC>2 for 3 hours. Researchers con-
jecture that such increased susceptibility to
infection may also be significant in the patho-
genesis of human lung disease.
Inhalation of NC>2 can produce other
systemic effects, although these are generally
secondary to the effects on the lungs. In
monkeys exposed to 28.2 to 94.0 mg/m3 (15
to 50 ppm) NC>2 for 2 hours, cellular changes
appeared in heart, liver, and kidney tissue. A
circulating substance, possibly a lung anti-
body, has been detected in the blood of
guinea pigs exposed to 9.4 mg/m3 (5.0 ppm)
for 4 hours daily, 5 days per week for 5.5
months. Rats and monkeys continuously
exposed to 3.8 mg/m3 (2.0 ppm) NO2 for 3
weeks developed marked polycythemia.
Methemoglobin has been detected in the
blood of several species exposed to NC>2 con-
centrations greater than 122 mg/m3 (70 ppm)
for 1 hour.
The small amount of information available
concerning the toxicological effects of the
oxides of nitrogen in man pertains to levels
higher than those found in ambient air.
Experimental exposure of volunteer subjects
to 9.4 mg/m3 (5 ppm) NC>2 for 10 minutes
has produced a substantial, but transient, in-
crease in airway resistance. Other data, de-
rived from occupational exposure to high-con-
centration mixtures of NO and NO2,are com-
plicated by the presence of other pollutants.
11-7
-------
Impaired pulmonary function, evidenced
by reduced maximal breathing capacity, in-
creased expiratory resistance, and occasional
decreased vital capacity, has been observed in
patients accidentally exposed to high concen-
trations of nitrous fumes for a few minutes.
Such evidence has persisted for more than 2
years after the exposure, in some cases. In one
case, occupational exposure to 169 mg/m3
(90 ppm) NC>2 for 30 minutes produced
pulmonary edema and a vital capacity 50
percent lower than expected 18 hours later.
Exposure to very high concentrations for
about 5 minutes has produced death within 2
days to 5 weeks.
The threshold for odor perception of NC>2
is about 225 jug/m3 (0.12 ppm).
J. EPIDEMIOLOGICAL APPRAISAL OF
NITROGEN OXIDES
Nitrogen dioxide, the only oxide of nitro-
gen examined in epidemiological surveys, can
be significantly correlated with increased
respiratory disease at mean 24-hour concen-
trations between 117 and 205 jug/m3 (0.062
and 0.109 ppm).
Effects of community exposure to NC>2
were studied in four residential areas of
greater Chattanooga. The ventilatory per-
formance (FEVg.vs) of children in a high-
NO2 area was significantly reduced, when
compared to the performance of children in
control areas. In addition, an 18.8 percent
relative excess of respiratory illness occurred
among families exposed to high NC>2 concen-
trations. A 10.4 percent excess occurred
among families in an elevated-particulate area.
The increased incidence of acute respiratory
disease was observed when the mean 24-hour
NC>2 concentration, measured over a 6-month
period, was between 117 and 205 iug/m3
(0.062 and 0.109 ppm) and the mean sus-
pended nitrate level was 3.8 Mg/m3 or greater.
In a retrospective study of the same Chatta-
nooga area, exposure to intermediate and high
levels of NC»2 in ambient air was associated
with a significant increase in the frequency of
acute bronchitis among infants exposed for 3
years and school children exposed for 2 and 3
years. When increase was observed, the mean
24-hour NC«2 concentration, measured over a
6-month period, had ranged between 118 and
156 Aig/m3 (0.063 and 0.083 ppm) and the
mean suspended nitrate level had been 2.6
Mg/m3 or greater.
A report from Czechoslovakia indicates
that NOX has produced several alterations in
the peripheral blood. Increased levels of
methemoglobin were observed in school chil-
dren residing in a town that had relatively
high ambient levels of nitrogen oxides. The
findings in that report require further clari-
fying investigation, however, before conclu-
sions can be drawn.
The Chattanooga studies have several impli-
cations in regard to respiratory illness-implica-
tions that can be extended to other cities.
Since NC>2 does not exhibit marked seasonal
variations (See discussion chapter 6, Section
B,2), direct comparison of the NASN yearly
averages with the lower limit at which health
effects were noted in the Chattanooga studies
is, therefore, possible. Any site that exhibits a
concentration of 113 jug/m3 (0.06 ppm) or
greater exceeds the Chattanooga health-
effect-related NC»2 value. Ten percent of cities
with populations of less than 50,000 show a
yearly average equal to or exceeding 113
jug/m3 (0.06 ppm). In the population range
from 50,000 to 500,000, 54 percent of the
cities in the United States equal or exceed a
yearly average of 113 Mg/m3 (0.06 ppm)
NO2- In the over-500,000 population class,
85 percent of the cities equal or exceed 113
Mg/m3 (0.06 ppm) NO2 on a yearly average.
K. AREAS FOR FUTURE RESEARCH
1. Environmental Aspects of Oxides of
Nitrogen
The fate of as much as 50 percent of the
nitrogen oxides that become incorporated
into the photochemical complex is still unde-
termined, for many of the nitrogen oxide
end products remain unidentified.
Even for the identified nitrogen oxides the
relationship between emissions and air quality
11-8
-------
needs further definition through improved
instrumentation, expansion of the number of
monitoring stations, and more accurate deter-
mination of the location and distribution of
sources.
A model for predicting upper limits of
photochemical oxidant pollutants from ob-
served HC and NOX levels has been presented,
but needs further definition, sophistication,
and revision before it can be applied on a
practical basis.
2. Effects on Vegetation and Materials
a. Materials
Further research is needed to define reli-
able dose-response relationships for vulnerable
materials. The effects of variables such as
temperature, relative humidity, sunlight, and
other pollutants on the damage potential of
the nitrogen oxides must also be determined.
b. Vegetation
The biochemical, enzymatic, and other
metabolic responses of plants to ambient
levels of the nitrogen oxides are in need of
research-based delineation. Evidence of diur-
nal variations in sensitivity suggests the exist-
ence of either extra-sensitive or protective
metabolites in some plants. Evidence of syner-
gistic effects of NOX in mixtures containing
other air pollutants should be investigated
further.
3. Toxicity of Oxides of Nitrogen
In order to ascribe toxicity to a specific
concentration range of NOX, the relation of
metabolic tissue changes to NO 2 concentra-
tion-time responses and the relative impor-
tance of low-concentration, long-time expo-
sures versus short-time, peak ambient concen-
trations should be studied. The interactions of
the oxides of nitrogen with particulate pollut-
ants in relation to biochemical, biophysical,
infectious, immunological, and ultrastructural
response parameters require further research
aimed at elucidating possible synergistic
damage or protection. Tolerance to NC>2 in
the presence of oxidant pollutants has been
suggested as a result of exploratory studies,
but the biologic importance of such protec-
tion needs to be defined.
Further examination of in vivo biochemical
and biophysical effects of exposure to typical
ambient concentrations of the oxides of nitro-
gen relative to: (1) qxidation of fatty acid
double bonds in lung surfactants; and (2)
denaturation or alteration of lung proteins
(collagen and elastin, enzymes, and cellular
membranes) is needed before optimal treat-
ment for, or protection from exposures can
be developed.
4. Epidemiology of Oxides of Nitrogen
In order to determine the effect of NOX on
the health of the general population, epidemi-
ological research must be expanded to in-
clude: (1) studies to determine which seg-
ments of the population are most susceptible
to the oxides of nitrogen; (2) studies to pre-
cisely delineate the relationship between
methemoglobin levels, peripheral blood altera-
tions, and nitrogen oxide concentrations; (3)
replication of studies of the enhanced suscep-
tibility to respiratory infection that occurs
with exposure to ambient levels of NOX; and
(4) studies to determine the relationship
between other pollutants and the oxides of
nitrogen and their material effect on human
health.
L. CONCLUSIONS
Derived from a careful evaluation of the
studies cited in this document, the conclu-
sions given below represent the best judgment
of the scientific staff of the Air Pollution
Control Office of EPA regarding the ef-
fects that may occur when various levels
of nitrogen oxides are reached in the ambient
air. More detailed information from which
the conclusions were derived, and the qual-
ifications that entered into the considera-
tions of these data, can be found in appro-
priate chapters of this document.
1. Nitric Oxide
a. Effects on Humans
No evidence shows that NO produces sig-
nificant adverse health effects at the ambient
11-9
-------
aimospheric concentrations thus far meas-
ured (chapter 9, section B.).
b. Effects on Materials and Vegetation
Damaging effects to materials at ambient
pollutant levels of nitrogen oxides have been
observed; however, concentrations of NO
producing these effects have not been pre-
cisely determined (chapter 7, sections C and
D).
When beans were exposed to concentra-
tions of 12.3 mg/m3 (10 ppm), apparent
photosynthesis was reduced 50 to 70 percent;
when exposed to 4.9 mg/nr5 (4 ppm), a 10
percent reduction occurred (chapter 8, sec-
tion B).
c. Effects on Laboratory Animals
A concentration of 3,075 mg/m3 (2,500
ppm) is lethal to mice after a 12-minute expo-
sure. Fully reversible inhibition of bacterial
hydrogenase activity occurs at a concen-
tration of 24.6 mg/m3 (20 ppm) (chapter 9,
section B).
2. Nitrogen Dioxide
a. Effects on Humans
(1) Short-Term Exposure. Limited studies
show that exposure to NC>2 for less than 24
hours continuously can have several concen-
tration-dependent effects.
1. The olfactory threshold value of NC>2 is
about 225 jug/m3 (0.12 ppm) (chapter 9,
section C.2.a.l).
2. Exposure to 9.4 mg/m3 (5 ppm) for 10
minutes has produced transient increase
in airway resistance (chapter 9, section
C.2.a.2).
3. Occupational exposure to 162.2 mg/m3
(90 ppm) for 30 minutes has produced
pulmonary edema 18 hours later, accom-
panied by an observed vital capacity that
was 50 percent of the value predicted for
normal function (chapter 9, section
C.2.b).
(2) Long-Term Exposure. An increased inci-
dence of acute respiratory disease was observed
in family groups when the mean range of 24-
hour NO? concentrations, measured over a 6-
month period, was between 117 and 205
(0.062 and 0.109 ppm) and the mean sus-
pended nitrate level during the same period
was 3.8 Mg/m3 or greater.
The frequency of acute bronchitis in-
creased among infants and school children
when the range of mean 24-hour NO2 concen-
trations, measured over a 6-month period, was
between 118 and 156 Mg/m3 (0.063 and
0.083 ppm) and the mean suspended nitrate
level during the same period was 2.6 Mg/m3 or
greater (chapter 10, section C. 1).
Yearly average NO2 concentrations exceed
the Chattanooga health-effect-related value of
113 Mg/m3 (0.06 ppm) in 10 percent of cities
in the United States with populations of less
than 50,000, 54 percent of cities with popula-
tions between 50,000 and 500,000, and 85
percent of cities with populations over
500,000 (chapter 10, section d.).
b. Effects on Materials and Vegetation
Although damage to materials has been
attributed to the oxides of nitrogen in ambient
atmospheres, the precise air-concentrations
producing these effects have not been deter-
mined (chapter 7, sections C and D).
Crops and ornamental plants can be classi-
fied into three groups with respect to NOX
sensitivity: sensitive, low sensitive, and resist-
ant. Several characteristic effects have been
observed among the sensitive plants studied
with regard to direct NO2 exposure.
1. Exposure to 470 Mg/m3 (0.25 ppm) of
NO2 for 8 months caused leaf abscission
and decreased yield among navel oranges
(chapter 8, section G).
2. Exposure to NO2 concentrations of 940
Mg/m3 (0.5 ppm) for 35 days resulted in
leaf abscission and chlorosis on citrus
fruit trees (chapter 8, section G).
3. Exposure to NO2 concentrations of 1.9
mg/m3 (1 ppm) for 1 day can cause
overt leaf injury to sensitive plants
(chapter 8, section G).
11-10
-------
c. Effects on Laboratory Animals
(1) Short-Term Exposure. Short-term effects
of NC>2 on animals can be summarized by the
analyses of five salient experiments.
1. Exposure of rats to either 940 Mg/m3
(0.5 ppm) for 4 hours, or 1.9 mg/m3
(1.0 ppm) for 1 hour has produced
degranulation of lung mast cells (chapter
9, section C.I.b.3).
2. Structural changes in collagen were ob-
served in rabbits exposed to 1.9 mg/m3
(1.0 ppm) for 1 hour (chapter 9, section
C.l.b.2).
3. The threshold for increased suscepti-
bility of mice to respiratory infection by
K. pneumoniae is 6.6 mg/m3 (3.5 ppm)
for 2 hours (chapter 9, section C.l.d).
4. Exposure of monkeys to 28.2 to 94.0
mg/m3 (15 to 50 ppm) for 2 hours has
produced damage to their lungs, heart,
liver, and kidneys and pulmonary
changes that resemble those seen in
human emphysema (chapter "9, sections
C.l.b.3 and C.I.c.l).
5. In rabbits exposed to 47.0 mg/m3 (25
ppm) for 3 hours interferon formation
and resistance to viral infection de-
creased (chapter 9, section C.l.d).
(2) Long-Term Exposure. Long-term expo-
sure to NO2 altered several functions in animal
circulatory and respiratory systems.
1. Structural changes were found in lung
tissue collagen from rabbits exposed to
470 Mg/m3 (0.25 ppm) 4 hours a day for
6 days (chapter 9, section C.l.b.2).
2. Enhanced susceptibility of mice to
respiratory infection by K. pneumoniae
was observed after 3 months of contin-
uous exposure to 940 Mg/m3 (0.5 ppm)
(chapter 9, section C.l.d).
3. Polycythemia has been reported in rats
and monkeys exposed continuously to
3.8 mg/m3 (2.0 ppm) for 3 weeks
(chapter 9, section C.l.c.3).
4. Changes resembling those seen in human
emphysema were reported in the follow-
ing: mice exposed 6 to 24 hours daily,
for a period of 3 to 12 months to 940
Mg/m3 (0.5 ppm) (chapter 9, section
C.l.b.3); rats continuously exposed to
18.8 to 47.0 mg/m3 (10 to 25 ppm) for
4 to 12 months (chapter 9, section
C.l.b.3); and dogs continuously ex-
posed to 47.0 mg/m3 (25 ppm) for 6
months (chapter 9, section C.l.b.3).
3. Other Nitrogen Oxide Effects
a. Photochemical Relationships
An observation-based model applied to
ambient NOX, HC, and oxidant interrelation-
ships showed that peak oxidant yield was
dependent on the concentration of both reac-
tants. Analysis of data from three urban areas
indicated that a reference concentration of
200 jug/m3 (0.1 ppm) maximum daily
1-hour-average OX could be associated with a
hydrocarbon range of 200 to 930 Mg/m3 (0.3
to 1.4 ppm C) 6- to 9-a.m. nonmethane
hydrocarbon, expressed as methane, when the
6- to 9-a.m. average NOX, expressed as NO2,
was below 80 Mg/m3 (0.04 ppm). A similar
observation related an NOX range of 80 to
320 Mg/m3 (0.04 to 0.16 ppm), expressed as
NO2, with 200 Mg/m3 (0.3 ppm C) nonmeth-
ane hydrocarbon.
b. Stress Corrosion
Nitrogen oxide reaction products have been
associated with corrosion and failure of elec-
trical components. In two cities where this
problem has been observed, the 1965 average
airborne particulate nitrate concentration
were 3.0 and 3.4 Mg/m3 with associated
average NOX levels of 124 and 158 Mg/m3
(0.066 to 0.084 ppm).
M. RESUME
Adverse health effects, as evidenced by a
greater incidence of acute bronchitis among
infants and school children, have been ob-
served, under the conditions prevailing in the
areas where studies were conducted, when the
mean 24-hour NO2 concentration, measured
by the Jacobs-Hochheiser method, over a
6-month period, varied from 118 to 156
Mg/m3 (0.063 to 0.083 ppm). On an annual
basis, a maximum 24-hour average as low as
284 Mg/m3 (0.15 ppm) would be expected to
be associated with a 6-month mean of 118
11-11
-------
Mg/m3. Adverse health effects, as 6videnced
by an increased incidence of acute respiratory
disease, have been observed in family groups
when the mean 24-hour NO2 concentration
measured over a 6-month period was between
117 and 205 Mg/m3 (0.062 and 0.109 ppm)
and the mean suspended nitrate level was 3.8
3 or greater.
An analysis of 3 years of data collected in
three American cities shows that on those
several days a year when meteorological con-
ditions are most conducive to the formation
of photochemical oxidant, and the 6- to 9-a.m.
nonmethane hydrocarbon concentration is
200 fjig/m3 (0.3 ppm C), a 6- to 9-a.m. NOX
concentration (measured by the continuous
Saltzman Method and expressed as NO2 ) that
ranges between 80 and 320 Mg/m3 (0.04 and
0.16 ppm) would be expected to produce a
1-hour photochemical oxidant level of 200
Mg/m3 (0. 1 ppm) 2 to 4 hours later. If this
same functional relationship exists at the low-
est levels at which photochemical oxidant has
been observed to adversely affect human
health, the corresponding nonmethane hydro-
carbon concentration would be approx-
imately 130 Mg/m3 (0.2 ppm C) and the 6- to
9-a.m. NOX level would be as high as 214
Mg/m3 (0. 1 1 ppm).
Adverse effects on vegetation such as leaf
abscission and decreased yield of navel
oranges have been observed during fumigation
studies when the NO2 concentration (mea-
sured by the continuous Saltzman Method)
was 470 Mg/m3 (0.25 ppm) during an
8-month period.
Nitrate compounds have been identified
with corrosion and failure of electrical com-
ponents. In two cities where these effects
were observed, the average airborne nitrate
particulate concentrations were 3.0 and 3.4
Mg/m3 with associated average NOX levels of
124 and 158 Mg/m3 (0.066 and 0.084 ppm).
It is reasonable and prudent to conclude
that, when promulgating ambient air quality
standards, consideration should be given to
requirements for margins of safety that would
take into account possible effects on health,
vegetation, and materials that might occur
below the lowest of the above levels.
N. REFERENCES
1. Air Quality Criteria for Photochemical Oxidants.
National Air Pollution Control Administration.
Washington, D.C. Publication No. AP-63. March
1970.
2. Shy, et al. The Chattanooga School Study:
Effects of Community Exposure to Nitrogen
Dioxide. Incidence of Acute Respiratory Illness.
To be published in J. Air Pollut. Contr. Ass.,
1970.
3. Pearlman, M. E., et al. Nitrogen Dioxide and
Lower Respiratory Illness. Submitted to
Pediatrics, 1970.
4. Henschler, P, et al. Olfactory Threshold of Some
Important Irritant Gases and Manifestations in
Man by Low Concentrations. Arch.
Gewerbepathol. Gewerbehgy., Berlin, 17:
547-570, 1960.
5. Mueller, P. K. and M. Hitchcock. Air Quality
Criteria-Toxicological Appraisal for Oxidants,
Nitrogen Oxides, and Hydrocarbons. J. Air
Pollut. Control Ass., 19: 670-676, 1969.
6. Thompson, C. R., et al. Effects of Continuous
Exposure of Navel Oranges to NO2- Atmos.
Environ. In Press, 1970.
7. Thomas, H. V., P. K. Mueller, and G. Wright.
Response of Rat Lung Mast Cells to Nitrogen
Dioxide Inhalation. J. Air Pollut. Contr. Ass., 17:
33-35, 1967.
8. Blair, W. H., M. C. Henry, and R. Ehrlich.
Chronic Toxicity of Nitrogen Dioxide: II. Effects
on Histopathology of Lung Tissue. Arch.
Environ. Health, 18: 186-192, 1969.
9. Ehrlich, R. and M. C. Henry. Chronic Toxicity of
Nitrogen Dioxide: I. Effects on Resistance to
Bacterial Pneumonia. Arch. Environ. Health, 17:
860-865, 1968.
10. Freeman, G., N..J. Furiosi and G. B. Haydon.
Effects of Continuous Exposure to 0.8 ppm N©2
on Respiration of Rats. Arch. Environ. Health,
13: 454-456, 1966.
11-12
-------
11. Freeman, G. and G. B. Haydon. Emphysema
After Low-Level Exposure to NC^. Arch.
Environ. Health, 8: 125-128, 1964.
12. Buell, G. C., Y. Tokiwa, and P. K. Mueller. Lung
Collagen and Elastin Denaturation In vivo
Following Inhalation of Nitrogen Dioxide. Cali-
fornia State Dept. of Public Health. (Presented at
the Annual Air Pollution Control Association
Meeting.) San Francisco. Paper No. 66-7, June
1966.
13. Heck., W. W. Plant Injury Induced by Photo-
chemical Reaction Products of Propylene-Nitro-
gen Dioxide Mixtures. J. Air Pollut. Contr. Ass.
14: 255-261, July 1964.
14. Freeman, G., et al. The Subacute Nitrogen
Dioxide - Induced Lesion of the Rat Lung. Arch.
Environ. Health, 18: 609-612, 1969.
15. Abe, M. Effects of Mixed NO2 - SO2 Gas on
Human Pulmonary Functions. Bull. Tokyo Med.
Dent. Univ., 14: 415-433, 1967.
16. Henry, M. C., R. Ehrlich, and W. H. Blair. Effects
of Nitrogen Dioxide on Resistance of Squirrel
Monkeys to Klebsiella pneumoniae Infection.
Arch. Environ. Health, 18: 580-587, 1969.
11-13
-------
-------
APPENDIX.
VOLUME TO MASS CONVERSION TABLES
-------
-------
VOLUME (ppm) TO MASS (Mg/m3) CONVERSION TABLE FOR NO
(ppm x 1230 = Mg/m3 at 25° C, 760 mm Hg)
ppm
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
0.11
0.12
0.13
0.14
0.15
0.16
0.17
0.18
0.19
0.20
0.21
0.22
0.23
0.24
0.25
0.26
0.27
0.28
0.29
0.30
0.31
0.32
0.33
0.34
0.35
jug/m3
10
20
40
50
60
70
90
100
110
120
140
150
160
170
180
200
210
220
230
250
260
270
280
300
310
320
330
340
360
370
380
390
410
420
430
ppm
0.36
0.37
0.38
0.39
0.40
0.41
0.42
0.43
0.44
0.45
0.46
0.47
0.48
0.49
0.50
0.51
0.52
0.53
0.54
0.55
0.56
0.57
0.58
0.59
0.60
0.61
0.62
0.63
0.64
0.65
0.66
0.67
0.68
0.69
0.70
Mg/m3
440
460
470
' 480
490
500
520
530
540
550
570
580
590
600
620
630
640
650
660
680
690
700
710
730
740
750
760
770
790
800
810
820
840
850
860
ppm
0.71
0.72
0.73
0.74
0.75
0.76
0.77
0.78
0.79
0.80
0.81
0.82
0.83
0.84
0.85
0.86
0.87
0.88
0.89
0.90
0.91
0.92
0.93
0.94
0.95
0.96
0.97
0.98
0.99
1.00
Mg/m3
870
890
900
910
920
930
950
960
970
980
1000
1010
1020
1030
1050
1060
1070
1080
1090
1110
1120
1130
1140
1160
1170
1180
1190
1210
1220
1230
A-l
-------
VOLUME (ppm) TO MASS (Mg/m3) CONVERSION TABLE FOR NO2
(ppm x 1880 = Mg/m3 at 25° C, 760 mm Hg)
ppm
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
0.11
0.12
0.13
0.14
0.15
0.16
0.17
0.18
0.19
0.20
0.21
0.22
0.23
0.24
0.25
0.26
0.27
0.28
0.29
0.30
0.31
0.32
0.33
0.34
0.35
Mg/m3
20
40
60
80
90
110
130
150
170
190
210
230
240
260
280
300
320
340
360
380
390
410
430
450
470
490
510
530
550
560
580
600
620
640
660
ppm
0.36
0.37
0.38
0.39
0.40
0.41
0.42
0.43
0.44
0.45
0.46
0.47
0.48
0.49
0.50
0.51
0.52
0.53
0.54
0.55
0.56
0.57
0.58
0.59
0.60
0.61
0.62
0.63
0.64
0.65
0.66
0.67
0.68
0.69
0.70
Mg/m3
680
700
710
730
750
770
790
810
830
850
860
880
900
920
940
960
980
1000
1020
1030
1050
1070
1090
1110
1130
1150
1170
1180
1200
1220
1240
1260
1280
1300
1320
ppm
0.71
0.72
0.73
0.74
0.75
0.76
0.77
0.78
0.79
0.80
0.81
0.82
0.83
0.84
0.85
0.86
0.87
0.88
0.89
0.90
0.91
0.92
0.93
0.94
0.95
0.96
0.97
0.98
0.99
1.00
Mg/m3
1330
1350
1370
1390
1410
1430
1450
1470
1490
1500
1520
1540
1560
1580
1600
1620
1640
1650
1670
1690
1710
1730
1750
1770
1790
1800
1820
1840
1860
1880
A-2
-------
SUBJECT INDEX
Acute plant injury, 8-18-2
necrosis (marginal, intercostal), 8-2
discoloration, 8-2
sensitivity, 8-2
Alveoli, 9-6-9-9
Anaerobic isoenzymes, 9-12
Anaesthetic, 9-17, 9-19. See also "Nitrous
oxide"
Analgesic, 9-17, See also "Nitrous oxide"
Antibody, See "Blood"
Annual variation
NOX concentrations, 6-4
Asthma, 10-6
B
Bacteria, 9-12-9-14
and tobacco, 9-13,9-14
Behavior, voluntary, 9-10
Blood 9-1, 9-10-9-12
antibody, 9-11
changes in cell morphology, 10-7
cyanosis, 9-1, 9-16
hemolysis, 10-7
immature red cells, 10-7
leucocytes, 9-11
methemoglobin, 9-1, 9-2, 9-11, 10-7, 10-8
polycythemia, 9-11
Bronchitis, acute, 10-6
lung, 9-10, See "Lung"
morphology changes, 9-49-10, 10-7
Cellulosics, 7-3, 7-4
Chattanooga, 10-1-10-9
Chemical properties of
Nitric oxides, 2-1
Nitrogen dioxide, 2-2
Nitrogen pentoxide, 2-4
Nitrogen sesquioxide, 2-4
Nitrogen tetroxide, 2-4
Nitrous oxide, 2-4
Children, effects on, 10-3-10-9
Chronic plant injury, 8-1, 8-2
Cleveland, 10-1
Cleveland Clinic fire, 9-17, 10-1
Collagen, 9-3-9-5
Concentration
of nitric oxide, See "NOX concentration"
of nitrogen dioxide, See "NOX concentra-
tion"
Control of man-made NOX, 3-4
Cotton fading, 7-3-7-5
Cyanosis, 9-1,9-16
Czechoslovakia, 10-7
D
Diurnal variation
NOX concentration, 6-16-2
plant sensitivity, 8-48-11
Dyes, 7-1-7-7
blue green, 7-1, 7-6
dye additives, 7-3, See also "Fading"
resistant, 7-2, 7-4, 7-7
Calibration, 5-15-6
of nitrogen dioxide methods, 5-3
of nitric oxide methods, 5-5
systems 5-1, 5-3, 5-5, 5-6
CAMP data, 6-8-6-15
Cells
blood, See "Blood"
E
Eastern air characteristics. 7-6
Edema, pulmonary, 9-2, 9-3, 9-6, 9-16, 9-17
Elastin, 9-3-9-5
Electric-arc welding, 9-16, 9-17
Emphysema, 9-7, See also "Lung"
1-1
-------
Enzymes, 9-2, 9-12
inhibition, 9-2
plant, 8-3, 8-10
systems, 9-12
Epidemiology, 10-1 10-9
Exhaust, diesel, 9-15
Exposure
effect on mortality rate, 10-1
high, 10-1, See also "Plant injury"
occupational, See "Occupational exposures"
Fading, 7-1-7-3,7-7
gas-fume, 7-17-3
resistance, 7-3
test (AATCC), 7-2
Ferric oxide, 9-10
Fibers, 7-4-7-5
cellulosics, 7-3, 7-4
cotton, 7-3-7-5
Nylon, 7-5
Rayon, 7-1,7-3
Spandex, 7-5
synthetics, 7-5
Formation of:
Nitric oxide, 2-1
Nitrogen dioxide, 2-1, 2-2
Fuel combustion, 3-1
Gas, silage, 9-16
Gas-fume fading, 7-17-3
Griess-Saltzman method, 5-1, See also
"Sampling"
H
HC-NOX-OX relationship
concentration variation, 4-104-13
Hemolysis, See "Blood"
Humidity, 7-3, 7-6, See afao"Synergism"
Hydrocarbons
ambient levels and maximum oxidant lev-
els, 4-3
concentration variation, 4-104-13
indication of oxidant levels, 4-2
role in oxidant formation, 4-1
Hyperplasia, 9-7
I
Immunologic effects, 9-139-15
Infection, 9-13-9-14
bacterial, 9-13
viral, 9-14
respiratory, succeptibility to, 10-1 10-6, 10-8
Influenza virus, 9-14, 10-3
Interferon formation, 9-14
J
Jacobs-Hochheiser method, 5-1, See also
"Sampling"
K
Klebsiella pneumoniae, 9-12
L
Light absorption by nitrogen dioxide, 2-4, 2-5
Lipid peroxidation, 9-5
Lung
alveoli, 9-6-9-8
antibody, 9-11
cells, 9-4-9-10
edema, 9-2, 9-3
function, 9^, 9-5, 9-15-9-17
mast cells, 9-6
proteins, 9-3-9-5
respiratory rate, 9-5, 9-17
smoking, 9-13,9-14, 10-3
M
Mast cells, 9-6
Materials, effects of NOX on, 7-1-7-7
Maximum concentration
calculation of, 6-56-7
Metals, 7-5-7-7
Eastern U.S. air damage to, 7-6
humidity and damage, 7-6
1-2
-------
Los Angeles, 7-5
New York, 7-6
Nickel-brass alloys, 7-5, 7-6
nickel-palladium, 7-6
participate nitrates, synergism, 7-7
stress-corrosion, 7-57-6
switches, 7-6
telephone relays, 7-5
Western U.S. air damage to, 7-5
wire relays, 7-57-6
zinc, 7-6
Meteorology
effect on NOX concentration, 6-76-8
Methemoglobin, 9-1, 9-2, 9-11, 10-7, 10-8
Methods
for measuring nitrogen dioxide
colorometric, 5-1
continuous, 5-2
correlation spectrometric, 5-2
gas chromatographic, 5-2
Griess-Saltzman, 5-1
Jacobs-Hochheiser, 5-1
long-path infrared, 5-2
manual, 5-1
oxidation, 5-3
reduction, 5-2
for measuring nitric oxide
chemiluminescent, 5-35-5
oxidation to nitrogen dioxide, 5-3
parallel mode, 5-4
series mode, 5-3, 5-4
for measuring total nitrogen oxides
chemiluminescent, 5-5,5-6
oxidation to nitrogen dioxide, 5-5
Monitoring networks, 6-86-37
Mortality, 9-2, 10-1
Mothers, effects of NC>2 on health of, 10-5
N
Narcosis, 9-1
NASN data, 6-32-6-37
Nickel-brass alloys, 7-5
Nickel-palladium, 7-6
Nitric acid fumes, 9-17, 9-18
Nitric oxide concentration, See "NOX concen-
tration"
toxicology, 9-21
Nitrogen oxides
ambient levels and maximum oxidant lev-
els, 44-4-10
concentration ,variation of, 4-104-13
definition, 2-1
indicators of oxidant levels, 4-2
role in oxidant formation, 4-1
NC>2 photolytic cycle, 4-14-2
NOX concentration
annual pattern, 6-4
calculation of, 6-5, 6-7
continuous monitoring, 6-86-37
definition, 2-1
diurnal pattern, 6-1-6-2
effect of meteorological factors, 6-76-8
seasonal pattern, 6-36-4
urban pattern, 6-86-32
Nylon, 7-5
O
Observational model
HC-NOX-OX relationship, 4-3
interpretations of, 4-134-18
limitations of, 4-13
reduction in photochemical precursors,
4-16-4-18
weekday, weekend effect, 4-144-16
Occupational exposures, 9-15-9-17, 10-7, 10-8
Odor perception, 9-14-9-15
Oxidants - See "Photochemical oxidants"
Ozone
formation of, 4-1
relationship to NO2 photolytic cycle,
4-1-4-2
Particulate - nitrates, 7-7, See also "Syner-
gism"
Pathology, 9-3-9-10, 9-20
Permeation tubes, 5-3
Peroxy nitrates
effects of, 8-1
formation of, 4-18
Phagocyte inhibition, 9-12
1-3
-------
Photochemical oxidants
concentration levels, 4-24-20
concentration variation, 4-104-13
maximum daily levels, 4-3-4-12
rates of formation, 4-1
relation to ambient hydrocarbon levels, 4-2
relation to ambient NOX levels, 4-44-10
variables of formation, 4-2
Physiological effects on plants - apparent
photosynthesis, 8-1, 8-3
enzyme inactivation, 8-3
leaf chlorosis, 8-2
leaf-drop, 8-2
Plant injury, 8-1-8-11, See also "Vegetation"
Plant response factors
low light intensity, 8-3
environmental factors, 8-3
Polycythemia, 9-11
Population density, 10-3
Precursor-product relationship, 4-1, 4-104-13
Pulmonary edema, 9-2, 9-3, 9-6, 9-16, 9-17
Pulmonary function, 94, 9-5, 9-15-9-19,
10-1-10-9
R
Rayon, 7-5
Respiratory illness, acute, 10-5
Respiratory infection, 10-1-10-8
Respiratory infection,
experimental, 9-12-9-14
Respiratory rate, 9-5,
Respiratory tract, 9-3-9-10
Sampling
calibration of methods, - See "Calibration"
CAMP, 6-8-6-32
continuous, 5-2, 5-6
intermittent, 5-1
NASN, 5-2
Seasonal variation
NOX concentration, 6-36-4
Silage gas, 9-16
Smoking, See "Bacteria", "Synergism"
Sources and emissions, 3-1, 3-2, 3-3
man-made, 3-1, 3-2, 3-3
natural, 3-1
nonurban, 3-1
Spandex,7-5
Stress-corrosion, 7-5, 7-6
Structural protein, 9-39-5
Sulfur dioxide, 10-2
Suspended particulate and NC>2, 10-1, 10-5
Synergism, 9-3-9-5,9-10
hydrocarbon-NOx, See "Hydrocarbons"
low-light intensity on plants, 8-3
moisture, on plants, 8-3, See also "Humid-
ity"
ozone, See "Ozone"
smoking, 9-10, 9-13, 9-14, 10-3
sulfhydryl groups and nitrous acid, 8-3
sulfur dioxide, 8-4, 9-15, 10-2-104, 10-6
suspended particulate-NO2, 10-1, 10-5
temperature-NO2, 9-3
Synthetics, 7-5
Systemic effects of NC>2
on animals, 9-10-9-14, 9-28
Tidal volume, 9-4, 9-7
Tissue recovery, 9-7
TNT plant, 10-2
Tobacco, 9-10, 9-13
Toxicology
NO, 9-21
NO2, 9-22-9-28
U
Urban NOX concentrations, 6-86-32
Vegetation
acute injury, 8-18-2
chronic injury, 8-2
physiological effects, 8-3
14
-------
response factors, 8-3 Welding, See "Electric-arc
dose-injury relationship, 8-4 welding"
Vitamin E, 9-5 Whites, yellowing of, 7-3
W Z
Weekend, weekday levels, 4-144-16
Weight, 9-10 Zinc, 7-6
1-5
-------