United States
Environmental Protection
Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road
Ann Arbor, Ml 48105
EPA-460/3-81-027
Air
Ammonia Health Effects

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             AMMONIA HEALTH EFFECTS
             with Contributions  by
   Bonnie L.  Carson               Harry V.  Ellis  III
   Cecily M.  Beall                Larry H.  Baker
                  TASK 3 REPORT
               September 17,  1981

            Contract No. 68-03-2928
            Task Specification No.  3

"Health Effects Support for the Emission Control
              Technology Division"

           MRI Project No.  4997-T(3)
                      For

      Emission Control Technology Division
  Office of Mobile Source Air Pollution Control
      U.S.  Environmental Protection Agency
               2565 Plymouth Road
           Ann Arbor, Michigan  48105

             Attn:  Robert J. Garbe

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                                 PREFACE
     This report on  health effects of ammonia was prepared by Midwest Re-
search Institute (MRI) as Task No. 3 under Contract No.  68-03-2928,  "Health
Effects Support for  the Emission  Control Technology Division" for the U.S.
Environmental Protection Agency.

     Health effects literature primarily related to inhalation exposures to
ammonia has been  collected,  evaluated,  tabulated, and summarized so that
this report can be used to derive a range of  concern for human exposure to
vehicular atmospheric emissions of ammonia.

     Task activities were  coordinated by the project leader, Mrs.  Bonnie L.
Carson, Senior Chemist, and task leader, Ms. Cecily M.  Beall, Assistant Sci-
entist.  Documents  were rated  and summarized by  senior  pharmacologist
Harry V. Ellis III,  of  MRI,  and epidemiologist Larry H. Baker, M.D., MRI
consultant, who is  an Associate Professor  in the Department of Community
Health at the University of Kansas Medical  Center.  Data were tabulated by
Ms. Beall; Joy L. McCann,  Assistant Scientist; and Ms. Carol Foret, Liter-
ature Aide.  Ms. Beall  and Mrs. Carson contributed to the  annotated bib-
liography.  This  study was  performed under  the  general  supervision of
Dr. Edward W.  Lawless, Head, Chemical Impact Assessment Section.

     Mr. Robert J.  Garbe  was the project monitor for the Emission Control
Technology Division,  U.S.  Environmental Protection Agency,  and Ms. Colleen
DeMeyer served as Branch Technical Representative.
Approved for:

MIDWEST RESEARCH INSTITUTE
Bruce W. Macy, Director
Center for Technoeconorftic Analysis
September 17, 1981
                                    111

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                                  SUMMARY
     The goal of this task is to compile and evaluate data from the litera-
ture on the health effects of inhalation exposure to NHs-   The results will
assist the Emission Control Technology Division (ECTD) of the U.S.  Environ-
mental Protection Agency  in  establishing a  range of  concern for NHg in ex-
hausts from vehicles equipped with emission control devices (e.g.,  catalytic
converters) and in providing guidance to automobile manufacturers.   The ex-
posures of particular  concern are those that may occur in traffic jams, in
public parking garages, in home and repair shop garages,  in tunnels, and in
other situations where  little  dilution of the exhaust is expected before
inhalation.  Most of the report (as directed by ECTD) is  in the form of tables
based on the literature reviewed.  Data from exposures at higher levels than
of primary concern  are included because strictly relevant information was
scarce and these related data might prove helpful in assessing health effects
at lower levels.
     Documents on inhalation effects of NHs identified from manual and com-
puterized literature searches were rated in a two-step process by the project
pharmacologist and  epidemiologist.   First,  the document received an A, B,
C, D  rating  according  to  its applicability  for deriving a range of concern
for NH3  in automobile  emissions.  Second, if the paper was not a  low-rated
foreign-language document,* a theoretical paper,  a review,  or a nontoxicology
experimental paper, it received a numerical score based on itemized features
that should be present in an ideal report.

     All A-  or B-rated documents were tabulated.  Occupational documents
receiving a  C  or D rating because of the possible presence of confounding
factors  were  included  if  the exposure to NHs  was  confirmed and of a low
level.

ANIMAL STUDIES

     A summary of  the  animal data for  exposures to £  36 mg NHs/m3 is  given
in Table S-l.   The complete data are  given in the tables in  Section  III.
   Most foreign-language articles rated C and D were usually not translated.
     Each foreign-language abstract tentatively rated A or B from an English-
     language  abstract  or  brief  examination  of  the paper was translated  in
     sufficient degree to judge the experimental design and details.  These
     papers were numerically scored from the translation.

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                       TABLE S-l.   SUMMARY  OF EXPERIMENTAL ANIMAL EXPOSURE TO


Level of
Exposure
(rag/m3)
36-36.7









7.2-32.4
14.4-21.6




14.4





0-8.6



2-3


0.2



Exposure
Time
48 h
4 wk or 33 d
3 h
2 d
12 d
2 h
19 or 71 d
6 wk
52 d
35 d
4 wk
10 wk
52 d or 7 mo


49 d
42 d
42 d
6 d
72 h

4-12 wk
5 wk

4 mo
12 wk
84 d or 4 mo


84 d
Effects
w
>, C "
c fci en c js
§JJ 14 tH OJ -^ 4
MR) U1O *J W Q> 0
CQjCv-IQ)M w o 1-1 e "* Comments
^
+

NOEL
Anorexia
-H- Bacterial exposure prior to NH3 exposure.
Decreased body weight gain when also exposed
to 300 mg/ra3 dust.

NOEL at 22°C; slight effect at 10°C.
Concurrent bacterial exposure.
NOEL, compared to more exposed groups.
Effect probably due to dust at 0.1-0.4 mg/ft .
Slight initial decrease in reflex response;
decreased vitamin levels in some organs;
biochemical changes in blood and urine.
Concurrent bacterial exposure.



-H- High level viral exposure following NH-j
exposure.

Feed consumption above groups exposed to
higher levels.
++ Concurrent bacterial exposure.
Only with concurrent high levels of dust (0.6-
1.0 mg/ft3).
NOEL (even following concurrent bacterial ex-
posure) other than slight inhibition of the
blood redox function in the first mo.
NOEL
*  In comparison  to control animals given the same microbial exposure.
i  Initial response, at early stages only.
D  Delayed response.
+  Slight symptoms.
++ Moderate symptoms.

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Acute Animal Studies

     Among the rodent studies, Lehmann (1886) found minor, reversible irri-
tation ("annoyance") in rats and guinea pigs given the lowest reported dose,
about 400  rag  NHs/m3 for 4 h.  The  one mouse study is not contradictory.
Lehmann (1886) found that higher doses (about 800 mg/m3 and up) produce de-
creased respiration, secretions, and other such obvious symptoms of irrita-
tion.  At  extreme  doses  (lethal  to  near  lethal) of  several thousand milli-
grams per  cubic meter, the lung reaction included hyperemia as well as edema.

     Both  Lehmann  (1886) and Richard et al.  (1978b) found similar thresholds
in rabbits.  In Richard et al.'s study, curarized rabbit preparations showed
bradycardia,  arrhythmias,  and extrasystoles at the toxic  levels  of NH3.

     Lehmann  (1886)  reported that the  same minimum  dose  in cats  (about  400
mg/m3) produced  reversible  irritation, with increased effects, especially
secretions, at higher doses.  Dodd and Gross (1980) made pulmonary function
tests on cats given 720 mg/m3 for 10 min.  This level was quite toxic, with
slow recovery.  One cat of 20 died of bronchopneumonia, presumably influenced
by the lung damage caused by NH3-

     In other species, Charles and Payne (1966a) found a decrease in respir-
ation rate in some chickens given  72  rag NHa/m3  for an unspecified period
and a small increase in blood pH in hens given 54 mg/m3.   In a test of sus-
ceptibility to  infection, Drummond  et  al.  (1978)  found that  swine given 36
mg/m3 of ammonia had increased retention of  viable aerosolized bacteria  and
increased  pulmonary weight, but no apparent  gross or histopathologic lesions.
These results correlate well with the  report of bronchopneumonia in the  cat.

Repeated Dose Animal Studies

     Anderson et  al.  (1964)  found that 4-wk exposure  of  mice and of  guinea
pigs to 14.4 mg NHg/m3 had no effect, but  6-wk exposure produced lung lesions
(hyperemia, edema,  congestion).  Anderson  et al.  (1964)  also found  that if
guinea pigs were exposed to 36  mg/m3  continuously for 6 wk, they devel-
oped similar but more severe lung lesions, plus congestion in the liver  and
spleen.   In  sharp contrast, Coon et al. (1970) found that 155 mg/m3 given
to guinea  pigs 40  h/wk for 6 wk  or 40  mg/m3  given to guinea pigs continuously
for  114 d  was nontoxic.   The strain of  guinea pig used in Anderson et al.
(1964) was not given, but these  differences  may be due to varying sensitivity
between strains.   Exposure to 770 mg/m3  8  h/d for 6 wk did cause lung lesions
(Coon et al., 1970).  These  studies imply  a  fairly good "C x t effect"  (con-
centration times time is constant for  similar effects).

     Many  relevant studies  have been  made with  rats.  In Russian studies
aimed at determining a maximum permissible concentration  (Saifutdinov,  1966
and  1968), 12-wk exposures to 0.2 mg/m3  had  no effects; exposure to 2 mg/m3
had negligible effects (inhibition of  blood  redox function in the first  few
weeks only);  and exposure to 20  mg/m3  had  some minor effects  (inhibition of
brain cholinesterase, increased  urinary  coproporphyrins), which disappeared
after exposure  ceased.   The observed  effects are minor and of questionable
toxicological importance,  further marred by a lack of experimental  detail.

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     In more usual  types  of  studies,  Stolpe and Sedlag  (1976)  found  that  a
52-d exposure to 21.6,  36, or  65 mg/m3  did not affect rats  dosed  at  normal
temperature, whereas the 36 and 65 mg/m3 levels were mildly toxic (decreased
weight gain with partial  recovery) to rats kept at  10°C.  Broderson  et al.
(1976) found some histopathologic changes in respiratory and olfactory epi-
thelia of rats exposed to 108 mg/m3 for 75 d or to 180 mg/m3 for 35 d.  Coon
et al.  (1970) found no effects in rats exposed to 155 mg/m3 40 h/wk for 6
wk, but severe effects  (including death of two-thirds of the rats) in those
exposed to 455  mg/m3;  no histopathology was done.  Richard et al. (1978a)
found that 360  mg/m3 for 5 d  or more was toxic,  with respiratory lesions
appearing after 3 wk.

     Broderson et al.  (1976)  exposed rats to varying levels of NHs  for 5
wk, and challenged them with an intranasal inoculation of infectious bacteria
on day 7.  While  even the lowest dose  (18 mg/m3) increased the infection
severity,  there were increasingly  severe effects at each level up to the
highest used (180 mg/m3).

     Only two studies reported results with rabbits.  Mayan and Merilan (1972)
found that both levels used (36 and 72 mg/m3) decreased the respiration rate
every time the brief (2.5-3 h) exposure was repeated (at unstated intervals).
Coon et al.  (1970)  exposed rabbits 40 h/wk for 6 wk.  His  higher dose of
770 mg/m3 caused  dyspnea and lacrimation during  the first  few days  only.
Repeated exposure to that dose beyond the first week or to 155 mg/m3 had no
effects.  Coon et al. (1970)  also tested dogs and monkeys with the same pro-
tocol.  Results in  beagle dogs were  identical to those  in rabbits.   The
squirrel monkeys were apparently unaffected; one  low-dose monkey  had focal
pneumonitis, but this is not unusual.

     Because closed, air-conditioned  livestock  and  poultry facilities are
widely available, many  studies have  involved swine and poultry.  Most of
these involved  combined exposures  (with manure gas, dust, and  similar con-
taminants);  but some studies do have useful, separate exposures.   Stombaugh
et al.  (1969) found inconsistent, but probably negligible,  effects in pigs
exposed to 44 or  9  mg NH3/m3  for 5 wk.  Higher levels  (74  and 104 mg/m3)
decreased feed  consumption and caused  coughing and nasal,  lacrimal, and
oral  secretions.  The highest  level  (201 mg/m3) was given to only one
animal which exhibited  severe  irritation symptoms and convulsed after 36-h
exposure,  but recovered 7 h after exposure.

     Curtis  et al.  (1975) found no consistent changes in pigs exposed to 36
mg NH3/m3 for 71  d  or to that dose plus 2.8 mg H2S/m3 for 19 d or to that
dose plus 10 mg dust/m3 for  27  d.  If the dust concentration was  increased
to 300 mg/m3, weight gain decreased.  Exposure to  54 mg NHs/m3 for  109 d
without added dust  had  no adverse effects, indicating that the high dust
levels gave  reduced weight gain.

     Doig and Willoughby (1971) found slight effects (conjunctivitis in the
first or second week, upper  respiratory tract epithelium reaction) in pigs
exposed for 6 wk  to 77  mg NH3/m3 alone or with ground corn dust  (10.6 or
213 mg/m3).

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     Anderson et al. (1964) found that exposure of chickens to 14.4 mg NH3/m3
for 24 h to 28 d caused a brief (up to 3 or 4 d) increase in mucus secretion,
but no pathology or obvious discomfort.  Exposure for 6 wk or longer produced
hyperemic, dense  lungs  with congestion, edema, and hemorrhage.  Valentine
(1964) studied  exposures  of chickens at rather widely varying NH3 levels,
apparently without controls, and reported a dose-response curve.  Decreased
weight gain and, at sufficiently high doses, eye ulcerations were observed.

     Charles and Payne  (1966a) found mild, somewhat inconsistent, toxic ef-
fects in two groups of  chickens exposed to 37 or 38 mg NH3/m3.  Larger doses
(56  and  72 mg/m3) gave decreased  feed  consumption  and weight gain  in  the
later parts of the studies.

     Anderson et al. (1964) did an interaction study in which chickens were
exposed to NH3 for 18 d and then given an aerosol of Newcastle disease virus.
At the lowest NH3 level studied (14.4 mg/m3), the lower virus dose  (3 ELDso'8
liter for  3 min) was not affected by the pretreatment, while the higher virus
dose  (6  ELDso's/liter)  infected all the pretreated birds  and half  of  the
controls.  With pretreatment at 36 mg/m3 and the higher virus dose, results
were similar.

     Anderson et  al.  (1964) found that turkeys  exposed  to 14.4 mg  NH3/m3
for  6 d followed by 36  mg/m3 for 2 d were unaffected.  However, exposure  to
36 mg/m3  for 12 d did  produce increasing lung effects (congestion, edema,
hemorrhage) plus anorexia  and decreased weight gain.  Anderson et al.  (1968)
reported  on  studies with  turkeys  exposed to  low (nontoxic)  levels  of  NH3
plus various levels of  dust.  The  dust  caused adverse effects, but  no  inter-
action between the NH3  and dust was reported.

Chronic Studies in Animals

     Coon  et al.  (1970) found that 114  d at 40 mg NH3/m3 and  90 d at 127  mg
NH3/m3 had no  adverse  effect on  rats.  However, 90 d at 262 mg/m3  caused
some symptoms (nasal discharge in  *• 25% of rats) while 470 mg/m3 was lethal
to most  rats, with  interstitial pneumonitis the  main  lesion.  Mikhailuts  et
al.  (1979) studied  in rats the interaction of exposure for 35 h/wk  for 4  mo
to  low  levels  of NH3 with intranasal exposure to pathogenic bacteria.  The
low  dose of 3 mg/m3 had no effect, but the high dose of 6 mg/m3 increased
bacterial  effects.   Particularly significant were  decreases  in the usual
protective effect of phagocytes.

     Coon  et al.  (1970) found that guinea pigs were much like rats, although
somewhat  less  sensitive,  with no  effects  from 114 d at  40 mg/m3 and some
deaths  from  interstitial pneumonitis after 90 d at 470 mg/m3.  They found
that rabbits were about as sensitive  as  guinea pigs (no deaths,  but lung
lesions  in the  three rabbits dosed at  470 mg/m3  for 90 d); marked eye  irri-
tation was noted.   Results in beagle dogs and  squirrel monkeys  followed the
pattern:   no adverse effects after 114  d at 40 mg/m3, interstitial  pneumonia
and  (in  dogs) irritation,  but no  deaths, in the  few animals  given 470  mg/m3
for  90 d.

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HUMAN STUDIES

     A summary of  all  the human experimental data is given in Table S-2,
and of the occupational data in Table S-3.

Experimental Studies

     A moderate  number  of experiments has been done on humans exposed to
ammonia at various  concentrations.   The details of acute experimental in-
halation  exposure  studies are  given in  Table  IV-1, with  repeated dose
studies in Table IV-2.

     The first observed effect at low levels of NH3 appears to be odor per-
ception.  Reported  threshold  values  vary considerably within studies and
between studies.   Sayfutdinov (1968)  reported perception thresholds for 22
subjects varying from  0.45  to 1.0 mg/m .  In contrast, Keplinger  et  al.
(1973) found that  one  subject (of 10)  could not detect 23 mg NH3/m3, al-
though he could detect 33.7 mg/m3.  In a poorly controlled study, Mikhailov
et al. (1969) found metabolic evidence of ammonia exposure (such as increases
in urinary ammonia  and urea)  after 8-h exposure to 13 mg NH3/m3, but not
after 3 mg/m3.   No adverse effects were reported; the alterations are within
normal metabolic ranges.

     The first adverse  effect of NH3 appears to be irritation of the nose
and/or eyes.   Keplinger et al. (1973) found no (subjective) irritation after
5-min exposure to  23 or 36 mg NH3/m3, but some  effects in 6 of 10  subjects
given 52 mg/m3.  In a more thorough study, Verberk (1977) found slight irri-
tation, but no effects  on pulmonary function or hypersusceptibility,  from
2-h exposures  to 36 mg NH3/m3.   Increasing the  concentration to  57.6 mg/m3
caused small (< 10%) decreases in pulmonary functions.   Even higher concen-
trations (79.2, 100.8 mg/m3) greatly increased irritation;  the higher level
was unbearable to  all  eight inexperienced subjects before the 2-h  exposure
was completed.   Other  studies,  generally at higher  concentrations for
shorter periods,  were consistent with these.

     The most useful repeated dose study was that of Ferguson et al. (1977)
involving 2 x 3-h  exposures,  5  d/wk  for 6 weeks, at concentrations of 18,
36, or 72 mg NH3/m3, in an industrial setting.   They found some dose-dependent
changes in respiratory  function  (increased  1-sec forced expiratory volume,
but not changes in ventilatory capacity) and consistent irritation signs only
at the highest concentration  (72 mg/m3).   Some other studies (Mikhailuts,
1977;  Sayfutdinov,  1968) report inhibition of odor thresholds to other com-
pounds and lowered  eye sensitivity to light at low concentrations  (0.32-
10.5 mg/m3) of NHs,  with minor, transient changes  in  cardiovascular and
respiratory functions at 6.1 and 10.5 mg/m3.  The importance of these find-
ings is dubious.

Occupational Exposures

     Several studies,  summarized in  Table S-3,  have involved workers occu-
pationally exposed  to NH3.  Most of  these studies have little value, their

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        TABLE  S-2.   SUMMARY OF  HUMAN  EXPERIMENTAL  EXPOSURE TO NH3
Level of
Exposure
(mg/m3)
360-403.2
(several
studies)
180-344
144
96.5-106
(several
studies)
50-79.2
(several
studies)
18-72
51.8-57.6
(several
studies)
36
(several
studies)
36
33.7
23
21.6
13
Exposure
Time
Acute
Acute
Acute
Acute
Acute
Repeated
Acute
Acute
Repeated
Acute
Acute
Acute
Acute
Table No.
1V-1
IV-1
IV-1
IV-1
IV-1
•IV-2
IV-1
IV-1
IV-2
IV-1
IV-1
IV-1
IV-1
Effects
Blood pressure decreased; NHj levels in the blood increased;
rapidly reversible changes in lung functions; lacrimation but
no coughing; widely varied subjective responses.
Changes in lung functions at rest and during exercise; changes.
in exercise cardiac frequency.
Lung function and slight cardiac changes.
Significant lung function and cardiac changes, at rest and exer
cise; some strong irritation of eyes, nose, mouth or throat,
though others were relatively unaffected.
Slight lung function changes in some ; reduced cardiac frequency
in some; definite eye and throat irritation in some, though
others relatively unaffected.
Occasional mild irritation; increased FEV-^ but not other
respiratory or blood pressure parameters; apparent adaptation
in the ability to withstand brief excursions to 144 mg/m^.
Slight decrease in lung functions; definite eye and slight
throat irritation at the higher level; slight irritation of
some at the lower level; odor detected.
No lung function changes; slight to moderate irritation in
some; odor detected.
No significant changes in lung function, blood pressure,
rate of irritation or neurological response.
Lowest concentration at which 4/4 detected the odor.
9/10 detected the odor; no irritation.
Faint irritation in some; odor detected.
Increased NHo levels in blood and urine; decreased 02 con-
10            Repeated


6.1           Repeated


3             Acute


2.2           Repeated

0.45-1.0      Acute

0.32-0.76     Repeated


0.32-0.65     Repeated
             sumption; no EKG changes;  rapid recovery.

IV-2         Some changes in lung functions, heart rhythm, and odor
             sensitivity.

IV-2         No change in lung functions  or heart rhythm; changes in  odor
             sensitivity.

IV-1         Tendency to decreased Oo consumption; insignificant EKG  changes;
             rapid recovery.

IV-2         Decreases in some lung functions  and camphor odor  theshold,

IV-1         Range of thresholds of NH^ perception for 22 people.

IV-2         The upper range changed cerebral  cortical activity; 0.32 mg/m^
             was the subthreshold level.

IV-2         Upper levels decreased eye sensitivity to light; 0.32 mg/m3 was
             the subthreshold value for eye sensitivity.

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                 TABLE  S-3.   SUMMARY OF OCCUPATIONAL EXPOSURE TO NH3
 Level of
 Exposure
 (mg/m3)

 3.6-144
 (plus CO,C02,
 H2S)

 50-75
 10-40
5-29
 Length
  of        Table
Exposure     No.
                              Effects
2-12 h/d     V-l     Mainly respiratory complaints; some eye irritation
                     and nausea.
    y        V-l     Increased cancer rates compared to non-NH3 produc-
                     tion workers, and the general population of the
                     GDR, especially of the lungs, stomach, lymphatic
                     tissue, and urinary tract.  Perhaps there was also
                     exposure to asbestos.

5-10 y       V-l     Various signs of overexcitability of the nerve
                     tracts by the end of the workday.

             V-l     Higher incidence of chronic bronchitis and dyspnea;
                     lower
 18.3-26.3
 (plus H2S04)
 6-26
 (plus

£20
 (plus
2 y
             V-l    ~507o had slight or moderate impairment of lung
                     function, the percentage decreasing over the years
                     with decreasing NH3 levels.
             V-l     Lower FEV1 values.
V-l     Increased incidence of upper respiratory tract dis-
        orders and xeroderma with increasing exposure time;
        biochemical changes indicating possible hepatic
        stress.

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major faults being  lack of precise exposure data and the presence of con-
founding variables  such as smoking (a known  source  of  MS exposure) and
exposure to other irritants.

     The most  useful study is  that of  Herrman and Viehrig  (1979).  Despite
its faults, especially  the few subjects involved, a decrease in ammonia ex-
posure  is  well correlated with a  decrease  in  impairments of  lung  function.
The inverse  effect  (increased  lung impairment with  increased NH3  exposure)
was reported by Kujawska  et al. (1977) and Giguz (1968).

Accidental Exposures

     Table V-2 contains details of  the reports of accidental overexposures,
generally  to  massive concentrations for a few minutes.  None gives actual
concentrations; most involve  only 1 or 2 persons.   However,  they  do  demon-
strate  that the effects of very high concentrations are qualitatively similar
to  those  seen from the lower  concentrations  reported for experimental and
occupational exposures.   The most  clear-cut dose-response curve is from Caplin
(1941), the  report  with the greatest number of exposed  persons  (47).  Nine
victims had  only  "mild"  exposure,  giving acute pharyngitis  and tracheitis
with  rapid recovery.  The 25  victims of "moderate"  exposure  had more  exag-
gerated  symptoms,   including acute bronchitis and bloody  sputum.  While
15/25  recovered  completely, 6  died, 3 from bronchopneumonia  (in those pre-
antibiotic years)  and 3  from  pulmonary edema.  The 11 victims of "severe"
exposure were  gravely ill, with pulmonary edema, intense dyspnea, etc.;  7
died.

     The basic pattern is irritative damage followed by death  or  recovery,
with  no evidence  of  late  sequelae  other than rare  pulmonary obstruction,
possibly due to scarring.

OTHER POSSIBLE EXPOSURES  TO AMMONIA

     To put the levels  of NHa  encountered  in  automobile exhaust in some per-
spective,  other  common ammonia exposure sources are  given here.  The most
obvious, and  a frequent  confounding  factor in human  studies, is  cigarette
smoke.  Estimates  of NHs  levels  in cigarette smoke vary with  the type  of
tobacco and  the investigator:   51-153 |Jg/nonfilter  cigarette,  36  pg/filter
cigarette  (Sloan  and Morie,  1974), and 25-29  [Jg/g of tobacco smoked  (~ 50%
being  retained by the smoker;  Bhown et al., 1971).

     Human breath itself  can contain measurable levels  of NHg, but it varies
with  the  subject:   0.029-0.520 mg/m3 (Larson  et al.,  1977),  0.1-1.50 mg/m3
in  healthy smokers, and 0.4-1.93 mg/m3 in  nonsmokers  (Nefedov et  al., 1969).

      Ammonia  can  also be present in the ambient air.   The average level of
ammonia in urban air has been estimated to be about 20 ppb (~  0.014  mg/m3;
NAS/NRC, 1972).  Limits have been  set  on the  levels which  are to  be allowed
in  the workplace air.  The American  Conference of  Governmental Industrial
Hygienists  gives  18 mg NHa/m3 as the time-weighted-average threshold limit
value,  and 27 mg/m3  as the short-term-exposure limit (ACGIH,  1981).   For

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^.comparison, the Maximum Allowable Concentrations in air in the USSR for 1972
 ,were 20 mg/m3 in the workplace, and 0.2 mg/m3 as both the one-time and aver-
 age limit in populated places (USSR, 1972).

 RECOMMENDED RANGE OF CONCERN

      The available  evidence  is  that the adverse effects of NH3 are due to
 its irritation of mucous membranes, particularly in the eye and respiratory
 tract.  Unless the  exposure  is lethal, recovery usually occurs.  The odor
 threshold is regularly reported as being less than the irritation threshold.
 Therefore the odor  threshold  (the  consensus  opinion is  about 5  ppm, 3.6 mg
 NHs/m3; NAS/NRC,  1972)  is  recommended as the upper bound of the  range of
 concern.

      Because of the  lack of  solid studies of effects  at lower levels, and
 the routine recovery from nonlethal over-exposure,  the lower bound would be
 an arbitrary margin of safety.  We recommend 0.36 mg NHg/m3, below the lowest
 reported odor threshold.

      Animal studies provide little assistance in setting ranges of concern
 because of the practical difficulties in determining an odor threshold in a
 nontalking creature.
                                      10

-------
                                 SECTION I

                               INTRODUCTION
     This report was compiled as the third of several tasks under Contract
No. 68-03-2928, "Health Effects Support for the Emission Control Technology
Division (U.S. Environmental Protection Agency,  Ann Arbor, Michigan)."  The
goal of  the  project is to evaluate health effects literature on specific
compounds emitted  from automobiles  equipped  with emission-control devices
(specifically catalytic converters), not for  the purpose of creating a cri-
teria document but to identify a range of concern or a no-observable-effect
level for each compound to serve as guidance  to automobile manufacturers in
their development of future emission-control  devices.

     The present report was meant to be largely a series of charts or tables
of pertinent  data  with the tests logically  ordered  according to exposure
levels.  The  narrative summary was not meant to describe again each paper
in detail.   There  are  admittedly some  disadvantages  in  not doing so;  e.g.,
some of the gradations in effect the authors  of a particular paper observed
may be diluted or lost when the details are spread throughout an exceptionally
large table, or between several tables.  Papers described in a largely narra-
tive fashion, however, often are difficult to compare.  Results that appear
within their source paper to be quite definitive may appear less so or even
anomalous when juxtaposed in tabular format with other results from similar
studies.  Hence, the present format was designed to facilitate comparisons.

     Literature related to health effects of inhaled NHs was collected mainly
by computer search of TOXLINE and TOXBACK and manual search through the NRC
Subcommittee report on ammonia.  Approximately 200 papers and other documents
were  evaluated,  but only about 50  contained original data suitable  for
tabulation.

     Experimental animal and human exposure studies were evaluated and sum-
marized by a senior Ph.D. pharmacologist.  Occupational exposures were rated
by an  epidemiologist with  an M.D.  degree.  Figure  1-1 is  the  form used  for
rating documents by the project pharmacologist and  epidemiologist.   Each
document was  rated in a two-step procedure according to the applicability
of its  subject matter and to the quality of the experimental methodology.
The letter  assigned in rating the document A, B, C, or D was derived from
the corresponding  lower case  letters under item 7 in Figure 1-1.  Thus, a
study  was  rated  A if  it directly  applies  to or assists in establishing a
range of concern for exposure to NHs-  The second part of the rating is the
methodology score.  The document reviewer checked off which score should be
                                     11

-------
                                                       Article No. 4997-3-
CHECK WHERE APPROPRIATE:
1. Do they state/limit the problem?
2. Adequacy of sample
3. Replicability
4. Controls/control procedures
5. Completeness and comprehensibility
of results
6. Validity of conclusions, inter-
pretation of data
PAPER
DEFECTIVE
0






PAPER IS
SUB-
STANDARD
1






STANDARD
QUALITY
2

'




SUPERIOR
PAPER
3






7.  Applicability to health effects of  ^3  as guidance for establishing a range
    of concern for NH3 in automobile exhaust.
      (.circle one)

a.  Clearly, directly applies/assists in establishing a range of concern
    (Chronic human studies; acute exposure of humans if minimal effects.)

b.  Research requires major inferences; potentially applicable.
    (Chronic animal studies; acute human, maximal effect; acute animal,
     minimal effects.)

c.  Useful hints or suggestions; tentatively applicable.
    (Acute animal, lethal effects; studies in above categories but effects
     reported not appropriate.)

d.  Not directly applicable (peripheral useful information).

                        Figure 1-1 - Form for Report Rating.
                                         12

-------
given for each of the first six items in Figure 1-1,  and the total was writ-
ten at the top of the page along with the letter that rated the paper's ap-
plicability.  In  some cases, such as reviews, theoretical papers, and  low-
rated foreign-language documents, a paper may have received an applicability
rating (generally C or D) but none on methodology.

     Data,  including the  MRI-assigned  rating, from the A-,  B-,  and some
C-rated papers were  tabulated  by a mid-level scientist.  Information  for
each topic  heading was  looked  for; so  if blanks  appear in  the table,  the
reader can generally assume the data were not given.   Information which was
unclear in  the  original document but needed for tabulation is preceded in
the tables  by a  qualifying word such  as "apparently."  Sometimes a group
published several papers that described the same tests.  To avoid redundancy,
all pertinent papers were cited and the test was described as well as possible
from all the papers'  descriptions.

     The  final written  summary  of  the  tabulated data was also performed by
a  senior  pharmacologist.   This  summary attempts to reflect  objectively the
scientific  community's  thought  as  a whole and does not  reflect the  tabular
material  by weight.   The tables reflect the amount of data generated, and
the summary puts  the evaluated  data  in perspective with the overall scien-
tific community's opinions.
                                      13

-------
                                SECTION II

                                 BIOASSAY
     The studies described  in Table II-l are considered bioassays because
they do not  deal with  intact  animals.  They are all concerned with the ef-
fect of NHs  on tracheal  ciliary activity, and so mucociliary clearance and
possibly the risk of microbial infection.  The tracheas were either removed
entirely or opened in situ and then exposed,  generally for S 45 min.

     There are a few possibly helpful hints to be gained from these studies.
The results of Dalhamn (1963) show a 95% reduction in the NHs concentration
in the  inhaled air by  the time it  reaches the trachea,  indicating that the
upper respiratory tract may be the site of much of the toxic symptoms.   There
appears to be a possible slight synergism between MS  and carbon particles
(Dalhamn, 1963;  Dalhamn and Reid,  1967).   The effect of lower levels of NH3
on ciliary movement is unclear, Dalhamn and Reid (1967) indicating no effect
at 73.7-85.5 mg NH3/m3 and  Dalhamn (1956) reporting a  rapid effect at 2.2-
64.8 mg NHs/m3.  The  former study is perhaps more useful because it deals
with the repeated  exposure  of live animals.   If so, the levels of NHs ex-
pected  to be encountered in automotive exhaust should  be of little concern
in this respect, except perhaps in the presence of particulates.
                                     15

-------
                                                               TABLE II-l.    BIOASSAYS
Compound (s) and
Concentration(s) in
mg/m3 (ppm)
NH3 1,440
(2,000)
Carbon particles
2
(95% < 3 pm)

Temperature
and Mode of
Humidity Exposure
Not given Not given






Preparation
Exposed Description of Tests and Duration
Live rabbits Exposure was to NH3 alone or with the
particles for 45 rain. Experimental de-
tails were not given, but the tracheas
were apparently exposed while in place
in the animals, and ciliary beat fre-
quency determined cinematographically .


Results
NH3 alone caused a reduction in ciliary
activity, though not its cessation.
There was a possible slight synergism
with carbon particles.

This level in the inhaled air resulted
Reference
and
Rating
DJ lhamn
(1963)
D-7



NH3     180-720
       (250-1,000)
NH,
        288-432
       (400-600)
                     37°
                     100%
                     30-31°
NH3
         54-121.7     34-37.5°
        (75-169)      100%
         73.7-85.5    Not given
       (102.3-118.7)
Carbon particles
          3.46
       (95% < 3 Mm)
NH
  3       2.2-64.8
         (3-90)
                     34°
                     90-95%
Chamber       Excised rabbit   Ciliary activity was observed (method
             trachea opened   not given) for a 20-min exposure.
             longitudinally
Constant      Excised'rabbit   Gas was delivered through a syringe at a
temperature   tracheal tissue  rate near natural rabbit air flow for
tissue                         10 min.
chamber
                              Ciliary activity was observed through a
                              microscope during exposure, and recovery
                              in humid air or Ringer's solution.

Thermo-       Excised rabbit   Ciliary activity, including frequency,
regulated     trachea opened   was observed (method not given) before
chamber       longitudinally   and after a 45-rain exposure to constant
                              level of NH3.

Not given     Live rats        Rats were exposed 5 h/d, 5 d/wk for 60 d,
                              apparently in vivo.  At the end, ciliary
                              beating frequency was determined (prob-
                              ably cinematographically) while rats
                              lay with tracheas exposed and opened
                              lengthwise (unclear, but probably not
                              while air flow was continuing).  Ex-
                              posure to Nil3 alone and with particles.

Chamber       Rat tracheas     Ciliary activity was continuously ob-
             (unclear if      served microscopically for < 10 min,
             they were ex-    with continuous gas flow over the
             cised or opened  tracheas.
             and exposed
             "in place")
in ~ 100 ppm in the tracheal  air in live
rabbits with cannulae inserted in the
tracheas.

Ciliary activity stopped (recovery not    Dalhamn and
considered) in ~ 5 min when exposed to    Sjb'holm
500-1,000 ppm.  The time required was     (1963)
* 20 min when exposed to ~ 250 ppm.       D-6

Cessation of ciliary activity without     Cralley
recovery in Ringer's solution occurred in (1942)
10 min at 600 ppm.  It occurred without   D-6
recovery in air in 5 or 10 min at 500 or
400 ppm, respectively.
                                                                                                           A  concentration of ~  100 ppm  seemed  to    Dalhamn
                                                                                                           be the critical level  influencing  ciliary (1963)
                                                                                                           beating.                                  D-7
NH3 alone had no effect on ciliary activ- Dalhamn and
ity.  Combined with carbon particles,     Reid
beat frequency decreased significantly.   (1967)
6/10 rats exposed to only NH3 had mod-    C-7
erate to severe histological damage to
the tracheal mucosa.
Very rapid loss of ciliary movement:      Dalhamn
after 5-s exposure to 90 ppm and after    (1956)
7-8 min exposure to 3 ppm.  Recovery was  C-6
also rapid, in 10 to 30 s after expo-
sure stopped.

-------
                                SECTION III

                 EXPERIMENTAL ANIMAL INHALATION EXPOSURES
     The essential parameters of numerous animal inhalation exposure experi-
ments are  tabulated  in  this  section  (Tables  III-l to 111-22).  The primary
organization of the data is by species, in order of increasing weight (bats
to swine  in  this  case).  Within a species,  studies are divided by dosing
duration:  acute exposure (S 24 h), repeated exposure,  and chronic exposure
(^ 90 d).  Within a single table, reported results are listed in order of
decreasing exposure level.

     The tables have been arranged in the aforesaid manner for the following
reasons:   (1) there were almost 200 separate tests being tabulated;  (2) there
are distinct differences in lung anatomy among the laboratory species used,
and the  differences  seen in  their  relative responses may have been largely
due to these anatomical differences; and (3) by putting the highest concen-
trations and worst  effects first,  one  can more  readily understand the  sig-
nificance of minor or less-severe changes occurring at lower levels.

     However, a composite Table S-l appears in the Summary.  Because of the
large amount of data, this table groups the results seen in various species
only at levels ^ 36 mg NH3/m3.

     In the animal exposure tables in this section, the column headed Total
Length of  Expt.  includes not only the total length of exposure to NH3 but
also any  recovery time  observed in the study.  This recovery time was in-
cluded to note the endurance or reversibility of the toxic effects.
                                     17

-------
                                      TABLE III-l.   BATS—ACUTE EXPERIMENTAL EXPOSURE TO NH,
oo
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 3,960 Not
(5,500) given







NH3 2,520 Not
(3,500) given






NH3 2,160-2,376 Not
(3,000-3,300) given






NH3 1,440 Not
(2,000) given






NH3 972 Not
(1,350) given







Mode of
Exposure
Inhala-
tion
chamber






Inhala-
tion
chamber





Inhala-
tion
chamber





Inhala-
tion
chamber





Inhala-
tion
chamber





Species/
Strain/
Age/Weight
Bats,
Macrotus
californi-
cus, 8.8-
15.0 g .




Bats,
Macrotus
californi-
cus, 8.8-
15.0 g



Bats,
Macrotus
californi-
cus, 8.8-
15.0 g



Bats,
Macrotus
californi-
cus, 8.8-
15.0 g



Bats,
Macrotus
californi-
cus, 8.8-
15.0 g



No. of
Test
Animals
Unknown
number
out of
group of
59 M+F
used in
study


Unknown
number
out of
group of
59 M+F
used in
study

Unknown
.number
out of
group of
59 M+F
used in
study

Unknown
numbe r
out of
group of
59 M+F
used in
study

Unknown
number
out of
group of
59 M+F
used in
study

Duration & Total
No. of Frequency Length of
Controls of Exposure Expt.
Appar- < 1 h < 1 h
ently once
served as
own con-
trols for
heart and
respira-
tory rates

Appar- S 4 h S 4 h
ently once
served as
own con-
trols for
heart and
respira-
tory rates
Appar- 9 h 9 h
ently once
served as
own con-
trols for
heart and
respira-
tory rates
Appar- 9 h 9 h
ently once
served as
own con-
trols for
heart and
respira-
tory rates
Appar- 9 h 9 h
ently once
served as
own con-
trols for
heart and
respira-
tory rates


Effects
Decrease in heart rate and
respiration, death in 40 min.
Brain greatly congested, lungs
edematous with large hemor-
rhages, distended heart, gal]
bladder, and urinary bladder,
greatly distended stomach and
intestines, and congested liver
and kidneys .
Decrease in heart rate and res-
piration, death in 4 h. Brain
greatly congested, lungs edema-
tons with large hemorrhages,
distended heart, gall bladder,
urinary bladder, greatly dis-
tended stomach and intestines,
and congested liver and kidneys.
The highest level "tolerated"
for 9 h was 3,000 ppm. At
3,300 ppm the bats changed from
nasal to mouth breathing. Oily
condition developed on body
hair.


In addition to eye irritation,
reddening of skin and inflamed
lips and mouth. Oily condition
developed on body hair.




Apparent eye irritation with
excessive lacrimation. Oily
condition developed on body
hair.




Reference
and
Rating
Mitchell
(1963)
B-9






Mitchell
(1963)
B-9





Mitchell
(1963)
B-9





Mitchell
(1963)
B-9





Mitchell
(1963)
B-9






-------
TABLE III-2.  MICE—ACUTE EXPERIMENTAL EXPOSURE TO NH3
Corapound(s) and
Concentration(s) in
n>g/m3 (ppra) Humidity
NH3 360 Not
(500) given
Followed by 10 min
exposure to an
aerosol of
Pasteurella
raultocida, with
no further. NH3.
Species/ No. of Duration & Total
Mode of Strain/ Test No. of Frequency Length of
Exposure Age/Weight Animals Controls of Exposure Expt. Effects
Exposure Mice, avg. 49 M A9 tt 8 h 13 d 21/49 died, not significantly
chamber wt 25 + 2 g different from control group.
(specific
pathogen
free)



Reference
and
Rating
Richard et al.
(1978a)
B-ll






-------
                                         TABLE  III-3.   MICE—REPEATED  DOSE EXPERIMENTAL EXPOSURE TO NH3
          Compound(s) and
         Concentration(s) in
            mg/m3 (ppm)

         NH3          360
                    (500)
         Followed by 10 rain
         exposure to an
         aerosol of
         Pasteurella
         multocida, with no
         further NH,.
                              Species/    No. of               Duration &     Total
                              Strain/      Test      No.  of     Frequency    Length of
                             Age/Weight   Animals   Controls   of Exposure     Expt.
                   Exposure   Mice,        49 M      50 M       168  h         19 d
                   chamber    avg.  wt
                             25 +  2 g
                      Effects
           42/49 died, a significant
           increase compared to the
           control group.  Mortality
           also higher than the group
           exposed to NH3 for only 8 h.
Reference
   and
  Rating

Richard et al.
(1978a)
B-ll
        Nil,
14.4    10-30%     Cabinet    Swiss
(20)               (336 ft3)  Albino mice,
                             3-4 wk
                                                                                   7 d
                                                                                   14 d
                                                                                   21 d
                                                                                   28 d
                                                                                   42 d
42 d       No effect up to 6 wk.  After
           6 wk,  lung tissue became dark
           red  and more dense than con-
           trol lung tissue, with pul-
           monary congestion, edema, and
           hemorrhage.
Anderson et al.
(1964)
B-12
N3
O

-------
TABLE III-4.  RATS—ACUTE EXPERIMENTAL EXPOSURE TO NH3
Compound(s) and
Concentration(s) in
mg/m3 (ppm)
NH3
NH3
NH3
NH3
NH3
NH3
NH3
22,500
(31,300)
9,580-11,150
(13,300-13,600)
8,780
(12,200)
1,640-1,800
(2,280-2,500)
1,555
(2,160)
590-1,030
(820-1,430)
346-410
(480-570)
Humidity
Not
given
Not
given
Not
given
Not
given
Not
given
Not
given
Not
given
Species/ No. of Duration S
Mode of Strain/ Test No. of Frequency
Exposure Age/Weight Animals Controls of Exposure
Well- Rats 50 0
ventilated
chamber
Well- Rats 41 0
ventilated
chamber
Well- Rats 40 0
ventilated
chamber
Well- Rats 15 0
ventilated
chamber
Well- Rats Groups 0
ventilated of 10
chamber and 11
Well- Rats 8 0
ventilated
chamber
Well- Rats 3 0
ventilated
chamber
32 min
3'h
once
4 h
once
2.5 h
once
4.5 h
once
5.5 h
once
4 h
once
Total
Length of
Expt. Effects
Died in 32 min after severe
dyspnea. Lung hemorrhages.
Slightly injured. No observ-
able symptoms after exposure.
Slightly injured. No observ-
able symptoms after exposure.
Same symptoms as after 1,555
mg/m3. Normal after exposure.
Some secretion. Respiration
fell to 10 then gradually rose
to 45. Eyes mostly closed.
Normal after exposure.
Quiet. Slight annoyance.
Normal after exposure.
Very slight annoyance. Normal
after exposure.
Reference
and
Rating
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9
Lehmann
(1886)
B-9

-------
                                TABLE 111-5.   RATS—REPEATED  DOSE EXPERIMENTAL EXPOSURE  TO NH3
Compound(s) and
Concentration(s) in Mode of
mg/ro3 (ppm) Humidity Exposure
NH3 770 + 55 50% Modified
(1,070) Rochester-
type in-
halation
chamber

NH3 455 + 23 50% Modified
(632 + 32) Rochester-
type in-
halation
chamber
NH3 360 Not Exposure
(500) given chamber






Species/ No. of Duration & Total
Strain/ Test No. of Frequency Length of
Age/Weight Animals Controls of Exposure Expt.
Sprague- 15 123 8 h/d, .6 wk
Dawley and (4 died) 5 d/wk,
Long-Evans 6 wk
rats


Sprague- 50 123 Continuous 65 d
Dawley and (4 died) 65 d
Long-Evans
rats

Rats, 27 M 27 M 1-8 wk 8 wk
avg. wt
196 + 7 g
(specific
pathogen
free)




Effects
No deaths. The lungs showed
consistent nonspecific inflnm-
matory changes. (Note the
milder effects compared to the
455 mg/m3 exposure, and the
different exposure schedules.)
32/51 died by 25 d. 50 died
by 65 d . All rats showed mild
signs of dyspnea and nasal ir-
ritation. No histopathologic
exams were made.
At wk 3, nasal irritation and
severe inflammation of the up-
per respiratory tract. No dif-
ference in the number of pul-
monary alveolar macrophages.
Food consumption and body
weight significantly less than
controls after 5 d.
NH3           180
             (250).
With intranasal
inoculation of
tlycoplasma pulmonis
on day 7  of NH3 ex-
posure, both test
and control groups.
51-69%    Exposure   Fischer      12       12
          chamber    rats, 2-4             (matched
                     mo  (specific          on age,
                     pathogen              sex, and
                     free)                 no./cage)
35 d
             35 d        Increased  incidence of gross
                         and microscopic  lung lesions,
                         and severity of  rhinitis,
                         otitis,  tracheitis, and pneu-
                         monia.   All symptoms are
                         characteristic of mycoplas-
                         mosis,  and seemed to increase
                         with increasing  NH3 concentra-
                         tion (25,  50, 100, 250 ppm).
                                                                                                                                  Coon et al.
                                                                                                                                  (1970)
                                                                                                                                  B-12
                                                                                                                                  Coon et al.
                                                                                                                                  (1970)
                                                                                                                                  B-12
                                                                                                                                  Richard et al
                                                                                                                                  (1978a)
                                                                                                                                  B-ll
Broderson et al.
(1976)
B-12
                                                                 (continued)

-------
TABLE  III-5.  (continued)
Compound (s) and
Concentration(s) in
mg/rn3 (ppm) Humidity
NH3 180 66 + 5%
(250)



NH3 155 + 32 50%
(215)



NH3 152.6 69 + 5%
(212)
With intranasal
inoculation of
Mycoplasraa pulmonis
on day 7 of NH3 ex-
posure, both test
and control groups.
NH3 108 Not
(150) given





NH3 77.8 69 + 5%
(108)
With intranasal
inoculation of
Mycoplasma pulmonis
on day 7 of NH3 ex-
posure, both test
and control groups.

Mode of
Exposure
Exposure
chamber



Modified
Rochester-
type in-
halation
chamber
Shoe box
cage with
no change
of bed-
ding



Shoe box
cages with
filter
caps, and
bedding
not
changed
Shoe box
cages
without
bedding
changes



Species/ No. of
Strain/ Test
Age/Weight Animals
Fischer 12
rats, 2-4
mo (specific
pathogen
free)
Sprague- 15
Dawley and
Long-Evans
rats

Fischer 22
rats, 2-4
mo (spe-
cific
pathogen
free)


Sherman 10
rats, 2-4
mo (spe-
cific
pathogen
free)

Sherman 24
rats






Duration &
No. of Frequency
Controls of Exposure
12 35 d
(matched
on age,
sex, and
no. /cage)
123 8 h/d,
(4 died) 5 d/wk,
6 wk


24 (NH3 37 d
level:
1.44 +
4.32 mg/
m3)



10 (NH3 75 d
level:
7.2 +
12.9 mg/
n.3)


23 (NH3 42 d
level:
7.9 +
13.7 mg/
m')



Total
Length of
Expt. Effects
35 d Nasal lesions and histologic
alterations in both respira-
tory and olfactory epithe-
lia in the test group only.

6 wk No deaths, visible signs of
toxicity, or gross tissue
abnormalities. Hematological
values normal.

37 d Snuffling, sporadic head shak-
ing, moderate dyspnea and apnea
by day 14, rough hair coats,
and hunched posture. Increased
incidence of lung lesions and
severity of entire respiratory
tract lesions in test animals
compared to controls.
75 d Excessive blinking of the eyes
after 1 wk. Nasal lesions in
the test group only. Histo-
logic changes in respiratory
and olfactory epithelia.


42 d Snuffling, sporadic head shak-
ing, moderate dyspnea and apnea
beginning day 14, rough hair
coats and hunched posture. In-
creased incidence of lung le-
sions and severity of respira-
tory tract lesions (except
otitis).
Reference
and
Rating
Broderson et
(1976)
B-12


Coon et al.
(1970)
B-12


Broderson et
(1976)
B-12





Broderson et
(1976)
B-12




Broderson et
(1976)
B-12








al.









al.







al.






al.







        (continued)

-------
TABLE  III-5.   (continued)
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 72 51-69%
(100)
With intranasal
inoculation of
Mycoplasma pulmonis
on day 7 of NH3 ex-
posure, both test
and control groups.
NH3 64.8 40-80%
(90)







NH3 36 51-69%
(50)
With intranasal
inoculation of
Mycoplasma pulmonis
on day 7 of NH3 ex-
posure, both control
and test groups.
NH3 36 50-80%
(50)





Mode of
Exposure
Exposure
chamber
(bedding
changed
daily)



Climate-
proof
case






Exposure
chamber
(bedding
changed
daily)



Climate-
proof
case



Species/
Strain/
Age/Weight
Fischer
rats, 2-4
mo (spe-
cific
pathogen
free)


Wistar
rats







Fischer
rats,
2-4 mo
(specific
pathogen
free)


Wistar
rats,
40-45 d,
90-140 g


No. of
Test
Animals
12







32 M
(3 sep-
arate
expts.
were done)




12







21 M
(2 trials
with 2
groups of
animals)

Duration & Total
No. of Frequency Length of
Controls of Exposure Expt.
12 35 d 35 d
(matched
on age,
sex, and
no. /cage)



32 M 50-56 d 56 d








12 35 d 35 d
(matched
on age,
sex, and
no. /cage)



28 M 50 or 52 d 52 d







Effects
Increased incidence of gross
and macroscopic lung lesions,
and increased severity of
rhinitis, otitis, tracheitis,
and pneumonia. All are typical
of mycoplasmosis .


Test done at 10°C: decreased
percent body weight increase
and food consumption at wk 4,
with some recovery by wk 7 .
Test done at 22°C: no effect
on body weight increase or
food consumption. All tests
showed increased hemoglobin
content.
Large increase in gross lesions
and slight increase in micro-
scopic lesions. Increased
severity of rhinitis, otitis,
and pneumonia. All symptoms
are typical of mycoplasmosis.


Test done at 10°C: reduced per-
cent body weight increase at
4 wk, near recovery by wk 7, and
food consumption was above that
of the controls. Test done at
22°C: no effect by wk 7 on body
Reference
and
Rating
Broderson et al
(1976)
B-12





Stolpe and
Sedlag (1976)
B-ll






Broderson et al
(1976)
B-12





Stolpe and.
Sedlag (1976)
B-ll



weight increase, food consumption,





or hematocrit values.

         (continued)

-------
                                                              TABLE  III-5.   (continued)
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 21.6 50-80%
(30)


KH3 20+0.1 Not
given



Mode of
Exposure
Climate-
proof
case

Exposure
chamber


Species/
Strain/
Age/Weight
Wistar
rats ,
40-45 d,
90-140 g
Albino
rats


No. of Duration & Total
Test No. of Frequency Length of
Animals Controls of Exposure Expt. Effects
13 M 13 M 52 d 52 d No effect on body weight in-
crease, food consumption, or
hematocrit values at 4 or 7
wks.
15 M 15 M 84 d 84 d About 15% decrease in the la-
tent period of reflex response
to faint electric stimulus only
in the 1st mo. Inhibition of
Reference
and
Rating
Stolpe and
Sedlag (1976)
B-ll

Saifutdinov
(1966 and 1968)
B-9
B-7
NJ
Ul
NH3           18
             (25)
With intranasal
inoculation of
Mycoplasma pulmonis
on day 7 of NH3 ex-
posure, both test
and control groups.
                           51-69%
     NH,
                    0.021
                          Not
                          given
Exposure
chamber
(bedding
changed
daily)

Exposure
chamber
Fischer
rats,
2-4 mo
(specific
pathogen
free)
Albino
rats
     NH,
              0.2 +  0.002
                     Not
                     given
                                     Exposure   Albino
                                     chamber    rats
24
                                                        15  M
24
(matched
on age,
sex,  and
no./cage)
                                                                  15 M
37 or 49 d    49  d
                                                                            84 d
                                                                                          84 d
                                                        15  M
                                                                 15 M
                                                                            84 d
                                                                                          84 d
                                                                                                           cholinesterase  activity  in, and
                                                                                                           redox  function  of,  the blood
                                                                                                           (recovery after exposure stopped).
                                                                                                           Increased coproporphyrin levels
                                                                                                           in the urine.   No macroscopic
                                                                                                           changes in the  organs.
                                              Greater incidence of gross  and
                                              microscopic lung lesions,
                                              otitis, and pneumonia in both
                                              trials.  Increased rhinitis
                                              and tracheitis in 1/2 trials.
                                              All symptoms are typical of
                                              mycoplasmosis.
Broderson et al.
(1976)
B-12
                                              No effect on latent period of
                                              reflex response,  blood cho-
                                              linesterase activity,  or urine
                                              coproporphyrin levels.  Some
                                              inhibition of blood redox func-
                                              tion during first month of ex-
                                              posure.

                                              No effect on latent period of
                                              reflex response,  blood cho-
                                              linesterase activity and redox
                                              function, or urine copro-
                                              porphyrin levels.   Author rec-
                                              ommends  this as the mean daily
                                              maximum  permissible concentration
                                              in the USSR.
Saifutdinov
(1966 and 1968)
B-9
B-7
Saifutdinov
(1966 and 1968)
B-9
B-7

-------
                                  TABLE  III-6.   RATS—CHRONIC  EXPERIMENTAL EXPOSURE  TO  NH,,

Compound(s) and
Concentration(s) in

NH









NH


rag/m3 (ppm) Humidity
3 470 + 16 50%
(653)








3 262 + 10 50%
(364)

Species/
Mode of Strain/
Exposure Age/Weight
Modified Sprague-
Rochester- Dawley and
type in- Long-Evans
halation rats
chamber





Modified Sprague-
Rochester- Dawley and
type in- Long-Evans
No. of
Test No. of
Animals Controls
15 123
(4 died)








49 123
(4 died)

Duration & Total
Frequency Length of
of Exposure Expt.
Continuous 90 d
90 d








Continuous 90 d
90 d



Effects
13/15 died. Hematological val-
ues did not vary from controls.
Histopathologic examination re-
vealed focal or diffuse inter-
stitial pneumonitis in all ani-
mals. Other histopathology of
the liver, kidneys, heart, and
bronchi seen, with similar but
lesser changes seen in the con-
trols .
No deaths or pronounced symp-
toms of toxicity. ~ 25% ani-
mals had mild nasal discharge.
Reference
and
Rating
Coon et al.
(1970)
B-12







Coon et al.
(1970)
B-12
NH,
NH,
            127 + 8
              (176)
             40 + 2
              (56)
50%
50%
                                halation   rats
                                chamber
Modified   Sprague-
Rochester- Dawley and
type in-   Long-Evans
halation   rats
chamber
48
          123        Continuous    90 d
          (4 died)   90 d
Modified   Sprague-
Rochester- Dawley and
type  in-
halation
15
          123        Continuous
          (4 died)   114 d
114 d
                                          Long-Evans
                                          rats
                                chamber
Hematological results  were
normal except that 4 rats had
slightly high leukocyte counts.
Microscopic examination showed
nonspecific circulatory and  de-
generative changes in lungs  and
kidneys but they may not be  re-
lated to ammonia inhalation.

No deaths or signs of toxicity    Coon et al.
in any of the animals:  hema-     (1970)
tological values, liver histo-    B-12
chemical results, or microscopic
exam for nonspecific inflamma-
tion of the lungs.

No deaths or signs of toxicity.   Coon et al.
Necropsy observations were nor-   (1970)
mal.  1 rat had lipid filled     B-12
macrophages in its lung, but it
was not deemed significant.
                                                                  (continued)

-------
                                                        TABLE  III-6.    (continued)
  Compound(s)  and
Concentration(s) in
    mg/m3 (ppm)
NH,
           20 + 0.6
HH,
          19 + 0.16
                     Not
                     given
Mode of
Exposure
Exposure
chamber
Species/
Strain/
Age/Weight
Albino
rats
No. of Duration &
Test No. of Frequency
Animals Controls of Exposure
11 M 9 M 5-6 h/d,
3-3.5 mo
Total
Length of
Expt.
3.5 mo
Effects
No significant changes in vita-
rains A, Bl( ascorbic acid, py-
ruvic acid levels in the blood,
body weight, or weight coeffi-
cients of the organs. Decrease
in total B2 content of the
blood, liver, and kidneys. De-
crease in nicotinamide coenzymes
in the adrenals, cerebral hemi-
spheres, and skeletal muscles.
Reference
and
Rating
Nizhegorodov
and Kalinin
(1967)
D-6
                     Not
                     given
Exposure   Albino
chamber    rats
NH3         6+0.1   Not
With 3 short intra-   given
nasal exposures  to
Staphylococcus strain
No. 209,  each followed
by 8-10 d without NH3
exposure.
Not
given
Rats
8 M       6  M       5-6 h/d,      7 mo        No change in liver vitamin A     Nizhegorodov
                    6.5-7 mo                  content.   Decreased vitamin Bt    and Kalinin
                                              in the blood and liver.   In-     (1967)
                                              creased total ascorbic acid      D-6
                                              content of the adrenals,
                                              liver, and skeletal muscles.
                                              Unchanged levels of nicotin-
                                              amide coenz'ymes.  Body weight
                                              loss of 10 g.  Increased  weight
                                              of spleen, lungs,  and brain.

64        64        7 h/d,        4 mo        By the end of the study,  the     Hikhailuts
          (32 with  5 times/wk,               test group had more histo-       et al.  (1979)
          microbial  for 4 mo                  chemical and pathomorpholog-     B-10
          exposure,                            ical changes of both the  up-
          32 with-                            per and lower respiratory
          out)                                tracts than the infection-
                                              control group.   Particularly
                                              decreased protective phagocytic
                                              action, increased histamine in
                                              the lung, and increased macro-
                                              phage but decreased glycogen
                                              index.
                                                                   (continued)

-------
                                                TABLE III-6. (continued)
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 3 + 0.08 Not
With 3 short iritra- given
nasal exposures to
Staphylococcus strain
No. 209, each followed
by 8-10 d without NH3
exposure.
Species/ No. of
Mode of Strain/ Test No. of
Exposure Age/Weight Animals Controls
Not Rats 32 64
given (32 with
raicrobial
exposure,
32 with-
out)

Duration & Total
Frequency Length of
of Exposure Expt.
7 h/d, 4 mo
5 times/wk,
for 4 mo




Reference
and
Effects Rating
Caused no reliable disturbances Mikhailuts
in the period after respiratory et al. (1979)
infection. B-10




K>
OO

-------
                           TABLE III-7.   GUINEA PIGS—ACUTE EXPERIMENTAL  EXPOSURE TO NH3
Compound(s) and
Concentration(s) in
mg/m? (ppm) Humidity
NH3 1,858-3,312 Not
(2,580-4,600) given









NH3 1,634-1,872 Not
(2,270-2,600) given




.


NH3 590-1,030 Not
(820-1,430) given

NH3 346-410 Not
(480-570) given

Species/ No. of
Mode of Strain/ Test
Exposure Age/Weight Animals
Well- Guinea 20
ventilated pigs
chamber








Well- Guinea 18
ventilated pigs
chamber






Well- Guinea 7
ventilated pigs
chamber
Well- Guinea 2
ventilated pigs
chamber
Duration &
No. of Frequency
Controls of Exposure
0 10 h,
once









0 8.33 h,
once
(exposed
4 day pre-
viously to
4,600 ppm
for 10 h)


0 5.5 h


0 4 h,
once

Total
Length of
Expt. Effects
Moderate symptoms of irritation.
Respiration 21, 13, 18, 25.
Some salivary secretion. Cor-
nea clear although eyes remained
open. Killed after 24 h with
CHC13. Entire lung hyperemic
and somewhat edematous. Upper
lobe had numerous small hemor-
rhages; left lower lobe com-
pletely empty of air. Trachea
without ecchymoses .*
Very quiet. Slight symptoms
of irritation. Corneas
slightly cloudy. Killed by
CHC13 immediately after the ex-
posure. Purulent-mucous bron-
chitis. Numerous hemorrhages
in the lower and middle lobes
of the lungs apparently from
the earlier exposure.
Symptoms of irritation. Res-
piration slowed to 10.

Slight symptoms of irritation.
Uninjured after exposure.

Referenrp
and

Rating_
Lehmann
B-9









Lehmann
B--9







Lehmann
B-9

Lehmann
B-9

(1886)










(1886)








(1886)


(1886)


Ecchymoses are small hemorrhagic spots in the skin or mucous membrane  forming nonelevated, rounded or irregular,  blue or purplish patches.

-------
TABLE III-8.   GUINEA PIGS—REPEATED  DOSE  EXPERIMENTAL  EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
mg/m3
NH3




NH3




NH3




NH3





(ppm) Humidity
770 + 55 50%
(1,070)



155 + 32 50%
(215)



36 10-30%
.(50)



14.4 10-30%
(20)




Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber
Modified
Rochester-
type in-
halation
chamber
Cabinet
(336 ft3)



Cabinet
(336 ft3)




Species/
Strain/
Age/Weight
Princeton-
derived
guinea
pigs

Princeton-
derived
guinea
pigs

Guinea
Pigs,
6-8 wk


Guinea
figs,
6-8 wk



No- of
Test No. of
Animals Controls
15 73




15 73




6 3




2 3
2 3
2 3
2 3
2 3

Duration & Total
Frequency Length of
of Exposure Expt.
8 h/d, 6 wk
5 d/wk,
6 wk


8 h/d, 6 wk
5 d/wk,
6 wk


6 wk 6 wk
continuous



7 d 6 wk
14 d
21 d
28 d
42 d
continuous


Effects
No deaths. Lungs showed con-
sistent nonspecific inflam-
matory changes.


No deaths, visible signs of
toxicity, or gross tissue
abnormalities. Hematological
values normal.

Dark red and dense lungs; pul-
monary edema, congestion, and
hemorrhage; congestion of the
liver; enlarged and congested
spleen.
No effect up to 6 wk. After
6 wk: dark red and dense lung
tissue, and .pulmonary conges-
tion, edema and hemorrhage.


Reference
and
Rating
Coon et al.
(1970)
B-12


Coon et al.
(1970)
B-12


Anderson et al.
(1964)
B-12


Anderson et al.
(1964)
B-12




-------
TABLE III-9.  GUINEA PIGS—CHRONIC EXPERIMENTAL EXPOSURE TO NH,
Compound(s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 470 + 16 50%
(653)








NH3 40+2 50%
(56)




Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber





Modified
Rochester-
type in-
halation
chamber
Species/ No. of
Strain/ Test No. of
Age/Weight Animals Controls
Princeton- 15 73
derived
guinea
pigs






Princeton- 15 73
derived
guinea
pigs

Duration & Total
Frequency Length of
of Exposure Expt. Effects
90 d 90 d 4 died. Hematological values
continuous did not vary from controls.
Histopathological examination
revealed focal or diffuse in-
terstitial pneumonitis in all
animals. Other histopathology
of the liver, kidneys, heart,
and bronchi seen in some ani-
mals, with similar but lesser
changes in the control group.
114 d 114 d No deaths or signs of toxicity.
continuous Necropsy observations were nor-
mal.


Reference
and
Rating
Coon et al.
(1970)
B-12







Coon et al.
(1970)
B-12



-------
                                 TABLE 111-10.  CHICKENS—ACUTE EXPERIMENTAL EXPOSURE TO NH3

Compound (s) and
Concentration(s) in

NH






NH




NH


mg/m3 (ppm) Humidity
3 72 Not
(100) given





3 72 Not
(100) given



3 54 Not
(75) given


Mode of
Exposure
"Cabinet"






Small
respi-
ration
chamber
(0.22 m3)
"Cabinet"


Species/
Strain/
Age/Weight
Adult hens,
8-10 mo





Adult hens,
11 mo



Adult hens


No. of
Test
Animals
Not
given,
but
probably
small


Unclear,
but
maybe 4


15



No. of
Controls
Served
as own
controls




Served
as own
controls


Served
a s own
controls
Duration & Total
Frequency Length of
of Exposure Expt. Effects
Not given Not given Significant decrease in res-
piration rates of 10.5-23.9%
as measured by pneumograph
or crissall feather movement.
Significant 12.5-14.7% decrease
in respiration depth in 2/3 ob-
servations .
Not given Not given Significant 23.1% decrease in
respiration rate, as measured
by indirect calorimetry of car-
bon dioxide production, in 1/2
tests .
15 min 30 rain Statistically significant in-
crease in blood pH (from bra-
chial vein) from 6.447 to
Reference
and
Rating
Charles and
Payne (1966a)
B-12




Charles and
Payne (1966a)
B-12


Charles and
Payne (1966a)
B-12
                                                                                     6.563.
OJ

-------
                             TABLE III-ll.   CHICKENS—REPEATED DOSE  EXPERIMENTAL  EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
rag/m
NH3


3 (ppm) Humidity
720 10-30%
(1,000)

Mode of
Exposure
Cabinet
(336 ft3)

Species/ No. of Duration & Total
Strain/ Test No. of Frequency Length of
Age/Weight Animals Controls of Exposure Expt.
Leghorn
chickens, 2 3
6-8 wk
Continuous 14 d
3 d

Effects
After 3 days: photophobia,
rubbing of eyes, and lacri-
mation.
Reference
and
Rating
Anderson
(1964)
B-12

et al.


NH,
              144     10-30%    Cabinet    Leghorn
             (200)              (336 ft3)  chickens,
                                          6-8 wk
                                                                          8 d
                                                                          14 d

2
2
2
2

3
3
3
3
Continuous
7 d
10 d
13 d
15 d
21 d
                                                                          17 d

                                                                          19 d

                                                                          21 d
After 8 days:   corneal opacities,
followed by erosions by the sur-
face layer of  the cornea.

After 14 days:   nearly all the
birds had bilateral corneal opa-
cities of varying severity, pul-
monary congestion, edema, and
hemorrhage as  well as congestion
of the liver and spleen and ero-
sion of the cornea.

Obvious signs  of discomfort dur- Anderson et  al.
            ing the first few days of expo-
            sure were considerable rubbing
            of the eyes, slight lacrimation,
            anoxeria, and weight loss.  At
            necropsy, gross changes were
            only in the respiratory system.
            All eye irritation had disap-
            peared.  Histopathological
            changes were pulmonary edema,
            congestion, and hemorrhage.
            The tissue had an ammonia odor.

            Above plus liver congestion and
            a slight clouding of the cornea.
                                (1964)
                                B-12
                                                                  (continued)

-------
                                                      TABLE  III-ll.  (continued)
OJ
-P-
Compound (s) and
Concentration(s) in
mg/m3 (ppm)
NH3 ~ 14.4-115.2
(~ 20-160)
(General increase
with time, with
many fluctuations)




NH3 72
(100)



NH3 72
(100)





NH3 ~ 7.2-57.6
(~ 10-80)
(Fluctuated with
time, generally
< 36 mg/m3 except
for last week)




Humidity
~ 6-9.5
grains of
water/ft3
of atmo-
sphere




Not
given



50.1%





•-
~ 6-9.5
grains of
water/ft3
atmo-
sphere




Mode of
Exposure
Environ-.
mental
pens






"Cabinet"




Exposure
chambers
with wire
floor for
removal
of drop-
pings
Environ-
mental
pens





Species/
Strain/
Age/Weight
Chicks of
a light/
heavy com-
mercial
broiler
cross, 1 d



Adult hens,
8-10 mo



White Rock
x Light
Sussex
broiler-
type
chickens,
4 wk
Chicks of
a light/
heavy com-
mercial
broiler
cross, 1 d


No. of
Test No. of
Animals Controls
120 F Appar-
exposed, ently
only 24 none
actually
measured
for ef-
fects


Not Served
given, as own
but controls
probably
small
10 M 10 M






120 F Appar-
exposed, ently
only 24 none
actually
measured
for ef-
fects

Duration & Total
Frequency Length of
of Exposure Expt.
Wks 7-10 10 wk
(exposed in
the first 6
wk to un-
known , but
mainly lower,
NH3 levels)


3 or 4 wk Not
given



19 d 37 d






Wks 7-10 10 wk
(exposed in
the first 6
wk to un-
known, but
mainly lower,
levels)



Effects
During wks 4-7, had higher
weights than chickens exposed
to 5-50, 10-80, or 10-45 ppm.
By wk 10, had significantly
lower weights than the other
groups. By the end of the
expt., 20/24 had ulcerations
of the eye, many more than the
other groups.
Significant 18.4% decrease in
respiration rate only for those
with 4 wk acclimatization, as
measured by crissal feather
movement.
Significant growth rate de-
crease in the last wk of expo-
sure, due to a 14.5% reduction
of voluntary food intake. Con-
sumption did not return to nor-
mal until 12 d after cessation
of NH3 exposure.
Significantly lower weight than
group exposed to 20-160 ppm,
during wks 3, 4, and 6. By wk
10, lower weight than the group
exposed to 10-45 ppm, but higher
weight than the group exposed to
20-160 ppm. 5/24 had eye ulcera-
tions .
Reference
and
Rating
Valentine
(1964)
B-10






Charles and
Payne (1966a)
B-12


Charles and
Payne (1966a)
B-12




Valentine
(1964)
B-10





                                                               (continued)

-------
                                                       TABLE  III-ll.   (continued)
u>
Ul
Compound(s) and
Coricentration(s) in
mg/ra3 (ppm) Humidity
NH3 56.2 64. 0%
(78)






NH3 38.2 64.7%
(53)







NH3 36.7 50.1%
(51)





NH3 36
(50)
Newcastle infectious
bronchitis (Mass.)
(NC-IB) vaccination
was administered at
21 d of age by aero-
sol means.














Mode of
Exposure
Exposure
chambers
without
litter,
and the
droppings
removed
daily
Exposure
chambers,
without
litter,
and the
droppings
removed
daily

Exposure
chambers
with wire
floor for
removal
of drop-
pings
Chambers
in an en-
vironmen-
tally
con-
trolled
building














Species/ No. of
Strain/ Test No. of
Age/Weight Animals Controls
White 27 F 27 F
Leghorn
chickens ,
11 wk,
1,250 g



White 27 F 27 F
Leghorn
chickens ,
11 wk,
1,250 g




White Rock 10 M 10 M
x Light
Sussex
broiler-
type
chickens ,
4 wk
Indian 312 M; 156 M
River • 156 for
broiler each ex-
cockerels, posure
1-d-old time
















Duration & Total
Frequency Length of
of Exposure Expt. Effects
7 wk 30 wk Significantly decreased food
consumption during wks 15-30
and live-weight gain during
last 4 wk of exposure. Came
into lay later, slightly larger
eggs, and sexual maturity de-
layed 2 wk.

7 wk 30 wk Significantly decreased egg
production (20%) during wks
23-26 (after exposure), and
slightly heavier eggs during
the whole period. Sexual ma-
turity delayed 1 wk. Slight
decrease in food consumption
from wk 15 to wk 38. No
change in live-weight gain.
33 d 33 d Food consumption decreased
slightly after day 12 of expo-
sure. No differences in growth
rate occurred.



28 d or 49 d No difference in avg. body wt.
49 d for either exposure time com-
pared to controls or other ex-
posure groups at any time. No
difference in feed efficiency
at day 28. By day 49, the avg.
feed efficiency of the 49-d ex-
posure group (2.44) was signifi-
cantly less than that of the
28-d group (2.16), all other
groups exposed to lower levels
(2.08-2.35), and the controls
(2.02). Scores for lesions of
the right posterior thoracic
air sac membrane were never
significantly different from
scores for control or other ex-
posure groups. No significant
di rforrnces in avg. paired lung
wts. <>r avg. biirsa of Fahririiis
wLs .
Reference
.inil
Rat i MR
Charles and
Pavne (1966a)
B-12





Charles and
Pay no (1966a)
B-12






Charles and
Payne (1 966a )
B-12




Paveny et al .
(1981)
C-13


















                                                                    (ronl iiincil)

-------
TABLE III-ll.   (continued)
Compound (s) and
Concentration(s) in
mg/m3 (ppm)
NH3 18 and 36
(25 and 50)
Newcastle infectious
bronchitis (Mass.)
(NC-IB) vaccination
was administered at
21 d of age by aero-
sol means .











NH3 36
(50)
Followed by a 3-min
exposure to an aero-
sol of Newcastle
disease virus (~ 6
ELD5o's/L), both
test and control
groups.
NH ~ 3.6-36
(~ 5-50)
(generally < 29
until the last
week)



NH3 ~ 7.2-32.4
(~ 10-45)
(some fluctuations,
and general in-
crease with time)





Humidity



















Not
given







~ 4.5-7
grains of
water/
ft3 of
atmo-
sphere


~ 5-6.5
grains of
water/ft3
of atmo-
sphere




Mode of
Exposure
Chambers
in an en-
vironmen-
tally con-
trolled
building













Con-
trolled
environ-
ment
cabinet
(336 ft3)



Environ-
mental
pens





Environ-
mental
pens





Species/
Strain/
Age/Weight
Indian
River
broiler
chickens,
1-d-old














Leghorn
chickens,
6-8 wk






Chicks of
a light/
heavy com-
mercial
broiler
cross, 1 d


Chicks of
a light/
heavy com-
mercial
broiler
cross, 1 d


No. of
Test
Animals
156 M


















12








120 F
exposed,
but only
24 ac-
tually
measured
for ef-
fects
120 F
exposed ,
but only
24 ac-
tually
measured
for ef-
fects

No. of
Controls
156 M


















12








Appar-
ently
none
done




Appar-
ently
none
done




Duration & Total
Frequency Length of
of Exposure Expt.
28 d at 36 49 d
mg/m3; 21 d
at 18 mg/m3
















48 h 17 d








Wks 7-10 10 wk
(exposed in
the first 6.
wk to un-
known, but
mainly lower,
levels)

Wks 7-10 10 wk
(exposed in
the first 6
wk to un-
known, but
mainly lower,
Icvrl.s)



Effects
No difference in avg. body wt. .
compared to controls or other
exposure groups at any time.
No differences in avg. feed ef-
ficiencies at d 28. By d 49,
avg. feed efficiency (2.35) was
significantly greater than that
for 49-d exposure to 36 mg/m3,
and less than controls (2.02)
or 28-d exposure to 18 mg/m3
(2.08). Scores for lesions
of the right posterior thoracic
air sac membranes were never
significantly different from
those for control or other ex-
posure groups. No significant
differences in the avg. wts . of
paired lungs or bursa of
Fabricius .
Significant increase in the
percent of birds infected in
the test group (100%) compared
to controls (~ 40%) . Gross
and microscopic pathology the
same in both groups.



During wks 4-7, significantly
lower weights than the group
exposed to 20-160 ppm. By wk
10, higher weights than that
group. Consistently lower
weights than group exposed to
10-45 ppm. No eye ulcerations.

By wk 10, significantly higher
weight than groups exposed to
20-160 or 10-80 ppm. No eye
ulcerations .




Reference
and
Rating
Caveny p.t al .
(1981)
C-13
















Anderson et al
(1964)
B-12






Valentine
(1964)
B-10





Valentine
(1964)
B-10





             I ront inueil)

-------
TABLE  III-ll.   (continued)
Compound(s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 ~ 30.2
(~ «)
Measurement was made
at the end of the
expt.; values prob-
ably varied during
exposure.








NH3 18
(25)
Newcastle infectious
bronchitis (Mass.)
(NC-IB) vaccination
was administered at
21 d of age by aero-
sol means.











NH3 ~ 16.6
(~ 23)
Measurement was made
at the end of the
expt.; values prob-
ably varied during
exposure.


Mode of
Exposure
Partially
enclosed
wire
cage,
with
accumu-
lation of
fecal
matter






Chambers
in an en-
vironmen-
tally con-
trolled
building













Partially
enclosed
wire
cage, and
weekly re-
moval of
fecal
matter
Species/ No. of Duration &
Strain/ Test No. of Frequency
Age/Weight Animals Controls of Exposure
White Rock 5 H 3 H 12 wk
chickens, 7 F 2 F,
4 wk exposed
to ~ 5.3
mg NHj/m1










Indian 312 M; 156 M 28 d or
River 156 for 49 d
broiler each ex-
chickens, posure
1-d-old time














White 7 M 3 M 12 wk
Rock 5 F 2 F, ex-
chickens, posed to
4 wk ~ 5.3 mg
NH3/m3



Total RofrrriK-r
Length of ••""'
Expt. Effects Rating
12 wk A statistically significant Caspar el al .
increase in the avg. rate of (1961)
hemoglobin formation by the C-9
4th wk of exposure. Then
a steady decrease in hemo-
globin formation, significantly
below other treatments and
"controls" by the 12th wk of
exposure. Differences between
sexes were reported. Birds
developed keratoconjunctivitis.
3/12 developed unilateral or
bilateral blindness. 2 of 5 M
died between 2nd and 3rd month.
No change in feed consumption.
49 d No difference in avg. body wt., Caveny et al .
for either exposure length, (1981)
compared to controls or other C-13
exposure groups at any time.
No differences in avg. feed ef-
ficiencies at day 28. By day 49,
the avg. feed efficiency (2.35)
of the 49-d exposure group was
less than that of the 28-d group
(2.08) and the controls (2.02),
and greater than that for the
group exposed to 36 mg/m3 for
49 d. Scores for air sac le-
sions were never significantly
different from those for con-
trols or other exposure groups.
No significant differences in
the. avg. wts. of paired lungs or
bursa of Fabricius.
12 wk No difference in the avg. rate Caspar et al .
of hemoglobin formation com- (1961)
pared to the "control" values. C-9
Rate of increase of hemoglobin
levels was higher in males than
females. No change in feed
consumption .

           (continued)

-------
                                                TABLE III-ll.   (continued)
00
Compound(s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 14.4 Not
(20) given
Followed by a 3-min
exposure to aerosol
of Newcastle disease
virus (6 ELD50's/L),
both test and control
groups.
NH3 14.4 Not
(20) given
Followed by a 3-min
exposure to an aerosol
of Newcastle disease
virus (3 ELD50's/L),
both test and control
groups.
NH3 14.4 10-30%
(20)



NH3 14.4 10-30%
(20)



NH3 14.4 10-30%
(20)







Mode of
Exposure
Con-
trolled-
environ-
ment
cabinet
(336 ft3)


Con-
trolled-
environ-
ment
cabinet



Cabinet
(336 ft3)



Cabinet
(336 ft3)



Cabinet
(336 ft3)






Species/ No. of Duration &
Strain/ Test No. of Frequency
Age/Weight Animals Controls of Exposure
Leghorn 12 12 72 h
chickens ,
6-8 wks





Leghorn 12 12 72 h
chickens ,
6-8 wks





Leghorn 6 3 Continuous
chickens, 12 wk
6-8 wk


Leghorn 3 3 Continuous
chickens, 6 wk
6-8 wk


Leghorn Continuous
chickens ,
6-8 wk 3 3 7 d

3 3 14 d

3 3 21 d
3 3 28 d
Total
Length of
Expt. Effects
18 d Significant increase in the
percent of birds infected in
the test group (100%) compared
to the control group (~ 50%) .
Gross and microscopic pathology
was the same in both groups.


18 d Statistically insignificant in-
crease in percent of birds in-
fected. Gross and microscopic
pathology of test and control
groups the same.



12 wk Lungs were dark red and more
dense when compared to the con-
trols. Microscopic examination
revealed pulmonary congestion,
edema, and hemorrhage.
6 wk Darker colored and denser lung
tissue than controls. Micro-
scopic examination revealed
pulmonary congestion, edema,
and hemorrhage.
28 d Exposure for 24 h was followed
by a slight increase in mucous
secretion. Condition disap-
peared after 3 or 4 days. No
significant pathology. No ob-
vious signs of discomfort.


Reference
and
Rating
Anderson el
(1964)
B-12





Anderson ot
(1964)
B-12





Anderson et
(1964)
B-12


Anderson et
(1964)
B-12


Anderson et
(1964)
B-12








al.







al.







al.




a] .




al.








-------
                                   TABLE  111-12.  RABBITS—ACUTE  EXPERIMENTAL EXPOSURE TO NH3
VO
Compound(s) and
Concentration(s) in
mg/ra3 (ppm) Humidity
NH3 14,400 Not
(20,000) given







NH3 7,200 Not
(10,000) given






NH3 5, AGO Not
(7,500) given.






NH3 4,320 Not
(6,000) given








Mode of
Exposure
Artifi-
cial
respi-
ration
of cu-
rarized
animals


Artifi-
cial
respi-
ration
of cu-
rarized
animals

Artifi-
cial
respi-
ration
of cu-
rarized
animals

Artifi-
cial
respi-
ration
of cu-
rarized
animals


Species/
Strain/
Age/Weight
"Fauve de
Bourgogne"
rabbits ,
avg. wt
2.5 kg




"Fauve de
Bourgogne"
rabbits ,
avg. wt
2.5 kg



"Fauve de
Bourgogne"
rabbits,
avg . wt
2.5 kg



"Fauve de
Bourgogne"
rabbits,
avg. wt
2.5 kg




No. of Duration &
Test No. of Frequency
Animals Controls of Exposure
Unknown Served 60 min
no. of M as own
(perhaps controls
just 1)





Unknown Served 60 min
no. of H as own
(perhaps controls
just 1)




Unknown Served 60 min
no. of M as own
(perhaps controls
just 1)




Unknown Served 60 min
no. of H as own
(perhaps controls
just 1)





Total
Length of
Expt. Effects
180 min Rapid increase in "total index
of intoxication": strong
bradycardia within 1 min, pro-
found changes in ECG, pulmonary
infarctions and edema, blood
acidosis and elevated p02 , and
deterioration of EEC near time
of death (after ~ 30 min of NH3
exposure).
180 min Rapid increase in "total index
of intoxication": strong
bradycardia within 1 min, ECG
profoundly changed within 20
min, pulmonary infarctions and
edema, blood acidosis and ele-
vated p02 , deterioration of EEC
near time of death.
180 min Rapid increase in the "total
index of intoxication": strong
bradycardia within 1 min, pro-
found changes in ECG within 20
min, pulmonary infarctions and
edema, blood acidosis and ele-
vated p02, and EEC changes near
the time of death (at 60 min).
180 min Increased "total index of intox-
ication" during exposure, rapid
increase after exposure: imme-
diate and strong bradycardia,
changes in ECG, increased blood
pressure, pulmonary infarctions
and edema, elevated p02 , blood
acidosis, and changes in EEC
near time of death.
Reference
and
Rating
Richard et
(1978b)
B-10






Richard et
(1978b)
B-10





Richard et
(1978b)
B-10





Richard et
(1978b)
B-10









al.








al.







al.







al.








                                                             (continued)

-------
                                                            TABLE  111-12.   (continued)

Compound(s) and
Concentration(s) in

Nil








NH


mg/m3 (ppra) Humidity
3 3,600 Not
(5,000) given







3 1,858-3,312 Not
(2,580-4,600)given


Mode of
Exposure
Artifi-
cial
respi-
ration
of cu-
rarized
animals


Well-
ventilated
chamber
Species/
Strain/
Age/Weight
"Fauve de
Bourgogne"
rabbits,
avg. wt
2.5 kg




Rabbits


No. of
Test No. of
Animals Controls
Unknown Served
no . o f M as own
(perhaps controls
just 1)





19 0


Duration & Total
Frequency Length of
of Exposure Expt. Effects
60 min 180 min Increase in the "total index of
intoxication," remaining at that
level during the recovery pe-
riod: foam in the trachea and
bronchial tree, zones of infarc-
tion, acute pulmonary edema,
bradycardia, arrhythmia, extra-
systoles, changes in blood pres-
sure, and blood acidosis.
10 h - Symptoms about the same as at
1,642-1,800 mg/m3. Respiration
12-15. Cornea clear although
Reference
and
Rating
Richard
(1978b)
B-10






Lehmann
B-9



et al.








(1886)


-O
o
      NH,
      NH,
 2,160    Not
(3,000)   given
                1,634-1,872 Not
            (2,270-2,600)   given
Artifi-
cial
respi-
ration
of cu-
rarized
animals
Well-
venti-
lated
chamber
"Fauve de
Bourgogne"
rabbits,
avg . wt
2.5 kg

Rabbits



Unknown   Served
no. of M  as  own
(perhaps  controls
just 1)
                                           17
60 min
180 min
                                                               8.33 h
                                                               once
the eyes were mostly open.
Killed with CHC13 24 h after ex-
posure.  Many fine hemorrhages
in the tracheal mucosa.   The
tracheal epithelia was partially
destroyed, voluminous purulent
mucous tracheal exudate.   Numer-
ous ecchymoses (extravasations
of blood under the skin)  and
large anectatic (undilated?)
regions in the lung.

Increase in the "total index of   Richard  et al.
intoxication."  Little apparent   (1978b)
recovery by 90 min.   Foam in     B-10
the trachea.  Bradycardia,
arrhythmia, and extrasystoles.
                                              Slight symptoms.   Respiration     Lehmann  (1886)
                                              18-26.  Cornea slightly cloudy.   B-9
                                              Ate immediately after test.
                                                                           (continued)

-------
TABLE 111-12.   (concluded)
Compound (s) and
Concentration(s) in

NH3






NH3




NH3



Nil 3



KH3






rag/m3 (ppm)
1,800
(2,500)





1,642-1,800
(2,280-2,500)



893-1,037
(1,240-1,440)


576-770
(800-1,070)


720
(1,000)





Humidity
Not
given





Not
given



Not
given


Not
given


Not
given





Mode of
Exposure
Artifi-
cial
respi-
ration
of cu-
rarized
animals
Well-
venti-
lated
chamber

Well-
venti-
lated
chamber
Well-
venti-
lated
chamber
Artifi-
cial
respi-
ration
of cu-
rarized
animals
Species/
Strain/
Age/Weight
"Fauve de
Bourgogne"
rabbits,
avg. wt
2.5 kg


Rabbits




Rabbit



Rabbits



"Fauve de
Bourgogne"
rabbits,
avg. wt
2.5 kg


No. of Duration & Total
Test No. of Frequency Length of
Animals Controls of Exposure Expt.
Unknown Served 60 min 180 min
no. of M as own
(perhaps controls
just 1)



12 0 2.5 h
once



45 0 7 h
once


50 7 h
once


Unknown Served 60 min 180 min
no. of M as own
(perhaps controls
just 1)



Reference

Effects
Increase in the "total index
of intoxication." Little ap-
parent recovery by 90 min.
Early bradycardia, often ac-
companied by arrhythmia and
extrasystoles.

Some symptoms of irritation.
Tearing. After 1 h, some sal-
ivary secretion began, which
persisted a long time. Some
milky secretions from the eye.
Slight symptoms. Respiration
fell from 78 to 25-32. Normal
after exposure.

Slight symptoms. Respiration
[sic] before the test 100-140
fell successively to 25. Some
salivary secretion.
An increase in the "total index
of intoxication." No discus-
sion of individual effects.
Some recovery by 90 min.



and
Rating
Richard
(197Rh)
B-10




Lehm.inn
B-9



Lehmann
B-9


Lehmann
B-9


Richard
(1978b)
B-10






el al.






(1886)




(1886)



(1886)



et al.







-------
TABLE 111-13.   RABBITS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO NH3
Compound(s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 770 + 55 50%
(1,070)







NH3 155 + 32 50%
(215)



NH3 72 Not
(100) given








NH3 36 Not
(50) given









Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber




Modified
Rochester-
type in-
halation
chambe r
Constant
temper-
ature
chamber






Constant
temper-
ature
chamber






Species/ No. of
Strain/ Test
Age/Weight Animals
New Zealand 3 M
Albino
rabbits






New Zealand 3 M
Albino
rabbits


New Zealand 7 F
White
rabbits







New Zealand 9 F
White
rabbits








No. of
Controls
12 M








12 M




Served
as own
controls
(values
obtained
immedi-
ately
after ex-
posure
included)
Served
as own
controls
(values
obtained
immedi-
ately
after ex-
posure
included)
Duration &
Frequency
of Exposure
8 h/d,
5 d/wk,
6 wk






8 h/d,
5 d/wk,
6 wk


2.5-3 h
(the second
of 3 con-
secutive
equal time
periods)




2.5-3 h
(the second
of 3 con-
secutive
equal time
periods)




Total
Length of
Expt.
6 wk








6 wk




7.5-9 h
(Expt. re-
peated 43
times at
unknown
intervals)




7.5-9 h
(Expt. re-
peated 33
times at
unknown
intervals)




Reference

Effects
No deaths. Mild to moderate
dyspnea and lacrimation during
the first week, disappearing
during the second week. No
further indications of toxicity
or irritation were noted at
necropsy or during heraatolog-
ical and histopathological exam,
attributable to NH3.
No deaths, visible signs of tox-
icity, or gross tissue abnormal-
ities. Hematological values
no rma 1 .

Significant 67% decrease in
respiration rate. Possibly in-
creased depth of respiration
(indirectly measured) . Peri-
odicity of respiratory volume
changes not affected. No his-
topathological changes found.



Significant 34% decrease in
respiration rate. No change in
the periodicity of relative
changes in respiratory volume.
Perhaps an increase in the
depth of respiration (indi-
rectly measured) .



and
Rating
Coon et
(1970)
B-12






Coon et
(1970)
B-12




al.








al.




Mayan and
Merilan
B-ll







(1972)








Mayan and
Merilan
B-ll







(1972)









-------
                                TABLE  111-14.   RABBITS—CHRONIC  EXPERIMENTAL EXPOSURE TO  NH3
Compound (s) and
Concentration(s) in Mode of
rag/m3 (ppra) Humidity Exposure
NH3 470 + 16 50% Modified
(653) Rochester-
type in-
Species/ No. of
Strain/ Test
Age/Weight Animals
New Zealand 3 M
Albino
rabbit
Duration & Total
No. of Frequency Length of
Controls of
Exposure Expt.
12 M Continuous 90 d
90

d

Effects
No deaths. Marked

eye irrita-
tion: heavy lacrimation and
erythema, dischargt
:, and opac-
Rrference
and
Rating
Coon et al.
(1970)
B-12
NH,
40
             (56)
                     50%
                               halation
                               chamber
                    Modified   New Zealand
                    Rochester- Albino
                    type  in-   rabbit
                    halation
                    chamber
3 M
         12 M
                    Continuous
                    114 d
114 d
ity over  1/4 to 1/2 of the
cornea.   Moderate lung conges-
tion in 2/3.  No difference in
hematological values.  Histo-
pathological examination re-
vealed focal or diffuse inter-
stitial pneumonitis in all animals.
Other histopathological changes
seen in the heart, liver, kidneys,
and bronchi, with similar but
lesser changes in the control
group.

No death  or signs of toxicity    Coon et al.
in any of the animals.  Nee-     (1970)
ropsy observations were normal.  B-12

-------
TABLE 111-15.   CATS—ACUTE EXPERIMENTAL EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
"iK/m3 (ppm) Humidity
NH3 893-1,037 Not
(1,240-1,440) given




NH3 590-1,030 Not
(820-1,430) given






NH3 576-770 Not
(800-1,070) given





NH3 720 Not
(1,000) given







NH3 346-410 Not
(480-570) given






Species/ No. of Duration &
Mode of Strain/ Test No. of Frequency
Exposure Age/Weight Animals Controls of Exposure
Well- Cats 44 0 7 h
venti- once
lated
chamber


Well- Cats 6 0 5.5 h
venti- once
lated
chamber




Well- Cats, 4 0 7 h
venti- half-grown once
lated
chamber



Head ex- Stray, 20 2, for 10 min
posure mixed patho-
plethys- breed cats logical
mograph changes
chamber only.
Served
as own
controls
otherwise.
Well- Cat 1 0 4 h
venti- once
lated
chamber




Total
Length of
Expt. Effects
Nose bleeds. Eyes remained
clear. Killed immediately
after the expt. with CHC13.
Suppurative tracheitis, lungs
hyperemic with 6-8 fine ecchy-
moses.
Symptoms of irritation stronger
than when exposed to 800 to
1,070 ppm (576-770 mg/m3). Res-
piration slowed (7-9), dyspneic.
Distinct evidence of pain.
After exposure, some nasal ca-
tarrh, which cleared up very
quickly.
Slight symptoms of irritation,
interruption of motion, persis-
tent salivary secretion of vari-
able consistency. Respiration
12-20. After exposure, the sal-
ivary secretion continued for
2 h and then was normal.
35 d All suffered severe dyspnea,
anorexia, and dehydration.
1/20 died of bronchopneumonia.
Pulmonary function tests indi-
cate 2 stages of dysfunction:
acute and chronic. Good corre-
lation between function data
and pathological lesions found.

Some symptoms of irritation
from the beginning, secretion
of saliva, retarded respira-
tion. Then normal behavior,
very quiet. Then at the end
of the expt. again highly
fluid salivary secretion. No
symptoms of harm after the test.
Reference
and
Rating
Lehmann
(1886)
B-9



Lehmann
(1886)
B-9





Lehmann
(1886)
B-9




Dodd and
Gross (1980)
B-ll






Lehmann
(1886)
B-9






-------
TABLE 111-16.   MONKEYS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
mg/m3
NH3




NH3





(ppm) Humidity
770 + 55 50%
(1,070)



155 + 32 50%
(215)




Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber
Modified
Rochester-
type in-
halation
chamber

Species/
Strain/
Age/Weight
Squirrel
monkeys
(Saimiri
sciureus)

Squirrel
monkeys
(Saimiri
scieureus)


No. of Duration & Total
Test No. of Frequency Length of
Animals Controls of
3 M 8 M 8
5
6


3 M 8 M 8
5
6



Exposure Expt.
h/d, 6 wk
d/wk,
wk


h/d, 6 wk
d/wk,
wk



Effects
No deaths. No signs of irri-
tation or toxicity were noted.



No deaths, visible signs of
toxicity, or gross abnormal-
ities in organs or tissues.
Histopathological examination
showed evidence of focal pneu-
monitis in the lung of 1 monkey.
Reference
and
Rating
Coon et
(1970)
B-12


Coon et
(1970
B-12





al.




al.






-------
TABLE III-17.  MONKEYS—CHRONIC EXPERIMENTAL EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 470 + 16 50%
(652)






NH3 40+2 50%
(56)







Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber



Modified
Rochester-
type in-
halation
chamber



Species/ No. of
Strain/ Test
Age/Weight Animals
Squirrel 3 M
monkeys
(Saimiri
sciureus)




Squirrel 3 M
monkeys
(Saimiri
sciureus)




Duration & Total
No. of Frequency Length of
Controls of Exposure Expt. Effects
8 M Continuous 90 d No deaths. No change in hema-
90 d tological values. Focal or
diffuse interstitial pneumonitis
in all animals. Other histo-
pathological changes seen in the
heart, liver, kidneys, and bron-
chi, with similar but lesser
changes in the control group.
8 M Continuous 114 d No deaths or signs of toxicity
114 d in any of the animals. Nec-
ropsy observations were normal.
Histopathological examination
revealed lipid filled macro-
phages in the lung of 1 monkey.
This finding was judged to be
clinically insignificant.
Reference
and
Rating
Coon et al.
(1970)
B-12





Coon et al.
(1970)
B-12






-------
TABLE III-18.  DOGS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 770 + 55 50%
(1,070)







NH3 155 + 32 50%
(215)




Mode of
Exposure
Modified
Rochester-
type in-
halation
chamber




Modified
Rochester-
type in-
halation
chamber
Species/ No. of
Strain/ Test
Age/Weight Animals
Purebred 2 M
beagle dog







Purebred 2 M
beagle dog



Duration &
No. of Frequency .
Controls of Exposure
12 M 8 h/d,
5 d/wk,
6 wk






12 M 8 h/d,
5 d/wk,
6 wk


Total
Length of
Expt. Effects
6 wk No deaths. Mild to moderate
dyspnea and lacrimation during
the first week, disappearing
during the second week. No
further signs of irritation or
toxicity were noted at necropsy
or hematological and histopatho-
logical exam, attributable to
NH3.
6 wk No deaths, visible signs of
toxicity, or gross tissue ab-
normalities. Hematological
values normal.

Reference
and
Rating
Coon et al.
(1970)
B-12






Coon et al.
(1970)
B-12



-------
                                  TABLE 111-19.   DOGS—CHRONIC  EXPERIMENTAL  EXPOSURE TO NH3
Compound (s) and
Concentration(s) in
mg/t
NH3


n3 (ppn>) Humidity
470 + 16 50%
(652)

Mode of
Exposure
Modified
Rochester-
type in-
Species/
Strain/
Age/Weight
Purebred
beagle dog

No. of
Test
Animals
2 M



No. of
Controls
12 M


Duration &
Frequency
of Exposure
Continuous
90 d

Total
Length of
Expt.
90 d




Effects
No deaths. No change in hema-
tological values. Heavy lacri-
mation and nasal discharge
Reference
and
Rating
Coon et al.
(1970)
B-12
                               halation
                               chamber
NH,
40 +
 (56)
50%
Modified   Purebred
Rochester- beagle dog
type  in-
halation
chamber
                                                     2 M
                                                               12 M
                                                                         Continuous
                                                                         114 d
114 d
noted.   Hemorrhagic lesion in
the lung of 1  dog.  Focal or
diffuse interstitial pneumonitis
in all  animals.  Other histo-
pathological changes seen in the
heart,  liver,  kidneys and bronchi,
with similar but lesser changes
in the  control group.

No deaths or signs of toxicity   Coon et al.
in any  of the  animals.  Nee-     (1970)
ropsy observations were normal.  B-12
Histopathologic examination re-
vealed  lipid filled macrophages
in the  lungs of both dogs.
This was deemed to be of no clin-
ical significance.

-------
TABLE 111-20.  TURKEYS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO NH3
Compound(s) and
Concentration(s) in
rag/in3 (ppm)
NH3 72
(100)







NH3 36
(50)



NH3 36
(50)-


NH3 14.4-21.6
(20-30)

Dust 0.6-1.0 rag/ft3







Species/
Mode of Strain/
Humidity Exposure Age/Weight
10-30% Cabinet Bronze
(336 ft3) turkeys,
4 wk






10-30% Cabinet Bronze
(336 ft3) turkeys,
4 wk


10-30% Cabinet Bronze
(336 ft3) turkeys,
4 wk

~ 40-85% Growth Broadwhite
chambers turkeys,
2 wk








No. of
Test No. of
Animals Controls






2 3
2 3
2 3


2 3

2 3
2 3



600 M Appar-
600 F ently
(3 expts . none
with 400
turkeys
each)





Duration & Total
Frequency Length of
of Exposure Expt.
Continuous 18 d
(all animals
previously
exposed to
13 d of 36
mg/m3)
1 d
3 d
5 d
Continuous 12 d

10 d

12 d
Continuous 8 d
2 d (after
6 d exposure
to 14.4 mg/m3)
10 wk, 2 wk
continuous ,
with turkeys
removed
every 2 wk
for autopsy







Effects
Gradually increasing pulmonary
edema, congestion, and hemor-
rhage. Turkeys also exhibited
anorexia and slow weight gains.





Gradually increasing pulmonary
congestion, edema, and hemor-
rhage. Turkeys also exhibited
anorexia and slow weight gain.

Nothing significant.



Averaged 3.1% mortality for the
10-wk period, and 2.79 Ib of
feed/lb of turkey (feed conver-
sion) at 12 wk. No difference
from the other treatments done.
Histopathological changes in
the respiratory tract seen. The
16.2% airsacculitis was due to
the high dust level, not the NH3
level. No interaction was seen
between the dust and the NH3.
Reference
and
Rating
Anderson et al.
(1964)
B-12






Anderson et al.
(1964)
B-12


Anderson et al.
(1964)
B-12

Anderson et al.
(1968)
B-13








                               (continued)

-------
TABLE 111-20.  (continued)
Compound (s) and
Concentration(s) in
mg/m3
(ppm) Humidity
NH3 14.4-21.6 ~ 40-85%


Dust 0.1-0







NH3






NH3


Dust 0.6-1

(20-30)

.4 tag/ ft3







14.4 10-30%
(20)





0-5.8 ~ 40-85%
(0-8)

.0 mg/ft3

Species/
Mode of Strain/
Exposure Age/Weight
Growth Broadwhite
chambers turkeys,
2 wk








Cabinet Bronze
(336 ft3) turkeys,
4 wk




Growth Broadwhite
chambers turkeys ,
2 wk


(both increased grad-
ually with
fluctuated
time, and
, generally


No. of
Test
Animals
600 M
600 F
(3 expts.
with 400
turkeys
each)






2

2

2
2
600 M
600 F
(3 expts.
with 400
turkeys
each)



No. of
Controls
Appar-
ently
none









3

3

3
3
Appar-
ently
none





-Duration & Total
Frequency Length of
of Exposure Expt.
10 wk, 12 wk
continuous,
with tur-
keys removed
every 2 wk
for autopsy





Continuous 6 d
1 d

2 d

4 d
6 d
10 wk, 12 wk
continuous ,
with tur-
keys removed
every 2 wk
for autopsy


stable by wk 8)

NH3


Dust 0.1-0






0-5.8 ~ 40-85%
(0-8)

.4 mg/ft3






Growth Broadwhite
chambers turkeys,
2 wk







600 M
600 F
(3 expts.
with 400
turkeys
each)




Appar-
ently
none







10 wk, 12 wk
continuous,
with tur-
keys removed
every 2 wk
for autopsy





Effects
Averaged 3.6% mortality in the
10 wk period and 2.73 Ib of
feed/lb of turkey (feed conver-
sion) at wk 12, with no signi-
ficant differences from other
treatments done. Histopatho-
logical changes in the respira-
tory tract seen. The 11.0% air
sacculitis is low, due to the
low dust level. No interaction
between dust and NH3.
Exposure for 1 d increased
mucous secretion from the up-
per respiratory tract, symptoms
disappearing in 3-4 d. No
other effect.


Averaged 3.2% mortality for the
10-wk period, and 2.84 Ib of
feed/lb of turkey (feed conver-
sion) at wk 12. No differences
from other treatments done.
Histopathological changes in
the respiratory tract. Averaged
18.2% airsacculitis, due to high
dust levels, not the NH3. No in-
teraction between dust and NH3.
Averaged 3.6% mortality in the
10 wk period, and 2.74 Ib of
feed/lb of turkey (feed conver-
sion) at wk 12. No differences
from the other treatments .
Histopathological changes did
not occur, even by wk 12. The
7.1% airsacculitis was the low-
est of all the treatments.
Reference
and
Rating
Anderson et
(1968)
B-13








Anderson et
(1964)
B-12




Anderson et
(1968)
B-13







Anderson et
(1968)
B-13









al.










al.






al.









al.









-------
TABLE 111-21.  SWINE—ACUTE EXPERIMENTAL EXPOSURE TO NH3
Compound(s) and
Concentration(s) in
mg/ra3 (ppm) Humidity
m3 54 Not
(75) given
Exposed to an aero-
sol of a nonpatho-
genic strain of E.
coli immediately
before NH3 exposure.
NH3 36 Not
(50) given
Exposed to an aero-
sol of a nonpatho-
genic strain of E.
coli immediately
before KH3 exposure.

Mode of
Exposure
Exposure
chamber





Exposure
chamber





Species/
Strain/
Age/Weight
.Conven-
tional
crossbred
pigs, avg.
age 6.2 d


Conven-
tional
crossbred
pigs, avg.
age 15.5 d


No. of Duration &
Test No. of Frequency
Animals Controls of Exposure
40 40 2 h
(also ex-
posed to
nonpatho-
genic E.
coli
aerosol)
40 40 2 h
(also ex-
posed to
nonpatho-
genic E.
coli
aerosol)
Total
Length of
Expt. Effects
2+ h Test animals had 75% more vi-
able bacteria in their lungs
than did the control animals.




2+ h Test animals had 46% more vi-
able bacteria in their lungs
than did the controls. In-
creased lung weight and
lung weight-body weight
ratio. No gross or histo-
pathological changes.
Ref eronce
and
Rating
Drumnioml et al .
(1978)
B-10




Drummond et a 1 .
(1978)
B-10





-------
                              TABLE  111-22.   SWINE—REPEATED DOSE EXPERIMENTAL EXPOSURE TO NH,
Compound (s) and
Concentration(s) in
mg/m3
NH3

(ppm)
~ 200.6
(~ 280)
Humidity
Not
given
Mode of
Exposure
Environ-
mental
Species/
Strain/
Age/Weight
Gilt
(young fe-
No. of
Test
Animals
1 F


No. of
Controls
None

Duration &
Frequency
of Exposure
36 h

Total
Length of
Expt.
43 h



Effects
Immediate frothing of the
mouth, lasting 3 h. Secretions
Reference
and
Rating
Stombaugh
(1969)



et al

NH,
         avg.  104.4
            (US)
77%
NH3            76.6
             (106.4)
Corn starch dust
(3-5 pro)  213 mg/m3
19-47%
NH3           76.6
             (106.4)
Ground corn dust
(3-5 Mm)  10.6 mg/m3
19-47%
                                chamber    male swine),
                                          30 kg
Environ-
mental
chamber
(with
wastes
removed
daily)
Environ-
mental
chamber
(with
removal
of
wastes)
Environ-
mental
chamber
(with
removal
of
wastes)
                     Duroc        18
                     pigs, avg.
                     wt 54 kg
Yorkshire
Landrace
pigs, 1 wk
Yorkshire
Landrace
pigs, 1 wk
                      Appar-
                      ently
                      none
                                                      5 wk
                                           (chamber
                                           air had
                                           8.9 ppm
                                           NH,)
1-5 wk
1-5 wk
                                                                                of the  mouth  and  nose, short     B-ll
                                                                                and irregular breathing,  sneez-
                                                                                ing and headshaking persisted.
                                                                                Convulsions by 36 h.  Apparent
                                                                                return  to  normal  7 h after ex-
                                                                                posure  stopped.
                                                          Stombaugh et al.
                                                          (1969)
                                                          B-ll
5 wk        Feed consumption at the level
            of the 103 ppm group,  and be-
            low that of the 12  and 61 ppm
            groups.   Avg.  daily gain fluc-
            tuated in relationship to other
            groups.   Feed  conversion not
            affected.   Nasal,  lacrimal, and
            mouth secretions decreasing with
            time.  Increased cough rate.
5 wk        Conjunctivitis began the  first   Doig  and
            day,  and lasted 2 wk.   No clin-  Willoughby
            icopathological or microbiolog-  (1971)
            ical  changes.   No epithelial     B-ll
            thickening,  or decrease in gob-
            let cell number.   Difference  in
            effects from NH3  alone possibly
            due to gas  absorption onto the
            particles,  and removal in the
            nasal passages.

5 wk        Slight conjunctivitis during     Doig  and
            the first wk.   No tracheal or   Willoughby
            turbinate epithelial thicken-   (1971)
            ing.   Decrease in epithelial     B-ll
            goblet cell  number,  similar to
            that  of NH3  alone.
                                                                   (continued)

-------
TABLE  111-22.   (continued)
Compound(s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 76.6 19-47%
(106.4)











NH3 avg. 74.2 77%
(103)








NH3 avg. 43,9 77%
(61)





NH3 54 Not
(75) given


Mode of
Exposure
Environ-
mental
chamber
(with
removal
of
wastes)






Environ-
mental
chamber
(with
wastes
removed
daily)



Environ-
mental
chamber
(with
waste
removed
daily)
Exposure
chamber

Species/ No. of
Strain/ Test
Age/Weight Animals
Yorkshire 6
Landrace
pigs, 1 wk










Duroc 18
pigs, avg.
wt. 54 kg







Duroc 18
pigs, avg.
wt. 54 kg




Crossbred 8
pigs, avg.
wt. 9.1 kg
Duration &
No. of Frequency
Controls of Exposure
6 1-6 wk
(chamber
air had
8 ppm NH3)









Appar- 5 wk
ently
none
Total
Length of
Expt. Effects
6 wk Slight conjunctivitis during
the first wk. No clinicopath-
ologic or microbiologic changes.
Some subpleural hemorrhage and
lobular atelectasis in both
test and control groups. Tra-
cheal and turbinate epithelia
had increased thickness and de-
creased numbers of goblet cells.
No lower respiratory tract
changes, indicating high NH3 re-
moval in the upper tract. No
weight loss.
5 wk Feed consumption lower than
that for the 12 and 61 ppm
groups, and about equal to that
Reference
and
Rating
Doig and
Willoughby
(1971)
B-ll









Stombaugh et al
(1969)
B-ll
of the 145 ppm group. Avg. daily






Appar- 5 wk
ently
none




8 46, 78, or
109 d

gain varied in relationship to
other groups. Feed conversion
not affected. Nasal, lacrimal,
and mouth secretions decreasing
with time. Increase in cough
rate.
5 wk Feed consumption slightly be-
low that of pigs exposed to 12
ppm, and above the 103 and 145
ppm groups. Avg. daily gain
varied in relationship to the
other groups. Feed conversion
was unaffected.
109 d No effect on mean daily body-
weight gain. No changes in
respiratory-tract structure.






Stombaugh et al
(1969)
B-ll




Curtis et al.
(1975)
B-12
           (continued)'

-------
TABLE 111-22.  (continued)
Compound (s) and
Concentration(s) in
mg/m3 (ppm) Humidity
NH3 36 Not
and (50) given
Dust 300 mg/m3
NH3 36 Not
and (50) given
Dust 10 mg/m3
NH3 36 Not
and (50) given

H2S 2.8
(2)
NH3 36 Not
(50) given



NH3 avg. 8.6 77%
(12)







Mode of
Exposure
Exposure
chamber

Exposure
chamber

Exposure
chamber



Exposure
chamber



Environ-
mental
chambers
(with
waste
removed
daily)

Species/ No. of
Strain/ Test No. of
Age/Weight Animals Controls
Crossbred 12 12
pigs

Crossbred 4 4
pigs, avg.
wt. 8.2 kg
Crossbred 3 3
pigs, avg.
wt. 20.9 kg


Crossbred 16 16
pigs, avg.
wt. 8.2-
31.8 kg

Duroc 18 Appar-
pigs, avg. ently
initial none
wt. 54 kg




Duration & Total
Frequency Length of
of Exposure Expt. Effects
24, 57, or 71 d Decreased mean daily body-
71 d weight gain. No effect on res-
piratory-tract structure.
27 d 27 d No effect on mean daily body-
weight gain. No changes in
respiratory-tract structure.
19 d 19 d No effect on mean daily body-
weight gain. No changes in
respiratory-tract structure.


24-71 d 71 d No effect on mean daily body-
weight gain. Mild conjunctiv-
itis and blepharitis in 1/16.
No changes in respiratory-
tract structure.
5 wk 5 wk Feed consumption slightly
higher than pigs exposed to
50 ppm, and above that of pigs
exposed to 100 or 150 ppm.
Avg. daily gain varied with time
in relationship to other expo-
sures. No effect on feed con-
version.
Reference
and
Rating
Curtis et al.
(1975)
B-12
Curtis et al.
(1975)
B-12
Curtis et al.
(1975)
B-12


Curtis et al .
(1975)
B-12


Stombaugh et al
(1969)
B-ll






-------
                                SECTION IV

                  EXPERIMENTAL HUMAN INHALATION EXPOSURES
     Tables IV-1 and IV-2 describe acute and repeated dose laboratory human
exposures to NHs, respectively.  Table S-2 in the summary condenses all the
information regarding experimental  human exposure,  from about 40 mg/m3 to
< 0.5 mg/m3.  The American Conference of Governmental Industrial Hygienists
gives 18.0  mg/m3 as the  time-weighted-average threshold limit value and 27
mg/m3 as the short-term-exposure limit (ACGIH, 1981).
                                     55

-------
                               TABLE  IV-1.   HUMANS—ACUTE EXPERIMENTAL INHALATION EXPOSURE TO NH-
Compound(s) and
Concentration (s)
in ng/m3 (ppm)
NH3 381.6-403.2
(530-560)










Mode of
Exposure
Room
(unspeci-
fied)








No. of Duration and Total
Test No. of Frequency of Length of
Subjects Controls Exposures Expt. Effects
1 M Served as 4 h, once 7 h The levels of nonprotein nitro-
own control gen and NH3 in the blood plasma
increased with increasing expo-
sure time. The urea and creati-
nine content of the blood showed
no change from normal values.
The carbon dioxide-combining power
of the blood plasma was not impaired.
Pulse rate was constant, and blood
pressure (probably systolic) decreased
in the first 35 min of inhalation.
Reference
and
Rating
Schmidt and
Vallencourt
(1948)
B-8







     NH3 360
            (500)
Ln
     NH3 avg. 235;
     range  180-344,
     increasing with
     exposure time
Mask over
nose and
mouth
7 M
          Served
          as own con-
          trols
30 min,  once    45-60 min
Exposure
chamber
(with
oro-nasal
mask and
3-way
valve box
during
exercise)
18 M
(with
~ 60 min
preced-
ing expo-
sure to
72-122
mg NH3/
m3)
Served as
own con-
trols on
days 1 and
3 of ex-
periment



35-60 min,
once, on day
2 of experi-
ment. In-
cluded an
8-min exer-
cise period.


Three con-
secutive 0.
sessions







.5-d







Expired air ammonia at equili-
brium varied from  252 to 346
mg/m3, occurring from 10 to
27 min after exposure began.
Respiratory rate was slightly
elevated,  and minute volume in-
creased from 50 to 250% over that
of control levels, both parameters
quickly returning  to normal after
exposure ended.  Lung ventilation
showed a cyclic variation during expo-
sure in 2/7.   No coughing was induced.
Reflexly induced lacrimation occurred
in 2/7.  Subjective reactions varied
widely.

Increased exercise cardiac
frequency and respiratory fre-
quency.  Decreased ventilation
minute volume and  exercise
tidal volume. No  material dis-
comfort.
Silverman et al.
   (1949)
    A-11
                                                                                                           Cole et al.
                                                                                                               (1977)
                                                                                                               B-ll
                                                                      (continued)

-------
TABLE  IV-1.   (continued)
Compound (s) and
Concentration(s )
in mg/ra3 (ppm)
NH3 avg. 144;
range 115-158,
increasing with
exposure time








Mode of
Exposure
Exposure
chamber
(with
oro-nasal
mask and
3-way
valve box
during
exercise)


No. of
Test
Subjects
18 M
(with
~ 60 min
preceding
exposure
to 115-
158 mg
NH3/m3, as
near as can
be deter-
mined from

No. of
Controls
Served as
own con-
trols on
days 1 and
3 of exper-
iment





Duration and Total
Frequency of Length of
Exposures Expt.
35-60 min, Three con-
once, on secutive
day 2 of 0.5 d ses-
experiment. sions
. Included
an 11-min
exercise
period.





Effects
Slight decrease in exercise car-
diac frequency. Significantly
reduced ventilation minute volume
due to reduced tidal volume, de-
spite a significant increase in
respiratory frequency. No mate-
rial discomfort.




Reference
and
Rating
Cole et al.
(1977)
B-ll








the methodo-

NH3 avg. 106; range
72-122, increasing
with exposure time





NH3 100.8 (140)










M3 96.48 (134)




NH3 79.2 (110)








Exposure
chamber
(with oro-
nasal mask
and 3-way
valve box
during
exercise)
Exposure
chamber
(25 m3)








Inhala-
tion
chamber
(700 L)
(head only)
Exposure
chamber
(25 m3)





logy given)
18 M







7 M 1 F
"experts"

6 M 2 F
"nonex-
perts"





8 M
2 F



7 M 1 F
"experts"

6 M 2 F
"nonex-
perts"



Served as
own con-
trols on
days 1 and
3 of ex-
periment


Served as
own con-
trols













Served as
own con-
trols






35-60 min, Three con-
once, on secutive
day 2 of 0.5 d ses-
experiment. sions
Included
an 8-min
exercise
period.
•2 h, once










5 min, once




2 h, once








Significant increases in exer-
cise cardiac frequency and
exercise tidal volume. Decreased
ventilation minute volume due to a
slightly reduced respiratory fre-
quency. No material discomfort.


< 10% decrease in VC, FEV1( and
FIV!. No hypersusceptibility
to nonspecific irritants, as
measured by the histamine
threshold. Strong eye and throat
irritation, with cough, in the
"nonexperts," becoming unbearable
so 8/8 had to leave before 2 h.
"Experts" had perceptible eye and
throat irritation, with slight
cough.
10/10 detected the odor. 5-8/10
reported lacrimation and irri-
tation to the eyes, nose, mouth,
or throat. 1/10 reported slight
irritation to the chest.
< 10% decrease in VC, FEVj , and
FIV^ No hypersusceptibility to
nonspecific irritants, as mea-
sured by the histamine threshold.
Definite eye irritation, percep-
tible throat irritation, slight
cough. "Nonexperts" generally more
uncomfortable than "experts-"

Cole et al.
(1977)
B-ll





Verberk
(1977)
A-13








Keplinger et al
(1973)
A-12


Verberk
(1977)
A-13





           (continued)

-------
                                                           TABLE  IV-1.    (continued)
00
Compound (s) and
Concentration (s)
in mg/m3 (ppm)
NH3 avg. 71; range
50-79, increasing
with exposure time





NH3 57.6 (80)






NH3 51.84
(72)




NH3 36 (50)






NH3 36 (50)





NH3 36 (50)






Mode of
Exposure
Exposure
chamber
(with oro-
nasal mask
and 3-way
valve box
during ex-
ercise)
Exposure
chamber
(25 m3)




Inhala-
tion
chamber
(700 L)
(head
only)
Exposure
chamber
(25 m3)




Inhala-
tion
chamber
(700 L)
(head
only)
Rochester
chamber,
head
exposure
only

No. of
Test
Subjects
18 M







7 M 1 F
"experts"

6 M 2 F
"nonex-
perts"

8 M
2 F




7 M 1 F
"experts"

6 M 2 F
"nonex-
perts"

8 M
2 F




6 M





Duration and
No. of Frequency of
Controls Exposures
Served as 35-60 min,
own con- once, on
trols on second day
days 1 and of experi-
3 of ex- ment
periment


Served as 2 h, once
own con-
trols




5 min, once





Served as 2 h, once
own con-
trols




5 min, once





Served as 10 min
own con-
trols



Total
Length of
Expt. Effects
3 consecutive Exercise cardiac frequency was
0.5 d ses- reduced. No effect on ventila-
sions tion minute volume, exercise
tidal volume, or mean respiratory
frequency. No material discomfort.



< 10% decrease in VC, FEVj, and
FIVi. No hypersusceptibility to
nonspecific irritants, as mea-
sured by histamine threshold.
Definite eye and slight throat
irritation. Generally, "non-
experts" more uncomfortable.
10/10 detected the odor.
2/10 had slight eye irritation.
1/10 had slight eye irritation,
and dry nose and mouth.
1/10 had dry mouth.
1/10 had dry nose and mouth.
No change in VC, FEVi, or FlVt
of more than 10% after exposure.
No hypersusceptibility to non-
specific irritants, as measured
by histamine threshold. Odor
was detected. Some slight eye
and throat irritation.
10/10 detected the odor. No
significant signs of irritation
(subjective evaluation).



4/6 described moderate eye and
nasal irritation. 1/6 described
a faint nonpainful irritation.
1/6 had no irritation. All des-
cribed a strong, highly penetrat-
ing odor.
                                                                                                                                   Reference
                                                                                                                                      and
                                                                                                                                    Rating	

                                                                                                                                   Cole  et  al.
                                                                                                                                     (1977)
                                                                                                                                     B-ll
                                                                                                                                   Verberk
                                                                                                                                    (1977)
                                                                                                                                    A-13
Keplinger  et al.
     (1973)
      A-12
                                                                                                                                   Verberk
                                                                                                                                    (1977)
                                                                                                                                     A-13
                                                                                                                                   Keplinger et al.
                                                                                                                                        (1973)
                                                                                                                                         A-12
                                                                                                                                   MacEwen  et al.
                                                                                                                                       (1970)
                                                                                                                                        C-8
                                                                     (continued)

-------
                                                        TABLE IV-1.   (concluded)
Cpmpound(s) and
Concentration(s)
in mg/m3 (ppra)
m3 33.7 (46.8)


NH3 23 (32)





NH3 21.6 (30)





NH3 13



Mode of
Exposure
Exposure
chamber

Inhala-
tion
chamber
(700 L)
(head
only)
Rochester
chamber,
head
exposure
only

Exposure
chamber
(5 n.3)
No. of Duration and Total
Test No. of Frequency of Length of
Subjects Controls Exposures Expt. Effects
4 Not given, Odor threshold, the lowest con-
once centration at which all 4
panelists recognized the odor.
8 H 5 min, once 9/10 detected the odor. No sig-
2 F nificant signs of irritation
(subjective evaluation).



5 M Served 10 min 2/5 felt faint, nonpainful
as own nasal and eye irritation, and
controls described moderate odor intensity.
3/5 detected no irritation and
described a strong, highly pene-
trating odor.
6 H 5 M 8 h ~24 h Immediately after exposure, 50-
100% increase in NH3 and urea
levels in urine, and NH3 levels
Reference
and
Jteting
Leonardos et
(1969)
A-ll
Kepi inger et
(1973)
A-12



MacEwen et al
(1970)
C-8



Mikhailov et
(1969)
C-8



al.


al.











al.


NH3 3
NH3 0.45 - 1.0
Exposure
chamber
(5 m3)
                 6 M
           5 M
                       8 h
-24 h
Not given
22
                       Not given
Not given
in blood.   Significant  decrease
in 02 consumption by 20%.   Insig-
nificant changes  in EKG,  and  no
change in arithmetic ability.
Any changes observed were gone by
the day after exposure.

Immediately after exposure, no
changes in NH3 levels in  blood
and urine, urea levels  in urine,
or ability to make arithmetical
calculations.  Tendency to decrease
the coefficient of C<2 consumption.
Insignificant changes in  EKG.  Any
changes observed  were gone the day
after exposure.

Thresholds of ammonia perception
determined:
  1.0  mg/m3 for  2/22,
  0.75 mg/m3 for  7/22,
  0.55 mg/m3 for  9/22,  and
  0.45 mg/m3 for  4/22
Mikhailov et al.
     (1969)
       C-8
Sayfutdinov
   (1968)
     B-7

-------
TABLE IV-2.  HUMANS—REPEATED  DOSE EXPERIMENTAL INHALATION EXPOSURE TO NH3
Compound(s) and
Concent ration (s)
in rag/m3 (ppm)
NH3
regime
week
1
2
3
4
5
6






NH3
regime:
week
1
2
3
4
5
6



NH3 36












concn.
18
36
72
18
36
72








concn.
72
36
18
18
36
72



(50)










No. of
Mode of Test
Exposure Subjects
Indus- 2 M
trial
work sta-
tion (am-
monium bi-
carbonate
plant with
slight arti-
ficial NH3
enrichment)





Indus- 2 M
trial
work sta-
tion (am-
monium bi-
carbonate
plant with
slight arti-
ficial NH3
enrichment)


Indus- 1 F
trial 1 M
work sta-
tion (am-
monium bi-
carbonate
plant with
slight
artificial
NH3 enrich-
ment)
Duration and Total
No. of Frequency of Length of
Controls Exposures Expt.
Appeared 3 h, twice 6 wk
to serve a day, 5 d/wk,
as own 6 wk
controls
during a
1-3 d non-
exposure
period in
the middle
of the test.





Appeared to 3 h, twice 6 wk
serve as a day, 5 d/wk,
own con- 6 wk
trols dur-
ing a 1-3 d
nonexposure
period in
the middle
of the test.



Appeared to 3 h, twice 6 wk
serve as a day, 5 d/wk,
own con- 6 wk
trols dur-
ing a 1-3 d
nonexposure
period in
the middle
of the test.


Re f e rence
and
Effects Rating
Statistically significant in- Ferguson ft al.
crease in FEVj with increased (1977)
NH3 concentration. No change A-ll
in respiration, pulse, blood
pressures, or FVC. As observed
by a physician, mild irritation
of the eye, nose, or throat was
nonexistent for weeks 4 and 5, and
not statistically different from
the no-exposure periods for week 6.
Brief excursions to 144 mg/m3 during
weeks 2 and 6 caused only 1 case of
increased irritation. All subjects
reported some watering of the eyes
and dryness of the nose and throat.
Slight increase in FEVj with in- Ferguson et al.
creased NH3 . As observed by a (1977)
physician, mild eye, nose and A-ll
throat irritation decreased after
week 2, to control levels. No
change in respiration, pulse,
blood pressures or FVC. Brief
excursions to 144 mg/m3 during
weeks 2 and 6 caused some water-
ing of the eyes and dryness of
nose and throat, and no increase of
physician-observed irritation.
No significant changes in per- Ferguson et al.
spiration, pulse, systolic and (1977)
diastolic blood pressures, A-ll
FVC, FEVj, or rate of mild eye
irritation were found at any
time. No abnormalities of the
chest, vital organs, neurological
response, or significant weight
changes were found.


                              (continued)

-------
TABLE  IV-2.  (continued)
Compound (s) and
Concentration(s)
in mg/m3 (ppm)
NH3 10.5 ± 0.85






Mode of
Exposure
NH3 in
air de-
livered
at 15 L/min
through a
funnel in
No. of
Test
Subjects
26






No. of
Controls
Served as
own con-
trols



Duration and Total
Frequency of Length of
Exposures Expt.
4 h (test
repeated 3-4
times at un-
known inter-
vals)

the "breath-



NH3 6.1 ± 0.71









ing zone"


NH3 in
air de-
livered
at 15 L/
min
through
a funnel
in the
"breath-
ing zone"



19 peo-
ple,
2-4 d
after
conva-
lescence
from
acute
diseases of
the upper



26 "prac-
tically
healthy"
people









4 h (tests
repeated 2-4
times at un-
known inter-
vals)





respiratory


NH3 2.2 ± 0.39














NH3 in
air de-
livered
at 15 L/
rain
through
a funnel
in the
"breath-
ing zone"



tract.

19 peo-
ple,
2-4 d
after
conva-
lescence
from
acute
diseases
of the
upper res-
piratory
tract


26 "prac-
tically
healthy"
people











4 h (tests
repeated 2-4
times at un-
known inter-
vals)








Reference
and
Effects Rating
Decrease in the rate of exhala- Mikhailuts
tion during pneumotachometry . (1977)
Duration of the transient pro- B-9
cess of the heart rhythm during
cardiointervalography grew by
an average of 14.6%. Increased
latent period of smell-motion
reaction. Inhibition of the
reduction of odor sensitivity
after loading.
In the test group, there were de- Mikhailuts
creased odor thresholds for ben- (1977)
zene, valerian, and camphor (in B-9
55-67% of the cases), but with
possible exhaustion of the "odor
analyzer." Rate of forced inha-
lation and expiration decreased
with an intensity of the transient
process of the heart rhythm. Con-
trol group had decreased camphor
thresholds by 12-16% of the time
to the transient process, and no
change in other indexes.
In the test group, there was a Mikhailuts
tendency to decrease the forced (1977)
rate of inhalation and exhala- B-9
tion (in 57.1-69% of the obser-
vations), and a lowering of the
odor threshold of camphor (in
71.4% of the observations). Con-
trol group had decreased threshold
odor of camphor, but also a rapid
reduction in odor sensitivity.
Control group pneumotachometry and
cardiointervalography were unchanged.

        (continued)

-------
TABLE IV-2.  (continued)
Compound(s) and No. of
Concentration(s) Mode of Test No. of
in mg/m3 (ppm) Exposure Subjects Controls
NH3 2.16 ± 0.06 Hermeti-
cally
Original Russian sealed
document reported 6 m3
a concentration chamber
of 2.16 mg/cm3;
assumed to be a
typographical error.









NH3 0.32 - 0.65 Not 3 (at Served as
given least 1 own con-
female) trols





NH3 0.32 - 0.76 Not given 5 Served as
own con-
trols







Duration and Total
Frequency of Length of
Exposures ExpJ^.
35 d 38 d
















40 min,
(tests re-
peated 3
times at un-
known inter-
vals)


12 min (tests Not given
repeated 3
times, at un-
known inter-
vals)







Effects
No significant effect on the
level of gas and energy metab-
olism and acid-base equilibrium.
An insignificant increase in 02
consumption. No changes in the
morphological composition of the
peripheral blood. NH3 levels in
blood and breath increased with
the length of exposure. Urea
concentration in the urine in-
creased only on day 32. Inhibi-
tion of the oxidative-reductive
processes, indicated by decreased
blood catalase activity and in-
creased acetone levels in the
breath. All changes disappeard
by the 3rd day post-exposure.
A concentration of 0.45 mg NH3/m3
lowered eye sensitivity to light
in 2/3, while 0.32 mg/m3 was in-
active. In 1/3, the threshold
odor perception concentration
which affected eye sensitivity to
light was 0.65 mg/m3, and the sub-
threshold value was 0.5. mg/m3.
In 3/5 test persons whose odor
threshold was 0.55 mg/m3, cere-
bral cortical activity was
affected by 0.35 mg/m3, de-
creased in 2 and enhanced in 1 .
In the other 2/5, with odor thres-
holds of 0.76 mg/m3, the "activ-
ity" concentration was 0.44 mg/m3
and the subthreshold level was
0.32 mg/m'3.
Reference
and
Rating
Savina et al .
•(1980)
R-7














Sayfutdinov
(1968)
R-7





Sayfutdinov
(1968)
B-7








-------
                                 SECTION V

                               EPIDEMIOLOGY
OCCUPATIONAL EXPOSURES

     Data for  occupational  exposures  to ammonia as shown in Table V-l are
not especially useful  for deriving a  range of concern for ammonia in  auto-
mobile,  emissions  because  occupational exposures are higher,  and  so many
other possibly toxic  factors  are present.  Table S-3 in the  Summary  con-
denses the occupational exposure data.

ACCIDENTAL EXPOSURES

     Data for exposures to NHs due to a wide variety of accidents are given
in Table  V-2.  These  are not very useful  because of the unknown  (but  prob-
ably high)  levels  of  ammonia encountered, but  were  included  because the
description of organs  affected  and symptoms caused may have  some helpful
suggestions.
                                    63

-------
                                       TABLE  V-l.   STUDIES OF OCCUPATIONAL  EXPOSURE  TO  AMMONIA
o\
       Cqmpound(s)
     Concentration(s)
       mg/m3  (ppm)
         Duration

     NH3  3.6-144 (5-200)

     CO
       (2-200)
     C02
       (800-10,000)
     H2S  7.1-14.2
       (5-10)
     2-12 h/d
     7  d/wk
NH3 50-75,  with
  occasional
  levels above
  this for  a
  short time.

Asbestos (ac-
  cording to
  Bittersohl,
  1971a).

  80% of the em-
  ployees worked
  for > 10  y.
                           Description

                     Workers in swine con-
                     finement units
                                      Population Group
          Controls
  11
                          Workers  in plants pro-
                          ducing or manufactur-
                          ing ammonia.
Unknown   Cancer
no. out   statis-
of 30,000 tics for
employ-   the GDR
ees in
the
study.
    NH3 ~ 10-40
      5-10 y
                     Workers in a NH3 pro-
                     duction plant.
 45 M
 28 F
55
                Description

          Over 50% complained of:
          coughing, increased sputum
          or phlegm, chest tightness,
          wheezing, stuffy nose,
          shortness of breath,  or
          sneezing.  Some eye irrita-
          tion, headache, dizziness,
          nausea,  and vomiting.  Vet-
          erinarians surveyed had
          similar  responses.
          Cancer of the lungs,  stomach,
          lymphatic tissue,  and
          urinary tract was  seen,  ac-
          counting for 40-60% of all
          deaths.   Cancer  in NH3 pro-
          duction plants exceeded
          that in other production
          plants by 5-6 times the
          rate of malignant  tumors,
          and 15 times higher fre-
          quency of cancers  than in
          the whole chemical factory.
          Male cancer  rates  per
          10,000 employees generally
          higher than  female cancer
          rates, probably  due to
          longer employment  times.
At the end of the work day
versus the beginning, sub-
jective data showed an in-
crease in headaches (27.56%
versus 12.71%), vertigo
9.45% versus 3.4%), stagger-
ing (6.30% versus 3.06%),
and tremors (24.26% versus
18.82%).   Other signs of
overexcitability of various
nerve tracts were seen:
anorexia, drowsiness, and
forgetfulness.
   Remarks

Confounding with other gases
and dust.  Gas concentra-
tions varied with season,
and no correlation made with
possible variability in
symptoms.  Strictly descrip-
tive study, no controls.
Presence of seasonal varia-
bility demonstrates need for
adequate control group.  Num-
bers obviously too small for
any inference to be drawn.

No mention of possible ex-
posure to other compounds
in the plants.
The cancer rates were not
age-adjusted, although dif-
ferences between sexes
were noted.
Both articles are obviously
about the same study, but
the short summary article
(Bittersohl, 1971b) does
not mention asbestos.
According to the other
article, all production em-
ployees were exposed to as-
bestos, and those also ex-
posed to NH3 had the highest
cancer rates, suggesting
possible co-carcinogenicity.

Actually a descriptive study
with poor utilization of in-
ternal controls.   This type
of comparison introduces
strong interviewee bias.  Be-
ginning versus end-of-day
data was not collected while
the individuals were not ex-
posed to NHs (i.e., off work
or in different area).   Could
not determine the comparabil-
ity of external controls.
Exposure levels are not given
and therefore not correlated
with symptoms.
                                                             Reference and
                                                             	Rating

                                                             Donham et a I.
                                                             (1977)
                                                             C-6
                                                             Bittersohl (1971a)
                                                             D-8
                                                             Bittersohl (1971b)
                                                             C-6
Kirkov (1977)
C-5
                                                                      (continued)

-------
                                                             TABLE  V-l.    (continued)
.  Compound(s)
Concentration(s)
  rag/m3 (ppm)
    Duration

NH3 5-29
Not given
               Population  Group
    Description

Workers exposed to ir-
ritating dusts and
gases.
143 H
         Controls
67 H
NH3
~ 18.3-26.3,
H2S04 aerosols un-
  known but appar-
  ently much less
  than NH3 concen-
  trations.
Not given.
Workers in a cuprammonium  50  M
rayon spinning mill.      .30  F
           56 M
           14 F
      Description

Higher incidence of chronic
bronchitis  and dyspnea.
Lower FEVt  values in those
workers.  Occupational  ex-
posure to NHa to some degree
connected with lowering of
FEV|  values.
           24% had slight and 28% mod-
           erate  impairments of  lung
           function.  Study done 3 y
           later, when NH3 levels had
           decreased to ~ 12.3 mg/m3,
           showed a decrease to  13%
           with moderate impairment.
           No trends found with  age,
           weight, smoking habits, or
           exposure duration.
                                                            Remarks
                                                                       Reference and
                                                                          Rating
Epidemiological design:  De-  Kujawska et al.
scriptive study relies on     (1977)
FEVt as relatively crude      B-10
outcome measure.  Internal
controls are apparently util-
ized, but it is difficult to
determine if they are compar-
able for relevant character-
istics, i.e., age.  Age, height
weight are listed in appendix.
Exposure variables are poorly
defined, especially duration
of exposure.  Also true for
confounding variables such as
smoking.  Only data on whether
or not the workers ever smoked
is utilized.
Strongest point is that clinical
systems can be related to FEVx
measurements so that if expo-
sure research could be refined,
meaningful data could be ob-
tained.

Nonconcurrent/concurrent pro- Herrraan and
spective design (retrospec-   Viehrig
tive cohort) using an ap-     (1979)
propriate control group.      A-9
Stratification performed
on both age and duration
of exposure and reversibil-
ity of outcome measures.
Numbers are relatively small
to place much confidence in
conclusion.  However, corre-
lation with decreased NH3
levels is impressive and cer-
tainly valuable information
in assessing levels of con-
cern.  Selection bias and com-
parability of controls is
always a concern but cannot
be assessed from the data
given here.
                                                                   (continued)

-------
                                                          TABLE  V-l.    (continued)
  Compound(s)
Concentration(s)
  mg/m3 (ppm)
    Duration
                           Description
                Population Group
                         Exposed   Controls
                             Description
                                         Remarks
                                Reference and
                                   Rating	
NH3 6-26
NO  12-61
NH3 exceeded
  20 mg/m3 in
  25.5% of 800
  samples.
  Workers exposed to ir-   216 M
  ritating dusts and
  gases.
            67 M
Workers in the main
  shops of tanneries
   46
NHs generally
  < 20
NO   avg.  <  MAC
  tnot given)
3 or 6 h/d for
  2 y
Adolescents undergoing
  vocational training in
  a fertilizer  factory
  or a chemical works.
  300
(HO re-
peatedly)
             85
  Occupational exposure to
  dusts, NH3 and NO  was con-
  nected with the lowering
  of fEVi values, perhaps
  more so than NH3 alone.

  Variations in the diurnal
  curves for 8 physiological
  functions were seen, par-
  ticularly in muscular
  endurance, mean pressure,
  and pulse, particularly
  towards the end of the
  day.  Probably due to the
  manual labor involved.
At the end of 1 y, an 11% in-
crease in the incidence of
disorders of the upper res-
piratory tract, and a 27%
increase in xeroderma.
After 2 y, there were sta-
tistically significant in-
creases of 24 and 36%, re-
spectively.  Changes in
certain biochemical indexes
indicated possible stress on
hepatic functions.
                                                      Confounding  due  to multiple
                                                      gases  and  dusts  present.
  Stricly descriptive study,
  primarily focused on
  diurnal variations in
  physiologic function.
  The study does not relate
  these changes to variations
  in NH3 concentrations.  In
.  -the absence of controls the
  meaning of these changes is
  not clear.  Most helpful in-
  formation is the absence of
  H2S and the presence of NH3,
  but S02 is variably present.
  Clinical measures (i.e.,
  respiratory symptoms or
  respiratory functions) are
  not made.

Apparent concurrent prospec-
tive design comparing per-
sons exposed to NH3 and
and NO  to persons unex-
      v    r
posed "training in different
area of the same school).
Comparability of the control
group and methodology to pre-
vent selection bias is not
given.  "Repeated examination"
suggests period prevalence and
not incidence data, but one
cannot be certain.  Although
sample size is sufficient, ap-
propriate point estimates are
not made (i.e., relative risk)
with confidence limits and
acute versus chronic effects
are not described.  Rates
based on exposure times would
be possible, but are not given.
                                Kujawska et al.
                                (1977)
                                B-10
                                                                                    Sinitsyna
                                                                                      (1965)
                                                                                       D-6
Giguz (1968)
B-6
                                                                  (continued)

-------
                                                          TABLE  V-l.   (concluded)
  Compound(s)
Concent ration(s)
  mg/m3 (ppm)
    Duration

NHs, unknown,
  avg.  exposure  time
  of 16.1 y
                 Population Group
      Description

Workers in an  Egyptian
ice factory.
                                   Controls
28
NH3,  unknown but
  probably very low
  to  moderate, avg.
  6.8 y of employ-
  ment
  Workers in a  frozen  food  19 M
  warehouse who routinely    1 F
  worked inside the
  freezer,  where inter-
  mittent NHs leaks  oc-
  curred.
      Description

Differences in lung  function
tests  found,  but perhaps
due to differences in  age
and body size between  the
2 groups.   Differences in
response to a chest  symp-
tomology questionnaire were
considered insignificant
after  consideration  of smok-
ing habits.
          Degree  of discomfort  ranged
          from  severe nausea and head-
          aches to mild  throat  and eye
          irritations.   No serious in-
          juries  sought.
                                                                                      Remarks
                                                                      Reference and
                                                                         Rating	
This study is a poor attempt  El-Sewefy and
at a noncurrent prospective   Awad
design.  Numbers are insuf-   (1971)
ficient for appropriate       C-6
stratifications (i.e., age,
smoking, habits, exposure
variables, etc.) in the anal-
ysis.  Either matching was
not performed or a breakdown
in age-matched groups occurred.
(use of average age by group
is not sufficient when small
numbers are involved.)  Con-
clusion of article is not
valid.  A lack of statistical
significance does not demon-
strate a lack of association
(when small numbers are in-
volved).  The relative risk is
1.4 (20% versus 14%), but num-
bers are small and confidence
limits are not given (see con-
clusion, pp. 309-310 of ar-
ticle).  This difference would
be likely to disappear with ap-
propriate stratification on age
and smoking habits.

Only interviews were done.    Hollett
No physical or lung function  (1977)
exams.  Descriptive study of  C-7
acute affects of NH3 tox-
icity, but there was a strong
possibility for interviewee
bias.  No precautions were
exercised to prevent this bias,
and no control group was used.

-------
                                      TABLE V-2.   HUMANS—STUDIES  OF  ACCIDENTAL EXPOSURES  TO  AMMONIA
Compound (s) and
Concent ration(s)
in mg/m3
Duration of
Exposure
Accident
Description(s)
No. of
Accident
Victims
Description
Reference
.ind
Rating
       NH3, unknown
Not given
Not given
          , unknown
Not given
Not given
oo
          > unknown
Not given
Not given
      NHs, unknown,  but
      high
< 1 min  to  a
few minutes
Vent stack overflowed
with pure liquid  ammonia,
dousing men 100 ft below
2            Two victims  with  moderate  intensity acute phase      Voisin et al.
             damage (burns  to  upper  respiratory tract without        (1970)
             apparent pulmonary  involvement).  One victim, at          B-ll
             the end of 2 y, had pulmonary  function values
             very close to  the theoretical  lower limits of normal,
             and normal blood  gases.  The other victim, followed
             for 1 y, had mixed  ventilation difficulty of medium
             severity, and  normal blood gases and exchanges.

2 M          Victims with medium clinical results in the acute    Voisin et al.
             phase (involvement  of the  upper respiratory tract).     (1970)
             After 1.5 y, one  victim had a  restrictive ventila-        B-ll
             tion problem of medium  severity, and normal arter-
             ial blood gases.  The other victim showed major
             mixed respiratory difficulties after one wk, and even
             1 y later had  significant ventilation difficulty
             with preponderant obstructive  disease, increased
             residual volume,  moderate  hypoxemia, and decline in
             the pulmonary  diffusing capacity of CO.

4 (at least  Victims with major  clinical results (parenchymatous  Voisin et al.
2 M)         effect is dominant,  pulmonary  edema extremely            (1970)
             acute) in the  acute phase.  One victim showed a            B-ll
             gradual deterioration of pulmonary functions over
             A y, the alteration of  blood gas exchanges, and
             chronic bronchitis.  A  second  victim showed respira-
             tory insufficiency  >l y after  exposure.  A third
             victim showed  ventilation problems of the mixed
             restrictive-obstructive type 1 y after exposure.
             There was pre-existing  anthracosilicosis.  The fourth
             victim, 1 y  after exposure, had great ventilation
             difficulty of  a mixed type with major obstructive
             involvement.

2 M          The victim with the  shorter exposure had dyspnea,    Walton
             chest pain,  blepharospasm, burning throat, exten-    (1973)
             sive blisters, tachycardia, and moist sounds,        B-ll
             both bases.  Lung functions improved for 2 y, but
             still below  normal  after 5 y.  The transfer factor
             is nearly normal.  The  more exposed victim lost con-
             sciousness,  and suffered dyspnea, chest pain,
             blepharospasm, burning  throat, blisters and sloughs
             of oral mucosa and  exposed skin, conjunctivitis, and
             bronchitis.  Later became a physical training tea-
             cher, with above  normal lung functions.
                                                                         (continued)

-------
                                                         TABLE V-2.   (continued)
Compound(s) and
Concent rat ion (s)
in mg/m3
Duration of
Exposure
Accident
Description(s)
No. of
Accident
Victims
Description
Reference
and
Ra t i ng
NHs, unknown,  but
high
NHs,  unknown,  but
high
                       <  1 min
                       Not given
NHs, unknown,  but       Not given
high
NHs, unknown,  but      Not  given
high
NHa, unknown,  but      <  30 rain
high
                                       Dismantling a valve on
                                       an ammonia high-pressure
                                       line.
                                       Doused with ammonia
                                       liquor from a 130 ft
                                       tower
                                                                  1  M
                                                                  2  M
                                       Compressor pump burst
                                       under pressure, releasing
                                       an.ammonia cloud.
                                       Metal fragment pierced a
                                       pipe of an ammonia con-
                                       denser in an occupied
                                       bomb-shelter.
                                                                  2  M
                                                                  47
                                       Car driving into a por-
                                       tion of exploding tank
                                       truck carrying anhydrous
                                       ammonia.
                                                                  1  F
                                                                  2  M
Experienced blepharospasm and bronchospasm.   Ven-     W.ilton
tilation tests normal  after 1 y,  but transfer        (1973)
factor still depressed after 5 y,  which could be      B-11
associated with smoking.

One victim experienced dyspnea, coughing up          Walton
frothy pink mucus, severe burns of the face and      (1973)
mouth, red, congested  and edematous fauces, no        B-ll
bronchospasm, and normal  chest radiograph.   Mixed
lung functions 5 y later.  The second victim,
possibly exposed longer,  experienced pain in throat
and eyes, pink frothy  sputum and burns of the face
and mouth, with clear  chest radiograph.  Progressive
improvement in ventilation, but consistent depression
of the transfer factor.  Both victims continued to
smoke.

One man died in the accident.  The other victim      Walton
suffered tightness of  chest, blepharospasm, blood-   (1973)
stained sputum, and loss  of voice.  Gradual im-      B-ll
provement to normal ventilation values and low
normal transfer factor after 5 y.

9/47:  Relatively "mild"  exposure.  Main features     Caplin
were acute pharyngitis and tracheitis.  Improved     (1941)
rapidly.                                              B-10

25/47:  "Moderate" exposure.  Main features were
acute bronchitis, cough with bloodstained sputum,
and exaggeration of the symptoms of the mild cases.
3/25 developed and died of pulmonary edema, 3/25
died of bronchopneumonia, 15/25 recovered completely.

11/47:  "Severe" exposure.  Pulmonary edema, slight
cyanosis, intense dyspnea, and cough with frothy
sputum.  7/11 had deterioration in their general conr
dition and died.  4/11 recovered.

Exposure to both liquid and gaseous ammonia.  Two     Close
victims had epithelial defects of the cornea         (1980)
bilaterally and full-thickness burns of the face      B-9
and mucous membranes of the upper airways and
particularly the larynx.   On follow-up (1 y or
2 mo), there were no significant pulmonary
sequelae with regard to activity restriction.
Third victim was exposed  longer,  had additional
injuries (burns of the entire airway and over-
whelming pulmonary edema), and eventually died.
                                                                    (continued)

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                                                          TABLE V-2.   (continued)
Compound(s) and
Concentration(s)
    in mg/m3

NHs, unknown, but
high
NHs. unknown,  but
"moderate"
NHs, unknown,  but
high
Duration of
  Exposure

> 30 min
5-10 min
< 30 min
NHsi  unknown,  but
high
< 1 min
   Accident
Description(s)

Drove into an ammonia
cloud from an explod-
ing tank truck.
In a car in the vicinity   3
of an exploding tank
truck containing anhydrous
ammonia.

Train derailment causing   2  F
a cloud of anhydrous
ammonia fumes.
No. of
Accident
Victims
                Spray from a safety re-
                lief valve on an anhy-
                drous ammonia nurse tank.
                                           1  M
                                Description

             First degree burns of the face,  eyes,  and exposed
             skin, and no upper airway obstruction, although
             some had greater than first degree burns.  Then
             gradual deterioration of pulmonary functions over
             2 to 6 mo,  followed by slight improvement with no
             subsequent change over 2 y.

             Few clinical findings: conjunctival irritation.
             Essentially no long-term pulmonary sequelae.
             One victim suffered convulsions,  burns of skin,
             soft palate and oropharynx,  corneal damage,  and
             respiratory distress.   One year later, had bi-
             lateral pneumonia and  acute  right heart failure.
             Two years later, had hypoxemia, decreased vital
             capacity, and respiratory pathology.

             Second victim had burns of the soft palate and
             oropharynx.  Two years later,  continued cough,
             shortness of breath, greenish  sputum,  and lung
             function studies indicative  of obstruction of the
             small airways.

             Facial burns, pulmonary edema, pneumonitis,  and
             inflammation and edema of the  upper airways.   No
             residual lung damage occurred.
Reference
    and
  Rating

Close (1980)
     B-9
Close (1980)
    B-9
                                                                                                             Kass et al.
                                                                                                               (1972)
                                                                                                                 B-9
                                                                                            Helmers  et  al.
                                                                                                 (1971)
                                                                                                   B-8
   ,  unknown
  1 min
   .  unknown
< 1 h
                Ruptured refrigerator
                tubing
                           1 F
Explosion in an ice  cream
factory due to the burst-
ing of a pipe conveying
ammonia gas.
                                           6  F
             Immediate dyspnea  and burning  eyes.   Hospitalized    Sestier et al.
             20 d later in respiratory distress.   Condition          (1969)
             degenerated,  suggestive  of subacute  bronchiolo-            B-8
             alveolitis,  complicated  by pneumomediastinum fol-
             lowed by coma.   One  year later,  still had  clinical
             symptoms of  chronic  bronchitis,  radiological signs
             of bronchiectasis, and lung functions indicative
             of obstructive  syndrome.

             All suffered  from  shock  and skin burns.  Some had    Slot  (1938)
             conjunctivitis,  tracheitis,  and  bloodstained vomi-         B-7
             tus probably  due to  the  pharynx.   Several  developed
             bronchitis, or  aggravated existing bronchitis.  3/6
             had some "nervous" symptoms: minor delirium,  migraine
             headaches, continued  anxiety,  or insomnia.   One vic-
             tim died,  with  acute  laryngotracheitis,  tracheo-
             bronchitis and  bronchopneumonia,  and  evidence of  tox-
             emia from the burns manifested by nephritis.
                                                                   (continued)

-------
                                                         TABLE V-2.   (concluded)
Compound (s) and
Concentration (s)
in rag/m3
Duration of
Exposure
Accident
Description(s)
No. of
Accident
Victims
Description
Reference
and
Rating
NH3,  unknown
Not given       Explosion of a tank  con-
                taining NHs gas,  in  a
                soda factory.
All suffered from burning eyes and pharynx,
dyspnea, cough,  and  some degree of difficulty in
swallowing.   Some had dizziness, violent headaches,
nausea, or inflammation of the digestive tract.
One developed pulmonary edema.  3/4 still had
slight respiratory insufficiency (possibly due to
obesity or smoking and drinking habits), otherwise
no sequelae.
Pernot et al.
   (1972)
     B-6

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                               BIBLIOGRAPHY*
3-007   ACGIH, American  Conference  of Governmental Industrial Hygienists
        Subcommittee on Threshold Limits.  1946.   Report of the Subcommittee
        on Threshold Limits.  In:  Proceedings of the Eighth Annual Meeting
        of the ACGIH.  Chicago, Illinois.  April  7-13.  pp. 54-57.

        D—.**  In 1946, the M.A.C.  for NH3 was 100 ppm.

3-208   ACGIH, American Conference of Governmental Industrial Hygenists TLV
        Airborne Contaminants  Committee.   1981.  TLVs Threshold Limit Val-
        ues  for  Chemical Substances and Physical Agents  in  the Workroom
        Environment with  Intended Changes  for 1981.  ACGIH.  Cincinnati,
        Ohio.

        D--.   The TLV  time-weighted-average  for  NH3 is 25 ppm  (18 mg/m3)
        and the short-term-exposure-limit TLV is  35 ppm (27 mg/m3).

3-220   AIHA, American Industrial Hygiene Association.  1978.  Hygienic Guide
        Series; Anhydrous Ammonia.  American Industrial Hygiene Association.
        Akron, Ohio.  5 pp.

        D—.   Brief review.

3-176   Anderson, D. P., C. W. Beard, and R.  P. Hanson.  1964.  The Adverse
        Effects of  Ammonia  on Chickens Including Resistance  to Infection
        with Newcastle Disease Virus.  Avian Dis.  8:369-379.

        B-12.  Four species were exposed to different levels of ammonia for
        varying lengths of time, up to 6 wk.   Pathological changes were seen,
        varying with time, NHs level, and species.  Little significant path-
        ology was seen in animals exposed to 20 ppm NHs or less for periods
        of less  than 6 wk.   Prior exposure to MS increased the number of
        chickens infected when  challenged with  Newcastle disease virus.

3-175   Anderson, D. P.,  C.  W. Beard, and R. P.  Hanson.  1966.  Influence
        of Poultry House Dust, Ammonia and Carbon Dioxide on the Resistance
        of Chickens  to Newcastle Disease Virus.   Avian Dis.   10:177-188.

        C-ll.  Groups of 20 chickens were exposed to dust alone, a combina-
        tion of dust, MS (30 ppm) and C02 (5,000 ppm), or a combination of
        the gases alone  for different time intervals, from 6  h  to  8 d. Ex-
        posures including NHa caused some loss of cilia in the upper trachea
*   MRI document acquisition numbers are given in the left margins.
**  MRI rating system is described on pages 11-13.
                                     73

-------
        and the turbinates.   Subsequent exposure to Newcastle disease virus,
        and no further air pollutant exposure, had no effect on mean death
        time or percent mortality.

3-177   Anderson, D. P.,  R.  R.  Wolfe,  F.  L.  Cherms, and W.  E. Roper.   1968.
        Influence of Dust and Ammonia  on the Development of Air Sac Lesions
        in Turkeys.  Am.  J.  Vet.  Res.   29:1049-1058.

        B-13.  About the best  of the  poultry/farm studies  reviewed.   Tur-
        keys exposed to  combinations  of  low or high dust and NHg for 2-10
        wk were  not significantly  affected with regard  to  mortality and
        feed conversion.  High concentrations of both components increased
        the incidence of air sac lesions and respiratory histopathological
        changes.   No experiments were  done with NHs alone.

3-109   Bagramyan,  S. B. , A.  S.  Pogosyan, E. A. Babayan, R. D. Ovanesyan,
        and S. M. Charyan.   1976.  Mutagennoe Deistvie Malykh Kontsentratsii
        Letuchikh  Veshchestv,  Vydelyayushchikhsya  iz Polikhloroprenovykh
        Lateksov LNT-1 i MKh, pri Sovmestnom Postuplenii ik v Organizm [Muta
        genic Action of Small Concentrations of Volatile Substances Emitted
        from Polychloroprene Latexes  LNT-1  and MKh During  Their Combined
        Uptake by the Animal].   Biol.  Zh. Arm.   29 (4): 98-99.

        D-2.  Albino rats exposed to a mixture of chloroprene (0.89 mg/m3) ,
        dodecylmercaptan (0.12 mg/m3), and NH3  (2.07 mg/m3)  for  1-120 days
        had increased  frequency  of  chromosomal rearrangements compared to
        controls, with a maximum at the end of the exposure period.  Eleven
        shoe factory workers occupationally exposed to a mixture of these
        compounds  (4-10 mg NHg/m3)  had a statistically significant increase
        in the frequency of chromosomal  aberrations in the lymphocytes of
        the peripheral blood.

3-178   Banister,  J. ,  G. Fegler,  and  C.  Hebb.   1949.  Initial Respiratory
        Responses  to the Intratracheal Inhalation of Phosgene or Ammonia.
        Quart. J. Exp.  Physiol.  35:233-250.
        C-10.  Sixteen  intact  dogs and 13 intact cats were exposed to
        (1/1,000 to 1/250, vol. /vol.) for less than 1 min, resulting in ac-
        celerated, shallower breathing.   Other respiratory details varied
        with  species.   Tests  were also done  on  rabbits,  vagotomized and
        sympathectomized cats and dogs, and isolated dog lungs.

3-110   Barrow, C. S.,  Y. Alarie,  and M.  F. Stock.   1978.  Sensory  Irrita-
        tion and Incapacitation Evoked by Thermal Decomposition Products of
        Polymers and Comparisons with Known Sensory Irritants.  Arch. Environ.
        Health.  33(2):79-88.

        C-10.  Negligible data  given for the single chemicals, considered
        as "standard irritants."  For each NR^ concentration four mice were
        exposed for 30 min,  decreases in respiratory rates monitored, and a
        dose-response curve  constructed.   From this curve, the RDso  (50%
        decrease in respiratory rate) for ammonia was 303 ppra.


                                     74

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3-111   Battista Raffi, G. , D. Cascella, F. Morisi, and R. Caudarella.  1979.
        Correlazione tra Inquinamento Gassoso Ambientale e Precocita di Com-
        parsa della Pneumoconiosi nei Fonditori di Ghisa [Correlation Between
        Atmospheric Gaseous Pollutants and the Appearance of Pneumoconiosis
        in Cast Iron Foundries].  Ingegneria. No. 9-10:270-272.
        D--.  Morbidity from exposure to Si02, NHa (3-15 ppm) ,  CO, S02, phenol,
        and HCHO  is  linked  to number of years' exposure rather than by job
        even though  relative  concentrations  of the compounds are given by
        job.  The  numbers  of  workers (total 185) by job,  however, are not
        given.

3-010   Bhown,  A. S., B. B. Maitrya, and M. Bhown.  1971.   Ammonia Retention
        by Smokers:  A Comparative Study.   Indian J. Med.  Res.   59:1296-1299.

        D-9.  Ammonia  retention  from cigarette smoke was studied in human
        experiments.   Too  complex a mixture  to  be useful for our task.

3-013   Bittersohl, G.  1968.   Gesundheitsscha'den durch Ammoniak [Illnesses
        from Ammonia] .  Z. Gesamte Hyg.  14:803-806.

        C--.  Review from the point of view of exposure of the agricultural
        worker during application of fertilizer
3-012   Bittersohl,  G.    1971a.   Epidemiologische  Untersuchungen uber
        Krebserkrankungen  in der  Chemischen Industrie  [Epidemiological
        Study  of  Cancer  Morbidity  in  the  Chemical  Industry].   Arch.
        Geschwulstforsch.  38:198-209.

        D-8.  An  epidemiological  study  of a chemical  factory with 30,000
        employees exposed to asbestos found the most frequent occurrence of
        malignant  neoplasms  in those operations  also  involving NH3.  Work-
        room air exceeded the M.A.C. of 25 mg NHs/m3 by 2-3 times.  No data
        on  specific  chemicals or  industrial  sections  given.  Probably  con-
        founding due to other compounds and smoking.

3-011   Bittersohl, G.  1971b.  Epidemiologic Study on Cancer of Workers in
        a Chemical Plant.   Presented at the XVI International Congress on
        Occupational Health, Tokyo,  1969.  Toyko, Japanese Industrial Safety
        Association,   pp. 250-252.

        C-6.  Apparently  the same study as Bittersohl (1971a) [3-012].  A
        better rating was given because of the clearer distinctions between
        the NH3 group and others.   No asbestos exposure discussed.  Workers
        in ammonia production plants (50-75 mg/m3) had higher rates of cancer
        (lung, stomach, lymphatic tissue, urinary tract) than other workers
        in  the  chemical  industry.   Both groups of workers exceeded cancer
        rates for the general population of the GDR (especially respiratory
        and digestive systems  in  men, and breast, genitals, and lymphatic
        system for women).   Possible exposure to  other factors wasn't  men-
        tioned and apparently age-adjusted rates were not used.
                                     75

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3-015   Boyd,  E.  M. ,  M.  L.  MacLachlan,  and W.  F.  Perry.   1944.   Experimental
        Ammonia Gas Poisoning in  Rabbits  and  Cats.   J.  Ind.  Hyg.  Toxicol.
        26:29-34.

        C-8.  Two to seven cats and 11-17 rabbits were exposed to 7,000 mg
        NHs/m3 (a very high level, in the  LDso range) for 1 h,  then followed
        immediately or in the second day by analysis of  the respiratory tract.
        There were increases in:   output of tracheal tract fluid,  iron con-
        tent  (especially tracheal), blood hemoglobin 24 h after gassing,
        and plasma lipids involving the cholesterol  fraction.  Respiratory
        tract water and  chloride  content  and  serum  chloride content were
        unaffected.

3-182   Broderson, J. R. , J.  R.  Lindsey,  and  J.  E.  Crawford.   1976.   Role
        of Environmental Ammonia  in Respiratory Mycoplasmosis of Rats.   Am.
        J. Path.   85(1):115-130.

        B-12.   Doses used were rather high (150-250  ppm) , but the study was
        well done.  The "controls" were exposed to ~ 10  ppm,  apparently con-
        sidered a no-effect dose  by the authors.

3-018   Caplin, M.  1941.  Ammonia-Gas  Poisoning.   Forty-seven Cases in a
        London Shelter.   Lancet.   2:95-96.

        B-10.   Gaseous ammonia was released in an occupied bomb shelter when
        a flying metal fragment pierced a  pipe of an ammonia condenser.  No
        quantitative exposure data.  Paper  does  a good  job of describing
        symptoms.  Note the reversibility  of the mild cases.   Deaths following
        moderate exposures were due to bronchopneumonia;  antibiotics would
        have helped.

3-221   Caveny, D. D. ,  C.  L. Quarles,  and G.  A.  Greathouse.   1981.  Atmo-
        spheric  Ammonia  and Broiler Cockerel Performance.  Poult.  Sci.
        60(3):513-516.

        C-13.  Exposure  of chickens to 25 and/or 50  ppm  NH3  for 28 or  49 d
        had no effect on avg. body wts . , number of air sac lesions, or paired-
        lung  and bursa  of Fabricius wts.  Feed efficiencies were  inversely
        related  to  ambient  air  levels  of  NHs and the length of exposure.
3-179   Charles, D. R. ,  and C.  G. Payne.  1966a.  The Influence of Graded
        Levels of Atmospheric Ammonia on Chickens.  I.  Effects on Respira-
        tion and on the Performance of Broilers and Replacement Growing Stock.
        Br. Poul. Sci.  7:177-187.

        B-12.  Chickens exposed to 50-100 ppm NH3 for 19-56 days showed de-
        creased food consumption, and decreased growth rate and respiration
        rate at the higher NHs concentration.

3-180   Charles, D. R. ,  and C.  G. Payne.  1966b.  The Influence of Graded
        Levels of Atmospheric Ammonia on Chickens.  II.  Effects on the Per-
        formance of Laying Hens.  Br. Poul. Sci.  7:189-198.


                                     76

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        C-ll.   Groups of 27  or 36 chickens were exposed to 50 or 100 ppm
        MS for 10  or  22  weeks.  At the higher concentration,  egg produc-
        tion,  food intake,  and live-weight gain were decreased,  with no re-
        covery of production  after  exposure  stopped.   Trials run at high
        temperatures had more severe effects .   A supplemented diet was  able
        to overcome  the deleterious effects  of NHa on  egg  production.

3-113   Close, L.  G. , F. I. Catlin,  and A. M.  Conn.   1980.   Acute and Chronic
        Effects of Ammonia Burns on the Respiratory Tract.   Arch. Otolaryngol.
        106(3):151-158.
        B-9.  Twelve survivors of an accidental NHs spill fell into two groups
        (short exposure to high concentrations, and longer exposure to lower
        concentrations), each with different medical problems.

3-114   Cole, T. J., J. E. Cotes, G. R. Johnson, H. DeV.  Martin,  J. W. Reed,
        and M. J. Saunders.  1977.  Ventilation, Cardiac  Frequency and Pat-
        tern of Breathing During Exercise in Men Exposed  to 0-Chlorobenzyl-
        idene Malononitrile (CS) and Ammonia Gas in Low Concentrations.  Q.
        J. Exp. Physiol. Cogn. Med. Sci.  62(4) :34l-352.

        B-ll.  Ammonia  was  used as a "standard irritant" in an experiment
        exposing 12 or 18 men to fairly high levels, 71-235 mg/m3, for about
        20 min.  During submaximal  exercise, ventilation minute volume was
        reduced about 6% by apparently different mechanisms at low and high
        doses.  No effect was seen on cardiac frequency.

3-020   Cook, W. A.   1945.  Maximum Allowable  Concentrations  of Industrial
        Atmospheric Contaminants.  Ind. Med.  14:936-946.

        D--.  List of M.A.C.'s for 1945.  That for NH3 was 100 ppm.

3-021   Coon, R. A., R. A. Jones, L. J. Jenkins, Jr., and J. Siegel.  1970.
        Animal Inhalation Studies on Ammonia, Ethylene Glycol, Formaldehyde,
        Dimethylamine , and Ethanol.  Toxicol. Appl. Pharmacol.  16:646-655.

        B-12.  Five species were repeatedly or chronically exposed to 40-770
        mg NHs/m3, with varied effects.

3-022   Couturier, Y. ,  M. Barbotin, P.  Bobin,  and  J.-P. Derrien.   1971.  A
        propos de  trois cas de poumon toxique par vapeurs d'ammoniaque et
        d'hydrogene  sulfure [Three Cases of Toxic  Lung  from  Ammonia and
        Hydrogen Sulfide Vapors].   Bull. Soc. Med. Afr. Noire Lang.  Fr.
        16:250-252.

        C-5.  Short-term  exposure  to  wastewater,  both the  liquid  and  the
        toxic gas mixture, caused the rapid death of one  sailor,  and cardiac
        and respiratory problems with eventual recovery in two other sailors.

3-023   Cralley, L.  V.   1942.   The Effect of Irritant Gases Upon the Rate
        of Ciliary Activity.  J. Ind.  Hyg. Toxicol.  24:193-198.
                                     77

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        D-6.  Exposure to  600  ppm MS for 10 rain caused the cessation of
        ciliary activity without recovery in excised rabbit tracheal tissue.

3-024   Curtis, S. E.   1972.   Air Environment and Animal Performance.   J.
        Anim. Sci.  35:628-634.

        D--.  A review of the literature and a discussion of the problem of
        studying the effects of all types of airborne pollutants on live-
        stock.

3-025   Curtis, S. E.,  C.  R.  Anderson, J. Simon, A. H. Jensen,  D.  L.  Day,
        and K. W. Kelley.  1975.  Effects of Aerial Ammonia, Hydrogen Sul-
        fide  and  Swine-House Dust on Rate of Gain  and Respiratory-Tract
        Structure in Swine.  J. Anim. Sci.  41:735-739.

        B-12.  Pigs were exposed to NHa at 50 or 75 ppm, alone  or with dust
        or hydrogen sulfide.   Useful interaction study.

3-027   Dalhamn,  T.  1956.   Mucous Flow and Ciliary Activity in the Trachea
        of Healthy Rats and Rats Exposed to Respiratory Irritant Gases (S02,
        H3N, HCHO).  VIII.  The Reaction of the Tracheal Ciliary Activity
        to Single Exposure to Respiratory Irritant Gases and Studies of the
        pH.  Acta Physiol.  Scand.  36(Suppl.  123):93-105.

        C-6.  Groups of  two  or three rats were exposed to 3, 6.5,  10, 20,
        45, or 90 ppm NH3 until ciliary activity stopped.  This occurred at
        8 min  and 5  sec  for the  lowest and highest  concentrations,  respec-
        tively, with recovery  of ciliary movement within 30 s  after expo-
        sure stopped.

3-026   Dalhamn,  T.  1963.  Effect  of Ammonia Alone and  Combined with Car-
        bon Particles on Ciliary Activity in the Rabbit In Vivo, with Studies
        of  the Absorption  Capacity  of  the Nasal  Cavity.  Air Water  Pollut.
        7:531-539.

        D-7.  Groups of  10 extirpated  rabbit tracheas  were  exposed  to high
        levels of NH3  (75-2,000  ppm) for  45 min, alone or with  carbon par-
        ticles.  100 ppm was  the threshold MS  level  to cause  slowing of
        ciliary beating, and there was only a slight possible synergism be-
        tween NH3 and carbon particles.  There was considerable NH3 absorp-
        tion in the nasal cavity.

3-028   Dalhamn,  T. , and L.  Reid.  1967.  Ciliary Activity and Histologic
        Observations in  the Trachea After Exposure to  Ammonia  and  Carbon
        Particles.  In:  Inhaled Particles  and Vapors II.  Proceedings of
        an  International Symposium.  1965.  C.  N.  Davies,  ed.   Pergamon
        Press.  New York, New York.  pp. 299-306.

        C-7.  Two  groups of  10 rats were exposed to 100 ppm NH3, alone or
        in  combination with 7.0 mg carbon/m3 in repeated doses for 60 days.
                                     78

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        On day 60  only  the group exposed to both NHs and carbon showed a
        decreased rate of  tracheal ciliary beating, and all groups had in-
        creased mucosal damage although the combination group had the most
        severe damage.

3-029   Dalhamn,  T.,  and J. Sjoholm.  1963.  Studies of S02, N02, and NH3:
        Effect on Ciliary Activity in the Rabbit Trachea of Single  In Vitro
        Exposure and Resorption in Rabbit Nasal Cavity.   Acta  Physiol.  Scand.
        58:287-291.

        D-6.  Single  excised  rabbit  tracheas  were exposed to  a  concentra-
        tion of NH3  in  the range of 200-1,000 mg/L for  20 min.   For 5 min
        exposure, 500-1,000 mg/L NH3 was  needed to cause  cessation of
        ciliary activity.   There was 93-96% resorption of 2,000  mg/L NH3 in
        the rabbit nasal cavity.

3-116   Dautov, F. F.  1977.   K Gigienicheskoi Kharakteristike Uslovii Truda
        v Proizvodstve Organicheskikh Perekisei  [Hygienic Characteristics
        of the Working Conditions in the Production of Organic Peroxides].
        Kazan. Med. Zh.   58(3):89-91.

        D-5.  Work  atmosphere polluted by many  compounds,  including NH3
        (1-15 mg/m3).  Workers suffered from grippe,  angina, acute  respira-
        tory disease, and pneumonia.

3-117   Dautov, F. F.  1978.   Gigienicheskaya Otsenka Zagryazneniya Vozdukha
        Benz(a)pirenom  i  Toksicheskimi  Veshchestvami  v  Proizvodstvakh
        Polietilena Vysokogo Davleniya i Organicheskikh Perekisei [Hygienic
        Evaluation of Air  Pollution  by Benz[a]pyrene and Toxic  Substances
        in the Production of High Pressure Polyethylene  and Organic Peroxides]
        Gig. Tr.  Prof. Zabol.   No. 2:1-4.

        D--.  NH3 was one of numerous compounds found in the air during the
        title processes at or below the maximum allowable  concentration.
        No health  effects  information  is  given in this  article.  Hygienic
        measures are  described for lowering the benzpyrene  concentrations.

3-183   Diesch, S.   1974.  Potential Occupational Health Hazards of Live-
        stock Producers Working in Animal Confinement Units.  In:  Proceed-
        ings of the Society for Occupational and Environmental Health:   Con-
        ference on Agricultural Health and Safety, University of Iowa,  Iowa
        City, Iowa.  Sept. 4-5, 1974.  Society for Occupational  and Environ-
        mental Health.  New York, New York.   141-152.

        D--.  Review  of the possible hazards due to toxic  gases, and the
        survival of pathogens  in animal manure.

3-118   Dodd, K. T. ,  and  D.  R. Gross.   1980.   Ammonia Inhalation Toxicity
        in Cats:   A  Study of Acute  and Chronic  Respiratory Dysfunction.
        Arch. Environ. Health.  35(1):6-14.
                                     79

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        B-ll.   A group of 20 cats was exposed to 1,000 ppm NHs for 10 rain.
        There was good correlation between the pulmonary function tests  (7)
        and lung histological samples taken at intervals up to 35 days after
        exposure.  The acute effects of the initial insult were followed by
        indications of chronic respiratory dysfunction.   Good pathophysiol-
        ogy for high doses.

3-030   Doig,  P. A.,  and  R.  A.  Willoughby.  1971.  Response  of  Swine to
        Atmospheric Ammonia  and Organic Dust.  J.  Am.  Vet.  Med. Assoc.
        159:1353-1361.

        B-ll.   Pigs were  exposed  at the fairly high level of  100 ppm for
        1-6 weeks,  alone  and in combination with  dust.   Histopathologic
        changes were seen in the nasal and tracheal epithelium after  2 weeks.
        Swine a  very  useful analog  for human skin and digestive  system and
        adequate for the respiratory system.  A nice study, with the  fairly
        high  levels  (~ 100  ppm) and  few  numbers being  the only limits.

3-031   Doll,  R., M. P. Vessey,  R.  W. R.  Beasley,  A. R.  Buckley,  E.  C. Fear,
        R. E. W. Fisher,  E.  J.  Gammon, W. Gunn, G. 0.  Hughes, K. Lee, and
        B. Norman-Smith.   1973.   Mortality of Gasworkers — Final Report of a
        Prospective Study.  Br.  J.  Ind. Med.  29:394-406.

        D-ll.   Excess mortality from bronchitis was found in workers  exposed
        to NHs,  benzene,  S, tar, etc., in  "retort house."  Too complicated
        a mixture for the purposes of this task.

3-119   Donham, K.  J. , M.  Rubino,  T. D. Thedell, and J.  Kammermeyer.   1977.
        Potential Health  Hazards to Agricultural Workers  in Swine Confine-
        ment Buildings.  J.  Occup.  Med.  19(6) : 383-387 .
        C-6.  NHs was  one  of four gases measured in 13 swine confinement
        buildings, exceeding the TLV in two units in the summer, and meeting
        or  exceeding the TLV in 12 units in the winter.  The 11 full-time
        and 10 part-time employees and 35 veterinarians surveyed complained
        of  adverse respiratory  symptoms, and a physical examination of two
        workers did not reveal the pathogenesis of their symptoms.

3-120   Drummond, J. G. , S.  E.  Curtis, and J.  Simon.   1978.   Effects of
        Atmospheric Ammonia  on  Pulmonary  Bacterial  Clearance in the Young
        Pig.  Am. J.  Vet. Res.  39(2) :211-212.

        B-10.  Young pigs  were  exposed to an aerosol  of nonpathogenic E.
        coli, then retained for a 2-h clearance period in 50 or 75 ppm NHa.
        Viable bacteria  counts  in the lungs were greater  in the  ammonia-
        exposed groups than in the controls.

3-033   El-Sewefy, A.  Z.,  and S.  Awad.  1971.   Chronic Bronchitis  in an
        Egyptian Ice Factory.  J.  Egypt. Med.  Assoc.  54:304-310.

        C-6.  The paper reports on a poorly designed epidemiological study.
        There were no quantitative exposure data.
                                     80

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3-207   Ernst, R. A.  1968.  The Effect of Ammonia on Poultry.   Feedstuffs.
        40(32):40.

        D--.  A very short review, with no references.

3-174   Fairhall, L. T.  1949.  Industrial Toxicology.  Williams and Wilkins.
        Baltimore, Maryland,  pp. 13-14.

        D — .  A short review of the properties, sources and uses, toxicity,
        and analysis of
3-122   Ferguson, W. S., W. C. Koch, L. B. Webster, and J. R. Gould.  1977.
        Human Physiological Response and  Adaptation to Ammonia i  J. Occup.
        Med.  19(5):319-326.

        A-ll.  Six  unacclimated volunteers were exposed to 25, 50,  and  100
        ppm NHg for 6 h/d over 6 weeks in an industrial environment.  After
        2-3 weeks acclimation, there was  inurement to eye, nose and throat
        irritation, no impairment of ability to perform job duties, no change
        in vital functions measured, and toleration of occasional brief ex-
        posures to 200 ppm.

3-034   Fieldner, A.  C.,  S.  H.  Katz,  and S.  P.  Kinney.   1921.  Ammonia.
        In:  Gas Masks  for Gases  Met  in  Fighting Fires.  Bureau of Mines
        Technical Paper  248.  U.S.  Government  Printing Office, Washington.,
        B.C.  pp. 13-14.
        D--.  A very  short review of the hazards  of NHs,  and minor  first
        aid  after  exposure, for  firemen.   Not  relevant  to this study.

3-186   Flury, F., and F. Zernik.  1931.  Ammoniak [Ammonia].  In:  Schadliche
        Gase. Da'mpfe, Nebel, Rauch-und  Staubarten [Noxious Gases — Vapors,
        Mist, Smoke, and Dust Particles],  Julius Springer, Berlin, Germany.
        pp.  150-154.

        B--.  Review  of  acute  and chronic animal  and human MS  exposure.

3-036   Gadaskina,  I.  D.  1972.  Ammonia  (NH3),  Ammonium ((NH4) ).   In:
        Encyclopedia  of  Occupational Health and  Safety,  Vol.  1.  Inter-
        national Labour Office, McGraw-Hill.  New York, New York.  pp. 97-98.

        D — .  Short review of  occurrence,  production, uses, hazards, and
        safety measures.                    l

3-123   Gallagher, J. T.,  R.  L. Hall, P. K. Jeffery, R. J. Phipps, and P.
        S. Richardson.  1978.  The Nature and Origin of Tracheal Secretions
        Released in Response to Pilocarpine and Ammonia.  J. Physiol. (London).
        275:36P-37P.

        D-7.  Scant methodology given,  referring to other  papers.   Short
        exposure to 2,000 ppm NH3 increased the output of 3H-labeled mucus,
        and  caused  the  discharge of mucus from  glands, goblet cells, and
        the  release of a distinct glycoprotein from the surface of ciliated
        cells .
                                     81

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3-181   Caspar,  E.,  P.  H.  Sammelwitz,  C.  R.  Richards,  and M.  S.  Cover.   1961;
        The Influence of Atmospheric  Ammonia  on Blood Hemoglobin Levels.
        Am. Soc. Anim.  Science N.  Atlantic Section Proc.   3:68-74.

        C-9.  Exposure of  chickens  to 7.4,  23, or 45  ppm NHs for 12 wk
        caused changes in  rate of hemoglobin formation only at the highest
        concentration.   That  level  also  caused  keratoconjunctivitis  and
        blindness.

3-037   Gaume, J. G. , P.  Bartek,  and J.  H. Rostami.  1971.  Experimental
        Results of Time of Useful  Function (TUF)  After Exposure  to  Mixtures
        of Serious Contaminants.   Aerosp. Med.   42:987-990.

        C-8.  Mice were exposed to gas mixtures and timed until  collapse on
        an exercise wheel, which occurred within minutes.  Useful interaction
        study, but high concentrations  (0.25-1.5% NHs) were tested and no
        straight NHs testing was done.

3-038   Giguz, T. L.   1968.   Effect of Low Concentrations of Ammonia and
        Nitrogen Oxides on Adolescents Undergoing Vocational Training  in
        the Chemical Industry.  Hyg. Sanit.   33(7-9):431-434.

        B-6.  Occupational  exposure of adolescents to both ammonia and  ni-
        trogen oxides at  concentrations  lower  than the  maximum allowable
        (e.g., 20 rag NH3/m3)  caused definite changes in  fat metabolism  and
        protein metabolism  and caused a  higher incidence of upper respira-
        tory tract diseases.  Any effects due to  NHs are confounded by  the
        presence of NO .

3-040   Golyakova, L. P.   1971.   Present-day  State of Industrial Hygiene
        Problems in Hydrometallurgical Production of Tungsten and Molybdenum
        Salts and Oxides.   PB 254580T, National Technical Information Ser-
        vice, U.S. Department of  Commerce,  Springfield, Virginia.   10 pp.

        D-6.  Dust,  NHs, H2S, and HC1 were  encountered.   The most frequent
        NHs concentration in working areas was in the range of tens and hun-
        dreds of milligrams per cubic meter.  No real exposure data, little
        toxicity data.

3-041   Haggard, H.  W.   1924.  Action of Irritant Gases Upon the Respira-
        tory Tract.  J. Ind. Hyg.   5:390-398.

        D—.  A description of mechanisms.  Obsolete.

3-128   Hatton,  D.  V.,  C.  S.  Leach,  A.  L.  Beaudet, R.  0.  Dillman,  and
        N. Di Ferrante.  1979.  Collagen Breakdown and Ammonia  Inhalation.
        Arch. Environ. Health.  34(2):83-87.

        C-10.  Three young boys and one female (17-y-old), accidentally ex-
        posed to  concentrated ammonia vapors,  had increased urinary meta-
        bolites  of hydroxylysine,  compared  to two other normal  children.
                                     82

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        This indicates considerable  collagen  degradation,  perhaps related
        to the  pulmonary and upper  respiratory  lesions  and inflammation
        observed on clinical examination.

3-042   Heifer, U.  1970.   Kasuistischer  Beitrag zur akuten,  letalen,  in-
        halatorischen Ammoniakvergiftung  [Casuistical Report  on an Acute,
        Lethal, Inhalation Poisoning by Ammonia].  Lebensversicherungsmedizin.
        22:60-62.

        C-8.  A 30-year-old office worker was accidentally exposed to a high
        concentration of NH3  fumes  after  losing consciousness following a
        thrombosis.  Death  was due to the ensuing glottal,  epiglottal, and
        hemorrhagic lung edema.   There was also toxic hemorrhagic liver cell
        necrosis.

3-043   Helmers, S., F.  H.  Top,  Sr., and L. W. Knapp, Jr.   1971.  Ammonia
        Injuries in Agriculture.   J.  Iowa Med. Soc.   61:271-280.

        B-8.  Case reports of exposures to very high NH3levels.

3-044   Henderson, Y., and H. W.  Haggard.   1943.  Noxious Gases  and the Prin-
        ciples of  Respiration Influencing Their  Action.  2nd ed.  Reinhold
        Publishing Corporation,  New York,  New York.   pp.  125-126.

        D--.  A  short  review of  properties, sources, and health effects.

3-129   Herrman, G., and J. Viehrig.   1979.   Irritative Atemwegserkrankungen
        durch Ammoniak und Schwefelsaureaerosole in einer Kuoxamseidespinnerei
        [Irritative Respiratory Tract Diseases from Ammonia and Sulfuric
        Acid Aerosols  in a Cuprammonium Rayon Spinning Mill].  Z.  Gesamte
        Hyg.  25(8):581-584.

        A-9.  Lung  functions  of the  exposed workers were impaired compared
        to control  group of workers.  Some consideration of possible com-
        pounding factors, such as sex and smoking habits.

3-130   Hilado, C.  J., H.  J.  Gumming, A. M. Machado, C. J. Casey, and A.
        Furst.  1978.   Effect of Individual Gaseous Toxicants on Mice.   Proc.
        West. Pharmacol.  Soc.  21:159-160.

        D-8.  Groups of four male mice were used to determine a  30-min LCso
        for NH3 of 21,430 ppm.

3-131   Hollett, B. A.  1977.  Health Hazard Evaluation/Toxicity Determina-
        tion Report 76-91-371, Safeway  Stores, Inc. Distribution Center,
        Landover, Maryland.  PB-270859,  National Technical Information Ser-
        vice, U.S.  Department of  Commerce,  Springfield,  Virginia.   12 pp.

        C-7.  Evidence that humans can stand intermittent,  moderate exposure
        to NH3 with no obvious  aftereffects.   NH3 concentrations from air
        samples taken considered invalid,  so precise level of exposure unknown.
                                     83

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3-045   Horvath,  A. A.   1924/1925.   The  Action of Ammonia Upon the Lungs.
        Proc.  Soc.  Exp.  Biol.  Med.   22:199-200.

        D-6.   A much less detailed report of the same experiment described
        in Horvath (1926) [3-046].

3-046   Horvath,  A. A.   1926.   The  Action of Ammonia Upon the Lungs (Part
        I).  Jap.  Med.  World.   6:17-29.

        C-7.   A single rabbit or guinea pig was exposed to an ammonia con-
        centration in the range of  1,200-15,200 ppm for 4-53 days.  There
        were no macroscopic  changes  in the respiratory organs of guinea pigs
        exposed to the lower level,  both species died at the higher concen-
        tration,  and there were pathological findings in both species exposed
        to the intermediate  concentrations .

1-0172  ILO.   1970.  Permissible Levels of Toxic Substances in the Working
        Environment.  Occupational Safety and Health Series 20, International
        Labour Office, Geneva, Switzerland,   pp. 194-198.

        C — .   Maximum Acceptable Concentrations in Czechoslovakia.

                       Normal MAC     Short, Single Exposure MAC
                        (mg/m3)       _ (mg/m3) _

        Acrolein           0.5                    1.0
        NH3               40                     80
        HCHO               2                      5
        HCN                3                     15
        MeOH             100                    500
        H2S               30                      -

3-104   ILO/WHO,  International  Labour Office/World  Health Organization.
        1969.   Permissible Levels of Occupational Exposure to Airborne Toxic
        Substances.  Sixth Report of the Joint ILO/WHO Committee.  WHO Tech-
        nical Report  Series No. 415, World  Health Organization, Geneva,
        Switzerland.  16 pp.

        D — .  Discussion  of the general principles and problems in recom-
        mending international  limits on  occupational  exposure.   The  recom-
        mended "safe concentration zone" for MS was 20-35 mg/m3.
3-047   ILO/WHO,  International  Labour Office/World  Health Organization.
        1970.   Permissible Levels  of Toxic Substances  in the Working
        Environment.  In:   Sixth  Session of the  Joint  ILO/WHO  Committee  on
        Occupational Health.  June 4-10,  1968.  International Labour Office.
        Geneva, Switzerland,  pp.  13, 194, 199, 212,  217,  222, 229,  242,
        244, 253, 263-264, 267-268, 276,  290, 329-330, 345.

        D — .  A  compilation of  various national M.A.C.'s  for  the working
        environment, those for NH3 ranging  from 20 to 70 mg/m3.  Variations
        between states in the United States included.
                                     84

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3-132   Ivanov, N. G.  1978.  Metodicheskie Podkhody k Opredeleniyu Poroga
        Razdrazhayushchego Deistviya Promyshlennykh  Yadov [Methodological
        Approaches to Determining the Threshold of the Irritating Action of
        Industrial Poisons].   Gig. Tr.  Prof.  Zabol.   No.  2:26-30.

        C-7.   The threshold  of  irritating action for 4-h NHa exposure of
        white rats was 215 +8.4 mg/m3.  Several indexes  were used,  includ-
        ing respiratory frequency, acuity of sense of smell,  and intensified
        cell migration to the surface of the mucosa of the upper respiratory
        tract and lungs.

3-133   Jedrychowski, W., K.  Prochowska, J. Garlinska, and J. Bruzgielewicz.
        1979.  Wystepowanie Przewjektych Nieswostych Chorob Ukjadu Oddechowego
        Wsrod Pracownikiv  Zak^adu Zywic Winylowych [Occurrence of Chronic
        Nonspecific Diseases of the Respiratory Tract in Workers of a Vinyl
        Resin Plant].  Przegl. Lek.  36(9):679-682.

        D-7.   Workers were examined, from different departments with different
        atmospheres.  One  group  may have been more exposed  to NHs (0.42-
        13.39 mg/m3), along with other compounds, and had significantly higher
        incidence of chronic bronchitis and lower FEVj values.

3-212   Kachnyi, G.  G., and  V. G.  Vinogradov.   1980.  Sostoyanie Slizistoi
        Obolochki Verkhnikh  Dykhatel'nyk'n Putei u  Tkachikh i Rabochikh
        Karasil'no-Karbonizatsionnogo  Tsekha  [State  of Upper Respiratory
        Tract Mucosa  in Weavers  and Workers in  the Textile Dyeing and Car-
        bonizing Departments] .  Zh. Ushn., Nos. Gorl. Bolezn.  No. 3:35-38.

        D—.   Workers who  dyed  and cleaned wool by carbonization were ex-
        posed to vapors of 3.0-5.0 mg  CH3C02H/m3, 0.5-1.0 mg H2S04/m3, 10-
        20 mg NH3/m3, 2-6.0 mg dust/m3, and 0.06-0.08% C02.

3-134   Kane, L. E., C. S. Barrow, and Y. Alarie.  1979.   A Short-Term Test
        to Predict Acceptable Levels of Exposure  to Airborne Sensory Irri-
        tants.  Am. Ind.  Hyg. Assoc. J.  40(3):207-229.

        C-6.   A  discussion of the use of the short-term test described in
        Barrrow et al.  (1978) [3-110]  in proposing threshold limit values,
        short-term exposure limits, etc.

3-052   Kass, I., N. Zamel, C. A. Dobry, and M. Holzer.  1972.  Bronchiectasis
        Following Ammonia  Burns  of the Respiratory Tract.  A Review of Two
        Cases.  Chest.  62:282-285.

        B-9.   High  dose  symptoms;  actual  exposure unknown,  but extreme.

3-053   Kazasov, P.  L.  Balabayeva,  G. Petrova,  and  M.  Mikhov.  1971.
        Prouchvane  Zamyrsyavaneto  na  Atmosferiya Vyzdukh v Raiona na
        Azotnotoroviya Zavod Krai  Stara  Zagora i Vliyanieto  mu Vyrkhu
        Zdraveto na Haselenieto  [Study of Air Pollution Around the Nitrogen
        Fertilizer Plant Near Stara Zagora and Its Effects on the Health of
        the Population].   Khig.  Zdraveopa.  14:46-56 (Bui).


                                     85

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        D-4.   The atmosphere in the region around a nitrogen fertilizer plant
        was polluted with  several  measured compounds, including NHs (some
        areas exceeding the M.A.C.  in 1968 and 1969).   A study of the popu-
        lation indicated several possible  changes in  the blood and immuno-
        biological states.

3-135   Kent, P. W. , and J. G. Widdicombe.  1977.  Neurophysiological Con-
        trol of Glycoprotein Secretion in the Tracheal Epithelium.   Biochem.
        Soc.  Trans.  5(2) :4U-417.

        D-7.   The  trachea  of  an anaesthetized cat was labeled with 3H and
        35S medium, followed  by  exposure to NHs (1:100).   The labeled se-
        creted mucus obtained afterwards was released from goblet cells and
        had a low sulfate and high sialic acid content.

3-048   Keplinger, M.  L. , K. J. Schadeberg, J. W. Goode, and J. C.  Calandra.
        1973.   Irritation  Threshold Evaluation  Study with Ammonia.   In:
        Report to  International  Institute  of Ammonia Refrigeration.  In-
        dustrial Bio-Test  Laboratories,  Inc.  Northbrook, Illinois.   13 pp.

        A- 12.  Subjective  evaluation  of the respiratory irritation due to
        acute exposure  of  human  adults to low levels of NHs (32-134 ppm) .
5-367   Kettner, H.  1978.  Indoor Contamination by Chemical Substances and
        Their Hygienic Significance.  In:  Org. Verunreinig. Umwelt:  Erkennen,
        Bewerten, Vermidern, K. Aurand, V. Haesselbarth, E. Lahmann, G.Muller,
        and W.  Niemitz,  eds.   Erich Schmidt Verlag.  Berlin, Germany,  pp.
        448-453 (Ger.).

        C--.   Maximum  allowable indoor  air  concentrations in the  USSR:

        Acrolein            0.1 mg/m3
        NH3                 0.2 mg/m3
        HCN                 0.002 mg/m3
        HCHO                0.01 mg/m3
        MeOH                0.5 mg/m3

3-136   Kirkov, V.  1977.  Kyrkhu Nevro-Vegetativnata Reaktivnost na Rabotnitsi
        ot Amonyachnoto Proizvodstvo [Neuroautonomic Response of Workers in
        the Ammonia Industry].  Suvrem. Med.   28(10): 10-13  (Bui).

        C-5.   Signs of overexcitability in various nerve tracts were seen
        at the end of  the workday  in  employees  of  a NHa production plant
        (perhaps 10-50 mg/m3 in the atmosphere).

3-210   Klavis,  G.  1958.  Ammoniakvergiftungen und ihre  Folgen unter
        Beriicksichtigung  neuer Kasuistik [Ammonia Poisoning and  its Conse-
        quences,  with  New  Case Reports].  Arch.  Toxikol.   17:155-158.

        C — .   Severe poisoning  symptoms in workers after acute exposures to
        NH3 escaping from a defective safety valve were described.  Exposure
        levels were not measured.  Klavis believed that workers can tolerate
                                     86

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        < 100 mg NH3/m3 without chronic irritation (the MAC was 70 mg/m3).
        Protective masks should be worn at higher concentrations.

3-137   Kondrashov, V. A.   1978.   0 Sootnosheniyakh Opasnosti Otravleniya
        Parami i Gazami Toksicheskikh Veshchestv pri Kozhnom i Ingalyatsionnam
        Putyakh Vozdeistviya  [Relative Hazards of Poisoning with Fumes and
        Gases of Toxic  Substances  with Their Dermal and Inhalation Routes
        of Action].  Gig.  Tr. Prof. Zabol.  No.2:34-38.

        C-8.  The 5-min to  1-h LC50 for  rats by inhalation of NH3 is 100
        mg/ m3  compared to  1,300-200 mg/m3 by skin absorption in the same
        period.

3-054   Kornienko,  A. P.  1972.  Gigenicheskaya Otsenka  Smesi Aerozolya  Sernoi
        Kisloty, Sernistogo Angidrida, Okislov Azota i Ammiaka kak Zagrayaznitelei
        Atmosfernogo Vozdukha  [Hygienic Evaluation of a  Mixture of Sulfuric
        Acid Aerosol, Nitrogen Oxides, and Ammonia as an Atmospheric Pollutant].
        Gig. Sanit.  37(4):8-10.

        D—.  A study primarily aimed  at  investigating the joint action of
        a mixture of  compounds.   The effect obtained was of the summation
        type.  Human odor threshold  and EEG and  fat  resorptive action, de-
        fensive reflex action, cholinesterase activity,  liver function,  blood,
        and tissue studies were done.

3-138   Krystev, E., M. Kolev, and P. Konstantinov.  1978.  Prouchvaniya
        Vyrkhu Mikroklimata  i  Smyrtnostta pri Puicheta Broileri [Microcli-
        mate and the Mortality Among Turkey Poult Broilers],   Vet.  Med.  Nauki.
        15(1):8-13 (Bui).

        C-7.  Groups of 23  turkeys  exposed for 20-25 days to 14, 26, or 55
        mg  NHa/m3 and  apparently  no ^S showed  statistically significant
        increased mortality  (8.55,  24.00,  36.90%)  with increased NH3 con-
        centration.  Apparently no controls were used.

3-171   Kujawska  et al.  1977.   Analiza  Sprawnosci Wentylacyjnej  PJuc
        Pracownikow Narazonych na Dziatonie  Gazow i Pyjow Drazniazcych
        [Analysis of Lung Function in Workers Exposed to Irritating Dusts
        and Gases].  Med.  Pr.  28(5):4l9-426.

        B-10.  Men  occupationally  exposed to NHs alone or in combination
        with dust and NO  had decreased FEVi  values.   The effect was further
                        x
        enhanced in smokers.

3-055   Kustov, V.  V.   1967.   Means for Determining the Maximum Allowable
        Concentration of Toxic Products  of Natural Human Metabolism.  In:
        Obshchiye Voprosy Promyshlenoy Toksikologii  [General Questions  of
        Industrial Toxicology].  Moscow,  U.S.S.R.  NASA Technical Transla-
        tion, TT F-11,358,  National Aeronautics and Space Administration,
        Washington, D.C.  pp. 63-65.
                                     87

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        C-7.   Gives some biochemical  indexes  that may be useful for esti-
        mating exposure.

3-187   Larson, T. V., D.  S.  Covert,  R.  Frank,  and R. J. Charlson.   1977.
        Ammonia in the Human Airways:   Neutralization of Inspired Acid Sul-
        fate Aerosols.  Science.   197:161-163.

        B-ll.  In humans, natural expired NHg concentrations ranged from  7
        to 520 |jg/m3,  varying with the last airway segment traversed.   Pos-
        sible neutralization of H2S04  aerosols by
3-140   Lee, S. T. , and Y. J. Lee.  1977.  Survey on Status of Working En-
        vironment in Some Industries.   Koryo Taehakkyo Uikwa Taehak Chapchi.
        14(1):161-170 (Kor).

        D-7.  Only one data  point for NH3 is given:   43 ppm in the air of
        an ammonia room in the chemical industry.   No toxicity data are given.

3-219   Legters, L.  1980.  Biological Effects of Short, High-Level Exposure
        to  Gases:   Ammonia.   AD-A094501, National Technical  Information
        Service, U.S. Department  of  Commerce, Springfield, Virginia.  87
        pp.

        A — .  Extensive review of the animal and man NHs exposure literature
        (mainly English), primarily in narrative form.  Includes an appendix
        with summaries and critical analyses of the literature.

3-058   Lehmann, K.  B.   1886.  Experimentelle  Studien  iiber den Einfluss
        technisch und hygienisch wichtiger Case und Dampfe auf den Organismus.
        (Teil I und  II--Amoniak und Salzauregas) [Experimental Studies on
        the Effect of Technically and Hygienically Important Gases and Vapors
        on  the  Organism.   (Parts  I and II — Ammonia and Hydrogen  Chloride
        Gas)].  Arch. Hyg.  5:1-126.

        B-9.  Dose-response  experiments  with cats,  rabbits, guinea  pigs,
        and rats.

3-059   Leonardos, G. , D.  Kendall,  and N. Barnard.  1969.  Odor Threshold
        Determinations of 53 Odorant Chemicals.  J. Air Pollut. Control Assoc.
        19:91-95.

        A- 11.  Definitive paper on the subject.

3-060   Lepine, C.,  and  R. Soucy.   1962.  La  bronchopneumopathie  d'origine
        toxique.  Evolution physiopathologique  [Bronchopneumopathy of Toxic
        Origin:  Physiopathological Evolution].  Union  Med. Can.   91:7-11;
        copyrighted English  translation  provided by  the National  Institute
        of Occupational Safety and Health, Rockville, Maryland.

        C-7.  The victim of an occupational accidental exposure to NHs (con-
        centration and duration not given) showed decreased maximum  respira-
        tory capacity and vital capacity over a 16-mo period.
                                     88

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3-202   Lillie, R. J.   1970.   Air Pollutants Affecting the Performance of
        Domestic Animals:  A Literature  Review.   Agriculture Handbook No.
        380.  Animal Science Research  Division,  Agriculture Research Ser-
        vice, United  States  Department  of  Agriculture,  Washington,  D.C.
        pp. 14-19.

        D--.  Primarily a review article with 28 references.  One short sec-
        tion comparing poultry and human susceptibility to NHs,  indicating
        that poultry may have a slightly higher tolerance.

3-189   Lotoshnikova, Yu. V.   1979.  K Gigienicheskoi Otsenke Epoksidno-
        Furfurol'nogo Pokrytiya  [Hygienic Assessment  of  an Epoxy-Furfural
        Coating].  Khim. Prom-st., Ser.:   Toksikol.  Sanit.  Khim.  Plastmass.
        No. 4:29-30.

        D-4.  Epoxy-furfural coating,  used  on concrete for anti-corrosion
        purposes, emits many substances  after its application,  especially
        NH3 and furfural.  At no time did levels exceed the maximum allowable
        concentrations, and only traces were  left after 4 mo.  Slight odor
        was detected (0.0126 mg furfural/m3, 0.042 mg NH3/m3).  Significant
        changes in human dark adaptation were seen.

3-062   MacEwen, J. D. , J. Theodore, and E. H. Vernot.  1970.  Human Expo-
        sure to E.E.L. Concentrations of Monoethylhydrazine.  AMRL-TR-70-102
        Paper No. 23.  Aerospace Medical Research Laboratory, Aerospace Med.
        Div., Air Force Systems Command,  W-P AFB, Ohio.  9  pp.

        C-8.  Six men  tested found 30  and 50  ppm NHs to have  a moderate or
        strong odor intensity,  and no to moderate nasal and eye irritation.
        Subjective evaluation only.

3-144   Makshanova, E.  I.   1977.  Hekotorye  Pokazateli  Zabolevaemosti i
        Nespetsificheskoi Reaktivnosti Organizma Robachikh Otdelochnogo
        Tsekha Kozhevenogo Proizvodstva  [Some Morbidity  Indexes and Non-
        specific Responses of Leather Industry Finishing Department Workers].
        Zdravookhr.  Beloruss.   No.9:85-86.

        D-5.  The air in the title area is polluted by NH3, esters, xylene,
        toluene, and turpentine  in concentrations at or somewhat above the
        maximum permissible limits.  The workers suffered  from catarrh of
        the upper respiratory tract,  angina, bronchitis,  hypertonic disease,
        neuralgia, neuritis,  and radiculitis.

3-172   Marschang, F.,  and C.  Petre.  1971.  Der NH3-Gehalt  der Stalluft
        und  sein  Einfluss  auf  die  Morbiditat und  die Tierverluste in
        Rindmaststallen [The NH3 Content of Stall Air and Its Influences on
        Morbidity and Animal Losses in Cattle Fattening Houses].   Zentralbl.
        Vet. Med. B.  18:646-654.

        C-8.  There was a direct relationship between too high concentration
        of NH3 (3-2,000 ppm by volume)  in the buildings,  and the development
        of disease and the severity of signs of the disease (mainly respira-
        tory disorders).

                                     89

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3-173   Martin,  W.,  and A.  C.  Stern.   1974.   The World1s  Air Quality Man-
        agement  Standards, Vol. I.  EPA-650/9-75-001-a, U.S. Environmental
        Protection Agency, Washington,  B.C.   15 pp.

        D--.  In seven other  countries,  the  ambient air quality standards
        were 0.1-0.5 mg NH3/m3, for 24  h.

3-064   Mayan, M.  H., and C. P. Merilan.   1972.  Effects of Ammonia Inhala-
        tion on Respiratory Rate  of Rabbits.   J. Anim. Sci.  34:448-452.

        B-ll.  Exposure of rabbits to 50  or 1QO ppm for 3  h caused increased
        depth of respiration,  increased blood urea nitrogen and C02,  and no
        pathological changes in several organs examined.

3-145   Mickiewicz,  L.  1978.   Effect of  Industrial Pollution on the  Mucous
        Membrane of  Upper Respiratory Tract.   Med. Pr.   29(1):65-68.

        D—.  A review of upper respiratory tract effects  of ammonia  as well
        as of cotton, wood, and rock salt dusts; HC1; H2S04; and F compounds.

3-065   Mikhailov, V. I., Z. I. Pilipyuk,  V.  S. Georgievsky, B. S. Katkovsky,
        and A. N. Kalinina.   1969.  Vliyanie Malykh Kontsentratsii Ammiaka
        na Nekotonye Biokhimicheskie i  Fiziologicheskie Pokazateli u Cheloveka
        [The Effect of Low Concentrations of Ammonia on Certain Biochemical
        and Physiological Indices in Man].   Gig. Tr. Prof. Zabol.  13(10):53-55.

        C-8.  Experimental acute exposure of men to low levels of NH3 (3 or
        13 mg/m3)  temporarily altered oxygen consumption.

3-146   Mikhailuts,  A. P.   1977.   Vliyanie Nizkikh Kontsentratsii Ammiaka
        na  Lits,  Perenesshikh  Ostrye Zabolevaniya Verkhnikh Dykhatel'nykh
        Putei [The  Effect of  Low Concentrations of Ammonia on Persons Re-
        covered from  Acute  Diseases of the Upper  Respiratory Tract].   Gig.
        Sanit.  9:16-19.

        B-9.  People in the 2 to 4 days after convalescence were more sensi-
        tive  to the action of low concentrations of NHs  than practically
        healthy people.  Odor thresholds  of other chemicals, pneumotachometry,
        and cardiointervalography were  studied.

3-213   Mikhailuts,  A. P.  1980.  Vozdeistvie Zagryaznenii Atmosfernogo Vozdukha
        Territorii Khimicheskogo Predpriyatiya na Rabotayushchikh, Imeyushchikh
        Khronicheskie Ishemicheskuyu Bolezn1  Serdtsa, Bronkhit i Pnevmoniyu
        [Effect of Air Pollution in the Area of a Chemical Plant on Workers
        with  Chronic Ischemic Heart Disease,  Bronchitis, or Pneumonia].
        Gig. Tr. Prof. Zabol.   No. 7:1-3.

        D--.  Chemical plant  workers afflicted with the title  diseases  and
        exposed during 68-72% of their work shift to NH3,  NO , S02, and H2S04
        [presumably  as a  mixture]  at total concentrations or 0.43-0.61  the
        MAC (MPC)  values  showed rapid loss of olfactory response to benzene
                                     90

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        vapors and an increase of heartbeat and breathing rates despite only
        light to moderate exertion.   Changes absent or barely detectable in
        healthy controls.

3-147   Mikhailuts, A. P., V.  A.  Poponnikov, I. V.  Golubev,  and S.  A.  Lambina.
        1979.  Vliyanie Ammiaka i Dvuokisi Azota na Razvitie Respiratornykh
        Mikrobnykh Infektsii  [Effect of Ammonia and Nitrogen  Dioxide  on
        Respiratory Microbial Infections].  Gig. Sanit.  No.  8:8-11.

        B-10.  Chronic exposure of rats to  low  concentrations of NHa (3 or
        6 mg/m3) and repeated innoculation with respiratory-infection microbes
        caused increased pathomorphology compared to rats with no gas  exposure.

3-206   Mitchell, H.  A.   1963.   Ammonia Tolerance of the California Leaf-
        Nosed Bat.  J. Mammal.  44(4):543-551.

        B-9.  Acute  exposure  of  bats to 500-5,500 ppm NHg indicates that
        they are much less sensitive than humans.  Organ damage and decreased
        respiratory and heart rates  were seen.   The maximum sublethal concen-
        tration tolerated for 9 h was 3,000 ppm.

3-148   Montague, T. J., and A. R. Macneil.  1980.   Mass Ammonia Inhalation.
        Chest.  77(4):496-498.

        C-10.  Fourteen men, accidentally exposed to high concentrations of
        ammonia vapors for  up to several minutes, were differentiated by
        physical  examination  into mildly  or moderately  affected groups.
        All had significant respiratory distress, some combination of pharyn-
        geal or pleuristic chest pains, cough or dyspnea.   Those with abnormal
        chest findings on admission had longer hospital stays,  but both groups
        responded well to treatment.

3-066   Mulder, J. S., and  H.  0.  van der  Zalm.   1967.  A Fatal Case of Am-
        monia Poisoning.  Tijdschr.  Soc. Geneeskd.   45:458-460; copyrighted
        English translation provided by the National Institute of Occupa-
        tional Safety and Health, Rockville, Maryland.

        C-8.  During an accidental spill, a male worker was exposed to roughly
        30,000 ppm NH3  for  several  minutes during physical exertion.   The
        first cardiac arrest occurred about 4 h after exposure, and the fatal
        cardiac arrest 6 h later.  On autopsy,  destruction of deep lung tissue;
        pharyngeal,  epiglottal, and  pulmonary  edema; and other respiratory
        damage were found.

3-067   Nakatani, T., and S. Sugano.   1971.  Survey Report Concerning Damages
        Caused by Air Pollution  Due  to Waste Gases from Sanitation Center
        in Yabase.  Part I.   Effects on the Human Body.   Nakadori Byoin Iho
        [Nakadori Hosp. Bull.].  11:796-800.

        D--.  The acute and chronic  respiratory complaints of 46 people with-
        in 500 m  of  a sanitation  center.   It was believed that most of the
        problems were  due to  nitrogen  compounds but. no concentrations were
        given.  No controls.

                                     91

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3-068   NAS/NRC,  National Academy of Science/National Research Council Com-
        mittee on Toxicology.   1972.   Guides  for Short-Term Exposures of
        the Public to Air Pollutants.  IV.  Guide for Ammonia.  PB-244336,
        National  Technical Information Service,  ILS.  Department of Commerce,
        Springfield,  Virginia.   10 pp.

        A—.   Review of effects on humans, animals, plants, and materials.

3-214   Nefedov,  Yu.  G., V.  P.  Savina, N. L.  Sokolov, and V.  E.  Ryzhkova.
        1969.  Issledovanie Mikroprimesei v Vydykhaemom Chelovekom Vozdukhe
        [Trace Contaminants  in  the  Air Exhaled  by Man].   Kosm. Biol.  Med.
        3(5):71-77.

        D—.   Ammonia levels found in  the breath of healthy 25 to 35-y-old
        people were  0.1-1.50 mg/m3 in smokers  and 0.4-1.93 mg/m3  in nonsmokers.

6-124   Newsome,  J.  R.,  V.  Norman, and V. L.  Zaratzian.   1965.   Vapor  Phase
        Analysis  of  Cigarette  Smoke.  Tob. Sci.   9:102-110;  or Tobacco
        l6l(4):24-32.

        D—.   Levels  in tobacco smoke (|Jg/40 ml  puff):

                       Unfiltered     Filtered
        Methanol
        HCHO
        Acrolein
        HCN
        H2S
        NH3
13
 4.1
 8.2
32
 3.4
12
10
 3.6
 7.9
29
 3.1
13
3-203   Niden, A. H.  1968.  Effects of Ammonia Inhalation on the Terminal
        Airways.  Eleventh Aspen Emphysema Conference.   11:41-44.

        D-4.  An expanded abstract, so few data are given.  Acute exposure
        of mice  to  NHs  (up  to 280,000 ppm)  caused changes in capillaries,
        alveoli, and nonciliated bronchiolar cells (examination by electron
        microscopy).

3-190   NIOSH, National Institute for Occupational Safety and Health.   1979.
        Working Safely with Anhydrous Ammonia.   PB80-184427,  U.S.  Department
        of Health,  Education, and Welfare, Cincinnati,  Ohio.   23 pp.

        D--.  A  general common  sense safety booklet.  It  stresses the tox-
        icity, rapid changes of volume and pressure, and the  cooling capac-
        ity of  ammonia.   First  aid for NH3 exposure consists of flushing
        with water  and  calling  a doctor.   Accident avoidance is using the
        proper equipment in the proper way.   Lists causes of  most accidents.

3-070   Nizhegorodov, V.  M., and  I. T. Kalinin.   1967.  The Effect  of Pro-
        longed  Exposure to  Low Ammonia Concentrations  on the  Content of
        Vitamins A,  Bj, 63,  PP and Ascorbic Acid in Animals.  Hyg.  Sanit.
        32(1-3)-.277-280.
                                     92

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        D-6.   Exposing rats to 20 mg NHs/m3 for 3-7 mo affected metabolism
        significantly as well as  the  contents of  vitamins  B1?  82,  PP,  and
        ascorbic acid in the animals.

3-071   Nizhegorodov, V. M. ,  and  Ya.  L. Markhotskii.  1971.   Vitamin  B6
        Requirement  for  Workers  Occupied in the Manufacture of  Nitrogen
        Fertilizers.   Hyg.  Sanit.   36(7-9):478-480.

        C-7.   The vitamin  Bg  requirement of workers exposed to MS, NO  ,
        and CO was increased, but only the CO concentration was given in
        the article.

3-211   NRC,  National Research Council,  Committee  on Medical  and Biologic
        Effects of Environmental  Pollutants, Subcommittee on Ammonia.   1979.
        Ammonia.  University  Park Press.   Baltimore,  Maryland.   38A pp.

        A--.   Authoritative review  of  properties,  chemical interactions,
        monitoring,  sources and  sinks,  transportation, toxicology, human
        health effects,  and effects on materials.

3-215   OAQPS, Office of Air  Quality  Planning and Standards.   1977.  Air
        Pollutant Assessment  Report on Mobile Source  Ammonia  Emissions.
        Strategies and Air Standards Division, Office  of Air Quality Plan-
        ning and Standards, Office of  Air and Waste Management, Environmental
        Protection Agency.   Research Triangle Park,  North Carolina.  27 pp.

        C--.   Tailpipe emissions  from  cars  equipped with  catalytic converters
        averaged 3.5  mg NH3/m3 when properly adjusted and 14 mg NH3/m3  when
        improperly adjusted.  Extensive  discussion  of a  series of tests,
        and possible  NH3 levels  in enclosed areas  and in  congested traffic.
        Includes a review of NH3  health effects literature.

3-074   Patty, F. A.   1963.   Alkaline  Materials.   In:  Industrial Hygiene
        and Toxicology.  Vol. 2.   Toxicology.   2nd ed.  D. W.  Fassett  and
        D. D.  Irish, eds.   Interscience Publishers, New York, New York.
        pp. 859-869.

        D--.   Short review of properties, uses, and toxicity of NH3 and other
        compounds.  Considers mostly relatively high concentrations.

3-075   Pernot, C. ,  C. Huriet, A.  Midon, and G.  Grun.  1972.   L'intoxica-
        tion aique professionnelle par le gaz ammoniac.  A propos de quarte
        observations.  [Acute Occupational  Poisoning by Ammonia Gas.  A Study
        of Four Cases]   Arch. Mai.  Prof. Med. Trav.  Secur. Soc.   33:5-12.

        B-6.   Accidental exposure of four men  following the explosion of a
        tank containing NHs gas.   Some acute symptoms, and apparent recovery
        with few or no sequelae.

3-204   Phipps, R. J., and P.  S.  Richardson.  1976.   The  Effects  of Irrita-
        tion at Various Levels of the Airway Upon Tracheal Mucus Secretion
        in the Cat.  Am.  J. Physiol.  261:563-581.
                                     93

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        D-6.   A mechanism study.  NHs exposure caused coughing followed by
        slow,  deep breathing.   Inhalation into the lower airways  caused in-
        creased mucus output from the isolated trachea.

3-107   Pliskovskaya, G.  N. , A.  L. Germanova,  N.  G.  Ivanov,  E.  A.  II1 in,  V.
        M. Milyavskii and A. D. Noskin.  1975.  Opredelenie Soderzhaniya v
        Atmosfere Maketov Biosputnikov Ammiaka i  Podkhod k ego  Normirovaniyu
        [Determination of the Ammonia Content in  the Atmosphere of Biosatel-
        lite Mockups  and a Method  for  Its  Normalization].   Kosm. Biol.
        Aviakosmicheskaya Med.   9 (2): 27-32.
        C-6.  Tests with 60 rats exposed to NHa concentrations for 4 h de-
        termined the threshold  of  irritating  action to be 228 mg/m3, the
        threshold of acute action to be 462 mg/m3, and the no-effect level
        to be 115 mg/m3.  Rats held for 30 days in conditions of hypokinesia
        before testing  had threshold  values  roughly half those for normal
        rats.

3-151   Quarles, C. L. , and D.  J. Fagerberg.   1979.  Evaluation of Ammonia
        Stress and Coccidiosis on Broiler Performance.   Poult.  Sci.  58(2):
        465-468.

        C-10.  Groups  of 80 broiler chickens were exposed to 0, 50, or 100
        ppm NHs  from 28 to 53 days of  age, and were orally inoculated with
        coccidia at 36 days of age.   By day 42, the exposed groups had sig-
        nificantly decreased body weights,  and the ammonia-exposed groups
        with coccidiosis infection had mild intestinal and airsac  lesions,
        the birds exposed to 50 ppm NH3 the most affected.

3-185   Quarles, C. L., and H.  F. Kling.   1974.  Evaluation of Ammonia and
        Infectious Bronchitis Vaccination Stress on Broiler Performance and
        Carcass Quality.  Poult. Sci.   53:1592-1596.

        C-9.  A total of 320 broiler chicks was exposed to 0, 25, or 50 ppm
        MS  from 4-8 weeks  of age,  and were vacinnated  in that time.  By
        week 8,  broilers exposed to ammonia had significantly  reduced body
        weights and feed  efficiencies.  At weeks 6 and  8, broilers had a
        severe airsacculitis condition.

3-152   Reece, F. N. ,  B. D. Lott, and  J. W. Beaton.  1980.  Ammonia in the
        Atmosphere During Brooding Affects Performance of Broiler Chickens.
        Poult. Sci.  59 (3): 486-488.

        C-10.  Less useful model than  the swine reports.   Eighty chicks were
        exposed to 50,  100, or  200 ppm for 28  days, which caused  decreased
        body weight,  with recovery to  normal weight within 8 days after ex-
        posure stopped  for  the  lower  levels.   100 and 200 ppm caused con-
        siderable mortality, but  authors  suggest that low levels are more
        damaging to performance on a per-unit-of-ammonia basis.

3-199   Renne, R. A., and K. E. McDonald.  1979.  Toxic Effects of Geothermal
        Effluents:   Acute  and  Subacute Inhalation Toxicology of  Hydrogen


                                     94

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        Sulfide and Ammonia in Rodents.   In:   Pac.  Northwest Lab.  Annu.  Rep.
        1979 DOE.   Assist.  Sec. Environ.   Pt.  1:   Biomedical Science,  p.  275.

        D--.  Part of an annual report,  so this reference is just  a summary.
        An initial 7-day exposure to 250 ppm NHa  caused no significant changes
        in rats or  guinea  pigs.   A subsequent 7-day exposure to the same
        level caused a mild increase in the incidence of acute respiratory
        tract inflammatory lesions in guinea pigs.   Subsequent exposure in-
        stead to 220 ppm H2S  caused mild interstitial pneumonitis.  Mild
        chronic nephritis was  also present in both groups.

3-155   Richard, D., G.  Bouley, and C.  Boudene.  1978a.   Effects  of Ammonia
        Gas Continuously Inhaled by Rats and Mice.   Bull. Eur. Physiopathol.
        Respir.  14(5)=573-582.

        B-ll.  A good study,  the only limit being the high NH3 level  used
        (500 ppm).  Rats seemed  able to adapt  to this exposure.  Mice were
        more susceptible to airborne infection after 7-d exposure.

3-154   Richard, D. , J. M. Jouany, and C. Boudene.  1978b.  Toxicit£ aigue
        par voie a^rienne  du  gaz  ammoniac chez le lapin   [Acute Inhalation
        Toxicity of Ammonia in Rabbits].   C.  R.  Acad.  Sci.  [D]  (Paris).
        287(4):375-378.

        B-10.  Acute exposure of  rabbits to very high levels  (1,000-20,000
        ppm) by artificial ventilation (and so of limited use in this  task)
        caused pulmonary edema and cardiovascular dysfunction.

3-157   Richardson, P.  S., R.  J.  Phipps, K. Balfre, and  R. L. Hall.   1978.
        The Role  of Mediators, Irritants and  Allergens  in Causing Mucin
        Secretion from the Trachea.  Ciba Found.  Symp.  54:111-131.

        C-6.  An anaesthetized cat with 3 cannulae inserted into the trachea
        was exposed to NHs between 0.33 and 0.1%, directly into the lungs
        or into the  trachea  in different experiments.  Coughing and rapid
        breathing occurred during lung exposure.   Increased 35S-labeled mucin
        output in the tracheal segment occurred during both exposures.  This
        response was apparently  both nervously mediated and partly due to
      .  local excitation.

3-217   Rumyantsev, G.  I.,  T.  A. Kozlova, I.  K. Atyakina, E. P. Vishnevskaya,
        S. M.  Novikov, V.  A.  Relsov, and L. A. Porokhova.   1980.   Problems
        of Industrial Hygiene in Ammonium Sulfate Production.  Gig. Sanit.
        No. 8:66-67 (Russ.).

        D--.  Workers were exposed to H2S04,  S02, NHs, and dust,  none  exceed-
        ing the permissible limits.  Heart-contraction  frequency,  arterial
        pressure, hetnodynamic index, response time of erythemal-motor reactions,
        and other  parameters  indicate that the workers belong in the  first
        and second category of severity.
                                     95

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3-160   Sadasivudu, B.,  and C.  Radha Krishna Murthy.   1978.   Effects of Am-
        monia on Monoamine Oxidase and Enzymes of GABA Metabolism in Mouse
        Brain.  Arch.  Int.  Physiol.  Biochim.  86(l):67-82.

        D-8.  Groups of  six  mice were exposed for 2 or 5 days to unknown
        but high concentrations  of NHg vapor.  After 2 days, monoamine ox-
        idase activity had decreased  in the brain stem and cerebellum, and
        increased in the cerebral  cortex.   On day 5,  MAO activity had in-
        creased in  the  cerebellum,  increased further in the  cortex,  and
        showed no  change in  the brain stem over day 2.  Enzyme levels of
        GABA  (gamma-aminobutyric  acid)  metabolism also  fluctuated.   The
        implications are discussed.

3-159   Sadasivudu, B., T. Indira  Rao,  and C. Radhakrishna  Murthy.   1979.
        Chronic Metabolic Effects of  Ammonia  in Mouse Brain.  Arch. Int.
        Physiol. Biochim.  87(5)=871-875.

        D-8.  Methods the same as Sadasivudu and Radhakrishna Murthy (1978.).
        Glutamate,  aspartate, alanine, glutamine, GABA, RNA, protein,  (Na
        and K )-ATPase, and  the enzymes  in glutamate metabolism were mea-
        sured in three  regions  of the brain (cerebellum, cerebral cortex,
        and brain  stem).  Results  indicated that the brain was in a state
        of more depression and less of excitation.

3-076   Saifutdinov, M. M.   (alternatively transliterated  as Sayfutdinov)
        1966.  Maximum Permissible  Concentration  of  Ammonia in the Atmos-
        phere.  Hyg. Sanit.   31(4-6):   171-176.

        B-9.  Rats  exposed to low levels  (0.2-20.0 mg/m3) of NH3 had short-
        ened reflex response time and some altered blood and urine chemistry.
        Few actual  data given.

3-216   Savina, V.  P., L. N.  Mukhamedieva, M.  P. Kalandarova, V.  V.  Zhuravlev,
        K. N. Mikos, T.  I.  Kuznetsova, E. I.  Nikitin, and K. V.  Grishina.
        1980.  Evaluation of the Effect of Prolonged and Continuous Exposure
        of a  Human Subject  to Low  (2 mg/m3)  Ammonia Concentrations under
        Conditions  of an Airtight Chamber.  Gig. Tr.  Prof.  Zabol.   No. 12:63
        (Russ.).

        B-7.  Exposure of humans to 2.16 rag NH3/m3 for 35 d caused a slight
        increase in 02  consumption,  increased NHs levels in the blood and
        exhaled breath and inhibition of the oxidative-reductive processes.
        All changes disappeared 3 d after exposure stopped.

3-078   Sayfutdinov, M. M.   1968.   Experimental Data Proposed as a Basis
        for the Determination of Maximal Allowable Ammonia Concentration in
        Atmospheric Air.  In:  USSR Literature on Air Pollution and Related
        Occupational Diseases; A Survey.   B. S.  Levine (Translator).  17:67-76.
        PB180-522T, National Technical Information Service,  U.S.  Department
        of Commerce, Springfield, Virginia.
                                     96

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        B-7.   The effect of low NHs concentrations on the cerebral-cortical
        electrical activity of five people.

3-079   Sayfutdinov, M. M.  1973.  Sanitary Characteristics of Ammonia and
        Validation of  Its Maximum Permissible Concentration in Atmospheric
        Air.   In:  American Institute of Crop  Ecology (AICE)  Survey of USSR
        Air Pollution  Literature.  Vol.  19.   M.  Y.  Nuttonson,  ed., Silver
        Spring, Maryland,   pp. 58-61.

        C-4.   A very brief review of several studies by the author, abstracted
        elsewhere in this bibliography.

3-080   Schmidt, F. C., and D. C. Vallencourt.  1948.  Changes  in the Blood
        Following Exposure  to Gaseous  Ammonia.   Science.  108:555-556.

        B-8.   The effects on blood pressure and concentrations  of non-protein
        nitrogen, urea, and creatinine  in the blood  from breathing 530-560
        ppm NHs by one human male for 4 h are  described.
3-081   Sestier, F. , J.  Bernier,  and R. Charbonneau.   1969.   Bronchopneu-
        mopathie d'origine toxique par  inhalation de vapeurs ammoniacales.
        A propos d'un  cas  [A Case History of Bronchopneumopathy Caused by
        the Inhalation of  Ammonia Vapors].   Union Med.  Can.  98:1903-1910.

        B-8.  A young  woman  accidentally exposed to NH3 when refrigerator
        tubing ruptured  suffered  extensive  and long-term respiratory com-
        plications.

3-082   Shimkin, M. B., A.  A. de Lorimier, J. R. Mitchell, and T. P.  Burroughs.
        1954.  Appearance of Carcinoma Following Single Exposure to a Refriger-
        ation Ammonia-Oil  Mixture.   Report  of  a Case and  Discussion of the
        Role of Cocarcinogenesis.   A.M. A. Arch. Ind. Hyg. Occup. Med.   9:186-193.

        C-7.  Cannot separate  effects of oil  (and its contaminants);  need
        more case  studies  (ammonia and interactions).   Tannic  acid is as
        likely a co-carcinogen as NH3 in this case (if not more so—repeated
        use, known tissue reactions).

3-083   Silver, S.  D. ,  and F. P. McGrath.  1948.  A Comparison of Acute Tox-
        icities of Etnylene Imine and Ammonia to Mice.   J. Ind. Hyg.  Toxicol.
        30:7-9.

        C-ll.  Exposure of mice for 10 min to very high levels of NH3 yielded
        an LDso of 7.06 + 0.32 mg/L.  Practically all deaths occurred during
        actual exposure, with  rapid recovery after exposure of those who
        did not die.

3-084   Silverman,  L. , and J.  L.  Whittenberger.  1949.   Blood Changes Due
        to Ammonia Inhalation?  Science (Comments and Communic.).  109:121-122.

        C-8.  Comments on  the  study by  Schmidt and  Vallencourt (1948), and
        comparisons to the study by Silverman et al. (1949) [3-085].


                                     97

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3-085   Silverman, L., J. L. Whittenberger, and J. Muller.  1949.  Physio-
        logical Response of Man to Ammonia in Low Concentrations.  J. Ind.
        Hyg.  Toxicol.   31:74-78.

        A-ll.  Human males were  experimentally  exposed to 500 ppm NHs in
        air,  which is  high by pollution standards.

3-200   Sim,  M. ,  and R. E.  Pattle.   1957.   Effect of Possible Smog Irritants
        on Human Subjects.   J.  Am.  Med. Assoc.   165:1908-1913.

        D-7.   The effects of  sulfuric  acid mist exposure for 50 min on an
        unknown number of men  were alleviated  when NHs was introduced in
        "sufficient" concentration.

3-086   Sinitsyna, E.  L.   1965.  Investigations  into Certain Aspects of the
        Health of People Working in the Main Shops  of Tanneries.   Hyg.  Sanit.
        30(4-6) :336-340.

        D-6.   Variations in the diurnal curves  of tannery employees exposed
        to unknown,  but probably low, levels of
3-087   Sloan, C.  H. ,  and G.  P.  Morie.   1974.   Determinations of Ammonia in
        Tobacco and Tobacco  Smoke  with an Ammonia Electrode.  Anal.  Chim.
        Acta.  69:243-247.

        D-12.  The  amounts of NHs  in smoke per cigarette (smoked down to a
        27-mm butt) found according to tobacco and/or  filter  type were:
        dark tobacco,  153 Hg; hurley,  102 pg;  flue-cured,  51 [Jg; nonfilter,
        blended tobacco,  67  |Jg; and  filtered, blended tobacco,  36  pg.

3-088   Slot, G.  M. J.  1938.  Ammonia  Gas Burns.   An Account of Six Cases.
        Lancet.   2:1356-1357.

        B-7.  Six  cases  of  ammonia burns and  respiratory symptoms are de-
        scribed.   Exposure was due  to  explosion of a pipe conveying ammonia
        gas in an ice  cream factory.

3-090   Smirnova,  N. A., and N.  P.  Granik.  1971.   Ob Otdalennykh Posledstviyakh
        Professional'nykh Ostrykh Porazhenii Dykhatel'nykh Piitei Razdrazhayiishchimi
        Gazami [Late After-Ef fects  of  Occupational Acute Damage to Respiratory
        Passages  by Irritating Gases].   Gig. Tr.  Prof. Zabol.  15(11) : 16-19.

        D--.  Of 88 cases of occupational poisoning  by irritating gases,
        only two had  been affected by NHg. These two poisonings were ac-
        companied by  edema of the  mucous membrane of  the pharynx with sub-
        sequent necrosis  of  the tonsils.   In one of the cases,  subatrophic
        pharyngo-laryngitis was late after-effect.

3-162   Sobonya,  R.  1977.  Fatal Anhydrous Ammonia Inhalation.  Hum. Pathol.
        8(3):293-299.
                                     98

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        C-10.   Morphologic and raorphometric pulmonary alterations  in a male
        patient with anhydrous NH3 inhalation (accidental,  high levels) dying
        2 mo after exposure are described.   Terminal nocardial (microbially
        caused pulmonary  infection) pneumonia,  cylindrical bronchiectasis
        of the lower  lobes,  and fibrous obliteration of the small airways
        were found.  The latter may be responsible for the  chronic obstruc-
        tive lung disease in the survivors  of an episode of NH3 inhalation.

3-108   Stolpe, J., and  R.  Sedlag.   1976.   Die Einzel- und Komplexwirkung
        von Ammoniak  und Schwefelwasserstoff  in  der Luft  a  uf kleine
        Versuchestiere  (Ratten)  bei unterschiedlichen Umweltbedingungen.
        1.  Meitteilung:  Die Wirkung von Ammoniak [Single  and Complex Effect
        of Ammonia and Hydrogen Sulfide in the Air on Small Laboratory Animals
        (Rats) Under Various Environmental Conditions.  1.   Effect of Ammonia].
        Arch.  Exp. Veterinaermed.  30(4):533-539.

        B-ll.   Little effect was  seen on rats  exposed to 30 ppm NH3.   Good
        controls, but fairly small sample sizes in all groups.

3-092   Stombaugh, D. P.,  H.  S. Teague, and W. L. Roller.   1969.   Effects
        of Atmospheric  Ammonia on  the  Pig.   J.  Anim. Sci.   28:844-847.

        B-ll.   Good dose  range,  to  10 ppm.  Exposure  of pigs  to dose  range
        (10-150 ppm)  which  included levels useful for pollution studies.
        Little respiratory effect seen, particularly after  2 weeks, but ad-
        verse effect on feed consumption.

3-218   Stupfel, M.,  F.  Romary,  M.  Magnier, and J. Polianski.  1971.   Com-
        parative Acute Toxicity, in Male and Female Mice, of Some  Atmospheric
        Pollutants:  Automobile  Exhaust, NO  ,  S02, 03, NH3, and CO.   C. R.
        Soc. Biol.  165:1869-1872 (Fre).   X

        D—.  Mice were  exposed to  12,000  ppm  NH3  for 20 min  or 11,000 ppm
        NH3 for 40 min, with overall mortalities of 71 and  54%, respectively.
        Differences were reported in the mortality rates of.the sexes, those
        for males being greater.

3-209   Taiganides, E., and R. K. White.  1969.  The Menace of Noxious Gases
        in Animal Units.  Trans. ASAE (Am.  Soc. Agric. Eng.).   12(3):359-362.

        D--.  A review of the occurrence of H2S, NH3, COg,  and CH4 in animal
        units, and their toxicities to  different  species.   Includes a  dis-
        cussion of potentially lethal  situations  and preventive measures.

3-163   Trubitskaya, G. P., A. N. Boiko, R. F. Komarova, and N. P. Cherednichenko.
        1978.   Vozdeistsvie Khimicheskogo Faktora Maloi Intensivnosti na Organizm
        Detei v Usloviyakh Primeneniya Polimernykh Materialov v Stroitel'stve
        [Effect of a Low-Intensity Chemical Factor on Children Under Conditions
        of the Use of Polymeric Materials in Construction].  Pediatriya (Moscow).
        No. 8:26-29.
                                     99

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        D-7.   Four hundred and three children (2- to 7-y-old)  in three dif-
        ferent schools were studied for possible effects of air pollutants
        from the use of polymeric construction materials.   Test groups (with
        0.124 or 0.134 mg  NH3/m3,  trace or 0.124 mg phthalates per cubic
        meter, and 0.010 or  0.017  mg HCHO/m3) showed increased immunobio-
        logic changes and  allergic-type  reactions  compared to the control
        group (0.92 mg NH3/m3, trace of phthalates, and 0.010 mg HCHO/m3).

3-164   Ulfvarson,  U.   1978.   Chemical Hazards in the Paint Industry.   Proc.
        Int.  Symp.  Control Air Pollut.  Work.  Environ.   Part 2:62-75.

        D-8.   Measurements of dust, NH3, and  solvent levels in 10 factories
        of the Swedish paint industry indicated that all were  generally above
        hygienic health standards.   Twenty-six percent of the  244 employees
        (in nine different job categories) interviewed had some skin changes
        on their hands or  under  their arms.   However, NH3 concentrations
        were poorly presented, not correlated with types of jobs and skin
        changes, and  the employees washed their hands with solvents or
        solvent-containing soaps.

5-424   Urban, C. M. , and R. J.  Garbe.   1980.  Exhaust Emissions from Mal-
        functioning Three-Way Catalyst-Equipped  Automobiles.  S.A.E. Tech.
        Pap.  Ser. 1980, 80051.   11  pp.

        C--.   Maximum emission rates (mg/m3)  in four malfunctioning,  three-
        way catalyst-equipped automobiles:

        NH3            254
        CN              67
        H2S              8
        HCHO             3

3-094   USSR  State  Committee of the  Ministers for Construction.  1972.
        Sanitarnyye Normy  Proyektirovaniya  Promyshlennykh Predpriyatiy
        [Sanitary Norms  for  Industrial Enterprise Design].  Izdatel'stvo
        Literatury po Stroitel'stvu [Publishing House of Literature on Con-
        struction].  Moscow.   96 pp.

        C--.   In the  USSR,  the  MAC for NH3 in workplaces was  20 mg/m3 and
        in populated places was 0.2 mg/m3 (one-time and avg.).

3-189   Valentine,  H.  1964.  A  Study of the Effect of Different Ventila-
        tion Rates on the Ammonia Concentrations in the Atmosphere of Broiler
        Houses.  Br. Poul. Sci.   5:149-159.

        B-10.  The effect of increased NH3 levels on chickens, and some useful
        information on relative humidity and  NH3 concentration.

5-413   Van Gemert, L. J., and A.  H. Nettenbreijer.   1977.  Compilation of
        Odour Threshold  Values in  Air and Water.  National Institute for
        Water Supply.   Leidschendam, The Netherlands, and Central Institute
        for Nutrition and Food  Research, TNO,  Zeist,  The Netherlands.
                                     100

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        A—.   Compilation of odor  threshold values reported by different
        researchers, for many compounds,  including:

        Ammonia        0.03-37  mg/m3
        HCN            < 1.1-6  mg/m3
        H2S            0.001-2  mg/m3
        HCHO           0.033-2.2 mg/m3
        Methanol       4.3-11,700 mg/m3
        Acrolein       0.05-4.1 mg/m3

3-165   Verberk, M. M.  1977.  Effects of Ammonia in Volunteers.   Int.  Arch.
        Occup. Environ. Health.  39(2):73-82.

        A-13.  "Experts" (members of the Subcommittee on Toxicology,  familiar
        with the literature  on NH3) and "nonexperts"  (nonscience students)
        were exposed to NHs with no change in lung function tests,  and varying
        subjective responses.  No actual lung function data given.  Authors
        felt that results justified Public Emergency Limits as high as 100,
        75, and 50 ppm for, respectively, 10, 30, and 60 min.

3-097   Vigliani, E.  C., and N.  Zurlo.   1955.  Erfahrungen der Clinica del
        Lavoro mit  einigen maximalen Arbeitsplatzkonzentrationen (MAX) von
        Industriegiften [Experience of the Labor Clinic with Several  Maximal
        Workplace  Concentrations  (MAC)  of Industrial  Poisons].   Arch.
        Gewerbepathol. Gewerbehyg.   13:528-534.

        D—.   Review.  The maximum allowable concentration was 50 ppm NH3
        rather than the 100 ppm set by the ACGIH.

3-098   Vikshraitis, Ch.  Yu., and N. P. Motejunene.  1972.   Kol'poskopicheskoe
        Vyyavlenie  Predrakasheiki  Matki  u Zhenshchin, Razbotayushchikh s
        Nekotorymi  Promyshlennymi  Yadami [Colposcopic Recognition of the
        Cervical Precancer in Females Working with Certain Industrial Poisons].
        Vopr. Onkol. 18(12):4l-45.

        D—.   Three hundred ninety-three female pharmaceutical workers occu-
        pationally  exposed to  a  complex  air mixture  including  7.2-136.2 mg
        NH3/m3 had increased percentage of precancerous lesions of the cervix
        compared to the control group.

3-166   Vilisov, B. A., N. S.  Irger, L. M. Kremko, Z. N. Pavlyutina, I. G.
        Tseluiko,  Y.  S.  Danishevich,  and  S.  S.  Khudnitskii.  1980.
        Gigienicheskaya Otsenka Nekotorykh Sinteticheskikh Smol i Ikh Vliyanie
        na Zabolevaemost1 Rabochikh Liteinykh Tsekhov [Hygienic Evaluation
        of Some  Synthetic Resins and their Effect  on the Health of Molding
        Department Workers].   Zdravookhr. Beloruss.  No. 1:31-34.

        D-7.   Foundry core workers usng phenol-formaldehyde copolymer, urea-
        formaldehyde, and  furan  resins suffered  a  higher rate  of disorders
        of the skin, liver, kidney and respiratory organs compared to workers
        involved in machine  building.   Metal casting workers  using  these
        resins were ill  about  half as often  and half as long  as the core


                                     101

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        makers.   The casters were more exposed to phenol, NH3, CO, and HCN
        than the core makers, who were more exposed to HCHO, methanol, and
        furyl alcohol.

3-168   Visek,  W. J.  ,  S.  K.  Clinton, and C. R. Truex.  1978.  Nutrition
        and Experimental Carcinogenesis .   Cornell Vet.   68(l):3-39.

        D — .   The ammonia ultimately produced in the alimentary tract from
        ingested protein may be implicated in colon carcinogenesis.

3-099   Voisin,  C., F.  Guerrin,  H.  Robin, D.  Furon,  and F.  Wattel.   1970.
        Sequelles fonctionelles respiratoires des intoxications par I1 ammoniac
        (A propos de  8  observations)  [Respiratory Functional Sequelae of
        Ammonia  Poisoning].  Poumon Coeur 26:1079-95;  copyrighted English
        translation provided by the National Institute  for Occupational Safety
        and Health, Rockville,  Maryland.

        B-ll. A good study for late effects.   The pulmonary functional changes
        of eight victims of accidental NHs exposures, with different degrees
        of severity of the initial acute phase,  were  followed for 1-5 y after
        exposure.

3-100   Walton,  M.  1973.   Industrial  Ammonia Gassing. Brit. J.  Ind. Med.
        30:78-86.

        B-ll.  Seven cases  of  ammonia gassing with 5-y  follow-up for six
        survivors and post mortem findings for the fatal case are described.
        NB:  Interaction with smoking described.  No quantitative exposure
        data.

3-101   Weatherby, J. H.   1952.   Chronic Toxicity of Ammonia Fumes by In-
        halation.  Proc. Soc.  Exp. Biol.  Med.  81:300-301.
        D-7.  Twelve male guinea pigs were exposed to a variable NHs concen-
        tration (140-200 ppm) ,  with  170 ppm the desired concentration, in
        repeated daily doses  for 6-18 weeks.  Only in  the 18-week exposure
        group were mild,  though definite, changes seen in the spleens, kid-
        neys, livers, and adrenal glands.  No consistent changes were found
        in hearts, lungs, stomachs, or small intestines.

3-102   Weedon, F. R. , A. Hartzell, and C. Setterstrom.  1940.  Toxicity of
        Ammonia, Chlorine,  Hydrogen Cyanide, Hydrogen Sulphide, and Sulphur
        Dioxide Gases.  V.  Animals.  Contrib. Boyce Thompson Inst.   11:365-385.

        C-8.  A group of eight  rats  and  four mice was  exposed  to 1,000 ppm
        NHa for 16  h,  and  autopsies were performed 5  months  later  on  two
        rats.  A few slight eye and respiratory symptoms were observed dur-
        ing exposure, and there were no findings on autopsy.

3-170   Wood, R. W.   1979.   Behavioral Evaluation of Sensory Irritation Evoked
        by Ammonia.   Toxicol. Appl. Pharmacol.   50(1) : 157-162.  >    '
                                     102

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        D-ll.   Behavioral response of six mice to 0.05-0.2% (500-2,000  ppm)
        NHs for a maximum of 60 s.  The duration of exposure decreased and
        the percentage of ammonia deliveries terminated by the  trained  mice
        in response to the NH3 exposure increased with increasing MS concen-
        tration.

3-105   Yelfimova,  Ye. V., N.  S.  Yevseyenko, Ya.  K.  Yushko, N.  N.  Pushkina,
        S. K.  Nenosheva, and G. N. Kuznetsova.  1971.  Sanitary Evaluation
        of Air Pollution in Areas Around Ferrous  Metallurgical  Plants.   In:
        American Institute of  Crop  Ecology (AICE) Survey of U.S.S.R. Air
        Pollution Literature.   Vol.  7.  M.  Y. Nutlonson, ed., Silver Spring,
        Maryland,   pp. 22-26.

        D-6.  Ammonia (0.3 to 8.0 mg/m3) was only a  minor component of gases
        emitted from the metallurgical plants.  Children living within 1,000 m
        of the plant showed more  upper respiratory,  somatic, and infectious
        diseases than did the  children living 12,000 m from plant No. 1,
        which caused heavy SQz pollution in its environs.
                                     103

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                                    TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
1. REPORT NO.
  EPA 460/3-81-027
                                                             . RECIPIENT'S ACCESSION'NO.
4. TITLE AND SUBTITLE
  Ammonia Health Effects
                                                            5. REPORT DATE
                                                                        1981
                                                            6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
  Bonnie L. Carson,
  Cerilv M. Beall
                                                            8. PERFORMING ORGANIZATION REPORT NO.
                         Harry V. Ellis  III,  and
                         Larr  H. Baker
9. PERFORMING ORGANIZATION NAME AND ADDRESS
  Midwest Research Institute
  425 Volker Boulevard
  Kansas City, Missouri   64110
                                                            10. PROGRAM ELEMENT NO.
                                                            11. CONTRACT/GRANT NO.

                                                              68-03-2928
12. SPONSORING AGENCY NAME AND ADDRESS
 Environmental Protection Agency
 Office  of Mobile Source Air Pollution Control
 Emission Control Technology Division
       Plvmouth Road,, Ann Arbor. Michigan  48102
                                                             13. TYPE OF REPORT .'.NO PERIOD COVERED
                                                              Final "Report"
                                                                        AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT            •                                .
     Health effects  literature primarily related to inhalation exposures  to  ammonia
  was collected,  evaluated, tabulated, and  summarized.   Approximately  200 documents
  were collected  from computerized and manual  literature searches covering the period
  1886-1981.  Pharmacologists and an M.D. epidemiologist rated the documents according
  to their applicability to the study and their methodology.  The approximately 50
  documents considered useful for deriving  a  range of concern for human exposure to
  ammonia from  automotive emissions were tabulated.  The 50 pages of  tables detail
  the results of  acute, repeated dose, and  chronic testing of bats, mice, rats, guinea
  pigs, chickens, rabbits, cats, monkeys, dogs, turkeys, swine, and humans as well as
  human occupational and accidental studies.   Most of the documents evaluated are
  described in  an annotated bibliography.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS
                                                                          c.  COSATI Field/Group
  Toxicity
  Ammonia
  Mammals
  Bibliographies
                       Toxic Tolerances
                       Occupational Diseases
                       Respiratory System
                                                Inhalation Health  Effects
                                                                               06T
  Release  Unlimited
                                               19. SECURITY CLASS (This Report)
                                                     Unclassified
                                                                          21. NO. OF PAGES
                                                                                107
                                               20. SECURITY CLASS (This page)
                                                     Unclassified
                                                                          22. PRICE
EPA Form 2220-1 (9-73)

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