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 ------- 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 ------- 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 ------- 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. ------- 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. ------- 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. ------- 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). ------- 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. ------- 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 ------- 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. ------- 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. ------- 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 ------- ^.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) ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- < 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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) ------- |