83 Ammonia ( CAS No. 7664 41 7) Draft, Unpublished Version. Government of Canada, Environment Canada.:

Arillo, A., Margiocco, C., Melodia, F., Mensi, P., and Schenone, G. 1981. Ammonia toxicity mechanism in fish: studies on rainbow trout ( Salmo gairdneri Rich.). Ecotoxicol. Environ. Safety 5: 316 328. Kloppic, E., Jasobasch, G., and Rapoprt, S. 1967. Enhancement of the glycolytic rate by action of ammonium ion on phosphofructokinase activity. Original in German. Acta. Biol. Med. 18: 37 42. Fromm, P. O., and Gillette, J. R. 1968. Effect of ambient ammonia on blood ammonia and nitrogen excretion of rainbow trout ( Salmo gaidneri). Comp. Biochem. Physiol. 26: 887 896. Person LeRuyet, J., Boeuf, G. Zambonin Infant, J., Helgason, S., and Le Roux, A. 1998. Short term physiological changes in turbot and seabream juveniles exposed to exogenous ammonia. Comp. Biochem. Physiol. 119A: 511 518. Randall, D. J., and Wicks, B. J. 1999. Fish: ammonia production, excretion, and toxicity. In press. Paper presented in the Fifth International Symposium on Fish Physiology, Toxicology, and Water Quality. University of Hong Kong.

4.9 ADDITIONAL REMARKS ( a) Remarks: The toxicity of ammonia to aquatic organisms is highly dependent on physicochemical factors, most notably pH because of its importance in chemical speciation. The acute toxicity of ammonia is also influenced to a lesser degree by temperature, carbon dioxide, dissolved oxygen, and salinity. In aqueous solution, ammonia exists primarily in two forms, un ionized ammonia ( NH3) and ammonium ion ( NH4 +), which are in equilibrium with each other according to the following established relationship:

NH3( aq) + H2O   NH4 + + OH

In general, as pH increases, the fraction of the total ammonia which is un ionized increases. It is this un ionized ammonia ( NH3) which is generally considered to be the primary cause of toxicity in aquatic systems. Un ionized ammonia ( NH3) is more toxic to aquatic organisms than the ammonium ion ( NH4 +) because the un ionized form is readily soluble in the lipid of the cell membrane and is rapidly absorbed by the gill. In contrast, the charged ion is not readily passed through the charged line hydrophobic space in the membrane. EPA studies indicate that un ionized ammonia is 190 times more toxic to guppies than ammonium. 84 Ammonia ( CAS No. 7664 41 7) Multiple EPA studies have shown that over the pH range of 6.5 9.0, the toxicity of un ionized ammonia ( NH3) increases as the pH decreases. This is either because the additional hydrogen ion ( H+) concentration at lower pHs increases the toxicity of unionized ammonia or because the ammonium ion ( NH4 +) exerts some level of toxicity at lower pH. However, it would be an oversimplification to attribute the toxic action to only the ammonium ion at low pH and to only unionized ammonium at high pH because most likely both forms participate when total ammonia concentration is high enough to cause toxicity symptoms. A joint toxicity model has been proposed, with ammonium causing most toxicity at high pH values and ammonium ion also contributing to toxicity at lower pH values. This is supported through studies demonstrating that at a low pH a new inward flux of ammonium ion can occur across the gills of aquatic species. Reference: Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C. Erickson, R. J. 1985. An evaluation of mathematical models for the effects of pH and temperature on ammonia toxicity to aquatic organisms. Water Res. 19: 1047 1058. Evans, D. E. and Cameron, J. N. 1986. Gill ammonia transport. J. Exp. Zool. 239: 17 23. Thurston, R. V., Russo, R. C., Phillips, G. R. 1983. Acute toxicity of ammonia to fathead minnows. Trans. Am. Fish. Soc. 112: 705 711. U. S. Environmental Protection Agency ( USEPA). 1998c. 1998 Update of Ambient Water Quality Criteria for Ammonia. Office of Water, Washington, D. C. EPA 822 R 98 008. U. S. Environmental Protection Agency ( USEPA). 1985. Ambient Water Quality Criteria for Ammonia   1984. Washington, D. C.: Office of Water Regulations and Standards, Criteria and Standards Division. EPA 504/ 5 85 006.

( b) Remarks: The amount of un ionized ammonia as a percent of total ammonia in aqueous solution is dependent on pH and temperature. The authors derive this relationship and provide a table showing the percent of un ionized ammonia at various pH values and temperatures. Reference: Emerson, K., Russo, R. C., Lund, R. E., and Thurston, R. V. 1975. Aqueous ammonia equilibrium calculations: effect of pH and temperature. J. Fish. Res. Board Can. 32: 2379 2383. 85 Ammonia ( CAS No. 7664 41 7) 5. TOXICITY * 5.1 ACUTE TOXICITY 5.1.1 ACUTE ORAL TOXICITY Not an applicable route of exposure.

5.1.2 ACUTE INHALATION TOXICITY ( a) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Rat ( Wistar) Exposure Time: 60 minutes Value: LC50 ( male) = 9,850 mg/ m3 air ( 14,111 ppm) LC50 ( female) = 13,770 mg/ m3 air ( 19,727 ppm) Method: Male and female SPF bred rats were exposed to an ammonia atmosphere. Each dose group consisted of 5 males and 5 females and they were exposed to an ammonia/ air mixture at a rate of 25 L/ min. Animals were exposed for 10, 20, 40, or 60 minutes. After exposure, they were housed 5 per cage for an observation period of 14 days. Food and water were available during the observation period, but were withheld during exposure. Body weight was recorded at days 1, 2, 4, 7, and 14. GLP: Yes [ ] No [ ] ? [ X] Test substance: Liquid ammonia ( NH3) in a pressurized cylinder ( UKF SBB, The Netherlands) Remarks: Clinical symptoms included eye irritation, especially in animals exposed for 60 minutes, wet noses, and nasal discharge. Autopsy revealed haemorrhagic lungs. Reference: Appelman, L. M., ten Berge, W. F., and Reuzel, P. G. J. 1982. Acute inhalation toxicity study of ammonia in variable exposure periods. Am. Ind. Hyg. Assoc. J. 43( 9): 662 665.

( b) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Albino ICR mice Exposure Time: 1 hour Value: LC50 = 4230 ppm un ionized NH3 Method: Groups of 12 mice each were exposed simultaneously to three concentrations of NH3 gas ( 1,190 4,860 ppm depending on which of the three experiments) in air using a dynamic inhalation exposure system. The control group was exposed to air only. The mice were allowed free access to food and water during the experiment, except while in chamber tubes. The mice were acclimated for at least 1week prior to the experiment. Sampling 86 Ammonia ( CAS No. 7664 41 7) and analyses were conducted every 3 5 minutes. Animals were observed for 14 days following exposure. GLP: Yes [ ] No [ ] ? [ X] Test substance: Ammonia ( NH3) gas ( Matheson, East Rutherford, NJ) Remarks: At high NH3 concentrations, mortality usually occurred within 30 minutes of initiation of exposure. Twenty five percent of animals exposed to 3950 ppm and greater did not survive. Percent mortality in higher concentrations ( 4220 4860 ppm) ranged from 41.6 to 100%. The lungs of animals that died during exposure were congested with evidence of hemorrhage. The lungs of animals from every treatment group sacrificed displayed a mild to moderate degree of chronic focal pneumonitis histologically. The liver and heart weights were increased in animals that died during exposure to 4860 ppm. Reference: Kapeghian, J. C., Mincer, H. H., Jones, A. B., Verlangieri, A. J, and Waters, I. W. 1982. Acute inhalation toxicity of ammonia in mice. Bull. Environ. Contam. Toxicol. 29: 371 378.

( c) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Rat Exposure time: 1 hour Value: LC50 = 5137 mg/ m3 ( 7338 ppm) Method: Rats were exposed for one hour to several concentrations of ammonia. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: Inhalation produced immediate nasal and eye irritation followed by labored breathing in all test groups. Surviving rats necropsied after 14 days showed moderate mottling of the liver at the 5474 and 6888 mg/ m3 ( 7820 and 9840 ppm) test levels. Reference: MacEwen, J. D. and Vernot, E. H. 1972. Toxic hazards research unit annual technical report. NTIS AD 755 358. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( d) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ X] Species/ strain: Rat Exposure time: 5, 15, 30 or 60 minutes Value: LC50 ( 5 m) = 18,693 mg/ m3 ( 26,704 ppm) LC50 ( 15 m) = 11,342 mg/ m3 ( 17,372 ppm) LC50 ( 30 m) = 7035 mg/ m3 ( 10,050 ppm) LC50 ( 60 m) = 7939 mg/ m3 ( 11,342 ppm) NOEL ( 5, 15, 30, & 60 m) = 100 mg/ m3 ( 144 ppm) Method: White rats were exposed to high concentrations of ammonia ( 6000, 3000, and 1000 mg/ m3, equivalent to 6814, 4307 and 1436 ppm) via inhalation. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas 87 Ammonia ( CAS No. 7664 41 7) Remarks: Other effects included dyspnoea, irritation of the respiratory tract and eyes, cyanosis of the extremities, and increased excitability. In associated studies, rats exposed to 3000, 1000 or 300 mg/ m3 ( 4307, 1436, 431 ppm) exhibited a drop in static muscular tension and other sublethal effects. No effects were observed in rats exposed to 100 mg/ m3 ( 144 ppm) for 5, 15, 30 or 60 minutes. Reference: Propkopieva, A. S. et al. 1973. Materials for a toxicological characteristic of the long term effect of ammonia on the organisms of animals after brief exposure. Gig. Tr. Prof. Zabol. ( Russian) 6: 56 57. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( e) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Mouse Exposure time: 1 hour Value: LC50 = 3386 mg/ m3 ( 4837 ppm) Method: Mice were exposed for one hour to several concentrations of ammonia. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: Inhalation produced immediate nasal and eye irritation followed by labored breathing in all test groups. Mild congestion of the liver was also observed in surviving mice in the two highest dose levels of 3185 and 4004 mg/ m3 ( 4550 and 5720 ppm). Reference: MacEwen, J. D. and Vernot, E. H. 1972. Toxic hazards research unit annual technical report. NITS AD 755 358. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( f) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Mouse Exposure time: 10 minutes Value: LC50 = 7060 mg/ m3 ( 10,152 ppm) Method: Groups of 20 mice were exposed to 9 concentrations. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: The LC50 was calculated from the mortality observed at 10 days. Most deaths occurred rapidly, with equally rapid recovery of survivors. Reference: Silver, S. D. and McGrath, F. P. 1948. J. Ind. Hyg. Toxicol. 30: 7 9. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( g) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] 88 Ammonia ( CAS No. 7664 41 7) Species/ strain: Rabbit, cat Exposure time: 1 hour Value: See remarks Method: Animals were placed in a static gassing chamber of 400 L capacity and exposed to from 3.5 to 8.7 mg un ionized NH3/ L. Experiments were performed upon 54 rabbits and 18 cats subdivided into 6 groups. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: Exposure to ammonia increased the respiratory tract fluid output two to three fold in cats and rabbits. Inhalation of ammonia had no appreciable effect upon the water content of respiratory tract tissues of rabbits and cats. Following gassing with ammonia, the iron content of the tracheal, bronchial, and alveolar portions increased in rabbits. There was an initial slight drop in blood hemoglobin in the first 4 or 5 hours of exposure, followed by a return to normal levels by 8 hours in both cats and rabbits. Definite lipemia was observed in rabbits. Reference: Boyd, E. M., MacLachlan, M. L., and Perry, W. F. 1944. Experimental ammonia gas poisoning in rabbits and cats. J. Ind. Hyg. Toxicol. 26: 29 34.

( h) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] ( RD50) Species/ strain: Male Swiss Webster mice Exposure time: 30 minutes Value: A concentration of 212 mg/ m3 ( 303 ppm) decreases the respiratory frequency by 50% ( RD50) in mice. Method: Mice were exposed to atmospheric concentrations ranging from 70 560 mg/ m3 ( 100 1000 ppm). GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: Ammonia is a sensory irritant to rodents. Reference: Barrow, C. S., Alarie, Y. and Stock, M. F. 1978. Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants. Arch. Environm. Health 33: 79 88. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( i) Type: LC0 [ ]; LC100 [ ]; LC50 [ X]; LCL0 [ ]; Other [ ] Species/ strain: Wistar rats ( male and female) Exposure time: 10, 20, 40, or 60 minutes Value: LC50 ( 10 m) = 28,130 mg/ m3 ( 40,300 ppm) LC50 ( 20 m) = 19,960 mg/ m3 ( 28,595 ppm) LC50 ( 40 m) = 14,170 mg/ m3 ( 20,300 ppm) LC50 ( 60 m) = 11,590 mg/ m3 ( 16,600 ppm) Method: Ten animals ( 5 males, 5 females) were exposed to each of a series of ammonia concentrations in an inhalation cylinder for 89 Ammonia ( CAS No. 7664 41 7) 10, 20, 40 or 60 minutes. After exposure, rats were housed in wire mesh cages for an observation period of 14 days. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas evolved from a pressurized cylinder of liquid ammonia. Remarks: Clinical signs of restlessness, eye irritation, nasal discharge, mouth breathing, and labored respiration were seen during exposure. Reference: Appelman, L. M., ten Berg, W. F., and Reuzel, P. G. J. 1982. Acute inhalation toxicity study of ammonia in rats with variable exposure periods. Am. Ind. Hyg. Assoc. J. 43( 9): 662 665.

( j) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ ] Species/ strain: ICR mice ( male) Exposure time: 1 hour Value: LC50 = 2960 mg/ m3 ( 4,230 ppm) Method: Four groups of 12 mice were exposed to each of three concentrations of NH3 gas in air. The 1 hour exposure was followed by a 14 day observation period. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia ( NH3) gas Remarks: Lungs of mice that died during exposure were diffusely haemorrhagic. A mild to moderate degree of chronic focal pneumonitis was also observed. Reference: Kapeghian, J. C., Mincer, H. H., Jones, A. B., Verlangieri, A. J., and Waters, I. W. 1982. Acute inhalation toxicity of ammonia in mice. Bull Environ. Contam. Toxicol. 29: 371 378.

( k) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] Species/ strain: Cat Exposure time: 10 minutes Method: Twenty cats were randomly placed into four groups of five cats each. Baseline pulmonary function tests were performed. All the animals were exposed to 1,000 ppm ammonia gas for 10 min. One group was euthanized after 24 hours and the other three groups were tested on days 7, 21, and 35 post exposure. GLP: Yes [ ] No [ ] ? [ X] Test substance: Anhydrous ammonia ( NH3) Remarks: Twenty four hours after exposure, cats had severe dyspnea, anorexia, and dehydration. Auscultation revealed bronchial breath sounds, sonorous and sibulent ronchi, and course rales. Lungs showed varying degrees of congestion, hemorrhage, edema, interstitial emphysema, and collapse. There was no significant change in Anatomical Dead Space ( ADS). The only significant change in Functional Residual Capacity ( RFC) was on day 21, at which time this value almost doubled. Seven days after exposure to ammonia gas, the epithelial damage was healed. 90 Ammonia ( CAS No. 7664 41 7) Reference: Dodd, K. T. and Gross. D. R. 1980. Ammonia inhalation toxicity in cats: a study of acute and chronic respiratory dysfunction. Arch. Environ. Health 35( 1): 6 14.

( l) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] Species/ strain: New Zealand White rabbit Exposure time: 2.5 to 3.0 hours Value: BUN ( pre exposure) = 19.4 mg/ 100 mL BUN ( post exposure) = 24.6 mg/ 100 mL Blood pH ( pre exposure) = 7.34 Blood pH ( post exposure) = 7.36 Blood CO2 ( pre exposure) = 14.3 meq/ L plasma Blood CO2 ( post exposure) = 18.9 meq/ L plasma Method: Sixteen adult female rabbits were exposed to 50 ppm in experiment 1 and 100 ppm ammonia in experiment 2. Each experiment ran from 7.5 to 9 hours duration with ammonia exposure occurring only during the second 2.5 to 3.0 hour segment. GLP: Yes [ ] No [ ] ? [ X] Test substance: Anhydrous ammonia ( NH3) Remarks: The decline in respiration rate was essentially linear over the 7.5 hour period for both groups under control conditions. The decrease in respiration rate upon exposure to ammonia was highly significant and essentially the same for the 50 ppm and 100 ppm exposure levels. BUN = Blood Urea Nitrogen. Reference: Mayan, M. H. and Merilan, C. P. 1972. Effects of ammonia inhalation on respiration rate of rabbits. J. Anim. Sci. 34( 3): 447 452.

( m) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] Species/ strain: Guinea pigs Exposure time: 6 to 18 weeks Method: Twelve male guinea pigs were used for experimentation and 6 for controls. Exposure to ammonia was for 6 hours per day, 5 days per week. At intervals of 6 weeks, 4 experimental and 2 control animals were sacrificed. GLP: Yes [ ] No [ ] ? [ X] Test substance: Anhydrous ammonia ( NH3) Remarks: Animals exposed for 6 and 12 weeks showed no abnormalities which could be attributed to ammonia. After 18 weeks, animals showed considerable congestion of spleens, livers and kidneys, and early degenerative changes in the suprarenal gland. Upper tubules of the kidneys showed fairly marked cloudy swelling with precipitated albumen in the lumens and some casts. Reference: Weatherby, J. H. 1952. Chronic toxicity of ammonia fumes by inhalation. Proc. Soc. Exp. Biol. Med. 81: 300 301.

( n) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] 91 Ammonia ( CAS No. 7664 41 7) Method: Summary of animal inhalation studies for ammonia. Remarks: The acute effects of ammonia in animals was reviewed as part of a health effects assessment prepared in 1990 for The Fertilizer Institute. In summary, acute exposure to high concentrations of ammonia in air to animals can result in death [ LC50 values as low as 2961 mg/ m3 ( 3796 ppm) in mice and 5137 mg/ m3 ( 6586 ppm) in rats for a one hour exposure.] Acute exposures to ammonia in the range of 200 700 mg/ m3 ( 256 897 ppm) resulted in excessive irritation and nasal and mouth secretions, depressed respiratory rates, and lung edema and hemorrhage [ it should be noted that some experiments showed no ill effects at levels as high as 700 mg/ m3 ( 897 ppm)]. One frequently observed result of acute exposure is the cessation of tracheal ciliary activity. For directly exposed tracheas, ciliary beating stopped after exposure to as low as 2.1 mg/ m3 ( 3 ppm). However, experiments which produced cessation without recovery utilized concentrations in the range of 280 1400 mg/ m3 ( 359 1795 ppm). Reference: Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C.

( o) Type: LC0 [ ]; LC100 [ ]; LC50 [ ]; LCL0 [ ]; Other [ X] Species/ strain: Duroc pigs Exposure time: 5 weeks Values: NOAEL = 61 ppm. Methods: Duroc pigs were exposed for 5 weeks to the following ammonia concentrations: 8, 43, 72 and 102 mg/ m3 ( 12, 61, 103, and 146 ppm). Exposures were conducted under controlled environmental conditions of 21.1oC dry bulb temperature and 77% relative humidity. Thirty six pigs with an average initial weight of approximately 54 kg were allotted into four 2.7 x 4.9 m. compartments. Ammonia was introduced into three of the four compartments in the supply air ducts. To control introduction, a corrosion resistant pressure regulating valve was mounted on the bulk tank. The ammonia was metered from this valve into a low pressure chamber that was maintained at 0.14 to 0.21 kg per square centimeter gauge pressure. Three stainless steel needle valves led from the low pressure chamber through rotameters and then into the supply air ducts of the three compartments. Ammonia levels were measured daily by bubbling a known quantity of air through dilute sulfuric acid and back titrating with dilute sodium hydroxide. GLP: Yes [ ] No [ X] ? [ ] Results: Coughing and nasal, lacrimal, and oral secretions were observed in pigs exposed for 5 weeks to 103 and 146 ppm ammonia. No significant effects were seen at 12 and 61 ppm for the same exposure duration. Test Substance: Atmospheric ammonia ( NH3) 92 Ammonia ( CAS No. 7664 41 7) Remarks: The authors reported that ammonia exposures ( 12 146 ppm) caused a highly significant adverse effect upon feed consumption and average daily gain. However, no statistical evaluations were performed and furthermore, the data presented do not appear to support these conclusions. Reference: Stombaugh, D. P., Teague, H. S., and Roller, W. L. 1969. Effects of atmospheric ammonia on the pig. J. Anim. Sci. 28( 6): 844 847.

5.1.3 ACUTE DERMAL TOXICITY Remarks: No data are available regarding systemic effects of dermal exposure to ammonia or ammonium compounds. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. 93 Ammonia ( CAS No. 7664 41 7) 5.1.4 ACUTE TOXICITY BY OTHER ROUTES OF ADMINISTRATION ( a) Type: LD0 [ ]; LD100 [ ]; LD50 [ X]; LDL0 [ ]; Other [ ] Species/ strain: Mus musculus ( Albino mice) and Gallus domesticus ( White Leghorn chicks) Exposure Time: 1 hour Value: LD50 ( intravenous; chicks) = 2.72 mmol CH3COONH4/ kg LD50 ( intravenous; mice) = 5.64 mmol CH3COONH4/ kg LD50 ( intraperitoneal; chicks) = 10.44 mmol CH3COONH4/ kg LD50 ( intraperitoneal; mice) = 10.84 mmol CH3COONH4/ kg Method: A total of 200 chicks and 180 mice were used. One half to 1.5 mL isotonic saline containing ammonium acetate was injected rapidly into the wing vein of the chicks and into a tail vein of the mice for intravenous studies, and into the peritoneal cavity for the intraperitoneal studies. Ten animals were exposed to each of eight to eleven concentration groups. Animals were observed continually until all signs of acute toxicity disappeared and the survivors counted after 1 hour. GLP: Yes [ ] No [ ] ? [ X] Test substance: Ammonium acetate ( CH3COONH4) Remarks: In the intravenous studies, reaction began immediately in both species, characterized by hyperventilation and clonic convulsions. In individuals who died, clonic convulsions were followed by a fatal tonic extensor convulsion. Mice which survived showed signs of hyperventilation and hyperirritability, but did not go into a coma. Chicks exhibited clonic convulsions followed by a gradual onset of coma and completely recovered in 50 60 minutes. The reaction to the intraperitoneal dose was similar between the two species. Clonic convulsions accompanied by a gradual onset of coma began 10 15 minutes after injection. Animals either died of a fatal tonic extensor convulsion or recovered in 50 60 minutes. Reference: Wilson, R. P., Muhrer, M. E., and Bloomfield, R. A. 1968. Comparative ammonia toxicity. Comp. Biochem. Physiol. 25: 295 301.

( b) Type: LD0 [ ]; LD100 [ ]; LD50 [ X]; LDL0 [ ]; Other [ ] Species/ strain: Rat Value: LD50 ( intraperitoneal dose) = 8.2 mmol NH4OCOCH3/ kg Method: Intraperitoneal injection GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia acetate Remarks: Signs included hyperventilation, clonic convulsions, coma and death. These signs did not appear until 15 30 minutes after administration. Reference: Greenstein, J. P., Winitz, M., Gullino, P., Birnbaum, S. M., and Otey, M. C. 1956. Studies on the metabolism of amino acids and related compounds in vivo. III. Prevention of ammonia toxicity by arginine and related compounds. Arch. Biochem. 94 Ammonia ( CAS No. 7664 41 7) Biophys. 64: 342 354. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. ( c) Type: LD0 [ ]; LD100 [ ]; LD50 [ X]; LDL0 [ ]; Other [ ] Species/ strain: Mouse Value: LD50 ( intravenous dose) = 6.23 mmol NH4OCOCH3/ kg LD50 ( intravenous dose) = 5.05 mmol NH4HCO3/ kg LD50 ( intravenous dose) = 4.47 mmol NH4CO3/ kg LD50 ( intravenous dose) = 6.75 mmol NH4Cl/ kg LD50 ( intravenous dose) = 2.53 mmol NH4OH/ kg Method: Intravenous injection GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonium acetate ( NH4OCOCH3), ammonium bicarbonate ( NH4HCO3), ammonium carbonate ( NH4CO3), ammonium chloride ( NH4Cl) and ammonium hydroxide ( NH4OH) Remarks: Toxic signs included immediate hyperventilation and clonic convulsions followed by coma, tonic convulsions and death. Surviving animals recover rapidly and completely. Reference: Warren, K. S. 1958. The differential toxicity of ammonium salts. J. Clin. Invest. 37: 497 501. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( d) Type: LD0 [ ]; LD100 [ ]; LD50 [ ]; LDL0 [ ]; Other [ X] Species/ strain: White rat Exposure Time: 3 hours Value: Minimum lethal dose = 6.80 mL ( NH4) 2CrO4; ( 0.072 mg ( NH4) 2CrO4 N) Minimum lethal dose = 6.74 mL NH4Cl; ( 0.072 mg NH4Cl N) Minimum lethal dose = 6.21 mL ( NH4) 2HPO4; ( 0.061 mg ( NH4) 2HPO4 N) Minimum lethal dose = 7.87 mL No. 1 NH4HCO3; ( 0.073 mg No. 1 NH4HCO3 N) Minimum lethal dose = 5.60 mL No. 2 NH4( H) CO3; ( 0.055 mg No. 2 NH4( H) CO3 N) Minimum lethal dose = 6.75 mL NH4NO3; ( 0.065 mg NH4NO3 N) Minimum lethal dose = 10.00 mL ( NH4) 2SO4; ( 0.094 mg ( NH4) 2SO4 N) Minimum lethal dose = 6.20 mL NH4Br; ( 0.055 mg NH4Br N) Minimum lethal dose = 6.30 mL ( NH4) 2CO3 + carbamide; ( 0.055 mg ( NH4) 2CO3 + carbamide N) Minimum lethal dose = 4.80 mL ( NH4) 3PO4 neutral; ( 0.0384 mg ( NH4) 3PO4 neutral N) Minimum lethal dose = 7.56 mL ( H2) NH4PO4; ( 0.05708 mg ( H2) NH4PO4 N) Minimum lethal dose = 6.00 mL NH4I Minimum lethal dose = 7.40 mL NH4CrSO4 Method: All salts ( ammonium oxalate, carbonate, chromate, chloride, nitrate, citrate, sulfate, tartrate, hydrogen phosphate, acetate, 95 Ammonia ( CAS No. 7664 41 7) sarcolactate, and lactate) were made to approximate 5 percent solution and injected into white rats. The nitrogen in the form of NH3 was determined in three 5 percent solutions. Six animals were used for each series. GLP: Yes [ ] No [ X] ? [ ] Test substance: Various ammonium salts ( ammonium oxalate, carbonate, chromate, chloride, nitrate, citrate, sulfate, tartrate, hydrogen phosphate, acetate, sarcolactate, and lactate) Remarks: Contrary to previous reports by Rachford and Crane ( 1902), the current study demonstrated that the toxicity of ammonium salts to white rats is directly proportional to the amount of un ionized ammonia present ( i. e. rather than on the form of salt used). Note that while this study is old ( 1922), it does provide evidence that the anion of the salt is less important with respect to toxicity than un ionized ammonia. Reference: Underhill, F. P. and Kapsinow, R. 1922. The comparative toxicity of ammonium salts. J. Biol. Chem. 54: 451 457.

5.2 CORROSIVENESS/ IRRITATION 5.2.1 SKIN IRRITATION/ CORROSION Remarks: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant. Most of the information is human clinical data and is described in Section 5.11. Reference: World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

5.2.2 EYE IRRITATION/ CORROSION ( a) Remarks: Subacute and chronic exposure of animals to ammonia in the range of 200 1000 ppm has been found to produce eye damage. At 100 200 ppm, moderate to severe eye irritation occurred. Reference: BIBRA. 1995. Toxicology Profile: Ammonia. BIBRA International.

( b) Remarks: Ammonia, partly because of its lipid solubility, penetrates the corneal membrane rapidly. In rabbits, conjunctival oedema with ischaemia and segmentation of the limbal vessels were noted within 30 minutes. In rabbits with corneal burns, neovascularization occurred after 1 week, but it was delayed in animals with both corneal and limbal burns. Reference: National Research Council ( NRC). 1979. Ammonia. Subcommittee on Ammonia. Committee on Medical and Biologic Effects of Environmental Pollutants. Division of 96 Ammonia ( CAS No. 7664 41 7) Medical Sciences, Assembly of Life Sciences. National Research Council. Baltimore: University Park Press. NTIS No. PB 278 027.

5.3 SKIN SENSITISATION Remarks: No specific skin sensitization studies were identified.

* 5.4 REPEATED DOSE TOXICITY ( a) Species/ strain: Male and female Sprague Dawley and Long Evans rats, male and female Princeton derived Guinea pigs, male New Zealand albino rabbits, male squirrel monkeys and purebred male beagle dogs Route of administration: Inhalation Exposure period: 54, 90 or 114 days Frequency of treatment: Repeated dose or continuous exposures Dose: 155 ( 221 ppm) or 770 ( 1100 ppm) mg/ m3 ( repeated dose) 127 ( 181 ppm), 262 ( 374 ppm), 455 ( 650 ppm), 470 ( 671 ppm) mg/ m3 ( continuous dose) 40 mg/ m3 ( continuous dose) Control group: Yes [ X]; No [ ]; No data [ ] NOEL: See results LOEL: See results Results: No mortality occurred in any species exposed to either 155 or 770 mg/ m3 in the repeated dose studies. In the 770 mg/ m3 exposure, mild to moderate lacrimation and dyspnea were evident in the rabbits and dogs in the first week, but symptoms disappeared by the second week. In rats and guinea pigs, the lungs showed nonspecific inflammatory changes. In the continuous exposure studies with rats, no mortality or other treatment related effects were observed at 127 mg/ m3. No mortality was observed at 262 mg/ m3, although about 25% of the rats had mild nasal discharge. Continuous exposure of rats to 455 mg/ m3 resulted in the death of 50 of 51 rats by day 65. All showed mild signs of dyspnea and nasal irritation. Continuous exposure of rats to 470 mg/ m3 resulted in the mortality of 13 of 515 rats and 4 of 15 guinea pigs. Marked eye irritation was noted in dogs and rabbits. In a separate experiment, all species were exposed to a continuous concentration at 40 mg/ m3 for 114 days. No mortality or signs of toxicity were noted in any of the animals. Observations at necropsy were normal, and no treatment related histopathological findings were observed. Method: In repeated exposure studies, there were 30 8 hr/ day, 5 day/ week exposures. In the continuous exposure studies, rats were exposed 24 hours/ day for 90 days. In separate 97 Ammonia ( CAS No. 7664 41 7) experiments, all species were exposed continuously for 114 days. The rate of air flow to the inhalation chambers was maintained at 1.2 m3/ min at a temperature of 77 ° F. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonium hydroxide ( NH4OH) Reference: Coon, R. A., Jones, R. A., Jenkins, Jr., L. J., and Siegel, J. 1970. Animal inhalation studies on ammonia, ethylene, glycol, formaldehyde, dimethylamine, and ethanol. Toxicol. Appl. Pharmacol. 16: 646 655.

( b) Species/ strain: White rats Sex: Female [ ]; Male [ ]; Male/ Female [ ]; No data [ X] Route of administration: Inhalation Exposure period: 3 months Frequency of treatment: 25 or 60 minutes every 48 hours Dose: 30 and 100 mg/ m3 ( 43 and 143 ppm) Control group: Yes [ X]; No [ ]; No data [ ] NOEL: 30 mg/ m3 LOEL: 100 mg/ m3 Results: At 100 mg/ m3 there was mild leucocytosis. However, there were no differences from control with regard to oxygen consumption, neuromuscular excitation threshold, heart rate, blood sugar, blood residual nitrogen and total serum protein. No effects were reported at the low dose level. GLP: Yes [ ] No [ X] ? [ ] Test substance: Unspecified ammonia gas Reference: Propkopieva, A. S. and Yushkov, G. G. 1975. Toxicology of ammonia in animals repeatedly exposed for short lengths of time. Gig. Tr. Prof. Zabol. ( Russian) 9: 54 55. In World Health Organization ( WHO). 1986. Ammonia Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. In Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C.

( c) Species/ strain: Sherman and Fisher rats Sex: Female [ ]; Male [ ]; Male/ Female [ ]; No data [ X] Route of administration: Inhalation Exposure period: 75 days Frequency of treatment: Not specified Dose: average concentration of 105 mg/ m3 ( 150 ppm) Control group: Yes [ X]; No [ ]; No data [ ] NOEL: See results LOEL: See results Results: Histological changes in the olfactory and respiratory epithelia of the nasal cavity were similar for all exposed rats, showing increased thickness, pyknotic nuclei, and hyperplasia. The submucosa was oedematous with marked dilation of the small vessels. Lesions decreased posteriorly. 98 Ammonia ( CAS No. 7664 41 7) Method: Rats were exposed via inhalation for 75 days to ammonia from natural sources. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia gas ( NH3) Reference: Broderson, J. R., Lindsey, J. R. and Cranford, J. E. 1976. The role of environmental ammonia in respiratory mycoplasmosis of rats. Am. J. Pathol. 85: 115 130. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( d) Species/ strain: Rat Sex: Female [ ]; Male [ X]; Male/ Female [ ]; No data [ ] Route of administration: Inhalation Exposure period: Up to 8 weeks Frequency of treatment: Continuous Dose: 350 mg/ m3 ( 500 ppm) Control group: Yes [ X]; No [ ]; No data [ ] NOEL: See results LOEL: See results Results: The animals were sacrificed after different times of exposure to establish a time dependency of the effects. Nasal irritation began on the 4th day of exposure. After 3 weeks, the exposed rats showed nasal irritation and inflammation of the upper respiratory tract but no effects were observed in the bronchioles and alveoli. After 8 weeks, none of these inflammatory lesions were present. Method: Twenty seven young male rats were exposed to a continuous atmospheric concentration of ammonia. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia gas ( NH3) Reference: Richard, D., Bouley, G. and Boudene, C. 1978. Effets de l'inhalation continue d'ammoniac chez the rat et la souris. Bull. Eur. Physiopathol. Resp. 14: 573 582. ( Original in French.) In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( e) Species/ strain: Sherman and Fisher rats Sex: Female [ ]; Male [ ]; Male/ Female [ ]; No data [ X] Route of administration: Inhalation Exposure period: 35 days Frequency of treatment: Not specified Dose: 175 mg/ m3 ( 250 ppm) Control group: Yes [ X]; No [ ]; No data [ ] NOEL: See results LOEL: See results Results: Histological changes in the olfactory and respiratory epithelia of the nasal cavity were similar in all exposed rats, showing 99 Ammonia ( CAS No. 7664 41 7) increased thickness, pyknotic nuclei and hyperplasia. The submucosa was oedematous with marked dilation of small vessels. Lesions decreased posteriorly. Method: Rats were exposed via inhalation for 35 days to purified ammonia. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia gas ( NH3) Reference: Broderson, J. R. et al. 1976. Am. J. Pathol. 85: 115 130. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( f) Species/ strain: Guinea pig Sex: Female [ ]; Male [ X]; Male/ Female [ ]; No data [ ] Route of administration: Inhalation Exposure period: 18 weeks Frequency of treatment: 6 hours/ day; 5 days/ week Post exposure observation period: Dose: About 119 mg/ m3 ( 170 ppm) [ range 98 140 mg/ m3 ( 140 200) ppm] Control group: Yes [ X]; No [ ]; No data [ ] NOEL: See results LOEL: See results Results: There were no significant findings after 6 and 12 weeks. In animals sacrificed after 18 weeks, there was relatively mild but definite congestion of the liver, spleen, and kidneys with degenerative changes in the adrenal glands, and hemosiderosis in the spleen indicating hematotoxicity. There was cloudy swelling in the epithelium of the proximale tubules of the kidney as well as albumin precipitation in the lumen with some casts. Method: Twelve male guinea pigs ( plus 6 controls) were exposed to anhydrous ammonia gas released into the air of an exposure chamber. GLP: Yes [ ] No [ X] ? [ ] Test substance: Anhydrous ammonia gas ( NH3) Reference: Weatherby, J. H. 1952. Chronic toxicity of ammonia fumes by inhalation. Proc. Soc. Exp. Biol. Med. 81: 300 301.

* 5.5 GENETIC TOXICITY IN VITRO A. BACTERIAL TEST ( a) Type: Bacterial gene mutation assay System of testing: Salmonella typhimurium and E. coli Concentration: Up to 25,000 ppm 100 Ammonia ( CAS No. 7664 41 7) Metabolic activation: With [ ]; Without [ ]; With and without [ X]; No data [ ] Results: Cytotoxicity conc: With metabolic activation: 25,000 ppm Without metabolic activation: 25,000 ppm Genotoxic effects: + ?  With metabolic activation: [ ] [ ] [ X] Without metabolic activation: [ ] [ ] [ X] Method: The cells were exposed to concentrations of the ammonia gas up to 25,000 ppm. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia gas ( NH3) Remarks: With and without liver metabolic activation system. Reference: Shimizu H. et al. 1985. Jap. J. Ind. Health. 27: 400. ( cited in BIBRA 1995).

( b) Type: Bacterial gene mutation assay System of testing: Salmonella and Saccharomyces Remarks: WHO and Clement report that ammonium sulfate was found to be non mutagenic in studies performed by Litton Bionetics, Inc. Reference: Litton Bionetics, Inc. 1975. Mutagenic Evaluation of Compound FDA 73 42 Ammonium Sulfate, Granular, Food Grade, Washington, D. C. Litton Bionetics. ( NTIS PB 245506). In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C.

B. NON BACTERIAL IN VITRO TEST Type: Cytogenetic assay System of testing: Chick fibroblasts Concentration: Unspecified Metabolic activation: With [ ]; Without [ ]; With and without [ ]; No data [ X] Method: Not specified GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonia gas ( NH3) Remarks: The original reference reported that ammonia induced clumping of chromosomes, arrested spindle formation, and induced polyploidy in chick fibroblasts. The original study was reported in 1932. Reference: Rosenfeld, M. 1932. Experimental modification of mitosis by ammonia. Arch. Exp. Zellforsch. Gewebezuecht. 14: 1. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. 101 Ammonia ( CAS No. 7664 41 7) * 5.6 GENETIC TOXICITY IN VIVO Type: Drosophila mutagenicity test Species/ strain: Drosophila melanogaster Remarks: WHO, BIBRA, and Clement all report early studies suggesting mutagenic activity occurred upon exposure to ammonia. However, this activity was only evident at doses that killed 98% of the flies, which casts significant doubt on the validity of the results. The Clement report concludes that there are no data to show that ammonia is mutagenic in mammals. Reference: World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C. BIBRA. 1995. Toxicology Profile: Ammonia. BIBRA International.

5.7 CARCINOGENICITY ( a) Species/ strain: Swiss and C3H mice Sex: Female [ ]; Male [ ]; Male/ female [ X]; No data [ ] Route of administration: Drinking water Exposure period: Life time Frequency of treatment: Ad libitum Control group: Yes [ ]; No [ ]; No data [ X]; Concurrent no treatment [ ]; Concurrent vehicle [ ]; Historical [ ] Results: Life long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain. GLP: Yes [ ] No [ X] ? [ ] Test substance: Ammonium hydroxide ( NH4OH) Doses: Unspecified Remarks: The compound tested was NH4OH, which forms an equilibrium with NH3 when ammonia is dissolved in water. No further information is given in source. Reference: Toth, B. 1972. Hydrazine, methylhydrazine and methylhydrazine sulfate carcinogenesis in Swiss mice. Int. J. Cancer. 9: 109. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( b) Species/ Strain: All 102 Ammonia ( CAS No. 7664 41 7) Remarks: WHO and Clement note that there is no reliable evidence indicating that ammonia is carcinogenic. BIBRA notes a poorly reported study ( Gaafar et al 1992) in which one of 50 adult mice exposed 15 minutes/ day, 6 days/ week for 8 weeks to " ammonia vapour" ( derived from a 12% ammonia solution, but not further specified) developed nasal cancer. However, there was a low incidence of other microscopic changes in the nasal tissues suggestive of a tumorigenic response. Reference: World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C. BIBRA. 1995. Toxicology Profile: Ammonia. BIBRA International.

( c) Species/ Strain: Humans Remarks: Epidemiological studies by Bittershol that have been widely cited, have shown excess incidence of cancers in manufacturing plants. However, the study has methodological flaws and confounding influences from carcinogens in the ambient environment. Reference: Bittershol, G. ( 1971) Epidemiologic study on cancer of workers in a chemical plant. Arch. Gesh. 38: 198 209 ( Original in German). Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C.

* 5.8 TOXICITY TO REPRODUCTION Type: Fertility [ ]; One generation study [ X]; Two generation study [ ]; Other [ ] Species/ strain: Yorkshire x Hampshire x Chester White gilts ( a young sow) Sex: Female [ ]; Male [ ]; Male/ Female [ X]; No data [ ] Route of Administration: Inhalation of ammonia in air environment Exposure Period: 6 weeks; 10 weeks Frequency of treatment: Continuous Postexposure observation period: Premating exposure period: male: female: 6 weeks Duration of the test: 6 weeks Doses: mean 7 ppm NH3, mean 35 ppm NH3 Control group: Yes [ ]; No [ X]; No data [ ]; Concurrent no treatment [ ]; Concurrent vehicle [ ]; Historical [ ] NOAEL Prenatal: See results NOAEL F1 Offspring: See results NOAEL F2 Offspring: See results 103 Ammonia ( CAS No. 7664 41 7) Results: At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain ( MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetusto corpus luteum ratio were all similar between the two groups. Method: From 2 4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low ( mean 7 ppm) or moderate ( mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain ( MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. GLP: Yes [ ] No [ ] ? [ X] Test substance: Ammonia ( NH3) obtained by flushing of manure pits weekly. Remarks: These data indicate that exposure of gilts to mean aerial ammonia concentrations of 36 ppm depressed MDG for 2 weeks but failed to alter onset of puberty or litter size through day 30 of gestation. ( relative to exposure to 7ppm). Reference: Diekman, M. A., Scheidt, A. B., Sutton, A. L., Green, M. L., Clapper, J. A., Kelly, D. T., and Van Alstine, W. G. 1993. Growth and reproductive performance, during exposure to ammonia, of gilts afflicted with pneumonia and atrophic rhinitis. Am. J. Vet. Res. 54( 12): 2128 2131.

* 5.9 DEVELOPMENTAL TOXICITY/ TERATOGENICITY Remarks: No specific studies on developmental or teratorgenic effects were identified.

5.10 OTHER RELEVANT INFORMATION A. SPECIFIC TOXICITIES ( NEUROTOXICITY, IMMUNOTOXICITY etc.)

B. TOXICODYNAMICS, TOXICOKINETICS ( a) Type: Animal [ X]; Aquatic [ ]; Plant [ ]; Terrestrial [ ]; 104 Ammonia ( CAS No. 7664 41 7) Other [ ] Results: At the 2 lowest concentrations, there was no increase in bloodammonia However, after 8 hours at 220 and 826 mg/ m3 unionized NH3, significant increases of 3.26 and 4.18 mg NH3/ L were noted indicating pulmonary absorption of ammonia. These levels declined over time at higher concentrations, suggesting that compensation was occurring. Findings suggest that environmental ammonia concentrations found in animal holding rooms would have minimal adverse effects in healthy rats. Remarks: Four groups of rats, 8 per group, were exposed to average ammonia concentrations of 11, 23, 220 or 826 mg/ m3 ( 15, 32, 310, or 1,157 ppm) for 24 hours. Reference: Schaerdel, A. D., White, W. J., Lang, C. M., Dvorchik, B. H., and Bohner, K. 1983. Localized and systemic effects of environmental ammonia in rats. Lab. Anim. Sci. 33( 1): 40 45.

( b) Type: Results: Remarks: Mucosal cell migration rate appears to be accelerated by longterm administration of 0.01% ammonia, especially in the antrum. The effect of ammonia on cell kinetics differs between the antral and body mucosa. The toxicity of NH3 NH4 + solution to rat gastric mucosa was enhanced with an increase in pH of the solution. The amount of un ionized NH3 increases with increasing pH, and it causes cell damage. In the body mucosa, which is an acid secreting mucosa, the cytotoxicity of ammonia is lessened by secreted hydrochloric acid to form NH4Cl. The pH in the antral mucosa is higher than that on the body mucosa, which may explain the different effects of ammonia on the gastric mucosal cell migration rate. References: Tsujii, M., Kawano, S., Tsuji, S., Ito, T., Nagano, K., Sasaki, Y., Hayashi, N., Fusamoto, H., and Kamada, T. 1993. Cell kinetics of mucosal atrophy in rat stomach induced by longterm administration of ammonia. Gastroenterol. 104: 796 801.

* 5.11 EXPERIENCE WITH HUMAN EXPOSURE ( a) Type: Occupational exposure Results: There were no differences in symptoms, sense of smell, acute changes in lung function during exposure, or changes in baseline lung function in exposed workers compared to control workers. There was no relationship demonstrated between the level of exposure to ammonia ( average of 9.2 ppm) and acute changes in lung function over the work shift. No chronic effects on lung function that could be related to the length of exposure were demonstrated. 105 Ammonia ( CAS No. 7664 41 7) Remarks: The chronic effects of ammonia on industrial workers to levels less than 50 ppm were assessed. The study also examined the acute effects of ammonia exposure on the respiratory system, eyes, and skin. A total of 52 soda ash plant workers, 6 maintenance workers, and 35 control workers were assessed. All participants were male, mean age 40.5 years, and plant tenure approximately 15 years. Exposed workers were assessed on 2 workdays; on the first and last workdays of their workweek. The study was carried out over a period of one week. Maintenance workers were assessed on one workday in the middle of their workweek. The control group was assessed twice on two separate days during the same week. All participants completed a questionnaire regarding past occupational exposures, working conditions, smoking history, and respiratory symptoms and eye and skin complaints. Each participant's sense of smell was assessed at the beginning and end of the workweek. Spriometry was performed at the beginning and end of each work shift on both test days so that each worker had four tests done. The average concentration of ammonia to which workers were exposed during their work shifts was determined using NIOSH recommended procedures. Exposed and control workers were sampled over one work shift. The average sample collection period was 8.4 hours. The mean time weighted average ( TWA) ammonia exposure of the exposed group was 9.2 ppm, 0.3 ppm for the control group. Three workers were exposed to TWA concentrations in excess of 25 ppm. Reference: Holness, D. G., Purdham, J. T., and Nethercott, J. R. 1989. Acute and chronic respiratory effects of occupational exposure to ammonia. Am. Ind. Hyg. Assoc. J. 50( 12): 646 650.

( b) Type: Inhalation exposure by human volunteers Results: After acclimation, continuous exposure to 100 ppm, with occasional excursions to 200 ppm, is easily tolerated with no observed effect on general health. Remarks: Six unacclimated male and female volunteers were exposed six hours per day over a six week period to concentrations of 25, 50, and 100 ppm ammonia in an industrial environment, under strict medical surveillance. Inurement to eye, nose, and throat irritation was demonstrated after two to three weeks in addition to short term subjective adaptation. There were no significant differences between subjects or controls on common biological indicators, in physical examinations, or in performance of normal job duties. References: Ferguson, W. S., Koch, W. C., Webster, B. A., and Gould, J. R. 1977. Human physiological response and adaptation to ammonia. J. Occup. Med. 19( 5): 319 326.

( c) Type: Inhalation exposure by human volunteers. 106 Ammonia ( CAS No. 7664 41 7) Results: Concentrations of 72 ppm or higher caused discomfort and probably would not be tolerated by some human subjects. Concentrations of 50 ppm or less could be tolerated for at least five minutes and probably much longer. The level of 50 ppm appeared to be below the threshold concentration causing discomfort. Remarks: Ten human subjects were exposed for five minutes to concentrations of 32, 50, 72, or 134 ppm in a dynamic chamber. The results indicated irritation at 72 or 134 ppm with more irritation at the higher level. There was some dryness of the nose in one or two subjects exposed to 32 or 50 ppm, but there was not a definite irritation at these levels. Reference: Keplinger, M. L. 1973. Report to International Institute of Ammonia Refrigeration: Irritation Threshold Evaluation Study With Ammonia. Industrial BIOTEST Laboratories, Inc.

( d) Type: Inhalation exposure by human volunteers Results: Silverman et al. ( 1949) reported on 7 human volunteers exposed to a concentration of 300 mg/ m3 ( 500 ppm) ammonia for 30 min using an oral nasal mask. All 7 experienced upper respiratory irritation, which lasted up to 24 hours in 2 of the volunteers. Two subjects experienced marked lachrymation, in spite of the exposure being by oro nasal mask. The average respiratory minute volume increased markedly compared with control values, and in the 5 subjects in which minute by minute expired volumes were measured, there was a marked cyclical variation in minute volume with a period of 4 7 min. No coughing was noted. After exposure, respiratory minute volumes fell to levels below the pre exposure rate, but returned to pre exposure values within 5 min of exposure. Ammonia retention decreased progressively until an equilibrium of 24% retention ( ranging from 4 to 30%) was reached at approximately 19 min ( range 10 27 min). The indices of nitrogen metabolism ( BUN, NPN, urine urea, and urine ammonia) remained normal. The carbon dioxide combining power did not change. Remarks: Seven male volunteers were exposed to 350 mg/ m3 ( 500 ppm) NH3 for 30 minutes. Reference: Silverman, L., Whittenberger, J. L., and Muller, J. 1949. Physiological response of man to ammonia in low concentrations. J. Ind. Hyg. Toxicol. 31: 74 78. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

( e) Type: Inhalation exposure by human volunteers. Results: No effect on vital capacity ( VC), forced expiratory volume [ 1 sec] ( FEV1), or forced inspiratory volume [ 1 sec] ( FIV1). 107 Ammonia ( CAS No. 7664 41 7) Remarks: Sixteen volunteers, eight experts ( 29.53 yr) and eight nonexperts ( students, 18 30 yr), were exposed for two hours to ammonia in concentrations of 50, 80, 110 and 140 ppm. None of the test subjects were considered to be hypersusceptible to non specific irritants or demonstrated a decrease in respiratory function. Before leaving the test chamber, every subject described at least one symptom as " unbearable"; three times this was irritation of throat, two times urge to cough, and one time each for smell, irritation of eyes, nose or breast, headache, and general discomfort. All subjects perceived a hypo esthesia of the exposed skin and two noted excessive lacrimation. Reference: Verberk, M. M. 1977. Effects of ammonia in volunteers. Arch. Occup. Environ. Hlth. 39: 73 81.

( f) Remarks: As reported in NRC ( 1979), gaseous ammonia can elicit the following effects at the concentration specified. 400 ppm ( in air) = Immediate throat irritation 700 ppm ( in air) = Eye irritation   1700 ppm ( in air) = Coughing 2500  6500 ppm ( in air) = Life threatening after 0.5 hour 500  10000 ppm ( in air) = Mortality Reference: National Research Council ( NRC). 1979. Ammonia. Subcommittee on Ammonia. Committee on Medical and Biological Effects of Pollutants. Division of Medical Sciences, Assembly of Life Sciences. National Research Council. Baltimore: University Park Press. NTIS No. PB 278 027. 108 Ammonia ( CAS No. 7664 41 7) 6. REFERENCES 29 CFR 1910.1000. June 1, 1998. In Hazardous Substances Database ( HSDB). Ammonia. 1999. National Library of Medicine, Bethesda, MD.

Admiraal, W. 1977. Tolerance of estuarine benthic diatoms to high concentrations of ammonia, nitrite ion, nitrate ion, and orthophosphate. Mar. Biol. 43: 307 315.

Anderson, D. P., Beard, C. W., and Hanson, R. P. 1964. The adverse effects of ammonia on chickens including resistance to infection with newcastle disease virus. Avian Dis. 8: 369 379.

Ankley, G. T., Schubauer Berigan, and Monson, P. D. 1995. Influence of pH and hardness on toxicity of ammonia to the amphipod Hyalella azteca. Can. J. Fish. Aquat. Sci. 52: 2078 2083.

Anthonisen, A. C., Loehr, R. C., Prakasam, T. B. S., and Srinath, E. G. 1976. Inhibition of nitrification by ammonia and nitrous acid. J. Water Poll. Control Fed. 48: 835 852.

Appelman, L. M., ten Berge, W. F., and Reuzel, P. G. J. 1982. Acute inhalation toxicity study of ammonia in variable exposure periods. Am. Ind. Hyg. Assoc. J. 43( 9): 662 665.

Arthur, J. W., West, C. W., Allen, K. N., and Hedtke, S. F. 1987. Seasonal toxicity of ammonia to five fish and nine invertebrate species. Environ. Contam. Toxicol. 38: 324 331.

Asman, W. A. and Janssen, A. J. 1987. A long range transport model for ammonia and ammonium for Europe. Atmos. Environ. 21( 10). In Constable, M., Jensen, F., McLernon, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Asman, W. A., Pinksterboer, E. F., Mass, H. F., Erisman, J. W., Waijers Ypelaan, A., Slanina, J., and Horst, T. W. 1989. Gradients of the ammonia concentration in a nature reserve: Model results and measurements. Atmos. Environ. 23( 10): 2259. In Constable, M., Jensen, F., McLernon, J., Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Austin, E. R. and Lee, G. F. 1973. Nitrogen release from lake sediments. J. Water Pollut. Control Fed. 45: 870 879.

Bader, J. A. and Grizzle, J. M. 1992. Effects of ammonia on growth and survival of recently hatched channel catfish. Amer. Fish. Soc. 4: 17 23.

Baker, J. H. et al. 1959. Determination of application losses of anhydrous ammonia. Agronomy Journal 51: 361 362. In U. S. Environmental Protection Agency ( USEPA). 1998b. Emission Factor Documentation for AP 42 Section 9.2.1. Draft. Research Triangle Park: Office of Air Quality Planning and Standards. 109 Ammonia ( CAS No. 7664 41 7) Barrow, C. S., Alarie, Y. and Stock, M. F. 1978. Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants. Arch. Environ. Health. 33: 79 88. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Barton, L. V. 1940. Toxicity of ammonia, chlorine, hydrogen cyanide, hydrogen sulphide, and sulphur dioxide gases. IV. Seeds. Contrib. Boyce Thompson Inst. 11: 357 363. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

BASF AG, Abteilung Analytik; unveroeffentlichte Untersuchung ( BRU 92.004). In European Commission 1996. Ammonia. International Uniform Chemical Information Database.

BASF AG, Sicherheitsdatenblatt Ammoniak fluessig ( 27.04.94). In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Beaumont, A. R. and Budd, M. D. 1984. Marine. Poll. Bull. 15: 402 405. In Vorlaeufige Ergebnisse des F+ E Vorhabens Bewertung wassergefaehrdender Stoffe. 1985. vgl. Datenblaetter zum Katalog wassergefaehrdender Stoffee, KBwS, Nr. 5. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Benedict, H. M. and Breen, W. H. 1955. The use of weeds as a means of evaluating vegetation damage caused by air pollution. Proc. 3rd Natl. Pollution Symp. Pasadena, Calif. Pp. 177 190. Zitiert nach: DSM, Inventory of data on chemicals, Ammonia, Delft, 1992. RO471001/ 4150J. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Betterton, E. A. 1992. In Nriagu, J. O. ( ed.). In Gaseous Pollutants: Characterization and Cycling. New York: John Wiley & Sons, Inc. Pp. 1 50.

BIBRA. 1995. Toxicology Profile: Ammonia. BIBRA International.

Bittershol, G. 1971. Epidemiologic study on cancer of workers in a chemical plant. Arch. Gesh. 38: 198 209 ( Original in German).

Booth, N. H. and McDonald, L. E. 1982. Veterinary Pharmacology and Therapeutics. 5th edition. Pp. 938 939.

Boyd, E. M., MacLachlan, M. L., and Perry, W. F. 1944. Experimental ammonia gas poisoning in rabbits and cats. J. Ind. Hyg. Toxicol. 26: 29 34.

Broderson, J. R., Lindsey, J. R. and Cranford, J. E. 1976. The role of environmental ammonia in respiratory mycoplasmosis of rats. Am. J. Pathol. 85: 115 130. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Brown, V. M.; Jordan, D. H. M.; and Tiller, B. A. 1969. The acute toxicity to rainbow trout of fluctuating concentrations and mixtures of ammonia, phenol and zinc. J. Fish. Biol. 1: 1 9. 110 Ammonia ( CAS No. 7664 41 7) Buckley, J. A. 1978. Acute toxicity of un ionized ammonia to fingerling coho salmon. Prog. Fish Cult. 40( 1): 30 32.

Budavari, S. ( ed.). 1996. Merck Index. 12th ed. Whitehouse Station: Merck Research Laboratories.

Burkhalter, D. E. and Kaya, C. M. 1977. Effects of prolonged exposure to ammonia on fertilized eggs and sac fry of rainbow trout ( Salmo gairdneri). Trans. Amer. Fish. Soc. 106( 5): 470 474.

Calamari, D., Marchetti, R., and Vailati, G. 1981. Effects of long term exposure to ammonia on the developmental stages of rainbow trout ( Salmo gairdneri Richardson). Rapp. P. v. Reun. Cons. Int. Explor. Mer. 178: 81 86.

Cameron, J. N. and Heisler, N. 1983. Studies of ammonia in the rainbow trout: physicochemical parameters, acid base behaviour and respiratory clearance. J. Exp. Biol. 105: 107 125.

Canadian Fertilizer Institute ( CFI). 1996. 1995 Emissions inventory, update. Ottawa. In Constable, M., Jensen, F., McLeron, J. Craig, G., Moore D. 1996. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, environment Canada.

Charles, D. R. and Payne, C. G. 1966. The influence of graded levels of atmospheric ammonia on chickens. II. Effects on the performance of laying hens. Br. Poult. Sci. 7: 189 198. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Chen, J. C. and Kou, Y. Z. 1993. Accumulation of ammonia in the haemolymph of Penaeus monodon exposed to ambient ammonia. Aquaculture 109: 177 185.

Clement Associates, Inc. 1990. Health Effects Assessment for Ammonia. Prepared for The Fertilizer Institute, Washington, D. C.

Coffee, R. C. and Bartholomew, W. V. 1964. Some aspects of ammonia sorption by soil surfaces. Soil Sci. Soc. Proc. 28: 485 490.

Colt, J. and Tchobanoglous, G. 1978. Chronic exposure of channel catfish Ictalurus punctatus, to ammonia: effects on growth and survival. Aquaculture 15: 353 372.

Compressed Gas Association, Inc. 1990. Handbook of Compressed Gases. 3rd ed. Pp. 259 260. In Compressed Gas Association, Inc. 1999. American National Standard Safety Requirements for the Storage and Handling of Anhydrous Ammonia. 5th ed. Arlington: Compressed Gas Association, Inc. 111 Ammonia ( CAS No. 7664 41 7) Constable, M., Jensen, F., McLeron, J. Craig., G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Coon, R. A., Jones, R. A., Jenkins, Jr, L. J., and Siegel, J. 1970. Animal inhalation studies on ammonia, ethylene, glycol, formaldehyde, dimethylamine, and ethanol. Toxicol. Appl. Pharmacol. 16: 646 655.

Dabrowski, H. and Skiora, H. 1986. Acute toxicity of ammonia to common carp ( Cyprinus carpioL.). Pol. Arch. Hydrobiol. 33( 1): 121 128.

Day, D. L., Hansen, E. L, and Anderson, S. 1965. Gases and odors in confinement swine buildings. Trans. Am. Soc. Agric. Eng. 8: 118 121. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Denmead, O. T. et al. 1982. Atmospheric dispersion of ammonia during application of anhydrous ammonia fertilizer. J. Environ. Qual. 11( 4): 568 572. In U. S. Environmental Protection Agency ( USEPA). 1998a. AP 42. Draft. Vol. 1 5th ed. Research Triangle Park: Office of Air Quality Planning and Standards.

Denmead, O. T. et al. 1977. A direct field measurement of ammonia emission after injection of anhydrous ammonia. Soil Sci. Soc. Amer. J. 41: 1001 1004. In U. S. Environmental Protection Agency ( USEPA). 1998a. AP 42. Draft. Vol. 1 5th ed. Research Triangle Park: Office of Air Quality Planning and Standards.

Diamond, J. M., Mackler, D. G., Rasnake, W. J., and Gruber, D. 1993. Derivation of site specific ammonia criteria for an effluent dominated headwater stream. Environ. Toxicol. Chem. 12: 649 658.

Diekman, M. A., Scheidt, A. B., Sutton, A. L., Green, M. L., Clapper, J. A., Kelly, D. T., and Van Alstine, W. G. 1993. Growth and reproductive performance, during exposure to ammonia, of gilts afflicted with pneumonia and atrophic rhinitis. Am. J. Vet. Res. 54( 12): 2128 2131.

Directive 92/ 32 of April 30, 1992. 1992. Official Journal of the European Communities, No. L154 of June 5, 1992.

Dodd, K. T. and Gross. D. R. 1980. Ammonia inhalation toxicity in cats: a study of acute and chronic respiratory dysfunction. Arch. Environ. Health. 35( 1): 6 14.

DSM, Inventory of Data on chemicals, Ammonia, Delft. 1992. LRO471001/ 4150J. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Ecological Analysts, Inc. 1981. The Sources, Chemistry, Fate, and Effects of Ammonia in Aquatic Environments. Washington DC: American Petroleum Institute.

Emerson, K., Russo, R. C., Lund, R. E., and Thurston, R. V. 1975. Aqueous ammonia equilibrium calculations: effect of pH and temperature. J. Fish. Res. Board Can. 32: 2379 2383. 112 Ammonia ( CAS No. 7664 41 7) Environment Canada. 1984. Technical Information for Problem Spills: Ammonia. Ottawa, Ontario: Environmental Protection Service, Technical Services Branch.

Epifanio, C. E. and Srna, R. F. 1975. Toxicity of ammonia, nitrite ion, nitrate ion, and orthophosphate to Mercenaria mercenaria and Crassostrea virginica. Mar. Biol. 33: 241 246.

Erickson, R. J. 1985. An evaluation of mathematical models for the effects of pH and temperature on ammonia toxicity to aquatic organisms. Water Res. 19( 8): 1047 1058.

European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Evans, D. E. and Cameron, J. N. 1956. Gi11 ammonia transport. J. Exp. Zool. 239: 17 23.

Fenn, L. and Hossner, L. 1985. Ammonia volatilization from ammonia or ammonium forming nitrogen fertilizers. In Advances in Soil Science. Vol. I. New York: Springer Verlag. In Constable, M., Jensen, F., McLernon, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act., Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Ferguson, W. S., Koch, W. C., Webster, L. B., and Gould, J. R. 1977. Human physiological response and adaptation to ammonia. J. Occup. Med. 19( 5): 319 326.

Fromm, P. O., and Gillette, J. R. 1968. Effect of ambient ammonia on blood ammonia and nitrogen excretion of rainbow trout ( Salmo gaidneri). Comp. Biochem. Physiol. 26: 887 896.

Fuhrer, J. 1985. Formation of secondary air pollutants and their occurrence in Europe. Experientia ( Basel) 41: 286 301.

Gersich, F. M. and Hopkins, D. L. 1986. Site specific acute and chronic toxicity of ammonia to Daphnia magna Straus. Environ. Toxicol. Chem. 5: 443 447.

Graedel, T. E. and Allara, D. L. 1977. Pp. 467 473. EPA 600/ 3 77 001A, PB 264.

Greenstein, J. P., Winitz, M., Gullino, P., Birnbaum, S. M., and Otey, M. C. 1956. Studies on the metabolism of amino acids and related compounds in vivo. III. Prevention of ammonia toxicity by arginine and related compounds. Arch. Biochem. Biophys. 64: 342 354. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Hales, J. M. and Drewes, D. R. 1979. Solubility of ammonia in water at low concentrations. Atmos. Environ. 13: 1133 1147.

Harader, R. R. and Allen, G. H. 1983. Ammonia toxicity to chinook salmon parr: reduction in saline water. Trans. Amer. Fish. Soc. 112: 834 837. 113 Ammonia ( CAS No. 7664 41 7) Hazardous Substances Data Bank ( HSDB). 1999. Ammonia. National Library of Medicine, Bethesda, MD.

Hermanutz, R. O., Hedtke, S. F., Arthur, J. W., Andrew, R. W., Allen, K. N., and Helgen, J. C. 1987. Ammonia effects on microinvertebrates and fish in outdoor experimental streams. Environ. Poll. 47: 249 283. Hickey, C. W. and Vickers, M. L. 1994. Toxicity of ammonia to nine native New Zealand freshwater invertebrate species. Arch. Environ. Contam. Toxicol. 26: 292 298.

Holness, D. G., Purdham, J. T., and Nethercott, J. R. 1989. Acute and chronic respiratory effects of occupational exposure to ammonia. Am. Ind. Hyg. Assoc. J. 50( 12): 646 650.

Hutchinson, G. L. and Viets, F. G., Jr. 1969. Nitrogen enrichment of surface water by absorption of ammonia volatilized from cattle feedlots. Science 166: 514 515.

IFDC. 2002. North America Fertilizer Capacity, January 2002.

Indorato, A. M. et al. 1985. First International Symposium on Toxicity Testing using Bacteria. Burlington, Ontario, Canada 17 19 May 1983. In Datenblaetter zum Katalog wassergefaehrdender Stoffe, KBwS. Nr. 5. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Jofre, M. B., and Karasov, W. H. 1999. Direct effect of ammonia on three species of North American anuran amphibians. Environ. Toxicol. Chem. 18( 8): 1806 1812.

Jones, K. 1973. Ammonia. In Bailar, J. C., Jr., Emeleus, H. J., Nyholm, R. and Trotman Dickenson, A. F., ( ed.). Comprehensive Inorganic Chemistry. New York: Pergammon Press. 2, Pp. 199 227.

Kapeghian, J. C., Mincer, H. H., Jones, A. B., Verlangieri, A. J., and Waters, I. W. 1982. Acute inhalation toxicity of ammonia in mice. Bull. Environm. Contam. Toxicol. 29: 371 378.

Keeney, D. R. 1972. The Fate of Nitrogen in Aquatic Ecosystems. Literature Review No. 3. Madison: University of Wisconsin Water Resources Center.

Keplinger, M. L. 1973. Report to International Institute of Ammonia Refrigeration: Irritation Threshold Evaluation Study with Ammonia. Industrial BIOTEST Laboratories, Inc.

Keyes, W. F. 1975. Nitrogen. In Mineral facts and problems. Washington DC: US Department of the Interior. P. 749 760. In World Health Organization ( WHO). Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Kloppic, E., Jasobasch, G., and Rapoprt, S. 1967. Enhancement of the glycolytic rate by action of ammonium ion on phosphofructokinase activity. Original in German. Acta. Biol. Med. 18: 37 42. In Constable, M., Jensen, F., McLernon, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for 114 Ammonia ( CAS No. 7664 41 7) Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Knepp, G. L. and Arkin, G. F. 1973. Ammonia toxicity levels and nitrate tolerance of channel catfish. Prog. Fish Cult. 35( 4): 221 224.

Knoph, M. B. 1992. Acute toxicity of ammonia to Atlantic Salmon ( Salmo salar) parr. Comp. Biochem. Physiol. 101C( 2): 275 282.

Landfair, S. W., Brown, E. L., Israel, R. J., and Kreis, P. B. 1993. The EC's seventh amendment: Fundamental changes in the regulation of chemical substances manufactured and imported into the European community. International Environmental Reporter 0149 8738/ 93: 785 790.

Langowska, I., and Moskal, J. 1974. Effect of ammonia and urea on nitrobacteria in water environment. Pol. Arch. Hydrobiol. 21( 1): 119 123. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Lide, D. R. ( ed.). 1999. CRC Handbook of Chemistry and Physics. 80th Edition. Boston: CRC Press.

Linden, E., Bengtsson, B. E., Svanberg, O., and Sundstrom, G. 1979. The acute toxicity of 78 chemicals and pesticide formulations against two brackish water organisms, the bleak ( Alburnus alburnus) and the harpacticoid ( Nitocra spinipes). Chemosphere 11/ 12: 843 851.

Litton Bionetics, Inc. 1975. Mutagenic Evaluation of Compound FDA 73 42 Ammonium Sulfate, Granular, Food Grade, Washington, D. C. Litton Bionetics. ( NTIS PB 245506). In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

MacEwen, J. D. and Vernot, E. H. 1972. Toxic hazards research unit annual technical report. NTIS AD 755 358. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Mackay, D., Shiu, W. Y., and Ma, K. C. 1994. Level I, II and III Fugacity Calculations for the Illustrated Handbook for Physical chemical Properties and Environmental Fate for Organic Chemicals. New York: CRC Press.

Marsalek, J., and Ng, H. Y. F. 1989. Evaluation of pollution loadings from urban nonpoint sources: Methodology and applications. J. Great Lakes Res. 15( 3): 444 451. In Constable, M., Jensen, F., McLernon, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada. Government of Canada, Environment Canada.

Mayan, M. H. and Merilan, C. P. 1972. Effects of ammonia inhalation on respiration rate of rabbits. J. Anim. Sci. 34( 3): 447 452. 115 Ammonia ( CAS No. 7664 41 7) Mayes, M. A., Alexander, H. C., Hopkins, D. L., and Latvaitas, P. B. 1986. Acute and chronic toxicity of ammonia to freshwater fish: a site specific study. Environ. Toxicol. Chem. 5: 437 442.

McCormick, J. H., Broderius, S. J., and Fiandt, J. T. 1984. Toxicity of ammonia to early life stages of the green sunfish Lepomis cyanellus. Environ. Poll. ( Series A) 36: 147 163.

Miller, D. C., Poucher, S., Cardin, J. A., and Hansen, D. 1990. The acute and chronic toxicity of ammonia to marine fish and a mysid. Arch. Environ. Contam. Toxicol. 19: 40 48.

Monda, D. P., Galat, D. L., Finger, S. E., and Kaiser, M. S. 1995. Acute toxicity of ammonia ( NH3 N) in sewage effluent to Chironomus riparius: II. Using a generalized linear model. Arch. Environ. Contam. Toxicol. 28: 385 390.

Mosier, A. R. 1978. Inhibition of photosynthesis and nitrogen fixation in algae by volatile nitrogen bases. J. Environ. Qual. 7( 2): 237 240.

Mount, D. I. and Norberg, T. J. 1984. A seven day life cycle cladoceran toxicity test. Environ. Toxicol. Chem. 3: 425 434.

National Institute for Occupational Safety and Health ( NIOSH). 1997. NIOSH Pocket Guide to Chemical Hazards P. 359 National Research Council ( NRC). 1979. Ammonia. Subcommittee on Ammonia. Committee on Medical and Biologic Effects of Environmental Pollutants. Division of Medical Sciences, Assembly of Life Sciences. National Research Council. Baltimore: University Park Press. NTIS No. PB 278 027.

Neufeld, R. D., Hill, A. J., and Adekoya, D. O. 1980. Phenol and free ammonia inhibition to Nitrosomonas activity. Water Res. 14( 12): 1695 1703. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Nimmo, D. W. R., Link, D., Parrish, L. P., Rodriguez, G. J., and Wuerthele, W. 1989. Comparison of on site and laboratory toxicity tests: derivation of site specific criteria for un ionized ammonia in a Colorado transitional stream. Environ. Toxicol. Chem. 8: 1177 1189.

OECD. 1997. SIDS Manual. OECD Secretariat, 3rd Revision, July 1997.

Overrein, L. N., Seip, H. M., and Tollan, A. ( eds.). 1980. Acid Precipitation: Effects on Forest and Fish. Final Report. Oslo. SNSF Project 1972 1980.

Person LeRuyet, J., Boeuf, G. Zambonin Infant, J., Helgason, S., and Le Roux, A. 1998. Short term physiological changes in turbot and seabream juveniles exposed to exogenous ammonia. Comp. Biochem. Physiol. 119A: 511 518. 116 Ammonia ( CAS No. 7664 41 7) Powers, W. L., Terry, R. V., and Murphy, L. S. 1977. Fate of nitrogen from manure disposal. In Proceedings of the National Conference on Disposal of Residues on Land. Pp. 156 160.

Propkopieva, A. S. and Yushkov, G. C. 1975. Toxicology of ammonia in animals repeatedly exposed for short lengths of time. Gig. Tr. Prof. Zabol. 9: 54 55. ( Russian). In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Propkopieva, A. S. et al. 1973. Materials for a toxicological characteristic of the long term effect of ammonia on the organisms of animals after brief exposure. Gig. Tr. Prof. Zabol. 6: 56 57. ( Russian). In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Qureshi, A. A., Flood, K. W., Thompson, S. R., Janhurst, S. M., Iniss, C. S., and Rokosh, D. A. 1982. Comparison of luminescent bacterial test with other bioassays for determining toxicity of pure compounds and complex effluents. Aquatic Toxicology and Hazard Assessment: Fifth Conference, ASTM STP 766. Pearson, J. G., Foster, R. B., and Bishop, W. E. ( eds.). American Society for Testing and Materials ( ASTM). Pp. 179 195.

Randall, D. J., and Wicks, B. J. 1999. Fish: ammonia production, excretion, and toxicity. In press. Paper presented in the Fifth International Symposium on Fish Physiology, Toxicology, and Water Quality. University of Hong Kong.

Rice, S. D. and Bailey, J. E. 1980. Survival, size, and emergence of pink salmon, Oncorhynchus gorbuscha, alevins after short and long term exposures to ammonia. Fish. Bull. 78( 3): 641 648.

Richard, D., Bouley, G. and Boudene, C. 1978. Effets de l'inhalation continue d'ammoniac chez the rat et la souris. Bull. Eur. Physiopathol. Resp. 14: 573 582. ( Original in French). In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Richardson, J. 1997. Acute ammonia toxicity for eight New Zealand indigenous freshwater species. NZ J. Mar. Freshwater Res. 31: 185 190.

Rosenfeld, M. 1932. Experimental modification of mitosis by ammonia. Arch. Exp. Zellforsch. Gewebezuecht. 14: 1. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Rubin, A. J. and Elmaraghy, G. A. 1977. Studies on the toxicity of ammonia, nitrate and their mixtures to guppy fry. Water Res. 11: 927 935.

Ruyet, J. P. and Quemener, H. C. 1995. Comparative acute ammonia toxicity in marine fish and plasma ammonia response. Aquaculture 136: 181 194.

Schaerdel, A. D., White, W. J., Lang, C. M., Dvorchik, B. H., and Bohner, K. 1983. Localized and systemic effects of environmental ammonia in rats. Lab. Anim. Sci. 33( 1): 40 45. 117 Ammonia ( CAS No. 7664 41 7) Schlesinger, W. H. 1991. Biogeochemistry: An Analysis of Global Change. New York: Academic Press.

Schubauer Berigan, M. K., Monson, P. D., West, C. W., and Ankley, G. T. 1995. Influence of pH on the toxicity of ammonia to Chironomus tentans and Lumbriculus variegatus. Environ. Toxicol. Chem. 14( 4): 713 717.

Shah, K. D. 1988. Hazardous properties of ammonia, Draft. zitiert nach: DSM, Inventory of data on chemicals, Ammonia, Delft. 1992. RO471001/ 4150J. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Sheehan, R. J. and Lewis, W. M. 1986. Influence of pH and ammonia salts on ammonia toxicity and water balance in young channel catfish. Trans. Amer. Fish. Soc. 115: 891 899.

Shimizu H. et al. 1985. Jap. J. Ind. Health. 27: 400. Silver, S. D. and McGrath, F. P. 1948. A comparison of acute toxicities of ethylene imine and ammonia to mice. J. Ind. Hyg. Toxicol. 30: 7 9. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Silverman, L., Whittenberger, J. L., and Muller, J. 1949. Physiological response of man to ammonia in low concentrations. J. Ind. Hyg. Toxicol. 31: 74 78. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Soderberg, R. W. and Meade, J. W. 1992. Effects of sodium and calcium on acute toxicity of unionized ammonia to Atlantic salmon and lake trout. J. Appl. Aquaculture 1( 4): 83 92.

Stombaugh, D. P., Teague, H. S., and Roller, W. L. 1969. Effects of atmospheric ammonia on the pig. J. Anim. Sci. 28( 6): 844 847.

Tam, N. F. Y. and Wong, Y. S. 1996. Effect of ammonia concentrations on growth of Chlorella vulgaris and nitrogen removal from media. Bioresource Technol. 57: 45 50.

Thornton, N. C. and Setterstrom, C. 1940. Toxicity of ammonia, chlorine, hydrogen cyanide, hydrogen sulphide, and sulphur, dioxide gases. III. Green Plants. Contrib. Boyce Thompson Inst. 11: 343 356. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Thurston, R. V., Russo, R. C., Luedtke, R. J., Smith, C. E., Meyn, E. L., Chakoumakos, C. and Brown, C. J. D. 1984. Chronic toxicity of ammonia to rainbow trout. Trans. Amer. Fish. Soc. 113: 56 73.

Thurston, R. V., Chakoumakos, C., and Russo, R. C. 1981. Effect of fluctuating exposures on the acute toxicity of ammonia to rainbow trout ( Salmo gairdneri) and cutthroat trout ( S. clarki). Water Res. 15: 911 917. 118 Ammonia ( CAS No. 7664 41 7) Thurston, R. V. and Russo, R. C. 1983. Acute toxicity of ammonia to rainbow trout. Trans. Amer. Fish. Soc. 112: 696 704.

Thurston, R. V.; Russo, R. C.; and Phillips, G. R. 1983. Acute toxicity of ammonia to fathead minnows. Trans. Amer. Fish. Soc. 112: 705 711.

Thurston, R. V., Russo, R. C. and Smith, C. E. 1978. Acute toxicity of ammonia and nitrite to cutthroat trout fry. Trans. Amer. Fish. Soc. 107( 2): 361 368.

Tomasso, J. R. and Carmichael, G. J. 1986. Acute toxicity of ammonia, nitrite, and nitrate to the Guadalupe bass, Micropterus treculi. Bull. Environ. Contam. Toxicol. 36: 866 870.

Tomasso, J. R., Goudie, C. A., Simco, B. A., and Davis, K. B. 1980. Effects of environmental pH and calcium on ammonia toxicity in channel catfish. Trans. Amer. Fish. Soc. 109: 229 234.

Toth, B. 1972. Hydrazine, methylhydrazine and methylhydrazine sulfate carcinogenesis in Swiss mice. Failure of ammonium hydroxide to interfere in the development of tumors. Int. J. Cancer. 9: 109. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Tsujii, M., Kawano, S., Tsuji, S., Ito, T., Nagano, K., Sasaki, Y., Hayashi, N., Fusamoto, H., and Kamada, T. 1993. Cell kinetics of mucosal atrophy in rat stomach induced by long term administration of ammonia. Gastroenterol. 104: 796 801.

Underhill, F. P. and Kapsinow, R. 1922. The comparative toxicity of ammonium salts. J. Biol. Chem. 54: 451 457.

U. S. Environmental Protection Agency ( USEPA). 1998a. AP 42. Draft. Vol. 1. 5th ed. Research Triangle Park: Office of Air Quality Planning and Standards.

U. S. Environmental Protection Agency ( USEPA). 1998b. Emission Factor Documentation for AP 42 Section 9.2.1. Draft. Research Triangle Park: Office of Air Quality Planning and Standards.

U. S. Environmental Protection Agency ( USEPA). 1998c. 1998 Update of Ambient Water Quality Criteria for Ammonia. Washington, D. C.: Office of Water. EPA 822 R 98 008.

U. S. Environmental Protection Agency ( USEPA). 1985. Ambient Water Quality Criteria for Ammonia. 1984. Washington, D. C.: Office of Water Regulations and Standards, Criteria and Standards Division. EPA 50415 85 006.

U. S. Environmental Protection Agency ( USEPA). 1999. Development of Chemical Categories in the HPV Challenge Program. www. epa. gov/ chemrtk/ catdoc29. pdf.

Valentine, H. 1964. A study of the effect of different ventilation rates on the ammonia concentrations in the atmosphere of broiler houses. Br. Poult. Sci. 5: 149 159. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. 119 Ammonia ( CAS No. 7664 41 7) Verberk, M. M. 1977. Effects of ammonia in volunteers. Arch. Occup. Environ. Hlth. 39: 73 81.

Verschueren, K. 1996. Handbook of Environmental Data and Organic Chemicals. New York: John Wiley & Sons, Inc.

Vezina, C. 1997. National Ammonia Inventory. Draft. Ottawa: Environment Canada, Pollution Data Brarnch. In Constable, M., Jensen, F., McLeron, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Vines, H. M. and Wedding, R. T. 1960. Some effects of ammonia on plant metabolism and a possible mechanism for ammonia toxicity. Plant Physiol. 35: 820 825.

Wallingford, G. W. 1977. Fate of nitrogen from fertilizer practices. In Disposal of residues on land. Rockville: Information Transfer, Inc. Pp. 152 155.

Walsh, L. M. 1977. Updating the nitrogen cycle. In Disposal of residues on land. Rockville: Information Transfer, Inc. Pp. 146 151.

Warren, K. S. 1958. The differential toxicity of ammonium salts. J. Clin. Invest. 37: 497 501. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Warren Spring Laboratory. 1982. Acidity of rainfall in the United Kingdom.

Weatherby, J. H. 1952. Chronic toxicity of ammonia fumes by inhalation. Proc. Soc. Exp. Biol. Med. 81: 300 301.

Weiler, R. R. 1979. Rate of loss of ammonia from water to the atmosphere. J. Fish Res. Board Can. 36: 685 689.

Williams, K. A., Green, D. W., and Pascoe, D. 1986. Studies on the acute toxicity of pollutants to freshwater macroinvertebrates. Arch. Hydrobiol. 106( 1): 61 70.

Wilson, R. P., Muhrer, M. E., and Bloomfield, R. A. 1968. Comparative ammonia toxicity. Comp. Biochem. Physiol. 25: 295 301.

Zimmerman, P. W. 1949. Impurities in the air and their influence on plant life. In Proceedings of the First National Air Pollution Symposium. Pasadean, California. Pp. 135 141. Zitiert nach: DSM, Inventory of data on chemicals, Ammonia, Delft. 1992. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database. In World Health Organization ( WHO). 1986. Ammonia Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety. 120 Ammonia ( CAS No. 7664 41 7) Zischke, J. A. and Arthur, J. W. 1987. Effects of elevated ammonia levels on the fingernail clam, Musculium transversum, in outdoor experimental streams. Arch. Environ. Contam. Toxicol. 16: 225 231. APPENDIX A  SIDS DATA AVAILABILITY SUMMARY Ammonia ( CAS No. 7664 41 7) SIDS DATA AVAILABILITY SUMMARY DATE: January 27, 2003 Ammonia CAS No: 7664 41 7 Information OECD Study GLP Other Study Estimated Method Acceptable SIDS Testing Recommended STUDY Y/ N Y/ N Y/ N Y/ N Y/ N Y/ N Y/ N PHYSICAL CHEMICAL DATA 2.1 2.2 2.3 2.4 2.5 2.6 2.12 Melting Point Boiling Point Density Vapour Pressure Partition Coefficient Water Solubility pH and pKa Values Oxidation: Reduction Potential Y Y Y Y Y Y Y Y N N N N Y N N N N N N N Y N N N N N N N N N Y N N N N N N N N N Y Y Y Y Y Y Y Y N N N N N N N N OTHER P/ C STUDIES RECEIVED Y N N Y N Y N ENVIRONMENTAL FATE and PATHWAY 3.1.1 3.1.2 3.2 3.3 3.5 Photodegradation Stability in Water Monitoring Data Transport and Distribution Biodegradation Y Y Y Y Y N N N N N N N N N N N Y N Y N N N N N N Y Y Y Y Y N N N N N OTHER ENV FATE STUDIES RECEIVED Y N N Y N Y N ECOTOXICITY 4.1 4.2 4.3 4.5.1 4.5.2 4.6.1 4.6.2 4.6.3 Acute Toxicity to Fish Acute Toxicity to Daphnia Toxicity to Algae Chronic Toxicity to Fish Chronic Toxicity to Daphnia Toxicity to Soil Dwelling Organisms Toxicity to Terrestrial Plants Toxicity to Birds Y Y Y Y Y N Y Y N N N N N N N N N N N N N N N N Y Y Y Y Y N Y Y N N N N N N N N Y Y Y Y Y  Y Y N N N N N N N N OTHER ECOTOXICITY STUDIES RECEIVED Y N N Y N Y N TOXICITY 5.1.1 5.1.2 5.1.3 5.4 5.5 5.6 5.8 5.9 5.11 Acute Oral Acute Inhalation Acute Dermal Repeated Dose Genetic Toxicity in vitro . Gene mutation . Chromosomal aberration Genetic Toxicity in vivo Reproduction Toxicity Development/ Teratogenicity Human Experience N Y N Y Y Y Y Y N Y N N N N N N N N N N N N N N N N N N N N N Y N Y Y Y Y Y N Y N N N N N N N N N N  Y  Y Y Y Y Y  Y N N N N N N N N N N OTHER TOXICITY STUDIES RECEIVED Y N N Y N Y N APPENDIX B  COMPREHENSIVE BIBLIOGRAPHY COMPREHENSIVE BIBLIOGRAPHY Achorn, F. P., Balay, H. L., Myers, E. D., and Grisso, R. D. 1971. A pollution solution for granulation plants. Farm Chem. Croplife 134( 8): 28 31.

Admiraal, W. 1977. Tolerance of estuarine benthic diatoms to high concentrations of ammonia, nitrite ion, nitrate ion, and orthophosphate. Mar. Biol. 43: 307 315.

Agency for Toxic Substances and Disease Registry ( ATSDR). 1990. Toxicological Profile for Ammonia.

Aickin, C. C., Deisz, R. A., and Lux, H. D. 1982. Ammonium action on post synaptic inhibition in crayfish neurons: implications for the mechanism of chloride extrusion. J. Physiol. 329: 319 339.

Al Dabbagh, S., Forman, D., Bryson, D., Stratton, I., and Doll, R. 1986. Mortality of nitrate fertiliser workers. British J. Ind. Med. 43: 507 515.

Alarie, Y. 1981. Dose response analysis in animal studies: prediction of human responses. Env. Health Perspect. 42: 9 13.

Alexander, H. C., Latvaitis, B., and Hopkins, D. L. 1986. Site specific toxicity of un ionized ammonia in the Tittabawassee River at Midland, Michigan: Overview. Environ. Toxicol. Chem. 5: 427 435.

Alger, B. E. and Nicoll, R. A. 1983. Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells. J. Neurophy. 49: 1381 1391.

Allen, G. I., Eccles, J., Nicoll, R. Z., Oshima, T., and Rubia, F. J. 1977. The ionic mechanisms concerned in generating the IPSPs of hippocampal pyramidal cells. Roc. R. Soc. Lond. B. 198: 363 384.

Alliance Technologies Corporation for the U. S. EPA 1987. Ammonia Emission Factors for the NAPAP ( National Acid Precipitation Assessment Program) Emission Inventory. EPA/ 600/ 7 87/ 001.

Al Mashhadani, E. H. and Beck, M. M. 1985. Effect of atmospheric ammonia on the surface ultrastructure of the lung and trachea of broiler chicks. Poul. Sci. 64: 2056 2061.

Alpatov, I. M. 1964. A study of gaseous ammonia toxicity. Gig. Tr. Prof. Zabol 2: 14 18. ( Russian).

Alpatov, I. M. and Mikhailov, V. I. 1963. Inquires into gaseous ammonia toxicity  communications. Gig. Tr. Prof. Zabol 12: 51 53. ( Russian).

American Conference of Governmental Industrial Hygienists, Inc. ( ACGIH). 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati: ACGIH. Pp. 27. American Society of Testing and Materials ( ASTM). 1984. Standard test method for estimating sensory irritancy of airborne chemicals. E 981 984. Ames, R. G. 1991. Multiple episode conjunctivitis outbreak among workers at a nut processing facility. J. Occup. Med. 34: 505 509.

Anderson, D. P., Beard, C. W., and Hanson, R. P. 1964. The adverse effects of ammonia on chickens including resistance to infection with newcastle disease virus. Avian Dis. 8: 369 379.

Anghileri, L. J. 1975. Tumor growth inhibition by ammonium chloride induced acidosis. Int. J. Pharmacol. 12: 320 326.

Ankley, G. T., Schubauer Berigan, and Monson, P. D. 1995. Influence of pH and hardness on toxicity of ammonia to the amphipod Hyalella azteca. Can. J. Fish. Aquat. Sci. 52: 2078 2083.

Anonymous. 1988a. Ammonia makers are bullish in ' 88. Chem. Mktg. Rep. 233: 3 28.

Anonymous. 1988b. Ammonia runs full, but prices in question. Chem. Mktg. Rep. 234: 3 32.

Anonymous. 1988c. Inorganics: Despite 1987' s growth, output of many products was below levels of late 1970' s. Chem. Eng. News June. 20: 41.

Anonymous. 1988d. Nitrogen: Output edged higher but remained well below recent peak. Chem. Eng. News June. 20: 43.

Anonymous. 1988e. Output will be up this year and next for nearly all major chemicals and polymers: inorganic chemicals. Chem. Eng. News Dec. 12: 30.

Anonymous. 1988f. World: Chemical and polymer production growth, 1986 2000. Chem. Mktg. Rep. Pp. 14.

Anonymous. 1959. The Chemistry of Industrial Toxicology. In Elkins, H. B. ( ed.). New York: J. Wiley & Sons, Inc.

Anthonisen, A. C., Loehr, R. C., Prakasam, T. B. S., and Srinath, E. G. 1976. Inhibition of nitrification by ammonia and nitrous acid. J. Water Poll. Control Fed. 48: 835 852.

Appelman, L. M., ten Berge, W. F., and Reuzel, P. G. J. 1982. Acute inhalation toxicity study of ammonia in rats with variable exposure periods. Am. Ind. Hyg. Assoc. J. 43: 662 665.

Arillo, A., Margiocco, C., Melodia, F., Mensi, P., and Schenone, G. 1981. Ammonia toxicity mechanism in fish: studies on rainbow trout ( Salmo gairdneri Rich.). Ecotoxicol. Environ. Safety 5: 316 328. Armstrong, D. A., Chippendale, D., Knight, A. W., and Colt, J. E. 1978. Interaction of ionized and un ionized ammonia on short term survival and growth of prawn larvae, Macrobrachium rosenbergii. Biol. Bull. 154: 15 31.

Arthur, J. W., West, C. W., Allen, K. N., and Hedtke, S. F. 1987. Seasonal toxicity of ammonia to five fish and nine invertebrate species. Environ. Contam. Toxicol. 38: 324 331.

Asman, W. A. and Janssen, A. J. 1987. A long range transport model for ammonia and ammonium for Europe. Atmos. Environ. 21( 10). In Constable, M., Jensen, F., McLernon, J. Craig, G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada Austin, E. R. and Lee, G. F. 1973. Nitrogen release from lake sediments. J. Water Pollut. Control Fed. 45: 870 879.

Bacon, C. W. 1986. Effects of broiler litter volatiles and ammonia on fungal spore germination. Poul. Sci. 65: 710 716.

Bader, J. A. and Grizzle, J. M. 1992. Effects of ammonia on growth and survival of recently hatched channel catfish. Amer. Fish. Soc. 4: 17 23.

Baker, J. H. et al. 1959. Determination of application losses of anhydrous ammonia. Agronomy Journal 51: 361 362. In U. S. Environmental Protection Agency ( USEPA). 1998b. Emission Factor Documentation for AP 42 Section 9.2.1. Draft. Research Triangle Park: Office of Air Quality and Standards.

Barrow, C. S., Alarie, Y., and Stock, M. F. 1978. Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants. Arch. Environ. Health 33: 79 88.

Barrow, C. S., and Steinhagen, W. H. 1980. NH3 concentrations in the expired air of the rat: Importance to inhalation toxicology. Toxicol. Appl. Pharmacol. 53: 116 121.

Barton, L. V. 1940. Toxicity of ammonia, chlorine, hydrogen cyanide, hydrogen sulphide, and sulphur dioxide gases. IV. Seeds. Contrib. Boyce Thompson Inst. 11: 357 363. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Barzel, U. S. 1975. The effect of chronic ammonium chloride ingestion on parathyroid hormone function. Nephron. 14: 339 346.

Barzel, U. S. and Jowsay, J. 1969. The effects of chronic acid and alkali administration on bone turnover in adult rats. Clin. Sci. 36: 517 524.

BASF AG, Sicherheitsdatenblatt Ammoniak fluessig ( 27.04.94). In European Commission. 1996. Ammonia. International Uniform Chemical Information Database. BASF AG, Abteilung Analytik; unveroeffentlichte Untersuchung ( BRU 92.004). In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Batshaw, M. L. and Monahan, P. S. 1987. Treatment of Urea Cycle Disorders. Recent Adv. Inborn Errors of Metabolism Proc. 4th Int. Congr., Sendai Enzyme 38: 242 250.

Bauer, C. F. 1985. Emissions of vapor phase fluorine and ammonia from the Columbia coalfired power plant. Environ. Sci. Tech. 19: 1099 1103.

Beaumont, A. R. and Budd, M. D. 1984. Marine. Poll. Bull. 15: 402 405. In Vorlaeufige Ergebnisse des F+ E Vorhabens Bewertung wassergefaehrdender Stoffe. 1985. vgl. Datenblaetter zum Katalog wassergefaehrdender Stoffee, KBwS, Nr. 5. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Benedict, H. M. and Breen, W. H. 1955. The use of weeds as a means of evaluating vegetation damage caused by air pollution. Proc. 3rd Natl. Pollution Symp. Pasadena, Calif. Pp. 177 190. Zitiert nach: DSM, Inventory of data on chemicals, Ammonia, Delft, 1992. RO471001/ 4150J. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Benjamin, A. M. 1981. Control of glutaminase activity in rat brain cortex in vitro: Influence of glutamate, phosphate, ammonium, calcium and hydrogen ions. Brain Res. 208: 363 377.

Benyajati, S. and Goldstein, L. 1975. Renal glutaminase adaptation and ammonia excretion in infant rats. Am. J. Physiol. 228: 693 698.

Bergerhouse, D. L. 1993. Lethal effects of elevated pH and ammonia on early life stages of hybrid striped bass. In: Tave, D. ( ed.). Strategies and Tactics for Management of Fertilized Hatchery Ponds. New York: The Haworth Press, Inc. Pp. 81 101.

Bergerhouse, D. L. 1992. Lethal effects of elevated pH and ammonia on early life stages of walleye. N. Amer. J. Fish. Man. 12: 356 366.

Beri, S., Takagaki, G., Clarke, D. D., and Waelsch, H. 1962. Metabolic compartments in vivoammonia and glutamic acid metabolism in brain and liver. J. Biol. Chem. 237: 2562 2569.

Besser, J. M., Ingersoll, C. G., Leonard, E. N., Mount, D. R. 1988. Effect of zeolite on toxicity of ammonia in freshwater sediments: implications for toxicity identification evaluation procedures. Environ. Toxicol. Chem. 17( 11): 2310 2317.

Bessman, S. P. and Pal, N. 1982. Ammonia intoxication: Energy metabolism and brain protein synthesis. Isr. J. Med. Sci. 18: 171 175.

Bessman, S. P. and Bessman, A. N. 1955. The cerebral and peripheral uptake of ammonia in liver disease with a hypothesis for the mechanism of hepatic coma. J. Clin. Invest. 34: 622 628. Betterton, E. A. 1992. In Nriagu, J. O. ( ed.). Gaseous Pollutants: Characterization and Cycling. New York: John Wiley & Sons, Inc. Pp. 1 50.

Beyenbach, K. W. 1985. Comparative physiology of the renal proximal tubule. Renal Physiol. 8: 222 236.

Bhattacharya, S. and Mukherjee, S. 1976. Activity of the hepatopancreatic protease and esterase in fish exposed t industrial pollutants. Comp. Physiol. Ecol. 1: 45 50.

BIBRA. 1995. Toxicology Profile: Ammonia. BIBRA International.

Bimbaum, S. M., Winitz, M., and Greenstein, J. P. 1957. Quantitative nutritional studies with water soluable chemically defined diets. III. Individual amino acids as sources of " nonessential nitrogen. Arch. Biochem. Biophys. 72: 428 436. Bittershol, G. 1971. Epidemiologic study on cancer of workers in a chemical plant. Arch. Gesh. 38: 198 209. ( Original in German).

Blade, M. C., Arola, L. and Alemany, M. 1988. Rapid detoxification of infused ammonium by the anesthetized rat. Biochem. Internatl. 16: 859 867.

Blalock, J. E. 1989. A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiol. Rev. 69: 1 32.

Bloomfield, R. A., Kearley, E. O., Creach, D. O., and Muhrer, M. E. 1963. Ruminal pH and absorption of ammonia and VFA. J. Anim. Sci. 22( 1): 833.

Bolon, B., Bonnefoi, M. S., Roberts, K. C., Marshall, M. W., and Morgan, K. T. 1991. Toxic interactions in the rat nose: pollutants from soiled bedding and methyl bromide. Toxicological Pathol. 19( 4 pt. 2): 571 579.

Bond, G. G., Shellenberger, R. F., Flores, G. H., Cook, R. R., and Fishbeck, W. A. 1985. A case control study of renal cancer mortality at a Texas chemical plant. Am. J. Ind. Med. 7: 123 140.

Booth, N. H. and McDonald, L. E. 1982. Veterinary Pharmacology and Therapeutics. 5th edition. Pp. 938 939.

Bouhuys, A. 1977. Environmental lung diseases. The Physiology of Breathing.

Boutros, A. R., Esfandiari, S., Orlowski, J. P., and Smith, J. S. 1980. Reye syndrome: A predictably curable disease. Pediatr. Clin. North Am. 27: 539 552.

Bower, C. E. and Bidwell, J. P. 1978. Ionization of ammonia in seawater: effects of temperature, pH, and salinity. J. Fish. Res. Board Can. 35: 1012 1016.

Boyd, E. M., MacLachlan, M. L., and Perry, W. F. 1944. Experimental ammonia gas poisoning in rabbits and cats. J. Ind. Hyg. Toxicol. 26: 29 34. Boyd, E. M. and Seymour, K. G. W. 1946. Ethylenediamine dihydrochloride or " chlor ethamine". Exp. Med. Surg. 4: 223 227.

Bradford, H. F. and Ward, H. K. 1975. Glutamine as a metabolic substrate for isolated nerveendings Inhibition by ammonium ions. Biochem. Soc. Trans.  559th Meeting. 3: 1223 1226.

Braun, E. J. 1985. Comparative aspects of the urinary concentrating process. Renal Physiol. 8: 249 260.

Braunwald, E., Isselbacher, K. J., Petersdori, R. G., Wilson, J. D., Martin, J. B., and Fauci, A. S. 1987. Harrison's Principles of Internal Medicine. McGraw Hill Publ. Pp. 1054.

Bressani, R. and Brahma, J. E. 1977. Effect of frequency of feeding on blood serum urea changes in dogs. Nutr. Rep. Int. 16: 305 316.

Brock, T. D. 1970. Biology of Microorganisms. Englewood Cliffs, NJ.: Prentice Hall, Inc. Broderius, S., Drummond, R., Fiandt, J., and Russom, C. 1985. Toxicity of ammonia to early life stages of the smallmouth bass at four pH values. Environ. Toxicol. Chem. 4: 87 96.

Broderson, J. R., Lindsey, J. R., and Crawford, J. E. 1976. The role of environmental ammonia in respiratory mycoplasmosis of rats. Am. J. Pathol. 85: 115 130. In World Health Organization ( WHO). 1986. Ammonia Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Brown, D. A. and McLeay, D. J. 1975. Effect of nitrite on methemoglobin and total hemoglobin of juvenile rainbow trout. Prog. Fish Cult. 37( 1): 36 38.

Brown, V. M. 1968. The calculation of the acute toxicity of mixtures of poisons to rainbow trout. Water Res. 2: 723 733.

Brown, V. M., Jordan, D. H. M., and Tiller, B. A. 1969. The acute toxicity to rainbow trout of fluctuating concentrations and mixtures of ammonia, phenol and zinc. J. Fish. Biol. 1: 1 9.

Buckley, J. A. 1978. Acute toxicity of un ionized ammonia to fingerling coho salmon. Prog. Fish Cult. 40( 1): 30 32.

Buckley, L. A., Jiang, X. Z., James, R. A., Morgan, K. T., and Barrow, C. S. 1984. Respiratory tract lesions induced by sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74: 417 429.

Budavari, S. ( ed.). 1996. Merck Index. 12th ed. Whitehouse Station: Merck Research Laboratories.

Burkhalter, D. E. and Kaya, C. M. 1977. Effects of prolonged exposure to ammonia on fertilized eggs and sac fry of rainbow trout ( Salmo gairdneri). Trans. Amer. Fish Soc. 106( 5): 470 474. Cadle, S. H. 1985. Seasonal variations in nitric acid, nitrate, strong aerosol acidity, and ammonia in an urban area. Atmos. Environ. 19: 181 188.

Cadle, S. H., Countess, R. J., and Kelly, N. A. 1982. Nitric acid and ammonia in urban and rural locations. Atmos. Environ. 16: 2501 2506.

Calamari, D., Marchetti, R., and Vailati, G. 1981. Effects of long term exposure to ammonia on the developmental stages of rainbow trout ( Salmo gairdneri Richardson). Rapp. P. v. Reun. Cons. int. Explor. Mer 178: 81 86.

Cameron, J. N. and Heisler, N. 1983. Studies of ammonia in the rainbow trout: physicochemical parameters, acid base behaviour and respiratory clearance. J. Exp. Biol. 105: 107 125.

Canadian Fertilizer Institute ( CFI). 1996. 1995 Emissions inventory, update. Ottawa. In Constable, M., Jensen, F., McLeron, J. Craig, G., Moore D. 1996. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, environment Canada.

Caplin, M. 1941. Ammonia gas poisoning: Forty seven cases in a London shelter. Lancet Pp. 95 97.

Challoner, K. R. and McCarron, M. M. 1988. Ammonium nitrate cold pack ingestion. J. Emergency Med. 6: 289 293.

Charles, D. R. and Payne, C. F. 1966. The influence of graded levels of atmospheric ammonia on chickens. I. Effects on respiration and on the performance of broilers and replacement growing stock. Br. Poult. Sci. 7: 177 187.

Charles, D. R. and Payne, C. G. 1966. The influence of graded levies of atmospheric ammonia on chickens. II. Effects on the performance of laying hens. Br. Poult. Sci. 7: 189 198.

Chassin, J. L. and Slattery, L. R. 1953. Jejungal structure due to ingestion of ammonia: Report of a case complicated by severe potassium deficiency. J. Am. Med. Assoc. 152: 134 136.

1996. Chem. Eng. News. 74: 13. In Hazardous Substances Database ( HSDB). 1999. Ammonia. National Library of Medicine, Bethesda, MD.

1980. C and EN's top fifty chemical products. Chem. Eng. News. 16. In World Health Organization ( WHO). 1986. Ammonia Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Chen, J. C. and Kou, Y. Z. 1993. Accumulation of ammonia in the haemolymph of Penaeus monodon exposed to ambient ammonia. Aquaculture 109: 177 185. Clawson, A. J. and Amstrong, W. D. 1981. Ammonium polyphosphate as a source of phosphorus and nonprotein nitrogen for monogastrics. J. Anim. Sci. 52: 1 7.

Clement Associates Inc. 1990. Health Effects Assessment for Ammonia. The Fertilizer Institute: Washington, D. C.

Close, L. G., Catlin, F. I., and Cohn, A. M. 1980. Acute and chronic effects of ammonia burns of the respiratory tract. Arch. Otolaryngol. 106: 151 158.

Coffee, R. C. and Bartholomew, W. V. 1964. Some aspects of ammonia sorption by soil surfaces. Soil Sci. Soc. Proc. 28( 4): 485 490.

Cole, T. J., Cotes, J. E., Johnson, G. R., de V. Martin, H., Reed, J. W. and Saunders, M. J. 1977. Ventilation, cardiac frequency and pattern of breathing during exercise in men exposed to o chlorobenzylidene malononitrile ( CS) and ammonia gas in low concentrations. Quart. J. Exper. Physiol. 62: 341 351.

Colt, J. and Tchobanoglous, G. 1978. Chronic exposure of channel catfish Ictalurus punctatus, to ammonia: effects on growth and survival. Aquaculture 15: 353 372.

Cometto Muniz, J. E. and Hernandez, S. M. 1990. Odorous and pungent attributes of mixed and unmixed odorants. Perception and Psychophysics 47( 4): 391 399.

Compressed Gas Association, Inc. 1990. Handbook of Compressed Gases. 3rd ed. Pp. 259 260. In Compressed Gas Association, Inc. 1999. American National Standard Safety Requirements for the Storage and Handling of Anhydrous Ammonia. 5th ed. Arlington: Compressed Gas Association, Inc.

Conn, H. E. 1972. Studies of the source and significance of blood ammonia IV. Early ammonia peaks after ingestion of ammonium salts. Yale J. Biol. Med. 45: 543 549.

Constable, M., Jensen, F., McLeron, J. Craig., G., Moore, D. 1999. Canadian Environmental Protection Act, Priority Substances List II: Supporting Document for Ammonia in the Aquatic Environment. Draft, Unpublished Version. Government of Canada, Environment Canada.

Coon, R. A., Jones, R. A., Jenkins, Jr, L. J., and Siegel, J. 1970. Animal inhalation studies on ammonia, ethylene, glycol, formaldehyde, dimethylamine, and ethanol. Toxicol. Appl. Pharmacol. 16: 646 655.

Corpron, K. E. and Armstrong, D. A. 1983. Removal of nitrogen by an aquatic plant, elodea densa, in recirculating macrobrachium culture systems. Aquaculture 32: 347 360.

Cralley, L. V. 1942. The effect of irritant gases upon the rate of ciliary activity. J. Ind. Hyg. Tox. 24: 193 198. Cribb, G. S. 1964. Nitrogen. Mellor's Comprehensive Treatise on Inorganic and Theoretical Chemistry. London: Longmans, 276 327.

Crook, B., Robertson, J. F., Travers Glass, S. Z., Botheroyd, E. M., Lacey, J., and Topping, M. D. 1991. Airborne dust, ammonia, microorganisms, and antigens in pig confinement houses and the respiratory health of exposed farm workers. Am. Ind. Hyg. Assoc. J. 52( 7): 271 279.

Curtis, S. E., Anderson, C. R., Simon, J., Jensen, A. J., Day, D. L., and Kelley, K. W. 1975. Effects of aerial ammonia, hydrogen sulfide and swine house dust on rate of gain and respiratorytract structure in swine. J. Anim. Sci. 41: 735 739.

Dabrowski, H. and Sikora, H. 1986. Acute toxicity of ammonia to common carp ( Cyprinus carpio L.). Pol. Arch. Hydrobiol. 33( 1): 121 128.

Dalhamn, T. 1963. Effect of ammonia alone and combined with carbon particles on ciliary activity in the rabbit trachea in vivo, with studies of the absorption capacity of the nasal cavity. Int. J. Air. Wat. Poll. 7: 531 539.

Dalhmanm, T. 1963. Mucous flow and ciliary activity in the trachea of healthy rats exposed to respiratory irritant gases ( SO2, H3N, HCHOO). VIII. The reaction of the tracheal ciliary activity to single exposure to respiratory irritant gases and studies of the pH. Acta. Physiol. Scand. 123S: 93 105.

Dalhamn, T. 1956. The reaction of the tracheal ciliary activity to single exposure to respiratory irritant gases and studies of the pH. Acta. Physiol. Scand. 36S: 93 105.

Dalhamn, T. and Reid, L. Ciliary Activity and Histologic Observations in the Trachea After Exposure to Ammonia and Carbon Particles. In Davis, C. N. ( ed.). Inhaled Particles and Vapors. II. Proceedings of an International Symposium. New York: Pergamon Press. Pp. 299 306.

Dalhamn, T. and Sjoholm, J. 1963. Studies on SO2, NO2, and NH3: Effect on ciliary activity in rabbit trachea of single in vitro exposure and resorption in rabbit nasal cavity. Acta. Physiol. Scand. 58: 287 291.

Daoust, P. Y. and Ferguson, H. W. 1984. The pathology of chronic ammonia toxicity in rainbow trout, Salmo gairdneri Richardson. J. Fish Dis. 7: 199 205.

Day, D. L., Hansen, E. L, and Anderson, S. 1965. Gases and odors in confinement swine buildings. Trans. Am. Soc. Agric. Eng. 8: 118 121. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

De, S. N. and Bhattacharya, S. 1976. Effect of some industrial pollutants on fish thyroid peroxidase activity and role of cytochrome c thereon. Indian J. Exp. Biol. 14: 561 563.

Deaton, J. W., Reece, F. N., and Lott, B. D. 1984. Effect of atmospheric ammonia on pullets at point of lay. Poult. Sci. 63: 384 385. Deaton, J. W., Reece, F. N., and Lott, B. D. 1982. Effect of atmospheric ammonia on laying hen performance. Poult. Sci. 61: 1815 1817.

Deaton, J. W., Reece, F. N., and Thornberry, F. D. 1986. Atmospheric ammonia and incidence of blood spots in eggs. Poult. Sci. 65: 1427 1428.

Demerec, M., Bertani, G., and Flint, J. 1951. A survey of chemicals for mutagenic action on E. coli. Amer. Natural. 85: 119 136.

Denmead, O. T. et al. 1982. Atmospheric dispersion of ammonia during application of anhydrous ammonia fertilizer. J. Environ. Qual. 11( 4): 568 572. In U. S. Environmental Protection Agency ( USEPA). 1998a. AP 42. Draft. Vol. 1. 5th ed. Research Triangle Park: Office of Air Quality Planning and Standards.

Denmead, O. T. et al. 1977. A direct field measurement of ammonia emission after injection of anhydrous ammonia. Soil Sci. Soc. Amer. J. 41: 1001 1004. In U. S. Environmental Protection Agency ( USEPA). 1998a. AP 42. Draft. Vol. 1. 5th ed. Research Triangle Park: Office of Air Quality Planning and Standards.

Diamond, J. M., Mackler, D. G., Rasnake, W. J., and Gruber, D. 1993. Derivation of site specific ammonia criteria for an effluent dominated headwater stream. Environ. Toxicol. Chem. 12: 649 658.

Diekman, M. A., Scheidt A. B., Sutton, A. L., Green, M. L., Clapper, J. A., Kelly, D. T., and Van Alstine, W. G. 1993. Growth and reproductive performance, during exposure to ammonia, of gilts afflicted with pneumonia and atrophic rhinitis. Am. J. Vet. Res. 54( 12): 2128 2131.

Directive 92/ 32 of April 30, 1992. 1992. Official Journal of the European Communities, No. L154 of June 5, 1992.

Dodd, K. T. and Gross, D. R. 1980. Ammonia inhalation toxicity in cats: A study of acute and chronic respiratory dysfunction. Arch. Environ. Health 35: 6 14.

Doig, P. A. and Willoughby, R. A. 1971. Response of swine to atmospheric ammonia and organic dust. J. Am. Vet. Med. Assoc. 159: 1353 1361.

Donham, K. J. and Popendorf, W. J. 1985. Ambient levels of selected gases inside swine confinement buildings. Am. Hyg. Assoc. J. 46: 658 661.

Donham, K. J. and Zavala, D. C. 1984. Acute effects of work environment on pulmonary function of swine confinement workers. Am. J. Ind. Med. 5: 367 375.

Douglas, R. B. and Coe, J. E. 1987. The relative sensitivity of the human eye and lung to irritant gases. Ann. Occup. Hyg. 31: 265 267.

Doyle, G. J., Tuazon, E. C., Graham, R. A., Mischke, T. M., Winer, A. M., and Pitts, Jr., J. N. 1979. Simultaneous concentrations of ammonia and nitric acid in a polluted atmosphere and their equilibrium relationship to particulate ammonium nitrate. Environ. Sci. Tech. 13( 11): 1416 1419. Drummond, J. G., Curtis, S. E., Simon, J., and Norton, H. W. 1980. Effects of aerial ammonia on growth and health of young pigs. J. Anim. Sci. 50( 6): 1085 1091.

DSM, Inventory of Data on chemicals, Ammonia, Delft. 1992. LRO471001/ 4150J. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Duda, G. D. and Handler, P. 1958. Kinetics of ammonia metabolism in vivo. J. Biol. Chem. 232: 303 314.

du Ruisseau, J. P., Greenstein, J. P., Winitz, M., and Birnbaum, S. M. 1957. Studies on the metabolism of amino acids and related compounds in vivo. VI. Free amino acid levels in the tissues of rats protected against ammonia toxicity. Arch. Biochem. Biophysiol. 68: 161 171.

Ecological Analysts, Inc. 1981. The Sources, Chemistry, Fate, and Effects of Ammonia in Aquatic Environments. Washington, DC: American Petroleum Institute.

Egle, Jr., J. L. 1973. Retention of inhaled acetone and ammonia in the dog. Am. Ind. Hyg. Assoc. J. 34: 533 539.

Ehrlich, R. 1966. Effect of nitrogen dioxide on resistance to respiratory infection. Bact. Rev. 30: 604 614.

Elissa, M. G. 1983. Arch. Hydrobiol. 98( 3): 327 343.

Ellen, G. and Schuller. 1982. No volatile N nitrosamines detected in blood and urine from patients ingesting daily large amounts of ammonium nitrate. Fd. Chem. Toxic. 20: 879 882. Elliott, L. F., Schuman, G. E., and Viets, F. G., Jr. 1971. Volatilization of nitrogen containing compounds from beef cattle areas. Soil Sci. Soc. Amer. Proc. 35: 752 755.

Emerson, K., Russo, R. C., Lund, R. E., and Thurston, R. V. 1975. Aqeuous ammonia equilibrium calculations: effect of pH and temperature. J. Fish. Res. Board Can. 32: 2379 2383.

Environment Canada. 1984. Technical Information for Problem Spills: Ammonia. Ottawa, Ontario: Environmental Protection Service, Technical Services Branch.

Epifanio, C. E. and Srna, R. F. 1975. Toxicity of ammonia, nitrite ion, nitrate ion, and orthophosphate to Mercenaria mercenaria and Crassostrea virginica. Mar. Biol. 33: 241 246.

Erickson, R. J. 1985. An evaluation of mathematical models for the effects of pH and temperature on ammonia toxicity to aquatic organisms. Water Res. 19( 8): 1047 1058.

European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Evans, D. E. and Cameron, J. N. 1956. Gi11 ammonia transport. J. Exp. Zool. 239: 17 23.

Fazekas, I. G. 1954. Enlargement of the parathyroids by treatment with simple acidotic compounds. Arch. Pathol. Anat. Physiol. 324: 531 542. Fazekas, I. G. 1939. Experimental suprarenal hypertrophy induced by ammonium hydroxide. Endokrinologie. 21: 315 337. ( German).

Fazekas, J. F. 1949. Experimental data on influencing ovarian functions by simple compounds. Orv. Hetil. 90: 77 781.

Fazekas, J. F., Ticktin, H. E., Ehrmantraut, W. R., and Alman, R. W. 1956. Cerebral metabolism in hepatic insufficiency. Amer. J. Med. 21: 843 849.

Felipo, V., Minana, M. D., and Grisolia, S. 1988. Paradoxical protection of both protein free and high protein diets against acute ammonium intoxication. Biochem. Biophys. Res. Commun. 156: 506 510.

Fenn, L. B. and Hossner, L. R. 1985. Ammonia volatilization from ammonium or ammonium forming nitrogen fertilizers. Adv. Soil Sci. 1: 123 169.

Ferguson, W. S., Koch, W. C., Webster, L. B., and Gould, J. R. 1977. Human physiological response and adaptation to ammonia. J. Occup. Med. 19: 319 326.

Feth, J. H. 1966. Nitrogen compounds in natural water   A review. Water Resources Res. 2: 41 58.

Flaks, A., Hamilton, J. M., and Clayson, D. B. 1973. Effect of ammonium chloride on incidence of bladder tumors induced by 4 ethylsulfonylnaphthalene 1 sulfonamide. J. Natl. Cancer Inst. 51: 2007 2008.

Flis, J. 1963. Anatomicohistopathological changes induced in carp ( Cyrinus carpio L.) by ammonia water. Part II. Effects of subtoxic concentrations. Acta. Hydrobiol. 10: 225 238.

Flury, K. E., Dines, P. E., Rodarte, J. R., and Rodgers, R. 1983. Airway obstruction due to inhalation of ammonia. Mayo. Clin. Proc. 58: 389 393.

Frank, J. F. 1948. The toxicity of sodium chlorate herbicides. Can. J. Comp. Med. 12: 216 218.

Freedman, L. R. and Beeson, P. B. 1961. Experimental pyelonephritis   VIII. The effect of acidifying agents on susceptibility to infection. Yale J. Biol. Med. 33: 318 332.

Frizzola, J. B. and Baier, J. H. 1975. Contaminants in rainwater and their relation to water quality. Water Sewage Works 122: 94 95.

Fuhrer, J. 1985. Formation of secondary air pollutants and their occurrence in Europe. Experientia ( Basel) 41: 286 301.

Gaafar, H., Girgis, R., Hussein, M., and El Nemr, F. 1992. The effect of ammonia on the respiratory nasal mucosa of mice. A histological and histochemical study. Acta. Otolaryngol. 112: 339 342.

Ganong, W. F. 1985. Gas transport between the lung and tissues. Review of Medical Physiology. 12th ed.

Gargas, M. L. and Andersen, M. E. 1988. Physiologically based approaches for examining the pharmacokinetics of inhaled vapors. In Gardner, D. E., Carpo, J. D., Massaro, E. J., ( eds.). Toxicology of the Lung. New York: Raven Press. Gerald, M. J. and Slot, M. D. 1938. Ammonia gas burns ( an account of six cases). Lancet Pp. 1356 1357.

Gersich, F. M. and Hopkins, D. L. 1986. Site specific acute and chronic toxicity of ammonia to Daphnia magna Straus. Environ. Toxicol. Chem. 5: 443 447.

Gibson, G. E., Zimber, A., Krook, L., and Visek, W. J. 1971. Nucleic acids and brain intestinal lesions in ammonia intoxicated mice. Nutrition 578ABS: 2145.

Giguz, T. L. 1968. Effect of low concentrations of ammonia and nitrogen oxides in adolescents undergoing vocational training in the chemical industry. Hyg. Sanit. 33: 491 434.

Gilliam, J. W., Daniels, R. B. and Lutz, J. F. 1974. Nitrogen content of shallow ground water in the North Carolina coastal plain. J. Environ. Qual. 3: 147 151.

Glasglow, A. M. 1983. Hypoglycin toxicity: Studies of ammonia metabolism. Biochem. Pharmacol. 32: 746 748.

Goldhaber, M. B. and Kaplan, I. R. 1974. The sulfur cycle. In: Goldberg, D. ( ed.). The Sea: Ideas and Observations in Progress in the Study of the Seas. Vol. 5, New York: John Wiley Sons, Inc. Pp. 569 655.

Goldman, A. S. and Yakovac, W. C. 1964. Salicylate intoxication and congenital anomalies. Arch. Env. Health 8: 648 656.

Gomaa, H. M. and LeBlanc, J. R. 1985. Environmental considerations for the nitrogen fertilizer industry. Fertilizer News 30: 23 37.

Gould, W. D., Hagedorn, C., and McCready, R. G. L. 1986. Urea transformations and fertilizer efficiency in soil. Adv. Agronomy 40: 209 238.

Graedel, T. E. and Allara, D. L. 1977. Pp. 467 473. EPA 600/ 3 77 001A, PB 264.

Grayson, M. 1978. Kirk Othmer Encyclopedia of Chemical Technology. Vol. 2, New York: John Wiley and Sons, Inc.

Greenstein, J. P., Winitz, M., Gullino, P., Bimbaum, S. M., and Otey, M. C. 1956. Studies on the metabolism of amino acids & related compound in Vivo Prevention of ammonia toxicity by arginine & related compounds. Arch. Biochem. Biophys. 64: 342 354.

Griffiths, R. F. and Megson, L. C. 1984. The effect of uncertain ties human toxic response on hazard range estimation for ammonia and chlorine. Atmos. Environ. 18: 1195 1206. In World Health Organization ( WHO). 1986. Ammonia   Environmental Health Criteria 54. Geneva: International Programme on Chemical Safety.

Grossi, C. E., Prytz, B., and Rousselot, L. M. 1968. Adensoine triphosphate in prevention of ammonia intoxication in dogs. Surgical Forum 19: 363 369.

Gupta, B. N., Khanna, R. N., and Datta, K. K. 1979. Toxicological studies of ammonium sulfamate in rat after repeated oral administration. Toxicol. 13: 45 49. Hales, J. M. and Drewes, D. R. 1979. Solubility of ammonia in water at low concentrations. Atmos. Environ. 13: 1133 1147.

Hanst, P. L., Wong, N. W., and Bragin, J. 1982. A long path infra red study of Los Angeles smog. Atmos. Environ. 15: 969 981.

Harader, R. R. and Allen, G. H. 1983. Ammonia toxicity to chinook salmon parr: reduction in saline water. Trans. Amer. Fish. Soc. 112: 834 837.

Harris, D. J., Siegel, E., and Baska, R. D. 1987. Transient hyperammonaemia. A. Inher. Metab. Dis. 10: 269.

Harward, C. N., McClenny, W. A., Hoell, J. M., Williams, J. A., and Williams, B. S. 1982. Ambient ammonia measurements in coastal southeastern Virginia. Atmos. Env. 16: 2496 2500.

Haussinger, D. 1986. Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. Adv. Enzyme Regue. 25: 159 180.

Haussinger, D. and Gerok. 1986. Metabolism of amino acids and ammonia. In Thurma, R. G., Kauffman, F. C., Jungermann, K. ( eds.). Regulation of Hepatic Metabolism: Intra and Intercellular Compartmentation. New York: Plenum Publ. Pp. 253 291. Hawkins, R. A., Miller, A. L., Nielsen, R. C., and Veech, R. L. 1973. The acute action of ammonia on rat brain metabolism in vivo. Biochem. J. 134: 1001 1008.

Hazardous Substances Data Bank ( HSDB). 1999. Ammonia. National Library of Medicine, Bethesda, MD.

Helmers, S., Top, F. H., and Knapp, L. W. 1971. Ammonia injuries in agriculture. J. Iowa Med. Soc. 61: 271 280.

Hemens, J. 1965. The Institute of Sewage Purification Southern African branch memorandum to the honourable the minister of water affairs, on effluent standards. J. Inst. Sew. Purif. 65: 265 271.

Herbert, D. W. M. and Shurben, D. S. 1964. The toxicity to fish of mixtures of poisons. I. Salts of ammonia and zinc. Ann. App. Biol. 53: 33 41.

Hermann, G. and Viehrig, J. 1979. [ Irritative respiratory tract diseases from ammonia and sulfuric acid aerosols in a cuprammonium rayon spinning mill]. Z. Gesamte Hyg. 25: 581 584. ( Russian).

Hermanutz, R. O., Hedtke, S. F., Arthur, J. W., Andrew, R. W., Allen, K. N., and Helgen, J. C. 1987. Ammonia effects on microinvertebrates and fish in outdoor experimental streams. Environ. Poll. 47: 249 283.

Heuner, A., Azar, C., Mildenberger, S., and Silbernagl, S. 1988. Renal handling of glutathione. Contr. Nephrol. 63: 49 52.

Heymans, C. and Es, J. J. 1949. Blood Changes due to ammonia inhalation? Science 109: 121 122. Hickey, C. W. and Vickers, M. L. 1994. Toxicity of ammonia to nine native New Zealand freshwater invertebrate species. Arch. Environ. Contam. Toxicol. 26: 292 298.

Hidy, G. M. 1974. Characterization of Aerosols in California ( ACHEX). Thousand Oaks, California: Rockwell International.

Hillaby, B. A. and Randall, D. J. 1979. Acute ammonia toxicity and ammonia excretion in rainbow trout ( Salmo gairdneri). J. Fish. Res. Board Can. 36: 621 629.

Hoeft, R. G., Kenney, D. R., and Walsh, L. M. 1972. Nitrogen and sulfur in precipitation and sulfur dioxide in the atmosphere in Wisconsin. J. Environ. Qual. 1: 203 208.

Holness, D. L., Prudham, J. T., and Nethercott, J. R. 1989. Acute and chronic respiratory effects of occupational exposure to ammonia. Am. Iond. Hyg. Assoc. J. 50( 12): 646 650.

Hou, S., Zhang, Y. G., Lao, D. F., He., J., and Zhong, N. S. 1991. The chronic latent lung function damage in workers exposed to mild ammonia pollution. Am. Rev. Resp. Dis. 143( 4pt. 2): A105.

Hunt, R. D. 1977. Measurement of partial pressure of ammonia in breath and arterial blood. Evidence for secretion of ammonia into expired gas by metabolism of monoamines in the lung. Diss. Abstr. Int. Ser. B. 37: 3279.

Hutchinson, G. L., Mosier, A. R., and Andre, C. E. 1982. Ammonia and amine emissions from a large cattle feedlot. J. Environ. Qual. 11: 288 293.

Hutchinson, G. L. and Viets, F. G., Jr. 1969. Nitrogen enrichment of surface water by absorption of ammonia volatilized from cattle feedlots. Science 166: 514 515.

Iles, J. F. and Jack, J. J. B. 1980. Ammonia: Assessment of its action on postsynaptic inhibition as a cause of convulsion. Brain 103: 555 578.

Indorato, A. M. et al. 1985. First International Symposium on Toxicity Testing using Bacteria. Burlington, Ontario, Canada 17 19 May 1983. In Datenblaetter zum Katalog wassergefaehrdender Stoffe, KBwS. Nr. 5. In European Commission. 1996. Ammonia. International Uniform Chemical Information Database.

Industrial BIO TEST Laboratories, Inc. 1973. Report to International Institute of Ammonia Refrigeration   Irritation Threshold Evaluation Study with Ammonia. March 23. IBT No. 663 03161.

Institution of Chemical Engineers. 1988. Second Report on the Toxicity Working Party. Ammonia Toxicity Monograph. Warwidkshire, England.

Jacobsohn, D. and Jorgensen, C. B. 1955. Survival and function of auto and homografts of adenohypophysial tissue in the toad, Bufo bufo ( L). Acta. Phys. Scandinav. 36: 1 12.

Jaffe, H. L., Bodansky, A., and Blair, J. E. 1932. The effects of parathormone and ammonium chloride on the bones of rabbits. J. Exp. Med. 55: 695 701. Jaffe, H. L., Bodansky, A., and Chandler, J. P. 1932. Ammonium chloride decalcification, as modified by calcium intake: The relation between generalized osteoporosis and ostitis fibrosa. J. Exp. Med. 56: 823 834.

Janicki, R. H. 1970. Renal adaptation during chronic NH4Cl acidosis in the rat: No role for hyperplasia. Am. J. Physiol. 219: 613 618.

Jofre, M. B., and Karasov, W. H. 1999. Direct effect of ammonia on three species of North American anuran amphibians. Environ. Toxicol. Chem. 18( 8): 1806 1812.

Jojima, T. and Sato, T. 1975. Pollution abatement in a urea plant. Chem. Age India. 26: 524 529.

Jones, K. 1973. Ammonia. In Bailar, Jr., J. C., Emeleus, H. J., Nyhom, R., Trotman Dickenson, A. F. ( eds.). Comprehensive Inorganic Chemistry. Vol. 2, New York: Pergammon Press. Pp. 199 227.

Jones, S. R. 1945. Ammonia and the nervous system. J. Am. Med. Assoc. Pp. 620.

Jungermann, K. 1988. Metabolic zonation of liver parenchyma. Semin. Liver Dis. 8: 329 341. Kagota, K., Iwase, T., and Kojima, T. 1979. Diammonium citrate addition to a diet restricted nonessential amino acids for young pigs. Jap. J. Vet. Sci. 41: 131 138.

Kane, L. E., Barrow, C. S., and Alarie, Y. 1979. A short term test to predict acceptable levels of exposure to airborne sensory irritants. Amer. Inc. Hyg. Assoc. 40: 207 229.

Kane, L. E. Dombroske, R., and Alarie, Y. 1980. Evaluation of sensory irritation from some common industrial solvents. Am. Ind. Hyg. Assoc. J. 41: 451 455.