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SIDS INITIAL ASSESSMENT PROFILE 

CAS Nos. 7664-41-7; 1336-21-6; 

7783-18-8; 12593-60-1 

Chemical Names Ammonia category: ammonia, aqueous ammonia, ammonium thiosulfate, 

ammonium phosphate sulfate 

Structural Formula 

NH3; NH4OH; (NH4)2S2O3; (NH4)2H2PO4HSO4 

SUMMARY CONCLUSIONS OF THE SIAR 

Category Rationale 

The ammonia category includes anhydrous ammonia, aqueous ammonia, ammonium thiosulfate and 

ammonium phosphate sulfate. In biological fluids and in aquatic environments, every substance of the 

category will dissociate to yield, respectively; ammonium ion (NH4

+

), hydroxide ion (-OH), thiosulfate 

ion (S2O3

2-), phosphate ion (H2PO4-

) and sulfate ion (SO4

2-). Each of the compounds of the category 

contains the ammonia/ammonium ion functional group. The sulfate, thiosulfate and phosphate ions are 

normal constituents of the blood, and when in excess, are excreted via the urine. Among these 

compounds, un-ionized ammonia is considered the most toxic and is the basis for read-across for the 

category members. 

The category is based on the dissociation of all the category members into the ammonium ion (NH4

+

) 

and the corresponding anions in aqueous environments, where the ammonia/ammonium ion will exist 

in equilibrium between NH3 and NH4

+

, depending on the pH. At ambient environmental conditions, the 

category members are stable substances that show normal acid/base chemical activity with the 

following equilibria: 

 NH4

+

 + H2O 3

 + H3O+

NH3 + H2O 4

+ + OHThus for many environmental conditions (pH =5 to 8), the predominant form will be NH4

+

. At pH =9 

the ratio of ammonia to ammonium ion (NH3/ NH4

+

) should approach unity; at higher pHs the 

proportion of ammonia (NH3) should increase. As inorganic salts that ionize in the aquatic 

environment, the category members can be considered chemically and structurally similar for the 

purposes of this category evaluation. As pH decreases, the concentration of ammonium ion increases 

with respect to decreases of unionized ammonia concentrations. However, the toxicity of the unionized 

ammonia is considered several orders of magnitude greater than the more abundant ammonium ion. 

The ammonium ion toxicity is considered to contribute to the overall toxicity. 

Analog Rationale 

Data for ammonium sulfate (SIAM 19; CAS No. 7783-20-2), sodium sulfate (SIAM 20; CAS No. 

7757-82-6), ammonium chloride (SIAM 17; CAS No. 12125-02-9), sodium thiosulfate (CAS No. 
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7772-98-7) and di-ammonium phosphate (SIAM 24; CAS No. 7783-28-0) are used to fill the data gaps 

for SIDS endpoints. These substances all dissociate to their respective cations and anions at 

physiological pH, whose data are used to support the respective cations or anions of the category 

members. 

Human Health 

After uptake into a biological system the salts in the ammonia category will dissociate directly into 

ammonium ion and the corresponding anions, i.e. phosphate, thiosulfate and sulfate. The anions will 

enter the body electrolyte pool, and are not expected to play a significant toxicological role at low 

doses. After intestinal absorption, ammonium ions are converted to urea in the liver, and subsequently 

excreted in urine (within 6 hours). The ratio of ammonium ion to neutral ammonia is about 100 in 

blood of normal pH range. 

The acute oral LD50 values range from 1,950 to >2,000 mg/kg bw in rats for the ammonium salts. 

Aqueous ammonia has a higher oral toxicity (LD50 of 350 mg/kg bw in rat) than the other compounds 

in the group. Clinical signs include sedation, staggering, abnormal posture, convulsions, tremors, 

ataxia, prostration, ptosis, exophthalmus, chromodacryorrhea, unilateral ocular opacity, salivation, 

labored and irregular breathing and diarrhea. Acute dermal LD50 values are >2,000 mg/kg bw for 

ammonium sulfate and diammonium phosphate (DAP). The inhalation LC50 values range from >900 

mg/m3

 for ammonium sulfate (guinea pig) to 13,770 mg/m3 for ammonia (rat). Clinical signs observed 

after inhalation include eye irritation, labored breathing and nasal discharge, pulmonary hemorrhages. 

Ammonia concentrations of 348-6953 mg/m3 may lead to death in humans. The LD50 and LC50 values 

are taken from studies whose reliability rating is a 4 (unassignable) and whose data are used on a 

weight of evidence basis. 

Aqueous ammonia is corrosive to skin and eyes in animal studies and humans due to the high pH. The 

ammonium salts are slightly irritating to skin and moderately irritating to eyes in animal studies. In 

humans, slight respiratory irritation was observed at 50 mg/m3

 ammonia and at 1 mg/m3 concentrations 

of ammonium sulfate, pulmonary function was affected. No data are available on the sensitization 

potential of the category members. However, human data suggest that DAP may be sensitizing to the 

respiratory tract. In repeated-dose inhalation studies, with ammonia (rats) and aqueous ammonia (rats, 

rabbits, guinea pigs and dogs), the main effects observed are irritation, and inflammation of the 

respiratory tract at 105 mg/m3

 and above. For ammonia, the NOAEL of 6.4 mg/m3 was determined 

based on an occupational study and the lack of evidence of decreased pulmonary function or changes 

in subjective symptoms. No LOAEL was established. In rats, the LOAEL was determined to be 17.4 

mg/m3

 based on increased severity of rhinitis and pneumonia with respiratory lesions. A NOAEL was 

not established. 

For ammonium sulfate, inhalation studies in rats showed respiratory effects (enlarged alveoli, alveolar 

ducts and sacs) at 1 mg/m3

. In a semi-chronic study [input exposure duration], enhanced bronchiolar 

cell hyperplasia and fibrosis were reported at 0.5 mg/m3

. In a sub-chronic inhalation study with rats, 

exposure to 26.8 mg/m3

 of ammonium thiosulfate resulted in systemic effects such as growth 

reduction, increased levels of acid and alkaline phosphatase, effects on calcium, CNS effects and 

cardiovascular changes. 

In a 13 week repeated-dose feeding study in rats given ammonium sulfate up to 1,975 mg/kg bw/day, 

no effects were observed on body weight, food consumption or hematological and clinical parameters. 

However, increased kidney weights (in males and females) and increased liver weights (females) were 

observed at the highest dose without histopathological changes. The NOAEL was 1,975 mg/kg bw/day 

for females and 886 mg/kg bw/day for males (diarrhea). In a combined repeateddose/reproduction/developmental oral gavage screening study in rats exposed to 0. 250, 750 and 1,500 

mg/kg bw DAP for 35 days, a NOAEL of 250 mg/kg bw was derived based on increased alkaline 

phosphatase and decreased total protein in blood. 

Ammonia, ammonium thiosulfate and the analogues ammonium sulfate and DAP did not induce effects 

in tests on gene mutations and chromosomal aberrations. Ammonium sulfate was negative, in vivo,

when tested for chromosomal effects. Ammonia is not carcinogenic when administered to rats in the 

drinking water. However, ammonia did have promoting effects in gastric cancer induced by N-methylN’-nitro-N-nitrosoguanidine (MMNG). Ammonium sulfate showed no promoting effect. 
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No histopathological changes to the reproductive organs were found in repeated-dose toxicity studies 

with ammonium sulfate. No effects on reproduction and development were found in studies with 

ammonia (at 24.3 mg/m3

). In a reproduction/developmental toxicity screening test (similar to OECD 

422) rats (5 males and 10 females/group) were administered DAP by oral gavage at doses of 0, 250, 

750 and 1,500 mg/kg bw/day. Animals were exposed two weeks prior to mating, during mating (both 

sexes) and for an additional three and a half weeks through gestation until lactation day 4 (females). 

No effects on reproduction were reported up to 1,500 mg/kg bw/day. No developmental effects were 

observed up to 1,500 mg/kg bw/day. The NOAEL for reproductive and developmental toxicity for DAP 

was 1,500 mg/kg bw. 

Environment 

The melting points for ammonia, aqueous ammonia, ammonium thiosulfate, and ammonium phosphate sulfate are 

-78o

C, -77oC, 150oC, and 235oC, respectively. The boiling points are -33oC, 36oC, for ammonia and aqueous 

ammonia, respectively, while ammonium thiosulfate and ammonium phosphate sulfate decompose at 150o

C and 

>235o

C, respectively. The vapor pressure for ammonia is 8611hPa at 20oC; aqueous ammonia, 2878hPa at 25oC; 

ammonium thiosulfate, 18 mm Hg at 70o

F (21.1oC), and ammonium phosphate sulfate – (not applicable). The water 

solubility for the category substances is in the range of 430 to > 1000 g/L at 20o

C. The pH for ammonia is 10.6-11.6 

(0.01-1%) at 25o

C and aqueous ammonia is expected to be similar. The pKa for ammonia is 9.25. Ammonium 

thiosulfate (200 g/L at 20o

C) and ammonium phosphate sulfate (10% solution in water) pH values are in the range of 

6.5-7.2 and 4.5-5.5o

C, respectively. 

All substances from the ammonia category are very soluble in water and dissociate upon release into water. 

Anhydrous and aqueous ammonia are volatile. Ammonia toxicity depends on the pH and temperature of the media, as 

well as the amount of ammonia already present. Increasing pH, and temperature to a lesser degree, results in the 

presence of more un-ionized ammonia (percentage of total ammonia present as NH3 in aqueous solutions at 20 oC is 

0.039% at pH 6 and 3.82% at pH 8). 

Upon application of ammonium fertilizers, ammonium can be taken up by plants or adsorbed onto clay particles in the 

soil. Leaching or run-off may occur via cation exchange dependent on soil texture, clay content, pH and ionic strength 

of the irrigation water. Soil bacteria may convert ammonium to nitrate. Nitrate can be taken up by plants or denitrified 

again to yield nitrogen and nitrous oxide gas. Ammonia may also directly volatilize from the soil. Transport via the 

atmosphere will mainly be due to diffusion and air concentrations will decrease quickly with increasing distance from 

the source. Ammonium ion and the anions from the substances of the ammonia category are all subject to nitrification. 

The fate and behaviour of the substances, such as bioaccumulation, are also closely related to nitrogen cycles in air, 

soil and water. In anaerobic environments, sulfate is biologically reduced to (hydrogen) sulfide by sulfate reducing 

bacteria, or incorporated into living organisms as a source of sulfur, and thereby included in the sulfur cycle. In acidic 

aqueous environments, thiosulfate is similarly expected to dissociate to sulfur and sulfur dioxide and enter the sulfur 

cycle and/or the atmosphere. Phosphate salts released into the environment will be distributed between water and soil. 

Land-applied phosphate and ammonium are adsorbed to soil particles. In water the phosphate salts may result in 

eutrophication (caused by ammonium and phosphate ions), which may lead to increased algal growth. Decomposition 

of the algae may in turn result in lower dissolved oxygen concentrations. If dissolved oxygen concentrations are 

lowered significantly, suffocation of other aquatic organisms may occur. 

LC50 values for fish toxicity range between 6.9 and 175 mg total NH3/L for the ammonium substances dependent on 

pH and temperature during the test. Long-term exposure of fish to ammonium compounds may induce reproductive 

changes starting at 100 mg/L. EC50 values for invertebrates range from 21.8 mg total NH3/L for ammonium chloride 

to > 25.7 mg total NH3/L for ammonium sulfate. Long-term studies with invertebrates showed slightly lower NOEC 

values of 3.1-3.47 mg total NH3/L. The algae Chlorella vulgaris EC50 (biomass; 0-5d) was 1300mg/L using 

ammonium chloride). In a 21-day test with Chlorella vulgaris and ammonium sulfate, an EC50 of 25,476 mg/L (2700 

mg N/L) was established from exponential growth on day 11-18. Ammonia that is unionized is toxic to aquatic 

organisms at concentrations below 1 mg/L. 

Exposure 

For the year 2004 the global market for the ammonia category was estimated to be ca. 65,000 ktonnes. For the United 

States (Sponsor country) production was estimated at 9 ktonnes. The substances are mainly used as intermediates in 

the production of fertilizers, fibers and plastics, explosives, solvents and household cleaning products. Environmental 

exposure occurs through naturally occurring mechanisms whereby microorganisms break down organic nitrogen 

products such as urea and proteins found in manure as well as via the use of fertilisers and household cleaning 
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products. According to the information in the USEPA Toxics Release Inventory database for 2004, the total reported 

emissions of ammonia were 171,179,218 lbs (77,647 tonnes). 

Occupational exposure may occur during the production, transportation and processing of ammonia containing 

compounds. Field exposure to workers is possible during use as fertilizers via both the dermal and inhalation routes of 

exposure. A generic Threshold Limit Value (TLV) of 10 mg/m3, as a nuisance dust, exists for the solids of the 

ammonia category. The Occupational Safety and Health Administration (OSHA) has set a Permissible Exposure Limit 

(PEL) of 50 ppm (35 mg/m3) averaged over 8 hours for ammonia and 15 mg/m3 for sodium thiosulfate. The National 

Institute for Occupational Safety and Health (NIOSH) has recommended an airborne exposure limit of 25 ppm (18 

mg/m3) averaged over a 10 hour period and not to exceed 35 ppm (27 mg/m3) during any 15 minute work period for 

ammonia. Similarly, the American Conference of Governmental Industrial Hygienists (ACGIH) has recommended a 

25 ppm (18 mg/m3)airborne exposure limit averaged over 8 hours with a short term exposure limit (STEL) of 35 (27 

mg/m3)ppm. 

Consumer exposure can occur during the use of cleaning products and fertilizers. 

RECOMMENDATIONS AND RATIONALE FOR THE RECOMMENDATION 

AND NATURE OF FURTHER WORK RECOMMENDED 

Human Health: The chemicals are currently of low priority for further work. The chemicals possess hazards for 

human health (irritant to corrosive, acute toxicity). Based on data presented by the Sponsor country, adequate risk 

management measures are being applied. Countries may desire to check their own risk management measures to find 

out whether there is a need for additional measures. In the environment, ammonia degrades to nitrite. It is 

recommended that the use of the chemicals as fertilizers be taken into account when assessing the exposure of nitrite 

and nitrate to humans through drinking water. 

Environment: The chemicals are currently of low priority for further work. The chemicals possess properties 

indicating a hazard to the environment (acute aquatic EC/LC50 values between 1 and 100 mg/L). Unionized ammonia 

toxicity to aquatic organisms is reported at < 1 mg/L. The pH and temperature of water bodies can affect the EC/LC50

values. The chemicals are of low priority for further work for the environment because of their rapid nitrification. 

Ammonia has indirect and long-term effects on ecosystems, e.g. eutrophication, groundwater pollution and soil 

acidification due to the nitrification of ammonia.