Registration Dossier

Administrative data

Description of key information

Acute toxicity:
- oral: LD50 = ca. 1576 mg/kg bw (OECD 401)
- dermal: LD50 = >2000 mg/kg bw (OECD 403; Analogy CAS 7783-20-0)
- inhalative: LC50 >4.74 mg/l (EPA OTS 798.1150; Analogy CAS 144-55-8)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
1 576 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
4 740 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral:

The acute oral toxicity of ammonium hydrogen carbonate was analyzed in a study performed according to OECD guideline 401. Five Wistar rats per sex and dose received 10 ml of 215, 681, 1470 and 2150 mg/kg bw ammonium hydrogen carbonate in 0.5% aqueous carboxymethyl cellulose by gavage (BASF, 1989). During the 14 day observation period, clinical signs including dyspnea, staggering and tonic convulsions and mortality was noted in the 1470 and 2150 mg/kg bw dose groups. Pathological examinations revealed general congestions and glandular stomach as well as slight reddened mucosa. Thus, a LD50 of ca. 1576 mg/kg bw was calculated for males and females.

A LD50 of <2000 mg/kg bw was found in another study by the same author, which was also conducted in compliance with OECD guideline 401 (BASF, 1990). In this limit test, 5 males and five female Wistar rats were dosed with 2000 mg/kg bw ammonium hydrogen carbonate. During the 14 day observation period, clinical signs like dyspnea, staggering and tonic convulsions were noted. While all females died, 3 of 5 males survived treatment.

 

Inhalation:

Since no data on inhalation toxicity testing with ammonium hydrogen carbonate could be found, a study with sodium bicarbonate (CAS 144-55-8) was used for assessment. As stated in guideline EPA OTS 798.1150 (Acute inhalation toxicity), five male and five females Sprague-Dawley rats were exposed to a concentration of 4.74 ± 1.03 mg/l sodium bicarbonate for 4.5 h (Wnorowski, 1992). The analysis revealed a mass median aerodynamic diameter of 2.9 ± 1.77 µm and 2.7 ± 2.04 µm, measured in two samplings of two minutes duration, respectively. While ocular and/or nasal discharge in 6/10 rats was observed within one day after exposure, no mortality was noted. Therefore, the LC50 was found to be > 4.74 mg/l. Since the hydrogencarbonate ion is a dissociation product of sodium bicarbonate similar as it is after dissociation of ammonium hydrogencarbonate, the same result could be expected for ammonium hydrogen carbonate.

 

In a published study, male ICR mice were exposed to concentrations of 2408, 2954 and 3402 mg/m3 (4860, 3440, and 4220 ppm) ammonia for 1h and a LC50 of ca. 2.96 mg/l was found (Kapghian, 1982). Since ammonia ion is a dissociation product of ammonium hydrogencarbonate with a maximum possible release quantity of 21.5%, roughly calculation with the observed LC50 value of ammonia leads to a LC50 of 13.8 mg/l/h for ammonium bicarbonate dust. This LC50 value is however not taken into account for risk assessment and classification as ammonia is corrosive which ammonium hydrogencarbonate is not (not irritating) and therefore mortality due to corrosion in the respiratory tract can be ruled out. The calculation of an LC50 value based on the data of ammonia is therefore not appropriate due to different properties (corrosive vs. not irritating) of the two substances. The LC50 value of 3.45 mg/l/4h for ammonium hydrogencarbonate dust calculated according to Haber's law based on the data of ammonia would be too low.

Based on all available data it can be assumed that the LC50 for ammonium hydrogencarbonate dusts is greater than 5 mg/l/4 hours.

 

Dermal:

Since no study on acute dermal toxicity testing of ammonium hydrogen carbonate was available, a study with the ammonium sulfate (CAS 7783-20-0) was used for assessment. As suggested in OECD guideline 403, three males and three Wistar rats received an application of 2000 mg/kg bw ammonium sulfate under open conditions (Yamanaka, 1990). Since no mortality was observed during the 14 day observation period, the LD50 was >2000 mg/kg bw. Because the ammonium ion is a dissociation product of ammonium sulfate similar as it is after dissociation of ammonium hydrogencarbonate, the same result could be expected for ammonium hydrogen carbonate.

Read across justification:

Ammonium bicarbonate rapidly dissociates in biological fluids to yield ammonium ion (NH4+) and bicarbonate ion (HCO3-). Ammonium ion then reaches equilibrium with ammonia (NH3) in a pH-dependent fashion and both are integral components of normal metabolic processes and play an essential role in the physiology of man and other species. Bicarbonate ion reaches equilibrium with CO2and H2O in aqueous solution and this equilibrium reaction acts as the major extracellular buffer system in blood and interstitial fluids of vertebrates.

Inorganic salts which are releasing either ammonium or bicarbonate ions are therefore in general suitable as read across substances for ammonium bicarbonate. These substances include: Sodium hydrogencarbonate, ammonium sulphate, ammonium carbamate, ammonium chloride etc.

Justification for classification or non-classification

Ammonium hydrogencarbonate is listed in Annex I of Directive 67/548/EEC. It carries the R-phrase R 22. Assessment of available data for actute toxicity of ammonium hydrogencarbonate supports and confirms this classification. Hence the present EU classification will be maintained. Assessment of available data indicates that ammonium chloride is "harmful to health after single ingestion" and needs to be classified as a Cat. 4 acute toxicant pursuant to the criteria stipulated under Regulation No. 1272/2008 (EC) for the Classification, Labeling and Packagingof Substances and Mixtures (CLP).

Concerning acute dermal and inhalation toxicity, no classification is required according to Directive 67/548/EEC Annex VI or 1272/2008 Annex I (CLP).