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Key value for chemical safety assessment

Additional information

In vitro:

Genetic toxicity in vitro was evaluated in a study performed equivalent to OECD guideline 471, where bacteria strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, TA92, TA94 and TA2637 were exposed up to 25 mg/plate with and without metabolic activation by polychlorinated biphenyls induced rat liver microsome S9 mix by the preincubation method (Ishidate, 1984). As result, no genotoxicity was found.

In the same publication, a chromosomal aberration test was reported to be performed according OECD guideline 473. Chinese hamster fibroblast cells were treated with ammonium hydrogencarbonate at a maximum dose up to 25 µg/plate with and without metabolic activation by a rat liver microsome S9 mix. As result, the number of polyploid cells was 0%, while the number of observed structural aberrations was 2.0%. Thus, ammonium hydrogen carbonate was found to be negative.

A negative result was also found in another Ames test study with two bacteria strains S. typhimurium TA 97 and TA 102, when they were treated with ammonium hydrogen carbonate at concentrations of 0 - 25 mg/plate (0 - 0316 mmol/plate) with and without metabolic activation by a S-9 mix (Fujita, 1994).

Also no genotoxicity was found in another study performed according to OECD guideline 471, where bacteria strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and 1538 as well as Saccharomyces cerevisiae were treated with concentrations of 4.25, 8.5 and 17 mg/ml with and without metabolic activation by rat S-9 mix (Litton, 1977). At the highest concentration used, cytotoxicity was noted.

Due to the lack of data on gen mutation toxicity in mammalian cells, reliable studies with ammonium sulfate (CAS 7783-20-2) and ammonium carbamate (1111-78-0) are taken into account for assessment. In the study with ammonium sulfate, a HPRT test was conducted according to OECD 476 and GLP requirements (BASF/ Harlan CCR 2010). CHL V79 cells were treated with the test substance in concentrations of 82.5 to 1320 µg/mL with or without metabolic activation. The test substance was negative in the HPRT test in all treatments while the vehicle controls (acetone) and positive controls (ethylmethanesulphonate and 7,12-dimethylbenzanthracene) showed valid results. In the study with ammonium carbamate, a HPRT test was conducted according to OECD 476 and GLP requirements (BASF 2010). CHO cells were treated with the test substance in concentrations of 100 - 800 µg/mL with or without metabolic activation. The test substance was negative in the HPRT test in all treatments while the vehicle controls (culture medium) and positive controls (ethylmethanesulphonate and methylcholanthrene) showed valid results.

 

In vivo:

Due to the lack of data on genetic toxicity in vivo, a study with ammonium chloride (CAS 12125-02-9) is taken into account for assessment.

In this study, a micronucleus assay was conducted in large part equivalent to OECD guideline 474 with bone marrow in ddY male mice (Hayashi, 1988). The animals received either a single dose or four doses spaced 24 hours apart by intraperitoneal injection. The single dose test and the 4 times dose test were dosed with 62.5 - 500 mg/kg bw and 31.3 - 250 mg/kg bw as MTD (maximum tolerance dose), respectively. Mitomycin C served as positive control. After 24 h the bone marrow was prepared and analyzed for erythrocytes with micronuclei. Since no increase was observed in any group, ammonium chloride was found to be not genotoxic in vivo. Since the ammonium ion is a dissociation product of ammonium chloride similar as it is after dissociation of ammonium hydrogencarbonate, the same result could be expected for ammonium hydrogencarbonate.

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.

Short description of key information:
Genetic toxicity:
- in vitro: negative (Ames; HPRT by analogy to CAS Nos. 7783-20-2 and 1111-78-0; Chromosome aberration test)
- in vivo: negative (MNT by analogy to CAS No. 12125-02-9)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Classification is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.