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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

No study data on the toxicity on reproduction by ammonium hydrogencarbonate was available. However, ammonium bicarbonate rapidly dissociates in biological fluids to yield ammonium ion (NH4+) and bicarbonate ion (HCO3-), which are both are integral components of normal metabolic processes and play an essential role in the physiology of man and other species. NH4+ ions are immediately transformed into urea by the liver and do not exist in the blood in relevant amounts unless in case of liver failure. Together with the absence of genotoxicity, carcinogenicity and developmental toxicity, the data suggest that there is no substantial evidence for toxicity on reproduction by ammonium hydrogencarbonate which is also supported by data of other ammonium salts, that showed no effects on reproductive organs. The performance of a 2-Generation Study is therefore not warranted.


Short description of key information:
Ammonium bicarbonate rapidly dissociates in biological fluids to yield ammonium ion (NH4+) and bicarbonate ion (HCO3-), which are both are integral components of normal metabolic processes and play an essential role in the physiology of man and other species. NH4+ ions are immediately transformed into urea by the liver and do not exist in the blood in relevant amounts unless in case of liver failure. Together with the absence of genotoxicity, carcinogenicity and developmental toxicity, the data suggest that there is no substantial evidence for toxicity on reproduction by ammonium hydrogencarbonate which is also supported by data of other ammonium salts, that showed no effects on reproductive organs. The performance of a 2-Generation Study is therefore not warranted.

Effects on developmental toxicity

Description of key information
Developmental toxicity:
- oral: NOAEL >= 340 mg/kg bw/d ( Analogy CAS 144-55-8, sodium hydrogencarbonate)
Additional information

Due to the lack of data on teratogenicity with ammonium hydrogencarbonate, a study with sodium bicarbonate (CAS 144-55-8) was taken into account for assessment.

25 female Wistar rats per dose were treated daily with an aqueous solution containing 3.4, 15.8, 73.3 and 340 mg/kg sodium bicarbonate by gavage during the days 6 - 15 of gestation (FDA, 1974). At the end of study period, the fetuses were examined for the presence of external congenital abnormalities, detailed visceral abnormalities and for skeletal defects. The examinations showed that sodium bicarbonate did not affect implantation or the survival of dams and fetuses. The number of abnormalities seen in either soft or skeletal tissues of the test group did not differ from the number occurring spontaneously in the sham-treated controls, while the number was increased in animals treated with the positive control (Aspirin, 250 mg/kg bw). Therefore the NOAEL for developmental toxicity was >= 340 mg/kg bw/d. Similar negative results were reported by analogue studies for mice and rabbits for daily doses from 5.8 - 580 mg/kg bw and 3.3 - 330 mg/kg bw, respectively (FDA, 1974). Since the hydrogencarbonate ion is a dissociation product of sodium hydrogencarbonate similar as it is after dissociation of ammonium hydrogencarbonate, the same result could be expected for ammonium hydrogencarbonate.

This view is also supported by the likewise long history of safe use in humans.

Besides this, an epidemiological study evaluated the use of cough mixtures containing ammonium bicarbonate as an excipient by pregnant women and did not find any statistically significant association between the maternal use and adverse neonatal outcomes (Colley, 1982). In addition other ammonium salts like ammonium chloride were not teratogenic in animal tests.

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

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.