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Toxicological information

Carcinogenicity

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Description of key information

Based on all available data of trometamol, there is no evidence of a carcinogenic potential. Further testing is not required under Regulation (EC) 1907/2006, Annex XI, section 1.2.

Key value for chemical safety assessment

Additional information

Trometamol did not induce tumors when tested in male Syrian golden hamsters receiving 0.2 mL of a mixture of TRIS-based buffer and 0.9% NaCl intratracheally into the lungs once per week for life (Ketkar et al., 1979). There are no standard animal data available on carcinogenicity or on chronic toxicity of 2-amino-2-(hydroxymethyl)-1,3-propanediol (Trometamol). However, it can be assumed that trometamol has no carcinogenic potential based on the fact that the substance was not shown to be mutagenic or clastogenic in the available genetic toxicity studies and bears no structural similarity to known carcinogens. Furthermore, trometamol has no functional groups associated with carcinogenicity and did not produce any evidence of neoplasia in the available repeated dose toxicity studies. The Cramer classification (related mainly to the oral route) also indicates a low toxicological concern for trometamol. In addition, trometamol is also used in clinical applications e.g. to correct acute or respiratory acidosis or it can be used to alkalinise body fluids and promote diuresis in order to enhance the elimination of salts of weak acids such as salicylate or barbiturate (Nahas, 1962, 1963). Due to its therapeutic indication, trometamol is well investigated in animals and humans. There was no evidence of a carcinogenicity of trometamol

in pharmacokinetic studies. Therefore, it is concluded that trometamol does not have a carcinogenic potential.

Literature not cited in the IUCLID

Nahas, G.G. (1962) The pharmacology of tris(hydroxymethyl)aminomethane during CO2 load. Am. J. Physiol. 204:113-118

Nahas, G.G. (1963) The clinical pharmacology of THAM (tris(hydroxymethyl)-aminomethane).Clin. Pharmacol. Ther. 4:784-803

Justification for classification or non-classification

Based on all available data of TRIS AMINO within the analogue approach, no carcinogenic potential is expected. The available data do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and therefore are conclusive but not sufficient for classification.