Tris[(2-hydroxyethyl)ammonium] citrate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No substance-specific data on the skin sensitizing properties of tris[(2 -hydroxyethyl)ammonium] citrate are available. However, according to Article 13 of the REACH legislation, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Tris[(2 -hydroxyethyl)ammonium] citrate is a salt of monoethanolamine and citric and is expected to dissociated into the respective monoethanolammonium cation and dihydrogen citrate anion (which may subsequently undergo (partial) dissociation to monohydrogen citrate and citrate anions) upon uptake by the body. Therefore it is considered to be acceptable to derive lacking information on toxicological properties of tris[(2 -hydroxyethyl)ammonium] citrate by read-across from its starting materials.

Citric acid is an important intermediate of the Krebs cycle (also known as citric acid cycle), and therefore occurs naturally as a metabolite in virtually all living organisms. It is also used as a natural food preservative and a food additive. The average daily intake (ADI) is not limited according to the evaluation ofJoint FAO/WHO Expert Committee on Food Additives (1973), which concluded that the substance is non-hazardous to men. Therefore the toxicological behavior of tris[(2 -hydroxyethyl)ammonium] citrate is expected to be governed primarily by the toxicity of monoethanolamine. Nevertheless available data on citric acid have also been taken into account.

The sensitising potential of monoethanolamine was studied using the guinea pig maximisation test (Wahlberg and Boman, 1996). Groups of 15 animals were induced intradermally and epicutaneously with 0.6 % (intradermal) and 10.3 % (epicutaneous) solution of monoethanolamine, and then challenged epicutaneously after three weeks with 0.41, 2.05 and 4.1 % test substance at the virgin site. Prior to the topical induction, pretreatment with 10% sodium dodecyl sulphate was carried out. The challenge reactions were read blindly 48 and 72 h after application or the patches. Control groups of twelve animals were given the same treatment except for the inducing amine. After challenge with 4.1 %, 2.05 % and 0.41 % of 2-aminoethanol, 3/15, 2/15 and 3/15 animals reacted positively after 72 hours. Two out of 15 animals showed a reaction to the vehicle. Of the 12 control animals, none reacted to monoethanolamine or the vehicle. Based on these results, monoethanolamine is considered to be not sensitizing to skin.

No skin sensitization studies on citric acid are available. However, taken into account its widespread use for many decades, also in food products, and the lack of reports on human sensitization associated with its use, it is highly unlikely that citric acid may possess a skin sensitizing potential.

Respectively, tris[(2 -hydroxyethyl)ammonium] citrate is considered to be not sensitizing.

Migrated from Short description of key information:
Based on the read-across from starting materials monoethanolamine and citric acid, tris[(2-hydroxyethyl)ammonium] citrate is not sensiting to skin.

Justification for classification or non-classification

Based on the read-across from the starting materials monoethanolamine and citric acid, classification of the substance for skin sensitization is not warranted in accordance with EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.