Registration Dossier

Administrative data

Description of key information

Skin: not irritating
Eye: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation:

Several skin irritation studies with 2 -amino-2 -(hydroxymethyl)-1,3 -propanediol (trometamol) are available.

In a study performed according to OECD 404 on rabbits, 0.5 g trometamol (moistened with water) was applied to shaved skin and covered with a semi-occlusive dressing for 4 hours (Prakash, 2011). No erythema or edema was observed in any of the animals 1, 24, 48 and 72 hours after exposure ended. This finding is confirmed by the absence of skin irritation effects in an acute dermal toxicity study (OECD 402) performed on rats using semi-occlusive exposure to 5000 mg/kg bw trometamol for 24 hours (Mohan Kumar, 2011).

In addition, several non-guideline studies with limited information are available. Baldwin (1961) reported that a saturated solution of the test substance caused very slight skin irritation in rabbits after 4 hours exposure, while the undiluted solid and a 25% solution did not lead to any skin effects. In a study by Machle et al. (1940), 4 hours’ open exposure to the test substance on 5 consecutive days did not cause skin irritation effects in rabbits. By applying a principle component analysis (TSAR), a prediction can be made regarding the likely corrosive or non-corrosive classification of a substance (Barratt, 1996). Using the known physical-chemical characteristics logP, molecular volume and melting point, trometamol was predicted to be non-corrosive under the conditions of the TSAR model. 

Taking the available data into account, trometamol is not considered to be skin-irritating.

Eye irritation:

In a study performed by Prakash (2011), according to OECD 405, 0.1 g of trometamol was instilled into one eye of each of 3 rabbits. The eyes remained unwashed and were assessed for irritation 1, 24, 48 and 72 hour after the instillation. Slight to moderate effects on the conjunctiva (score 1-2) and chemosis (score 1-2) were observed from the 1-hour reading time point in 3/3 rabbits. The maximum mean scores for both effects on the conjunctiva and chemosis were 1.33 for 1/3 rabbits, and 0.33 for 2/3 rabbits, respectively. The irritation effects had cleared completely in 2/3 rabbits within 48 hours and in the remaining rabbit with the highest mean scores within 72 hours. No damage to the iris or cornea was observed at any reading time point. 

In a brief report, Power (1975) noted that the test substance, production trometamol concentrate, did not cause eye irritation. 

Taking the available data into account, trometamol is considered not to be eye irritating.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.