2,3,3-trimethyl-3H-indole-5-carboxylic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

other: indicative assessment based on non-testing methods: QSAR, physical-chemical data, toxicological data

Adequacy of study:

other information

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Report date:

2018

Materials and methods

Principles of method if other than guideline:

Indicative assessment of potential skin sensitizing properties based on non-testing methods

Test material

Test material information

Constituent 1

Reference substance name:

2,3,3-trimethyl-3H-indole-5-carboxylic acid

EC Number:

282-162-4

EC Name:

2,3,3-trimethyl-3H-indole-5-carboxylic acid

Cas Number:

84100-84-5

Molecular formula:

C12H13NO2

IUPAC Name:

2,3,3-trimethyl-3H-indole-5-carboxylic acid

Results and discussion

Any other information on results incl. tables

This indicative assessment of potential skin sensitizing properties is based on the physico-chemical properties of the substance, on Structure Activity Relationship information, and on available toxicological data. Experimental studies and/or animal studies have not been performed for this assessment.

2,3,3-Trimethyl-3H-indole-5-carboxylic acid shall be registered under REACH as transported isolated intermediate (Article 18 < 1000 t/a).

2,3,3-Trimethyl-3H-indole-5-carboxylic acid is a brown solid with a molecular weight of 203 g/mole. The substance is moderately soluble in water and a log Kow (octanol/water) of + 3.84 was estimated via EPI Suite version 4.11 . Based on these physical-chemical parameters dermal absorption can be expected (ECHA Guidance on Information Requirements, Chapter R7c, 2017).

Toxicological data:

The substance was shown to be not harmful after single oral uptake of high doses and not irritating to rabbit’s skin and eyes. No skin irritating or skin sensitizing effects were reported in occupational settings. The substance exerted no mutagenic properties in an Ames test in Salmonella typhimurium and E.coli.

In silico data:

As in silico tools for the prediction of skin sensitization the QSAR OECD Toolbox 4.0 was used. The outcome of the mechanistic/endpoint relevant profilers for skin sensitization potential is:

Protein binding alerts:

No protein binding alerts were identified by OASIS v1.4 and OECD for the substance.

Protein binding potency:

Not possible to classify (Remark: It could be noted that the protein-binding potency profiler only predicts the reactivity quantitatively if the protein-binding mechanism is of Michael addition-type or Nucleophilic substitution type 2.).

Specific profilers for protein binding:

No activity in the Direct Peptide Reactivity Assay (DPRA) with regard to cysteine and lysine peptide depletion and no h-CLAT activity were foreseen. With regard to keratinocyte gene expression the substance is out of mechanistic domain.

The absence of an electrophilic (DNA-reactive) potential of 2,3,3-Trimethyl-3H-indole-5-carboxylic acid was shown in a bacterial mutagenicity test with negative outcome.

Discussion and conclusion:

This indicative assessment of skin sensitizing properties is based on physico-chemical, toxicological, and in silico data. Experimental studies have not been performed for this endpoint.

The substance is of low acute oral toxicity in vivo and is not irritating to rabbit’s skin. In occupational settings no skin effects as skin irritation or skin sensitization were reported. The substance showed no electrophilicity in an Ames test in vitro.

According to the physico-chemical properties of the substance (solid, moderate solubility in water, log Pow 3.84) dermal absorption is not favoured but possible. However, the substance exerts no skin irritation potential that would facilitate penetration through the stratum corneum. No skin sensitization alerts were identified in silico by the OECD Toolbox.

In conclusion, the limited available information in this indicative evaluation does not point to a relevant skin sensitization potential in vivo.

Applicant's summary and conclusion

Conclusions:

In conclusion, the limited available information in this indicative evaluation does not point to a relevant skin sensitization potential in vivo.