Amines, N-(C16-18 and C18-unsatd. alkyl)-N,N',N'-trimethyltrimethylenedi-

Endpoint summary

Description of key information

No test data available. Profiling and QSARs indicate a low risk for sensitisation, and due to use in industrial and professional setting only, with the application of adequate PPE related to the severe corrosive properties of the etheramine, exposures are limited. There are no reports on incidents of sensitisation to diamine methylated available.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There are no reports on incidences of sensitisation from industrial production and use of the substance.

 

The molecular structure of the diamines does not contain toxicophores indicating a concern for sensitization. Profiling in QSAR Toolbox (v.4.3) indicate that Diamine methylated is not expected to bind to protein,:

General mechanistic

- Protein binding by OASIS: No alert found

- Protein binding by OECD: No alert found

- Protein binding potency: Not possible to classify according to these rules (GSH)

- Protein binding potency Cys (DPRA 13%): Grey zone 9-21%

- Protein binding potency Lys (DPRA 13%): Less than 9%

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Endpoint specific

- Keratinocyte gene expression: Not possible to classify according to these rules

- Protein binding alerts for skin sensitization according to GHS: No alert found

- Protein binding alerts for skin sensitization by OASIS: No alert found

- Protein Binding Potency h-CLAT: No alert found

- Respiratory sensitisation: No alert found

No metabolism/transformations are predicted for:

- Autoxidation simulator

- Autoxidation simulator (alkaline medium)

- Dissociation simulator

- Hydrolysis simulator (acidic, basic, neutral)

Metabolism is predicted by the Skin metabolism simulator. The skin simulator was developed as a simplified mammalian liver metabolism simulator (assuming that metabolism in liver microsomes is similar to that of skin compartment). This predicts successive demethylation of the methyl-groups from the terminal Nitrogen with subsequent oxidation to formaldehyde and formic acid. However, extensive metabolism is not expected.

 

The Toolbox automated process for prediction of skin sensitisation predicted negative. (By read-across to 1,14-Tetradecanediol, which is not considered structurally relevant)

Other QSARs for sensitisation:

- DEREK: Skin sensitisation in mammal is NON-SENSITISER- No misclassified or unclassified features

- TOPKAT: Non-Sensitizer (low validity)

- VEGA (CAESAR v2.1.6): Sensitizer (good reliability), although substances from training set includes: sulfates, nitrogen-oxygen-ring structures and acid chloride, but no tert. amines!

- Danish QSAR DB battery model (1.0) – Out of domain (Leadscaope 1.0: Pos; SciQSAR 1.0: Neg.)

 

Discussion: dermal

There is no data on sensitisation available forDiamine methylated. Available studies indicate that the substance is highly corrosive. There are no consumer exposures, only industrial/professional use under circumstances involving the use of PPM following the classification as corrosive cat. 1B. Consequently, due to limited exposures, animal testing is not required.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Diamine methylatedhas a low vp pressure (2.3E-04 Pa at 20°C, experimental) and its use is limited to industrial settings that do not involve the forming of aerosols, particles or droplets of an inhalable size. So exposure to humans via the inhalation route will be unlikely to occur.

Additionally, information from profiling for expected protein interaction and QSARs for sensitisation result to a low concern.

Justification for classification or non-classification

There is no information available from testing. Available data is not robust enough to derive a definite conclusion. However the lack of structural alerts in DEREK, without misclassified or unclassified features, indicates a low likelihood for sensitisation.