Hexadecyl hydrogen maleate

Endpoint summary

Description of key information

non skin irritant

eye irritant

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:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The in vitro study was performed in order to evaluate the potential of the test item to evoke skin irritation in a reconstructed human epidermis (RhE) test method. The test procedure was performed following the EU-Method B.46 and the OECD 439. Three tissues of the human skin model EpiDermTM were treated with the test item for 60 minutes. The test item was applied directly to each tissue and spread to match the tissue size (0.63 cm2). DPBS-buffer was used as negative control and 5% SDS solution was used as positive control. After exposure of the tissues with the test item, the test item was rinsed from the tissues and cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution. All validity criteria were met. The mean value of relative tissue viability was increased to 138.2 % after tretament with the test item. This value is above the threshold for skin irritation potential (50%). Therefore, the test item is considered non-irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.

 

Eye irritation

The Eye Hazard Potential of the test item was evaluated in a RhCE model in an in vitro study according to the OECD Guideline 492. The test item was applied to a three-dimensional human cornea tissue model in duplicate for an exposure time of 6 hours. The solid test item was applied to two tissue replicates. After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution. Concurrent negative (demineralised water) and positive control (methyl acetate) run in parallel. All validity criteria were met. After treatment with the test item, the mean value of relative tissue viability was 2.5%. This value is well below the threshold for eye hazard potential (≤ 60 %). Under the conditions of the test, the substance is considered either eye irritant or inducing serious eye damage in the EpiOcularTMEye Irritation Test.

Based on the in vitro results and according to the OECD Guideline 492, the EpiOcularTM Eye Irritation Test does not allow discrimination between eye irritation/reversible effects on the eye (Category 2) and serious eye damage/irreversible effects on the eye (Category 1). For these purposes, further testing with other suitable test methods is required.

The evaluation of the test item in the Bovine Corneal Opacity and Permeability (BCOP) Test Method was performed following following OECD Guideline 437 and EU Method B.47. The test item was applied onto the corneas of a bovine eyes (three replicates) which had been previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured. The negative control ( Hank’s Balanced Salt Solution (HBSS)) showed no irritating effect on the cornea and the calculated mean IVIS (In Vitro Irritancy Score) was 0.77. The positive control (Dimethylformamide (DMF) undiluted) induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated mean IVIS was 97.69.

The test item was tested neat and incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. Under the conditions of this study, the test item showed effects on the cornea of the bovine eye. The calculated mean IVIS was 7.23. According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage with the BCOP study only. In this case no prediction can be made.

The eye irritation of the substance is evaluated in a weight of evidence approach. Considering the results of both in vitro studies, it can be concluded that the substance is an Eye irritant.

Justification for classification or non-classification

Skin irritation

Based on the in vitro results and on the OECD 439 criteria, the test item is not classified fos skin irritantion as per the CLP Regulation (EC) No 1272/2008.

Eye Hazard Potential

Considering the results obtained in the OECD 492, the substance can be considered either as a substance causing eye irritation/reversible effects on the eye (Category 2) or serious eye damage/irreversible effects on the eye (Category 1). However, considering the results obtained in the OECD 437, the classification in Cat 1 is excluded since IVIS is > 3. In a weight-of-evidence approach, the substance is classified as Eye Irritant (H319) as per the CLP Regulation (EC) No. 1272/2008.