C8-18 (even numbered) and C18 (unsaturated) sarcosinates, 2-hydroxypropylammonium salt

Endpoint summary

Description of key information

Skin Irritation in vitro (OECD 439): at least irritating to skin, but no unequivocal prediction on classification possible; in vitro skin corrosion test (OECD 431) commissioned
Skin corrosion in vitro (OECD 431): in progress
Eye irritation in vitro (OECD 437 BCOP): irritating to eyes (IVIS = 19), but no concluding prediction on classification possible; in vivo eye irritation test (OECD 405) commissioned
Eye irritation in vivo (OECD 405): in progress, final study plan attached

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The irritation/corrosion potential of the test substance has been investigated in an integrated approach on testing and assessment (IATA) as recommended by authorities in the interest of sound science and animal welfare. As a consequence, validated in vitro tests for skin and eye irritation/corrosion should be performed before in vivo tests are conducted.

Skin irritation:

The skin irritation potential of the test substance has been assessed by an in vitro skin irritation test using a human three dimenional epidermal model (EPISKIN Small Model (EPISKIN-SM) (Eurlings, 2016). The test item has been topically applied to a functional stratum corneum which has differentiated from human-derived epidermal keratinocytes cultured for 13 days on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. After exposure of 3 tissue replicates to the test item for 15 min the cells were incubated for another 42 hours before cell viability was assessed by the MTT-assay. Three separate tests have been performed in the scope of this study. In the first test relative mean tissue viability was 59% compared to the negative control tissues. Since two of the individual viabilities were above 50% and one was below, no conclusion could be made and a repeat test was performed. In this second test mean tissue viabilities were 11% compared to the negative control tissues. Since the mean relative tissue viability for the test substance treated tissues was below 50% the substance was considered to be irritant. However, since the difference to the first test was 48% and the test substance is a viscous liquid a repeat test with additional washing was performed to make sure the test substance was removed properly. In the third test relative mean tissue viability after test substance treatment was 10% compared to the negative control tissues. Since it was below 50% the test substance was considered to be irritant. As one equivocal result and two clearly positive results had been obtained it was concluded that the test substance was irritant in the in vitro skin irritation test under the conditions of the study.

However, due to the nature of this test system no unequivocal prediction on classification (Category 1 or Category 2) can be made without additional information on corrosivity. Therefore, an additional in vitro skin corrosion test according to OECD guideline 431 had been commissioned in the scope of the sequential testing strategy.

Skin corrosion:

The in vitro skin corrosion test according to OECD guideline 431 was commissioned prior to registration. An update of the registration dossier as soon as the results are available is planned.

Eye irritation:

For the assessment of the eye irritation potential of the test substance the Bovine Corneal Opacity and Permeability (BCOP) test, according to OECD guideline 437, has been chosen as one of the validated in vitro tests addressing serious eye damage in an IATA (Eurlings, 2016).

As the test substance is a surfactant, a 10% dilution has been applied to isolated bovine corneas in this test, according to the recommendation of the guideline. The corneas treated with the test substance for 10 minutes showed opacity values ranging from 5.5 to 6.3 and permeability values ranging from 0.807 to 0.981. The corneas were slightly translucent after the treatment. Hence, the in vitro irritancy scores (IVIS) ranged from 18 to 20 after 10 minutes of treatment with a 10% dilution of the test substance (mean in vitro irritancy score: 19.3). As the IVIS were clearly below 55 a classification as corrosive could be excluded.

However, according to the criteria of UN GHS and as laid down in OECD guideline 437, no final prediction on the classification can be made when an IVIS > 3 ≤ 55 is obtained, and in the course of the sequential testing strategy an in vivo eye irritation test according to OECD guideline 405 had to be conducted in addition.

In vivo test results:

An in vivo eye irritation test according to OECD guideline 405 was in progress at the time of registration; the final study plan is attached. An update of the registration dossier as soon as the results are available is planned.

Justification for selection of skin irritation / corrosion endpoint:
Only the chosen study was available at the time of registration. Based on the available results no unequivocal prediction on the classification was possible; therefore, an additional in vitro study addressing skin corrosion according to OECD guideline 431 had been commissioned prior to registration, in accordance with a tiered testing strategy recommended by authorities. The results were not yet available at the time of registration. Proposed study period: 15 May 2016 - 30 Jun 2016. An update of the registration dossier is planned as soon as the data on skin corrosion are available.

Justification for selection of eye irritation endpoint:
Only the chosen study was available at the time of registration. Based on the available in vitro results no concluding prediction on the classification was possible; therefore, an additional in vivo study addressing eye irritation in the rabbit according to OECD guideline 405 had been commissioned prior to registration and was in progress at the time of registration, in accordance with a tiered testing strategy recommended by authorities and animal welfare considerations. The results were not yet available at the time of registration. Proposed study period: 13 Apr 2016 - 30 May 2016. An update of the registration dossier is planned as soon as the data on eye irritation are available.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

According to the criteria of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1271/2008 on classification, labelling and packaging of items and mixtures (including all amendments) the test item has to be classified as inducing Skin corrosion Category 1 and Eye irritation Category 2 considering the available data for skin and eye irritation. This classification represents a worst case assumption in the absence of further data. In order to generate the required information for a final classification additional studies for the assessment of skin corrosion in vitro and eye irritation in vivo have been commissioned and are in progress at the time of registration. The applied classifications have to be considered as a preliminary worst case assumption and will be subject to further updates as soon as the respective study data will be available.