N-lauroylsarcosine

Endpoint summary

Description of key information

Skin corrosion in vitro (OECD 431): non-corrosive, based on read-across
Skin irritation in vivo (OECD 404, 30%): not irritating, based on read-across
Skin irritation in vivo (U.S. Federal Hazardous Substances Act, 10% ): not irritating, based on read-across
Eye irritation in vivo (OECD 405, 30%): irritating, based on read-across
Eye irritation in vivo (OECD 405, 30%): corrosive, based on read-across
Eye irritation in vivo (U.S. Federal Hazardous Substances Act, 10% ): irritating, based on read-across

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

No sufficient data are available for the assessment of skin and eye irritation and corrosion properties of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.1.1 and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category members was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5., of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13).

Discussion

Skin irritation

In a publication (Shimizu, 1995), male Wistar rats were treated with a 1% N-lauroylsarcosine (CAS 97-78-9) ointment for 24 h. An amount of 0.1 g of the ointment was applied onto the shaved back of the animals under occlusive conditions. After 24 h treatment the skin effects were evaluated.

All animals showed moderate erythema with a score of 2 (maximum possible score 3). Furthermore, microscopic examinations of the treated skin showed induced degenerative changes of surface epithelium including necrosis, a slight vasodilation and perivascular infiltrates in the dermis.

However, the quality of the publication was not considered sufficient for assessment; therefore, in order to fulfil the standard information requirements set out in Annex VIII, 8.1.1 and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category member Sodium N-lauroylsarcosinate (CAS 137-16-6) was conducted.

The skin irritation properties of Sodium N-lauroylsarcosinate (CAS 137-16-6) have been investigated in several in vitro and in vivo studies.

The in vitro skin corrosion properties of Sodium N-lauroylsarcosinate (CAS 137-16-6) were tested in a study according to OECD guideline 431 under GLP conditions using the EPISKIN in vitro Reconstituted Human Epidermis Model (Warren, 2010). In the study, the tissues were treated with the unchanged test material for exposure periods of 3, 60 and 240 min. Positive and negative controls were included in the study. The corrosive potential of the test material was predicted from the relative mean tissue viabilities compared to the mean of the negative control tissues.

The positive and negative control substance gave the expected results. The relative mean tissue viabilities of the test compound were > 100% for all exposure periods. Thus, in the described test Sodium N-lauroylsarcosinate (CAS 137-16-6) is considered to be non-corrosive.

The skin irritation properties of Sodium N-lauroylsarcosinate (CAS 137-16-6) were tested in an in vivo study according to OECD guideline 404 under GLP conditions (Vaeth, 2004). In the study, 3 rabbits (Little russian) were exposed to a 30% (v/v) solution of the test substance in water. A sequential testing strategy was applied comprising an initial test in one animal and a confirmatory test with all animals. In the initial test, Sodium N-lauroylsarcosinate (CAS 137-16-6) was applied to the shaved skin of one animal for 3 min and 1 h using a semiocclusive dressing. In the confirmatory main test, the animals were similarly treated for an exposure period of 4 h. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application.

In the initial test, the animal showed well defined erythema immediately after application. In the main test, well defined erythema was observed in 1/3 animals, and very slight erythema in 2/3 animals. At the 24, 48 and 72 h reading time point, moderate to severe erythema and very slight oedema were observed in one animal and very slight erythema in the remaining two animals with mean erythema scores of 3, 1 and 1 for animal 1/2/3 over 24, 48 and 72 h, respectively. All effects on skin were fully reversible within 14 days.

Thus, the test material was considered to be non-irritating at 30% (v/v) solution in water in this test system.

Furthermore, Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested in a study according to a test method described in the U.S. Federal Hazardous Substances Act (U.S. Federal Register, 1973, Vol. 38, No. 187, Section 1500: 41) under GLP conditions (Haynes, 1987).

In the study, 6 female New Zealand white rabbits were exposed to a 10% (v/v) solution of the test substance in water applied onto both shaved (intact) and abraded skin for 24 h using an occlusive dressing. The treated skin was observed and evaluated at 24 and 72 h post-application. At the 24 h reading time point, well defined erythema was observed in all animals (intact and abraded skin) as well as defined oedema in 2 animals and slight oedema in 4 animals with intact skin. A decline of the irritant response was apparent at the 72 h reading; however well-defined erythema remained in 4 animals on intact and abraded skin, and very slight erythema remained in one animal on both intact and abraded skin. Very slight oedematous reaction was observed at three abraded sites and three intact sites and slight oedema on abraded skin in one animal was apparent. Thus, during the observation period of 72 h, the skin effects were not fully reversible. However, due to the short observation time and the observed decline of the irritant response, it cannot be excluded that the effects would have been reversible if a longer observation period would have been applied. Furthermore, only very slight to well defined erythema and very slight to slight oedema were observed, and no further local or systemic effects were reported. Thus, the test material at a 10% (v/v) solution in water was considered to be non-irritating based on an expert judgement.

In summary, Sodium N-lauroylsarcosinate (CAS 137-16-6) was considered to be non-corrosive in an in vitro skin corrosion test. Furthermore, Sodium N-lauroylsarcosinate (CAS 137-16-6) revealed under the experimental conditions as a 30% (v/v) solution no skin irritation properties in vivo. However, a 10% (v/v) solution of the test material showed non-reversible effects after 72 h of observation. Due to the short observation period in this study, and in combination with the declining tendency of the irritating effects, the result of the study was considered to be non-irritating at 10% (v/v).

Sodium N-lauroylsarcosinate (CAS 137-16-6) is therefore considered to be non-irritating at a specific concentration limit of 30%.

Classification as Skin irritation Category 2 for the neat substance is based on an expert judegment considering a worst case assumption.

Eye irritation

No studies are available investigating the eye irritation properties of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.2.1 and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category member Sodium N-lauroylsarcosinate (CAS 137-16-6) and Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was conducted.

Two studies investigating the eye irritation properties of Sodium N-lauroylsarcosinate (CAS 137-16-6) are available. In the first study, Sodium N-Laurylsarcosinate was tested in vivo in a study according to OECD guideline 405 under GLP conditions (Vaeth, 2004).

In a group of 3 rabbits (Little russian) 0.1 mL of the test substance as 30% (v/v) solution in water was instilled into one eye in a single application without washing. The eyes were observed and reactions were evaluated 1, 24, 48 and 72 h and 7, 14 and 21 days after instillation.

Corneal opacity and iritis were seen at 24, 48 and 72 h in all three animals, resulting in individual mean cornea and iris scores of ≥ 1 and 1, respectively. Effects on cornea and iris were fully reversible within at the maximum 21 days. All animals showed slight or well defined to moderate erythema of the conjunctivae at the 24, 48 and 72 h reading time points (mean erythema scores of animal 1/2/3 over 24, 48 and 72 h = 1/1.3/1) which were fully reversible within 14 days. Furthermore, all animals showed chemosis at the 24, 48 and 72 h reading time points (mean chemosis score animal 1/2/3 over 24, 48 and 72 h = 1.3/1.3/1.67) which were fully reversible within 7 days.

Thus, Sodium N-lauroylsarcosinate (CAS 137-16-6) at a 30% solution caused eye irritating effects in the animals.

In addition, Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested according to U.S. Federal Hazardous Substances Act (U.S) Federal Register, 1973, Vol. 38, No.187, Section 1500: 42 (Haynes, 1987). In a group of 6 New Zealand White rabbits, 0.1 mL of a 10% (v/v) solution in water was instilled into one eye. The eyes were observed, and reactions were evaluated 24, 48 and 72 h after instillation.

Iritis was apparent in the treated eye of 5/6 animals after 24 h and was not fully reversible within 72 h resulting in a mean iris score of 0.7 for all 6 animals over 24, 48 and 72 h. Corneal opacity was observed in 4/6 animals being not fully reversible within 72 h, either. Conjunctival redness ranged from very slight to well defined erythema (mean conjunctivae score out of all 6 animals over 24, 48 and 72 h = 1.6) and conjunctivae swelling from slight to severe effects with 4/6 animals showing a mean conjunctival swelling ≥ 2 (mean conjunctivae score out of all 6 animals over 24, 48 and 72 h = 2.2) being not fully reversible within 72 h in all animals.

Possibly due to the shorter observation period of 72 h effects were not reversible. However, regarding the calculated mean scores following grading at 24, 48 and 72 h, the test material is not considered to produce irreversible effects on the eye but rather irritating effects which would be reversible after a longer observation period.

In summary, both studies showed irritating effects to the eyes in concentrations of 10 and 30% (v/v) of the test substance. Sodium N-lauroylsarcosinate (CAS 137-16-6) is therefore considered to be irritating to the eye (Eye irrit 2) at concentrations of ≥ 1% and ≤ 30%.

Classification as Eye dam. 1 for concentrations > 30% and for the neat substance is based on an expert judgement considering a worst case assumption.

Eye irritation of Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was investigated in an in vitro bovine corneal opacity and permeability test, conducted according to OECD 437, and in compliance with GLP (Warren, 2012). Mean irritancy scores calculated were 2.6, 77.1, and 92.8 for the negative control, the test item, and the positive control, respectively. The positive control data were within the two standard deviations of the current historical control mean and therefore this assay was considered to be valid. Thus, Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) is concluded to be corrosive to the bovine eye in the in vitro bovine corneal opacity and permeability test. However, this study does not provide sufficient and adequate information on eye irritation for classification purposes.

In addition, the eye irritation properties of a mixture of Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) were assessed in a study similar to OECD guideline 405 in compliance with GLP (Reagan, 1989).

In a group of 6 New Zealand White rabbits, 0.1 mL of the unchanged test substance was instilled into one eye in a single application without washing. The eyes were observed and reactions were evaluated 24, 48 and 72 h and 7 days after instillation.

All animals showed positive ocular response following test article instillation resulting in mean scores of 2.06/0.72/2.83/2.33 for cornea score/iris score/conjunctivae score/chemosis score, respectively, for all 6 animals over 24, 48 and 72 h. After 7 days, effects on cornea, iris, conjunctivae redness and chemosis were not fully reversible in 4/6, 2/6, 6/6 and 5/6 animals, respectively.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across based on a category approach/read-across from a structural analogue and weight of evidence from these studies. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties among category members and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across based on a category approach/read-across from a structural analogue and weight of evidence from these studies. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties among category members and overall quality assessment (refer to the endpoint discussion for further details).

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of a substance structurally related to N-lauroylsarcosine (CAS 97-78-9) according to Regulation (EC) No 1907/2006, Annex XI, 1.5. meet the criteria for classification for skin irritation category 2 (H315) according to Regulation (EC) No 1272/2008 and as skin irritating (Xi; R38) according to Directive 67/548/EEC at concentrations > 30%.

The available data on eye irritation of a substance structurally related to N-lauroylsarcosine (CAS 97-78-9) according to Regulation (EC) No 1907/2006, Annex XI, 1.5. meet the criteria for classification for Eye dam. Category 1 (H318) at concentration > 30% and as Eye Irrit. 2 (H319) at concentrations ≤ 30% and ≥ 1% according to Regulation (EC) No 1272/2008 and as Risk of serious damage to eye (Xi; R41) at concentration > 30% and eye irritating (Xi; R36) at concentrations ≤ 30% and ≥ 5% according to Directive 67/548/EEC.

Therefore, N-lauroylsarcosine (CAS 97-78-9) is classified accordingly.