Registration Dossier

Administrative data

Description of key information

Skin irritation (WoE, OECD 404), rabbit: irritating

RA from source substances Sodium N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 3624-77-9), N-(1-oxooctadecyl)sarcosine (CAS 142-48-3), (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

Eye irritation (WoE, OECD 405), rabbit: serious eye damage

RA from source substances Sodium N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 3624-77-9), N-(1-oxooctadecyl)sarcosine (CAS 142-48-3), (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

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 (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data on skin and eye irritation / corrosion are available for the target substance (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine, compound with 2,2',2''-nitrilotri(ethanol) (1:1) (CAS 17736-08-2). Therefore, read across from the relevant source substances Sodium N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 3624-77-9), N-(1-oxooctadecyl)sarcosine (CAS 142-48-3) and (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) was applied to obtain information regarding both skin as well as eye irritation.

Skin irritation / corrosion

In a reliable skin irritation study performed according to OECD TG 404 and in compliance with GLP, three female Little Russian rabbits were exposed to 0.5 g of Sodium N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 3624-77-9) onto the shaved skin for 3 min, 1 h (initial test) and 4 h (confirmatory test) via semi-occlusive dressing (Frey-Tox, 2005a). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 h and 7, 14 and 21 days post-application. In the initial test, the animal showed well defined erythema immediately after application of the test substance. In the main test, well-defined to moderate and severe erythema were observed in all animals resulting in mean erythema scores over 24, 48 and 72 h of 2.33, 3 and 3, respectively. Erythema were fully reversible within 21 days in 2/3 animals whereas 1/3 animals still showed isolated scales 21 days after application of the test substance. In addition, slight to moderate edema were observed in 3/3 animals resulting in mean edema scores over 24, 48 and 72 h of 1.67, 2.3 and 2, respectively being fully reversible within 7 days in 3/3 animals. No further local or systemic effects were observed. Based on the study results and according to EU classification criteria, the test substance is considered to be irritating to the skin.

Furthermore, in a reliable skin irritation study performed according to OECD TG 404 and in compliance with GLP three female Albino rabbits (Chbb:HM) were exposed to 0.5 g N-(1-oxooctadecyl)sarcosine (CAS 142-48-3) onto the clipped skin for 4 h via semi-occlusive coverage (Frey-Tox, 2008). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 h and 7 and 14 days post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. In the initial test, the animal showed well defined erythema and only very slight edema formation immediately after application of the test substance. In the main test, slight to well-defined erythema formation was observed in all animals resulting in mean erythema scores over 24, 48 and 72 h of 2, 1 and 2, respectively. Erythema formation was not fully reversible in 2/3 test animals after the 14 days observation period as slight scurf and isolated sclaes were still visible. 1/3 animals was free of any signs of skin irritation 14 days after termination of exposure to the test substance. Moreover, no edema formation was observed in any animal at the 24, 48 and 72 h observations, resulting in an edema score of 0 (mean over all 3 animals and over 24, 48, and 72 h). Based on the study results and according to EU classification criteria, the test substance is considered to be irritating to the skin.

In another reliable skin irritation study performed according to OECD TG 404 and in compliance with GLP six male New Zealand White rabbits were exposed to 0.5 mL (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) onto the shaved skin for 4 h via semi-occlusive coverage (Hazleton, 1991). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 h and 7 and 14 days post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. At the 24, 48 and 72 h reading time point, well-defined to severe erythema (grade 2 - 4) and slight eschar formation were observed within the animals (mean erythema score out of all 6 animals = 2.89). Furthermore, edema formation was observed in all animals (mean edema score out of all 6 animals = 2.0). In addition, all animals showed burnt aspects and slight dryness of the skin at the application site at the 72 h reading time point. After 14 days, erythema and edema formation was fully reversible, however absence of hair on the whole application area was apparent in all animals. Based on the study results and according to EU classification criteria, the test substance is considered to be irritating to the skin.

 

Eye irritation

In the reliable eye irritation study with Sodium N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 3624-77-9) performed according to OECD TG 405 and in compliance with GLP 0.1 g of the neat test substance was instilled in the eye of three female Crl:CHBB Russian rabbits (Frey-Tox, 2013). The eyes were observed and reactions were evaluated according to the Draize scoring system 1, 8, 18, 24, 42, 48, 66 and 72 h and 7, 14, 21, 28, 35, 42, 49, 56, 30 and 70 days post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. No iridial irritation was recorded in any animal during the entire study period. Corneal opacity (grade 1) was recorded in 3/3 animals 1 h post-application of the test material and was fully reversible in 2/3 animals within 7 and 14 days of the observation period. In the remaining animal corneal opacity was not fully reversible within the 21-day observation period, thus the study period was extended to 70 days. Effects on corneal opacity were fully reversible within this 70-day observation period. Conjunctival irritation (grade 1) was observed in 3/3 animals being reversible within 7 days in 2/3 animals and 14 days in the remaining animal, respectively. Chemosis (grade 1 - 2) was also noted in 3/3 animals and was fully reversible within 7 days in 3/3 animals. The mean values for iridial irritation, corneal opacity, conjunctival irritation and chemosis were calculated to be 0, 1, 1 and 1.33, respectively. Based on the irreversible effects on the cornea within the 21-day observation period and according to EU classification criteria, the test substance is considered to cause serious eye damage.

In a further reliable eye irritation study with N-(1-oxooctadecyl)sarcosine (CAS 142-48-3) performed according to OECD TG 405 and in compliance with GLP 0.1 g of the neat test material was instilled in the eye of three Albino rabbits (Chbb:HM) (Frey-Tox, 2009). The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 h and 7, 14 and 21 days post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. Iridial irritation (grade 1) was recorded in 3/3 animals within 24 h after application of the test substance, but being fully reversible within 72 h in 1/3 animals and within 7 days in 2/3 animals, respectively. Corneal opacity (grade 1) was recorded in 3/3 animals but only being reversible in 1/3 animals within the 21 day observation whereas the remaining 2/3 animals showed irreversible effects on the cornea. Conjunctival irritation (grade 1 - 2) was observed in 3/3 animals being reversible within 14 days in 1/3 animals and 21 days in the remaining 2/3 animals, respectively. Chemosis (grade 1 - 2) was also noted in 3/3 animals and was reversible within 7 days in 2/3 animals and within 21 days in 1/3 animals, respectively. The mean values for iridial irritation, corneal opacity, conjunctival irritation and chemosis were calculated to be 1, 1, 2 and 2, respectively. Due to the irreversible effects on the cornea and according to EU classification criteria, the test substance is considered to cause serious eye damage.

The eye irritation properties of (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) were tested in a study performed according to US-EPA § 163.81-4, “Primary eye irritation study”, Federal Register, Vol 43, No. 163, August 22, 1978 (Ciba Geigy, 1981a). Groups of 3 male and 3 female New Zealand white rabbits were exposed to 0.1 mL of the neat test substance into the eye either without washing in 3 animals or with washing in the remaining 3 animals. The eyes were observed and reactions were evaluated according to the Draize scoring system 24, 48 and 72 h and 4 and 7 days post-application. No effects on iris were noted in any animal during the study period. Corneal opacity scores ≥1 were seen in the mean over 24, 48 and 72 h in 5/6 animals which were not fully reversible within the 7 days observation time. Moreover, all animals showed diffuse beefy redness of the conjunctivae resulting in a mean conjunctivae score out of all 6 animals over 24, 48 and 72 h of 3. Conjunctival redness was also not fully reversible within 7 days. After 7 days, obvious swelling with partial eversion of lids and discharge in various degrees were still apparent in all animals. No further local or systemic effects were reported. In summary, irreversible effects within an observation period of 7 days were observed in all animals. Thus, classification as Eye dam. Category 1 was based on an expert judgement considering a worst case assumption.

Justification for classification or non-classification

The available data on relevant read-across source substances for skin irritation/corrosion meet the criteria for classification for Skin Irritation, Category 2 (H315) according to Regulation (EC) No. 1272/2008 (CLP). Therefore, applying the RA-A approach, the target substance (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine, compound with 2,2',2''-nitrilotri(ethanol) (1:1) (CAS 17736-08-2) is also considered to meet the criteria for classification for Skin Irritation, Category 2 (H315) according to Regulation (EC) No 1272/2008 (CLP).

The available data on relevant read-across source substances for eye irritation/serious eye damage meet the criteria for classification for Eye Damage, Category 1 (H318) according to Regulation (EC) No. 1272/2008 (CLP). Therefore, applying the RA-A approach, the target substance (Z)-N-methyl-N-(1-oxo-octadecenyl)glycine, compound with 2,2',2''-nitrilotri(ethanol) (1:1) (CAS 17736-08-2) is also considered to meet the criteria for classification for Eye Damage, Category 1 (H318) according to Regulation (EC) No 1272/2008 (CLP).