N-(1-oxotetradecyl)sarcosine

Endpoint summary

Description of key information

Skin corrosion in vitro (OECD 431, WoE): corrosive

Skin corrosion in vivo (OECD 404, rabbit, WoE): corrosive

RA from N-lauroylsarcosine (CAS 97-78-9), Glycine, N-methyl, N-coco acyl derivs. (CAS 68411-97-2) and N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3)

Eye irritation (in vitro and in vivo): Data waiving

As the registered substance is classified for its skin corrosion properties as Skin Corr. 1B (H314), no eye irritation studies have to be conducted according to Regulation (EC) No. 1907/2006 (REACH), Annexes VII and VIII, Item 8.2, Column 2.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to analogue justification report provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 min

Value:

27

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2005a

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

60 min

Value:

6

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2005a

Additional in vitro skin corrosion studies also taken into account in the Weight-of-Evidence approach:

CAS 68411-97-2, Frey-Tox, 2005b: corrosive to skin (Skin Corr. 1B, H314)

EC 701-177-3, Frey-Tox, 2005c: not corrosive to skin

Interpretation of results:

other: Skin corr. 1, H314. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to analogue justification report provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(3 min exposure)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2004a

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(1h exposure)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 28 day

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2004a

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(3 min exposure)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2004a

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(1 h exposure)

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 28 day

Remarks on result:

other: Source: CAS 97-78-9, Frey-Tox, 2004a

Additional in vivo skin irritation / corrosion studies also taken into account in the Weight-of-Evidence approach:

CAS 68411-97-2, Frey-Tox, 2004b: corrosive to skin (Skin Corr. 1B, H314)

EC 701-177-3, Hazleton, 1991: irritating to skin (Skin Irrit. 2, H315)

Interpretation of results:

other: Skin corr. 1B, H314. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No studies are available investigating the skin irritation properties of N-(1-oxotetradecyl)sarcosine (CAS 52558-73-3). In order to fulfil the standard information requirements set out in Annex VIII of Regulation (EC) No. 1907/2006 (REACH), data available from the structurally related analogue substances N-lauroylsarcosinate (CAS 97-78-9), Glycine, N-methyl-, N-coco acyl derivatives (CAS 68411-97-2) and N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) were considered; the in vitro and in vivo data are accounted for in a Weight-of-Evidence approach.

Skin irritation / corrosion in vitro

The in vitro skin corrosion properties of N-lauroylsarcosine (CAS 97-78-9) were tested in a study according to OECD TG 431 under GLP conditions using the EpiDerm three-dimensional reconstructed human epidermis model (Frey-Tox, 2005a). In the study, the tissues were treated with the unchanged test material for exposure periods of 3 minutes and 1 hour. 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 controls gave the expected results. The relative mean tissue viabilities after exposure to the test compound were 27% after 3 min exposure and 6% after exposure for 1 h. Thus, in the described test N-lauroylsarcosine (CAS 97-78-9) was considered to be skin corrosive.

In a further in vitro study, the skin corrosion properties of Glycine, N-methyl-, N-coco acyl derivatives (CAS 68411-97-2) were tested in a study performed according to OECD TG 431 under GLP conditions using the EpiDermTM, reconstructed three-dimensional human epidermis (EPI-200) model (Frei-Tox, 2005b). In the study, the tissues were treated with the neat test material for exposure periods of 3 and 60 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 viability 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 36% after 3 min and 6% after 1 h. Thus, in the described test Glycine, N-methyl-, N-coco acyl derivatives (CAS 68411-97-2) is considered to be corrosive to the skin.

The in vitro skin corrosion properties of N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) were tested in a study according to OECD TG 431 under GLP conditions using the reconstructed human epidermis EST-200 assay (Frey-Tox, 2005c). In the study, the tissues were treated with the unchanged test material for exposure periods of 3 and 60 min. Positive and negative controls were included in the study and gave the expected results. The test substance decreased the cell viability in comparison to the control to 72% after 3 min and to 25% after 60 min of incubation. The cell viability after 3 min exposure was greater than 50% and the cell viability after 1 h exposure was greater than 15%. Thus, the test material is considered to be non-corrosive under the experimental conditions to reconstructed human epidermis in-vitro.

Skin irritation / corrosion in vivo

The skin irritation properties of N-lauroylsarcosine (CAS 97-78-9) in vivo were tested in a study according to OECD TG 404 under GLP conditions (Frey-Tox, 2004a). In an initial test the neat test substance was applied to the clipped skin of one female rabbit for exposure times of 3 min and 1 h. Since moderate to severe skin reactions were observed immediately after the 1 h exposure, the 4 h exposure and the use of further animals were skipped. In the area exposed for 3 min well-defined erythema was observed 24, 48 and 72 h after termination of exposure. After 7 days the site showed isolated scales which were fully reversible after 14 days. At the 1 h exposure site severe erythema to escar formation and moderate edema were observed 24, 48 and 72 h after exposure. After 7 days a solid brown eschar coat with different thickness limited to the patch area was observed. The crust cranially dropped off the skin on an area of 40%, and petechial bleeding was found underneath. After 14 days the eschar coat had dropped off completely and reddish granulation tissue was discernible underneath. After 21 days the skin in the exposure area appeared darker and markedly elevated. Growth of hair being limited to the patch area was revealed. After 28 days the effects had been fully reversible, and no pathological changes were macroscopically discernible anymore. Based on these findings, the test substance has been considered as corrosive to skin.

In the reliable skin irritation study performed according to OECD TG 404 and in compliance with GLP one female Albino rabbit was exposed to 0.5 mL of undiluted Glycine, N-methyl-, N-coco acyl derivs (CAS 68411-97-2) onto the clipped skin for 3 and 60 min via semi-occlusive dressing (Frey-Tox, 2004b). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48, 72 h and 7, 14, 21 and 28 days post-application. Since only a slight erythema was observed immediately after 60 min post application, the 4 h exposure was started. 1 h post application the animal showed severe erythema (grade 4) and edema (grade 2) formation. Hence, the 4 h exposure was immediately terminated and a confirmatory test was precluded. 24 to 72 h post application severe erythema (grade 4) and edema (grade 4) were still observed. Thus, mean erythema and edema scores over 24, 48 and 72 h of 4 and 3 were calculated, respectively. In spite of the reduced exposure of 1 h time and severe skin reactions the observation period was extended up to 28 days. Within this period severe skin reactions could be revealed and no pathological changes were discernible anymore. Based on the study results and according to EU classification criteria, the test substance is classified as corrosive to the skin.

Furthermore, the skin irritating properties of N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) were tested in a study according to OECD TG 404 (Hazleton, 1991). In the study, 6 male New Zealand White rabbits were exposed to the unchanged test substance onto the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h and 7 and 14 days post-application. At the 24, 48 and 72 h reading time point, well defined erythema to severe erythema to slight eschar formation were observed within the animals (mean erythema score out of all 6 animals = 2.89). Furthermore, oedema formation was observed in all animals (mean oedema score out of all 6 animals = 2.0). The authors described, that 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 oedema formation was fully reversible, however absence of hair on the whole application area was apparent in all animals. The test substance, therefore, turned out to be irritating to skin according to EU criteria for classification.

Conclusion on skin irritation / corrosion

Whereas all available in vitro and in vivo data obtained with the two analogue substances N-lauroylsarcosinate (CAS 97-78-9) and Glycine, N-methyl-, N-coco acyl derivatives (CAS 68411-97-2) resulted in skin corrosion effects leading to classification of the test items as Skin Corr. 1B, the studies performed with N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) indicate skin irritating properties only. The results derived from the three analogue substances indicate that the irritation / corrosion properties are decreasing with increasing length of the alkyl chain. Lauroyl (C12) and cocoyl (C12 and C14) sarcosines are corrosive but oleoyl (C18:1) sarcosine turns out to be irritating. Therefore, an increasing number of methylene moieties tends to reduce the corrosive effects to irritating results. Since N-lauroylsarcosinate (CAS 97-78-9) (C12) and Glycine, N-methyl-, N-coco acyl derivatives (CAS 68411-97-2) (C12 and C14) are more closely related to the registered substance (C14) in terms of structural analogy, the corrosive effects are carried forward to the hazard assessment and for classification of N-(1-oxotetradecyl)sarcosine (CAS 52558-73-3) in a worst case assumption.

Eye irritation

Regulation (EC) No. 1907/2006 (REACH) stipulates in its Annexes VII and VIII that tests for eye irritation / severe eye damage do not need to be conducted if the registered substance is classified as skin corrosion. Since N-(1-oxotetradecyl)sarcosine (CAS 52558-73-3) is classified as Skin Corr. 1B as a result of reliable in vitro and in vivo data of adequate structural analogue substances, testing for eye irritation / severe eye damage is deemed not suitable and necessary. As a result of the skin corrosion properties, contact by any route of exposure to the substance must be avoided and effects of the substance on eyes are avoided as well.

Justification for classification or non-classification

The available data on skin irritation / corrosion obtained with adequate analogue substances meet the criteria for classification as Skin Corr. 1B (H314) according to Regulation (EC) No. 1272/2008 (CLP). Therefore, applying the read-across approach, N-(1-oxotetradecyl)sarcosine (CAS 52558-73-3) is also considered to meet the criteria for classification as Skin Corr. 1B (H314).

No data on eye irritation / severe eye damage are available. Studies addressing the eye irritation / severe eye damage potential are not required due to the classification of the registered substance as skin corrosive (Skin Corr. 1B). In consequence, classification of N-(1-oxotetradecyl)sarcosine (CAS 52558-73-3) as Eye Damage 1 (H318) is implicit.