Glycine, N-methyl-, N-coco acyl derivs., sodium salts

Endpoint summary

Description of key information

Oral: (WoE, OECD 401), rat: LD50 > 5000 mg/kg bw

Data obtained with the registered substance and further supported by Weight-of-Evidence referring to the analogue substances Sodium N-lauroylsarcosinate (CAS 137-16-6) and N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3)

Inhalation: Data waiving as studies for two other routes, i.e. oral and dermal, are provided.

Dermal (WoE, OECD 402), rat: LD50 > 2000 mg/kg bw

Weight-of-Evidence approach referring to the analogue substances Sodium N-methyl-N-(1-oxotetradecyl)aminoacetate (CAS 30364-51-3), N-lauroylsarcosine (CAS 97-78-9) and Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 137-16-6, Toxicol Laboratories Ltd, 1987

Additional study taken into account in a Weight-of-Evidence approach:

EC 701-177-3, Ciba Geigy, 1981: LD50 (rat, m/f) > 5000 mg/kg bw

EC 701-177-3, BASF, 1979: LD50 (rat) = 9200 mg/kg bw

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Principles of method if other than guideline:

No data regarding the method applied is provided in the CIR report.

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 200 mg/kg bw

Based on:

test mat.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1 and 2) study data available from analogue substances with similar structures and intrinsic properties as for the registered substance. These data are considered in a Weight-of-Evidence approach to support the limited information as available for the registered substance (secondary quotation, Klimisch score 4). Read-across is justified based on common functional group(s), common precursors/breakdown products and similar physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from the analogue substances is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No. 1907/2006 (REACH). Therefore, the available information fulfils the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 (REACH).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 30364-51-3, Harlan, 2013

Additional studies taken into account in the Weight-of-Evidence approach:

CAS 97-78-9, Phycher, 2014: LD50 (rat, m/f) > 2000 mg/kg bw

CAS 68003-46-3, Frey-Tox, 2016: LD50 (rat, m/f) > 2000 mg/kg bw

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) study data available from analogue substances with similar structures and intrinsic properties as for the registered substance. These data are considered in a Weight-of-Evidence approach. Read-across is justified based on common functional group(s), common precursors/breakdown products and similar physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from the analogue substances is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No. 1907/2006 (REACH). Therefore, the available information fulfils the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 (REACH).

Additional information

Except for limited acute oral toxicity data available as secondary quotation, no further data on acute toxicity are available for the registered substance Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1). Therefore, acute toxicity data from the analogue substances N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3), Sodium N-lauroylsarcosinate (CAS 137-16-6), Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3), Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3) and N-lauroylsarcosine (CAS 97-78-9) were read-across in a Weight-of-Evidence approach for the assessment of the acute oral and dermal toxicity to be expected from the registered substance. With respect to inhalation, no data are provided, but a waiver has been included in IUCLID chapter 7.2.2.

 

Acute toxicity: oral

Data on acute oral toxicity for the registered substance Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) are available as a secondary quotation (CIR, 2001). Only an LD50 of 4200 mg/kg bw is reported. No further details are given.

With respect to the analogue substances, an acute acute oral toxicity study performed equivalent or similar to OECD TG 401 with N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) is available (Ciba Geigy, 1981). In this limit test five fasted Sprague-Dawley rats of each sex were administered a single dose of 5000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after administration. No mortality occurred during the study period and body weight gain was normal. Observed clinical signs included slight dyspnoea, slight exophthalmos and slight to moderate ruffled fur and slight to moderate diarrhoea as well as a slightly curved body position. All these clinical signs were fully reversible in all animals within 7 days. No substance-related findings were recorded at necropsy. Thus, the acute oral LD50 value was considered to be greater than 5000 mg/kg bw. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

In a further study with limited data given, N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) was tested for acute oral toxicity similar to OECD TG 401 (BASF, 1979). Rats were given the test material per oral administration. No further study details were provided. The authors determined the oral LD50 for rats to be greater than 9200 mg/kg bw.

 

The acute toxicity via the oral route of Sodium N-lauroylsarcosinate (CAS 137-16-6) has been investigated in rats in a study performed according to OECD TG 401 and in compliance with GLP (Toxicol. Laboratories Ltd., 1987). Groups of 5 Sprague Dawley rats of each sex were treated with the limit dose of 5000 mg/kg bw of the test substance via oral gavage. The observation period following administration was 14 days. During the study period, one female animal died at Day 2. No clinical signs of toxicity were observed in the surviving animals. All surviving animals showed normal body weight gain. The female animal found dead had been cannibalised and autolysed. Thus, no detailed post-mortem examination was possible. In surviving animals no abnormalities were noted at necropsy. Thus, the oral LD50 value for male and female rats was considered to be greater than 5000 mg/kg bw.

 

Acute toxicity: inhalation

No data on acute inhalation toxicity is required as data on two other routes of exposure, i.e. oral and dermal, are provided.

 

Acute toxicity: dermal

With respect to the analogue substances, a reliable acute dermal toxicity study was performed with N-Lauroylsarcosine (CAS 97-78-9) according to OECD TG 402 and in compliance with GLP (Phycher, 2014). In this limit test five Sprague-Dawley rats of each sex were exposed to a single dose of 2000 mg/kg bw of the neat test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred and no systemic clinical signs of toxicity related to the administration of the test item were observed up to the end of the 14-day observation period. Furthermore, no effect on body weight development was recorded during the study period. Macroscopic examination at the end of the study revealed no treatment-related changes. Cutaneous reactions (erythema, dryness and scab) were noted from Day 1 in all animals and remained until Day 14 (scab) in 5/5 females and in 1/5 males. Thus, the acute dermal LD50 value was considered to be greater than 2000 mg/kg bw.

 

A further reliable acute dermal toxicity study was performed with Sodium myristoylsarcosinate (CAS 30364-51-3) according to OECD TG 402 and in compliance with GLP (Harlan, 2013a). In this limit test five Wistar rats (RCCHan:WIST) of each sex were exposed to a single dose of 2000 mg/kg bw of the neat test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred and no systemic clinical signs of toxicity related to the administration of the test item were observed up to the end of the 14-day observation period. The test animals showed expected body weight gains during the study period with the exception of 1/5 female which showed bodyweight loss during the first week but expected weight gain during the second week. Macroscopic examination at the end of the study revealed no treatment-related changes. Very slight erythema (grade 1) formation was noted at the test sites of 7/10 animals being fully reversible within 5 days. No edema formation was observed in any animal at any time. Crust formation was also noted at the test site of 1/5 female being reversible within 9 days. There were no signs of dermal irritation noted at the test sites of the remaining animals. Thus, the acute dermal LD50 value was considered to be greater than 2000 mg/kg bw.

 

An acute dermal toxicity study was performed with Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3) according to OECD TG 402 and in compliance with GLP (Frey-Tox, 2016). In this limit test five Wistar rats of each sex were exposed to a single dose of 2000 mg/kg bw of the neat test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred and no systemic clinical signs of toxicity related to the administration of the test item were observed up to the end of the 14-day observation period. Furthermore, no effect on body weight development was recorded during the study period. Macroscopic examination at the end of the study revealed no treatment-related changes. On day 1, very slight erythema formation (grade 1) was observed in 2/10 animals, whereas slight to well defined erythema (grade 2) were observed in 7/10 animals. Additionally, very slight edema formation (grade 1) was observed in 2/10 animals. On day 2, very slight erythema (grade 1) were observed in 5/10 animals and slight to well defined erythema (grade 2) were recorded in 4/10 animals. Very slight erythema (grade 1) were also observed in 3/10 animals on day 3 after test material application. Furthermore, the treated skin areas of 6/10 animals displayed isolated scales (day 3). However, all skin reactions were fully reversible within 4 days after application of the test material until the end of the study period. Thus, the acute dermal LD50 value was considered to be greater than 2000 mg/kg bw.

Conclusion

Taken together, the available data on acute toxicity from adequate analogue substances do not indicate any relevant systemic toxicity.

Justification for classification or non-classification

The data from analogue substances available for both acute oral and acute dermal toxicity are conclusive but not sufficient for classification, and thus, the criteria for classification  according to Regulation (EC) No. 1272/2008 (CLP) are not met. Therefore, applying the read-across approach, the registered substance Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) is also considered not to meet the criteria for classification for acute oral and dermal toxicity. No data are, however, available regarding acute inhalation toxicity.