Registration Dossier

Administrative data

Description of key information

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

RA from N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3)

Inhalation (OECD 403), rat: LC50 = 1.37 mg/L air

RA from N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3)

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

RA from 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
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to analogue justification provided in IUCLID section 13
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: EC 701-177-3, Ciba Geigy, 1981a
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 an adequate and reliable (Klimisch score 2) study performed with an analogue substance showing similar structure and intrinsic properties as for the registered substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from this independent source is consistent and provides sufficient information 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.37 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Source: EC 701-177-3, BASF, 1979
Interpretation of results:
other: Acute tox. Inhalation 4, H332. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1.37 µg/m³
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study performed with an analogue substance showing similar structure and intrinsic properties as for the registered substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from this independent source is consistent and provides sufficient information 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 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 97-78-9, Phycher, 2014

Additional studies accounted for in the Weight-of-Evidence approach:

CAS 30364-51-3, Harlan, 2013a: 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) studies performed with analogue substances showing similar structure and intrinsic properties as for the registered substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from these independent sources 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

No data on acute toxicity is available for the Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7). Therefore, data from the analogue substances N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3), 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 considered, either for reading-across key information or in a Weight-of-Evidence approach.

Acute toxicity: oral

An acute oral toxicity study performed equivalent or similar to OECD TG 401 with the analogue substance N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) is available (Ciba Geigy, 1981a). 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.

Acute toxicity: inhalation

A reliable acute inhalation toxicity study was performed with N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) equivalent or similar to OECD TG 403 (BASF, 1979). Groups of 10 Sprague-Dawley rats of each sex were exposed via nose / head only to 0.3, 0.6, 2.2 and 3.7 mg/L air for 4 h. The animals were observed for a period of 14 days following administration. Mortality of male and female rats was recorded in the 0.6, 2.2 and 3.7 mg/L air dose groups (3/10, 10/10 and 8/10 for males and 1/10, 4/10 and 10/10 for females, respectively). Clinical signs of toxicity were observed in all surviving animals including flight attempts, gasping and noisy breathing, slight staggering, bloody nose area, low motility, hair loss in the head area and salivation in varying degrees. Surviving animals were free of symptoms from Day 2 - 8 after treatment and necropsy revealed no abnormalities. Body weight loss was observed in females of the 2.2 mg/L and in males of the 3.7 mg/L dose groups. In animals that died during the study period, clinical signs of toxicity such as acute dilatation, acute hyperemia, edema and hyperemia of the lungs, severe exhalation especially at the peripheral areas, severe edema formation and laminar bleedings of the lungs (high-dose group) were observed. Thus, the acute inhalation LC50 value is calculated to be 1.8 and 1.05 mg/L air for females and males, respectively, whereas the combined acute inhalation LC50 value is considered to be 1.37 mg/L air after 4 h exposure to the test material. Based on the study results, the test substance meets the criteria for classification for Acute Tox. 4 (H332) according to Regulation (EC) No. 1272/2008.

Acute toxicity: dermal

A reliable acute dermal toxicity study was performed with the analogue substance 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 N-methyl-N-(1-oxotetradecyl)aminoacetate (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.

Justification for classification or non-classification

The available data from relevant analogue substances for both acute oral and acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Therefore, the registered substance Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine is also considered not to meet the criteria for classification for acute oral and dermal toxicity.

The available data from a relevant read-across substance for acute inhalation toxicity meet the criteria for classification for Acute Tox. 4 (H332) by the inhalative route according to Regulation (EC) No. 1272/2008 (CLP). Therefore, applying the read-across approach, Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7) is also considered to meet the criteria for classification for acute inhalation toxicity.