N-lauroylsarcosine

Endpoint summary

Description of key information

Oral (OECD 401), rat (m/f): LD50 > 5000 mg/kg bw (limit test), based on read-across
Inhalation (OECD 403), rat (m/f): 1 mg/L < LC50 < 5 mg/L, based on read-across
Dermal (OECD 402), rat (m/f): LD50 > 2000 mg/kg bw (limit test), based on read-across

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance (reliability 2) with similar structure and intrinsic 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. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 000 mg/m³ air

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. The available study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. The available study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

There is no data available on the acute toxicity of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from 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 (grouping or 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.

Discussion

Acute oral

No studies are available investigating the acute oral toxicity of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VII, 8.5.1 and in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from the structurally related category members Sodium N-lauroylsarcosinate (CAS 137-16-6) and (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was conducted.

The acute toxicity via the oral route of Sodium N-lauroylsarcosinate (CAS 137-16-6) has been investigated in rats in accordance with OECD guideline 401 under GLP conditions (Haynes, 1987).

A group of 10 Sprague Dawley rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance by 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 for male and female rats is greater than 5000 mg/kg bw.

Two studies investigating the acute toxicity via the oral route of (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) are available (Sarasin, 1980; BASF, 1979).

One study was performed in Sprague-Dawley rats similar to OECD guideline 401 (Sarasin, 1980). A group of 10 rats (5 males and 5 females) was dosed with 5000 mg/kg bw of the test substance by gavage. The animals were observed for a period of 14 days following administration.

During the study period, no mortality occurred in any animal. Observed clinical signs included slight dyspnoea, slight exophthalmos and slight to moderate ruffled fur and slight to moderate diarrhoea and a slightly curved body position. All animals recovered within 7 days. No effects on body weight were noted and necropsy revealed no substance-related findings. Thus, the oral LD50 for male and female rats was considered to be greater than 5000 mg/kg bw.

In a further study with limited data given, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was tested for acute oral toxicity similar to OECD guideline 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.

In summary, the oral LD50 of (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine is considered to be greater than 5000 mg/kg bw.

Acute inhalation

No studies are available investigating the acute toxicity via the inhalation route of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2 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.

Two studies are available to investigate the acute inhalation toxicity potential of Sodium N-lauroylsarcosinate (CAS 137-16-6).

In the first available study (van Otterdijk, 2010), conducted according to OECD guideline 403 and in compliance with GLP, Wistar rats were treated with the neat test material (96.2% purity) via nose-only inhalation exposure for 4 h. Hereby, 5 males and 5 females each were exposed to concentrations of 5 and 1 mg/L, and 5 males each were exposed to concentrations of 0.55 and 0.055 mg/L. The powdered test material was fed to a stream of pressurised air to generate the test atmosphere. The animals were observed for mortality, clinical signs and effects on body weights for a period of 14 days following administration. At study termination, the animals were submitted to gross pathological examination. All animals of the 5 and 1 mg/L dose groups died within 1-2 h post-exposure. At 0.5 mg/L 4/5 males died within 1-2 days post-exposure. No mortality was noted in the low dose group (0.05 mg/L) throughout the study period. During exposure, animals of the 1 mg/L dose group showed laboured respiration. No clinical signs were noted during exposure in any animal of the remaining dose groups. After exposure, animals treated with 5 mg/L showed no clinical signs prior to death/sacrifice. At 1 mg/L lethargy, flat/hunched posture, laboured respiration, piloerection and red discolouration of the mouth and nose was noted among most females. No clinical signs were observed among males. At 0.5 mg/L lethargy, flat/hunched posture, laboured respiration, piloerection and red discolouration of the nose, and/or moribund condition was reported for males. No clinical signs were noted in males treated with 0.05 mg/L test material. Significant weight loss was observed for the single surviving male at 0.5 mg/L between Days 1 and 4. Body weight gain of males at 0.05 mg/L was within the range expected for rats of this strain and age used in this type of study. Gross pathology revealed red foci on the lungs, red contents of the small intestines/ileum, red discolouration of the thymus and or small intestines among most animals exposed to 5 mg/L. All animals of the 1 mg/L dose group showed red foci on the lungs or red discolouration of the lungs. Red foci on the lungs and/or thymus and/or red discolouration of the lungs were noted among most males treated with 0.5 mg/L test material. No abnormalities were noted in males exposed to a concentration of 0.05 mg/L. Based on the result of this study, the LC50 for both males and females for the neat, pulverised test substance was 0.05-0.5 mg/L. The neat test material meets therefore the criteria to be classified for acute inhalation toxicity Cat. 2, H330 according to Regulation (EC) No 1272/2008 and Toxicity by inhalation (T, R23) according to Directive 67/548/EC.

The second available study (van Huygevoort, 2013) was performed according to the OECD test guideline 403 and in compliance with GLP. Five Wistar rats per sex per dose were exposed to an aerosol of a 34.5% aqueous solution of Sodium N-lauroylsarcosinate (CAS 137-16-6) in a nose-only inhalation apparatus for 4 h. To generate the test atmosphere at concentrations of 0.5, 1 and 5 mg/L, the test material was nebulised and diluted with pressurised air, before entering the exposure chamber. Following treatment, the animals were observed for a period of 14 days following administration. Additionally to the recommended observations and examinations (mortality, clinical signs, body weights, gross pathology), histopathological examination of low and high dose animals was performed with special focus on the respiratory tract in order to consider the influence of the well-known irritant characteristics of the test substance on the results. No mortality occurred after exposure to 0.5 or 1 mg/L. At 5 mg/L, two females and three males were found dead immediately following the exposure, and the remaining animals were sacrificed for humane reasons within 1 hour after exposure. No further mortalities occurred throughout the study period. Clinical signs noted during exposure with 0.5 mg/L were shallow respiration in all animals. After exposure, the only clinical sign noted was the chromodacryorrhoea of the snout in one male on Day 2. At 1 mg/L, shallow respiration was noted in all animals during exposure. After exposure, hunched posture, slow breathing and/or piloerection was noted among all animals between Days 1 and 3. Slow breathing and laboured respiration were seen in all animals during treatment with 5 mg/L. After exposure, lethargy, hunched posture, slow breathing, laboured respiration and/or piloerection were observed in the animals that were sacrificed for humane reasons on the day of exposure. The overall body weight gain in surviving males and females was within the range expected for rats of this strain and age used in this type of study. Macroscopic post mortem examination of the animals revealed the following findings that were considered to be treatment-related: at 5 mg/L lungs with watery cloudy content were noted in 1/5 males and 4/5 females; the microscopic correlate was alveolar fibrinous material. The thymus was found to be dark red or with reddish foci in 5/5 males and 5/5 females; the microscopic correlate was congestion. The mandibular lymph nodes showed reddish discolouration in 3/5 males and 2/5 females; the microscopic correlate was congestion and erythrophagocytosis. In animals exposed to 1 mg/L the thymuses were found with reddish discolouration and dark red foci in 1/5 males and 1/5 females. The lung was reddish discoloured in 1/5 males. At 0.5 mg/L no treatment related findings were noted. Histopathological examination revealed local effects on the respiratory tract. Erosion in the trachea was present in one female treated with 0.5 mg/L at minimal degree and in most males and all females treated with 5 mg/L up to marked degree. Epithelial degeneration of the trachea with loss of cilia was present in all males and females treated with 5 mg/L up to moderate degree. Trachea ulceration was present in one male exposed to 5 mg/L at slight degree. Perivascular oedema of the lung was present in one female treated with 0.5 mg/L at slight degree and in most males and females of the 5 mg/L dose group up to moderate degree. Alveolar ectasia of the lung was present in one female treated with 0.5 mg/L at minimal degree and in all males and some females exposed to 5 mg/L at minimal degrees. All males and females treated with 5 mg/L showed alveolar fibrinous material in the lungs up to moderate degree. Epithelial necrosis of the larynx was noted in all males and females treated with 5 mg/L at marked degree; and granulocytic inflammation of the larynx up to slight degree was reported for all males and females exposed to 5 mg/L. Epithelial necrosis of the nasal pharynx (nasopharynx) up to massive degree was present in all males and females treated with 5 mg/L. The findings in the rats of the 5 mg/L dose group were considered to be markers of acute respiratory tract irritancy caused by the test item. The lack of findings in the males, and the few remaining lung and trachea findings in the females treated at 0.5 mg/L indicate that there was either no direct damage and/or good recovery. There was no indication for systemic toxicity. Based on the outcome of this study, the LC50 for both males and females for the 34.5% aqueous solution of the test substance, is 1-5 mg/L. The 34.5% aqueous solution of the test substance meets therefore the criteria to be classified for acute inhalation toxicity Cat. 4, H332 according to Regulation (EC) No 1272/2008 and Harmful by inhalation (Xn, R20) according to Directive 67/548/EC.

The substance is not produced or marketed in neat form. It is only produced and marketed as aqueous formulations at concentrations of approx. 35% and below. Therefore, the second study performed with a 34.5% aqueous formulation of Sodium N-lauroylsarcosinate (CAS 137-16-6), which is the highest technically attainable concentration during the manufacturing process, more closely reflects the potential for acute inhalation toxicity under realistic conditions and at concentrations relevant for human exposure. The data obtained from this study is used to determine specific concentration limits and to derive a classification for the marketed product. This is in compliance with the conditions under which N-lauroylsarcosine (CAS 97-78-9) is manufactured and marketed. Therefore, using the result of the acute inhalation toxicity study testing a 34.5% aqueous formulation of Sodium N-lauroylsarcosinate (CAS 137-16-6) for the hazard assessment of N-lauroylsarcosine (CAS 97-78-9) is appropriate.

Acute dermal

No studies are available investigating the acute toxicity via the dermal route of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.5.3 and in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from the structurally related category member Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was conducted.

The acute dermal toxicity of Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Bradshaw, 2013).

Groups of 10 rats (5 males and 5 females) were treated with the test substance moistened with arachis oil BP at the limit dose of 2000 mg/kg bw under semi-occlusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. No substance-related findings during necropsy were observed in any animal. No effects on body weight gain were observed with the exception of one female which showed bodyweight loss during the first week but expected weight gain during the second week. Evaluation of the dermal skin reactions showed very slight erythema (Draize scoring value: 1) at the test sites of 7/10 animals being fully reversible within at the most 5 days. No edema formation was observed in any animal. Crust formation was noted at the test site of one female being reversible within 9 days.

Thus, the dermal LD50 for male and female rats was considered to be greater than the tested limit dose 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on the acute oral toxicity of a substance structurally related to N-lauroylsarcosine (CAS 97-78-9) according to Regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, N-lauroylsarcosine (CAS 97-78-9) is not expected to exert acute toxicity, either, and the data are thus conclusive but not sufficient for classification.

The available data on the acute inhalation toxicity 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 Acute toxicity - inhalation category 4 (H332) according to Regulation (EC) No 1272/2008 and as Harmful by inhalation (Xn; R20) according to Directive 67/548/EEC at concentrations up to 34.5%. Furthermore, at concentrations > 34.5% the test item meets the criteria for classification for acute inhalation toxicity Cat. 2, H330 according to Regulation (EC) No 1272/2008 and Toxic by inhalation T, R23 according to Directive 67/548/EC. Therefore, N-Lauroylsarcosine (CAS 97-78-9) is classified accordingly.

The available data on the acute dermal toxicity of a substance structurally related to N-lauroylsarcosine (CAS 97-78-9) according to Regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, N-lauroylsarcosine (CAS 97-78-9) is not expected to exert acute toxicity, either, and the data are thus conclusive but not sufficient for classification.