N-lauroylsarcosine

Endpoint summary

Description of key information

NOAEL (chronic, rat) ≥ 1000 mg/kg bw/day, based on read-across 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2, due to read across) from a reference substance with similar structure and intrinsic properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Anney VIII-IX, 8.6 in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No sufficient data are available for repeated dose toxicity of N-lauroylsarcosine (CAS 97-78-9) In order to fulfil the standard information requirements set out in Annex IX, 8.6.2 and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from a structurally related category member 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 (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.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13).

Discussion

No studies are available investigating the repeated dose toxicity via the oral route of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex IX, 8.6.2 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.

Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested for chronic oral toxicity in a 2-year study in 200 rats (CIR, 2001; Technology Science Group Inc., 1994).

Groups of 25 Wistar rats per sex and dose were given 0.05, 0.2 and 1% of the test material in the diet, 7 days/week for 24 months. The concentration of the test material in the low dose group was increased to 2% (equiv. to 1000 mg/kg bw/day) after 6 months. A concurrent negative control group receiving the plain diet was included.

At one, three and six months no significant differences were observed in mortality, body weight gain and haematology. At the end of the study period, the only consistent difference observed in the gross pathology was minor hyperplasia of the stratified squamous epithelium with excess keratin formation of the cardiac mucosa of the stomach in rats receiving the highest exposure to the test article (group 1: 2%; group 3: 1% in the diet) due to the local irritating effects of the test substance. Furthermore, fertility assessment did not show any significant differences (no further information).

Based on the lack of adverse effects, a NOAEL of 1000 mg/kg bw/day (m, f) was identified in this study.

Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested for subchronic repeated dose oral toxicity in a 90-day study, conducted according to OECD test guideline 408, and in compliance with GLP (Mandella, 1997).

Groups of 15 Sprague-Dawley derived outbred albino rats per sex and dose received the test item at doses of 30, 100 and 250 mg/kg bw/day on 7 days per week for 91 or 92 days, respectively (depending on scheduled sacrifice). Concurrent negative control animals received the vehicle only (sterile, distilled water). No treatment-related mortality or clinical signs of toxicity were observed throughout the study period. Statistically significant decreased body weight gain with 7 and 9% decreased body weights at study termination compared to controls was observed for the mid-and high-dose males (100 and 250 mg/kg bw/day, respectively). In contrast, females of the same dose groups showed recognisable, but statistically not significant lower body weight gain with 4% decreased body weights at necropsy compared to controls. Since animals still gained weight, and the decrease of body weight in comparison to the controls was <10%, this effect is considered to be not adverse. At necropsy, increased absolute stomach weights, stomach/body and stomach/brain weight ratios were noted in both males and females of the 100 and 250 mg/kg bw/day dose groups. All values were statistically significant, except absolute stomach weight in mid-dose females. The effect was associated with increased stomach wall thickness and yellow discolouration of non-glandular gastric mucosa. Histopathological examination revealed increased incidence and severity of squamous cell hyperplasia, hyperkeratosis/parakeratosis, inflammation and oedema of the non-glandular gastric mucosa of both males and females in these dose groups. No effects were observed in low-dose animals (30 mg/kg bw/day). Since this effect was noted in a dose-related manner, it is considered to be treatment-related. However, the effects reported were localised to the stomach only, reflecting the irritant characteristics of the test substance, and no further signs of systemic toxicity were observed in any of the animals in any dose-group throughout the study period. Thus, the NOEL of this study is 30 mg/kg bw/day, the LOAEL for local effects in the stomach is 100 mg/kg bw/day, and the systemic NOAEL was set to ≥ 250 mg/kg bw/day.

In summary, both available oral repeated dose toxicity studies revealed local effects to the stomach only. Since the chronic study is the one with the longest study duration, and considering the lack of any systemic effects in both chronic and subchronic studies, the overall NOAEL for systemic toxicity for Sodium N-lauroylsarcosinate was set to 1000 mg/kg bw/day.

Conclusion for repeated dose toxicity, oral

In summary, a subchronic oral and a 2-year oral study with Sodium N-lauroylsarcosinate (CAS 137-16-6) showed no adverse systemic effects resulting in NOAELs of ≥ 250 derived from the subchronic study and 1000 mg/kg bw/day derived from the chronic study. Since the NOAEL of 1000 mg/kg bw/day was derived from the study with the longest study duration and no adverse effect was observed in the subchronic study up to and including the highest dose of 250 mg/kg bw/day tested, the higher value is considered to be the most reliable dose descriptor. Thus, as a weight of evidence approach, a NOAEL of 1000 mg/kg bw/day after chronic oral application is concluded.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the study with the longest duration and is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among the 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 repeated dose toxicity of a structurally related category member to N-lauroylsarcosine (CAS 97-78-9) do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.