Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate

Endpoint summary

Description of key information

Repeated dose toxicity - oral (no OECD TG applied, 2-year study), rat: NOAEL ≥1000 mg/kg bw/day

RA from source substance Sodium N-lauroylsarcosinate (CAS 137-16-6)

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 adequate, reliable (Klimisch scores 1 and 2) and consistent studies, from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties> (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex 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 data on repeated dose toxicity are available for the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7). Therefore, read across from the source substance sodium N-lauroylsarcosinate (CAS 137-16-6) was applied.

 

Repeated dose toxicity: oral

The source substance Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested for subchronic repeated dose oral toxicity in a 90-day study, conducted according to OECD TG 408 and in compliance with GLP (Huntingdon, 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 recognizable, 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 differences were statistically significant, except for 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 edema 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.

Moreover, the source substance Sodium N-lauroylsarcosinate (CAS 137-16-6) was also tested for chronic oral toxicity in a 2-year study in 200 rats (CIR, 2001). 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 (0.05%) 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.

Conclusion

In summary, a subchronic oral and a 2-year oral study with the source substance 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 and relevant dose descriptor. Thus, a NOAEL of 1000 mg/kg bw/day after chronic oral application is concluded also for the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7).

Justification for classification or non-classification

The available data on a relevant read-across source substance for repeated dose toxicity indicate no hazard and do not meet the criteria for classification for any hazard class, e.g. target organ toxicity, according to Regulation (EC) No. 1272/2008. Therefore, applying the RA-A approach, the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7) is also considered not to meet the criteria for classification according to Regulation (EC) No 1272/2008. Data therefore are conclusive but not sufficient for classification.