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Administrative data

Description of key information

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

Repeated dose toxicity - oral (OECD 408, 90-day), rat: NOAEL ≥ 250 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

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral, other
Remarks:
sub-chronic and chronic 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
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 other: % in the diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects
Remarks on result:
other: Source: CAS 137-16-6, CIR panel, 2001
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects
Remarks on result:
other: Source: CAS 137-16-6, CIR panel, 2001
Critical effects observed:
no

Additional study considered in a Weight-of-Evidence approach:

CAS 137-16-6, Huntingdon, 1997: NOAEL (90d, rat, m/f) > 250 mg/kg bw/day

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 and reliable (Klimisch score 1 and 2) studies from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) and similar physico-chemical, ecotoxicological and toxicological properties of the source and the target substances. 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 as a whole is 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 (REACH).

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 is available with Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7). Therefore, read across from the analogue substance Sodium N-lauroylsarcosinate (CAS 137-16-6) was applied with respect to the oral route. For the inhalative and the dermal route of exposure, waivers are provided (please refer to IUCLID section 7.5.2 and 7.5.3).

Repeated dose toxicity: oral

Sodium N-lauroylsarcosinate (CAS 137-16-6) was 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.

In addition, Sodium N-lauroylsarcosinate (CAS 137-16-6) was also 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 localized 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.

Conclusion

In summary, a 2-year oral and a subchronic 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, based on read-across, a NOAEL of 1000 mg/kg bw/day after chronic oral application is concluded for the registered substance.

Justification for classification or non-classification

With respect to repeated dose toxicity, the available data from the read-across substance Sodium N-lauroylsarcosinate (CAS 137-16-6) 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 (CLP). Therefore, applying the read-across approach, the registered substance Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7) is also considered not to meet the criteria for classification.