Sodium N-lauroylsarcosinate

Endpoint summary

Description of key information

NOAEL (oral, chronic, rat) ≥ 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

2-year chronic oral toxicity study in 200 rats.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Albino Sherman Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100-150 g
- Housing: animals were housed together (no further information)
- Diet: animal colony diet supplemented twice weekly with fresh meat, ad libitum
- Water: ad libitum

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
The substance powder was mixed intimately with the diet in the desired concentrations.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

24 months

Frequency of treatment:

7 days/week

Remarks:

Doses / Concentrations:
0.05, 0.2 and 1%
Basis:
other: nominal in the diet (Remark: the concentration of test material in the low dose group was increased to 2% after 6 months)

No. of animals per sex per dose:

25

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: dosage levels, to be fed for two years, were premised on a maximum possible exposure in humans.

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS: Yes (no further information)

BODY WEIGHT: Yes, at end of Week 1 and 2

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 30, Day 90, 6 months and 24 months
- Parameters: red and white blood cell count, haemoglobin content and differential count

OTHER
FERTILITY ASSESSMENT: Yes (no further information)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes. Liver, spleen, heart, lungs, stomach, large intestine, small intestine, adrenal glands, gonads, pancreas and brain.
HISTOPATHOLOGY: Yes. Liver, spleen, heart, lungs, stomach, large intestine, small intestine, adrenal glands, gonads, pancreas and brain.
Rats were killed at 1, 3, 6 and 24 months for necropsy and tissues collected for microscopic examinations (no further information)

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

2% and 1 % in the diet: at 24 months minor hyperplasia of the stratified squamous epithelium with excess keratin formation of the cardiac mucosa of the stomach

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: At 1, 3 and 6 months, no significant differences were observed in mortality.

BODY WEIGHT AND WEIGHT GAIN: At 1, 3 and 6 months, no significant differences were observed in body weight gain.

HAEMATOLOGY: At 1, 3 and 6 months, no significant differences were observed in haematology.

GROSS PATHOLOGY: At 24 months, the only consistent difference that could be attributed to the test article 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% in the diet after 6 months, group 3: 1% in the diet).

OTHER FINDINGS: No significant differences were observed in fertility in the 2 year study.

Dose descriptor:

NOAEL

Effect level:

>= 2 other: % in the diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

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

Critical effects observed:

not specified

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 subchronic and chronic studies performed with Sodium N-lauroylsarcosinate (CAS 137-16-6)

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

Discussion

Repeated dose toxicity: oral

Sodium N-lauroylsarcosinate (CAS 137-16-6) was tested for chronic oral toxicity in a 2-year study in 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 post exposure with the test material 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 (Huntington Life Science, 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 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 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 and 1000 mg/kg bw/day, respectively. 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 for systemic toxicity after chronic oral application is concluded.

Justification for classification or non-classification

The available data on repeated dose toxicity of Sodium N-lauroylsarcosinate (CAS 137-16-6) 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.