Glycine, N-methyl-, N-coco acyl derivs., sodium salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Peer-reviewed data. Only secondary source available.

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2001

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1997

Materials and methods

Principles of method if other than guideline:

2-year chronic oral toxicity study in 200 rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-lauroylsarcosinate

EC Number:

205-281-5

EC Name:

Sodium N-lauroylsarcosinate

Cas Number:

137-16-6

Molecular formula:

C15H29NO3.Na

IUPAC Name:

sodium [dodecanoyl(methyl)amino]acetate

Test animals

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

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.05 other: % nominal in the diet

Remarks:

The concentration of test material in the low dose group was increased to 2% after 6 months

Doses / concentrations 2

Dose / conc.:

0.2 other: % nominal in the diet

Doses / concentrations 3

Dose / conc.:

1 other: % nominal in the diet

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.

Examinations

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)

Results and discussion

Results of examinations

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.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

>= 2 other: % in the diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

2

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

Target system / organ toxicity

Critical effects observed:

not specified