Reaction products of fatty acid chlorides, C8-12 (even numbered) with glycine and sodium hydroxide

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:

Validity of the study assessmed by the CIR Expert Panel

Data source

Reference

Reference Type:

review article or handbook

Title:

Final report on the safety assessment of alkyl sarcosines and sodium alkyl sarcosinates

Author:

Cosmetic Ingredient Review Panel

Year:

2001

Bibliographic source:

Int. J. Toxicol. 20: 1-14, 2001

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: 2-year feeding toxicity study

Version / remarks:

The study integrates the mating of males and females

Principles of method if other than guideline:

2-year feeding toxicity study

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium lauroyl sarcosinate

IUPAC Name:

Sodium lauroyl sarcosinate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 years

Frequency of treatment:

daily (feeding)

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 000 mg/kg diet

Remarks:

0.05% of the test item in the diet for the first 6 months and 2.0% of the test item in the diet for the remaining 18 months

Doses / concentrations 2

Dose / conc.:

10 000 mg/kg diet

Remarks:

1.0% of the test item in the diet for 24 months

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg diet

Remarks:

0.2% of the test item in the diet for 24 months

Doses / concentrations 4

Dose / conc.:

0 mg/kg diet

Remarks:

Basal diet alone

No. of animals per sex per dose:

25 per sex per group

Control animals:

yes, plain diet

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:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

hyperplasia of squamous epithelium with keratin formation of the mucosa of the stomach at two highest dose groups

Histopathological findings: neoplastic:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

20 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effect up to the highest dose

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Citation:

"...Two hundred albino Sherman Wistar rats (25 rats/sex/group; 100-150 g) were fed Sodium Lauroyl Sarcosinate during a 2-year chronic oral toxicity study. Group 1 was fed 0.05% Sodium Lauroyl Sarcosinate in the daily diet for the first 6 months of the study and 2.0% of dies for the remaining 18 months. For the entire study period, group 2 was fed 0.2% of diet, group 3 was fed 1.0% of diet, and group 4 was fed the basal diet alone. Rats were killed at 1,3,6, and 24 months for necropsy and tissues collected for microscopic examination; organs examined included the liver, spleen, heart, lungs, stomach, large intestine, small intestine, adrenal glands, gonads, pancreases, and brain. Blood samples were drawn and analyzed at 30 days, 90 days, 6 months, and 24 months for red and white blood cell counts, hemoglobin content, and differential count. Males and females were housed together so that ferility could be assessed. At 1,3,6 months, no significant differences were observed in lesions, fertility, mortality, hematology, or body weight gain between rats of the control and treated groups. 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-group1 (2% in the diet after 6months) and group 3 (1% in the diet)...."

Applicant's summary and conclusion

Conclusions:

Sodium N-Lauroyl sarcosinate was investigated in rats for its chronic toxicity and reproduction toxicity in a 2 -year feeding study. The doses levels applied were 0, 0.2, 1 and 2% in the diet. Males and females were housed together so that fertility could be assessed. No effect on the fertility was found. Histopathological changes of stomach tissues were evident at dose levels of 1 and 2% in the diet. No significant systemic effect was found up to the highest dose level.

Executive summary:

The subacute toxicity of the registration substance Hostapon SLG was evaluated based on the read-across approach using the repeated dose toxicity data for sodium N-lauroyl sarcosinate

The registration substance and the read-across sources are amides of fatty acids and amino acids and can be characterized as "N-fatty acyl amino acids", of which endogeous occurence and metabolism are known. Based on the comparable chemical structure, comparable phys-chem data and expected comparable metabolism, these compounds are likely exhibit comparable toxicity profiles.

Sodium N-lauroyl sarcosinate was investigated in rats for its chronic toxicity and reproduction toxicity in a 2 -year feeding study. The doses levels applied were 0, 0.2, 1 and 2% in the diet. Males and females were housed together so that fertility could be assessed. No effect on the fertility was found. Histopathological changes of stomach tissues were evident at dose levels of 1 and 2% in the diet. No significant systemic effect was found up to the highest dose level.

Likewise, the registration substance Hostapon SLG is likely of low repeated dose toxicity.