Sodium glycinate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

See read across document in section 13

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycine

EC Number:

200-272-2

EC Name:

Glycine

Cas Number:

56-40-6

Molecular formula:

C2H5NO2

Specific details on test material used for the study:

Glycine (lot M5G2082; purity 100.0%) purchased from Nacalai Tesque, Inc.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

All animals were housed individually in metallic bracket cages in a breeding room kept at temperature of 20 to 26°C and a relative humidity of 30 to 70%, with an air ventilation cycle of 10 to 15 times/hour (all-fresh air ventilation) and a 12-hour light/ dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

6

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Twice daily clinical observations (pre- and post-dose), body weights recorded on study days 1, 3, 8, 15, 22, 28, and on the day prior to necropsy. Food consumption and water consumption recorded on study days 2-3, 7-8, 21-22, and 27-28.

Other examinations:

Urinalysis, hematology, blood chemistry.

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):

no effects observed

Haematological findings:

no effects observed

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

Daily urine volume and total amount of Cl excretion were significantly higher (p<0.05) in the 2000 mg/kg dose group, and urine pH and urinary protein showed lower trends in the glycine-treated groups. Not considered toxicologically significant as there were no correlations in histopathology in kidneys or urinary bladder or changes in the weights of those organs.

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (actual dose received)

Basis for effect level:

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Once-daily oral administration of glycine up to 2000 mg/kg/day for 4 weeks to male SD rats (Crl: CD (SD)) caused no toxicologically significant change in the animals. The no observed- adverse-effect level of glycine is at least 2000 mg/kg .

Executive summary:

Groups of 6 male rats were administered 500, 1000, or 2000 mg/kg bw/day glycine in water by oral gavage for 28 days. Clinical observations, body weights, food consumption, haematology, and urinalysis, and histopathology were performed. There were no effects on the measured parameters, and there were no deaths up to 2000 mg/kg bw/day.

NOAEL for male rats was 2000 mg/kg bw/day.