N-glycyl-L-tyrosine

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-09-14 - 1987-10-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1988

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: Intravenous infusion of either 20 or 25 mmol/kg bw at 250 ml/kg bw N-glycyl-L-tyrosine via the lateral tail vein for a single 8h period. Subsequently the animals were observed for 14 days.
- Short description of test conditions: Animals were housed singly and fed ad libitum with free access to water except overnight before the treatment. Dose administration was effected using a 27G Microflex infusion set (Vygon) connected to a 2 way stopcock, syringe and calibrated peristaltic infusion pump (Natson Marlow, England). The pH of the administered solution was 5.6. During the 8 h infusion period and for +2 h post infusion the animals were monitored continuously and observations recorded at 30 min intervals, in the subsequent 14 days the animals were observed at least twice daily, body weight was recorded daily. On day 15 after administration the animals were sacrificed and necropsies were performed. Additionally the organ weights of brain, liver, kidneys, heart, lungs, spleen and testes/ovaries were determined.
- Parameters analysed / observed: body weight, clinical signs, mortality, gross necropsy, organ weights.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-glycyl-L-tyrosine

EC Number:

211-525-1

EC Name:

N-glycyl-L-tyrosine

Cas Number:

658-79-7

Molecular formula:

C11H14N2O4

IUPAC Name:

glycyl-L-tyrosine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Males: 94-116 g; females: 95-189 g
- Fasting period before study: overnight
- Housing: singly in solid bottom polypropylene cages (42 x 27 x 20 cm) with stainless steel mesh tops
- Diet (e.g. ad libitum): ad libitum; Rat and Mouse (Modified) No.1 Diet SQC Expanded, supplied by Special Diet Services Limited, Stepfield, Witham, Essex, England
- Water (e.g. ad libitum): ad libitum; Domestic mains quality drinking water
- Acclimation period: 17 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 2°C
- Humidity (%): 55% ± 10%
- Air changes (per hr): 15-20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h light-dark cycle

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: electrolyte solution consisting of 50 mmol/L sodium and 10 mmol/L potassium (sodium chloride and potassium chloride respectively)

Details on exposure:

slow 8h infusion via the tail vein

Doses:

20 and 25 mmol/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, mortality

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 956 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Exposure time: 8 hour(s)

Mortality:

not observed

Clinical signs:

1/5 animals for each sex showed epistaxis

Body weight:

Body weight profiles were considered satisfactory with all animals showing a weight gain over the 14 day post infusion observation period.

Gross pathology:

Gross abnormalities observed at necropsy included areas of red/purple colouration on the kidneys and mottled appearance of the liver or kidneys. Since these findings were noted in occasional animals from the treatment groups, it is considered that they were incidental and independent of dosage level.

Applicant's summary and conclusion

Conclusions:

N-glycyl-L-tyrosine was intravenously administered via the tail vein within 8 hours to female and male Sprague-Dawley rats. The animals were observed for 14 days after administration and clinical signs, body weight, mortality, gross necropsy and organ weight were determined. No treatment related changes occurred during the 14 days observation period. Thus, the LD50 is considered to be > 5956 mg/kg bw.