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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991

Materials and methods

Principles of method if other than guideline:
No OECD guideline was followed, however after acute dosing the animals were observed for 2 weeks and multiple parameters were assessed.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
pathogen-free
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Weight at study initiation: 250-300g
- Fasting period before study: overnight
- Housing: 2 per stainless steel cage (7 X 7 X 10 in.)
- Diet: ad libitum Purina Rat Chow (5012)
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12-hr light (0600-1800 hr)/12-hr dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) methylcellulose, 0.1% (v/v) polysorbate 80 and distilled water
Details on oral exposure:
DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
309 or 618 mg/kg
No. of animals per sex per dose:
15
Control animals:
yes
Remarks:
15 vehicle control animals per dose and d-amphetamine as positive control reported elsewhere (Mullenix et al., 1989. Generation of dose-response data using activity measures. / Am. Coll. Toxicol. 8, 185-197)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency behavioral testing: daily
- Blood samples: immediately after behavioral testing
- Euthanisation: overdose pentobarbital
- Behavioral tests: A computer pattern recognition system was used. A control and test rat are placed simultaneously on either side of a clear Plexiglas box separated by a clear partition with small holes. The animals could see and smell each other while they explored the novel environment. Two video cameras at one frame per second were used to monitor and record the rats' spontaneous behavior. The video signals are transferred to a MICRO VAX I and a VAX 11/750 for pattern analysis and behavioral classification of the data. The specific behaviors identified by the computer consist of 5 major body positions: stand, sit, rear, walk, lying down; and eight modifiers: blank (no recognized ac- tivity), groom, head turn, turn, look, smell, sniff, wash face.
Statistics:
A student's t-test was applied, and a p < 0.05 was required for statistical significance.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 618 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
No significant altered bahavioral effect were observed at any dose. Tyrosine did not affect spontaneous behavior.
Body weight:
Not determined.
Gross pathology:
Not evaluated.
Other findings:
- Plasma level: elevated plasma concentrations of tyrosine after dosing
- Positive control: Amphetamine clearly increased the total time the rats engaged in walking, turning, and head turning, and thus influenced the overal behavior.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not acute toxic and the LD50 is > 618 mg/kg bw.
Executive summary:

In the current study the effect of a single oral administration of a high dose of tyrosine was investigated. More in detail the behavior of the rats was evaluated with a computer pattern recognition system. The study was not according to OECD or GLP, however, the animals were observed for 2 weeks. There were 2 dosing groups, 309 and 618 mg/kg, each containing 15 animals and each group was linked to a control group of 15 animals. Amphetamine was used as positive control.

No animals died and no adverse effects were observed during the course of the study. Amphetamine clearly increased the total time the rats engaged in walking, turning, and head turning, and thus influenced the overal behavior.

No LD50 was determined in the study, however, we can derive it and state that the LD50 is > 618 mg/kg bw.