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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:
key study
Study period:
Dec. 1970 to 1971-09-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report Date:
1971

Materials and methods

Test guideline
Qualifier:
no guideline followed
Guideline:
other: An OECD or other international guideline for acute oral toxicity was not available at the the year of the study. The study is similiar to OECD 403
Deviations:
not applicable
Principles of method if other than guideline:
Groups of ten rats (five males and five females) were administered 0, 10 and 16g/kg bw L-phenylalanine and observed during two weeks for mortality.
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CFY strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Carworth Europe, Alconbury, Huntingdon
- Weight at study initiation: 62 - 123 g
- Fasting period before study: 20 hours before dosing (and 4 hours after dosing)
- Housing: caged in groups according to sex and age

Administration / exposure

Route of administration:
other: Solution in water or as suspension in 1 % methyl cellulose and administered by gastric intubation.
Vehicle:
other: water or methyl cellulose plus water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30% solution in water or 30% suspension in 1% methyl cellulose

MAXIMUM DOSE VOLUME APPLIED:
Maximum dosage volume of 53.3 ml/kg bodyweight, equivalent to a maximum practical dose of 16g amino acid /kg bodyweight.
Dosage volumes in excess of 20 ml/kg were given in divided doses at two hourly intervals.
Doses:
0, 10 and 16 g/kg bw.
Rats dosed with the vehicle alone served as controls.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once a week
- Necropsy of survivors performed: yes
- Other examinations performed: body weight/behaviour
Statistics:
Method of Litchfield J.T., Wilcoxon F (1949), J. Pharmac. exp. Ther. 96, 99

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 10 000 - <= 16 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Based on:
test mat.
Dose descriptor:
approximate LD50
Effect level:
ca. 16 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: median Iethal oral dose
Mortality:
Three female rats died; one dosed at 10g/kg and two dosed at 16g/kg bw. Death occurred wlthin 46 hours of dosing and was preceded by coma. Autopsy of animals that died did not reveal any specific cause of death.
Clinical signs:
Lethargie behaviour was observed shortly after dosing.
Recovery of survivors, as judged by external appearance and behaviour was apparently complete within 3 days.
Body weight:
Bodyweight increases of treated rats were slightly depressed for the first week (except for males dosed at 10g/kg) but were normal during the second week.

Group mean body weight with 0g test substance (control groups):
Male: day 0: 83 g, day 7: 141 g, day 14: 201 g
Female: day 0: 86 g; day 7: 144 g; day 14: 183 g

Group mean body weight with 10g test substance:
Male: day 0: 87 g, day 7: 148 g, day 14: 213 g
Female: day 0: 81 g; day 7: 131 g; day 14: 171 g

Group mean body weight with 16g test substance:
Male: day 0: 79 g, day 7: 129 g, day 14: 175 g
Female: day 0: 82 g; day 7: 132 g; day 14: 168 g
Gross pathology:
Autopsy findings were normal.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
An acute oral toxicity study was performed with groups of 5 male and 5 female rats. The results indicate that the median lethal oral dose (LD 50) of L-phenylalanine is ca. 16g/kg bw.