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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:
02-12-1982 to 21-12-1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to guideline and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
To determine the acute oral LD50 of the test.
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state:Clear liquid
- Stability under test conditions:There was no apparent change in the physical state of the test article during administration.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Blue Spruce Farms, Altamont, New York
- Weight at study initiation: 180-280 grams after fasting
- Fasting period before study: 18 hours
- Housing: Rats were housed individually in stainless steel 1/2" wire mesh cages. Size in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council.
- Diet : Wayne Lab Blox, ad libitum, checked daily and added or replaced as needed. Feeders were designed to reduce soiling, bridging, and scattering.
- Water : Availability -fresh tap water, fit for human consumption, ad libitum, using an automatic watering system supplied by Edstrom Industries Inc., Waterford, Wisconsin.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3
- Humidity (%):30 to 70
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.25% methylcellulose
Doses:
1000, 1600, 2000, 2500 and 3200 mg/kg
No. of animals per sex per dose:
Dose-Range-Finding Study: 12, 2 males and 2 females per dose groups
LD50 determination: Fifty (50), 5 males and 5 females per group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed immediately and at one, four and twenty-four hours after dosing and twice daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: Body weights,Pharmacotoxic, CNS effects and mortality

Results and discussion

Preliminary study:
In the dose-range-finding study, four fasted animals, two per sex, were administered the test article at 500, 1600 and 5000 mg/kg, orally by gavage. Signs observed were body drop, ptosis, diarrhea, decreased activity, decreased body tone, poor grooming, abnormal stance, hypersensitivity, piloerection, chromodacryorrhea and prostration. None of the rats died at the 500 mg/kg level, one rat fied at 1600 mg/kg and four of the rats died at the 5000 mg/kg dose level.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 609.3 other: mg/kg
Based on:
test mat.
95% CL:
1 399.6 - 1 850.4
Remarks on result:
other: LD50 was calculated by Litchfield and Wilcox method
Sex:
male
Dose descriptor:
LD50
Effect level:
1 692.6 other: mg/kg
Based on:
test mat.
95% CL:
1 433.3 - 1 998.9
Remarks on result:
other: LD50 was calculated by Litchfield and Wilcox method
Mortality:
None of the animals died at the 1000 mg/kg dose level, five of the ten died at the 1600 mg/kg dose level, nine of ten died at 2000 mg/kg and ten of ten died at the 2500 mg/kg and 3200 mg/kg dose levels. .See table 2 for detail.
Clinical signs:
Sings observed included diarrhea, decreased activity, poor grooming, piloerection, exophthalmus, ataxia, chromodacryorrhea, hypersensitivity, hyperactivity, decreased body tone, tremors, dyspena, wheezing, prostration, abnormal stance, ptosis, abnormal gait and body drop. See table 3 & 4 for more details.
Body weight:
Not reported
Gross pathology:
Necropsy of animals dying on study revealed disteneded stomachs with hemorrhages of the gladular mucosa. Ref foci on the thymus, discoloured adrenals and fluid-filled bladders were also observed. Terminal necropsy revealed no visable lesions in the remaining animals.

Any other information on results incl. tables

Table 2. Summary of Mortality

 

Dose

mg/kg

Sex

No.of Rats

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total Mortality

1000

M

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

1000

F

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

1600

M

5

2

0

0

0

0

0

0

0

0

0

0

0

0

0

2/5

1600

F

5

2

0

1

0

0

0

0

0

0

0

0

0

0

0

3/5

2000

M

5

4

0

0

0

0

0

0

0

0

0

0

0

0

0

4/5

2000

F

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

5/5

2500

M

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

5/5

2500

F

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

5/5

3200

M

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

5/5

3200

F

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

5/5

 

Table 3. Onset and duration of signs at 1600 mg/kg in Males

 

Post Dose

Signs Observed

Immediate

Semi-prostration, prostration body drop

1 Hour

Body drop, ataxia, abnormal gait

4 Hour

Body drop, abnormal gait, decreased activity

Day 1

Semi-prostration, prostration, piloerection, body drop, abnormal gait, decreased activity, diarrhea

Day 2

Arched back, abnormal gait, piloerection

Day 3

Arched back, piloerection

Day 4

Arched back, abnormal gait, piloerection, slight ptosis

Day 5

Piloerection, body drop

Day 6

Piloerection, abnormal gait, body drop

Day 7

Piloerection, body drop

Day 8

Piloerection, wheezing

Day 9-14

No signs

 

Table 4. Onset and Duration of signs at 1600 mg/kg in females

 

Post Dose

Signs Observed

Immediate

Prostration, dyspnea, hyperactivity, body drop

1 Hour

Semi- prostration

4 Hour

Prostation, body drop, decreased activity

Day 1

Piloerection, decreased body tone, ataxia, body drop, diarrhea

Day 2

Semi-prostration, abnormal gait, piloerection, arched back

Day 3

Semi-prostration ,arched back, piloerection

Day 4

Arched back, piloerection, abnormal stance

Day 5-14

No signs

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Based upon the results of the acute oral acute oral toxicity study in rats, the calculated acute oral LD50 for male and female treated with Phenethyl alcohol was determined to be 1609.3 mg/kg with confidence limits of 1399.6 to 1850.4 mg/kg. The calculated acute oral LD50 for males was determined to be 1692.6 mg/kg with 95% confidence limits of 1433.3 to 1998.9 mg/kg. An attempt was made to calculate the acute oral LD50 in females but the data generated did not lend itself to the method of Litchfield and Wilcoxon.