Potassium phenylacetate

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Phenethyl Alcohol

IUPAC Name:

Phenethyl Alcohol

Constituent 2

Reference substance name:

2-phenylethanol

EC Number:

200-456-2

EC Name:

2-phenylethanol

Cas Number:

60-12-8

IUPAC Name:

2-phenylethanol

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 or test system 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 levels

Effect levels 1

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

Effect levels 2

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:

other: 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 ga

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.