2-methyl-4-phenylpentanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 09 June 1987 and 10 July 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with OECD guidelines and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pamplefleur

IUPAC Name:

Pamplefleur

Test material form:

other: liquid

Details on test material:

Received: 6/04/87
Label: IFF Study 87-209
Storage: The test article was stored at ambient room temperature and humidity.
Description of Test Article: Clear Liquid
Specific Gravity: 0.99

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Following a quarantine period of at least 5 days, five healthy male and five healthy female Wistar Albino rats/group were randomly selected using a computer program of statistics, which generated random numbers. The animals were received from Ace Animals on 5/19, 5/26, 6/09 and 6/16/87.
The pretest weight range was 207-298 g for males and 205-266 g for females.
The weight variation of the animals used did not exceed +/- 20% of the mean weight.
Animals were identified by cage notation and indelible body marks.
The animals were housed 5/sex/cage in suspended wire mesh cages. Bedding was placed beneath the cages. Fresh Purina Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was freely available at all times.
The animal room, reserved exclusively for rats on acute tests, had a 12 hour bight/dark cycle and was kept clean and vermin free. The temperature range was 18 to 23°C except for a one hour period, at which time the temperature dropped to 16 C. The relative humidity ranged.from 40 to 85%.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Sample Preparation: Used as received

The test article was administered orally, one time, by syringe and dosing needle at a dose level of 5.0 g/kg. Since compound related mortality occurred, additional dose levels were tested. For liquid materials, the dose was based on the sample weight as calculated from the specific gravity. The maximum volume of liquid administered at one time did not exceed 2.0 ml/100 g of body weight if the vehicle was water; or 1. 0 ml/100 g of body weight for vehicle other than water.

Doses:

The dose schedule follows:

GROUP DOSE, g/kg
Test article 2.6
3.2
4. 0
5. 0

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

EXPERIMENTAL DESIGN
The test article was administered orally, one time, by syringe and dosing needle at a dose level of 5.0 g/kg. Since compound related mortality occurred, additional dose levels were tested. For liquid materials, the dose was based on the sample weight as calculated from the specific gravity. The maximum volume of liquid administered at one time did not exceed 2.0 ml/100 g of body weight if the vehicle was water; or 1. 0 ml/100 g of body weight for vehicle other than water. The dose schedule follows:
G ROUP DOSE g/kg
Test article 2.6
3.2
4. 0
5. 0

TYPE AND FREQUENCY 0F OBSERVATIONS
In Vivo
Animals were observed 1, 2 and 4 hours post dose and once each morning and afternoon thereafter for 14 days for mortality, toxicity and pharmacological effects.
Body weights were recorded on the day of dosing, weekly, at death, and at termination in the survivors.
Post Mortem
All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.

Statistics:

The LD50 and 95% Confidence Limits were calculated, if possible, by the method of Litchfield J.T. Jr., & F. Wilcoxon JPE T 96:99, 1949 or Horn H.J.B iometrics 12:311, 1956.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

3 000 mg/kg bw

Based on:

test mat.

95% CL:

> 2 400 - < 3 800

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

95% CL:

> 3 400 - < 4 800

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 600 mg/kg bw

Based on:

test mat.

95% CL:

> 3 100 - < 4 200

Mortality:

Mortality response to the four dose levels was as follows:
Dose #Treated #Dead
g/kg M / F M / F
5.0 5 / 5 4 / 4
2.6 5 / 5 0 / 2
3.2 5 / 5 1 / 4
4.0 5 / 5 3 / 4

Clinical signs:

other: The deaths occurred by day 2 and were preceded by physical signs of lethargy, ataxia, ptosis, prostrati on, negative righting reflex, diarrhea, flaccid muscle tone, brown staining of body areas and wetness of the nose/mouth and anogenital areas. Physical

Gross pathology:

Necropsy of the deaths revealed abnormalities of the lungs, liver, spleen, kidneys and gastrointestinal tract, as well as brown staining of the nose/mouth area and wetness or brown staining of the anogenital area.
Necropsy results of survivors were normal.

Any other information on results incl. tables

LD50

Males                                     :       4.0 (3.4 - 4.8) g/kg

Females                                     :       3.0 (2.4 - 3.8) g/kg

Male and Females combined:       3.6 (3.1 - 4.2) g/kg  

Applicant's summary and conclusion

Interpretation of results:

other: LD50 - Males: 4.0 (3.4 - 4.8) g/kg Females: 3.0 (2.4 - 3.8) g/kg Male and Females combined: 3.6 (3.1 - 4.2) g/kg  

Conclusions:

The LD50 and 95% Confidence Limits are: males - 4. 0 (3.4 - 4.8) g/kg; females - 3. 0 (2.4 - 3.8) g/kg; and males & females combined - 3. 6 (3.1 - 4.2) g/kg of body weight.

Executive summary:

Acute toxicity in rats was examined in a study according to OECD 401. Five healthy male and five healthy female Wistar Albino rats were randomly selected and dosed orally with Pamplefleur at 5.0 g/kg of body weight. Since compound related mortality occurred, five healthy male and five healthy female Wistar Albino rats were dosed at 2.6, 3.2 and 4.0 g/kg of body weight. Mortality response to the four dose levels was as follows: at 5.0 g/kg 4/5 males and 4/5 females died, at 4.0 g/kg 3/5 males and 4/5 females dies, at 3.2 g/kg 1/5 males and 4/5 females died and at 2.6 g/kg 0/5 males and 2/5 females died. The deaths occurred by day 2 and were preceded by physical signs of lethargy, ataxia, ptosis, prostration, negative righting reflex, diarrhea, flaccid muscle tone, brown staining of body areas and wetness of the nose/mouth and anogenital areas. Necropsy of the deaths revealed abnormalities of the lungs, liver, spleen, kidneys and gastrointestinal tract, as well as brown staining of the nose/mouth area and wetness or brown staining of the anogenital area. Physical signs noted in survivors included lethargy, ptosis, ataxia, prostration, negative righting reflex, piloerection, diarrhea, chromodacryorrhea, brown staining of body areas and wetness of the anogenital area. Body weight increases and necropsy results of survivors were normal. The LD50 and 95% Confidence Limits are: males - 4. 0 (3.4 - 4.8) g/kg; females - 3. 0 (2.4 - 3.8) g/kg; and males & females combined - 3. 6 (3.1 - 4.2) g/kg of body weight.