2-methyl-4-phenylpentanol

Endpoint summary

Description of key information

An acute oral study according to OECD Guideline 401 was conducted at test concentrations up to 5000 mg/kg, the LD50 value was calculated to be 3600 mg/kg. 
Acute dermal: In a study performed according to OECD 402 the LD 50 was found to be greater than 2000 mg/kg of body weight. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

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%.

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.

Sex:

female

Dose descriptor:

LD50

Effect level:

3 000 mg/kg bw

Based on:

test mat.

95% CL:

> 2 400 - < 3 800

Sex:

male

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

95% CL:

> 3 400 - < 4 800

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.

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  

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 11 June 1987 and 25 June 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Following a quarantine period of at least one week, five healthy male and five healthy female New Zealand Albino rabbits were randomly selected using a computer program of statistics, which generated random numbers. The animals were received from Clifford Roedel on 5/15/87.
The pretest weight range was 2.4 - 2.9 kg for males and 2. 4 - 2.6 kg for females.
The animals were identified by cage notation and a uniquely numbered metal eartag.
The animals were housed 1/cage in suspended wire mesh cages. Bedding was placed beneath the cages. Fresh Purina Rabbit Chow ( Diet #5321) and water were freely available.
The animal room, reserved exclusively for rabbits on acute tests had a 12 hour light/dark cycle and was kept clean and vermin free. The temperature range was 19° to 24°C. The relative humidity ranged from 40 to 85%.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours prior to application of the test article, the dorsal area of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact.
The test article was applied to the prepared dermal site, one time, by syringe type applicator on a g/kg basis.

Duration of exposure:

24 hours

Doses:

2 g/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

EXPERIMENTAL DESIGN
The test article was applied to the prepared dermal site, one time, by syringe type applicator on a. g/kg basis. For liquid materials, the dose was based on the sample weight as calculated from the specific gravity. For solid materials, the dose was based on the dry weight of the test article and was slightly moistened with water prior to application. The test article was covered with a gauze patch and gentle pressure was applied to the gauze to aid the distribution of the test article over the prepared site. The torso was wrapped with plastic which was secured with nonirritating tape. At 24 hours, the patches were removed and site was washed gently with water or an appropriate solvent, if necessary. The dose schedule follows:
GROUP Dose, g/kg
Test Article 2.0

TYPE AND FREQUENCY 0F OBSERVATIONS
In Vivo
The test sites were scored for dermal irritation at 24 hours post dose and on days 7 and 14 using the numerical Draize scale.
Additional signs were described.
If necessary to evaluate reversibility, observations were extended.
The animals were observed 1, 2 and 4 hours post dose and twice daily for 14 days for mortality, toxicity and pharmacological effects.
Body weights were recorded pretest, weekly, at death and at termination.

Post Mortem
All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.


EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema Formation

No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimetre) 3
Severe edema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not reported.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Physical signs of diarrhea, yellow nasal discharge, few feces, emaciation, rales and soiling of the anogenital area were noted during the observation period.

Gross pathology:

Necropsy results were normal in 7/10 animals. Gastrointestinal tract abnormalities, brown staining of the anogenital area and emaciation were noted in the remaining animals.

Other findings:

Dermal reactions, absent to slight on days 1 and 7, were absent on day 14.

Interpretation of results:

other: not considered to be toxic

Remarks:

Criteria used for interpretation of results: other: less than one-half of the animals died at 2.0 g/kg

Conclusions:

The LD50 is greater than 2.0 g/kg of body weight.

Executive summary:

In a study performed according to OECD 402 five healthy male and five healthy female New Zealand Albino rabbits were dosed dermally with Pamplefleur at 2.0 g/kg of body weight. All animals survived the 2.0 g/kg dermal application. Physical signs of diarrhea, yellow nasal discharge, few feces, emaciation, rales and soiling of the anogenital area were noted during the observation period. Body weight changes were normal in 8/10 animals. Two animals lost weight during the study. Dermal reactions, absent to slight on days 1 and 7, were absent on day 14. Necropsy results were normal in 7/10 animals. Gastrointestinal tract abnormalities, brown staining of the anogenital area and emaciation were noted in the remaining animals. The LD 50 is greater than 2.0 g/kg of body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
The study was conducted according to OECD guidelines and can be classed as a klimisch reliability 1 study.

Justification for selection of acute toxicity – dermal endpoint
The study was conducted according to OECD guidelines and can be classed as a klimisch reliability 1 study.

Justification for classification or non-classification

The acute lethal oral and dermal dose to rats of Pamplefleur were higher than 2/0 g/kg bodyweight. Based on these results the substance is not considered to be classified for acute oral or dermal toxicity in accordance with DSD 67/548/EC and the CLP Regulation (EC) No. 1272/2008.