(1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol

Endpoint summary

Description of key information

In the key acute oral toxicity study in male and female rats, the LD50 was found to be 2050 mg/kg bw in male and females.

 

In a supporting acute oral toxicity study in male and female rats, all animals died at a single dose of 5000 mg/kg bw. The LD50 is thus <5000 mg/kg bw.

 

In an acute dermal toxicity study in male and female rabbits, all animals survived after a single dose of 5000 mg/kg bw. The LD50 is thus >5000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1979-03-12 to 1979-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

See "Principles of method other than guideline"

Principles of method if other than guideline:

- Principle of test: Acute oral toxicity test in rats
- Short description of test conditions: A single oral treatment was given to 5 male and 5 female Wistar rats. Animals were observed for signs of toxicity for 14 days and then subjected to gross pathology. No detailed description of environmental conditions and clinical signs is available. Body weights were recorded at the beginning and after the 14-day observation period.
- Parameters analysed / observed: Mortality, gross pathology

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Rationale for use of males: Both males and females were used
- Age at study initiation: Approx. 6-8 weeks
- Weight at study initiation: 192 - 258 g
- Fasting period before study: 18 hours
- Housing: In galvanized cages with indirect bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature-controlled room
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 15

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

The test article was used in 25% gravimetric suspension, warmed to liquification for dosing

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex were treated with a single dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter. Body weights were recorded at the beginning of the study and after the 14-day observation period.
- Necropsy of survivors performed: Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

< 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable

Remarks:

Not determinable because of 100% mortality at a single dose of 5000 mg/kg bw

Mortality:

All male and female animals died at 5000 mg/kg bw:
2/5 males died within 3 hours after administration and 3/5 males within 6 hours after administration;
5/5 males died within 3 hours after administration

Clinical signs:

other: Severe depression

Gross pathology:

The internal organs and superficial examination appeared normal

Interpretation of results:

study cannot be used for classification

Conclusions:

In an acute oral toxicity study in male and female rats, all animals died at a single dose of 5000 mg/kg bw. The LD50 is thus <5000 mg/kg bw.

Executive summary:

In a GLP compliant acute oral toxicity study in 5 male and 5 female albino rats, the test item was applied at a single dose of 5000 mg/kg bw in corn oil by oral administration. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. Severe depression was observed in all animals 1-3 hours after treatment. All animals died 6 hours after dosing by the latest. No gross pathological changes were observed. Thus the LD50 was found to be <5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-03-12 to 1979-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

See "Principles of method other than guideline"

Principles of method if other than guideline:

- Principle of test: Acute oral toxicity test in rats
- Short description of test conditions: Wistar rats were treated with different doses of the test item (5 males and 5 females per dose). Animals were observed for signs of toxicity for 14 days and then subjected to gross pathology. No detailed description of environmental conditions and clinical signs is available. Body weights were recorded at the beginning and after the 14-day observation period.
- Parameters analysed / observed: Mortality, gross pathology

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Rationale for use of males: Both males and females were used
- Age at study initiation: Approx. 6-8 weeks
- Weight at study initiation: 184 - 278 g
- Fasting period before study: 18 hours
- Housing: In galvanized cages with indirect bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature-controlled room
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 15

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

The test article was used in 25% gravimetric suspension, warmed to liquification for dosing

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%

Doses:

1260, 2000, 2520 and 3140 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter. Body weights were recorded at the beginning of the study and after the 14-day observation period.
- Necropsy of survivors performed: Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 050 mg/kg bw

Based on:

test mat.

95% CL:

> 1 630 - < 2 580

Mortality:

1260 mg/kg bw: 0/5 males and 2/5 females died
2000 mg/kg bw: 2/5 males and 3/5 females died
2520 mg/kg bw: 2/5 males and 4/5 females died
3140 mg/kg bw: 4/5 males and 3/5 females died

Clinical signs:

other: Clinical signs consisted of slight and severe depression,

Gross pathology:

The superficial examination appeared normal. In one male animals of the 1260 mg/kg bw group, a lesion on the left lobe of the lung was observed and one female animal of the 1260 mg/kg bw group showed a distended, gas filled stomach. In one male animal of the 2520 mg/kg bw group, fibrous tissue encasing heart and lungs was observed.

Conclusions:

In an acute oral toxicity study in male and female rats, the LD50 was found to be 2050 mg/kg bw in male and females.

Executive summary:

In a GLP compliant acute oral toxicity study in Wistar rats, the test item was applied at doses of 1260, 2000, 2520 and 3140 mg/kg bw to 5 males and 5 females per dose by oral administration. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Animals were weighted before start of the treatment and at day 14. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. From a dose of 1260 mg/kg bw (females) and 2000 mg/kg bw (males), slight to severe depression was observed in all animals in the first 24 hours. Body weight gain decreased with increasing doses. At 1260 mg/kg bw, 0/5 males and 2/5 females, at 2000 mg/kg bw, 2/5 males and 3/5 females, at 2520 mg/kg bw, 2/5 males and 4/5 females and at 3140 mg/kg bw, 4/5 males and 3/5 females died. Thus, the LD50 was found to be 2050 mg/kg bw for males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 050 mg/kg bw

Quality of whole database:

Reliable with restrictions

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:

1979-03-12 to 1979-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

See "Principles of method other than guideline"

Principles of method if other than guideline:

- Principle of test: Acute dermal toxicity test in rabbits
- Short description of test conditions: A single dermal treatment was given to 3 male and 3 female albino rabbits. The skin of three rabbits was abraded, the remaining animal's skin remained intact. The test side was occluded for 24 hours. Animals were observed for sign of toxicity for 14 days and then subjected to gross pathology. No detailed description of environmental conditions, dose preparation, vehicle identity and clinical signs are available. Body weights were not recorded during the study. Times of death were not described.
- Parameters analysed / observed: Mortality, gross pathology

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Rationale for use of males: Both males and females were used
- Age at study initiation: 3-4 months
- Weight at study initiation: 1.76 - 2.32 kg
- Housing: In galvanized cages with indirect bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature-controlled room
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 15

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test item was wiped off the skin after 24 hours
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

One single dose of 5000 mg/kg bw

No. of animals per sex per dose:

3 animals per sex were treated with a single dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter. Body weights were recorded at the beginning of the study and after the 14-day observation period.
- Necropsy of survivors performed: Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

None of the animals died within the treatment and post-treatment period.

Clinical signs:

other: No clinical signs observed

Gross pathology:

The internal organs and superficial examination appeared normal.

Other findings:

In two male animals with abraded skin, small scab has formed and detached.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study in male and female rabbits, all animals survived after a single dose of 5000 mg/kg bw. The LD50 is thus >5000 mg/kg bw.

Executive summary:

In a GLP compliant acute dermal toxicity study in 3 male and 3 female New Zealand white rabbits, the test item was applied at a single dose of 5000 mg/kg bw by occlusive administration to abraded (2 males and 1 female) and non-abraded (1 male, 2 females) skin. The test side was occluded for 24 hours. After the treatment period, the occlusive wrap and all remaining test item was removed. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. No deaths, clinical signs or changes in body weight gain were observed. Thus, the LD50 was found to be >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

Reliable with restrictions

Additional information

Acute oral toxicity, rat, RL2, key study

In an GLP compliant acute oral toxicity study in Wistar rats, the test item was applied at doses of 1260, 2000, 2520 and 3140 mg/kg bw to 5 males and 5 females per dose by oral administration. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Animals were weighted before start of the treatment and at day 14. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. From a dose of 1260 mg/kg bw (females) and 2000 mg/kg bw (males), slight to severe depression was observed in all animals in the first 24 hours. Body weight gain decreased with increasing doses. At 1260 mg/kg bw, 0/5 males and 2/5 females, at 2000 mg/kg bw, 2/5 males and 3/5 females, at 2520 mg/kg bw, 2/5 males and 4/5 females and at 3140 mg/kg bw, 4/5 males and 3/5 females died. Thus, the LD50 was found to be 2050 mg/kg bw for males and females.

 

Acute oral toxicity, rat, RL2, supporting study

In an GLP compliant acute oral toxicity study in 5 male and 5 female albino rats, the test item was applied at a single dose of 5000 mg/kg bw in corn oil by oral administration. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. Severe depression was observed in all animals 1-3 hours after treatment. All animals died 6 hours after dosing by the latest. No gross pathological changes were observed. Thus the LD50 was found to be <5000 mg/kg bw.

 

Acute dermal toxicity, rat, RL2, key study

In a GLP compliant acute dermal toxicity study in 3 male and 3 female New Zealand white rabbits, the test item was applied at a single dose of 5000 mg/kg bw by occlusive administration to abraded (2 males and 1 female) and non-abraded (1 male, 2 females) skin. The test side was occluded for 24 hours. After the treatment period, the occlusive wrap and all remaining test item was removed. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. No deaths, clinical signs or changes in body weight gain were observed. Thus, the LD50 was found to be >5000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral and dermal toxicity, the test item is not classified and labelled for acute toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.