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Diss Factsheets

Administrative data

Description of key information

Acute oral toxicity: Key study. Test method in accordance with OECD Test Guideline 423, following GLP. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off may be considered to be 5000 mg/kg body weight by oral route in the rat.

Acute oral toxicity: Supporting studies. Based on the experimental results obtained with the analogue substance camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw. Also, based on the experimental results obtained with the analogue substance alpha pinene, the acute oral LD50 of the reaction mass in rats is expected to be 3.7 g/kg bw (2.3 -5.1 g/kg bw).

Acute inhalation toxicity: Supporting studies. Based on the experimental results obtained with the analogue substance camphene, the acute inhalation LC0 of the reaction mass is expected to be equal or greater than 243 mg/kg. Also, based on the experimental results obtained with the analogue substance alpha pinene, the LC50 of the reaction mass (for the shortest period causing death) is predicted to be 625 mg/l/min in rats.

Acute dermal toxicity: Weight of evidence. Based on the experimental results obtained with the analogue substance camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw. Also, based on the experimental results obtained with the analogue substance alpha pinene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 5 g/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 700 mg/kg bw
Remarks on result:
other: confidence limit: 2300-5100 mg/kg bw

The acute oral LD50 value in rats was reported as 3.7 g/kg bw (2.3 -5.1 g/kg bw)

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute oral LD50 value in rats was reported as 3.7 g/kg bw (2.3 -5.1 g/kg bw)
Executive summary:

The acute oral LD50 value in rats was reported as 3.7 g/kg bw (2.3 -5.1 g/kg bw)

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw

The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.
Executive summary:

The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw

The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.
Executive summary:

The acute oral LD50 value in rats was reported as greater than 5 g/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance alpha pinene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 700 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 = 3700 mg/kg bw (confidence limit: 2300-5100 mg/kg bw)
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue alpha pinene, the acute oral LD50 of the reaction mass in rats is expected to be 3.7 g/kg bw (2.3 -5.1 g/kg bw)
Executive summary:

Based on read across from the analogue alpha pinene, the acute oral LD50 of the reaction mass in rats is expected to be 3.7 g/kg bw (2.3 -5.1 g/kg bw)

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 > 5000 mg/kg bw
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw.
Executive summary:

Based on read across from the analogue camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 > 5000 mg/kg bw
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw.
Executive summary:

Based on read across from the analogue camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 September 2017 - 10 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
RccHan: WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 173.8 to 201.8 g
- Fasting period before study: overnight prior to dosing until three hours post-dosing
- Housing: 3 females in polypropylene rat cages covered with stainless steel grid top. Autoclaved clean rice husk was used as the bedding material. Wooden blocks were provided as enrichment material.
- Diet (e.g. ad libitum): Ad libitum. Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA. The quality of feed is regularly monitored at Jai Research Foundation.
- Water (e.g. ad libitum): Ad libitum. UV sterilized water filtered through Reverse Osmosis water filtration system. The quality of water is regularly monitored at Jai Research Foundation.
- Acclimation period: 6 to 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 57 to 67%
- Air changes (per hr): At least 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours contimuous light (06.00 to 18.00 h) and 12 hours darkness.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.4 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: without preliminary information, the selected starting dose is 300 mg/kg body weight.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: toxicity and mortality at 30 min, 1h, 2 h, 3h, 4h, 6 h after adminitration. Morbidity and mortality twice a day and clinical sings daily during 14 days. Weighing= D0 (prior to dosing) then on D7, and D14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed.
- Other examinations performed:
Clinical observations: evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects and central nervous system effects, behavioural pattern, somatomotor activity and observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical sign was observed in rats treated with 300 and 2000 mg/kg body weight.
Body weight:
Normal gain in body weight was observed in all the rats treated with 300 and 2000 mg/kg body weight.
Gross pathology:
External and visceral examination of terminally sacrificed rats did not reveal any abnormality.

Table 1: Mortality

Dose

(mg/kg body weight)

Set

N°

Number of Rats Used

Mortality after Dosing

At Hour

On Day

0.5 - 4

6

1

2

3

4 - 7

8 - 14

300

I

3

0

0

0

0

0

0

0

II

3

0

0

0

0

0

0

0

2000

III

3

0

0

0

0

0

0

0

IV

3

0

0

0

0

0

0

0

Table 2: Individual and Mean Body Weight (g) and Body WeightChange (%)

Dose

(mg/kg body weight)

Rat

N°

Volume of Dose Administered (mL)

Body Weight (g) on Day

Percent Body Weight Change on Day

 

 

 

0

7

14

7

14

300

1

0.06

186.8

209.6

225.3

12.2

20.6

 

2

0.07

188.1

219.8

230.8

16.9

22.7

 

3

0.06

183.4

204.5

218.4

11.5

19.1

 

Mean

 

186.1

211.3

224.8

13.5

20.8

 

Standard Deviation (±)

 

2.4

7.8

6.2

2.9

1.8

 

4

0.07

191.1

216.6

224.8

13.3

17.6

 

5

0.07

201.1

236.8

247.9

17.8

23.3

 

6

0.06

186.7

214.2

227.4

14.7

21.8

 

Mean

 

193.0

222.5

233.4

15.3

20.9

 

Standard Deviation (±)

 

7.4

12.4

12.7

2.3

3.0

2000

7

0.47

201.8

212.8

228.8

5.5

13.4

 

8

0.43

187.3

204.5

223.6

9.2

19.4

 

9

0.43

184.5

203.8

218.5

10.5

18.4

 

Mean

 

191.2

207.0

223.6

8.4

17.1

 

Standard Deviation (±)

 

9.3

5.0

5.2

2.6

3.2

 

10

0.41

176.0

190.4

205.6

8.2

16.8

 

11

0.40

173.8

188.8

193.8

8.6

11.5

 

12

0.42

182.4

199.0

201.5

9.1

10.5

 

Mean

 

177.4

192.7

200.3

8.6

12.9

 

Standard Deviation (±)

 

4.5

5.5

6.0

0.5

3.4

Key: Day 0 = Before dosing

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off may be considered to be 5000 mg/kg body weight by oral route in the rat.
Executive summary:

The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 12 female Wistar rats divided in 4 groups were administered sequentially with test item by oral gavage. The first set of 3 female rats was given a single dose of 300 mg/kg body weight. No mortality was observed at this dose level, so the second set of 3 female rats was treated at the same dose level. No mortality was observed at this dose level, so the third set of 3 female rats was treated at the higher dose level of 2000 mg/kg bw. As no mortality was observed at this dose level, the fourth set of 3 female rats was treated at the same dose level of 2000 mg/kg bw. The body weight evolution of the animals remained normal during the study. No clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be 5000 mg/kg body weight by oral route in the rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Key study with Klimisch score = 1

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Test method was not according to any guideline. The species used was the rabbit. However, the recommended species for the acute inhalation toxicity is the rat. No GLP.
Principles of method if other than guideline:
- Principle of test: Studies on the pharmacological expectorant activity of nutmeg oil and camphene given by inhalation to rabbits arranged for the collection of respiratory tract fluid.
- Short description of test conditions: see below
- Parameters analysed / observed: volumen of respiratory tract fluid, expectorant activity and odor
GLP compliance:
no
Test type:
other: Study of the pharmacological expectorant activity of test substance
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young
- Weight at study initiation: 2-3 kg
- Housing: They were housed in boarding cages, one animal per cage.
- Diet (e.g. ad libitum): They were fed a standard rabbit ration of mixed natural foods, salts, and vitamins.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
In preparation for the collection of respiratory tract fluid, the rabbits were anesthetized with urethane (ethyl carbamate) given by intraperitoneal injection in a dose of 4.0 to 5.0 mL/kg body weight of a 25% (w/v) solution in distilled water. This produced a light anesthesia lasting over 24 hours with no reported effect on the volume and composition of respiratory tract fluid except that it augmented the concentration of potassium ion.
One arm of a T-shaped cannula was ligated into the trachea, a collecting tube attached to the second arm, and the third arm was connected with a reservoir of conditioned air maintained at 39 ºC and saturated with water vapor. The conditioned air was prepared by mixing laboratory air with steam from a thermostatically controlled water vaporizer. Steam generated by this vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit.
Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours.


Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
>= 4 - <= 6 h
Concentrations:
1, 3, 9, 27, 81, and 243 mg/kg
No. of animals per sex per dose:
4-6 male rabbits per dose
Control animals:
other: The controls were the same animals, before being treated.
Details on study design:
- Duration of observation period following administration: 24 hours, which is a standard method of expressing the volume output of respiratory tract fluid.
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
>= 243 other: mg/kg
Based on:
test mat.
Exp. duration:
6 h
Mortality:
No animals died during the study.
Clinical signs:
other: Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output

The LC 0 was equal or greater than 243 mg/kg.

Interpretation of results:
study cannot be used for classification
Conclusions:
The LC 0 was equal or greater than 243 mg/kg.
Executive summary:

Camphene was given by inhalation to male rabbits that were anesthetized with urethane (ethyl carbamate) for 24 hours and were arranged for collection of respiratory tract fluid. Test substance was dissolved in 1 mL of ethanol in amounts of 1, 3, 9, 27, 81, and 243 mg. Each dose was given to 4 to 6 rabbits. Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours. Steam generated by the water vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit. Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output of respiratory tract fluid varied with the season. The expectorant action began to disappear following inhalation of a dose of 81 mg/kg, which is well below the level detectable by odour (243 mg/kg) and far below the probably fatal dose. Based on these results, the LC0 was established to be equal or greater than 243 mg/kg.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Test animals inhaled saturated vapours of alpha pinene from steam distillation of wood.


Analytical verification of test atmosphere concentrations:
not specified
Concentrations:
26 mg/L
No. of animals per sex per dose:
no data
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
625 other: mg/L/min
Based on:
test mat.
Remarks on result:
other: Effect level is the LC for the shortest period causing death
Interpretation of results:
study cannot be used for classification
Conclusions:
The LC50 of the test item (for the shortest period causing death) is 625 mg/l/min in rats.
Executive summary:

Alpha pinene was given to rats through inhalation of saturated vapours (26 mg/L of alpha pinene) obtained from steam distillation of wood. The LC50 of the test item (for the shortest period causing death) was found to be 625 mg/l/min.

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
>= 243 other: mg/kg
Based on:
other: Read-across from an analogue
Exp. duration:
6 h
Remarks on result:
other: read-across from an analogue for which LC0 >= 243 mg/kg
Interpretation of results:
study cannot be used for classification
Conclusions:
Based on read across from the analogue camphene, the LC0 of the reaction mass is expected to be equal or greater than 243 mg/kg.
Executive summary:

Camphene was given by inhalation to male rabbits that were anesthetized with urethane (ethyl carbamate) for 24 hours and were arranged for collection of respiratory tract fluid. Test substance was dissolved in 1 mL of ethanol in amounts of 1, 3, 9, 27, 81, and 243 mg. Each dose was given to 4 to 6 rabbits. Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours. Steam generated by the water vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit. Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output of respiratory tract fluid varied with the season. The expectorant action began to disappear following inhalation of a dose of 81 mg/kg, which is well below the level detectable by odour (243 mg/kg) and far below the probably fatal dose. Based on these results, the read-across approach was applied and the LC0 of the reaction mass is expected to be equal or greater than 243 mg/kg.

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance alpha pinene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
625 other: mg/L/min
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LC50 = 625 mg/L/min (Effect level is the LC for the shortest period causing death)
Interpretation of results:
study cannot be used for classification
Conclusions:
Based on read across from the analogue alpha pinene, the LC50 of the mass reaction (for the shortest period causing death) is predicted to be 625 mg/l/min in rats.
Executive summary:

Alpha pinene was given to rats through inhalation of saturated vapours (26 mg/L of alpha pinene) obtained from steam distillation of wood. The LC50 of the test item (for the shortest period causing death) was found to be 625 mg/l/min. Based on these results, the read-across approach was applied and the LC50 for the reaction mass is expected to be 625 mg/l/min.

Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII, column 2: In addition to the oral route (Annex VII, 8.5.1.), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information is provided for dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Supporting studies with Klimisch scores = 3 and 4. An appropriate dose descriptor could not be deduced from these study reports.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method.
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
No data
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw

The acute dermal LD50 value in rabbits was reported as greater than 5 g/kg bw.

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute dermal LD50 value in rabbits was reported as greater than 5 g/kg bw.
Executive summary:

The acute dermal LD50 value in rabbits was reported as greater than 5 g/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method.
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
No data
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw

The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.
Executive summary:

The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on test method
GLP compliance:
not specified
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
No data
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw

The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.
Executive summary:

The acute dermal LD50 value in rabbits was reported as greater than 2.5 g/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance alpha pinene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 > 5000 mg/kg bw
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue alpha pinene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 5 g/kg bw.
Executive summary:

Based on read across from the analogue alpha pinene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 5 g/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 > 2500 mg/kg bw
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw.
Executive summary:

Based on read across from the analogue camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
other: Read-across from an analogue
Remarks on result:
other: read-across from an analogue for which LD50 > 2500 mg/kg bw
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
Based on read across from the analogue camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw.
Executive summary:

Based on read across from the analogue camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
Weight of evidence from several studies with Klimisch score = 4

Additional information

Acute oral toxicity: Key study: The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 12 female Wistar rats divided in 4 groups were administered sequentially with test item by oral gavage.The first set of 3 female rats was given a single dose of 300 mg/kg body weight. No mortality was observed at this dose level, so the second set of 3 female rats was treated at the same dose level. No mortality was observed at this dose level, so the third set of 3 female rats was treated at the higher dose level of 2000 mg/kg bw. As no mortality was observed at this dose level, the fourth set of 3 female rats was treated at the same dose level of 2000 mg/kg bw. The body weight evolution of the animals remained normal during the study.No clinical signs were observed.The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be 5000 mg/kg body weight by oral route in the rat.

Acute oral toxicity: Supporting studies. Based on the experimental results obtained with the analogue substance camphene, the acute oral LD50 of the reaction mass in rats is expected to be greater than 5 g/kg bw.. Also, based on the experimental results obtained with the analogue substance alpha pinene, the acute oral LD50 of the reaction mass in rats is expected to be 3.7 g/kg bw (2.3 -5.1 g/kg bw).

Acute inhalation toxicity: Supporting study. Camphene was given by inhalation to male rabbits that were anesthetized with urethane (ethyl carbamate) for 24 hours and were arranged for collection of respiratory tract fluid. Test substance was dissolved in 1 mL of ethanol in amounts of 1, 3, 9, 27, 81, and 243 mg. Each dose was given to 4 to 6 rabbits. Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours. Steam generated by the water vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit. Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output of respiratory tract fluid varied with the season. The expectorant action began to disappear following inhalation of a dose of 81 mg/kg, which is well below the level detectable by odour (243 mg/kg) and far below the probably fatal dose. Based on these results, the read-across approach was applied and the LC0 of the reaction mass is expected to be equal or greater than 243 mg/kg.

Acute inhalation toxicity: Supporting study. Alpha pinene was given to rats through inhalation of saturated vapours (26 mg/L of alpha pinene) obtained from steam distillation of wood. The LC50 of the test item (for the shortest period causing death) was found to be 625 mg/l/min. Based on these results, the read-across approach was applied and the LC50 for the reaction mass is expected to be 625 mg/l/min.

Acute dermal toxicity: Weight of evidence. Based on the experimental results obtained with the analogue substance camphene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 2.5 g/kg bw. Also, based on the experimental results obtained with the analogue substance alpha pinene, the acute dermal LD50 of the reaction mass in rabbits is expected to be greater than 5 g/kg bw.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.