Registration Dossier

Diss Factsheets

Administrative data

Description of key information

- Skin Corrosion/ irritation : Skin irritant cat.2, based on the rules of the CLP Regulation for classification of mixtures.

- Serious eye damage/ eye irritant: Eye irritant cat.2 , based on the rules of the CLP Regulation for classification of mixtures, but not an ocular corrosive or severe irritant (OECD 437, GLP, S, Rel.1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1971
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available, scores were not reported.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Principles of method if other than guideline:
Equivalent to US-FHSA test method for skin irritation
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 to 3.4 kg bw
Type of coverage:
occlusive
Preparation of test site:
other: one site clipped and one site abraded per animal
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
None
Remarks on result:
other: scores were not reported.
Irritant / corrosive response data:
Camphor was found to be moderately irritating to the rabbit skin.
Other effects:
None

None

Interpretation of results:
study cannot be used for classification
Conclusions:
Camphor was found to be moderately irritating to rabbit skin based on an expert judgement on the study.
Executive summary:

An acute dermal toxicity study revealed that severe edema and extensive necrosis of the rabbit skin resulted from treatment with Camphor at a single dose of 5 mL/kg bw. Therefore a primary skin irritation study was carried out to further define irritational response to this test material.

In this study, 0.5 mL of undiluted test material was applied on the clipped and abraded skin of the back of 6 rabbits. Test sites were covered with an occlusive dressing for 24 hours. Skin irritation was assessed and scored according to the Draize scale at after the removal of the patch. Scoring was repeated at 72 hours.

Camphor was found to be moderately irritating to rabbit skin.

Endpoint:
skin irritation / corrosion, other
Remarks:
Classification based on calculation rules for mixtures of the CLP Regulation
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline required
Principles of method if other than guideline:
Classification based on calculation rules for mixtures of the CLP Regulation
Irritation parameter:
other: classification
Remarks on result:
other: skin irritant category 2
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Executive summary:

The compound is composed of several identified constituents and in that, it can be considered as a mixture according to the definition of the CLP Regulation.

The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2017) was used to determine the skin irritation/corrosion hazard of the registered substance. The decision of classification as skin irritant was based on existing data on constituents (additivity principles): the registered substance has more than 10% of its constituents classified as Skin irritant Category 2 and should be classified as a skin irritant cat.2 without further testing according to the rules for classification of mixtures of Regulation (EC) No 1272/2008.

Constituent

CAS

Classification

Source

1-8 cineole

 

470 -82 -6

NC

 

ECHA C&L inventory–self classification

Dipentene

 

138 -86 -3

 

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Alpha pinene

 

80 -56 -8

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Bornan-2 -one

 

76 -22 -2

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Alpha terpineol

98-55-5

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Beta pinene

127-91-3

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

p-mentha-1,4-diene

99-85-4

NC

ECHA C&L inventory–self classification

p-cymene

99-87-6

NC

ECHA C&L inventory–self classification

p-mentha-1,5-diene

99-83-2

NC

ECHA C&L inventory–self classification

7-methyl-3-methyleneocta-1,6-diene

123-35-3

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Camphene

79-92-5

NC

ECHA C&L inventory–self classification

p-menth-1-en-4-ol

562-74-3

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

Sabinene

3387-41-5

NC

ECHA C&L inventory–self classification

p-mentha-1,4(8)-diene

586-62-9

Skin Irrit. 2 - H315

ECHA C&L inventory–self classification

5-isopropyl-2-methylbicyclo[3.1.0]hex-2-ene

2867-05-2

NC

ECHA C&L inventory–self classification

Source: ECHA disseminated dossiers or self classification

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
03 April 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and well described study in accordance with GLP and OECD Guideline 437 without any deviation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
other: Bovine eyes
Details on test animals or tissues and environmental conditions:
Not applicable
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
- The undiluted test item was applied in BCOP chamber for 10 minutes followed by an incubation period of 120 ± 10 minutes.
Observation period (in vivo):
- The condition of the cornea was visually assessed immediately after rinsing and at the final opacity measurement.
Number of animals or in vitro replicates:
Not applicable
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the test item and control items were removed from the anterior chamber and the cornea was rinsed three times with fresh complete minimum essential medium (MEM) containing phenol red before a final rinse with complete MEM. The anterior chamber was refilled with fresh complete MEM.

EVALUATION OF RESULTS:
- Results from the two test method endpoints, opacity and permeability, were combined in an empirically derived formula to generate an in vitro irritancy score.
- The following formula was used to determine the in vitro irritancy score:
In Vitro Irritancy Score = mean opacity value + (15 x mean OD492 value)
Additionally, the opacity and permeability values were evaluated independently to determine whether the test item induced a response through only one of the two endpoints.
Irritation parameter:
in vitro irritation score
Run / experiment:
Negative control
Value:
ca. 1.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
Test item
Value:
ca. 3.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
Positive control
Value:
ca. 38.7
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
Corneal epithelium condition: The corneas treated with the test item were clear post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation.

See the attached document for tables of results

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, Camphor white oil is considered not to be an ocular corrosive or severe irritant. No definitive conclusion can be established since the IVIS was > 3 and ≤ 55 (test item is not predicted as causing serious eye damage and not classified for eye irritation or serious eye damage).
Executive summary:

In an in vitro eye irritation study conducted according to the OECD Guideline 437 and in compliance with GLP, 3 bovine corneas were applied with 0.75 mL of undiluted Camphor white oil for 10 minutes at 32 ±1 ºC followed by an incubation period of 120 ± 10 minutes at 32 ±1 ºC. Negative and positive control items were tested concurrently. After incubation the BCOP holders were removed from the incubator and a final opacity reading was taken. Each cornea was visually observed. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an in vitro irritancy score.

The corneas treated with the test item were clear post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation. The in vitro irritancy score for negative and positive controls were 1.4 and 38.7, respectively and the values were within the respective ranges and therefore the study was considered valid. The in vitro irritancy score for the test item was 3.4, which is considered not to be an ocular corrosive or severe irritant.

 

Under the test conditions, Camphor white oil is considered not to be an ocular corrosive or severe irritant. No definitive conclusion can be established since the IVIS was > 3 and ≤ 55 (test item is not predicted as causing serious eye damage and not classified for eye irritation or serious eye damage).

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint:
eye irritation, other
Remarks:
Classification based on calculation rules for mixtures of the CLP Regulation
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline required
Principles of method if other than guideline:
Classification based on calculation rules for mixtures of the CLP Regulation
Irritation parameter:
other: Classification
Remarks on result:
other: Eye irritation category 2
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Executive summary:

The mixture is composed of several identified constituents and in that, it can be considered as a mixture according to the definition of the CLP Regulation. The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2017) was used to determine the serious eye damage/ eye irritant hazard of the registered substance. The decision of classification as irritant to the eyes was based on existing data on constituents (additivity principles) the registered substance has more than 10% of its constituents classified as Eye irritant Category 2 and should be classified as a Eye irritant Category 2 without further testing according to the rules for classification of mixtures of Regulation (EC) No 1272/2008.

Constituent

CAS

Classification

Source

1-8 cineole

470 -82 -6

NC

 

ECHA C&L inventory–self classification

Dipentene

138 -86 -3

NC

ECHA C&L inventory–self classification

Alpha pinene

 

80 -56 -8

NC

ECHA C&L inventory–self classification

Bornan-2 -one

 

76 -22 -2

Eye Damage 1 – H318

ECHA C&L inventory–self classification

Alpha terpineol

98-55-5

Eye Irrit. 2 – H319

ECHA C&L inventory–self classification

Beta pinene

127-91-3

NC

ECHA C&L inventory–self classification

p-mentha-1,4-diene

99-85-4

NC

ECHA C&L inventory–self classification

p-cymene

99-87-6

NC

ECHA C&L inventory–self classification

p-mentha-1,5-diene

99-83-2

NC

ECHA C&L inventory–self classification

7-methyl-3-methyleneocta-1,6-diene

123-35-3

Eye Irrit. 2 – H319

ECHA C&L inventory–self classification

Camphene

79-92-5

Eye Irrit. 2 – H319

ECHA C&L inventory–self classification

p-menth-1-en-4-ol

562-74-3

Eye Irrit. 2 – H319

ECHA C&L inventory–self classification

Sabinene

3387-41-5

NC

ECHA C&L inventory–self classification

p-mentha-1,4(8)-diene

586-62-9

Eye Irrit. 2 – H319

ECHA C&L inventory–self classification

5-isopropyl-2-methylbicyclo[3.1.0]hex-2-ene

2867-05-2

 NC

ECHA C&L inventory–self classification

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test material is composed of several identified constituents and in that, it can be considered as a mixture according to the definition of the CLP Regulation.


 


Skin irritation/corrosion:


The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2017) was used to determine the skin irritation/corrosion hazard of Camphor white oil. The decision of classification as skin irritant was based on the following arguments:


1/ Existing data on constituents (additivity principles): The registered substance has more than 10% of its constituents classified as Skin irritant Category 2 and more than 10% classified as Eye irritant Category 2 and should be classified as a skin irritant and eye irritant without further testingaccording to the rules for classification of mixtures of Regulation (EC) No 1272/2008.


2/ Existing supporting animal data: a supporting acute dermal toxicity study revealed that severe edema and extensive necrosis of the rabbit skin resulted from treatment with Camphor at a single dose of 5 mL/kg bw. Therefore a primary skin irritation study was carried out to further define irritational response to this test material. Skin irritation was observed in this rabbit skin irritation study performed similarly to US-FHSA guideline (Wong, 1971).


 


Eye irritation:


1/ A supporting study was identified (Warren, 2014, Rel.1). In this BCOP assay conducted according to the OECD Guideline 437 and in compliance with GLP, the in vitro irritancy score for the test item was 3.4.


Camphor white oil is not an ocular corrosive or severe irritant. However, based on this study, no definitive conclusion on eye irritation can be established since the IVIS was > 3 and ≤ 55 (test item is not predicted as causing serious eye damage and not classified for eye irritation or serious eye damage).


2/ Additivity principles were therefore applied to conclude on classification: all Camphor white oil oils having more than 10% of their constituents classified as Eye irritant Category 2 should be classified as eye irritant without further testing according to the Regulation (EC) No 1272/2008.


 


Skin irritation/Eye irritation:


 






















































































































Constituent



CAS



Skin Classification



Eye Classification



Source



1-8 cineole


 



470 -82 -6 



NC


 



NC


 



ECHA C&L inventory–self classification



Dipentene


 



138 -86 -3



Skin Irrit. 2 - H315



NC



ECHA C&L inventory–self classification



Alpha pinene


 



80 -56 -8



Skin Irrit. 2 - H315



NC



ECHA C&L inventory–self classification



Bornan-2 -one


 



76 -22 -2



Skin Irrit. 2 - H315



Eye Damage 1 – H318



ECHA C&L inventory–self classification



Alpha terpineol



98-55-5



Skin Irrit. 2 - H315



Eye Irrit. 2 – H319



ECHA C&L inventory–self classification



Beta pinene



127-91-3



Skin Irrit. 2 - H315



NC



ECHA C&L inventory–self classification



p-mentha-1,4-diene



99-85-4



NC



NC



ECHA C&L inventory–self classification



p-cymene



99-87-6



NC



NC



ECHA C&L inventory–self classification



p-mentha-1,5-diene



99-83-2



NC



NC



ECHA C&L inventory–self classification



7-methyl-3-methyleneocta-1,6-diene



123-35-3



Skin Irrit. 2 - H315



Eye Irrit. 2 – H319



ECHA C&L inventory–self classification



Camphene



79-92-5



NC



Eye Irrit. 2 – H319



ECHA C&L inventory–self classification



p-menth-1-en-4-ol



562-74-3



Skin Irrit. 2 - H315



Eye Irrit. 2 – H319



ECHA C&L inventory–self classification



Sabinene



3387-41-5



NC



NC



ECHA C&L inventory–self classification



p-mentha-1,4(8)-diene



586-62-9



Skin Irrit. 2 - H315



Eye Irrit. 2 – H319



ECHA C&L inventory–self classification



5-isopropyl-2-methylbicyclo[3.1.0]hex-2-ene



2867-05-2



NC



NC



ECHA C&L inventory–self classification



 


Source: ECHA disseminated dossiers or self classification

Justification for classification or non-classification

Harmonized classification:

Camphor white oil has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Based on the typical composition provided by the Lead Registrant, Camphor white oil is classified as Skin Irritant Category 2 (H315: Causes skin irritation) according to the criteria of the Regulation (EC) No.1272/2008 (CLP) and the GHS.

Based on the typical composition provided by the Lead Registrant, Camphor white oil is also classified as Eye irritant Category 2 (H319: Causes serious eye irritation) according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and the GHS.

No information was available regarding respiratory irritation.