Registration Dossier

Administrative data

Description of key information

- Skin irritation/corrosion: irritating, based on existing data and additivity principles.
- Eye irritation: not an ocular corrosive or severe irritant (OECD 437, GLP, K, Rel.1), irritating, based on additivity principles.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key 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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
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. certificate)
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:
other: In vitro irritancy score for negative control
Basis:
mean
Remarks:
3 corneas
Score:
1.4
Reversibility:
other: not applicable
Irritation parameter:
other: In vitro irritancy score for test item
Basis:
mean
Remarks:
3 corneas
Score:
3.4
Reversibility:
other: not applicable
Irritation parameter:
other: In vitro irritancy score for positive control
Basis:
mean
Remarks:
3 corneas
Score:
38.7
Reversibility:
other: not applicable
Irritant / corrosive response data:
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.
Other effects:
None

See the attached document for tables of results

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2013) 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 animal data: 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. Skin irritation was observed in this rabbit skin irritation study performed similarly to US-FHSA guideline (Wong, 1971).

2/ Existing data on constituents (additivity principles):

- all Camphor white oil having more than 10% of their constituents classified as Skin irritant Category 2, should be classified as a skin irritant without further testing according to the Regulation (EC) No 1272/2008

- all Camphor white oil having more than 20% of their constituents classified as Skin irritant - R38 - should be classified as a skin irritant without further testing according to the Directive 1999/45/EEC.

Constituent

Classification according to the Regulation (EC) No. 1272/2008 (CLP)

Classification according to the Directive 67/548/EEC

Source

Skin irritation

Eye irritation

Skin irritation

Eye irritation

Pinene

SCI2, H315

-

Xi ; R38

-

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d952924-c8ed-4614-e044-00144f67d249/DISS-9d952924-c8ed-4614-e044-00144f67d249_DISS-9d952924-c8ed-4614-e044-00144f67d249.html

Terpineol

SCI2, H315

EDI2, H319

Xi ; R38

Xi ; R36

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d944137-bb01-5d50-e044-00144f67d249/DISS-9d944137-bb01-5d50-e044-00144f67d249_DISS-9d944137-bb01-5d50-e044-00144f67d249.html

Myrcene

SCI2, H315

EDI2, H319

Xi ; R38

-

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d82fafa-8716-3e64-e044-00144f67d249/DISS-9d82fafa-8716-3e64-e044-00144f67d249_DISS-9d82fafa-8716-3e64-e044-00144f67d249.html

Linalool

SCI2, H315

EDI2, H319

Xi ; R38

-

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d93c699-8de9-6b59-e044-00144f67d249/DISS-9d93c699-8de9-6b59-e044-00144f67d249_DISS-9d93c699-8de9-6b59-e044-00144f67d249.html

p-cymene

SCI2, H315

EDI2, H319

Xi ; R38

Xi ; R36

http://apps.echa.europa.eu/registered/data/dossiers/DISS-d7f35eaa-981f-389d-e044-00144f67d031/AGGR-b9e03e4c-dc82-4f4c-99cd-2c0981c86ef2_DISS-d7f35eaa-981f-389d-e044-00144f67d031.html#L-5fc88447-f9cc-4eb8-a968-062a805f4b85

Limonene

-

-

Xi ; R38

-

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9eb16d5d-b83e-2831-e044-00144f67d031/DISS-9eb16d5d-b83e-2831-e044-00144f67d031_DISS-9eb16d5d-b83e-2831-e044-00144f67d031.html

Camphene

-

EDI2, H319

-

Xi ; R36

http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d953a2a-5979-54ee-e044-00144f67d249/AGGR-0651ae38-dab3-4f35-ae07-a705ef27ca16_DISS-9d953a2a-5979-54ee-e044-00144f67d249.html#L-17826d56-dca6-4aad-b9f3-e66a347a3c9a

Source: ECHA disseminated dossiers

Eye irritation:

A key 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).

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.

- all Camphor white oils having more than 20% of their constituents classified as Eye irritant - R36 - should be classified as eye irritant according to the Directive 1999/45/EEC.


Justification for selection of skin irritation / corrosion endpoint:
Available data indicates that the criteria are met for classification as irritating to the skin

Justification for selection of eye irritation endpoint:
Only one study available. The key study is GLP-compliant and of high quality (Klimisch score = 1). Available data indicates that the criteria are met for classification as irritating to the eyes.

Effects on skin irritation/corrosion: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

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:

- Irritating to skin (Xi; R38) according to the criteria of the Directive 1999/45/EEC,

- Skin Irritant Category 2 (H315: Causes skin irritation) according to the criteria of the Regulation (EC) No. 1272/2008 (CLP).

Based on the typical composition provided by the Lead Registrant, Camphor white oil is also classified as eye irritant: Irritating to eyes Category 2 (H319: Causes serious eye irritation) according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) but is not classified as eye irritant according to the criteria of the Directive 1999/45/EEC.

No information was available regarding respiratory irritation.