Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion (OECD TG 402 and exisiting data of the irritating properties of the constituents): irritating

Eye irritation (OECD TG 437 and exisiting data of the irritating properties of the constituents): irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
2 (reliable with restrictions)
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:
other: Skin irrit. 2, H315
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
The substance has more than 10% of constituents classified as Skin irritant Category 2 and should be classified as a skin irritant.
Executive summary:

The NCS 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 constituents classified as Skin irritant Category 2 and should be classified as a skin irritant without further testing according to the rules for classification of mixtures of Regulation (EC) No 1272/2008.

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
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Skin irritation was assessed in an acute dermal toxicity study.
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.2 to 3.3 kg bw
Type of coverage:
semiocclusive
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): 10 mL/kg bw
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
4 (2 males and 2 females)
Details on study design:
Animals were observed for mortality, clinical signs of toxicity and dermal reactions for 14 days.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
other: Animal died on day 4
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
other: animal died on day 4
Remarks on result:
other:
Remarks:
abraded skin
Irritant / corrosive response data:
Skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days.
Other effects:
None

None

Interpretation of results:
other: irritating
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Overall skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days. More specific, in the two rabbits with intact skin the average (24/48/72h) erythema and edema score was 1 in both rabbits. However the skin irritating effects in these two rabbits increased to slight and moderate effects during the 14 days. Under the conditions of the test the substance is considered to be a skin irritant.
Executive summary:

Rosemary oil was tested in an acute dermal toxicity study similar to OECD TG 402. Four New Zealand White rabbits were exposed to the test substance via dermal application. 2 males and 2 females were exposed to 10 mL/kg bw undiluted test substance under occlusive conditions for 24 hours. The substance was applied on the back and flanks of the rabbits. The skin was clipped and intact in two rabbits (one male and one female) and clipped and abraded in the other two animals. After an observation period of 14 days animals were necropsied. Gross signs of dermal irritation were determined and scored by the method of draize. Overall skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days. More specific, in the two rabbits with intact skin the average (24/48/72h) erythema and edema score was 1 in both rabbits. However the skin irritating effects in these two rabbits increased to slight and moderate effects during the 14 days. Under the conditions of the test the substance is considered to be a skin irritant.

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:
key study
Study period:
From 24 to 29 October 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
cattle
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:
mean of 3 cornea
Value:
3.1
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:
other: no prediction can be made
Conclusions:
Under the test conditions, the results obtained lead to the category “no prediction can be made”, as defined by the OECD guideline No. 437. Therefore, the test item is not predicted as causing serious eye damage (Category 1) or as not classified for eye irritation/serious eye damage (No category)
The test item 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 test item 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 0.8 and 45.5, 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 3.1, which is considered not to be an ocular corrosive or severe irritant.

 

Under the test conditions, the test item 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).

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:
2 (reliable with restrictions)
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 irritant category 2
Interpretation of results:
other: Eye Irrit. 2, H319
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
The substance has more than 10% of its constituents classified as Eye irritant Category 2 and should be classified as a Eye irritant Category 2.
Executive summary:

The NCS 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 Eye irritant category 2 is 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 testingaccording to the rules for classification of mixtures of Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

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 Rosemary oil. The decision of classification as skin irritant was based on the following arguments:

1) Existing animal data from irritation study: Skin irritation was observed in rabbits in an acute dermal toxicity study (Lynch, 1971) at the dose of 10 ml/kg bw. Skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days.

2) Existing human data: some evidence of irritation were observed in a human patch test (Bouhlal, 1989). In this study 25 healthy volunteers were treated with undiluted Rosemary oil absolute using epicutaneous test. Irritation was observed in 2/25 subjects.

3) Existing data on constituents (additivity principles): all Rosemary oils having more than 10% of their constituents classified as Skin Irritant Category 2, should be classified as a skin irritant according to the Regulation (EC) No 1272/2008 without further testing.

Constituent

CAS

Classification

Source

Alpha pinene

80-56-8

H315

ECHA C&L inventory

Dipentene

138-86-3

H315

Harmonized classification

Beta pinene

127-91-3

H315

ECHA C&L inventory

Terpineol (alpha & beta & gamma)

8000-41-7

H315, H319

ECHA C&L inventory

Myrcene beta

123-35-3

H315, H319

ECHA C&L inventory

Camphene

79-92-5

H319

ECHA C&L inventory

Linalool

78-70-6

H315, H319

ECHA C&L inventory

Source: ECHA disseminated dossiers

 

Eye irritation

A key study was identified (Warren, 2014, Rel.1). In this BCOP assay conducted on Rosemary oil (Tunesian form) according to the OECD Guideline 437 and in compliance with GLP, the in vitro irritancy score for the test item was 3.1. Rosemary oil (Tunesian form) 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 Rosemary oil oils having more than 10% of their constituents classified as Eye irritant Category 2 should be classified as eye irritant according to the Regulation (EC) No 1272/2008 without further testing.


Justification for classification or non-classification

Based on the available information, the substance should be classified for skin irritation (Skin Irrit. 2 / H315) eye irritation (Eye Irrit. 2 / H319) in accordance with the criteria outlined in EU CLP (EC no. 1272/2008 and its amendments).