Registration Dossier

Administrative data

Description of key information

- Skin irritation/corrosion: irritating (WoE).
- Eye irritation: not irritating (OECD 405, GLP, K, 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:
1973
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Reason / purpose:
reference to same study
Reason / purpose:
reference to other 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:
not specified
Details on test animals and environmental conditions:
None
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
5000 mg/kg bw
Duration of treatment / exposure:
No data
Observation period:
14 days
Number of animals:
10
Details on study design:
Animals were observed for mortality, clinical signs of toxicity and dermal reactions for 14 days.
Irritation parameter:
erythema score
Basis:
other: 5/10 animals
Remarks on result:
other: slight redness in 5/10 rabbits
Irritation parameter:
erythema score
Basis:
other: 3/10 animals
Remarks on result:
other: moderate redness in 3/10 rabbits
Irritation parameter:
edema score
Basis:
other: all animals
Remarks on result:
other: moderate oedema in 10/10 rabbits
Irritant / corrosive response data:
Slight redness (5/10 rabbits), moderate redness (3/10 rabbits) and moderate oedema (10/10 rabbits).
Other effects:
No mortality was observed.

None

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Dermal reactions noted were slight redness (5/10 rabbits), moderate redness (3/10 rabbits) and moderate oedema (10/10 rabbits) at the site of application.
Executive summary:

In an acute dermal toxicity study, 10 rabbits were administered a single dermal dose of eucalyptus oil at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

Dermal reactions noted were slight redness (5/10 rabbits), moderate redness (3/10 rabbits) and moderate oedema (10/10 rabbits) at the site of application.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1998
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data on constituents only
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
Method: Open mouse ear assay (Evans and Schmidt, 1979)
GLP compliance:
not specified
Species:
mouse
Strain:
other: albino
Type of coverage:
open
Preparation of test site:
not specified
Vehicle:
other: acetone
Controls:
no
Duration of treatment / exposure:
No data
Observation period:
24 and 48 h after exposure
Number of animals:
10
Irritation parameter:
other: ID50 (Irritant dose in 50 % individuals)
Basis:
mean
Time point:
other: 48 h
Score:
0.351 - 2.483
Reversibility:
no data
Other effects:
The ID50 values for 1,8-cineole, β-caryophyllene, citronellal, α-terpineol, p-cymene, cryptone were calculated to be 1.008, 2.483, 0.351, 0.706, 0.847 and 0.497 µg/5 µL, respectively.

None

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the test conditions, eucalyptus oil constituents were considered as possibly harmful and irritant to the skin.
Executive summary:

In a study, eucalyptus oil was obtained from the leaves of Eucalyptus globulus (source: waste and uncultivated areas of Lahore, Pakistan) and purified to isolate its active compounds: 1,8-cineole, β-caryophyllene, citronellal, α-terpineol, p-cymene, cryptone (9.39 %) and other minor constituents. Each fraction (10 mg) was dissolved in acetone (10 mL) and applied to the ear of groups of albino mice (10/dose) at the dose levels of 0.078125-20 µg/5 µL. The total number of red ears per dilution and ID50 (Irritant dose in 50 % individuals) were calculated by probit analysis.

The ID50 values for 1,8-cineole, β-caryophyllene, citronellal, α-terpineol, p-cymene, cryptone were calculated to be 1.008, 2.483, 0.351, 0.706, 0.847 and 0.497 µg/5 µL, respectively.

Under the test conditions, eucalyptus oil constituents were considered as possibly harmful and irritant to the 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 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 (2015) 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 without further testing according to the rules for classification of mixtures of Regulation (EC) No 1272/2008

Constituent

 

CAS

Classification

Source

Pinene alpha

80 -56 -8

H315

ECHA C&L inventoryself classification

Pinene beta

127 -91 -3

H315

ECHA C&L inventory - self classification

 Myrcene beta  123 -35 -3  H315

ECHA C&L inventory - self classification

 dipentene  138 -86 -3

H315

Harmonised classification Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation)

 alpha-terpineol  98 -55 -5

H315

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 vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2013-03-18 to 2013-03-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 405 and in compliance with GLP.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Monitoring Programme (inspected on 2012-07-10)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: New Zealand White (Hsdlf:NZW) strain rabbit
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: twelve to twenty weeks old.
- Weight at study initiation: 2.38 to 2.95 kg.
- Housing: individually housed in suspended cages.
- Diet (e.g. ad libitum): free access to food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (e.g. ad libitum): free access to drinking water.
The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Acclimation period: at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye of each rabbit served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
The eyes were not rinsed after administration of the test item.
Observation period (in vivo):
approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3
Details on study design:
ANALGESIA
Sixty to seventy minutes prior to administration of the test item, buprenorphine 0.01 mg/kg was administered by subcutaneous injection (SC) to provide a therapeutic level of systemic analgesia.

LOCAL ANESTHESIC
Nineteen and five minutes prior to administration of the test item, a local anesthetic (0.5% tretracaine hydrochloride) was applied to each eye.

PAIN MANAGEMENT
Eight hours following the test item administration, buprenorphine 0.01 mg/kg SC and meloxicam 0.5 mg/kg SC was administered to provide a therapeutic level of systemic analgesia. The treated animals were checked for signs of pain and suffering approximately twelve hours later. No further analgesia was required.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not rinsed after administration of the test item.

SCORING SYSTEM: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49.

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope.

OTHER
Any clinical signs of toxicity, if present, were also recorded.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: Mean 24-48-72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations. All treated eyes appeared normal at the 72-Hour observation.
Other effects:
One animal showed no gain in body weight and two animals showed expected gain in body weight during the study.

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

2 / 2 / 2

2 / 2 / 2

2 / 2 / 2

24 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 2 / 1

1 / 1 / 1

0 / 0 / 0

48 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

1 / 1 / 1

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0.7 / 1 / 0.7

0.7 / 0.7 / 0.7

0 / 0 / 0

Reversibility*)

-

-

-

c.

c.

c.

Average time (unit) for reversion

-

-

-

72 h

72 h

24 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0/0.0/0.0 for cornea opacity, 0.0/0.0/0.0 for iris lesions, 0.7/1.0/0.7 for redness of the conjunctivae and 0.7/0.7/0.7 for chemosis.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted Eucalyptus globulus oil was instilled initially into the right eye of a single New Zealand White rabbit. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. The eyes were not rinsed after administration of Eucalyptus globulus oil. The left eye of each rabbit served as control. Animals were observed 1, 24, 48 and 72 hours after dosing under a light source from a standard ophthalmoscope. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations. All treated eyes appeared normal at the 72-Hour observation.

One animal showed no gain in body weight and two animals showed expected gain in body weight during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0/0.0/0.0 for cornea opacity, 0.0/0.0/0.0 for iris lesions, 0.7/1.0/0.7 for redness of the conjunctivae and 0.7/0.7/0.7 for chemosis.

Under the test conditions, Eucaltus globulus oil is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

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

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
In accordance with section 1.1 (Use of existing data) of Annex XI to the REACH Regulation, the in-vitro eye irritation study (required in section 8.2) does not need to be conducted as a reliable in-vivo study is available and provides sound conclusive evidence that the substance is non-irritating.
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

A weight-of-evidence analysis, taking all existing and relevant data, was used to conclude on the skin irritation potential of Eucalyptus oil. The decision of classification as skin irritant was based on the following arguments:

1 - Existing human data: According to Saeed and Sahbir (1998), irritation due to Eucalyptus oil was observed in the local people, who deals with the manufacture of cosmetics and liniments, where this oil was used as their main ingredient. The composition of the Eucalyptus oil tested is not similar to the submitted dossier, therefore the data by itself was not considered sufficiently adequate to conclude on classification.

2 - Existing animal data from irritation study: Skin irritation was observed in a reliable acute dermal toxicity study (Moreno, 1973) at the dose of 5000 mg/kg bw. Dermal reactions noted were slight redness (5/10 rabbits), moderate redness (3/10 rabbits) and moderate oedema (10/10 rabbits) at the site of application. Adequate scoring of skin effects was not provided, therefore it was not possible to take a decision of classification based solely on this study.

3 - Existing data on constituents: As detailed on the publication of Saeed and Sahbir, irritant effect of Eucalyptus oil is mainly due to the monoterpenes present in oil. Indeed, more than 10% of the Eucalyptus oil constituents are classified as skin irritant (i.e. pinene, terpineol). Therefore according to the Regulation (EC) No 1272/2008, the mixture should be classified.

4- Classification of constituents: 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. Alpha pinene, Limonene, Terpineol alpha, Beta myrcene and beta pinene, are all classified as Skin irritant (self or harmonised classification) and are presents above the CLP generic concentration limit of 10%. Therefore, the registered substance is classified as skin irritant according to the Regulation (EC) No 1272/2008.

Eye irritation:

Eucalyptus oil is not a skin corrosive and no damage to the eyes was reported in existing in vitro and/or in vivo studies on more than 90% of Eucalyptus oil constituents. Based on the whole data available, an in vitro test to assess corrosivity was not justified. However, based on the complexity of the substance and on the absence on in vivo data on its major constituent, a new in vivo test was performed.

This in vivo eye irritation study was performed according to the OECD guideline No. 405, and in compliance with GLP (Pooles, 2013). No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations. All treated eyes appeared normal at the 72-Hour observation. One animal showed no gain in body weight and two animals showed expected gain in body weight during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0/0.0/0.0 for cornea opacity, 0.0/0.0/0.0 for iris lesions, 0.7/1.0/0.7 for redness of the conjunctivae and 0.7/0.7/0.7 for chemosis.

Under the test conditions, Eucalyptus globulus oil is not classified as irritating to eyes


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, GLP-compliant and of high quality (Klimisch score = 1).

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self-classification:

Based on the available information the substance is classified as:

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

No additional self-classification is proposed regarding eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EC. No information was available regarding respiratory irritation.