Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD404), although some effects were noted.
Eye irritation: not irritating (OECD405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo study was perfomed on rabbits
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 January 2003 - 02 February 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Performed under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Remarks:
Statement of Compliance
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste- 40260 Linxe, France
- Age at study initiation: no data
- Weight at study initiation: 2.30, 2.69 and 2.70 kg
- Housing: in individual boxes installed in conventional air conditioned animal husbanding
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 25 - 51
- Air changes (per hr): conventional air conditioned
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
other: intact
Vehicle:
unchanged (no vehicle)
Controls:
other: yes, 0.5ml of distilled water on the left flank of each animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100% (undiltued)
Duration of treatment / exposure:
4 hours
Observation period:
1 hour and then 24, 48 and 72 hours after removal of the patch, and thereafter daily for 12 days
Number of animals:
3
Details on study design:
TEST SITE:
- Area of exposure: undamaged skin area on the right flank of each animal
- % coverage: no data
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE: no data

SCORING SYSTEM: in compliance with OECD guideline 404, 1992. The skin reactions (Erythema and Eschar formation / Edema formation) were appreciated 1 hour and then 24, 48 and 72 hours after removal of the patch.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: intact skin
Irritant / corrosive response data:
Animal #1 showed slight dryness at day 2 and 9; dryness at day 7 and 8; roughtless, loss of litheness from day 3 to 6. The other 2 animals showed slight dryness at day 11; dryness at day 10; roughtless, loss of litheness from day 2 to 9.
24 hours after the test product application, a slight to moderate erythema associated with a moderate oedema was noted on the treated area. The oedematous reaction was totally reversible the 6th day of the test and the erythematous reaction between the 8th and the 11th day of the test.
Other effects:
The body weight of the animals was within the range commonly recorded for this strain.

The authors conclude that according to the classification established in the Journal Officiel de la Republique Francaise, dated February 21st, 1982, the results obtained, in these experimental conditions, enabled to conclude that the test product, COLD PRESSED ORANGE OIL, according to the scales of interpretation retained, is irritant to skin (Primary Skin Irritation (Psi) = 3.5).

Interpretation of results:
other:
Remarks:
CLP criteria not met
Conclusions:
Some erythema and oedema was observed in a skin irritation study according to OECD404, however according to EU criteria outlined in 1272/2008 (GHS/CLP), the substance does not have to be classified as irritating.
Executive summary:

A skin irritation study was conducted according to OECD guideline 404, 1992, using the test material Cold Pressed Orange Oil on the intact skin of 3 male albino rabbits. Each test site was treated with 0.5 ml of the undiluted test material and was semioccluded for 4 hours. Observations for dermal irritation were made at 1 hour, and then 24, 48 and 72 hours after removal of the patch, and thereafter daily for 12 days. The scoring system was in compliance with OECD 404. The skin reactions (Erythema and Eschar formation/Edema formation) were appreciated 1 hour and then 24, 48 and 72 hours after removal of the patch.

The mean Erythea/Eschar scores, calculated from the numerical values given to the skin irritation of each animal observed at the 24, 48, and 72 hour were 2.0, 1.7, and 2.0. The mean Oedema scores were 2.0, 1.3, and 1.3. Based on these results and according to EU criteria, outlined in 1272/2008 (GHS/CLP), the substance does not have to be classified as irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
an in vivo study was performed with rabbits
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 January 2003 - 30 January 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Performed under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Remarks:
Statement of Compliance
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste- F40260 Linxe, France
- Age at study initiation: no data
- Weight at study initiation: 2.18, 2.49 and 2.59 kg
- Housing: in individual boxes
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: 8 to 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 26 -51
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 100% (undiltued)
Duration of treatment / exposure:
at least 24 hours
Observation period (in vivo):
1 hour after installation, and 24, 48 and 72 hours after, and thereafter daily for 9 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE: no data

SCORING SYSTEM: The numerical scorings recorded were made in compliance with OECD guideline 405, 1987, scoring ocular lesions (corneal, iridic and conjunctival irritation). Ocular examinations were performed on both right and left eyes 1 hour after instillation and 24, 48 and 72 hours later.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal # 1, 2, and 3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal # 1, 2, and 3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal #1, 2, and 3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal #1
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal #2
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal # 3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
The ocular reactions observed during the study remained slight to moderate and only recorded at the conjunctivae level: slight redness in the 3 animals 1 hour after the test product administration and totally reversible between the 8th and the 9th day of the test, associated with a moderate chemosis 1 hour after the test product administration and totally reversible between the 7th and the 8th day of the test.
Other effects:
The body weight of the animals was within the range commonly recorded for this strain.

The authors conclude that according to the classification established in the Journal Officiel de la République Française, dated July 10th, 1992, the results obtained, in these experimental conditions, enabled to conclude that the test product, Cold Pressed Orange Oil, according to the scales of interpretation retained, is slightly irritant for the eye (Maximum Ocular Irritation Index (Max. O.I.=14.0).

Interpretation of results:
other:
Remarks:
not irritating, CLP criteria not met
Conclusions:
In an eye irritation study performed according to OECD405, orange oil did not induce significant or irreversible damage to the rabbit eye. Based on these results and according to the EU criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS), Cold Pressed Orange Oil does not have to be classified and has no obligatory labelling requirement with respect to eye irritation in rabbits.
Executive summary:

The primary eye irritation potential of Cold Pressed Orange Oil was investigated according to OECD test guideline no. 405, 1987. The test item was applied by instillation of 0.1 ml into one eye of each of 3 male New Zealand White rabbits.

The ocular reactions observed during the study remained slight to moderate and only recorded at the conjunctivae level. The mean score was calculated across the 3 scoring times for each animal for corneal opacity, iris lesion, redness and chemosis of the conjunctivae, separately, and was 0.0 for all three animals for corneal opacity and iris lesions, and 1.0 for reddening of the conjunctivae for all three animals. It is concluded that orange oil did not induce significant or irreversible damage to the rabbit eye. Based on these results and according to the EU criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS), Cold Pressed Orange Oil does not have to be classified and has no obligatory labelling requirement with respect to eye irritation in rabbits

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation study according to OECD404, orange oil was applied on the intact skin of three albino rabbits. In all animals, erythema and edema was observed, mean scores being 2.0, 1.7, 2.0 for erythema, and 2.0, 1.3, and 1.3.

The primary eye irritation potential of orange oil was investigated in a study according to OECD405 in three male New Zealand White rabbits. Mean scores were 0.0 for corneal opacity and iris lesions, and 1.0 for reddening of the conjunctivae for all three animals


Effects on skin irritation/corrosion: non irritating

Justification for classification or non-classification

Based on the available information, orange oil has been shown to have some irritating properties when applied to the skin. However, according to the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS), orange oil does not have to be classified as skin irritant.

The results of the primary eye irritation test indicate that the substance orange oil does not need to be classified as eye irritant according to the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).