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Diss Factsheets

Administrative data

Description of key information

Skin irritation: Read across within citrus oils and major constituent limonene: irritating

 

Eye irritation: Read across within citrus oils and major constituent limonene: not irritating

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:
July 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Very concise report, but the study seems reliable. No data on environmental conditions. No Guideline followed and study not performed under GLP.
Qualifier:
no guideline followed
Principles of method if other than guideline:
An Acute Dermal Toxicity Limit test was performed as a standard acute method. Six male/female rabbits were prepared by clipping their trunks free from hair. Two areas on the back of each rabbit were selected: one area of skin was abraded; the remaining area was left intact. A dose of 5 ml/kg of liquid Lemon oil was applied to the skin of each of a group of rabbits. Liquid test material was delivered under a rubber sleeve by using a hypodermic syringe; then the sleeve was covered with Webril padding. The rabbits were fitted with a collar to prevent the removal of the wrappings. 24 hours later, the binders were removed, and the local dermal reactions were scored according to the method of Draize. Toxic effects, dermal reactions, and mortality were recorded daily for 14 days. A necropsy was performed on animals that died during the course of the study and on those animals which were killed (by air embolism) at termination.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5-3.0 kg
- Housing: Individually
- Diet (e.g. ad libitum): Commercial diet
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS: No data

IN-LIFE DATES: No data
Type of coverage:
occlusive
Preparation of test site:
other: Intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 ml/kg
Duration of treatment / exposure:
24 hours
Observation period:
24 hours and 14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Not defined
- % coverage: 10% (240 cm2)
- Type of wrap if used: Rubber sleeve with Webril padding

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: after 24 hours the binders were removed

SCORING SYSTEM: Draize method
Irritation parameter:
erythema score
Time point:
other: 24 hours
Score:
>= 2 - <= 4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 6/6 animals
Irritation parameter:
edema score
Time point:
other: 24 hours
Score:
>= 1 - <= 3
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4/6 animals
Irritant / corrosive response data:
Skin irritation:
- Erythema score: between 2-4 in all animals
- Edema score: between 1-3 in 4 animals
- Discoloration: noted in 1 animal
- Scaling: noted in 5 animals
- Eschar formation: noted in 5 animals
Other effects:
1 out of 6 animals died during study.

Classification of skin irritation is based on acute dermal toxicity test. No tissue damage observed at termination.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
An Acute Dermal Toxicity Limit test was performed as a standard acute method. As no detailed scoring data is available, it is not possible to classify lemon oil according to the EU classification criteria outlined in 67/548/EEC and 1272/2008. However, the available scores at 24 hrs indicate lemon oil should be considered irritating to the skin.
Executive summary:

Skin irritation potential of lemon oil was determined in an acute dermal toxicity limit test, which was performed as a standard acute method. Six male/female rabbits were prepared by clipping their trunks free from hair. Two areas on the back of each rabbit were selected: one area of skin was abraded; the remaining area was left intact. A dose of 5 ml/kg of liquid Lemon oil was applied to the skin of each of a group of rabbits. The test material was delivered under a rubber sleeve by using a hypodermic syringe; then the sleeve was covered with Webril padding. The rabbits were fitted with a collar to prevent the removal of the wrappings. The binders were removed 24 hours later, and the local dermal reactions were scored according to the method of Draize. Toxic effects, dermal reactions, and mortality were recorded daily for 14 days. A necropsy was performed on animals that died during the course of the study and on those animals which were killed (by air embolism) at termination.

Observed skin irritation was as follows: erythema score: between 2-4 in all animals; edema score: between 1-3 in 4 animals; Discoloration: noted in 1 animal; Scaling: noted in 5 animals; Eschar formation: noted in 5 animals. 1 out of 6 animals died during study. As no detailed scoring data is available, it is not possible to classify lemon oil according to the EU classification criteria outlined in 67/548/EEC and 1272/2008. However, the available scores at 24 hrs indicate lemon oil should be considered irritating to the skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
14 January 2003 - 02 February 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Performed under GLP. Due to the read-across purpose it was given a Klimisch 2 rating, in accordance with the ECHA Practical guide #6 on the reporting of read-across in IUCLID.
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:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on theobserved erythema and oedema in a skin irritation study according to OECD404, and according to EU criteria, Cold Pressed Orange Oil was considered irritating to skin and must be classified R38 "Irritating to skin", according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with 67/548/EEC, 2001/59/EC and 99/45/EC. However according to the classification criteria outlined in 1272/2008 (GHS/CLP), the substance does not have to be classified as such.
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, Cold Pressed Orange Oil was considered irritating to skin and must be classified R38 "Irritating to skin", according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with 67/548/EEC, 2001/59/EC and 99/45/EC. The product must be characterised by the symbol "Xi" and the warning label "irritant”. However according to the classification criteria outlined in 1272/2008 (GHS/CLP), the substance does not have to be classified as such.

Endpoint:
skin irritation / corrosion, other
Remarks:
this is an in vivo study, already performed in 1971
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Documentation acceptable as basic data. No Guideline followed and study not performed under GLP.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Six rabbits (weighing 2.5 to 3.4 kg) were prepared by clipping their trunks free from hair. Two areas on the back of each rabbit were selected: one area of skin was abraded; the remaining area was left intact. 0.5 ml of the test material, Lime oil, was applied to each area. The areas of application were immediately covered with two single layers of gauze approximately one-inch square. The gauze was secured in place with adhesive tape, and the entire trunk wrapped with a nonabsorbent binder. The binder was removed after 24 hours, and the effects (erythema and edema) scored by the Draize method. Scoring was repeated at 72 hours.
GLP compliance:
no
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.

ENVIRONMENTAL CONDITIONS: No data

IN-LIFE DATES: No data
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact
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:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: The areas of application were immediately covered with two single layers of gauze approximately one-inch square. The gauze was secured in place with adhesive tape, and the entire trunk wrapped with a nonabsorbent binder.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: the binder was removed after 24 hours

SCORING SYSTEM: Draize method
Irritation parameter:
primary dermal irritation index (PDII)
Time point:
other: 24 and 72 hours
Score:
ca. 1
Reversibility:
no data
Remarks on result:
other: 6 rabbits
Irritation parameter:
erythema score
Basis:
mean
Remarks:
subtotal
Time point:
other: 24 and 72 hours
Score:
ca. 4
Reversibility:
no data
Remarks on result:
other: 6 rabbits
Irritation parameter:
edema score
Basis:
mean
Remarks:
subtotal
Time point:
other: 24 and 72 hours
Score:
ca. 0
Reversibility:
no data
Remarks on result:
other: 6 rabbits
Irritant / corrosive response data:
Mildly irritating
Other effects:
No data
Interpretation of results:
other: inconclusive
Remarks:
Criteria used for interpretation of results: not specified
Conclusions:
The individual Primary Irritation Index score obtained at 24 and 72 hours was 1.0. Erythema score was 4.0 and edema score was 0. Lime oil appeared to be mildly irritating to rabbit skin. As the report is very concise, the documentation is insufficient for an assessment, and interpretation of results remain inconclusive.
Executive summary:

A primary skin irritation study was carried out to define irritational responses to Lime oil. No guideline has been followed. Six rabbits (weighing 2.5 to 3.4 kg) were prepared by clipping their trunks free from hair. Two areas on the back of each rabbit were selected: one area of skin was abraded; the remaining area was left intact. 0.5 ml of the test material, Lime oil, was applied to each area. The areas of application were immediately covered with two single layers of gauze approximately one-inch square. The gauze was secured in place with adhesive tape, and the entire trunk wrapped with a nonabsorbent binder. The binder was removed after 24 hours, and the effects (erythema and edema) scored by the Draize method. Scoring was repeated at 72 hours. The individual Primary Irritation Index score obtained at 24 and 72 hours was 1.0. Erythema score was 4.0 and edema score was 0. Lime oil appeared to be mildly irritating to rabbit skin. As the report is very concise, the documentation is insufficient for an assessment, and interpretation of results remain inconclusive.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
July 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Test was conducted according to methods similar to OECD 402 (limit test) and was performed pre-GLP. A concise description of the protocol is available and results are acceptable as basic data.
Qualifier:
no guideline followed
Principles of method if other than guideline:
In this skin irritation test of Grapefruit Oil 10 rabbits were used. There are no data on the test system and study design. Mortality, symptomatology, and skin irritation are recorded.
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Duration of treatment / exposure:
No data
Observation period:
No data
Number of animals:
10
Other effects:
No Symptomatology. Mortality: 1 out of 10 rabbbits died.

Slight redness - 6/10

Moderate redness - 2/10

Slight edema - 7/10

Moderate edema - 3/10

No information on scoring system used.

Interpretation of results:
moderately irritating
Conclusions:
Skin irritation results are as follows: Slight redness - 6/10; Moderate redness - 2/10; Slight edema - 7/10; Moderate edema - 3/10. No information on scoring system used is given. Based on these results, the substance is considered moderately irritating.
Executive summary:
In this skin irritation test of Grapefruit Oil 10 rabbits were used. No guideline has been followed and there are no data on the test system and study design. Mortality, symptomatology, and skin irritation are recorded. No symptoms have been observed. 1 out of 10 rabbits died. Skin irritation results are as follows: Slight redness - 6/10; Moderate redness - 2/10; Slight edema - 7/10; Moderate edema - 3/10. No information on scoring system used is given. Based on these results, the substance is considered moderately irritating.
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:
weight of evidence
Study period:
November, 1963
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Very concise report. Chemical identity of substance not reported. No data on environmental conditions, housing and diet. No Guideline followed and study not performed under GLP.
Qualifier:
according to guideline
Guideline:
other: FDA guideline
Principles of method if other than guideline:
Three normal, healthy, albino rabbits were used in this experiment. The method of procedure is that suggested by Dr. Draize and described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", published by the Association of Food and Drug Officials of the. United States. Each animal had 0.1 ml of the test sample instilled into the right eye with no further treatment. The untreated left eye of each animal served as its own control. Both the treated and control eyes were examined every 24 hours for 4 days and then again on the 7th day. The scorings recorded were made according to the Draize scale for scoring ocular lesions.
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
Both the treated and control eyes were examined every 24 hours for 4 days and then again on the 7th day.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize method
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
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
ca. 2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1.6
Max. score:
3
Reversibility:
fully reversible within: 7 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: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis 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: 7 days
Irritant / corrosive response data:
Instillation of Lemon oil as described did not produce any corneal opacity or iris congestion. An intense conjunctival irritation did occur involving chemosis and discharge. On the 7th day of observation the treated eyes were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
Instillation of Lemon oil as described (5%) did not produce any corneal opacity or iris congestion. An intense conjunctival irritation did occur involving chemosis and discharge. On the 7th day of observation the treated eyes were normal. Based on the irritation scores and according to the EU classification criteria outlined in 1272/2008, Lemon oil does not have to be classified as irritating to eye.
Executive summary:

To determine if lemon oil (5%) produces any irritation when instilled into rabbits eyes, 3 normal, healthy, albino rabbits were used in this experiment. The method of procedure is that suggested by Dr. Draize and described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", published by the Association of Food and Drug Officials of the.United States. Each animal had 0.1 ml of the test sample instilled into the right eye with no further treatment. The untreated left eye of each animal served as its own control. Both the treated and control eyes were examined every 24 hours for 4 days and then again on the 7thday. The scorings were made according to the Draize scale for scoring ocular lesions.

Instillation of Lemon oil as described did not produce any corneal opacity or iris congestion. An intense conjunctival irritation did occur involving chemosis and discharge. On the 7thday of observation the treated eyes were normal. Based on irritation scores and according to the EU classification criteria outlined in 1272/2008, Lemon oil (5%) does not have to be classified as irritating to eye.

 

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
20 January 2003 - 30 January 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Performed under GLP. Due to the read-across purpose it was given a Klimisch 2 rating, in accordance with the ECHA Practical guide #6 on the reporting of read-across in IUCLID.
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:
GHS 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)

Additional information

Skin irritation

Three in vivo skin irritation studies with grapefruit, lemon and lime oil showed that these NCSs should be considered irritating, although these studies were not conducted according to the guideline (only one time point was included). The study with orange oil should according to CLP be classified as not skin irritating.

 

A study with D-limonene showed that this major constituent was irritating to the skin. D-limonene is also classified with R38. As D-limonene is present in all NCSs at levels higher than the thresholds mentioned for classification and labeling (in 1272/2008/EC and three studies showed evidence of skin irritation, these results were read across to the other NCSs: The whole citrus NCS group is considered to be irritating to the skin.

 

Eye irritation

Two in vivo eye irritation studies with orange and lemon oil showed that these NCSs are not irritating to the eye. A study with D-limonene showed that this major constituent also was not irritating to the eye. These results are read across to the other citrus NCSs and the whole group is considered non-irritating to the eye.This read across is considered valid because of:1) the similar origin of the oils in this group, 2) the dominant presence of D-limonene in all oils of this group, 3) the same and similar other constituents.


Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the available information, the substance lime oil needs to be classified for skin irritation according to the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).

Based on the available information, lime 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).