Orange, sweet, ext.

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Orange, sweet, ext.

EC Number:

232-433-8

EC Name:

Orange, sweet, ext.

Cas Number:

8028-48-6

Molecular formula:

This reference substance is a UVCB of the NCS type. It is a complex mixture of compounds and therefore molecular formula, molcular weight, and structural formula cannot be given.

IUPAC Name:

Essential oil of orange obtained from the peel of Citrus sinensis (Rutaceae) by expression and/or distillation, including cold pressed, distilled, terpenes and essence qualities

Constituent 2

Reference substance name:

Cold pressed Orange oil

IUPAC Name:

Cold pressed Orange oil

Details on test material:

- Name of test material (as cited in study report): Cold pressed Orange oil
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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.

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.