Registration Dossier

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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The study was conducted to determine the skin irritation index of tea tree oil in the rabbit by the Draize method.
- Short description of test conditions: The undiluted test item was applied to the intact and abraded skin of six New Zealand White rabbits.
- Parameters analysed / observed: Skin irritation reactions and clinical signs of toxicity or abnormal behaviour.
GLP compliance:
no
Specific details on test material used for the study:
- Batch no.: 88/375
- Purity: 100%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: Not specified.
- Age at study initiation: Young mature albino rabbits were used.
- Weight at study initiation: Not specified.
- Housing: Not described.
- Diet: Not specified.
- Water: Not specified.
- Acclimation period: Not specified.
- Temperature: 22°C.
- Humidity: Not specified.
- Air changes: Not specified.
- Photoperiod: Not specified.
Type of coverage:
not specified
Preparation of test site:
other:
Remarks:
Abraded and intact skin were examined for each animal.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Dose: 0.5ml.
Concentration: 100% (undiluted).
Duration of treatment / exposure:
72 hours.
Observation period:
All animals were observed for signs of toxicity and abnormal behaviour during the experimental period. The observation period is not specified.
Number of animals:
6 animals.
Details on study design:
Procedure: P.C.S method number 1 was used.
Area of exposure: Not specified.
Removal of test substance: Not described.
Observation time points: 24 hours and 72 hours.
The Draize scale for scoring skin reactions is shown in the attached scoring system.
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Remarks:
mean
Time point:
other: 24/72 h
Score:
2.5
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Remarks:
mean
Time point:
other: 24/72 h
Score:
3
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Remarks:
mean
Time point:
other: 24/72 h
Score:
3.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Remarks:
mean
Time point:
other: 24/72 h
Score:
3.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Remarks:
mean
Time point:
other: 24/72 h
Score:
3
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Remarks:
mean
Time point:
other: 24/72 h
Score:
3
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Remarks:
mean
Time point:
other: 24/72 h
Score:
1.5
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Remarks:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Remarks:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Remarks:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Remarks:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Remarks:
mean
Time point:
other: 24/72 h
Score:
1.5
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Timepoints
Remarks:
Only 24 h and 72 h timepoints were reported
Irritant / corrosive response data:
Irritation reactions were observed on both intact and abraded skin after treatment with the test sample. The primary irritation index was found to be 5.0.

Table 1. Details on skin irritation reactions.

 Animal No.  Intact Skin  Abraded Skin  Score  Time of Evaluation
 Erythema  Oedema  Erythema  Oedema
 1  2  1  2  1  6  24 hours
 3  2  3  2  10  72 hours
 2  3  2  3  2  10  24 hours
 3  2  3  2  10  72 hours
 3  3  2  3  2  10  24 hours
 4  2  4*  2  12  72 hours
 4  3  2  3  3  11  24 hours
 4  2  4*  2  12  72 hours
 5  3  2  3  2  10  24 hours
 3  2  4*  2  11  72 hours
 6  3  2  3  2  10  24 hours
 3  1  4  2  10  72 hours
 Total  28  29  57  24 hours
 31  34  65  72 hours
 Index  4.7  4.8  4.8  24 hours
 5.2  5.7  5.4  72 hours

Primary Irritation Index: 5.0

* erosion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Given mean values for erythema at 24 and 72 hours of more than 2.3 in all treated animals, Tea Tree Oil is considered to be a Category 2 Irritant.
Executive summary:

Acute dermal irritation testing was carried out on six young mature albino rabbits (NZ). The test sample was administered undiluted, as supplied. All animals were observed for signs of toxicity and abnormal behaviour during the experimental period. Irritation reactions were observed on both intact and abraded skin after treatment with the test sample. The Draize irritation index was found to be 5.0, indicating a severe irritant. Based on GHS criteria, and given mean values for erythema at 24 and 72 hours of more than 2.3 in all treated animals, Tea Tree Oil is considered to be a Category 2 Irritant.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
- Description: Clear colourless liquid.
- Source: Not specified.
- Batch No. of test material: D266
- Purity: 100%
- Expiration date of the batch: 30 November 2014
- Storage condition of test material: Approximately 4°C in the dark.
Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW
Details on test animals or tissues and environmental conditions:
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: Twelve to twenty weeks old
- Weight at study initiation: 2.79 kg or 2.85 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: Free access to food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet was considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Water: Free access to mains drinking water was allowed throughout the study. The drinking water was 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.
- Identification: Each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
- Temperature: The temperature was set to achieve limits of 17 to 23°C. Any occasional deviations from this target were considered not to have affected the purpose or integrity of the study.
- Humidity: The relative humidity was set to achieve limits of 30 to 70%. Any occasional deviations from this target were considered not to have affected the purpose or integrity of the study.
- Air changes: At least 15 changes per hour.
- Photoperiod: Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- Enrichment: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Justification for chosen species: The albino rabbit has been shown to be a suitable model for this type of study and is recommended in the test method. The results of the study are believed to be of value in predicting the likely irritancy potential of Tea Tree Oil to man.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Amount applied: 0.1 mL Tea Tree Oil
Duration of treatment / exposure:
Tea Tree Oil was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of Tea Tree Oil, and then released.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Number of animals or in vitro replicates:
Two rabbits.
Details on study design:
- Scoring system: Immediately after administration of Tea Tree Oil, an assessment of the initial pain reaction was made according to the six point scale shown in the attached Appendix 1. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the Draize Scale for Scoring Ocular Irritation (see the attached Appendix 2).

- Tool used to assess score: Light source from a standard opthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (see 'Any other information on results'). No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-hour observations. Both treated eyes appeared normal at the 72-hour observation.
Other effects:
Individual bodyweights and bodyweight changes are given in Table 3 (see 'Any other information on results'). One animal showed a slight bodyweight loss while the other animal showed expected gain in bodyweight during the study.

Table 1. Individual Scores and Individual Total Scores for Ocular Irritation.

 Rabbit Number and Sex  72426 Male  42463 Male
 IPR = 2  IPR = 2
 Time After Treatment  1 Hour  24 Hours  48 Hours  72 Hours  1 Hour  24 Hours  48 Hours  72 Hours
 CORNEA                
 E = Degree of Opacity  0  0  0  0  0  0  0  0
 F = Area of Cornea Involved  0  0  0  0  0  0  0  0
 Score (E x F) x 5  0  0  0  0  0  0  0  0
 IRIS                
 D  0  0  0  0  0  0  0  0
 Score (D x 5)  0  0  0  0  0  0  0  0
 CONJUNCTIVAE                
 A = Redness  2  2  1  0  2  1  1  0
 B = Chemosis  1  1  0  0  1  1  0  0
 C = Discharge  1  0  0  0  2  0  0  0
 Score (A + B + C) x 2  8  6  2  0  10  4  2  0
 Total Score  8  6  2  0  10  4  2  0

IPR = initial pain reaction

Table 2. Individual Total Scores and Group Mean Scores for Ocular Irritation.

 Rabbit Number and Sex  Individual Total Scores At:
 1 Hour  24 Hours  48 Hours  72 Hours
 72426 Male  8  6  2  0
 42463 Male  10  4  2  0
 Group Total  18  10  4  0
 Group Mean Score  9.0  5.0  2.0  0.0

Table 3. Individual Bodyweights and Bodyweight Changes.

 Rabbit Number and Sex  Individual Bodyweight (kg)  Bodyweight Change (kg)
 Day 0  Day 3
 72426 Male  2.85  2.82  -0.03
 42463 Male  2.79  2.93  0.14
Interpretation of results:
GHS criteria not met
Conclusions:
Tea Tree Oil produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. Tea Tree Oil does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Executive summary:

A GLP-compliant study was performed to assess the irritancy potential of Tea Tree Oil to the eye of the New Zealand White rabbit following the in vitro Bovine Corneal Opacity and Permeability study (Harlan Laboratories Ltd Project number 41104699) which showed the test item not be corrosive or severely irritating to the eye. The method was designed to be compatible with OECD Testing Guideline No. 405 "Acute Eye Irritation/Corrosion" and EU Method B.5 Acute Toxicity (Eye Irritation). A single application of Tea Tree Oil to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 72-hour observation. Tea Tree Oil produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. Tea Tree Oil does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
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)
GLP compliance:
yes
Specific details on test material used for the study:
- Description of test item: Clear colourless liquid
- Source: Not specified
- Batch No.of test material: D266
- Purity: 100%
- Expiration date of the batch: 30 November 2014
- Storage condition of test material: Approximately 4°C in the dark
- Preparation of test material: Tea Tree Oil was used as supplied.
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Eyes from adult cattle were obtained from a local abattoir as a by-product from freshly slaughtered animals. The eyes were excised by an abattoir employee and placed in Hanks' Balanced Salt Solution (HBSS), supplemented with Penicillin/Streptomycin, and transported to the laboratory on ice packs. The eyes were refrigerated on arrival and used within 24 hours of receipt.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
Amount applied: 0.75 mL of Tea Tree Oil or control item
Duration of treatment / exposure:
Tea Tree Oil was applied to isolated bovine corneas for 10 minutes.
Duration of post- treatment incubation (in vitro):
120 minutes
Number of animals or in vitro replicates:
Three corneas for the test material and each control.
Details on study design:
Preparation of corneas: The cornea from each selected eye was removed leaving a 2 to 3 mm rim of sclera to facilitate handling. The iris and lens were peeled away from the cornea. The isolated corneas were immersed (epithelial side uppermost) in a dish containing HBSS until they were mounted in Bovine Corneal Opacity and Permeability (BCOP) holders. The anterior and posterior chambers of each BCOP holder were filled with complete minimum essential medium (MEM) and plugged. The holders were incubated at 32 ± 1°C for at least 60 minutes. At the end of the incubation period each cornea was examined for defects. Only corneas free of damage were used.

Quality check of the corneas: All eyes were macroscopically examined before and after dissection. Only corneas free of damage were used.

Selection of corneas and opacity reading: The medium from both chambers of each holder was replaced with fresh complete MEM. A pre-treatment opacity reading was taken for each cornea using a calibrated opacitometer. The average opacity for all corneas was calculated. Three corneas were numerically allocated to Tea Tree Oil. Three corneas were also numerically allocated to the negative control item and three corneas to the positive control item.

Negative control used: 0.9% w/v sodium chloride solution, manufactured by Laboratoire AGUETTANT, Batch Number 3007650 03, used as supplied.

Positive control used: Ethanol, manufactured by Riedel-de Haën, Lot Number 51540 was used undiluted.

Treatment of corneas: The MEM was removed from the anterior chamber of the BCOP holder and 0.75 mL of Tea Tree Oil or control items were applied to the cornea. The holders were gently tilted back and forth to ensure a uniform application of the item over the entire cornea. Each holder was incubated, anterior chamber uppermost, at 32 ± 1°C for 10 minutes. At the end of the exposure period Tea Tree Oil and the control items were removed from the anterior chamber and the cornea was rinsed three times with fresh complete MEM containing phenol red before a final rinse with complete MEM. A post-treatment opacity reading was taken and each cornea was visually observed. The holders were incubated, anterior chamber facing forward, at 32 ± 1°C for 120 minutes ± 10 minutes. After incubation the holders were removed from the incubator and a final opacity reading was taken. Each cornea was visually observed.

Application of sodium fluorescein: Following the opacity measurement the permeability of the corneas to sodium fluorescein was evaluated. The medium from the anterior chamber was removed and replaced with 1 mL of sodium fluorescein solution (4 mg/mL). The dosing holes were plugged and the holders incubated, anterior chamber uppermost, at 32 ± 1°C for 90 minutes.

Permeability determinations: After incubation the medium in the posterior chamber of each holder was decanted and retained. 360 μL of medium representing each cornea was applied to a designated well on a 96-well plate and the optical density at 492nm (OD492) was measured using the Anthos 2001 plate reader. OD measured at 492nm is within the acceptable range for the measurement of sodium fluorescein. If values greater than 1.500 OD492 were obtained a 1 in 5 dilution of the medium in complete MEM was performed and the measurement repeated. The modified value was multiplied by 5 to reflect the 1 in 5 dilution.

Histopathology: The corneas were retained after testing for possible conduct of histopathology. Each cornea was placed into a pre-labelled tissue cassette fitted with a histology sponge to protect the endothelial surface. The casette was immersed in 10% neutral buffered formalin. It was considered unnecessary to proceed with tissue histopathology.

Scoring system: In Vitro Irritancy Score (IVIS)

Data interpretation: A test item that induces an In Vitro Irritancy Score ≥55.1 is defined as an ocular corrosive or severe irritant.

Criterion for an acceptable test: For an acceptable test the following positive control criterion must be achieved: Ethanol was used for positive control purposes. The test was acceptable if the positive control produced an In Vitro Irritancy Score which fell within two standard deviations of the historical mean for this testing facility. Therefore the In Vitro Irritancy Score should fall within the range of 30.9 to 67.7.
Irritation parameter:
in vitro irritation score
Run / experiment:
Tea Tree Oil
Value:
2.2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
Irritancy score = 2.3
Positive controls validity:
valid
Remarks:
Irritancy score = 44.5
Other effects / acceptance of results:
Individual and mean corneal opacity measurements and individual and mean corneal permeability measurements are given in Table 1 (see 'Any other information on results').

The condition of the cornea post treatment and at the final opacity measurement is given in Table 2 (see 'Any other information on results').

The corneas treated with Tea Tree Oil 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 positive control In Vitro Irritancy Score was within the range of 30.9 to 67.7. The positive control acceptance criterion was therefore satisfied.

Table 1. Individual and Mean Corneal Opacity and Permeability Measurements.

Treatment

Cornea

Number

Opacity              Permeability (OD)  In vitro Irritancy Score
Pre-Treatment Post-Treatment Post-Incubation

Post-Incubation -

Pre-Treatment

 Corrected

Value

 -

Corrected

Value

 (IVIS)

Negative

Control

 1  3  3  6  3  -  0.044  -  -
 2  2  1  3  1  - 0.035  -  -
 3  3  3  4  1  -  0.040  -  -
 -  -  -  -  1.7*  -  0.040**  -  2.3

Positive

Control

 4  3  31  27  24  22.3 2.010  1.970  -
 5  3  27  23  20  18.3 1.980  1.940  -
 6  5  24  24  19  17.3  1.180  1.140  -
 -  -  -  -  -  19.3*** -  1.684***  44.6

Tea Tree

Oil         

 7  3  4  5  2  0.3  0.059  0.019  -
 8  3  6  8  5  3.3  0.042  0.002  -
 9  2  4  6  4  2.3  0.063  0.023  -
 -  -  -  -  -  2.0***  -  0.015***  2.2

OD = Optical density

* = Mean of the post treatment - pre-treatment values

** = Mean permeability

*** = Mean corrected value

Table 2. Corneal Epithelium Condition Post Treatment and Post Incubation.

 Treatment  Cornea Number  Observation
 Post Treatment  Post Incubation
 Negative Control  1  Clear  Clear
 2  Clear  Clear
 3  Clear  Clear
 Positive Control  4  Cloudy  Cloudy
 5  Cloudy  Cloudy
 6  Cloudy  Cloudy
 Tea Tree Oil  7  Clear  Clear
 8  Clear  Clear
 9  Clear  Clear
Interpretation of results:
GHS criteria not met
Conclusions:
Tea Tree Oil was considered not to be an ocular corrosive or severe irritant.
Executive summary:

A GLP-compliant study was performed to assess the ocular irritancy potential of Tea Tree Oil to the isolated bovine cornea. The method was designed to be compatible with the OECD Testing Guideline No. 437 (2009) Bovine Corneal Opacity and Permeability Assay. Undiluted Tea Tree Oil was applied to isolated bovine corneas for 10 minutes followed by an incubation period of 120 minutes. Negative and positive control items were tested concurrently. 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 (IVIS). The in vitro Irritancy scores are as follows: Tea Tree Oil = 2.2; Negative Control = 2.3; Positive Control = 44.5. Tea Tree Oil was considered not to be an ocular corrosive or severe irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation:

Acute dermal irritation testing was carried out in New Zealand White rabbits (Bolt, 1989). Irritation reactions were observed on both intact and abraded skin after treatment with the test sample.  Based on CLP/GHS criteria, and given mean values for erythema at 24 and 72 hours of ≥ 2.3 - ≤ 4.0 in all treated animals, Tea tree oil is considered to be a Category 2 Irritant, H315: Causes skin irritation.

Eye irritation:

A study to assess the ocular irritancy potential of Tea Tree Oil to isolated bovine cornea (Warren, 2012) concluded that tea tree oil was not an ocular corrosive or severe irritant.  Subsequently, a study was performed to assess the irritancy potential of Tea Tree Oil to the eye of the New Zealand White rabbit (Sanders, 2013).  A single application of Tea Tree Oil to the non-irrigated eye of two rabbits produced mean conjunctival redness and chemosis scores of < 2 following grading at 24, 48 and 72 hours.  The treated eyes of both animals appeared normal at the 72-hour observation.  Based on CLP/GHS criteria, it is concluded that tea tree oil should not be classified on the basis of eye irritation potential.