Eucalyptus maculata citriodora, ext.

Endpoint summary

Description of key information

- Skin irritation: irritating

- Eye irritation: irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Maximization test (modified after JID 47:393-409):
- Principle of test: To determine the skin sensitizing and skin irriating potential of eucalyptys citriodora
- Short description of test conditions: Forty five healthy inmate volunteers were screened and 32 completed the study.
- Parameters analysed / observed: Skin sensitization and skin irritation.

GLP compliance:

no

Species:

other: human

Strain:

other: not applicable

Type of coverage:

occlusive

Preparation of test site:

other: Pretreatment with Sodium Lauryl sulfate (SLS)

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Not specified

Duration of treatment / exposure:

48 hours

Observation period:

72 hours

Number of animals:

32 humans

Details on study design:

TEST SITE
- Area of exposure: Volar aspects of the forearm
- Type of wrap if used: Occlusion

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified

OBSERVATION TIME POINTS
- 48h and 72h after exposure

SCORING SYSTEM:
-Assumed according to 'Magnusson and Kligman grading scale for the evaluation of challenge patch test reactions' or similar scoring system.

OTHER
-Materials were pretested to determine whether Sodium Lauryl Sulfate (SLS) pretreatment was required; all subjects were pretreated with 5% SLS (patch sites were pretreated for 24 hours). The materials were applied under occlusion on the volar aspects of the forearm for 5 alternate day 48 hour periods. After a 10 -14 day resting period, challenge patches were applied under occlusion to fresh sites for 48 hours. (Challenge application were preceded by 30 -minute applications of 5% SDS, and without SLS on the right side.)

Irritation parameter:

overall irritation score

Basis:

other: human

Time point:

other: observation period after challenge

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No reactions were considered significantly irritant or allergic in the subjects tested.

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of this study, the testing material gave no reactions that were considered significantly irritant or allergic. Based on this result, the test substance does not need to be classified for skin irritation in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

Executive summary:

The sensitizing and irritation potential of Eucalyptus Citrodora on humans was tested in a maximization procedure. Materials were pretested to determine whether Sodium Lauryl Sulfate (SLS) pretreatment was required; all subjects were pretreated with 5% SLS (patch sites were pretreated for 24 hours). The materials were applied under occlusion on the volar aspects of the forearm for 5 alternate day 48 hour periods. After a 10 -14 day resting period, challenge patches were applied under occlusion to fresh sites for 48 hours. (Challenge application were preceded by 30 -minute applications of 5% SDS, and without SLS on the right side.) Under the conditions of this study, the testing material gave no reactions that were considered significantly irritant or allergic. Based on this result, the test substance does not need to be classified for skin irritation in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

3 May - 15 June 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was performed according to methods similar to OECD guideline 402 and under GLP conditio ns. Test groups included only 3 animals of each sex and included animals with abraded skin.

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

For each of four dose levels three male and three female rabbits were used and the skin of two m ales and one female was abraded

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: a suitably licensed dealer
- Age at study initiation: no data
- Weight at study initiation: 1.47 to 2.25 kg
- Fasting period before study: no data
- Housing: galvanized or stainless steel cages
- Diet: growth and maintenance ration from a commercial producer
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

250, 1000, 2000, 3500 mg/kg bw

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 per sex per dose

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 1, 3, 6, and 24 hours; once per day thereafter. Weighing on the day of dosing, after 14 days or upon death
- Necropsy of survivors performed: yes, animals sacrificed at the end of the 14 day observation period as well as non-survivors
- Other examinations performed: clinical signs

SCORING SYSTEM:
- Method according to J.H. Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Remarks on result:

other:

Remarks:

dose 250 mg/kg bw

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.5

Max. score:

4

Remarks on result:

other:

Remarks:

dose 250 mg/kg bw

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1.5

Max. score:

4

Remarks on result:

other:

Remarks:

dose 1000 mg/kg bw

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.16

Max. score:

4

Remarks on result:

other:

Remarks:

dose 1000 mg/kg bw

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Remarks on result:

other:

Remarks:

dose 2000 mg/kg bw

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.5

Max. score:

4

Remarks on result:

other:

Remarks:

dose 2000 mg/kg bw

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Remarks on result:

other:

Remarks:

dose 3500 mg/kg bw

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.66

Max. score:

4

Remarks on result:

other:

Remarks:

dose 3500 mg/kg bw

Irritant / corrosive response data:

At dose 2000 mg/kg bw, following observations were made for 3 animals (#1,#3,#4): skin slightly reddenened and swolle, blanched.
At dose 3500 mg/kg bw, following observations were made for 3 animals (#2,#3,#5): skin slightly reddenened and swolle, blanched.

Other effects:

- Other adverse local effects: Scab formed over test site and sloughing
- Other adverse systemic effects: Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Clinical signs were only noted in the 2 highest dose groups and included slight and severe depression. Gross necropsy showed no effects in the lowest dose groups. From the 1000 mg/kg bw dose group effects on skin (blanching, reddening, swelling, scab formation) and some internal organs (liver and lungs discoloured, kidneys pitted, liver lesions) were observed.

Draize scores at 24 hours after patch removal

Dose	Animal #	Erythema/Oedema score
250 mg/kg bw	1	1/1
	2	1/1
	3	1/1
	4	1/1
	5	1/1
	6	1/1
1000 mg/kg bw	1	2/1
	2	0/0
	3	2/2
	4	1/1
	5	2/2
	6	2/1
2000 mg/kg bw	1	1/2
	2	1/2
	5	1/1
	6	1/1
3500 mg/kg bw	1	1/2
	4	1/1
	6	1/2

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of this study, the testing material is not considered to be a skin irritant and does not need to be classified for skin irritation in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

Executive summary:

Acute dermal toxicity was tested in a test similar to OECD guideline 402. New Zealand white rabbits were acclimated for at least 6 days and dosed in groups of six (3M:3F) at 250, 1000, 2000 and 3500 mg/kg bw. The skin of half the animals (2M:1F) was abraded. Each animal received a single dermal application of the test substance. The test sites were occluded for 24 hours after which the wrap and remaining substance was removed. Animals were observed for clinical signs and mortality 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. All animals were subjected to gross necropsy. Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Clinical signs were only noted in the 2 highest dose groups and included slight and severe depression. Gross necropsy showed no effects in the lowest dose groups. From the 1000 mg/kg bw dose group effects on skin (blanching, reddening, swelling, scab formation) and some internal organs (liver and lungs discoloured, kidneys pitted, liver lesions) were observed. Based on these results, the testing material is not considered a skin irritant and does not need to be classified in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Type of information:

other: constituent classification data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

ECHA database

Qualifier:

no guideline followed

Principles of method if other than guideline:

The classification of constituents of Eucalyptus Citriodora was studied (ECHA website) and used to derive a classification for the UVCB itself using the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) for eye irritation/damage.

GLP compliance:

no

Remarks on result:

other: Not relevant

Remarks on result:

other: Not relevant

The most important constituent with regard to eye irritation/eye damage was determined to be 1,(+)-Citronellal (CAS 2385-77-5), which is present in a typical concentration of 76% and is classified for serious eye irritation (Eye Irrit. 2 / H319).

Interpretation of results:

other: Serious eye irritation

Remarks:

based on CLP criteria

Conclusions:

The major constituent Citronellal is classified for serious eye irritation and is present well above the classification threshold of 10% for mixtures, as given in the CLP Regulation (1272/2008/EC). Based on this information, Eucalyptus Citriodora is also considered to be classified for serious eye irritation (Eye Irrit. 2 / H319).

Executive summary:

The classification of constituents of Eucalyptus Citriodora was studied (ECHA website) and used to derive a classification for the UVCB itself using the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) for eye irritation/damage. The most important constituent with regard to eye irritation/eye damage was determined to be1,(+)-Citronellal (CAS 2385-77-5), which is present in a typical concentration of 76% and is classified for serious eye irritation (Eye Irrit. 2 / H319). This is well above the classification threshold of 10% for mixtures, as given in the CLP Regulation (1272/2008/EC). Based on this information, Eucalyptus Citriodora is also considered to be classified for serious eye irritation (Eye Irrit. 2 / H319).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Acute dermal toxicity was tested in a test similar to OECD guideline 402. New Zealand white rabbits were acclimated for at least 6 days and dosed in groups of six (3M:3F) at 250, 1000, 2000 and 3500 mg/kg bw. The skin of half the animals (2M:1F) was abraded. Each animal received a single dermal application of the test substance. The test sites were occluded for 24 hours after which the wrap and remaining substance was removed. Animals were observed for clinical signs and mortality 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. All animals were subjected to gross necropsy. Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Clinical signs were only noted in the 2 highest dose groups and included slight and severe depression. Gross necropsy showed no effects in the lowest dose groups. From the 1000 mg/kg bw dose group effects on skin (blanching, reddening, swelling, scab formation) and some internal organs (liver and lungs discoloured, kidneys pitted, liver lesions) were observed. Based on these results, the testing material is not considered a skin irritant and does not need to be classified in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

The sensitizing and irritation potential of Eucalyptus Citrodora on humans was tested in a maximization procedure. Materials were pretested to determine whether Sodium Lauryl Sulfate (SLS) pretreatment was required; all subjects were pretreated with 5% SLS (patch sites were pretreated for 24 hours). The materials were applied under occlusion on the volar aspects of the forearm for 5 alternate day 48 hour periods. After a 10 -14 day resting period, challenge patches were applied under occlusion to fresh sites for 48 hours. (Challenge application were preceded by 30 -minute applications of 5% SDS, and without SLS on the right side.) Under the conditions of this study, the testing material gave no reactions that were considered significantly irritant or allergic. Based on this result, the test substance does not need to be classified for skin irritation in accordance with the criteria outlined in the CLP Regulation (1272/2008/EC).

Although the available study data suggests that the substance is not skin irritating, the major constituent 1,(+)-Citronellal (CAS 2385 -77 -5) is currently classified as skin irritant (Skin Irrit. 2 / H315). Based on the fact that this classified constituent represents typically 76% of the composition of Eucalyptus citriodora, which is well above the 10% classification limit for mixtures in the CLP Regulation, it was decided to that the substance needs to be regarded a skin irritant as well.

Eye irritation

The classification of constituents of Eucalyptus Citriodora was studied (ECHA website) and used to derive a classification for the UVCB itself using the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) for eye irritation/damage. The most important constituent with regard to eye irritation/eye damage was determined to be 1,(+)-Citronellal (CAS 2385-77-5), which is present in a typical concentration of 76% and is classified for serious eye irritation (Eye Irrit. 2 / H319). This is well above the classification threshold of 10% for mixtures, as given in the CLP Regulation (1272/2008/EC). Based on this information, Eucalyptus Citriodora is also considered to be classified for serious eye irritation (Eye Irrit. 2 / H319).

Justification for classification or non-classification

Based on the available data, Eucalyptus Citriodora is classified as a skin irritant (Skin Irrit. 2; H315) and eye irritant (Eye Irrit. 2; H319) in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).