Registration Dossier

Administrative data

Description of key information

Terpineol multiconstituent and alpha-terpineol were found to be irritating to skin in several studies conducted according to OECD guideline 404.

beta-Terpineol was not irritating to skin in rabbits and alpha-terpineol was not irritating to human skin.

Terpineol multiconstituent was found to be irritating to eyes in a GLP study conducted according to OECD guideline 405.

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:
key study
Study period:
2006-01-17 to 2006-02-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study following OECD guidelines without any deviation.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gerome, Linxe, France
- Weight at study initiation: between 2.23 kg and 3.08 kg
- Housing: kept in individual box installed in conventional air conditioned
- Acclimation period: 5 days
- Diet (e.g. ad libitum): supplied from UAR 112, Villemoisson s/Orge, France, ad libitum
- Water (e.g. ad libitum): tap water from public distribution system, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 17 and 22
- Humidity (%): between 30 and 49
- Air changes (per hr): at least 10 cycles
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2006-01-17 To: 2006-02 13
Type of coverage:
semiocclusive
Preparation of test site:
other: shorn by electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Type of wrap if used: strip of surgical adhesive tape
- Area of exposure: approximately 6 cm²

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h
- Washing (if done): residual product is removed, if necessary, using a swab soaked in distilled water or a suitable solvent

SCORING SYSTEM:
Erythema and Eschar formation
0....No erythema
1....Very slight erythema
2....Well definite erythema
3....Moderate to severe erythema
4....Severe erythema (beef redness) with eschars formation preventing grading of erythema
Oedema
0......No oedema
1......Very slight oedema
2......Slight oedema (contour clearly defined)
3......Moderate oedema (raised approx. 1mm)
4......Severe oedema (raised more than 1 mm, and extended beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritant / corrosive response data:
Application of the test substance Terpineol multiconstituent, was associated with a moderate erythema and a slight oedema 24 h after application. The reactions were totally reversible by the 6th day of the test. Skin recovered a normal aspect between the 11th and 14th day of the test.
Other effects:
Skin reactions such as dryness, slight dryness, scab, roughness/loss of lightness were observed from D2 to D12

Table 1: Individual and average scores after 4-hour exposure

OBSERVATIONS

INDIVIDUAL DATA

TOTAL OF INDIVIDUAL DATA

Skin reactions

Observation time

Animal n°

Weight (kg)

Animal n°

Weight (kg)

Animal n°

Weight (kg)

A 7158

Start : 2.64

A7181

Start : 2.23

A7182

Start : 2.43

End : 3.08

End : 2.52

End : 2.88

Erythema and eschar

24 h

48 h

72 h

3

3

3

9

3

3

3

9

3

2

2

7

Total

9                           8 

8

Mean

3.0                        2.7

2.7

Oedema

24 h

2

2

2

6

48 h

2

2

2

6

72 h

2

1

1

4

Total

6

5

5

 

Mean

2.0

1.7

1.7

 

Table 2: Individual skin reactions

OBSERVATIONS

INDIVIDUAL DATA

Skin reactions

Observation time

Animal n°

Weight (kg)

Animal n°

Weight (kg)

Animal n°

Weight (kg)

A 7158

Start : 2.64

A7181

Start : 2.23

A7182

Start : 2.43

End : 3.08

End : 2.52

End : 2.88

Erythema and eschar

1 h

2

2

2

24 h

3

3

3

48 h

3

3

3

72 h

3

2

2

Day 4

3

2

2

Day 5

0

0

0

Day 6

0

0

0

Day 7

0

0

0

Day 8

0

0

0

Day 9

0

0

0

Day 10

0

0

0

Oedema formation

1 h

2

2

2

24 h

2

2

2

48 h

2

2

2

72 h

2

1

1

Day 4

2

1

1

Day 5

0

0

0

Day 6

0

0

0

Day 7

0

0

0

Day 8

0

0

0

Day 9

0

0

0

Day 10

0

0

0

Interpretation of results:
irritating
Conclusions:
Terpineol multiconstituent should be classified as irritating to skin, in category 2 according to CLP regulation (EC) No 1272/2008.
Executive summary:

A dermal irritation study was conducted according to OECD guideline 404 in compliance with GLP. Three healthy adult New Zealand white rabbits were exposed to 0.5 mL/rabbit of Terpineol multiconstituent on clipped skin of the dorsal area for 4 hours in semi-occlusive conditions. Skin reactions were observed at 1, 24, 48 and 72 h after removal of the substance until day 10. 1 hour after patch removal there was moderate erythema with slight oedema in all animals. Mean individual scores for 24, 48 and 72 h observation time points were 3, 2.7 and 2.7 for erythma and 2, 1.7 and 1.7 for oedema. The reactions were reversible within 5 days for all animals. The skin recovered a normal aspect between the 11th and the 14th day of the test.

Terpineol multiconstituent should be classified as irritant category 2 according to CLP Regulation (EC) No 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Beta-terpineol one of the main impurities of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on beta-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: day 2
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: day 2
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: day 7
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: day 2
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: day 2
Irritant / corrosive response data:
Application of the test substance was associated with erythema in all animals 1 h after patch removal with complete reversibility of these effects at 24 h for 2 animals and after 7 days for the third animal. Two animals had very slight edema 1 and 24 h after patch removal, but completely reversed at 48 h (see table 1).
Other effects:
None

Table 1: individual scores for dermal reactions

 

Time score for erythema

Animal number

1 h

Day 1

Day 2

Day 3

Day 7

6766

1

1

0

0

0

6767

1

1

0

0

0

6768

1

2

2

1

0

 

Time score for edema

Animal number

1 h

Day 1

Day 2

Day 3

Day 7

6766

0

0

0

0

0

6767

1

1

0

0

0

6768

1

1

0

0

0

Interpretation of results:
not irritating
Conclusions:
beta-Terpineol does not need to be classified according to CLP Regulation (EC) No 1272/2008.
Executive summary:

A dermal irritation study was conducted according to OECD guideline 404. Three healthy female New Zealand white rabbits were exposed to 0.5 mL/rabbit of beta-terpineol for 4 hours in occlusive conditions. Skin reactions were observed at 1, 24, 48 and 72 h after removal of the patch and at day 7. Mean individual scores for 24, 48 and 72 h observation time points were 0.3, 0.3 and 1.7 for erythma and 0, 0.3 and 0.3 for edema. All reactions were reversible within day 2, except in one animal where erythema reactions were resersible within 7 days.

Therefore, beta-terpineol is not classified according to CLP Regulation (EC) No 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
overall irritation score
Remarks on result:
no indication of irritation
Other effects:
- No positive reaction was observed in the volunteers exposed to α terpineol.
- Positive control produced positive reactions in 16/30 volunteers.

None

Interpretation of results:
not irritating
Conclusions:
alpha-Terpineol is not a skin irritant in humans.
Executive summary:

In a dermal irritation study, 30 human volunteers were dermally exposed to 0.2 mL of α terpineol, under a Hill top chamber containing a Webril pad applied to upper arm for 4 hours. Irritation was scored at 24, 48 and 72 hours after exposure. Sodium dodecyl sulfate (20%) was used as concurrent positive control.

 

No positive reaction was observed in the volunteers exposed to alpha-terpineol. Positive control produced positive reactions in 16/30 volunteers.

 

Therefore, alpha-terpineol is not a skin iritant in humans.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
- Thickening and/or marked desquamation from skin surface was observed in all animals on Day 7
- See table 1 for individual animal scores
Other effects:
No data

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.

1*

2*

3**

Erythema

1 hour

0

2

2

24 hours

1

2

2

48 hours

2

2

2

72 hours

2

2

3

Day 7

1

2

3

Mean (24 hours + 48 hours + 72 hours)

1.7

2

2.3

Oedema

1 hour

1

2

2

24 hours

2

3

3

48 hours

2

2

3

72 hours

2

2

3

Day 7

1

1

3

Mean (24 hours + 48 hours + 72 hours)

2

2.3

3

* marked desquamation from skin surface after 7 days

** thickening and marked desquamation from skin surface after 7 days

Interpretation of results:
Category 2 (irritant)
Conclusions:
Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP, three albino rabbits were dermally exposed to 0.5 mL of undiluted alpha-terpineol, under a semi-occlusive patch for 4 hours to intact skin of the flank. Animals were then observed for 7 days. Irritation was scored by the method of Draize at 1, 24, 48 and 72 hours and 7 days after exposure.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1.67, 2, 2.3 for erythema score and 2, 2.3, 3 for oedema score. Signs of erythema and oedema, as well as desquamation from skin surface, were observed in all animals on Day 7; therefore the reversibility of the effects could not be assessed. In this study, alpha terpineol was found to be skin irritant when applied topically to the rabbit.

 

Therefore, based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272 /2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.17
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.59
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
- Slight to marked desquamation from skin surface was observed in all animals on Day 7
- See table 1 for individual animal scores
Other effects:
No data

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.

#1*

#2**

#3**

#4**

Erythema

1 hour

2

2

2

1

24 hours

2

2

2

2

48 hours

2

3

2

2

72 hours

2

3

2

2

Day 7

2

2

2

1

Mean (24 hours + 48 hours + 72 hours)

2

2.7

2

2

Oedema

1 hour

2

3

2

2

24 hours

3

3

3

2

48 hours

3

3

2

2

72 hours

3

3

3

1

Day 7

1

3

3

0

Mean (24 hours + 48 hours + 72 hours)

3

3

2.7

1.7

* marked desquamation from skin surface after 7 days

** slight desquamation from skin surface after 7 days

Interpretation of results:
Category 2 (irritant)
Conclusions:
Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP, four albino rabbits were dermally exposed to 0.5 mL of undiluted alpha-terpineol, under a semi-occlusive patch for 4 hours to intact skin of the flank. Animals were then observed for 7 days. Irritation was scored by the method of Draize at 1, 24, 48 and 72 hours and 7 days after exposure.

Mean individual scores at 24, 48 and 72 h after exposure for the 4 animals were 2, 2.67, 2, 2 for erythema score and 3, 3, 2.67, 1.67 for oedema score. Signs of erythema and oedema, as well as desquamation from skin surface, were observed in all animals on Day 7; therefore the reversibility of the effects could not be assessed. In this study, alpha terpineol was found to be skin irritant when applied topically to the rabbit.

 

Therefore, based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
1.92
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.08
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
- Slight to marked desquamation from skin surface was observed in all animals on Day 7
- See table 1 for individual animal scores
Other effects:
No data

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.

#1*

#2*

#3*

#4**

Erythema

1 hour

2

2

1

2

24 hours

2

2

2

2

48 hours

2

2

2*

2

72 hours

2

2

1*

2

Day 7

1

2

0

1

Mean (24 hours + 48 hours + 72 hours)

2

2

1.7

2

Oedema

1 hour

2

2

0

1

24 hours

3

2

1

3

48 hours

3

2

1

3

72 hours

2

2

0

3

Day 7

0

2

0

1

Mean (24 hours + 48 hours + 72 hours)

2.7

2

0.7

3

 

* slight desquamation from skin surface after 7 days

** marked desquamation from skin surface after 7 days

Interpretation of results:
Category 2 (irritant)
Conclusions:
Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP, four albino rabbits were dermally exposed to 0.5 mL of undiluted alpha-terpineol, under a semi-occlusive patch for 4 hours to intact skin of the flank. Animals were then observed for 7 days. Irritation was scored by the method of Draize at 1, 24, 48 and 72 hours and 7 days after exposure.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 4 animals were 2, 2, 1.7, 2 for erythema score and 2.7, 2, 0.7, 3 for oedema score. Signs of erythema and oedema, as well as desquamation from skin surface, were observed in all animals on Day 7; therefore the reversibility of the effects could not be assessed. In this study, alpha terpineol was found to be skin irritant when applied topically to the rabbit.

 

Therefore, based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Other effects:
No data

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.

1*

2*

3**

Erythema

1 hour

0

2

2

24 hours

1

2

2

48 hours

2

2

2

72 hours

2

2

3

Day 7

1

2

3

Mean (24 hours + 48 hours + 72 hours)

1.67

2

2.33

Oedema

1 hour

1

2

2

24 hours

2

3

3

48 hours

2

2

3

72 hours

2

2

3

Day 7

1

1

3

Mean (24 hours + 48 hours + 72 hours)

2

2.33

3

* marked desquamation from skin surface after 7 days

** thickening and marked desquamation from skin surface after 7 days

Interpretation of results:
Category 2 (irritant)
Conclusions:
Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a primary dermal irritation study performed similarly to OECD guideline 404 and in compliance with GLP, three female New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted alpha-terpineol, under a semi-occlusive patch for 4 hours to clipped dorsal skin (6 cm2). Animals were then observed for 7 days. Irritation was scored at 1, 24, 48, 72 and 168 hours after exposure.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1.7, 2, 2.3 for erythema score and 2, 2.3, 3 for oedema score.

Signs of erythema and oedema, as well as thickening and/or marked desquamation from skin surface, were observed in all animals on Day 7; therefore the reversibility of the effects could not be assessed.

In this study, alpha-terpineol was found to be skin irritant when applied topically to the rabbit.

 

Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272 /2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Alpha-terpineol is one of the main constituents of multiconstituent substance TERPINEOL MULTICONSTITUENT. Therefore, data on alpha-terpineol can be used for extrapolation to TERPINEOL MULTICONSTITUENT.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Other effects:
No data

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.

1*

2**

3**

4***

Erythema

1 hour

2.00

2.00

2.00

1.00

24 hours

2.00

2.00

2.00

2.00

48 hours

2.00

3.00

2.00

2.00

72 hours

2.00

3.00

2.00

2.00

Day 7

2.00

2.00

2.00

1.00

Mean (24 hours + 48 hours + 72 hours)

2.00

2.67

2.00

2.00

Oedema

1 hour

2.00

3.00

2.00

2.00

24 hours

3.00

3.00

3.00

2.00

48 hours

3.00

3.00

2.00

2.00

72 hours

3.00

3.00

3.00

1.00

Day 7

1.00

3.00

3.00

0.00

Mean (24 hours + 48 hours + 72 hours)

3.00

3.00

2.67

1.67

* slight desquamation after 7 days

** marked desquamation after 7 days

*** desquamation after 7 days

Interpretation of results:
Category 2 (irritant)
Conclusions:
Based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a primary dermal irritation study performed similarly to OECD guideline 404 and in compliance with GLP, four female New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted alpha-terpineol, under a semi-occlusive patch for 4 hours to clipped dorsal skin (2.5 cm2). Animals were then observed for 7 days. Irritation was scored at 1, 24, 48, 72 and 168 hours after exposure.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 4 animals were 2, 2.7, 2, 2 for erythema score and 3, 3, 2.7, 1.7 for oedema score. Signs of erythema and oedema, as well as desquamation from skin surface, were observed in all animals on Day 7; therefore the reversibility of the effects could not be assessed. In this study, alpha-terpineol was found to be skin irritant when applied topically to the rabbit.

 

Therefore, based only on the scores at 24, 48 and 72 h (reversibility of the effects not taken into account), alpha-terpineol is classified in ‘Category 2: Irritant’ according to CLP Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Several studies, identified as key studies because they were conducted according to OECD guideline 404, showed that terpineol multiconstituent and alpha-terpineol were irritating to skin in rabbits but that beta-terpineol was not (although it was used in occlusive conditions). Also, in a study with human volunteers, alpha-terpineol applied undiluted in occlusive conditions for 4 h was not irritating to human skin.

One GLP study conducted according to OECD guideline 405 using terpineol multiconstituent showed that it is irritating to eyes.


Justification for classification or non-classification

Terpineol multiconstituent and alpha-terpineol were found to be irritating to skin in rabbits in several GLP studies conducted according to OECD guideline 405. Therefore, terpineol multiconstituent is classified as irritating to skin in category 2 according to CLP Regulation (EC) No 1272/2008.

One study showed that terpineol multiconstituent was irritating to eyes, therefore terpineol multiconstituent is classified as irritating to eyes, in category 2 according to CLP Regulation (EC) No 1272/2008.