Registration Dossier

Administrative data

Description of key information

Skin corrosion: Not corrosive based on read-across from alpha-Terpineol: OECD TG 404

Skin irritation: Skin iritant Cat 2 based on read-across from alpha-Terpineol: OECD TG 404

Eye irritation: Eye irritation Cat 2 based on read-across from Terpineol multi: OECD TG 405

Respiratory inhalation: Not a respiratory irritant in absence of human data for Terpene hydrocarbon alcohols and Terpineols and absence of corrosion of Terpineol (alpha and multi)

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across from a guideline study
Justification for type of information:
The read-across justification is presented in the Endpoint summary Irritation. The accompanying files are also attached there.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: read-across from alpha-Terpineol
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.44
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: read-across from alpha-Terpineol
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
Remarks on result:
other: read-across from alpha-Terpineol
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.58
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: read-across from alpha-Terpineol
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
Remarks on result:
other: read-across from alpha-Terpineol
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
Remarks on result:
other: read-across from alpha-Terpineol
Interpretation of results:
other: Skin irritant Cat. 2
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
The substance is considered a skin irritant Cat 2.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
no details on test animals and environmental conditions; no details on patch material; observations not followed until the reversibility of the effects (only 7 days)
Justification for type of information:
The in vivo test was performed before the REACH regulation came into force, requesting in vitro studies. This information is used for read across to Terpene hydrocarbon alcohols
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
. There is no certificate of analysis of the test substance; no details on test animals and environmental conditions; no details on patch material; and observations are not followed until the reversibility of the effects (only 7 days).
GLP compliance:
yes
Species:
rabbit
Strain:
other: albino
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
Test 1: 3
Test 2&3: 4
Details on study design:
SCORING SYSTEM: Draize scoring system
- tested in a multi-patch study
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Test 1
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.44
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Test 1
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
Remarks on result:
other: Test 2
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
2.58
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Test 2
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
Remarks on result:
other: Test 3
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
Remarks on result:
other: Test 3
Irritant / corrosive response data:
Test 1: Two animals showed marked desquamation at the 7 day time interval. The other animal showed thickening and marked desquamation of the skin surface at the 7 day time interval.
Test 2: One animal showed slight desquamation at the 7 day time interval. The three other animals showed marked desquamation at the 7 day time interval.
Test 3: Two animals showed slight desquamation at the 7 day time interval. One animal showed slight desquamation at the 2, 3, and 7 day time interval. One animal showed marked desquamation at the 7 day time interval

 Test 1

 

1 hr

1 day

2 days

3 days

7 days

Mean (24, 48, 72 hrs)

Animal No. 1

Erythema

0

1

2

2

1

1.67

Oedema

1

2

2

2

1

2

Animal No. 2

 

Erythema

2

2

2

2

2

2

Oedema

2

3

2

2

1

2.33

Animal No. 3

 

Erythema

2

2

2

3

3

2.33

Oedema

2

3

3

3

3

3

 

Test 2

 

1 hr

1 day

2 days

3 days

7 days

Mean (24, 48, 72 hrs)

Animal No. 1

Erythema

2

2

2

2

2

2

Oedema

2

3

3

3

1

3

Animal No. 2

 

Erythema

2

2

3

3

2

2.67

Oedema

3

3

3

3

3

3

Animal No. 3

 

Erythema

2

2

2

2

2

2

Oedema

2

3

2

3

3

2.67

Animal No. 4

 

Erythema

1

2

2

2

1

2

Oedema

2

2

2

1

0

1.67

 

Test 3

 

1 hr

1 day

2 days

3 days

7 days

Mean (24, 48, 72 hrs)

Animal No. 1

Erythema

2

2

2

2

1

2

Oedema

2

3

3

2

0

2.67

Animal No. 2

 

Erythema

2

2

2

2

2

2

Oedema

2

2

2

2

2

2

Animal No. 3

 

Erythema

1

2

2

1

0

1.67

Oedema

0

1

1

0

0

0.67

Animal No. 4

 

Erythema

2

2

2

2

1

2

Oedema

1

3

3

3

1

3

Interpretation of results:
other: Skin irritant Cat. 2
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals of the first test were 1.67, 2 and 2.33 for erythema score and 2, 2.33 and 3 for edema score. For the second test the mean individual scores were 2, 2.67, 2 and 2 for erythema score and 3, 3, 2.67 and 1.67 for edema score. For the third test the mean individual scores were 2, 2, 1.67 and 2 for erythema score and 2.67, 2, 0.67 and 3 for edema score. Under the test conditions the substance is considered to be irritating to the skin because the average oedema score exceeded 2.5 (CLP) and the effects were not fully reversible within the observation period of 7 days
Executive summary:

In three primary dermal irritation studies performed according to OECD guideline 404 and in compliance with GLP, three or 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 3 animals of the first test were 1.67, 2 and 2.33 for erythema score and 2, 2.33 and 3 for edema score. For the second test the mean individual scores were 2, 2.67, 2 and 2 for erythema score and 3, 3, 2.67 and 1.67 for edema score. For the third test the mean individual scores were 2, 2, 1.67 and 2 for erythema score and 2.67, 2, 0.67 and 3 for edema score. Under the test conditions the substance is considered to be irritating to the skin because the average oedema score exceeded 2.5 and the effects were not fully reversible within the observation period of 7 days.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across information
Justification for type of information:
The read-across justification is presented in the Endpoint summary Irritation. The accompanying files are also attached there.
Reason / purpose:
read-across source
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: read-across from Terpineol multi
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: read-across from Terpineol multi
Interpretation of results:
other: Eye irritant Cat. 2
Remarks:
according to EU CLP (EC No.1272/2008 and its amendments).
Conclusions:
The substance is an Eye irritant Cat. 2.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-02-20 to 2006-02-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The in vivo test was performed before the REACH regulation came into force, requesting in vitro studies. This information is used for read across to Terpene hydrocarbon alcohols
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gerome, Linxe, France
- Weight at study initiation: between 2.15 and 2.57 kg
- Housing: individual box installed in conventional air conditioned
-Diet(ad libitum): supplied by UAR, Villemoison s/Orange, France, ad libitum
-Water(ad libitum): tap water from public distribution system, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20 and 22
- Humidity (%): between 30 and 37
-Air changes: at least 10 cycles per hour
-Photoperiod (hours dark / hours light): 12/12

IN-LIFE DATES: From: 2006-02-20 To: 2006-02-26
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
Duration of treatment / exposure:
24 hours, no washing done
Observation period (in vivo):
Observations performed at 1, 24, 48 and 72 h up to 21 days
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: According to the scale of lesion scores published in Directive n° 2004/73/EC and OECD guideline n°405
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Remarks:
conjunctiva
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Remarks:
lesion
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Moderate redness at the conjunctival level associated with moderate chemosis and moderate opacity at the corneal level. All effects were totally reversible within the 7th day at the latest.

Table 1: individual and mean scores of Conjunctivae, Iris and Cornea

Animal 

Time after treatment

CONJUNCTIVAE

IRIS

CORNEA

CHEMOSIS (A)

REDNESS (C)

LESION (D)

OPACITY (E)

A 7230

24 hours

1

2

0

2

48 hours

1

2

0

2

72 hours

1

2

0

2

TOTAL

MEAN

3

6

0

6

1.0

2.0

0.0

2.0

A 7231

24 hours

1

2

0

2

48 hours

1

2

0

2

72 hours

1

1

0

2

TOTAL

3

5

0

6

MEAN

1.0

1.7

0 .0

2.0

A 7232

24 hours

2

2

0

2

48 hours

2

1

0

0

72 hours

1

1

0

0

TOTAL

5

4

0

2

MEAN

1.7

1. 3

0.0

0.7

Interpretation of results:
other: Eye irritant Cat. 2
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
The occular reactions observed during the study have been moderate. The individual mean scores for conjunctival chemosis were 1.0, 1.0 and 1.7, conjunctival redness scores were 2.0, 1.7 and 1.3, cornea opacity scores were 2.0, 2.0 and 0.7 and iris lesion scores were 0.0 for all animals. At the conjuctivae level, a moderate redness, noted 24 h after the test item installation and totally reversible between the 6th and 7th day of the test, was associated with a moderate chemosis, noted 1h after the test item instillation and totally reversible between the 5th and 6th day of the test. At corneal level, moderate opacity was observed 24 h after the test substance administration and totally reversible between the 3rd and 6th day.
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy adults female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Terpineol multi in one eye while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded (scale of lesion scores according to Directive n° 2004/73/EC and OECD guideline 405).

The occular reactions observed during the study have been moderate. The individual mean scores for conjunctival chemosis were 1.0, 1.0 and 1.7, conjunctival redness scores were 2.0, 1.7 and 1.3, cornea opacity scores were 2.0, 2.0 and 0.7 and iris lesion scores were 0.0 for all animals. At the conjuctivae level, a moderate redness, noted 24 h after the test item installation and totally reversible between the 6th and 7th day of the test, was associated with a moderate chemosis, noted 1h after the test item instillation and totally reversible between the 5th and 6th day of the test. At corneal level, moderate opacity was observed 24 h after the test substance administration and totally reversible between the 3rd and 6th day. Under these test conditions, Terpineol multi is considered as irritating to eyes, Cat 2.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Terpene hydrocarbon alcohols skin and eye irritation is based on read-across from alpha-Terpineol and Terpineol multi. The executive summaries of the source information are presented below followed by the read-across rationale.

Alpha-Terpineol and its skin irritation

For alpha-Terpineol, an in vivo skin irritation study is available. In three primary dermal irritation studies performed according to OECD guideline 404 and in compliance with GLP, 3 or 4 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 of the first test were 1.67, 2 and 2.33 for erythema score and 2, 2.33 and 3 for oedema score. For the second test the mean individual scores were 2, 2.67, 2 and 2 for erythema score and 3, 3, 2.67 and 1.67 for oedema score. For the third test the mean individual scores were 2, 2, 1.67 and 2 for erythema score and 2.67, 2, 0.67 and 3 for oedema score. Under the test conditions the substance is considered to be irritating to the skin because the average oedema score exceeded 2 (DSD C&L) or 2.5 (CLP) and the effects were not fully reversible within the observation period of 7 days. These data indicate that alpha-Terpineol has irritating properties to the skin (Cat. 2).

Terpineol multi and its eye irritation

For Terpineol Multi, an in vivo eye irritation study according to OECD TG 405 and in compliance with GLP criteria is available. In this study, 3 healthy adult female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Terpineol multi in one eye while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded (scale of lesion scores according to Directive n° 2004/73/EC and OECD guideline 405). The ocular reactions observed during the study have been moderate. The individual mean scores for conjunctival chemosis were 1.0, 1.0 and 1.7, conjunctival redness scores were 2.0, 1.7 and 1.3, cornea opacity scores were 2.0, 2.0 and 0.7 and iris lesion scores were 0.0 for all animals. At the conjunctivae level, a moderate redness, noted 24 h after the test item installation and totally reversible between the 6th and 7th day of the test, was associated with a moderate chemosis, noted 1h after the test item instillation and totally reversible between the 5th and 6th day of the test. At corneal level, moderate opacity was observed 24 h after the test substance administration and totally reversible between the 3rd and 6th day. Under these test conditions, Terpineol multi is considered as irritating to eyes (Cat.2).

Terpene hydrocarbon alcohols respiratory irritation

For respiratory irritation mostly human data are used for the assessment because no suitable in vitro or in vivo tests are available that can identify respiratory irritation. There are no human data such as indicated in R7.2.3 of the ECHA guidance that indicate respiratory reactions of the substance e.g. from consumer experience or occupational exposure. In addition, the substance is not corrosive or severely irritating which further minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2).

The skin and eye irritation of Terpene hydrocarbon alcohols using read across from alpha-Terpineol (CAS# 98-55-5) and Terpineol Multi (CAS# 8000-41-7).

Introduction and hypothesis for the analogue approach

Terpene hydrocarbon alcohols have the followingconstituent types of substances: Solely hydrocarbons-terpene type, Alcohol-type, Ketone-type and Ether-type all having a saturated or unsaturated cyclic hydrocarbon backbone.For this substance no skin and eye irritation information is available. In accordance with Article 13 of REACH, lacking information can be generated by other means than experimental testing, i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin and eye irritation potential the information from the constituent Terpineol is used, which can represent the Terpene hydrocarbon alcohols.

Hypothesis: Terpene hydrodcarbon alcohols have the same skin and eye irritation potential as alpha-Terpineol and Terpineol multi.

Available information, Skin irritation: Alpha-Terpineol is tested in a rabbit skin irritation test (OECD TG 404, Rel. 1). The substance is considered to be irritating to the skin (Cat 2) because the average oedema score exceeded Draize score 2.5 and the effects were not fully reversible within the observation period of 7 days.

Eye irritation: Terpineol multi is tested in an in vivo eye irritation test (OECD TG 405, Rel. 1). Based on moderate ocular reactions, especially cornea opacity, though reversible within 7 days, result in eye irritation (Cat 2).

Target chemical and source chemical(s)

Constituent types of the target substance and chemical structure of the source substances are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for skin and eye irritation.

Purity / Impurities

Constituent types of the target substanceare covered by the presented constituent types, there are no other constituent that impacts the skin and eye irritation.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation, which is presented below.

Analogue selection: For Terpene hydrocarbon alcohols their key constituents alpha-Terpineol and Terpineol Multi (with alpha-Terpineol as its main constituent) being representative for at least 40% of the substance, wereselected as source because for these skin and eye information is available, which can be used for read across.

Structural similarities and differences: The Terpene hydrocarbon alcohol constituent types have alpha-Terpineol/Terpineol as key constituents and therefor the same structures. The differences with the other constituent types can be presented as follows. Alcohol-type has a saturated or unsaturated cyclohexyl ring with a secondary or tertiary alcohol. The ones with the saturated bonds are expected to be less electrophilic compared to the ones with the unsaturated bones. The unsaturated ones can also represent the Solely hydrocarbon-terpene type. The latter type has a very similar backbone but often have an additional unsaturated bond in the ring instead of an alcohol group. Also the Ketones have similar rings but the functional group is a ketone instead of an alcohol. These groups, alcohol, double bond, ketone have similar electrophilicity. The Ether in the aromatic Ether is not very electrophilic either. Its double bond adjacent to the aromatic ring is more electrophilic. In view of its presence in the Terpene hydrocarbon alcohols < 4%, this reactivity is covered in the overall skin and eye irritation potential.

Skin and eye tissue absorption: All Terpene hydrocarbon alcohol constituents have molecular weights, are liquids and physico-chemical properties, log Kow, that present potential absorption.

Skin and eye irritation reactivity: The Terpene hydrocarbon constituents have similar electrophilicity and therefore similar reactivity. The saturated Alcohol and Ketones types are slightly less and cis-Anethole slightly more reactive all have lower presence in the Terpene hydrocarbon alcohols and there the reactivity of this substance can be presented with alpha-Terpineol and Terpineol multi.

Uncertainty of the prediction: There are no uncertainties other than those already addressed above.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix.

Conclusions on skin and eye irritation for hazard and risk assessment

For Terpene hydrocarbon alcohols no skin and eye irritation information is available but for its key constituents alpha-Terpineol and Terpineol multi such information is available, which can be used for read across and fill the data gap. When using read across the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.This documentation is presented in the current text. For the source chemicals alpha-Terpineol and Terpineol Multi,reliable in vivoskin and eye irritation data is available (OECD TG 404 and 405, respectively, Rel. 1) resulting in skin irritation Cat 2 and eye irritation Cat 2. These data can be used directly for read-across to the Terpene hydrocarbon alcohols.

Final conclusion:The Terpene hydrocarbon alcohols have skin irritation (Cat 2) and eye irritation (Cat 2) properties.

Data matrixpresenting the skin and eye information relevant for read across to theTerpene hydrocarbon alcohols from alpha-Terpineol and Terpineol multi.

Terpene hydrocarbon alcohols

Terpineol hydrocarbon alcohols

Terpineol alpha and multi

 

Target

Source

Structure

Not applicable

(α-Terpineol and γ-Terpineol)

CAS

Not applicable

98-55-5 and 8000-41-7

EC No.

945-149-0

202-680-6 /232-268-1

Reach registration

2018

Registered

Molecular weight

136-154

154

Phys-chem properties

 

 

Appearance

Liquid

Liquid

Log Kow

4.9 (3.3-5.5; IFF)

2.6

Identity, Constituent type (%)

100%

 

Solely hydrocarbons

 

 

Terpinolene or Limonene type

0-15

 

Alcohol type

 

>80

Tertiary alcohols

40-90

 

Secondary alcohols

7-40

 

Ketone type

-

 

Camphor-Type

0-17.5%

 

Ether type

 

 

Aromatic ether type

<4%

 

Human health

 

 

Skin irritation

Skin irritant Cat 2

(Read across)

Skin irritant Cat 2

(OECDTG 404)

Eye irritation

Eye irritant Cat 2

(Read across)

Eye irritant Cat 2

(OECD TG 405)

 

Justification for classification or non-classification

The substance needs to be classified as Skin irritant Category 2 and shall be labelled with 'H315: Causes skin irritation', according to EU CLP (EC No. 1272/2008 and its amendments).

The substance needs to be classified as Eye irritant Category 2 and shall be labelled with 'H319: Causes serious eye irritation', according to EU CLP (EC No. 1272/2008 and its amendments).

The substance does not need to be classified for respiratory irritation according to EU CLP (EC No. 1272/2008 and its amendments).