Octahydro-4,7-methano-1H-indene-5-methanol

Endpoint summary

Description of key information

Based on a WOE approach of in vivo investigations in rabbits with the submission substance and the structural closely related octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol) it is concluded that no classification on skin irritation is required.

Based on a WOE approach of in vivo investigations in rabbits with the submission substance and the structural closely related octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol) it is concluded that the submission substance causes eye irritation (GLP: Cat. 2; GHS: Cat. 2A).

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:

Initiation: March 01, 1983 - Termination: March 08,1983.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No data about purity of the substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

May 12, 1981

GLP compliance:

no

Specific details on test material used for the study:

No information on purity. However, as it is stated in the section 13, the substance and its composition have remained essentially the same over the last decades.

Species:

rabbit

Strain:

Himalayan

Remarks:

Albino Himalayan (SPF Wiga)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Weight at study initiation: 1.7 - 2.2 kg (3 animals)
- Housing: individual cages in fully air-conditioned rooms
- Diet (e.g. ad libitum): feed for breeding rabbits ERKA Z 6000, ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12 hours per day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Remarks:

24 hours before test initiation

Vehicle:

unchanged (no vehicle)

Remarks:

0,5 mL

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:

Exposure time of 4 hours. After the exposure the remaining substance was carefully removed from the skin.

Observation period:

First assessment 30-60 minutes after the treatment. Then after 24, 48 and 72 hours and after 7 days.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorsal / lateral part.
- Coverage / Type of wrap: substance placed on the cellulose part of a plaster (specially designed from Baiserdorf AG, Hamburg, 2.5 cm x 2.5 cm).

REMOVAL OF TEST SUBSTANCE
- After the exposure the remaining substance was carefully removed from the skin.

OBSERVATION TIME POINTS
30-60 minutes, 24 hours, 48 hours, 72 hours and 7 days after the removal of the plaster.

SCORING SYSTEM:
- Method of calculation: numerical assessment for the formation of erythema and oedema according to the OECD guideline (Draize) and with the labelling of the respective observations.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

mean value of all animals and all time periods

Time point:

other: mean value from all time points between 30-60 minutes and 72 hours after exposure

Score:

2.8

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks:

but decrease of effect and only grade 1 observed on Day 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test item caused slight irritation under the conditions of this test.

Executive summary:

Based on an exposure of 4 hours of an undiluted solution of the test item, a PDII of 2.8 has been determined. It is calculated from the sum of the scoring for erytheme and oedeme observations (12 according to the grading of skin reactions of the OECD guideline) divided by a factor of 12 (number of animals and number of time points 3x4).

The test item caused well defined erythema and slight oedema in all rabbits within 24 hours after removal of the patch. The effect persisted until 72 hours (mean erythema scores for the individual animals after 24, 48 and 72 hours: 2.3, 2.0, 2.3;

mean edema scores for the individual animals after 24, 48 and 72 hours: 1.0, 1.0, 1.3 ) and subsided within 7 days except in one animal, which still showed slight erythema after 7 days (score 1).

Dry, chapped and squamos skin was found in 1 of 3 animals 72 hours after removal of the patch and in all animals after 7 days.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-guideline study comparable to guideline study with acceptable restrictions; 24 h occlusive application, no data on purity of test substance

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Method: other: Federal Register 38, No. 187, 27.9.1973, p 27019. Method used is similar to OECD Guideline 404 (Acute Dermal Irritation/Corrosion) with some deviations (exposure period 24 h, occlusive application, no data on test substance purity, reading times slightly different: in OECD TG 404: readings to be performed 24, 48, and 72 h after patch removal (i.e. 28, 52, and 76 h after dermal administration); here readings performed 24, 48, and 72 h after dermal application).

GLP compliance:

no

Species:

rabbit

Strain:

other: SPF-Albino-Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 1.5 - 2 kg
- Housing: individually caged
- Diet (e.g. ad libitum): compound feeds ERKA 8300 from Robert Koch oHG, Hamm, Germany
- Water (e.g. ad libitum): yes
- Acclimation period: no dat

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

Type of coverage:

occlusive

Preparation of test site:

shaved

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): pure test substance

Duration of treatment / exposure:

24 hour(s)

Observation period:

up to 48 hrs after patch removal

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: test substance was applied on surgical gaze covered with occlusive PVC sheeting. The rump of the animal was wrapped with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hrs

SCORING SYSTEM: Skin reactions were scored according to the table of OECD Guideline 404 (Draize).

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-48-72 h after dermal application

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24-48-72 h after dermal application

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

probability of weak irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 and 48 hrs after patch removal

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

other: slight erythrema (grade 1) were observed only at patch removal (end of 24 h exposure period).

Effects of the undiluted test substance on intact rabbit skin:

Slight irritation (erythema grade 1, no edema) was noted in 2 of 6 animals immediately after patch removal. No skin reaction was noted 24 and 48 hrs thereafter.

 

Animal	Skin reaction	After patch removal
		0 hrs	24 hrs	48 hrs
1	Erythema	0	0	0
	Edema	0	0	0
2	Erythema	1	0	0
	Edema	0	0	0
3	Erythema	0	0	0
	Edema	0	0	0
4	Erythema	0	0	0
	Edema	0	0	0
5	Erythema	1	0	0
	Edema	0	0	0
6	Erythema	0	0	0
	Edema	0	0	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

Only transient, slight erythema, but no edema, was noted in 2/6 animals after 24 hr occluded contact to intact rabbit skin. The substance was not irritating to the rabbit skin, even under worst case conditions (occlusion, 24 hr-exposure period).

Executive summary:

In a primary dermal irritation study six Himalayan rabbits were dermally exposed to 0.5 mL of octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM undiluted) for 24 hours to an area of approx. 6 cm². Animals then were observed for additional 48 hours. Irritation was scored by the method of Draize.

After 24 hours occlusive exposure, only 2 of 6 animals showed slight erythema (grade 1). No edema were observed. 24 hours after patch removal, the erythema had subsided. In this study, octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM) is minimally irritating to the skin (Hollander/Hoechst AG, 1975b).

This dermal irritation study in the rabbit is acceptable. It complies with the OECD guideline 404 with reasonable restrictions. Deviations are rather expected to enhance the irritating effect.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

The source substance is octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol), the target substance octahydro-4,7-methano-1H-indenemethanol, which differ only by one methanol group. Therefore ist seems justified to take data concerning the source substance also into account for the target substance. The exposure to the source substance was for 24 h, that of the target substance 4 h. Therefore the results for the source substance (not irritating) is attached more importance compared to the target substance. Though somewhat differing in their skin irritating properties, the read-across is supported by a comparable potency of eye irritation.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24-48-72 h after dermal application

Score:

0

Max. score:

4

Reversibility:

other: not applicable as no effect occurred

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-48-72 h after dermal application

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24-48-72 h after dermal application

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

probability of weak irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 and 48 h after patch removal

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 24 h after patch removal

Remarks on result:

other: slight erythema (grade 1) were observed only at patch removal (end of 24 h exposure period)

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the test substance was not irritating to the skin of rabbits.

Executive summary:

The study used as source investigated octahydro-4,7-methano-1H-indenedimethanol, the target substance is octahydro-4,7 -methano-1H-indenemethanol. The study results of the source compound were considered applicable to the target compound and were used for classification and labelling.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Initiation: March 01, 1983 - Termination: March 15,1983.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study; no data on TS purity reported

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

12 May 1982

GLP compliance:

no

Specific details on test material used for the study:

No information about purity. However, as it is stated in the section 13, the substance and its composition have remained essentially the same over the last decades.

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, conventional breeding
- Weight at study initiation: 1.7 - 1.8 kg (3 animals)
- Housing: individual cages in fully air-conditioned rooms
- Diet: feed for breeding rabbits ERKA Z 6000, ad libitum
- Water: deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %
- Photoperiod (hrs dark / hrs light): 12 hours per day
Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, the untreated right eye

Amount / concentration applied:

Concentration: 100 %
Amount applied: 0.1 ml

Duration of treatment / exposure:

24 hour(s)

Observation period (in vivo):

14 days with readings after 1, 24, 48, 72 hours and 7 and 14 days post application

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with physiological saline at 37°C
- Time after start of exposure: 24 h after application

SCORING SYSTEM: Draize (see guideline)

TOOL USED TO ASSESS SCORE: 0.01% fluorescein sodium solution and UV light (24 and 72 h post application)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.55

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

RS-Freetext:
The individual effects of the rabbit eye were scored as follows: 

Rabbit 1/2/3; 1h - 24hrs - 48 hrs - 72hrs - 7d -
14d
_______________________________________________
-Cornea:
1/1/1 - 1/1/2 - 1/1/2 - 0/1/2 - 0/1/2 - 0/0/1
     
-Iris
 1/1/1 - 1/1/1 - 0/0/1 - 0/0/1 - 0/0/0 - 0/0/0   
    
-Conjunctivae 
Redness: 
1/3/3 - 3/2/2 - 1/1/2 - 0/2/2 - 0/1/0 - 0/0/1         
Chemosis: 
1/2/2 - 2/2/1 - 1/2/1 - 0/1/2 - 0/0/1 - 0/0/0
_______________________________________________


The means of the effects were as follows:


           24 hrs      48 hrs    72 hrs
________________________________________
cornea     1.33       1.33       1.0
iris       1.0        0.33       0.33
Conjunc.
redness    2.33       1.33       1.33
chemosis   1.67       1.33       1.0  
________________________________________

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

CL-Freetext:
The TS caused moderate eye irritation in all animals.

The effects were reversible and were absent in two animals at 14 days after treatment. Cornea opacity and conjunctivae redness grade 1 persisted in one animal until the end of the observation period, however, the effects were less severe than after the beginning of the observation period. As it can reasonably be assumed, that the effects would have been fully reversible, if the observation period would have been extended to 21 days, it is concluded that the substance is irritating to the eyes (GHS Cat. 2A).

Executive summary:

Eye irritating effects have been investigated in rabbits according to OECD TG 405. At the end of the treatment period cornea opacity, as well as effects on the iris, and conjunctivae were observed (mean values after 24 -48 -72 hours for all three animals: 1.22, 0.55, 1.66 and 1.33, for cornea, iris, redness and chemosis, respectively). The effects were reversible and were absent in two animals at 14 days  after treatment. Cornea opacity  and conjunctivae redness grade 1 persisted in one animal  until the end of the 14 day observation period, however, the effects were less severe than after the beginning of the observation period.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-guideline study comparable to guideline study with acceptable restrictions; no data on purity of test substance

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Method: other: Federal Register Vol.38, No. 187, 1973. Method used is similar to OECD Guideline 405 (Acute Eye Irritation/Corrosion) with some deviations (no data on test substance purity).

GLP compliance:

no

Species:

rabbit

Strain:

other: SPF-Albino-Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 1.5 - 2 kg
- Housing: individually caged
- Diet (e.g. ad libitum): compound feeds ERKA 8300 from Robert Koch oHG, Hamm, Germany
- Water (e.g. ad libitum): yes
- Acclimation period: no dat

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

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye was used as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg (equivalent to approx. 0.1 mL)

Duration of treatment / exposure:

24 hrs

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline solution
- Time after start of exposure: 24 hrs

SCORING SYSTEM: according to Table E: Grading of Ocular Lesions in OECD Guideline 405 Acute Eye Irritation/Corrosion)

TOOL USED TO ASSESS SCORE: hand-slit lamp; for examinations following the 24 h reading, fluorescein (0.01% solution) was used for staining.

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal: #2, #3, #5, and #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #2, #3, #4, #5, and #6

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: #1, #3, #5, and #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

animal: #2 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Eye Irritating Effect of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alkohol DM)

(undiluted test substance)

 

Rabbit	Effect	Score (hours after application)					Score (days after application)
		1	7	24	48	72	7	14	21
1	Cornea	2	2	2	2	3	2	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	2	2	2	2	1	0	0	0
	Chemosis	1	1	1	0	0	0	0	0
2	Cornea	2	2	2	2	2	1	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	1	2	2	1	1	0	0	0
	Chemosis	0	1	0	0	0	0	0	0
3	Cornea	2	2	2	2	2	1	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	1	2	2	1	1	0	0	0
	Chemosis	1	1	1	0	0	0	0	0
4	Cornea	2	2	2	2	3	1	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	1	2	2	1	1	0	0	0
	Chemosis	1	0	0	0	0	0	0	0
5	Cornea	2	2	2	2	2	2	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	1	2	2	1	1	0	0	0
	Chemosis	1	1	1	0	0	0	0	0
6	Cornea	2	2	2	2	2	2	0	0
	Iris	0	0	0	0	0	0	0	0
	Conjunctivae	2	2	2	1	1	0	0	0
	Chemosis	1	1	1	0	0	0	0	0

mean scores (rabbits 1-6) of readings at 24hrs/48 hrs/72 hrs :

Cornea: 2 / 2 / 2.3 (max. possible: 4)

Iris:   0 / 0 / 0   (max possible: 2)

Conjunctivae  - Redness:   2 / 1.2 / 1 (max. possible: 3)

  - Chemosis:  0.7 / 0 / 0 (max. possible: 4)

Reversibility:

The effects subsided within 7 days and were absent 14 days after application.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test substance proved to be irritating to the eye.

Executive summary:

In a primary eye irritation study, 100 mg (equivalent to approx. 0.1 mL) of octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM) was instilled into the conjunctival sac of 6 Himalayan rabbits for 24 hours. After 24 hours eyes were washed with physiological saline solution. Animals then were observed for 21 days. Irritation was scored according to Table E: Grading of Ocular Lesions of OECD test guideline 405 (Acute Eye Irritation/Corrosion).

 

Irritation reactions of cornea and conjunctivae (redness and chemosis) developed within 1 to 24 hours after application. Effects on cornea had their peak at 72 hours, subsided thereafter and were absent at day 14. Effects on conjunctiva peaked within 24 to 72 hours, subsided thereafter and were not to be observed at days 7 (Hollander/Hoechst AG; 1975b).

 

In this study, octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM) is irritating to the eye based on EU legislation.

 

This eye irritation study in the rabbit is acceptable. It complies with OECD guideline 405 (Acute Eye Irritation/Corrosion).

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

The source substance is octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol), the target substance octahydro-4,7-methano-1H-indenemethanol, which differ only by one methanol group. The results of the target substance (eye irritating) are used to support the results of the source substance (eye irritating) in a WOE approach.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal: #2, #3, #5 and #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: #1, #3, #5 and #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: #2 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of this study the test substance was irritating to the eyes of rabbits.

Executive summary:

The study used as source investigated octahydro-4,7-methano-1H-indenedimethanol, the target substance is octahydro-4,7 -methano-1H-indenemethanol. The study results of the source compound were considered applicable to support the results for the target compound and were used in a WOE approach for classification and labelling.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an in vivo guideline study according to OECD TG 404 three rabbits were dermally exposed for 4 h toward 0.5 mL of the undiluted test item (submission substance octahydro-4,7-methano-1H-indenemethanol).

The test item caused well defined erythema and slight oedema in all rabbits within 24 hours after removal of the patch. The effect persisted until 72 hours (mean erythema scores for the individual animals after 24, 48 and 72 hours: 2.3, 2.0, 2.3; mean edema scores for the individual animals after 24, 48 and 72 hours: 1.0, 1.0, 1.3 ) and subsided within 7 days except in one animal, which still showed slight erythema after 7 days (score 1). Dry, chapped and squamous skin was found in 1 of 3 animals 72 hours after removal of the patch and in all animals after 7 days. Based on these results, the substance would be considered as irritating to skin (CLP and UN-GHS: Cat. 2).

In an in vivo guideline study comparable to OECD 404 6 rabbits were dermally exposed to 0.5 mL of octahydro-4,7-methano-1H-indenedimethanol (structural analogue) for 24 hours to an area of approx. 6 cm². Animals then were observed for additional 48 hours. Irritation was scored by the method of Draize. After 24 hours occlusive exposure, only 2 of 6 animals showed slight erythema (grade 1). No edema were observed. 24 hours after patch removal, the erythema had subsided. In this study, octahydro-4,7 -methano-1H-indenedimethanol (TCD Alkohol DM) is minimally irritating to the skin.

This dermal irritation study in the rabbit is acceptable. It complies with the OECD TG 404 with reasonable restrictions. Deviations from OECD guideline are rather expected to enhance the irritating effect.

Based on these results, the test substance would be considered as not irritating to skin.

Based on a WOE approach of in vivo investigations in rabbits with the submission substance octahydro-4,7-methano-1H-indenemethanol and the structural closely related octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol) it is concluded that no classification on skin irritation for the submission substance is required:

The results of the submission substance would indicate classification as skin irritating Cat 2 according to Regulation (EC) No. 1272/2008. However, the severeness of effect (erythema score 2.3) is equal to the lower boundary of the range for classification (>/= 2.3). Moreover, the closely structurally related octahydro-4,7-methano-1H-indenedimethanol, which differs only by one methanol group, was not irritating even after 24 h epicutaneous exposure duration (compared to 4 h for the submission substance). Considering the results of both studies, it was concluded that no classification with regard to skin irritation is required for the submission substance. A comparable potency for skin irritation is supported by a comparable eye irritating potency for submission and read-across substance (see below).

Eye irritating effects of the submission substance octahydro-4,7-methano-1H-indenemethanol have been investigated in rabbits according to OECD TG 405. At the end of the treatment period cornea opacity, as well as effects on the iris, and conjunctivae were observed (mean values after 24 -48 -72 hours for all three animals: 1.22, 0.55, 1.66 and 1.33 for cornea, iris, redness and chemosis, respectively). The effects were reversible and were absent in two animals at 14 days  after treatment. Cornea opacity  and conjunctivae redness grade 1 persisted in one animal  until the end of the 14 day observation period, however, the effects were less severe than after the beginning of the observation period. As it can reasonably be assumed, that the effects would have been fully reversible, if the observation period would have been extended to 21 days, it is concluded that the substance is irritating to the eyes (CLP: Cat. 2; UN-GHS: Cat. 2A).

Eye irritating effects of the structural analogue octahydro-4,7-methano-1H-indenedimethanol have been investigated in rabbits in a study comparable to OECD TG 405. Irritation was scored according to Table E: Grading of Ocular Lesions of OECD test guideline 405 (Acute Eye Irritation/Corrosion). Irritation reactions of cornea and conjunctivae (redness and chemosis) developed within 1 to 24 hours after application. Effects on cornea had their peak at 72 hours, subsided thereafter and were absent at day 14. Effects on conjunctiva peaked within 24 to 72 hours, subsided thereafter and were not to be observed at days 7. Based on these results, the substance is considered as irritating to eyes (GHS: Cat. 2; UN-GHS Cat. 2A).

Experimental data for both substances, the submission substance and the read across substance, indicate that the submission substance is irritating to the eyes and that full reversibility within 21 days can plausibly be assumed. Therefore it is concluded that the submission substance should be classified as irritating to the eyes (CLP: Cat. 2; UN-GHS: Cat. 2A).

 

Justification for classification or non-classification

Based on a WOE approach (see Additional information, above) of in vivo investigations in rabbits with the submission substance and the structural closely related octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol) it is concluded that no classification on skin irritation is required according to Regulation (EC) No. 1272/2008 and United-Nations Globally Harmonized System of Classification and Labelling (UN-GHS, 7th revised version, 2017).

Based on a WOE approach (see Additional information, above) of in vivo investigations in rabbits with the submission substance and the structural closely related octahydro-4,7-methano-1H-indenedimethanol (tricyclo[2.2.2.2~1,4~]decane-2,5-diyldimethanol) it is concluded that the submission substance has to be classifed as eye irritating Cat. 2 according to Regulation (EC) No. 1272/2008 and as eye irritating Cat. 2A according to the United-Nations Globally Harmonized System of Classification and Labelling (UN-GHS, 7th revised version, 2017).