Tricyclodecanedimethanol

Endpoint summary

Description of key information

Undiluted Octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol DM) is only minimally irritating to the skin of rabbits, but it is irritating to the eyes  (Hollander/Hoechst AG, 1975b).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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:

overall irritation score

Basis:

mean

Time point:

24/48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 24 hrs after patch removal

Remarks on result:

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

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal: #1, #2, #4, #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal: #2, #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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:

irritating

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 TM) 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 TM) 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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

In a primary dermal irritation study, six Himalayan rabbits were dermally exposed to 0.5 mL of undiluted octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM) 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. Octahydro-4,7-methano-1H-indenedimethanol showed to be not or only 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 tolerable restrictions (deviations are rather expected to enhance the irritating effect, e.g. 24 occlusive exposure instead of 4 h semi-occlusive exposure).

 

Eye irritation

In a primary eye irritation study,100 mg (equivalent to approx. 0.1 mL) of octahydro-4,7-methano-1H-indenedimethanol (TCD Alcohol TM) was instilled into the conjunctival sac of 6 Himalayan rabbits for 24 hours. Animals then were observed for 21 days. Irritation was scored according to OECD test guideline 405 (Acute Eye Irritation/Corrosion).

Irritation reactions of cornea and conjunctiva (redness and chemosis) developed within 1 to 24 hours after application and had subsided at day 14 (cornea) and at days 7 (conjunctiva) respectively. No iridial effects were noted.

In 4/6 animals mean cornea scores were 2. The remaining 2 animals showed a mean score of 2.3, each (reading times 24, 48, and 72 h). These effects were reversible within 14 days.

In 5/6 animals mean scores of conjunctival redness were 1.33, and one animal showed a mean score of 1.67. Effects were reversible within 7 days.

4/6 showed a mean chemosis score of 0.33 (all effects reversible within 48 hours), whereas 2 animals showed a score of 0 (at reading times 24, 48, and 72 h).

In this study, octahydro-4,7-methano-1H-indenedimethanol is irritating to the eye (Hollander/Hoechst AG, 1975b).

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

Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on eye irritation: irritating

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, octahydro-4,7-methano-1H-indenedimethanol (TCD Alcohol DM) has not to be classified for skin irritation.

According to Regulation (EC) No 1272/2008, octahydro-4,7-methano-1H-indenedimethanol (TCD Alcohol DM) has to be classified for eye irritation (irritating to eyes Category 2; mean cornea score 2 in 4/6 animals or 2.3 in 2/6 animals at 24/48/72 hours after application).

Based on the observation a classification for eye irritation in category 2A is requiredaccording to United nations GHS, 2013 (ST/SG/AC.10/30/Rev.5).