4,7-methanooctahydro-1H-indene-diyldimethyl bis(2-carboxybenzoate)

Endpoint summary

Description of key information

GLP guideline studies in rabbits are available for skin and eye irritation according to OECD 404 and OECD 405, respectively.

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

Study period:

1990-11-27 to 1990-12-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. An updated OECD guideline from 2002 is available; changes do not affect the reliability of this study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, UK
- Age at study initiation: No data
- Weight at study initiation: 3.5, 3.2, and 3.6 kg, all female
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Standard diet "Ssniff K 4", approx. 100-120 g per animal and day (fed in the morning)
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): Approx. 50 %
- Air changes (per hr): Approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12 (illumination from 6 to 18 hrs CET)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg, moistened

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: semiocclusive dressing (Fixomull-Stretch Klebevlies, Beiersdorf no. 2293)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With water
- Time after start of exposure: 4 h

SCORING SYSTEM:
According to DRAIZE

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Other effects:

No other effects.

Skin irritant effects of the TCD-emulsifier:

Animal No.	Body weight [kg]	Sex	Draize grade after												Irrit. index
			1 h		24 h		48 h		72 h		7 d		14 d
			e	o	e	o	e	o	e	o	e	o	e	o	e	o
L4	3.5	Female	0	0	0	0	0	0	0	0	0	0	-	-	0.0	0.0
L6	3.2	Female	0	0	0	0	0	0	0	0	0	0	-	-	0.0	0.0
K23	3.6	Female	0	0	0	0	0	0	0	0	0	0	-	-	0.0	0.0

e: erythema and eschar formation

o: oedema formation

-: not examined

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Irritant and/or corrosive effects of TCD-emulsifier were tested according to OECD uideline 404 and EU Method B.4. The test substance is not irritating to rabbit skin.

Executive summary:

In a primary dermal irritation study according to OECD guideline 404 and EU method B.4, adult albino rabbits (strain: HC:NZW) (3 female animals) were dermally exposed to 500 mg TCD-emulsifier in water for 4 hours, administered to 6 cm² at dorso-lateral areas of the animals' trunk. Animals then were observed for 7 days. Irritation was scored by the method of DRAIZE.

No irritation occurred. Based on the study results, TCD-emulsifier is not classified according to CLP Annex I as a dermal irritant.

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

Study period:

1990-11-27 to 1990-12-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. An updated OECD guideline 405 from 2012 is available; changes do not affect the reliability of this study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

84/449/EEC

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation:
- Weight at study initiation: 3.5, 3.2, and 3.6 kg, all female
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Standard diet "Ssniff K 4", approx. 100-120 g per animal and day (fed in the morning)
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): Approx. 50 %
- Air changes (per hr): Approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12 (illumination from 6 to 18 hrs CET)

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl (approx. 40 mg)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing with saline
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize Grades

TOOL USED TO ASSESS SCORE: Hand-slit lamp, fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.1

Max. score:

0.3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

Erythema

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1.2

Max. score:

1.3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.1

Max. score:

0.3

Reversibility:

fully reversible

Results for the grading of irritating effects on the eye:

Animal no./ Sex	Body weight	Tissue	Signs	DRAIZE grades							Irritation index
				1 h	24 h	48 h	72 h	7 d	14 d	21 d
M26/ Female	2.7 kg	Cornea	o	0	0	0	0	0	-	-	0.0
			a	0	0	0	0	0	-	-
		Fluorescein	i	-	1	1	0	-	-	-
			a	-	1^c	1^p	0	-	-	-
		Iris		0	0	0	0	0	-	-	0.0
		Conjunctivae	r	1	1	1	1	0			1.0
			s	1	0	0	0	0			0.0
		Aqueous humour		0	0	0	0	0	-	-
		Discharge		1	0	0	0	0	-	-
M25/ Female	2.9 kg	Cornea	o	0	0	0	0	0	-	-	0.0
			a	0	0	0	0	0	-	-
		Fluorescein	i	-	1	1	0	-	-	-
			a	-	2^c	1^c	0	-	-	-
		Iris		0	1	0	0	0	-	-	0.3
		Conjunctivae	r	1	2	1	1	0	-	-	1.3
			s	2	1	0	0	0			0.3
		Aqueous humour		0	0	0	0	0	-	-
		Discharge		3	0	0	0	0	-	-
K8/ Female	3.4 kg	Cornea	o	0	0	0	0	0	-	-	0.0
			a	0	0	0	0	0	-	-
		Fluorescein	i	-	0	-	-	-	-	-
			a	-	0	-	-	-	-	-
		Iris		0	0	0	0	0	-	-	0.0
		Conjunctivae	r	1	2	1	1	0	-	-	1.3
			s	1	0	0	0	0			0.0
		Aqueous humour		0	0	0	0	0	-	-
		Discharge		1	0	0	0	0	-	-

o: Opacity

a: Area

i: Intensity

r: Redness

s: Swelling

-: Not examined

c: Confluent diffuse areas

p: Scattered punctate

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The eye irritant/corrosive potential of the test item was assessed in rabbits according to OECD guideline 405 and EU method B.5. The test substance induced slight reactions of the mucous membranes and mild corneal effects which were fully reversible within 7 days. The substance is regarded as slightly irritating.

Executive summary:

In a primary eye irritation study in accordance with OECD guideline 405 and EU method B.5, 100 µl of TCD-emulsifier was instilled into the conjunctival sac of adult rabbits (strain: HC:NZW) (3 female) for 24 hours. The eyes were rinsed with saline after 24 h of exposure. Animals then were observed for 7 days. Irritation was scored by the method of DRAIZE.

The exposure induced slight reactions of the mucous membranes and mild corneal effects which were fully reversible within 7 days. Based on the study results, the test item is not classified as an eye irritant according to CLP Annex I.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The irritant/corrosive potential of the test substance was studied on the skin and eye of the rabbit in accordance with OECD guidelines 404 and 405. Whilst considering OECD interpretation guides, the results were interpreted in conjunction with the nature, intensity, and reversibility of the responses observed.

The results indicate that the test substance can be regarded as 'not irritating to the skin'.

Administration of the test substance to the eye caused slight reactions of the mucous membranes and mild corneal effects which proved to be fully reversible within 7 days. Therefore the test substance may be considered as 'slightly irritating to the eye' but does not fulfil the criteria of the CLP regulation for classification as eye irritant.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The results indicate that the test substance can be regarded as 'not irritating to the skin'.

Exposure of the test substance to the eye caused slight reactions of the mucous membranes and mild corneal effects which proved to be fully reversible within 7 days. Therefore the test substance may be considered as ‘slightly irritating to the eye' but does not fulfil the criteria of the CLP regulation for classification as eye irritant.