Reaction mass of (Z)-3-(9-octadecenyloxy)propane-1,2-diol and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-di[oxy[(hydroxymethyl)-1,2-ethanediyl]] and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-tri[oxy[(hydroxymethyl)-1,2-ethanediyl]]

Endpoint summary

Description of key information

CIMEXANE NB (CAS 71032-90-1) was found to be irritant to skin in a study conducted according to OECD guideline 404 and to be irritant to eyes in a  study conducted according to OECD guideline 405.

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:

16-31 October 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted in compliance with OECD Guideline 404 with minor deviations: age of the animals not reported; no details on the housing conditions; individual animal weights not reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

age of the animals not reported; no details on the housing conditions; individual animal weights not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

COFRAC accredidation on technical ability

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bertho, Yffiniac, France
- Average weight at study initiation: 2.3 kg
- Housing: Individual housing on floor grid
- Diet (e.g. ad libitum): Complete pelleted rabbit maintenance diet Energie H326, COFNA (Tours, France)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- In accordance with the requirements of the 86/609/EEC guideline.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Dorsal area of the trunk of the animals
- Type of wrap if used: Test substance was applied directly to the clipped skin under a gauze pad (2 cm X 2 cm) and held in place by means of a 5 x 5 cm wide ‘Micropore’ fastening tape. Then the animal's trunk was wrapped with a 10 cm wide stretch tape (varicose vein tape) fastened by adhesive tape of the same width.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the dressings, the residual test substance was removed using absorbent paper moistened with water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Scoring system same as recommended by OECD Guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

Well defined erythema to moderate-severe erythema associated with slight to moderate oedema was observed in all 3 animals. These reactions decreased after 7 days and were completely reversible in one rabbit. Very slight erythema and oedema were perceptible respectively in one and two animals up to Day 15.

Other effects:

None

Table 7.3.1/1: Individual skin reactions

 

Animal no.	Observation time				Mean (24, 48 and 72 h)
	1 h	24 h	48 h	72 h
Erythema
1	2	3	3	3	3
2	2	3	3	3	3
3	3	3	3	2	2.7
Oedema
1	2	2	3	3	2.7
2	2	3	3	3	3
3	2	3	3	2	2.7

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, CHIMEXANE NB - Batch M 752 is classified as ‘R38 Irritating to skin’ according to the criteria of Annex VI of the Directive 67/548/EEC and ‘Category 2: skin Irritant’ according to CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 , three male New Zealand White rabbits were dermally exposed to 0.5 mL of CHIMEXANE NB - Batch M 752, under a semi-occlusive dressing (2 cm x 2 cm) for 4 h to clipped skin of the dorsal area of the trunk. After removal of the dressings, the residual test substance was removed using absorbent paper moistened with water. Irritation was scored as outlined in the OECD Guideline 404 at approximately 1, 24, 48 and 72 h after removal of the dressing and then daily until the end of the observation period (Day 15).

 

Well defined erythema to moderate-severe erythema associated with slight to moderate oedema was observed in all 3 animals. These reactions decreased after 7 days and were completely reversible in one rabbit. Very slight erythema and oedema were perceptible respectively in one and two animals up to Day 15. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 3, 3, 2.7 for erythema and 2.7, 3, 2.7 for oedema score, respectively. In this study, CHIMEXANE NB - Batch M 752 is a skin irritant on male rabbits.

 

Under the test conditions, CHIMEXANE NB - Batch M 752 is classified as ‘R38 Irritating to skin’ according to the criteria of Annex VI of the Directive 67/548/EEC and ‘Category 2: skin Irritant’ according to CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

16 -24 October 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study conducted in compliance with OECD Guideline 405 with deviations: age at study initiation and individual animal weights not reported; environmental conditions not reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

age at study initiation and individual animal weights not reported; environmental conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

COFRAC accreditation on technical ability

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: elevage BERTHO, Yffiniac, France
- Weight at study initiation: 2.3 kg (mean)
- Housing: Animals were housed individually on floor grid.
- Diet: Complete pelleted rabbit maintenance diet Energie H326 (COFNA, Tours, France), ad libitum
- Acclimation period: 5 days

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted test item

Duration of treatment / exposure:

No washing was done.

Observation period (in vivo):

9 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: According to OECD Guideline 405

TOOL USED TO ASSESS SCORE:
- Ocular reactions were performed with a U. V. and white magnification light. After recording the observations at 24 h, the eyes of all rabbits were examined with the aid of fluorescein.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 9 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- One hour after instillation of the substance, redness of the palpebral and bulbar conjunctivae with abundant discharge and slight chemosis were observed.
- Slight iris congestion observed in three rabbits disappeared in less than 48 h.
- 24 h later, conjunctival reactions (redness and chemosis) increased slightly and a partial corneal opacity was noticed in two rabbits, it disappeared in less than 4 days.
- Complete reversibility occurred within about a week in all animals.

Other effects:

No data

Table 7.3.2/1: Results of eye irritation

Animal no.	4582						4583						4584
	Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea
	A	B	C	D	E	F	A	B	C	D	E	F	A	B	C	D	E	F
D1 (1 h)	1	2	2	1	0	0	1	3	2	1	0	0	1	3	2	1	0	0
24 h	3	1	3	1	2	1	1	1	2	0	0	0	1	1	3	1	1	1
48 h	1	1	3	0	1	1	1	1	2	0	0	0	1	1	2	0	1	1
72 h	1	1	3	0	1	1	1	0	2	0	0	0	1	1	2	0	0	0
M	1.7	1.0	3.0	0.3	1.3	1.0	1.0	0.7	2.0	0.0	0.0	0.0	1.0	1.0	2.3	0.3	0.7	0.7
D5	1	0	2	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0
D6	1	0	2	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0
D7	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
D8	0	0	1	0	0	0	-	-	-	-	-	-	-	-	-	-	-	-
D9	0	0	0	0	0	0	-	-	-	-	-	-	-	-	-	-	-	-

 

A: Chemosis; B: Discharge; C: Redness; D: Iris lesion; E: Opacity; F: Opacity area; M: Mean

Interpretation of results:

Category 2A (irritating to eyes)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Chimexane NB is classified as “R36 irritating to eyes”, according to the Annex VI of the Directive 67/548/EEC and "irritating to eyes (Category 2)" according to the Regulation (EC) N° 1272-2008 (CLP).

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test item Chimexane NB in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test item. At 24 h after treatment, fluorescein solution was instilled into the eyes and they were examined under UV-lamp to detect possible corneal damage. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and up to Day 9 after treatment and graded according to the method of OECD Guideline 405.

One hour after instillation of the substance, redness of the palpebral and bulbar conjunctivae with abundant discharge and slight chemosis were observed. Slight iris congestion observed in three rabbits disappeared in less than 48 h. 24 h later, conjunctival reactions (redness and chemosis) increased slightly and a partial corneal opacity was noticed in two rabbits, it disappeared in less than 4 days. Complete reversibility occurred within about a week in all animals. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1.3, 0.0, 0.7 for cornea score; 0.3, 0.0, 0.3 for iris score; 3.0, 2.0, 2.3 for conjunctivae score and 1.7, 1.0, 1.0 for chemosis score. In this study, Chimexane NB is an eye irritant on male rabbits.

Under the test conditions, Chimexane NB is classified as “R36 irritating to eyes”, according to the Annex VI of the Directive 67/548/EEC and ‘irritating to eyes (Category 2)’ according to the Regulation (EC) N° 1272-2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two studies, identified as key studies were conducted according to OECD guidelines 404 and 405. These studies showed that CHIMEXANE NB was irritant to skin and to eyes in rabbits.

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 skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Under the test conditions, CHIMEXANE NB - Batch M 752 is classified as ‘R38 Irritating to skin’ and 'R36 Irritating to eye' according to the criteria of Annex VI of the Directive 67/548/EEC and ‘Category 2: skin Irritant’ and 'Category 2: eye irritant' according to CLP Regulation (EC) N° (1272-2008).