Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and lauric acid

Endpoint summary

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:

August 11, 1992 to august 14, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This test was conducted in compliance with EEC Methods, and was performed to comply with GLP regulations.

Qualifier:

according to guideline

Guideline:

other: EEC Method Directive 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B.4. Acute toxicity (skin irritation)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 10 to 13 weeks
- Weight at study initiation: 2.5-3.5 kg
- Housing: Individually in metal cages with perforated floors.
- Diet (e.g. ad libitum): A standard laboratory diet SDS Stanrab (P) Rabbit Diet.
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 19°C
- Humidity (%): 30-70%
- Air changes (per hr): 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 -1900 hours) in each 24 hours period.

Type of coverage:

other: Each treatment site was covered with "Elastoplast" elastic adhesive dressing for a four hours period.

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.

Duration of treatment / exposure:

The experimental phase of the study was undertaken between 11 and 14 August 1992./Single dermal dose

Observation period:

Four hours

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.
- Type of wrap if used: Elastoplast

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with acetone to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: Each treatment site was covered with "Elastoplast" elastic adhesive dressing for a four hours period.

SCORING SYSTEM: Erythema and eschar formation and Oedema formation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No dermal response to treatment was observed in any animal throughout the observation period.

Rabbit #	E = ErythemaO = Oedema	Day1, 2, 3, 4
579	EO	0, 0, 0, 00, 0, 0, 0
580	EO	0, 0, 0, 00, 0, 0, 0
581	EO	0, 0, 0, 00, 0, 0, 0

Conclusions:

Under the study conditions, the test substance was not irritating to rabbit skin.

Executive summary:

An in vivo skin irritation study was conducted in accordance with Method B.4, Part B, EU DIrective 84/449/EEC, under GLP conditions. Three New zealand white rabbits were exposed to a single semi-occlusive application of 0.5 mL EB 3608 to intact skin for four hours. No dermal response to treatment was observed in any animal up to 72 hours post exposure. Under the study conditions, the test substance was not irritating to rabbit skin (Liggett, 1992).

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:

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

Adequacy of study:

key study

Study period:

From June 02 to 12, 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD guideline 405 with minor deviations: no certificate of analysis

Justification for type of information:

Justification for read-across has been mentioned in detail under section 13 of the dataset.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no certificate of analysis

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 6 weeks (at least)
- Weight at study initiation: 1.0 kg (at least)
- Housing: Housed individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Pelleted diet (K-H from SSNIFF® Spezialdiaten GmbH, Soest, Germany), 100 g/day; hay (TecniLab-BMI BV, Someren, The Netherlands) provided at least three times a week
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 5 days (at least)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2-21.5 °C
- Humidity (%): 45-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours fluorescent light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume with unit): 0.1 mL

Duration of treatment / exposure:

Not aplicable ( eye not rinsed)

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Three males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Not applicable

SCORING SYSTEM: Scoring system same as recommended by OECD Guideline 405

CORNEAL IRRlTATlON
- Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster): 0
Scattered or diffuse areas of opacity, details of iris clearly visible: 1
Easily discernible translucent area, details of iris slightly obscured: 2
Nacreous area, no details of iris visible, size of pupil barely discernible: 3
Opaque cornea, iris not discernible through the opacity: 4

- Area of cornea involved:
No ulceration or opacity: 0
One quarter or less but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4

IRIS
Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneaI hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive): 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2

CONJUNCTIVAL IRRlTATlON
- Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal: 0
Some blood vessels definitely hyperaemic (injected): 1
Diffuse, crimson color, individual vessels not easily discernible: 2
Diffuse beefy red: 3

- Chemosis (refers to lids and/or nictitating membranes):
No swelling: 0
Any swelling above normal (includes nictitating membranes): 1
Obvious sweIling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4

- Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals): 0
Any amount different from normal and/or lacrimation: 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs (considerable area around the eye): 3

TOOL USED TO ASSESS SCORE: Eye examinations were performed using fluorescein (2%) and/or an ophthalmic examination lamp (if standard lighting was inadequate)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

- Irritation of the conjunctivae which consisted of redness, chemosis and discharge, completely resolved within 72 hours
- Remnants of the test substance were present and on the outside of the eyelids throughout the observation period
- See table 1 and 2 for further details

Other effects:

- No mortality or symptoms of systemic toxicity
- Slight bodyweight loss observed in one animal but considered of no toxicological relevance, based on the absence of corroborative findings

Table 1: Individual eye irritation scores

Animal	Time after dosing (hours)	Cornea			Iris	Conjunctivae			Comments
		Opacity	Area	Fluor area (%)^2		Redness	Chemosis	Discharge
847^1	1	0	0	0	0	2	2	1	c
	24	0	0		0	1	0	1	c
	48	0	0		0	1	0	0	c
	72	0	0		0	0	0	0	c
859	1	0	0	0	0	2	2	1	c
	24	0	0		0	1	0	1	c
	48	0	0		0	1	0	0	c
	72	0	0		0	0	0	0	c
861	1	0	0	0	0	2	1	1	c
	24	0	0		0	1	0	1	c
	48	0	0		0	1	0	0	c
	72	0	0		0	0	0	0	c

¹Sentinel

²Green staining after fluorescein treatment (percentage of total corneal area)

c: Remnants of the test substance on the outside of the eyelids

Table 2: Mean (24, 48 and 72 hours) value eye irritation scores

Animal	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
847	0	0	0.7	0
859	0	0	0.7	0
861	0	0	0.7	0

Conclusions:

Under the study conditions, the test substance was not irritating to rabbit eyes.

Executive summary:

An in vivo eye irritation study was conducted with the read-across substance in rabbits according to the OECD Guideline 405 and in compliance with GLP. Three healthy male New Zealand White rabbits were exposed to 0.1 mL of undiluted test substance to one of the eyes 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 according to the method of OECD Guideline 405. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the three animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.7, 0.7 for conjunctivae score and 0, 0, 0 for chemosis score. Under the study conditions, the test substance was not irritating to rabbit eyes (Beerens-Heijnen CGM, 2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

An in vivo skin irritation study was conducted in accordance with Method B.4, Part B, EU DIrective 84/449/EEC, under GLP conditions. Three New zealand white rabbits were exposed to a single semi-occlusive application of 0.5 mL of the substance to intact skin for four hours. No dermal response to treatment was observed in any animal up to 72 hours post exposure. Under the study conditions, the test substance was not irritating to rabbit skin (Liggett, 1992).

Eye irritation

An in vivo eye irritation study was conducted with the read-across substance in rabbits according to the OECD Guideline 405 and in compliance with GLP. Three healthy male New Zealand White rabbits were exposed to 0.1 mL of undiluted test substance to one of the eyes 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 according to the method of OECD Guideline 405. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the three animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.7, 0.7 for conjunctivae score and 0, 0, 0 for chemosis score. Under the study conditions, the test substance was not irritating to rabbit eyes (Beerens-Heijnen CGM, 2008).

Justification for classification or non-classification

Based on the results of the in vivo skin irritation and eye irritation studies with the test substance and the read-across substance, no classification for skin and eye irritation is warranted according to EU CLP (Regulation EC/1272/2008) criteria.