1,4-butanediyl diacrylate

Endpoint summary

Description of key information

Skin: corrosive (BASF, 1979)

Eye: corrosive (BASF, 1978)

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: M. Gaukler, Offenbach
- Weight at study initiation: about 3 kg
- Diet: ad libitum (Ssniff K; supplying company: Intermast GmbH, Soest)
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

1 hour (2 animals, one male and one female) and 4 hours (2 animals both male)

Observation period:

8 days; reading:
(4 hours exposure): 4 hours, 1 day, 4 days and 8 days after the end of the exposure
(1 hour exposure): 1 hour, 1 day, 2 days, 8 days after the end of the exposure

Number of animals:

2 animals exposed for 1 hour, 2 other animals for 4 hours

Details on study design:

TEST SITE
- Area of exposure: trunk
- coverage: 2 x 2 cm

REMOVAL OF TEST SUBSTANCE
- Washing with lutrol or a water/lutrol mixture (1+1)
- Time after start of exposure: 1 and 4 hours after application

SCORING SYSTEM:
similar to the one described in 404 OECD guideline

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 and 48 hours

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 1 hour exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 and 48 hours

Score:

3.25

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 1 hour exposure

Other effects:

4h: Necrosis detected in both animals, though in one animal reduced to scaling at the end of the observation period.
1h: Scaling at the end of the obervation period. No necrosis occured.

Draize scores of individual animals:

1 hour exposure	time	animal 1	animal 2
erythema	1 h	2	2
	24 h	2	2
	48 h	3	3
	8 d	2	2
edema	1 h	2	2
	24 h	2	4
	48 h	3	4
	8 d	2	2

4 hours exposure	time	animal 1	animal 2
erythema	4 h	3	3
	24 h	3	3
	4 d	4	3	#1: necrosis
	8 d	4	4	#1: scaling, #2: necrosis
edema	1 h	4	3
	24 h	4	4
	4 d	2	3
	8 d	2	3

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Guideline:

other: Draize Test

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

8 days

Number of animals:

12 (6 intact skin, 6 abraded skin)

Details on study design:

TEST SITE
- Area of exposure: 1 inch x 1 inch

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 - 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

72 hours

Remarks on result:

other:

Remarks:

intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 72 hours

Score:

2.75

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

72 hours

Remarks on result:

other:

Remarks:

intact skin

rabbit number	intact skin		rabbit number	abraded skin
	24 hours	72 hours		24 hours	72 hours
	A-B	A-B		A-B	A-B
6792	4-4	4-2	6786	4-3	4-3
6793	4-3	4-2	6787	4-3	4-3
6794	4-3	4-3	6788	4-4	4-2
6795	4-3	4-2	6789	4-4	4-2
6796	4-3	4-3	6790	4-4	4-2
6797	4-3	4-2	6791	4-4	4-2
average:	7.2	6.3	average:	7.7	6.3

Primary Irritation Index: 6.9

A = erythema

B = edema

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Undiluted test substance (about 0.5 ml) was applied on the shaved backs or ears. Application time was 1, 5, 15 min (only back skin) and 20 hours under occlusive conditions. After the application time, the skin was washed with water which contained a mild detergent (Lutrol). The animals were observed for 8 days.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

undiluted test substance (ca. 0.5 ml)

Duration of treatment / exposure:

Exposure was 1, 5, 15 min and 20 hours.

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: shaved back of the animals
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: occlusive dressing; not further specified


REMOVAL OF TEST SUBSTANCE
After the application time, the skin was washed with water which contained a mild detergent (Lutrol).


SCORING SYSTEM:
similar to the one described in OECD 404 guideline

Irritation parameter:

erythema score

Basis:

mean

Remarks:

20h exposure

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

20h exposure

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

15 min exposure

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks:

scaling remained

Irritation parameter:

edema score

Basis:

mean

Remarks:

15 min exposure

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

irritant after exposure for 1-15min.
Necrosis occured after exposure times of 20h

Descriptions from original report were translated into Draize Scores by registrant

Erythema
Exposure time	Effects after	Animal #1	Animal #2
1 min	24h	3	2
	8 days	0	0
5 min	24h	3	2
	8 days	0 (scaling)	0 (scaling)
15 min	24h	3	3
	8 days	0 (scaling)	0 (scaling)
20h	24h	3	3
	8 days	necrosis	necrosis
20h (ear)	24h	4	4
	8 days	necrosis	necrosis

Edema
Exposure time	Effects after	Animal #1	Animal #2
1 min	24h	2	0
	8 days	0	0
5 min	24h	2	2
	8 days	0 (scaling)	0 (scaling)
15 min	24h	2	2
	8 days	0 (scaling)	0 (scaling)
20h	24h	4	4
	8 days	necrosis	necrosis
20h (ear)	24h	2	2
	8 days	necrosis	necrosis

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

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:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

- Observation period 7 days;

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The animals are caged individually and receive no hay or other extraneous material that might enter the eyes .

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animals

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single application

Observation period (in vivo):

The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material .

Number of animals or in vitro replicates:

6

Details on study design:

In general the techniques of tests as published by the FDA of the United States (Fed . Reg . 28 (119), 5582, 1963) and Draize and Kelley (Drug Cosmet . Industr . 71 (1952) 36) were followed . Six New Zealand White albino rabbits were used . The animals were caged individually and receive no hay or other extraneous material that might enter the eyes . The eyes of the animals were examined before testing and only those animals without observable eye defects were used . One tenth of a milliliter of the test substance was allowed to fall on the everted lower lid of one eye of each rabbit ; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material . The other eye remained untreated and served as a control . The eyes were not washed following instillation, and the animals were released immediately .

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-48-72

Score:

1.3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-48-72

Score:

0.7

Max. score:

2

Reversibility:

other: day 7: one animal had Draize score 1; all other 0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-48-72

Score:

2.1

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-48-72

Score:

2.6

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Draize scores of individual animals

	time	animal 1	animal 2	animal 3	animal 4	animal 5	animal 6
corneal opacity	24 h	2	1	1	1	1	1
	48 h	1	1	1	1	1	2
	72 h	2	1	1	2	2	2
	7 d	1	3	0	2	3	3
iris	24 h	1	1	1	1	1	1
	48 h	0	0	0	1	1	1
	72 h	0	1	0	1	1	1
	7 d	0	0	0	0	0	1
conjunctiva erythema/edma redness / chemosis	24 h	2/4	2/3	2/3	2/3	2/3	2/3
	48 h	3/4	2/2	2/3	2/2	2/2	2/2
	72 h	2/3	2/2	2/2	2/2	2/2	2/2
	7 d	2/2	2/2	1/0	2/2	2/2	2/2

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Additional information

In a study to assess skin irritation / corrosion 2 rabbits each were exposed to the 0.5ml of the undiluted test substance for either 1h or 4h under occlusive conditions (BASF 1979). After exposure for 1h, mean values for erythema and edema (24/ 48h) were 2.5 and 3.25, respectively. At the end of the 8h observation period, scaling was still observed, but no necrosis occured. After an exposure time of 4h, the mean values were 3 for erythema and 4 for edema. Necrosis was detected in both animals, but in one animal this finding was reduced to scaling at the end of the observation period. Despite the harsh occlusive conditions and the fact that full thickness necrosis was not confirmed, it is still proposed to classify the substance as skin corrosive.

In a second study, the shaved skin of 6 rabbits was treated with 0.5ml of the undiluted test substance for 24h under occlusive conditions (TNO 1978). Erythema and Edema scores were 2.75 and 4 (mean values over all animals within the first 72h). After one week necrosis was observed at the application sites. The edges of the scabs showed slight signs of healing. This study confirms corrosive properties of the test substance after longer exposure times.

In a third study, 0.5ml of the undiluted test substance was occlusively applied for 1, 5, 15min, or 20h to the backs of 2 rabbits each, or for 20h to the ears of 2 rabbits. As observed in the previous studies, shorter exposure times (1, 5, 15min) led to irritation in the first days after exposure. At the end of the 8 -day observation period, scaling was still seen in some of the animals. The longer exposure time of 20h led to necrosis of the back and ears in all animals.

Eye irritating properties were examined by instillation of 0.1ml of the undiluted test substance into the eyes of 6 New Zealand White rabbits. The procedure generally followed OECD guideline 405, but the animals were only observed for 7 days and the substance was not washed out. The average scores (24 -72h after installation) were 1.3 for corneal opacity, 0.7 for iritis, 2.1 for conjunctival redness, and 2.6 for chemosis. With the exception of iritis and chemosis in single animals, effects did not lessen until day 7. Corneal opacity even worsened in most animals and reached a score of 3 in 3/6 rabbits. Based on that, reversibility within 21 days is thought to be unlikely.

In a supporting study, the lower amount of 0.05ml was placed in the eyes of two rabbits. After strong signs of irritation on the first days after exposure, alterations subsided until only single spots of corneal opacity were observed in one animal on day 12, which are expected to be fully reversible, if the rabbits had been observed for 21 days. Consequently, the lower amount of 0.05ml causes no irreversible damage.

Justification for classification or non-classification

After occlusive exposures for up to 1h, severe irritation of the skin, but no necrosis was observed. Longer exposure times (4h to 20h) led to destruction of the skin. Consequently, the substance needs to be classified as Skin Corr. Cat. 1C according to Regulation EC No. 1272/2008 (CLP). It should be noted that the substance is legally classified as skin corrosive cat. 1B.

Installation of 0.1ml into the eyes of rabbits led to irreverible damage. Thus the substance is also classified to cause damage to the eye, cat. 1.