Glutaric anhydride

Endpoint summary

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:

supporting 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)

Deviations:

yes

Remarks:

only 3 minute and 1 hour exposure periods assessed. Separate animals used for each exposure period.

Principles of method if other than guideline:

The study was conducted in a similar manner to the OECD guideline, although only the 3 minute and 1 hour exposure periods assessed (due to the 4 hr exposure being covered in an additional study). There is no evidence in the report that the study was conducted according to GLP, however it appears to have been conducted in the spirit of GLP. Sufficient animals were used and the appropriate methodology used to assess the endpoint.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

3 minutes or 1 houre

Observation period:

7 days

Number of animals:

2 rabbits exposed for 3 minutes
6 rabbits exposed for 1 hour

Irritation parameter:

erythema score

Remarks:

following one-hour contact

Basis:

mean

Remarks:

3 males and 3 females

Time point:

7 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

following one-hour contact

Basis:

mean

Remarks:

3 males and 3 females

Time point:

7 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

following 3-minute contact

Basis:

mean

Remarks:

one male and one female

Time point:

14 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

following 3-minute contact

Basis:

mean

Remarks:

one male and one female

Time point:

14 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

None - no erythema, edema or other skin effects noted in any of the rabbits during the 7 day observation period.

Interpretation of results:

study cannot be used for classification

Conclusions:

On the basis of this study it can be concluded that following a 3 minute or 1 hour occluded exposure, the test material was not corrosive. However as recorded in an additional study where the exposure duration was 4 hours, the substance was demonstrated to be severly irritating.

Executive summary:

In previous skin irritancy test glutaric anhydride produced necrosis on 3 of 6 animals from 4 hours of occluded contact with 0.5 ml (BRRC Report 51-88). Therefore, further testing, using 2 shorter periods of occluded contact (one hour; 3 minutes), was conducted. A one-hour application of glutaric anhydride to covered rabbit skin resulted in no irritation on any of 6 rabbits. A 3- minute application of 0.5 ml did not produce any irritation on 2 of 2 animals tested. Therefore, glutaric anhydride was not "corrosive" to the skin in either the one-hour or the 3-minute test.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

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)

Deviations:

yes

Remarks:

Study considered only the 4 hr timepoint, no GLP

Principles of method if other than guideline:

Primary skin irritancy test appears to have been conducted in a similar manner to current guidelines although but only one exposure period was used (4 hr) rather than 3 minute, 1 hour and 4 hours. No evidence that GLP was conformed to although it appears to have been conducted 'in the spirit' of GLP.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

4 hours

Observation period:

7 days - observations at 5 hours, 1,2,3 and 7 days

Number of animals:

6; 3 male and 3 female

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

other: 5 hours

Score:

0.8

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

1.3

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

1.8

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

1.7

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animals

Time point:

other: 5 hours

Score:

0.2

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

0.5

Max. score:

2

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

1.3

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

1.2

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

other: desquamation and necrosis

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: no quantification possible

Other effects:

Evidence of moderate necrosis observed in 2 animals at day 1 and in an additional animal at day 2. This persisted until the end of the observation period. Desquamation was also observed in all animals at day 7.

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The overall scores for skin irritation (erythema and edema) observed in this study are inicative of an irritation response. Since necrosis was also observed it is clear that this substance is highly irritant. However the necrosis does not appear to have involved full thickness destruction of the skin thus it does not meet the criteria for corrosive. This substance is therefore Highly irritating.

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:

1988

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 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Male or female New Zealand White rabbits are dosed with volumes of 0.1, 0.01 and 0.005 ml (liquid or solid). The dose is instilled into the lower conjunctival sac of one eye per animal or is placed directly on the eye. The eyelids are held together for one second. Six eyes are dosed per test volume. The eyes are scored accoridng to Draize scoring system at one hour, approximately 4 hours, one day, 2 days, 3 days and 7 days after dosing. Additional readings are made, if necessary, at 14 and 21 days. Fluorescein (2%) staining is used to determine corneal injury before dosing and at readings after one day.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Dose applied directly to eyes. No indication of duration of exposure and no indication that eyes were washed after dosing. Thus it is not possible to accurately state the duration that the animals were exposed to the test substance.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

6

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

1.7

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

1.7

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

1.5

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Score:

0.3

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

14 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

1

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

0.8

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

0.7

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Score:

0.5

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

14 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

2.2

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

2.5

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

1.7

Max. score:

2

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Score:

0.8

Max. score:

2

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

14 d

Score:

0.6

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

2.7

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

2.3

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

1.5

Max. score:

3

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

7 d

Score:

0.3

Max. score:

1

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

14 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Instillation of 10 mg of sample into rabbit eyes resulted in moderate to severe corneal injury (opacity) in 5 of 6 animals. One treated eye had no corneal effects. Iritis was apparent in 6 eyes and moderate to severe conjunctival irritation developed in 6 rabbits. After 48 hours, all rabbits exhibited a pus-like ocular discharge. Two eyes had a normal appearance after 7 days. Corneal vascularization developed in one rabbit and another animal exhibited a hemorrhaged nictitating membrane. One animal died at 12 days. The treated eye of this animal had completely healed by 7 days. The death was not considered to be related to the treatment. By 14 days, 2 of the remaining 5 eyes had a normal appearance. Two others only had minor conjunctival irritation. All eyes were healed after 21 days.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance appears to have caused severe damage to the eyes that persisted through the first 72 hours after dosing. All lesions subsequently heald over the course of the observation period with no damage present at day 21. Due to the severity of the initial lesions and their persistance for more than 24 hours, this test material meets the criteria for classification as an eye irritant that may cause serious damage to the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available