Reaction mass of 5-[(Disubstituted-dihydrocarbopolycyclyl)diazenyl]-6-hydroxy-4-methyl-2-substituted-1-propyl-1,2-dihydropyridine-3-carbonitrile and 1-Butyl-5-[(disubstituted-dihydrocarbopolycyclyl)diazenyl]-6-hydroxy-4-methyl-2-substituted-1,2-dihydropyridine-3-carbonitrile

Endpoint summary

Description of key information

FAT 41048 is considered to be not irritating to skin and eyes of rabbit.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Other effects:

Orange staining produced by the test item was visible up to 24 hours after treatment in two animals and up to 48 hours after treatment in the third animal.

CORROSION

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

VIABILITY/MORTALITY/CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

BODY WEIGHTS

The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 41048 is considered to be "not irritating" to rabbit skin.

Executive summary:

Currently no study investigating skin irritation potential of FAT 41048 is available. However, the primary skin irritation potential of structural analogue, FAT 41039/A was investigated according to OECD Guideline 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.The application of FAT 41039/A to the skin resulted in no signs of irritation. The test item caused slight orange staining of the treated skin in all animals at the 1- and 24-hour reading and persisted in one animal at the 48-hour reading. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FAT 41039/A is considered to be "not irritating" to rabbit skin.

Using the principles of read across FAT 41048 is also considered to be not irritating to the rabbit skin.

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

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and 0.67 for reddening and 0.00 for Chemosis for all three animals, respectively.
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.
Slight to moderate reddening of the conjunctivae was noted in all animals at the 1-hour reading and persisted as slight reddening in all animals up to the 48-hour reading.
Obvious swelling (Chemosis) of the conjunctivae with partial eversion of lids was observed in two animals at the 1-hour reading.
Slight to moderate reddening of the sclerae was present in all animals at the 1-hour reading and persisted a"s slight reddening in two animals until the 24- and 48-hour examination, respectively.
Slight ocular discharge was seen in all animals at the 1-hour reading.
No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.

Other effects:

No staining of the treated eyes produced by the test item was observed.
Slight red remnants of the test item were observed in the eye or conjunctival sac of two animals at the 1 -hour reading.

CORROSION

No corrosion of the cornea was observed at any of the reading times.

BODY WEIGHTS

The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 41048 is considered to be "not irritating" to the rabbit eye.

Executive summary:

Currently, no study is available to assess the skin irritation potential of FAT 41048. However, the primary eye irritation potential of a structural analogue, FAT 41039/A was investigated according to OECD Guideline 405. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and Chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and

0.67 for reddening and 0.00 for Chemosis for all three animals, respectively. The instillation of FAT 41039/A into the eye resulted in moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and Chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. Slight red remnants of the test item were observed in the eye or conjunctival sac of two animals at the 1-hour reading. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), FAT 41039/A is considered to be "not irritating" to the rabbit eye. Using the principles of read across, FAT 41048 is also considered to be not irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN

Currently no study investigating skin irritation potential of FAT 41048 is available. However, the primary skin irritation potential of structural analogue, FAT 41039/A was investigated according to OECD Guideline 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.The application of FAT 41039/A to the skin resulted in no signs of irritation. The test item caused slight orange staining of the treated skin in all animals at the 1- and 24-hour reading and persisted in one animal at the 48-hour reading. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FAT 41039/A is considered to be "not irritating" to rabbit skin. Using the principles of read across, FAT 41048 is also considered to be not irritating to the rabbit skin.

EYE

Currently, no study is available to assess the skin irritation potential of FAT 41048. However, the primary eye irritation potential of a structural analogue, FAT 41039/A was investigated according to OECD Guideline 405. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and Chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and 0.67 for reddening and 0.00 for Chemosis for all three animals, respectively. The instillation of FAT 41039/A into the eye resulted in moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and Chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. Slight red remnants of the test item were observed in the eye or conjunctival sac of two animals at the 1-hour reading. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), FAT 41039/A is considered to be "not irritating" to the rabbit eye. Using the principles of read across, FAT 41048 is also considered to be not irritating to the rabbit eye.

Justification for classification or non-classification

The substance is considered to be not irritating to skin and eyes, hence it does not warrant classification according to Regulation (EC) No. 1272/2008 (CLP) criteria.