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 sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

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

Key result

Parameter:

SI

Value:

1.8

Test group / Remarks:

Group 2 (0.25% concentration)

Key result

Parameter:

SI

Value:

1.4

Test group / Remarks:

Group 3 (0.5% concentration)

Key result

Parameter:

SI

Value:

1.4

Test group / Remarks:

Group 4 (1% concentration)

STIMULATION INDEX

STIMULATION INDICES of 1.8, 1.4 and 1.4 were determined with the test item at concentrations of 0.25 %, 0.5 % and 1 % (w/v), respectively, in polyethylene glycol 300. No dose-response relationship was observed. Calculation of the EC 3 value was not performed because no test concentrations produced a STIMULATION INDEX (S.I.) of 3 or higher.

VIABILITY / MORTALITY

No deaths occurred during the study period.

CLINICAL SIGNS

No clinical signs of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

BODY WEIGHTS

The body weight of the animals, recorded prior to the first application and prior to necropsy, was within the range commonly recorded for animals of the strain and age.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 41048 is considered to be not sensitising to the skin.

Executive summary:

Currently no study is available for assessment of skin sensitisation potential of FAT 41048. However, a structural analogue FAT 41039/A was evaluated in a study conducted according to OECD Guideline 429. In order to study a possible contact allergenic potential of FAT 41039/A, three groups each of four female mice were treated daily with the test item at concentrations of 0.25, 0.5 and 1 % (w/v) in polyethylene glycol 300 by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. 1 % (w/v) was the highest technically applicable concentration in the vehicle. A control group of four mice was treated with the vehicle polyethylene glycol 300 only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions oflymph node cells were prepared from pooled lymph nodes which were subsequently washedand incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a ßscintillation counter. All treated animals survived the scheduled study period. No clinical signs were observed.

A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.)- In this study STIMULATION INDICES of 1.8, 1.4 and 1.4 were determined with the test item at concentrations of 0.25 %, 0.5 % and 1 % (w/v), respectively, in polyethylene glycol 300. FAT 41039/A was therefore found to be a non-sensitizer when tested up to the highest applicable concentration of 1 % (w/v) in polyethylene glycol 300. Using the principles of read across, FAT 41048 is also considered to be not sensitising to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Currently no study is available for assessment of skin sensitisation potential of FAT 41048. However, a structural analogue FAT 41039/A was evaluated in a study conducted according to OECD Guideline 429. In order to study a possible contact allergenic potential of FAT 41039/A, three groups each of four female mice were treated daily with the test item at concentrations of 0.25, 0.5 and 1 % (w/v) in polyethylene glycol 300 by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. 1 % (w/v) was the highest technically applicable concentration in the vehicle. A control group of four mice was treated with the vehicle polyethylene glycol 300 only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions oflymph node cells were prepared from pooled lymph nodes which were subsequently washedand incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a ßscintillation counter. All treated animals survived the scheduled study period. No clinical signs were observed.

A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.)- In this study STIMULATION INDICES of 1.8, 1.4 and 1.4 were determined with the test item at concentrations of 0.25 %, 0.5 % and 1 % (w/v), respectively, in polyethylene glycol 300. FAT 41039/A was therefore found to be a non-sensitizer when tested up to the highest applicable concentration of 1 % (w/v) in polyethylene glycol 300. Using the principles of read across, FAT 41048 is also considered to be not sensitising to the skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

FAT 41048 is considered to be not sensitising to the skin hence does not warrant classification for skin sensitisation according to Regulation (EC) No. 1272/2008 (CLP) criteria.