2-[2-[4-(diethylamino)phenyl]vinyl]-1,3,3-trimethyl-3H-indolium acetate

Endpoint summary

Description of key information

Based on the available data and applying the weight of evidence approach, it can be concluded that the test chemical can be considered to be not sensitizing to 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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Weight of evidence approach based on structurally similar chemicals

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on structurally similar chemicals

Principles of method if other than guideline:

The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of the test chemical

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach based on structurally similar chemicals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

no data available

Vehicle:

other: DMF, ethanol:water (7:3 v/v)

Concentration:

1. 2.5%, 5% and 10% (w/v) solutions
2 .0, 2.5, 5, 10 or 25% (w/v)

No. of animals per dose:

3

Details on study design:

The study is based on weight of evidence approach from the read across values

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

The study is based on weight of evidence approach from the read across values

Positive control results:

The study is based on weight of evidence approach from the read across values

Parameter:

SI

Test group / Remarks:

test group

Remarks on result:

other: not sensitizing

Cellular proliferation data / Observations:

The study is based on weight of evidence approach from the read across values

Interpretation of results:

other: not sensitizing

Conclusions:

Based on the available data and applying the weight of evidence approach, it can be concluded that the test chemical can be considered to be not sensitizing to skin.

Executive summary:

Based on the available studies, weight of evidence approach was applied to assess the dermal sensitization potential of the test chemical

Mouse Lymph node assay [LLNA] was performed on groups of female mice to assess the skin sensitizing potential of the test chemical. The assay was performed according to OECD 429 Guidelines.Three dose groups and a control group (receiving the vehicle only) of four female mice each, were chosen. Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with the2.5%, 5% and 10% (w/v) solutions of the test chemical. The application volume, 25 μl, was spread over the entire dorsal surface of each ear lobe once daily for 3consecutive days. The control group was treated with the vehicle. Five days after the first topical application, all mice were administered with radio-labelled thymidine (³HTdR) by intravenous injection via the tail vein. Approximately 5 hours after ³HTdR application all mice were killed. The draining lymph nodes were excised and pooled for each experimental group. After preparation of the lymph nodes, disaggregation and overnight precipitation of macromolecules, these precipitations were re-suspended and transferred to scintillation vials. The level of ³HTdR incorporation was then measured by scintillation counting. The proliferative response of lymph node cells is expressed as the ratio of ³HTdR incorporation into lymph node cells of treated animals relative to that recorded in control mice (stimulation index). α- hexylcinnamaldehyde was used as positive control, to show distinct increases in the stimulation index. The Stimulation Index (S.I.) was below 3 in all dose groups. No dose response relation was noted. Calculation of the EC 3 value was not performed as the S.I. value did not reach or exceed 3 for any test concentration. The positive control used affected an increase in stimulation index with an EC3 of 11.7%.

Based on the criteria of the test system, the test chemical was not a non-sensitizer when tested up to 10% in ethanol:water (7:3 v/v) in mice.

This is supported by the results of another LLNA study performed according to OECD 429 Guidelines for the test chemical.The test material was soluble in dimethylformamide (DMF). This vehicle was selected on the basis of the results from a previous solubility study showing that the test chemical was non-soluble in other recommended vehicles, and that 25% (w/v) in DMF was the maximal practicable concentration. α hexylcinnamaldehyde at 25% (v/v) in DMF used as positive control.The test substance, DMF or HCA was applied in dose concentration 1, 2.5, 5, 10 or 25% (w/v) on the ears (25 μL per ear) of the animals for 3 consecutive days designated as days 1, 2 and 3. After 2 days of resting(day 6), mice received a single intravenous injection of triturated methyl thymidine (3H-TdR). Lymph nodes draining the application sites (auricular nodes) were sampled, pooled per group, and the proliferation of lymphocytes was evaluated by measuring the incorporation of 3H-TdR.The values obtained were used to calculate stimulation indices (SI), and the EC3 was estimated (theoretical concentration resulting in a SI of 3). The irritant potential of the test chemical was assessed by measuring ear thickness on days 1, 2, 3 and 6.There were no irritation reactions and no lymphoproliferative responses, and the threshold SI of 3 values was not approached in any of the test groups.Hence, the test chemicalwas considered to be not sensitizing in mice by LLNA method.

Based on the available data and applying the weight of evidence approach, it can be concluded that the test chemical can be considered to be not sensitizing to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Based on the available studies, weight of evidence approach was applied to assess the dermal sensitization potential of the test chemical

Mouse Lymph node assay [LLNA] was performed on groups of female mice to assess the skin sensitizing potential of the test chemical. The assay was performed according to OECD 429 Guidelines.Three dose groups and a control group (receiving the vehicle only) of four female mice each, were chosen. Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with the2.5%, 5% and 10% (w/v) solutions of the test chemical. The application volume, 25 μl, was spread over the entire dorsal surface of each ear lobe once daily for 3consecutive days. The control group was treated with the vehicle. Five days after the first topical application, all mice were administered with radio-labelled thymidine (³HTdR) by intravenous injection via the tail vein. Approximately 5 hours after ³HTdR application all mice were killed. The draining lymph nodes were excised and pooled for each experimental group. After preparation of the lymph nodes, disaggregation and overnight precipitation of macromolecules, these precipitations were re-suspended and transferred to scintillation vials. The level of ³HTdR incorporation was then measured by scintillation counting. The proliferative response of lymph node cells is expressed as the ratio of ³HTdR incorporation into lymph node cells of treated animals relative to that recorded in control mice (stimulation index). α- hexylcinnamaldehyde was used as positive control, to show distinct increases in the stimulation index. The Stimulation Index (S.I.) was below 3 in all dose groups. No dose response relation was noted. Calculation of the EC 3 value was not performed as the S.I. value did not reach or exceed 3 for any test concentration. The positive control used affected an increase in stimulation index with an EC3 of 11.7%.

Based on the criteria of the test system, the test chemical was not a non-sensitizer when tested up to 10% in ethanol:water (7:3 v/v) in mice.

This is supported by the results of another LLNA study performed according to OECD 429 Guidelines for the test chemical.The test material was soluble in dimethylformamide (DMF). This vehicle was selected on the basis of the results from a previous solubility study showing that the test chemical was non-soluble in other recommended vehicles, and that 25% (w/v) in DMF was the maximal practicable concentration. α hexylcinnamaldehyde at 25% (v/v) in DMF used as positive control.The test substance, DMF or HCA was applied in dose concentration 1, 2.5, 5, 10 or 25% (w/v) on the ears (25 μL per ear) of the animals for 3 consecutive days designated as days 1, 2 and 3. After 2 days of resting(day 6), mice received a single intravenous injection of triturated methyl thymidine (3H-TdR). Lymph nodes draining the application sites (auricular nodes) were sampled, pooled per group, and the proliferation of lymphocytes was evaluated by measuring the incorporation of 3H-TdR.The values obtained were used to calculate stimulation indices (SI), and the EC3 was estimated (theoretical concentration resulting in a SI of 3). The irritant potential of the test chemical was assessed by measuring ear thickness on days 1, 2, 3 and 6.There were no irritation reactions and no lymphoproliferative responses, and the threshold SI of 3 values was not approached in any of the test groups.Hence, the test chemicalwas considered to be not sensitizing in mice by LLNA method.

Based on the available data and applying the weight of evidence approach, it can be concluded that the test chemical can be considered to be not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data and applying the weight of evidence approach, it can be concluded that the test chemical can be considered to be not sensitizing to skin.