Registration Dossier

Administrative data

Description of key information

Skin Sensitization:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential for target substance.

2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
in vivo
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:
other: Weight of evidence approach based on structurally similar read across chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar read across chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on structurally similar read across chemicals
Principles of method if other than guideline:
Weight of evidence approach based on structurally similar read across chemicals
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on structurally similar read across chemicals
Specific details on test material used for the study:
- Name of test material (as cited in study report):C.I. Basic Red 12
- IUPAC name: 1,3,3-trimethyl-2-[(1E)-3-[(2E)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]prop-1-en-1-yl]-3H-indol-1-ium chloride
- Molecular formula: C25H29N2.Cl
- Molecular weight: 392.971 g/mol
- Substance type: Organic
- Physical state: Solid
Species:
other: mice and guinea pigs
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data available
No. of animals per dose:
Weight of evidence approach based on structuraly similar read across chemicals
Details on study design:
The study is based on weight of evidence approach from the read across values
Challenge controls:
Weight of evidence approach based on structuraly similar read across chemicals
Vehicle:
other: Weight of evidence approach based on structuraly similar read across chemicals
Concentration:
Weight of evidence approach based on structuraly similar read across chemicals
No. of animals per dose:
Weight of evidence approach based on structuraly similar read across chemicals
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
Other effects / acceptance of results:
The study is based on weight of evidence approach from the read across values
Reading:
1st reading
Group:
test group
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation
Parameter:
SI
Remarks on result:
other: No indication of sensitization observed
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:
On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential for target substance.
2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be not sensitizing to skin.
Executive summary:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential for 2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride.

LLNA assay was conducted to determine the dermal sensitization potential of the structurally similar read across chemical. The study was performed according to OECD 429 Guidelines. 20 females (nulliparous and non-pregnant) CBA mice were used for the study. 10%, 25% and 50% of the test chemical in propylene glycol was applied to the ears of mice. Hexyl cinnamic aldehyde and propylene glycol were used as positive and vehicle controls respectively.

After few days following the initial application, draining lymph nodes were excised. A single cell suspension of LNC was prepared. Incorporation of [3H]TdR was measured, and recorded as mean cpm ± standard deviation (SD) per node of three mice for each group. The incorporation of [3H]TdR was measured using a liquid scintillation counter and expressed as mean counts per min (cpm) + standard deviation per node of three animals for each test group. Increases in [3H]TdR incorporation relative to vehicle-treated controls were calculated for each test group and expressed as stimulation indices (SI). The SI values calculated for the substance concentrations 5, 10 and 25% were 1.5, 1.9 and 6.1 respectively. An EC3 value of 13.9% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 2 and 20%. The results of the 6 monthly HCA reliability checks of the recent years were 9.5, 13.1, 14.1 and 13.8%.

The SI values calculated for the substance concentrations 10, 25 and 50% were 1.1, 2.1 and 2.7 respectively. Since there was no indication that the test substance elicits an SI>=3 when tested up to 50%, the test substance was considered not to be a skin sensitizer.

 

A Guinea pig Maximization test was performed to determine the dermal sensitization potential of the another structurally similar read across chemical. The study was conducted as per OECD 406 Guidelines. 15 (10 females in experimental group, 5 females in negative control group) Dunkin- Hartley Guinea pigs were used for the study.

Intradermal injection with a 1% concentration and epidermal occlusive exposure (both in induction and challenge phase) to a 50% concentration of the test chemical in water was applied to skin of the experimental group. The 5 females in negative control group were also treated in the similar way. The experimental and negative control guinea pigs were assessed for signs of erythema and reactions 24 and 48 hours after removal of the dressing (challenge exposure).

Green/brown staining was observed at all test substance treated skin sites, 24 and 48 hours after challenge. This staining did not hamper the scoring of the skin reactions.

The test chemical was considered to be not sensitizing to guinea pig skin.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that 1,3,3-trimethyl-2-[(1E)-3-[(2E)-1,3,3 -trimethyl-2,3-dihydro-1H-indol-2-ylidene]prop-1-en-1-yl]-3H-indol-1-ium chloride will also behave in similar manner that of the read across chemicals and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential for 2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride.

LLNA assay was conducted to determine the dermal sensitization potential of the structurally similar read across chemical. The study was performed according to OECD 429 Guidelines. 20 females (nulliparous and non-pregnant) CBA mice were used for the study. 10%, 25% and 50% of the test chemical in propylene glycol was applied to the ears of mice. Hexyl cinnamic aldehyde and propylene glycol were used as positive and vehicle controls respectively.

After few days following the initial application, draining lymph nodes were excised. A single cell suspension of LNC was prepared. Incorporation of [3H]TdR was measured, and recorded as mean cpm ± standard deviation (SD) per node of three mice for each group. The incorporation of [3H]TdR was measured using a liquid scintillation counter and expressed as mean counts per min (cpm) + standard deviation per node of three animals for each test group. Increases in [3H]TdR incorporation relative to vehicle-treated controls were calculated for each test group and expressed as stimulation indices (SI). The SI values calculated for the substance concentrations 5, 10 and 25% were 1.5, 1.9 and 6.1 respectively. An EC3 value of 13.9% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 2 and 20%. The results of the 6 monthly HCA reliability checks of the recent years were 9.5, 13.1, 14.1 and 13.8%.

The SI values calculated for the substance concentrations 10, 25 and 50% were 1.1, 2.1 and 2.7 respectively. Since there was no indication that the test substance elicits an SI>=3 when tested up to 50%, the test substance was considered not to be a skin sensitizer.

 

A Guinea pig Maximization test was performed to determine the dermal sensitization potential of the another structurally similar read across chemical. The study was conducted as per OECD 406 Guidelines. 15 (10 females in experimental group, 5 females in negative control group) Dunkin- Hartley Guinea pigs were used for the study.

Intradermal injection with a 1% concentration and epidermal occlusive exposure (both in induction and challenge phase) to a 50% concentration of the test chemical in water was applied to skin of the experimental group. The 5 females in negative control group were also treated in the similar way. The experimental and negative control guinea pigs were assessed for signs of erythema and reactions 24 and 48 hours after removal of the dressing (challenge exposure).

Green/brown staining was observed at all test substance treated skin sites, 24 and 48 hours after challenge. This staining did not hamper the scoring of the skin reactions.

The test chemical was considered to be not sensitizing to guinea pig skin.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that 1,3,3-trimethyl-2-[(1E)-3-[(2E)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]prop-1-en-1-yl]-3H-indol-1-ium chloride will also behave in similar manner that of the read across chemicals and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride can be not sensitizing to skin.

Hence by applying the weight of evidence approach, 2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium chloride can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.