Ferrate(4-), hexakis(cyano-C)-, methylated 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]benzenamine copper(2+) salts

Endpoint summary

Description of key information

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-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 various test chemicals

Justification for type of information:

Weight of evidence approach based on various test 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 various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment

Species:

guinea pig

Strain:

other: 2. albino; 3.not specified

Sex:

female

Route:

epicutaneous, open

Vehicle:

propylene glycol

Remarks:

study 2

Concentration / amount:

10%

Day(s)/duration:

three times weekly (Monday, Wednesday, Friday) for three consecutive weeks.

Adequacy of induction:

not specified

Route:

epicutaneous, open

Vehicle:

other: gum arabic

Remarks:

Study 3

Concentration / amount:

5% in 25% Aqueous solution of gum Arabic

Day(s)/duration:

5 days

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

10.0%, 5.0%, and 2 .5% in propylene glycol

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

No.:

#1

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

0.1ml of 0.01, 0.001, and 0.001% in saline

Adequacy of challenge:

not specified

No. of animals per dose:

2. 10
3. not specified

Details on study design:

2. Details on study design
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period:48 hour
- Test groups: 10
- Control group: no data
- Site: the left flanks of ten albino guinea pigs were shavedand the test material applied three times weekly( Monday,Wednesday,Friday)for three consecutiv weeeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area.
- Frequency of applications: three times weekly (Monday, Wednesday Friday) for three consecutive weeks.
- Duration: 3 weeks
- Concentrations:10%

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: Two week rest period
- Exposure period: 24 hour
- Test groups: 10
- Control group: No data available.
- Site: right flank of each guinea pig was shaved and test material applied on it.
- Concentrations: 10.0%, 5.0%, and 2.5%
- Evaluation (hr after challenge): 24 hour and 48 hours post-application

Other – The test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale (0 = no reaction, 1 -- slight reaction, 2 = moderate reaction, 3 = severe reaction. A positive reaction was defined as an erythema/edema value during the challenge phase of at least one skin grade higher than during the last induction phase.

3. RANGE FINDING TESTS: No data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: no data
- Exposure period: no data
- Test groups: No data
- Control group: No data
- Site: No data
- Frequency of applications: daily for 5 days
- Duration: 5 days
- Concentrations: 5% in 25% Aqueous solution of gum arabic

B. CHALLENGE EXPOSURE
- No. of exposures: no data
- Day(s) of challenge: no data
- Exposure period: no data
- Test groups: no data
- Control group: no data
- Site: no data
- Concentrations: 0.1ml of 0.01, 0.001, and 0.001% in saline
- Evaluation (hr after challenge): no data

Positive control substance(s):

yes

Remarks:

DNCB

Positive control results:

2. The positive control DNCB (2,4-dinitrochlorobenze) control at the 0.5% induction /challenge concentration elicited positive response in all animals tested.

Reading:

other: Challenge (WoE 2)

Hours after challenge:

24

Group:

test chemical

Dose level:

10.0%, 5.0%, and 2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

Reading:

other: Challenge (WoE 2)

Hours after challenge:

48

Group:

test chemical

Dose level:

10.0%, 5.0%, and 2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Group:

test chemical

Dose level:

0.1ml of  0.01, 0.001, and 0.001% in saline

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No dermal reaction were observed

Remarks on result:

no indication of skin sensitisation

Remarks:

WoE 3

Interpretation of results:

other: not sensitizing

Conclusions:

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Executive summary:

Various studies have been reviewed to evaluate the skin sensitization potential of the test chemical in living organisms. These include in vivo experimental studies performed on guinea pigs for the test chemical.

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of the test chemical. The test chemical was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5% in propylene glycol. During the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations in propylene glycol(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale. A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases. No erythema/edema was observed after application of test material. The test result was observed to be negative for the test substance. Therefore, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

This is supported by a Guinea pig maximization test performed to evaluate the dermal sensitization potential of the test chemical. The test material was applied topically 5% in 25%Aqueous solution of gum Arabic to the skin of guinea pigs for 5 days. After 2 weeks of rest period the challenge treatment was provided by epicuteneous injection of concentration 0.1ml of 0.01, 0.001, and 0.001% in saline. The guinea pigs were observed for signs of dermal sensitization after the challenge exposure. No signs of any skin allergic reaction were observed. Hence, the test chemical can be considered to be not sensitizing to guinea pig skin.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies have been reviewed to evaluate the skin sensitization potential of the test chemical in living organisms. These include in vivo experimental studies performed on guinea pigs for the test chemical.

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of the test chemical. The test chemical was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5% in propylene glycol. During the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations in propylene glycol(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale. A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases. No erythema/edema was observed after application of test material. The test result was observed to be negative for the test substance. Therefore, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

This is supported by a Guinea pig maximization test performed to evaluate the dermal sensitization potential of the test chemical. The test material was applied topically 5% in 25%Aqueous solution of gum Arabic to the skin of guinea pigs for 5 days. After 2 weeks of rest period the challenge treatment was provided by epicuteneous injection of concentration 0.1ml of 0.01, 0.001, and 0.001% in saline. The guinea pigs were observed for signs of dermal sensitization after the challenge exposure. No signs of any skin allergic reaction were observed. Hence, the test chemical can be considered to be not sensitizing to guinea pig skin.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.