9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs.

Endpoint summary

Description of key information

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. Based on the summarized studies,it can be concluded that the testchemical is unable to cause skin sensitization and considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it 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:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on 3 skin sensitization studies as- WoE-2, WoE-3 and WoE-4.
Skin sensitization potential of test chemical was determined by tests on guinea pigs and humans.

GLP compliance:

not specified

Type of study:

other: 1,2.a modified Buehler and Klecak method 3.patch test

Justification for non-LLNA method:

not specified

Species:

other: 1,2.guinea pig 3.Human

Strain:

other: 1,2.Albino 3. Not applicable

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: 1,2.epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

10% (0.1mL)

Day(s)/duration:

3 weeks

Adequacy of induction:

not specified

Route:

other: 3.epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

2%

Day(s)/duration:

7 days

Adequacy of induction:

not specified

No.:

#1

Route:

other: 1,2.epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

10.0%, 5.0%, and 2.50%

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No.:

#1

Route:

other: 3.epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

2%

Day(s)/duration:

7 days

Adequacy of challenge:

not specified

No. of animals per dose:

1,2.10
3. 27 patients

Details on study design:

1,2.MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 24 hour
- Test groups: 10
- Control group: no data
- Site: shaved left flanks of ten albino guinea pigs 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 hours
- Test groups: 10
- Control group:
- Site: shaved left flanks of ten albino guinea pigs
- Concentrations: 10.0%, 5.0%, and 2.50%
- Evaluation (hr after challenge): 24 hour and 48 hours

3. The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.The reactions of the patients were graded as ?+. + and ++ categories.

Positive control substance(s):

yes

Remarks:

1,2.0.5% DNCB 3.Not specified

Positive control results:

1,2.The positive DNCB (2, 4-dinitrochlorobenze) control at the 0.5% induction /challenge concentration elicited positive response in all animals tested.

Reading:

other: 1,2.1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10.0%, 5.0%, and 2.50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No erythema/edema was observed after 24 and 48 hours post-application.

Remarks on result:

no indication of skin sensitisation

Reading:

other: 3. 1st reading

Hours after challenge:

168

Group:

test chemical

Dose level:

2%

No. with + reactions:

0

Total no. in group:

27

Clinical observations:

None of the treated patients showed allergic contact dermatitis.

Remarks on result:

no indication of skin sensitisation

1,2.

All 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 and

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.

Table 1:  Patch test results

 

Chemical	No of patients tested	?+	+	++
Test chemical  (2%pet..)	27	0	0	0

Interpretation of results:

other: Not sensitizing

Conclusions:

The test chemical was considered to be skin sensitizing to the skin of guinea pigs and humans.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

 

Skin sensitization studies for two structurally similar read across chemicals were conducted in guinea pig using modified Buehler and Klecak method for open epicutaneous testing. In each study, for the induction phase, the left flanks of 10 albino guinea pigs were shaved and the test material was applied three times weekly (Monday, Wednesday Friday) for three consecutive weeks. Each animal received 0.1 ml of the 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 concentration (10.0%, 5.0%, and 2.50%of the induction concentration). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. 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. No erythema/edema was observed after 24 and 48 hours post-application. Hence the test substances were considered as not sensitizing to the guinea pigs skin.

 

The above results were further supported by the patch test study performed on another similar read across chemical to determine the allergic contact dermatitis caused by the chemical on human patients. The dye was applied on27patients in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories.None of the treated patients showedany signs ofallergic contact dermatitis. Hencethe test chemical can be considered as non-sensitizer to human skin.

 

Based on the above summarized studies for target chemical and its structurally and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

 

Skin sensitization studies for two structurally similar read across chemicals were conducted in guinea pig using modified Buehler and Klecak method for open epicutaneous testing. In each study, for the induction phase, the left flanks of 10 albino guinea pigs were shaved and the test material was applied three times weekly (Monday, Wednesday Friday) for three consecutive weeks. Each animal received 0.1 ml of the 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 concentration (10.0%, 5.0%, and 2.50%of the induction concentration). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. 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. No erythema/edema was observed after 24 and 48 hours post-application. Hence the test substances were considered as not sensitizing to the guinea pigs skin.

 

The above results were further supported by the patch test study performed on another similar read across chemical to determine the allergic contact dermatitis caused by the chemical on human patients. The dye was applied on27patients in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories.None of the treated patients showedany signs ofallergic contact dermatitis. Hencethe test chemical can be considered as non-sensitizer to human skin.

 

Based on the above summarized studies for target chemical and its structurally and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance andits structurally and functionally similar read across substanceswere observed in various studies. From the results obtained from these studies it is concluded that the chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.