9,10-Anthracenedione, 1,4-diamino-, N,N'-mixed 2-ethylhexyl and hexyl and octyl derivs.

Endpoint summary

Description of key information

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,the test chemicalcan 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 report based in various test chemicals

Justification for type of information:

Weight of evidence report based in 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 report based in various test chemicals

Principles of method if other than guideline:

Weght of evidence report based in various test chemicals. The study 2,3 are referred as study

GLP compliance:

not specified

Type of study:

other: Weight of evidence report based in various test chemicals

Justification for non-LLNA method:

Currently no LLNA Study is available for assessment.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Route:

intradermal

Vehicle:

other: water-in-oil type emulsion

Concentration / amount:

aliquots of 0.1 ml each of a water-in-oil type emulsion (distilled water: FCA =1:1) were injected intradermally into the four corners of a previously shaved shoulder region (2 cm×4 cm)

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.1 ml of purified test preparation (1, 0.1 and 0.01%)

Day(s)/duration:

24 h

Adequacy of induction:

not specified

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

a 0.1 ml intradermal injection of Freund’s Complete Adjuvant (FCA) diluted to 50% in sterile isotonic saline

Day(s)/duration:

day 0, day 10

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 ml of undiluted test chemical

Day(s)/duration:

three times per week at 2-day intervals

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.5 ml aqueous solution of the test chemical at a concentration of 25% (w/w)

Day(s)/duration:

48 h

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.1 ml of purified test preparation (1, 0.1 and 0.01%)

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No. of animals per dose:

1. 20 guinea pigs
2. no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

no dermal reactions observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

Based on the available data for the various studies, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Not Classified”.

Executive summary:

Various studies have been summarized to ascertain the level of dermal sensitization caused by the test chemical in living organisms. These results include in vivo experimental studies performed on guinea pigs for the various test chemicals.

A study was performed to determine the Contact Sensitization caused by the test chemical in Guinea Pigs. Two preliminary studies were conducted to determine the challenge concentration of the test compound to be used in the principal study. Twenty (20) Hartley albino guinea pigs -10 males, 10 females were used for the study. The treatment region for each animal was clipped once a week. Guinea pigs were administered a 0.1 ml intradermal injection of Freund’s Complete Adjuvant (FCA) diluted to 50% in sterile isotonic saline on days 1 and 10 of the study. Beginning on day 1 of the study, 0.5 ml of undiluted test chemical was applied topically to the treatment site (which was just above the injection site) three times per week at 2-day intervals and once at the beginning of the fourth week. It was applied using a 2 cm² square of gauze that was moistened with water and kept in place by an occlusive patch. Treatment was suspended on day 24; the challenge application of a 0.5 ml aqueous solution of the test chemical at a concentration of 25% (w/w) was administered on untreated skin on the clipped left flank of the guinea pigs on day 36 of the study. This application was left on the skin for 48 hours under an occlusive patch. The skin was evaluated for evidence of sensitization, e.g. erythema and oedema, at 1, 6, 24 and 48 hours after removal of the patch. Treatment sites were biopsied 6-7 hours after patch removal due to staining of the skin that prevented evaluation of erythema at the treatment site. Four males and one female died during the course of the study; these deaths were not attributed to compound administration. No oedema was observed during the study. No abnormal histopathological findings were observed. Hence,the test chemical can be considered to be not sensitizing to the skin of guinea pigs.

This is supported by a study in which a modified guinea pig testing technique, the adjuvant and patch test was adapted to evaluate the contact hypersensitivity of test chemical on Hartley strain female albino guinea pigs. In intradermal induction, aliquots of 0.1 ml each of a water-in-oil type emulsion (distilled water: FCA =1:1) were injected intradermally into the four corners of a previously shaved shoulder region (2 cm×4 cm). At the injection sites, scratches in the shape of agrid were made with the needle used for injection.During topical induction, a closed patch with 0.1 ml of purified test preparation (1, 0.1 and 0.01%) was applied to the sites for 24 h. Abrasions and sample applications were repeated on the following 2 days. One week after the initial sensitization, 10% sodium lauryl sulfate in petrolatum was applied to the intradermal injection sites. On the next day, a closed patch of the test preparation was applied at the same sites for 48 h. After a rest period of 2 weeks, animals were challenged with the same purified test preparations (1, 0.1 and 0.01%) onto the shaved skin of the back. The excess substance was removed from the skin by washing with acetone at 24 h after the challenge application procedure. The skin reactions, fractional response (FR) and mean response (MR), were scored at 1, 24 and 48 h after the washing. The fractional response (FR) and mean response (MR) was observed to be 0.0 at each tested concentration. Since no response was detected to purified test preparation (1, 0.1 and 0.01%) in test and control group, the chemical was considered to be not sensitizing to the skin of Hartley strain female albino guinea pigs.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 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 summarized to ascertain the level of dermal sensitization caused by the test chemical in living organisms. These results include in vivo experimental studies performed on guinea pigs for the various test chemicals.

 

A study was performed to determine the Contact Sensitization caused by the test chemical in Guinea Pigs.

Two preliminary studies were conducted to determine the challenge concentration of the test compound to be used in the principal study.

Twenty (20) Hartley albino guinea pigs -10 males, 10 females were used for the study. The treatment region for each animal was clipped once a week. Guinea pigs were administered a 0.1 ml intradermal injection of Freund’s Complete Adjuvant (FCA) diluted to 50% in sterile isotonic saline on days 1 and 10 of the study. Beginning on day 1 of the study, 0.5 ml of undiluted test chemical was applied topically to the treatment site (which was just above the injection site) three times per week at 2-day intervals and once at the beginning of the fourth week. It was applied using a 2 cm² square of gauze that was moistened with water and kept in place by an occlusive patch. Treatment was suspended on day 24; the challenge application of a 0.5 ml aqueous solution of the test chemical at a concentration of 25% (w/w) was administered on untreated skin on the clipped left flank of the guinea pigs on day 36 of the study. This application was left on the skin for 48 hours under an occlusive patch. The skin was evaluated for evidence of sensitization, e.g. erythema and oedema, at 1, 6, 24 and 48 hours after removal of the patch. Treatment sites were biopsied 6-7 hours after patch removal due to staining of the skin that prevented evaluation of erythema at the treatment site. 

Four males and one female died during the course of the study; these deaths were not attributed to compound administration. No oedema was observed during the study. No abnormal histopathological findings were observed.

Hence, the test chemical can be considered to be not sensitizing to the skin of guinea pigs.

This is supported by a study in which a modified guinea pig testing technique, the adjuvant and patch test was adapted to evaluate the contact hypersensitivity of test chemical on Hartley strain female albino guinea pigs.

In intradermal induction, aliquots of 0.1 ml each of a water-in-oil type emulsion (distilled water: FCA =1:1) were injected intradermally into the four corners of a previously shaved shoulder region (2 cm×4 cm). At the injection sites, scratches in the shape of agrid were made with the needle used for injection.

During topical induction, a closed patch with 0.1 ml of purified test preparation (1, 0.1 and 0.01%) was applied to the sites for 24 h. Abrasions and sample applications were repeated on the following 2 days. One week after the initial sensitization, 10% sodium lauryl sulfate in petrolatum was applied to the intradermal injection sites. On the next day, a closed patch of the test preparation was applied at the same sites for 48 h. After a rest period of 2 weeks, animals were challenged with the same purified test preparations (1, 0.1 and 0.01%) onto the shaved skin of the back. The excess substance was removed from the skin by washing with acetone at 24 h after the challenge application procedure.

The skin reactions, fractional response (FR) and mean response (MR), were scored at 1, 24 and 48 h after the washing.

 

The fractional response (FR) and mean response (MR) was observed to be 0.0 at each tested concentration.

Since no response was detected to purified test preparation (1, 0.1 and 0.01%) in test and control group, the chemical was considered to be not sensitizing to the skin of Hartley strain female albino guinea pigs.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,the test chemicalcan 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 data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,the test chemicalcan be classified under the category “Not Classified”.