1-(3-chlorophenyl)-4-(3-chloropropyl)piperazinium chloride

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 behave in similar manner and was estimated to be  sensitizing to skin. Thus it can be further classified under the category “Skin Sensitizer 1” as per CLP regulation.

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. the study 2, 3 are referred as study 1,2

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach based on various test chemicals

Justification for non-LLNA method:

not specified

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: HRP Inc. (Denver, PA).
- Age at study initiation: 5-7 weeks old
- Weight at study initiation: 278-444 grams

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion.
Epicutaneous induction - 0.2 ml of 50% piperazine

Adequacy of induction:

other: The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was considered for the epicutaneous induction.

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion.
Epicutaneous induction - 0.2 ml of100% test chemical

Adequacy of induction:

other: The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was considered for the epicutaneous induction.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

25%

Day(s)/duration:

24 hours

Adequacy of challenge:

highest non-irritant concentration

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

100%

Day(s)/duration:

24 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 male and 10 female guinea pigs

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

challenge concentration

Total no. in group:

20

Clinical observations:

signs of dermal sensitization observed

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

other: Sensitizing

Conclusions:

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 behave in similar manner and was estimated to be sensitizing to skin. Thus it can be further classified under the category “Skin Sensitizer 1” as per CLP regulation.
 

Executive summary:

The dermal sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

The dermal sensation potential of the test chemical was evaluated in guinea pigs following the method described by Magnusson and Kligman. 10 male and 10 female Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs weighing 278-444 grams were used for the study.Range finding studies were conducted to select the appropriate concentration for induction and challenge exposures.

Animals were inspected 24 and 48 h after dosing for signs of necrosis and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the epicutaneous induction, and the highest concentration that did not produce irritation was used for the epicutaneous challenge.

The concentrations obtained for the test chemical were – 5% intradermal induction, 50% epicutaneous induction,25% epicutaneous challenge. In the main sensitization study,0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion were injected on 2 sites each of the clipped shoulder skin of guinea pigs. After 7 days of intradermal induction, epicutaneous inductions were performed. 0.2 ml of 50% test chemical was applied in saturation to a 2*4cm filter paper, which was then placed on the test site and secured with a tape. The patches were left in place for 48 hours and after removal of the patches, the skin was wiped free of the excess test material. During the challenge phase, 25% piperazine was soaked in 2*2 cm filter paper squares was applied to a previously untreated site(right flank) 14 days after epicutaneous induction. Patches were left in place for 24 hours, and the sites were inspected for signs of irritation and scored 24 -48 hours after removal of patches.

The skin sensitization response for the test chemical was 2 5% when tested in 19 guinea pigs. The normalized skin sensitization response was 0.020.

The test chemical appeared to be moderate sensitizer based on the normalized response

Hence, the test chemical can be considered to be sensitizer to the skin of Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs.

This is supported by the results of another dermal sensation study performed to evaluate the dermal sensitization in guinea pigs following the method described by Magnusson and Kligman. 10 male and 10 female Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs weighing 278-444 grams were used for the study. Range finding studies were conducted to select the appropriate concentration for induction and challenge exposures.

Animals were inspected 24 and 48 h after dosing for signs of necrosis and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the epicutaneous induction, and the highest concentration that did not produce irritation was used for the epicutaneous challenge.

The concentrations obtained for the test chemical were – 5% intradermal induction, 100% epicutaneous induction,100% epicutaneous challenge. In the main sensitization study,0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion were injected on 2 sites each of the clipped shoulder skin of guinea pigs. After 7 days of intradermal induction, epicutaneous inductions were performed. 0.2 ml of 50% piperazine was applied in saturation to a 2*4cm filter paper, which was then placed on the test site and secured with a tape. The patches were left in place for 48 hours and after removal of the patches, the skin was wiped free of the excess test material. During the challenge phase, 100% test chemical was soaked in 2*2 cm filter paper squares was applied to a previously untreated site(right flank) 14 days after epicutaneous induction. Patches were left in place for 24 hours, and the sites were inspected for signs of irritation and scored 24 -48 hours after removal of patches.

The skin sensitization response for the test chemical was 1% when tested in 19 guinea pigs. The normalized skin sensitization response was 0.001.

The test chemical was considered to have a low potential to cause skin sensitization based on the normalized response

Hence, the test chemical can be considered to be sensitizer to the skin of Dunkin Hartley Haz:(DH)fBR albino male and female 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 behave in similar manner and was estimated to be  sensitizing to skin. Thus it can be further classified under the category “Skin Sensitizer 1” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The dermal sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

The dermal sensation potential of the test chemical was evaluated in guinea pigs following the method described by Magnusson and Kligman. 10 male and 10 female Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs weighing 278-444 grams were used for the study.Range finding studies were conducted to select the appropriate concentration for induction and challenge exposures.

Animals were inspected 24 and 48 h after dosing for signs of necrosis and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the epicutaneous induction, and the highest concentration that did not produce irritation was used for the epicutaneous challenge.

The concentrations obtained for the test chemical were – 5% intradermal induction, 50% epicutaneous induction,25% epicutaneous challenge. In the main sensitization study,0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion were injected on 2 sites each of the clipped shoulder skin of guinea pigs. After 7 days of intradermal induction, epicutaneous inductions were performed. 0.2 ml of 50% test chemical was applied in saturation to a 2*4cm filter paper, which was then placed on the test site and secured with a tape. The patches were left in place for 48 hours and after removal of the patches, the skin was wiped free of the excess test material. During the challenge phase, 25% piperazine was soaked in 2*2 cm filter paper squares was applied to a previously untreated site(right flank) 14 days after epicutaneous induction. Patches were left in place for 24 hours, and the sites were inspected for signs of irritation and scored 24 -48 hours after removal of patches.

The skin sensitization response for the test chemical was 2 5% when tested in 19 guinea pigs. The normalized skin sensitization response was 0.020.

The test chemical appeared to be moderate sensitizer based on the normalized response

Hence, the test chemical can be considered to be sensitizer to the skin of Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs.

This is supported by the results of another dermal sensation study performed to evaluate the dermal sensitization in guinea pigs following the method described by Magnusson and Kligman. 10 male and 10 female Dunkin Hartley Haz:(DH)fBR albino male and female guinea pigs weighing 278-444 grams were used for the study. Range finding studies were conducted to select the appropriate concentration for induction and challenge exposures.

Animals were inspected 24 and 48 h after dosing for signs of necrosis and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the epicutaneous induction, and the highest concentration that did not produce irritation was used for the epicutaneous challenge.

The concentrations obtained for the test chemical were – 5% intradermal induction, 100% epicutaneous induction,100% epicutaneous challenge. In the main sensitization study,0.1ml intradermal induction injections containing 50% (v/v) Freunds complete adjuvant (FCA) water emulsion, 5% test material, and the test material in FCA/water emulsion or FCA/water emulsion were injected on 2 sites each of the clipped shoulder skin of guinea pigs. After 7 days of intradermal induction, epicutaneous inductions were performed. 0.2 ml of 50% piperazine was applied in saturation to a 2*4cm filter paper, which was then placed on the test site and secured with a tape. The patches were left in place for 48 hours and after removal of the patches, the skin was wiped free of the excess test material. During the challenge phase, 100% test chemical was soaked in 2*2 cm filter paper squares was applied to a previously untreated site(right flank) 14 days after epicutaneous induction. Patches were left in place for 24 hours, and the sites were inspected for signs of irritation and scored 24 -48 hours after removal of patches.

The skin sensitization response for the test chemical was 1% when tested in 19 guinea pigs. The normalized skin sensitization response was 0.001.

The test chemical was considered to have a low potential to cause skin sensitization based on the normalized response

Hence, the test chemical can be considered to be sensitizer to the skin of Dunkin Hartley Haz:(DH)fBR albino male and female 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 behave in similar manner and was estimated to be  sensitizing to skin. Thus it can be further classified under the category “Skin Sensitizer 1” as per CLP regulation.

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 behave in similar manner and was estimated to be  sensitizing to skin. Thus it can be further classified under the category “Skin Sensitizer 1” as per CLP regulation.