Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Endpoint summary

Description of key information

Guinea pig maximisation test: not sensitising (OECD guideline 406; GLP); Induction: intradermal (0.5% in water) + epicutaneous (10% in petrolatum); Challenge: topical (1% in pretrolatum)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted prior to the availabilty of the LLNA skin sensitisation test.

Species:

guinea pig

Strain:

other: Pirbright white, Crl:HA

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Kißlegg, Germany
- Age at study initiation: Not stated
- Weight at study initiation: Main test: 356–426 g (males); 344–383 g (females)
- Housing: 5/cage
- Diet: pelleted diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): ca. 16
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

water

Concentration / amount:

0.5%

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

10%

Day(s)/duration:

2

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1%

Day(s)/duration:

1

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

test group: 5 males and 5 females
control group: 3 males and 2 females

Details on study design:

RANGE FINDING TESTS:
Intra-dermal injection of 5, 2.5 and 1% of the test substance caused skin reactions. At a concentration of 0.5% test substance no skin reactions were observed.
Dermal applications of 50, 25 and 5% of the test substance showed skin reactions. No skin reactions were observed after the dermal application of the test article at a concentration of 1%.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal
- Test groups:
1) FCA 50% (v/v) diluted in aqua ad iniectabilia,
2) test substance 0.5% in aqua ad iniectabilia,
3) test substance 0.5% in aqua ad iniectabilia/FCA
- Control group:
1) FCA 50% (v/v) diluted in aqua ad iniectabilia,
2) aqua ad iniectabilia,
3) aqua ad iniectabilia 50% (v/v) diluted in FCA

Epicutaneous
- Exposure period: 48 h
- Test groups: 10% test substance in petrolatum
- Control group: vehicle
- pretreatment with 10% SDS to induce irritation

B. CHALLENGE EXPOSURE
- Day(s) of challenge: day 21
- Exposure period: 24 h
- Test groups: 1% test substance in petrolatum
- Control group: 1% test substance in petrolatum
- Evaluation (hr after challenge): 24, 48

Positive control substance(s):

yes

Remarks:

Benzocaine

Positive control results:

Sensitisation rate (50% test substance) at 24 h: 60%
Sensitisation rate (50% test substance) at 48 h: 70%
Sensitisation rate (25% test substance) at 24 h: 30%
Sensitisation rate (25% test substance) at 48 h: 30%

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5% interdermal induction, 1% challenge

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0% interdermal induction, 1% challenge

No. with + reactions:

0

Total no. in group:

5

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5% interdermal induction, 1% challenge

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0% interdermal induction, 1% challenge

No. with + reactions:

0

Total no. in group:

5

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

Positive controls are assessed on regular basis in the laboratory

Interpretation of results:

GHS criteria not met

Conclusions:

The registration substance was not a skin sensitizer in this GPMT test. Thus, the test substance is not classified for skin sensitisation according to the criteria laid down in Regulation (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

Executive summary:

The skin sensitizing potential of the lyophilised registration substance (100% a.i.) was tested in 10 Pirbright white Guinea pigs using the Guinea pig maximisation test, according to EC method B.6 (1996) and OECD guideline 406 (1992). The intradermal induction concentration was 0.5%, the epicutanous induction was 10% and the challenge concentration tested was 1% of the test item.

No deviations from the methods described by the guideline were reported.

No allergic skin reactions occurred in test animals 24 and 48 h after the end of the challenge procedure with the test item at a challenge concentration of 1% in petrolatum. The sensitisation rate was 0%.

Thus, Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid was not a skin sensitizer in this GPMT test and is is not classified for skin sensitisation according to the criteria laid down in Regulation (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitizing potential of the registration substance (100% a.i.) was tested in 10 Pirbright white Guinea pigs using the Guinea pig maximisation test, according to EC method B.6 (1996) and OECD guideline 406 (1992). The intradermal induction was 0.5% in water, the epicutaneous induction was 10% in petrolatum and the challenge concentration tested was 1% of the test item in petrolatum. No allergic skin reactions occurred in test animals 24 and 48 h after the end of the challenge procedure with the test item at a concentration of 1% in petrolatum. The sensitisation rate was 0%.Thus, the registration substance was not a skin sensitizer in this GPMT test.

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account. For skin sensitisation, there is no reason to believe that results obtained in guinea pigs would not be applicable to humans.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on relevant, reliable and adequate data, Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid does not have to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 and GHS-UN with respect to skin sensitisation.