1-Butanaminium, 4-hydroxy-N,N,N-trimethyl-4-oxo-, inner salt

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed under GLP and in accordance with OECD-/EU-testing guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Details on test material:

- Substance number: 94/243
- Physical state & aspect: Liquid, yellowish
- Storage condition of test material: refrigerator

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH - Wiga, Kisslegg, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 307-359 g
- Housing: housed in groups à 5 animals in Makrolon, type IV cages
- Diet (e.g. ad libitum): Kliba-Labordiät 341, Klingenthalmühle AG; Kaiseraugst, Switzerland
- Water (e.g. ad libitum): tab water
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 h darkness; 12 h continuous light

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

unchanged (no vehicle)

Remarks:

test solution was applied as such

Induction 2

Concentration / amount:

INDUCTION
1. Intradermal induction:
- test substance 5% in 0,9% aqueous NaCl-solution
- Freund's adjuvant/0.9% aqueous NaCl - solution (1:1)
2. Percutaneous induction:
- test substance unchanged (40% aqueous solution)

CHALLENGE
1. Concentration of test material and vehicle used for each challenge:
- test substance unchanged (40% aqueous solution)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

test solution was applied as such

Challenge 2

Concentration / amount:

INDUCTION
1. Intradermal induction:
- test substance 5% in 0,9% aqueous NaCl-solution
- Freund's adjuvant/0.9% aqueous NaCl - solution (1:1)
2. Percutaneous induction:
- test substance unchanged (40% aqueous solution)

CHALLENGE
1. Concentration of test material and vehicle used for each challenge:
- test substance unchanged (40% aqueous solution)

No. of animals per dose:

Number of animals in test group: 10
Number of animals in negative control group: 5

Positive control substance(s):

yes

Remarks:

tested in a separate study; alpha-Hexlycinnamaldehyde

Study design: in vivo (LLNA)

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

Tested in a separate study; alpha-Hexlycinnamaldehyde showed a sensitizing response in 11 out of 18 animals. Five animals died in this study, however the effects was not treatment-related. Macroscopic examination revealed that 4 animals suffereds from pneumonia, while one animal showed agonal congestion.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

SKIN REACTIONS

- Maximum concentration not causing irritating effects in preliminary test: 100 %
- Signs of irritation during induction: Intradermal induction with 5% test substance preparations caused well-defined erythema, slight edema
- After the percutaneous induction with the unchanged test substance incrustation, partially open (caused by the intradermal induction) in addition

to well-defined erythema and slight edema could be observed in the test group animals

OTHER OBSERVATIONS

- 1 animal of control group 1 died 22 days after the beginning of the study

- another animal of control group 1 died 23 days after the beginning of the study

Macroscopic examination revealed that the cause of death was not substance-induced.

Applicant's summary and conclusion

Interpretation of results:

other: the aqueous solution does not have any classification/labelling requirements; for the concentrated test material there are no test results available, therefore a final classification for this quality can not be made.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The aqueous solution was found to be non-sensitizing to guinea pigs; for the concentrated test material there are no test data available.

Executive summary:

The test was performed 1995 under GLP according to the EU standard testing method B.6, maximization test (Directive 67/548/EEC). The study was performed on 10 test and five control animals (females). The intradermal induction with 5% test substance preparations caused slight to well-defined signs of irritation in the test group animals. After the percutaneous induction with the unchanged test substance, incrustation, partially open (caused by the intradermal induction) in addition to well-defined erythema and slight edema could be observed in the test group animals.

There were no animals with skin findings after the challenge (21 days after intradermal induction).