Ethyl 4,4,4-trifluoroacetoacetate

Endpoint summary

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

Study period:

September - November 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

the maximization test was performed before the LLNA test methods was available

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall, Darley Oaks, Newchurch, Burton on Trent, Staffordshire, England
- Age at study initiation: 6-8 weeks
- Housing: gang housing; 5 animals of same sex per cage
- Diet (e.g. ad libitum): Guinea-pig F.D.1., from Special Diets Services Limited, Witham, Essex, England
- Water (e.g. ad libitum): Tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C
- Humidity (%): 55%
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

After consideration of the primary irritation screen results and the criteria for selection of treatment concentrations, the following regime was adopted:

First induction*:
- 50% v/v P5II7 in purified water
- 50% v/v P5II7 in FCA

Second induction*
- 10% v/v PSII7 in purified water

Challenge*
- 10% v/v P5II7 in purified water
- 3% v/v P5II7 in purified water

* Initially the first induction was undertaken employing 50% v/v formulations, however, due to ulceration of the administration sites the study was stopped. The study was restarted, with additional animals, using 5% v/v formulations

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

After consideration of the primary irritation screen results and the criteria for selection of treatment concentrations, the following regime was adopted:

First induction*:
- 50% v/v P5II7 in purified water
- 50% v/v P5II7 in FCA

Second induction*
- 10% v/v PSII7 in purified water

Challenge*
- 10% v/v P5II7 in purified water
- 3% v/v P5II7 in purified water

* Initially the first induction was undertaken employing 50% v/v formulations, however, due to ulceration of the administration sites the study was stopped. The study was restarted, with additional animals, using 5% v/v formulations

No. of animals per dose:

- Control group: 5 animals per sex and group
- Test group: 10 animals per sex and group

Details on study design:

INDUCTION:
1. Primary induction
Three pairs of injections (0.1 m!) were made deep into the dermis, such that on either side of the dorsal median line there were three injection sites in a row parallel to the spinal column. AIl injection sites lay near the periphery of a dermal test site 2 cm wide x 4 cm long, overlying the scapulae. The anterior and middle sites were positioned close together and distant from the posterior sites.

Injection sites Test group treatment Control group treatment
Anterior sites (A) FCA FCA
Middle sites (B) Test material in vehicle Vehicle
Posterior sites (C) Test material in FCA Vehicle in FCA

2. Secondary induction
On Day 8, the dermal site overlying the scapulae were treated by topical application of 0.6 ml ofa test material formulation to test animals, while controls received 0.6 ml of the vehicle. Each dose was applied to a 4 x 2.5 cm absorbent patch (Whatman No. 3 filter paper) which was applied to the skin and covered by an occlusive dressing (Blenderm and Elastoplast) for 48 hours. The application site was wiped with a paper tissue moistened with the vehicle immediately after removal of the bandage.

CHALLENGE:
Both flanks of all animals were clipped on Day 21. On Day 22 these areas were wet shaven to reveal a 5 x 5 cm area on the left flank and a 10 x 5 cm area on the right flank. Approximately one hour later the left site was treated by topical application of 0.03 ml of the vehicle while the right side received 0.03 ml of the maximum non-irritant concentration (as determined by Phase 3 of the primary skin irritation screen) to one site and a dilution to a second site. The doses were applied to 1 cm diameter absorbent patches (AI-test) and cover ed by an occlusive dressing (Blenderm and Elastoplast) for 24 hours. The test site was wiped with a paper tissue moistened with vehicle immediately after removal of the bandage. Reactions to challenge were assessed approximately 24 and 48 hours after removal of the occlusive dressings. The observations were made without knowledge of the number or group identity of the animal under examination.

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

purified water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: purified water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

purified water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: purified water. No with. + reactions: 0.0. Total no. in groups: 10.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10% test item in purified water

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10% test item in purified water. No with. + reactions: 1.0. Total no. in groups: 10.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10% test item in purified water

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10% test item in purified water. No with. + reactions: 4.0. Total no. in groups: 10.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

3% test item in purified water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 3% test item in purified water. No with. + reactions: 0.0. Total no. in groups: 10.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

3% test item in purified water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 3% test item in purified water. No with. + reactions: 0.0. Total no. in groups: 10.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

purified water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: purified water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

purified water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: purified water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% test item in purified water

No. with + reactions:

5

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% test item in purified water. No with. + reactions: 5.0. Total no. in groups: 20.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% test item in purified water

No. with + reactions:

8

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% test item in purified water. No with. + reactions: 8.0. Total no. in groups: 20.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

3% test item in purified water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3% test item in purified water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

3% test item in purified water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3% test item in purified water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Slight erythema or a more marked reaction were observed in eight of twenty test and four often control animals following challenge with 10% P5117 in purified water and in no animal following challenge application of 3% P5117 in purified water (the maximum non-irritant concentration). No animal showed a reaction to challenge application of purified water alone.

Since the incidence and severity of responses to challenge with the 10% formulation was the same in the test and control animals and none of the responders showed a reaction after challenging with 3% P5117, it is considered that they reflected primary irritation rather than dermal sensitization. No positive responses to challenge with 3% P5117 were found.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

It is concluded that, under the conditions of this study, repeated applications of P5117 did not cause delayed contact hypersensitivity in the guinea-pig.

Executive summary:

The skin sensitisation potential of P5117 was assessed in maximization test (Magnusson & Kligman) according to methds OECD no. 406 and EU B.6 on guinea pigs. 20 animals were used in the test group and 10 animals in the control group. Concentrations of 3% and 10% test item in purified water were tested. Challenge application of 10% test item in purified water gave rise to slight erythema or a more marked reaction in eight of twenty test and four of ten control animals. It is considered that these responses reflected primary irritation rather than dermal sensitization. Challenge application of 3% test item caused no positive response in test or control animals. Challenge application of purified water alone caused no significant response. It was concluded that, under the conditions of this study and the criteria of the EC, repeated administration of P51117 did not cause delayed contact hypersensitivity in guinea-pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
SKIN SENSITISATION:
The skin sensitisation potential of P5117 was assessed in maximization test (Magnusson & Kligman) according to methds OECD no. 406 and EU B.6 on guinea pigs. Challenge application of 10% test item in purified water gave rise to slight erythema or a more marked reaction in eight of twenty test and four of ten control animals. It is considered that these responses reflected primary irritation rather than dermal sensitization. Challenge application of 3% test item caused no positive response in test or control animals. Challenge application of purified water alone caused no significant response. It was concluded that, under the conditions of this study and the criteria of the EC, repeated administration of P51117 did not cause delayed contact hypersensitivity in guinea-pigs.

Justification for selection of skin sensitisation endpoint:
Klimisch 1 guideline study; GLP

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Source: GLP report

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP).