2-fluoro-6-trifluoromethylpyridine

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline 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

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not provided in the report

Specific details on test material used for the study:

Substance ID: F6TF
Lot #: 8922/16
Purity: 99.7%

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 380-486 g
- Housing: five per cage in cages suitable for animals of this strain and the weight range expected during the course of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): Artificial, giving 12 hours light, 12 hours dark

Route:

intradermal and epicutaneous

Vehicle:

other: corn oil or Freund's Complete Adjuvant

Concentration / amount:

Induction Phase (each animal received three injections plus a week later, the topical application)
Injection 1: Freund's Complete Adjuvant plus corn oil in the ratio 1:1
Injection 2: 10% w/v preparation of the test substance in corn oil
Injection 3: 10% w/v preparation of the test substance in Freund's Complete Adjuvant plus corn oil in the ratio 1:1
Topical Application: 0.2-0.3 mL undiluted test substance

Challenge Phase (each animal received the 2 topical applications)
Topical Application: 0.05-0.1 mL undiluted test substance
Topical Application: 0.05-0.1 mL 75% test substance in corn oil

Route:

epicutaneous, occlusive

Vehicle:

other: corn oil or Freund's Complete Adjuvant

Concentration / amount:

Induction Phase (each animal received three injections plus a week later, the topical application)
Injection 1: Freund's Complete Adjuvant plus corn oil in the ratio 1:1
Injection 2: 10% w/v preparation of the test substance in corn oil
Injection 3: 10% w/v preparation of the test substance in Freund's Complete Adjuvant plus corn oil in the ratio 1:1
Topical Application: 0.2-0.3 mL undiluted test substance

Challenge Phase (each animal received the 2 topical applications)
Topical Application: 0.05-0.1 mL undiluted test substance
Topical Application: 0.05-0.1 mL 75% test substance in corn oil

No. of animals per dose:

Test substance - 20
Control - 10

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
An area approximately 5 x 5 cm on the scapular region of each animal was clipped free of hair with a pair of veterinary clippers and a row of three injections (0.05-0.1 mL each) was made on each side of the mid-line. The injections were:

i) Top: Freund's Complete Adjuvant plus corn oil in the ratio 1: 1;
ii) Middle: a 10% w/v preparation of the test substance in corn oil;
iii) Bottom: a 10% w/v preparation of the test substance in a 1: 1 preparation of Freund's Complete Adjuvant plus corn oil.

Control animals were treated the same as the test animals, except that they were treated with corn oil in place of the test substance. The injections were checked for any adverse effects approximately 1 day after dosing. One week after intradermal injection, the scapular area was clipped again and treated with a topical application of the undiluted test substance. This preparation (0.2-0.3 mL) was applied on filter paper (approximate size 4 cm x 2 cm) which was held in place by a piece of surgical tape. The tape was covered by a strip of adhesive bandage (approximate size 20-30 cm x 5 cm) and secured by a piece of self-adhesive PVC tape. This occlusive dressing was kept in place for at least 48 hours. Control animals were similarly treated except that the test substance was not applied to the filter paper. The application sites were checked approximately 1 day after removal of the dressings, and twice further prior to challenge.

B. CHALLENGE EXPOSURE
Two weeks after the topical inductions, an area, approximately l5 cm x 5 cm, on both flanks of all the test and control animals, was clipped free of hair with a pair of veterinary clippers. An occlusive dressing was prepared which consisted of two pieces of filter paper (approximate size l cm x 2 cm) stitched to a piece of rubber sheeting (approximate size l2 cm x 5 cm). The undiluted test substance (0.05-0.l mL) was applied to one of the pieces of filter paper and a 75% w/v preparation in com oil (0.05-0.l mL) was applied to the second piece of filter paper. The dressing was placed on the shorn flank of the guinea pig so that the undiluted test substance was on the left and the 75% w/v preparation was on the right. It was then covered with a strip of adhesive bandage (approximate size 25-40 cm x 7.5 cm) which was secured by a self-adhesive PVC tape. After at least 24 hours, the dressings were carefully cut, using blunt-tipped scissors, removed and discarded. The position of the pieces of filter paper on the skin were identified using a black waterproof marker-pen. Skin sites were examined approximately I and 2 days after removal of the dressings.

Positive control substance(s):

yes

Remarks:

A positive control study using hexylcinnamaldehyde was carried out at approximately 6 month intervals to ensure that the test system continued to respond to known sensitizers.

Positive control results:

The net percentage response was calculated to be 65% and, under the conditions of the test, hexylcinnamaldehyde was classified as a strong skin sensitizer.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

75% w/v

No. with + reactions:

15

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

75% w/v

No. with + reactions:

16

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Undiluted and 75% w/v

No. with + reactions:

0

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Undiluted and 75% w/v

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

undiluted

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

undiluted

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

75%

No. with + reactions:

0

Total no. in group:

20

Slight erythema was observed in test animals following intradermal induction.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is not sensitising in the guinea pig Maximisation Test.

Executive summary:

The sensitisation potential of the test substance was assessed using a method based on the maximisation test according to the guidelines OECD 406 and EU method B.6.

The skin sensitization potential of the test substance was assessed in a group of 20 guinea pigs. For the induction phase, the test substance was dosed intradermally as a 10% w/v preparation in corn oil (with or without Freund's Complete Adjuvant) and a week later, as an undiluted topical application. Two weeks after the topical induction the challenge phase was conducted with a topical application of a 75% test substance preparation in corn oil and undiluted test substance. Skin treatment sites were examined 24 hours later.

 

Slight erythema was seen in the test animals following intradermal induction. Following challenge of the induced guinea pigs with the test substance, there was no erythematous response in any of the test or control animals. The test substance was not a sensitizer under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization potential was assessed in guinea pigs. In the induction phase, the test substance was dosed intradermally as a 10% w/v preparation in corn oil (with or without Freund's Complete Adjuvant) and a week later, as an undiluted topical application. Two weeks after the topical induction, the challenge phase was conducted with a topical application of a 75% test substance preparation in corn oil and undiluted test substance. Following challenge of the induced guinea pigs with the test substance, there was no sensitization response in any of the test animals.

Migrated from Short description of key information:
OECD 406; no sensitization was observed in guinea pigs. Reliability = 1

Justification for classification or non-classification:

There was no evidence of dermal sensitization in guinea pigs. The substance does not need to be classified for sensitization according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Respiratory sensitisation

Endpoint conclusion

Additional information:

Justification for classification or non-classification:

There was no evidence of dermal sensitization in guinea pigs. The substance does not need to be classified for sensitization according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.