1-bromo-3,4,5-trifluorobenzene

Endpoint summary

Description of key information

In a study according OECD TG 406 performed on guinea-pigs the substance is not to be classified as skin sensitizer (reference 7.4.1 -1).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

07-1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

not further specified

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed in 1995

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, UK
- Age at study initiation: 8 – 12 weeks
- Weight at study initiation: 360 – 427 g
- Housing: singly or in pairs in solid-floor PP cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 23
- Humidity (%): 48 – 68
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

Route:

intradermal

Vehicle:

arachis oil

Concentration / amount:

0.1 mL of 25 % (w/v) in arachis oil B.P., 25 % (w/v) in a mixture of Freund's Complete Adjuvant plus distilled water (1:1)

Day(s)/duration:

day 0

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Filter patch saturated with the undiluted test material

Day(s)/duration:

Application on day 7 over 48 hours

Adequacy of induction:

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

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

arachis oil

Concentration / amount:

Filter patch saturated with the undiluted test material (100 and 75% (v/v))

Day(s)/duration:

day 21 over 24 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

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

Details on study design:

RANGE FINDING TESTS: The concentrations for the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test material.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and topical)
- Test groups:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) a 25% w/v formulation of the test material in arachis oil B.P.
c) a 25% w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.

One week later (Day 7), the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the undiluted test material. A filter paper patch saturated with the undiluted test material was applied to the prepared skin and held in place with a strip of surgical adhesive tape covered with an overlapping length of aluminium foil. This occlusive dressing was kept in place for 48 hours.

- Control group:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) arachis oil B.P.
c) 50% w/v formulation of arachis oil B.P. in a 1:1 mixture of Freund's Complete Adjuvant/distilled water

The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper. Skin reactions were quantified as for the test animals.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (topical)
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups:
A square filter paper patch, saturated with the undiluted test material was applied to the shorn right flank of each animal and was held in place with a strip of surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 75% v/v in arachis oil B.P. was similarly applied to a skin site on the left shorn flank. The patches were occluded with an overlapping length of aluminium foil and secured with a strip of elastic adhesive bandage wound in a double layer around the torso of each animal.

After 24 hours, the dressing was carefully cut using blunt-tipped scissors, removed and discarded. The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material. The position of the treatment sites was identified by using a black indelible marker-pen. Prior to the 24-hour observation the flanks were clipped using veterinary clippers to remove regrown hair.

Challenge controls:

yes

Positive control substance(s):

no

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

75 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

75 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

75 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Group:

positive control

No. with + reactions:

7

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Bodyweight

Bodyweight gains-of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Positive control

SUMMARY OF POSITIVE CONTROL DATA FOR THE MAGNUSSON AND KLIGMAN MAXIMISATION STUDY (NOVEMBER 1993 TO NOVEMBER 1994)

Project Number	Date Start	Date End	Number of Animals and Sex*		Positive Control Material	concentration Induction		Challenge	Incidence of Sensitisation
			Test	Control		Intradermal	Topical
039/62	19/10/93	12/11/93	10 Female	5 Female	alpha-hexylcinnamaldehyde Tech. 85%	25% in arachis oil B.P.	100%	100% and 75% in arachis oil B.P.	70% (7/10)
039/70	01/03/94	25/03/94	10 female	5 Female	2-Mercaptobenzothiazole	10% in arachis oil B.P.	50% in 95% aqueous ethanol	25% in 95% aqueous ethanol	80% (8/10)
039/85	13/07/94	06/08/94	18 Female	10 Female	Ethyl 4 aminobenzoate 98%	3% in a 6% preparation of acetone in arachis oil B.P.	25% in 80% aqueous ethanol	10% and 5% in 80% aqueous ethanol	39% (7/18)
039/108	31/10/94	24/11/94	9 Male	5 Male	2,4-Dinilrochlorobenzene	0.1 % in arachis oil B.P.	1 % in arachis oil B.P.	0.1% and 0.05% in arachis oil B.P.	100% (9/9)

 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study the test item can be assessed as a non sensitiser to guinea pig skin.

Executive summary:

The purpose of this GLP study performed according to OECD TG 406 was to assess the contact sensitisation potential of the test material in the albino guinea pig. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal induction: 25 % (w/v) in arachis oil B.P.

Topical induction: undiluted as supplied

Topical challenge: 100 and 75% (v/v) in arachis oil B.P.

Skin reactions after intradermal induction: Well-defined to moderate to severe erythema was noted at all induction sites at the 24 and 48-hour observations in the test group animals. Very slight erythema was noted at all treatment sites at the 24-hour observation and one treatment site at the 48-hour observation in the control group animals.

Skin reactions after topical induction: Very slight erythema was noted at eight induction sites at the 1-hour observation with no dermal reactions at the 24-hour observation in the test group animals. No dermal reactions were noted at the 1 or 24-hour observations at the treatment sites of the control group animals.

Skin reactions after topical challenge: No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations at the 100% or 75% concentrations.

Bodyweight gains of guinea pigs in the test group, between days 0 – 24, were comparable to those observed in the control group animals over the same period.

The test item produced a 0 % (0/10) sensitisation rate in guinea pigs.

Based on the results of this study the test item can be assessed as a non sensitiser to guinea pig skin.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A study according to OECD TG 406 was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal induction: 25 % (w/v) in arachis oil B.P.

Topical induction: undiluted as supplied

Topical challenge: 100 and 75% (v/v) in arachis oil B.P.

Skin reactions after intradermal induction: Well-defined to moderate to severe erythema was noted at all induction sites at the 24 and 48-hour observations in the test group animals. Very slight erythema was noted at all treatment sites at the 24-hour observation and one treatment site at the 48-hour observation in the control group animals.

Skin reactions after topical induction: Very slight erythema was noted at eight induction sites at the 1-hour observation with no dermal reactions at the 24-hour observation in the test group animals. No dermal reactions were noted at the 1 or 24-hour observations at the treatment sites of the control group animals.

Skin reactions after topical challenge: No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations at the 100% or 75% concentrations.

Bodyweight gains of guinea pigs in the test group, between days 0 – 24, were comparable to those observed in the control group animals over the same period.

The test item produced a 0 % (0/10) sensitisation rate in guinea pigs.

Based on the results of this study the test item can be assessed as a non sensitiser to guinea pig skin (reference 7.4.1 -1).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this information, the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.