Registration Dossier

Administrative data

Description of key information

Skin irritation, rabbits, 4-hour occlusive application; Not irritating

Eye irritation, rabbits; Not irritating

Irritating to the respiratory tract based on clinical signs, macroscopic and microscopic evidences from acute and repeated dose studies by the inhalation route

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 March 2012 - 23 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to EC and OECD test guidelines and in compliance with GLP; on this basis the result is considered reliable without restrictions.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Skin Irritation (2-1-4), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 35 or 36 weeks
- Weight at study initiation: 3.55 - 4.94 kg
- Housing: Housed individually in plastic cages with perforated floors
- Diet: Animals were provided with 125 g of standard laboratory rabbit diet per day. A dietary supplement of hay was also available.
- Water: Free access to drinking water
Acclimatisation: At least ten weeks prior to study start

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20°C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12 hours light : 12 hours dark

IN-LIFE DATES: From: 11 March 2012 To: 23 March 2012
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 minutes, one hour, and four hours (intial animal, received three exposures).
Four hours (2 animals).
Observation period:
72 hours (observations made at 1, 24, 48, and 72 hours)
Number of animals:
3
Details on study design:
TEST SITE
25 mm x 25 mm gauze pad, covered with a square peice of aluminium foil (55 mm x 55 mm), sealed with impermeable surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30 - 40°C) to remove any residual test substance. The treatment area was blotted dry with absorbent paper.

SCORING SYSTEM:
Refer to "Any other information on materials and methods", below.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no erythema was seen in any animal
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no erythema was observed at any timepoint
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no erythema was observed at any timepoint
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no oedema was seen at any timepoint
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no oedema was seen at any timepoint
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no oedema was seen at any timepoint
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No dermal reaction was observed in any animal throughout the duration of the study.
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the criteria of the Globally Harmonised System and European Commission regulation 1272/2008 2-Bromo-3,3,3-trifluoropropene did not produce irritation or corrosivity and did not require any classification and labelling.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 June 2012 to 10 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to EC and OECD test guidelines and in compliance with GLP; on this basis the result is considered reliable without restiction.
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approximately 31 weeks
- Weight at study initiation: 4.25 to 4.50 kg
- Housing: Housed individually in plastic cages with perforated floors
- Diet: 125 g of standard laboratory rabbit diet were offered per day; a dietary supplement of hay was offered during acclimatisation until two days prior to dose instillation.
- Water: Drinking water was provided ad libitum.
- Acclimation period: 13 Weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 29 June 2012 To: 10 July 2012
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
The test substance was administered as a single dose of 0.1 mL instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated.
Observation period (in vivo):
An initial assessment of the pain response was made immediately after instillation.
Ocular reactions to treatment were assessed 1, 24, 48, and 72 hours after treatment.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Please refer to "Any other information on materials and methods", below.

TOOL USED TO ASSESS SCORE: An opthalmoscope or pencil beam torch was available for use to facilitate inspection of the eyes.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
other: Not applicable as no corneal irritation was observed at any timepoint
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
other: Not applicable as no corneal irritation was observed at any timepoint
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
other: Not applicable as no corneal irritation was observed at any timepoint
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
other: Not applicable as no iridial irritation was observed at any timepoint
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
other: Not applicable as no iridial irritation was observed at any timepoint
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
other: Not applicable as no iridial irritation was observed at any timepoint
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no chemosis was observed at any timepoint
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no chemosis was observed at any timepoint
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable as no chemosis was observed at any timepoint
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
20
Reversibility:
other: Not applicable as no indication of conjunctival irritation was observed at any timepoint
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
20
Reversibility:
other: Not applicable as no indication of conjunctival irritation was observed at any timepoint
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
20
Reversibility:
other: Not applicable as no indication of conjunctival irritation was observed at any timepoint
Irritant / corrosive response data:
No sign of reaction to treatment was apparent in any animal at any time during the observation period.

Instillation of the test material gave rise to practically no or slight initial pain response.
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2-Bromo-3,3,3-trifluoropropene did not produce irritation, accordingly under the criteria Kay and Calandra (1962) it was classified as “non-irritating” to the eye and did not require labelling in accordance with the Globally Harmonised System and European Commission Regulation 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was conducted to determine the skin irritation properties of 2-Bromo-3,3,3-trifluoropropene (Huntingdon Life Sciences, 2012, Study code WAG0010). The study was performed according to OECD test guideline 404 and EC guideline B4, and in compliance with GLP.

Three New Zealand White rabbits received a single occlusive dermal application of the test substance for four hours; animals were observed for four days after exposure. None of the exposed animals displayed any sign of dermal reaction (irritation) to the treatment..

On the basis of these results it was concluded that 2-bromo-3,3,3-trifluoropropene is not irritant to skin.

 

A study was conducted to determine the eye irritation properties of 2-Bromo-3,3,3-trifluoropropene (Huntingdon Life Sciences, 2012, Study code WAG0011). The study was performed according to OECD test guideline 405 and EC guideline B5, and in compliance with GLP.

Three New Zealand White rabbits received a single ocular application of the test substance; animals were observed for four days after exposure. None of the exposed animals displayed any sign of dermal reaction (irritation) to the treatment..

On the basis of these results it was concluded that 2-bromo-3,3,3-trifluoropropene is not irritant to eyes.

 

Although no specific study to assess irritation to the respiratory tract was conducted, irritation effects were observed in the respiratory tract of rats in the acute and repeat dose studies by the inhalation route.

In the acute toxicity study (Huntingdon Life Sciences, Report No.02-5449, 2004), clinical signs noted immediately following the exposures of BTP included clear or red nasal discharge. Macroscopically, rats from both exposure levels had red discolorations of the lungs. Fluid was present in the lungs of one male from the higher level exposure of 26,580 ppm. Microscopically, test substance related effects were observed in lungs of rats in the higher level exposure of 26,580 ppm. All of the rats, in this group only, had bronchiolar lesions consisting of desquamated epithelium, bronchiolar/peribronchiolar acute/subacute inflammation.

In the repeated dose study (Huntingdon Life Sciences Report No. WAG0014, 2013) including the range finding studies (Huntingdon Life Sciences Reports No. WAG0013 and WAG0024, 2012), treatment-related, but transient, clinical signs (shallow breathing, piloerection, grinding teeth and hunched posture), related to inhalation of an irritant material, were evident during and after exposure.Histopathological changes related to treatment were seen in the nasal turbinates, larynx and trachea and were related to exposure to an irritant material. Overall, the most marked changes were in the nasal cavity, with less severe changes in the larynx and trachea.Histopathological changes included atrophy/disorganisationand inflammation of the olfactory epithelium, atrophy of the olfactory nerve fibres, inflammatory exudate in the airways, perivascular and peribronchiolar inflammatory infiltrate and bronchiolar epithelial hyperplasia in the lungs, epithelial hyperplasia and sub epithelial inflammation in the larynx and epithelial hyperplasia at the tracheal bifurcation.

Justification for selection of skin irritation / corrosion endpoint:

The study was conducted according to official (EC, OECD, US EPA, JMAFF) test guidelines and in compliance with GLP; the study is considered a reliable source on this basis.

Justification for selection of eye irritation endpoint:

The study was conducted according to official (EC, OECD, US EPA, JMAFF) test guidelines and in compliance with GLP; the study is considered a reliable source on this basis.

Justification for classification or non-classification

In-vivo skin and eye irritation studies each concluded that the substance did not show any irritant properties. The substance therefore does not meet the classification criteria for skin or eye irritation.

The irritation observed in the respiratory tract in the acute and repeated dose studies by the inhalation route are the basis of the classification of BTP as a STOT single exposure 3 (H335: may cause respiratory irritation) under the CLP regulation.