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Administrative data

Description of key information

AgBr was tested in an in-vitro test system for skin (OECD439; Heppenheimer 2013) and for eye (OECD437; Heppenheimer 2013). Both in-vitro assays were negative. As a consequence, and in absence of a clear positive response in the in-vitro assays, further in vivo testing was required. The consequent in-vivo assays (OECD404 (Pooles 2013) for skin and OECD405 (Pooles 2013) for eye) confirmed that AgBr was not irritating or corrosive towards skin or eye.


Note that these in-vitro and in-vivo testing pre-dates Regulation (EU) 2016/863 in which it is specified that conclusive negative in-vitro evidence is sufficient to fill the skin and eye irritation/corrosion endpoints, and that in-vivo testing should only be used as a last resort if no conclusion can be made using alternative methodologies.

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:
2013-03-05 to 2013-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2012-11-30
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.68 to 2.73 kg
- Housing: animals were individually housed in suspended cages
- Diet (ad libitum): 2930C Teklad Global Rabbit diet (supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23°C
- Relative humidity: 30 to 70%
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test item, moistened sufficiently with the vehicle

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL of distilled water
Duration of treatment / exposure:
Initial animal: 3 minutes, 1 hour and 4 hours
Confirmatory animals: 4 hours
Observation period:
immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later
(the initial animal was also observed on Day 7)
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure, type of wrap if used and removal of test substance: on the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site the test item, moistened sufficiently with the vehicle to achieve a paste, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with the test item, moistened sufficiently with the vehicle to achieve a paste. One patch was applied to the back of the rabbit and was allowed to remain in contact with the skin for a period of four hours.

SCORING SYSTEM: according to the Draize scale
Any other skin reactions and clinical signs of toxicity were also recorded.
Individual body weights were recorded on the day of dosing and at the end of the observation period.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
3-minute exposure period
No evidence of skin irritation was noted during the study.
1-hour exposure period
No evidence of skin irritation was noted during the study.
4-hour exposure period
No evidence of skin irritation was noted during the study
Other effects:
All animals showed expected gain in body weight during the study.
Interpretation of results:
GHS criteria not met
Remarks:
Silver bromide not irritant to the skin.
Conclusions:
The test substance is not irritating to the skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not irritating to the skin.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.
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:
2013-03-28 to 2013-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2012-11-30
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.58 to 2.87 kg
- Housing: animals were individually housed in suspended cages
- Diet (ad libitum): 2930C Teklad Global Rabbit diet (supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23°C
- Relative humidity: 30 to 70%
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes.
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

INITIAL TEST AND CONFIRMATORY TEST
Initially, a single rabbit was treated. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to a six point scale (please refer to "Any other information on materials and methods incl. tables" below).
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM: according to the Draize scale
Any other ocular effects were also noted.
Any clinical signs of toxicity were also recorded.
Individual body weights were recorded the day of dosing and at the end of the observation period.

TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Initial pain reaction: slight initial pain; Slight discharge (grade 1) was observed at the one hour observation.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Slight iridial inflammation (grade 1) was observed at the one hour observation.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Moderate conjunctival redness (grade 2) was observed at the one hour observation.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Slight chemosis (grade 1) was observed at the one hour observation.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Initial pain reaction: slight initial pain; Slight discharge (grade 1) was observed at the one hour observation.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Slight iridial inflammation (grade 1) was observed at the one hour observation.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Moderate conjunctival redness (grade 2) was observed at the one hour observation.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Slight chemosis (grade 1) was observed at the one hour observation.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: Initial pain reaction: slight initial pain; Slight discharge (grade 1) was observed at the one hour observation.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: Slight iridial inflammation (grade 1) was observed at the one hour observation.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Moderate conjunctival redness (grade 2) was observed at the one hour observation.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Moderate chemosis (grade 2) was observed at the one hour observation.
Irritant / corrosive response data:
No corneal effects were noted during the study.
Iridial inflammation was noted in all treated eyes one hour after treatment.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in two treated eyes at the 24-hour observation with minimal conjunctival irritation noted in all treated eyes at the 48-hour observation.
All treated eyes appeared normal at the 72-hour observation.
Other effects:
All animals showed expected gain in body weight during the study.
Interpretation of results:
GHS criteria not met
Remarks:
Silver bromide is not irritating to the eyes.
Conclusions:
The test substance is not irritating to the eyes.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not irritating to the eyes.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
AgBr was not irritating/corrosive to skin in an in-vitro test system (Heppenheimer, 2013). As specified in EU REACH REGULATION (EC) No 1907/2006 at the time of the experimental testing and REACH dossier generation, further in-vivo testing was required.An in-vivo study (OECD 404; Pooles, 2013) confirmed this result.

Justification for selection of eye irritation endpoint:
AgBr was not irritating/corrosive to eye in an ex-vivo test system (BCOP; Heppenheimer, 2013). As specified in EU REACH REGULATION (EC) No 1907/2006 at the time of the experimental testing and REACH dossier generation, further in-vivo testing was required.An in-vivo study (OECD 405; Pooles 2013) confirmed this result.

Justification for classification or non-classification

AgBr was not irritating or corrosive towards skin or eye in both in-vitro and in-vivo test systems, respectively, when comparing the study results to the classification criteria (CLP regulation). No classification for these hazard classes is requried.