Potassium bromide

Endpoint summary

Description of key information

Skin: No dermal irritation responses were observed in any animal at any reading time point during the observation period
Eye: Treated eyes appeared normal within 7 or 14 days after treatment. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 0.7, 0.7 for cornea score; 1, 0.7, 1 for iris score; 2, 2, 2 for conjunctivae score and 2, 1.3, 1.3 for chemosis score. The substance is classified and labelled with respect to ocular irritancy in accordance with Regulation (EC) No. 1272/2008.

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:

1995-09-13 to 1995-09-16

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 404 and EU Method B.4 with minor deviation: animals were not weighed at the end of 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

animals were not weighed at the end of study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Sandbach, UK.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.52-2.66 kg
- Housing: Animals were individually housed in suspended metal cages.
- Diet: Food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd., Witham, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-21 °C
- Humidity: 58-65 %
- Air changes: Approximately 15 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 1995-09-13 To: 1995-09-16

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: distilled water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of test material moistened with 0.5 ml of distilled water and applied.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: Dorsal flank area; test item was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize method

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

- Very slight erythema was confined to one treated skin site at the 1-hour observation.
- No other signs of dermal irritation were noted.

Other effects:

None

Table 7.3.1/1: Results of skin irritation

Skin Reaction	Observation Time (hours)	Individual Scores – Rabbit Number and Sex
		576 Male	582 Female	588 Female
Erythema/Eschar Formation	1	0	1	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
	Mean (24, 48 and 72 h)	0	0	0
Oedema Formation	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
	Mean (24, 48 and 72 h)	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Potassium bromide is not classified as irritating to skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272 -2008).

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and EU Method B.4 in compliance with GLP, three New Zealand White rabbits were dermally exposed to 0.5 g of Potassium bromide for 4 hours under a semi-occlusive dressing. After removal of the residual test item with moistened cotton wool, irritation was scored according to Draize method at 1, 24, 48 and 72 hours after removal of dressings.

Very slight erythema was confined to one treated skin site at the 1-hour observation. No other signs of dermal irritation were noted. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for erythema and 0, 0, 0 for edema score, respectively. In this study, Potassium bromide is not a skin irritant on rabbits.

Under the test conditions, Potassium bromide is not classified as irritating to skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272 -2008).

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:

1995-09-18 to 1995-10-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 405 and EU Method B5 with minor deviation: animals were not weighed at the end of 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

animals were not weighed at the end of study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Sandbach, UK.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.42-2.73 kg
- Housing: Animals were individually housed in suspended metal cages.
- Diet: Food (Teklad Rabbit Diet 9603, Harlan Teklad, Bicester, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-21 °C
- Humidity: 56-68 %
- Air changes: Approximately 15 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 1995-09-18 To: 1995-10-04

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Eyes were not rinsed throughout study

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 (1 male and 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize method

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- Dulling of the normal lustre of the corneal surface was confined to one treated eye 1 hour after treatment. Diffuse corneal opacity was noted in all treated eyes at the 24 and 48 hour observations and persisted in one eye at the 72 hour and 7 day observations. Slight vascularisation along the bottom edge of the cornea, approximately 2 mm in length and invading up to 1 mm onto the cornea was noted in one treated eye at the 7-day observation. No other corneal effects were noted.

- Iridial inflammation was noted in all treated eyes one hour after treatment, at the 24 and 48-hour observations and in two treated eyes at 72-hour observation. No other iridial effects were noted.

- Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at 24, 48 and 72-hour observations. Minimal conjunctival irritation was noted in two treated eyes at 7 days observation. Petechial haemorrhage of the nictitating membrane was noted in one treated eye one hour after treatment. Haemorrhage of the nictitating membrane was noted in all treated eyes at the 24, 48 and 72-hour observations and in one treated eye at the 7 days observation.

- Treated eyes appeared normal within 7 or 14 days after treatment.

Other effects:

No data

Table 7.3.2/1: Results of eye irritation

Animal no.	578 Male						31 Female						34 Female
	Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea
	A	B	C	D	E	F	A	B	C	D	E	F	A	B	C	D	E	F
1 h	2pt	2	3	1	d	2	2	2	2	1	0	0	2	2	3	1	0	0
24 h	2H	2	3	1	1	2	2H	2	3	1	1	1	2H	2	2	1	1	2
48 h	2H	2	0	1	1	2	2H	1	2	1	1	1	2H	1	1	1	1	1
72 h	2H	2	0	1	1	2	2H	1	1	0	0	0	2H	1	1	1	0	0
Mean	2	2	-	1	1	-	2	1.3	-	0.7	0.7	-	2	1.3	-	1	0.7	-
Day 7	1H	0	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0V	0
Day 14	0	0	0	0	0	0	-	-	-	-	-	-	0	0	0	0	0	0

 

A: Redness; B: Chemosis; C: Discharge; D: Iris lesion; E: Degree of opacity; F: Area of opacity; H: Haemorrhage of the nictitating membrane; V: slight vascularisation along bottom edge of the cornea, approximately 2 mm in length and invading up to 1 mm onto the cornea; d: dulling of the normal lustre of the corneal surface; Pt: petechial haemorrhage of the nictitating membrane

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Potassium bromide is classified as "R36 irritating to eyes" according to the criteria of Annex VI to the Directive 67/548/EEC and "Category 2 irritating to eyes" according to CLP Regulation (EC) N° (1272-2008).

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and EU Method B5 and in compliance with GLP, 3 New Zealand White rabbits were exposed to 100 mg of Potassium bromide in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test item. The eyes were examined and the changes were observed at 1, 24, 48 and 72 hours and 7 and 14 days after treatment and graded according to the Draize method.

Dulling of the normal lustre of the corneal surface was confined to one treated eye 1 hour after treatment. Diffuse corneal opacity was noted in all treated eyes at the 24 and 48 hour observations and persisted in one eye at the 72 hour and 7 day observations. Slight vascularisation along the bottom edge of the cornea, approximately 2 mm in length and invading up to 1 mm onto the cornea was noted in one treated eye at the 7-day observation. No other corneal effects were noted. Iridial inflammation was noted in all treated eyes one hour after treatment, at the 24 and 48-hour observations and in two treated eyes at 72-hour observation. No other iridial effects were noted. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at 24, 48 and 72-hour observations. Minimal conjunctival irritation was noted in two treated eyes at 7 days observation. Petechial haemorrhage of the nictitating membrane was noted in one treated eye one hour after treatment. Haemorrhage of the nictitating membrane was noted in all treated eyes at the 24, 48 and 72-hour observations and in one treated eye at the 7 days observation. Treated eyes appeared normal within 7 or 14 days after treatment. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 0.7, 0.7 for cornea score; 1, 0.7, 1 for iris score; 2, 2, 2 for conjunctivae score and 2, 1.3, 1.3 for chemosis score. In this study, Potassium bromide is an eye irritant on rabbits.

 

Under the test conditions, Potassium bromide is classified as "R36 irritating to eyes" according to the criteria of Annex VI to the Directive 67/548/EEC and "Category 2 irritating to eyes" according to CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Potassium bromide is an inorganic salt that dissociates to its composite ions in aqueous solutions at environmental pH and temperature. Comparison of the available data on the various bromide salts have shown that the bromide ion is the relevant ion for determination of the toxicological profile with simple cations such as potassium, sodium or ammonium, that are ubiquitous in nature, having little or no influence on the bromide ion properties. It is therefore justified to read-across data from other inorganic bromide salts to potassium bromide.

Skin

In a primary dermal irritation study performed according to OECD Guideline 404 and EU Method B.4 in compliance with GLP, three New Zealand White rabbits were dermally exposed to 0.5 g of Potassium bromide for 4 hours under a semi-occlusive dressing. After removal of the residual test item with moistened cotton wool, irritation was scoredaccording to Draize methodat 1, 24, 48 and 72 hours after removal of dressings.

Very slight erythema was confined to one treated skin site at the 1-hour observation. No other signs of dermal irritation were noted. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for erythema and 0, 0, 0 for edema score, respectively. In this study, Potassium bromide is not a skin irritant on rabbits.

In a further key study on sodium bromide the test substance was moistened with water and administered dermally to a small patch of shaven skin of 6 female rabbits and covered for 4 hours each. Observations of the resulting skin condition were made 30 minutes after test substance removal, and daily thereafter for 4 days.

All 6 animals showed no response to treatment.

Eye

In a key eye irritation study conducted according to the OECD Guideline 405 and EU Method B5 and in compliance with GLP, 3 New Zealand White rabbits were exposed to 100 mg of Potassium bromide in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test item. The eyes were examined and the changes were observed at 1, 24, 48 and 72 hours and 7 and 14 days after treatment and graded according to the Draize method.

Dulling of the normal lustre of the corneal surface was confined to one treated eye 1 hour after treatment. Diffuse corneal opacity was noted in all treated eyes at the 24 and 48 hour observations and persisted in one eye at the 72 hour and 7 day observations. Slight vascularisation along the bottom edge of the cornea, approximately 2 mm in length and invading up to 1 mm onto the cornea was noted in one treated eye at the 7-day observation. No other corneal effects were noted. Iridial inflammation was noted in all treated eyes one hour after treatment, at the 24 and 48-hour observations and in two treated eyes at 72-hour observation. No other iridial effects were noted. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at 24, 48 and 72-hour observations. Minimal conjunctival irritation was noted in two treated eyes at 7 days observation. Petechial haemorrhage of the nictitating membrane was noted in one treated eye one hour after treatment. Haemorrhage of the nictitating membrane was noted in all treated eyes at the 24, 48 and 72-hour observations and in one treated eye at the 7 days observation. Treated eyes appeared normal within 7 or 14 days after treatment. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 0.7, 0.7 for cornea score; 1, 0.7, 1 for iris score; 2, 2, 2 for conjunctivae score and 2, 1.3, 1.3 for chemosis score. In this study, Potassium bromide is an eye irritant on rabbits.

The substance is classified and labelled with respect to ocular irritancy in accordance with Regulation (EC) No. 1272/2008.

Potassium bromide is not irritating to skin but is classified Category 2 "irritating to eyes" according to CLP Regulation(EC) No. 1272/2008

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the in vivo experimental results, potassium bromide is not classified with respect to dermal irritation but is classified as Category 2 "irritating to eyes" according to CLP Regulation (EC) No. 1272/2008.