Lithium bromide

Endpoint summary

Description of key information

Lithium bromide was irritating to eyes and skin of New Zealand White rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1988-01-20 to 1988-02-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Status and principle of method according OECD guideline 404 as adopted in 1981.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania, USA
- Age at study initiation: young adults
- Weight at study initiation: 3.10 - 3.31 kg
- Housing: individually in stainless steal cages
- Diet: Purina High Fiber Rabbit Chow 5326, ad libitum
- Water: fresh tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 - 71
- Humidity (%): 33 - 59
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: the test substance was moistened with saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: scapular to the pelvic region
- Type of wrap if used: cheesecloth bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were wiped with clean gauze moistened with methanol, then rinsed with tap water.
- Time after start of exposure: four hours

SCORING SYSTEM: Draize J. H. et al. (1944)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Irritant / corrosive response data:

Two rabbits exhibited slight to mild erythema and slight to moderate edema over the test sites during the study. One rabbit had severe erythema, edema, eschar, exfoliation and burned areas over the sites. Irritation effects on two of the rabbits had not resolved by day 14 of the study.

Other effects:

The skin of one animal appeared to be burned.

- The following results are based on results obtained on one of the two application sites on each animal; the site where the effects were more pronounced:

Animal 1 - Erythema average score (24, 48, 72 hours): Scoring 2 (out of 4) - Not reversible in 14 days

Animal 2 - Erythema average score (24, 48, 72 hours): Scoring 0 (out of 4)

Animal 3 - Erythema average score (24, 48, 72 hours): Scoring 3 (out of 4) - Not reversible in 14 days

Animal 1 - Edema average score (24, 48, 72 hours): Scoring 1.6 (out of 4) - Reversible in 4 days

Animal 2 - Edema average score (24, 48, 72 hours): Scoring 0 (out of 4)

Animla 3 - Edema average score (24, 48, 72 hours): Scoring 2 (out of 4) - Reversible in 7 days

Animal 3 also exhibited eschar, exfoliation and test sites which appeared to be burned.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of the study performed with New Zealand White rabbits and under the conditions of this study, the test substance lithium bromide was regarded to be irritant to the skin.

Executive summary:

Three New Zealand White rabbits were treated topically on each of two test sites which were previously clipped free of hair. 0.5 g of lithium bromide anhydrous was placed in contact with each test site. The test sites were covered with gauze patches and the trunk of each animal was wrapped with a sheet of cheesecloth. The test material was in contact with the skin for 4 hours, after which the animals were unwrapped and the test material removed. Approximately 30 minutes after the end of the exposure period, the test sites were scored for irritation using the method of Draize. The test sites were scored daily thereafter for 14 days. Slight to severe erythema and slight to severe edema were noted on the test sites during the study. One rabbit also exhibited eschar, exfoliation and appeared to be burned on the test sites. Irritation on two of the rabbits had not resolved by day 14 of the study. The primary irritation index was 2.1. Under the conditions of this study and based on the Primary Irritation Index, the test material was evaluated to be irritating to intact skin when applied topically to New Zealand White rabbits. (FMC, 1988)

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1996-10-14 to 1997-01-22

Reliability:

other: Study itself has a reliability of 1, but was considered as disregarded since a 52 - 54 % solution was tested.

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 17th 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 29th, 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP, Inc., Denver, PA, USA
- Age at study initiation: young adults
- Weight at study initiation: 2.11 - 2.37 kg
- Housing: individually in stainless steel cages
- Diet: Purina Fiber Rabbit Chow 5326, ad libitum
- Water: fresh tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67 - 70
- Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of the undiluted test material
- Concentration (if solution): 52 - 54 wt.% in water

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

6 animals (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: scapular to the pelvic region
- coverage: 6 cm²
- Type of wrap if used: a piece of plastic sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: with tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize, J.H. et al. (1944)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hours

Score:

4.5

Max. score:

8

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 hours

Score:

4

Max. score:

8

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 hours

Score:

4

Max. score:

8

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

4.3

Max. score:

8

Irritant / corrosive response data:

Within 60 minutes following the unwrapping, necrosis was noted on four of the test sites and well defined to moderate erythema and very slight to slight edema were noted on the remaining test sites; one of the latter sites also had abrasions. Within 48 hours of dosing, all test sites had necrosis and skin thickening. Irritation persisted through study day 7, at which time eschar, necrosis, skin thickening, ulceration and desquamation were observed. The study was terminated following the day 7 scoring to minimize pain.

- The following results are based on results obtained on one of the two application sites on each animal, the site where the effects were more pronounced

Animal 1 - Erythema average score (24, 48, 72 hours): 3 - Not reversible in 7 days

Animal 2 - Erythema average score (24, 48, 72 hours): 4 - Not reversible in 7 days

Animal 3 - Erythema average score (24, 48, 72 hours): 4 - Not reversible in 7 days

Animal 4 - Erythema average score (24, 48, 72 hours): 4 - Not reversible in 7 days

Animal 5 - Erythema average score (24, 48, 72 hours): 4 - Not reversible in 7 days

Animal 6 - Erythema average score (24, 48, 72 hours): 4 - Not reversible in 7 days

Animal 1 - Edema average score (24, 48, 72 hours): o - Not reversible in 7 days

Animal 2 - Edema average score (24, 48, 72 hours): 0 - Not reversible in 7 days

Animal 3 - Edema average score (24, 48, 72 hours): 0 - Not reversible in 7 days

Animal 4 - Edema average score (24, 48, 72 hours): 0 - Not reversible in 7 days

Animal 5 - Edema average score (24, 48, 72 hours): 0 - Not reversible in 7 days

Animal 6 - Edema average score (24, 48, 72 hours): 0 - Not reversible in 7 days

All animals showed necrosis (already 60 minutes after application) and skin thickening effects during the study.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Under the study conditions and based on the results of this skin irritation study on New Zealand White rabbits the test substance lithium bromide (as solution) was regarded to be corrosive to the skin.

Executive summary:

A skin irritation study has been conducted with lithium bromide solution according to OECD guideline 404 and EU method B.4. One-half milliliter of lithium bromide solution was topically applied to each of three male and three female New Zealand White rabbits. Each test site was covered with a gauze patch, then a piece of plastic sheeting was placed around the trunk of each animal and taped at both ends with hypoallergenic tape. The test material was in contact with the skin for 4 hours, after which the plastic sheeting, gauze patch and residual test material were removed. Approximately 60 minutes after the end of the exposure period, each test site was scored for irritation using the method of Draize. Each test site was scored again at 24, 48 and 72 hours after patch removal and daily thereafter through day 7.

The primary irritation index is 4.3 (the maximial scoring is 8)

Within 60 minutes following unwrapping, necrosis was noted on four of the test sites and well defined to moderate erythema and very slight to slight edema were noted on the remaining two test sites; one of the latter sites also had abrasions. Within 48 hours of dosing, all test sites had necrosis and skin thickening. Irritation persisted through study day 7, at which time eschar, necrosis, skin thickening, ulceration and desquamation were observed. The study was terminated following the day 7 scoring to minimize pain.

Under the conditions of this study, the test material was considered to be corrosive cat. 1B when applied topically (as solution) to the intact skin of New Zealand White rabbits. (FMC, 1997).

This study is disregarded due to the fact that lithium bromide anhydrous is going to be registered under REACH Registration 1906/2007 and not a 52 - 54 % solution.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2010-10-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Deviations:

no

Principles of method if other than guideline:

Corrositex TM is a quantitative in vitro corrosivity test. The model is based on the time required for the test substance to pass through a biobarrier membrane and produce a change in a chemical detection system.

GLP compliance:

not specified

Remarks:

No specification on GLP compliance was given in the study record.

Details on study design:

The international Corrositex assay kit is an in vitro method for determining the corrosive potential of chemical substances. The results of this assay were used to determine the United Nations Transport Regulations Packaging Group. For detailed test procedure see Sect. "Any other information on materials and methods incl. tables"

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

mean of breakthrough time of 4 replicates

Value:

> 60

Remarks on result:

no indication of irritation

One run has been performed with 4 replicates. Each run was longer than > 60 minutes and so is the mean time of the 4 replicates.

Based on the results of the Corrositex TM Assay, the test article, lithium bromide has not to be classified as corrosive according to the UN Dangerous Goods Transport Regulations.

Interpretation of results:

GHS criteria not met

Conclusions:

Lithium bromide was tested for corrosive properties in the Corrositex TM Assay which is used for assigning the packaging group according to UN Dangerous Goods Transport Regulations. Lithium bromide was found in this test to be not corrosive.

Executive summary:

Lithium bromide was tested for corrosive properties in the Corrositex TM Assay in a single trial (four replicates) that examines the mean breakthrough time in order to determine the packing group classification. The mean breakthrough time of the 4 replicates was > 60 minutes, therefore, based on the evaluation of the test results (see "any other information on materials and methods") lithium bromide was not considered to be corrosive. (FMC, 1999)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-01-20 to 1988-02-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP study with slight deviations to the correspondent OECD guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Please refer to the section "Principles of method if other than guideline"

Principles of method if other than guideline:

The study was conducted with four instead of three animals. The eyes of two of them were washed with water shortly after the instillation. The other two animals remained unwashed.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania, USA
- Age at study initiation: young adults
- Weight at study initiation: 3.10 - 3.24 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Purina High Fiber Rabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 - 71
- Humidity (%): 29 - 59
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The left untreated eye served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

20-30 seconds

Observation period (in vivo):

16 days

Number of animals or in vitro replicates:

four animals (three males, one female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Washing was done with fresh tap water in two out of four animals. The other two remained unwashed.
- Time after start of exposure: 20-30 seconds

SCORING SYSTEM: Draize, J.H. et al. (1944)

TOOL USED TO ASSESS SCORE: The eyes were assessed with a penlight type lamp as well as with the aid of 2 % sodium fluorescein dye.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritation parameter:

cornea opacity score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritation parameter:

conjunctivae score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye not washed

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: eye washed with tap water

Irritant / corrosive response data:

One hours post-dosing, mild to severe conjunctivitis and slight corneal opacities were noted. Irritation worsened after 24 hours at which time one eye also developed a hemorrhagic conjunctivae and one eye had a white conjunctivae. After 48 hours, irritation gradually subsided and was completely resolved by study day 16. Washing the eyes with tap water shortly after exposure increased the severity of the irritation observed.

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of this study, the test material was considered to be not irritating to both washed and unwashed eyes.

Executive summary:

An eye irritation study was conducted with lithium bromide anhydrous according to a non-definitive eye irritation protocol from FMC. Lithium bromide anhydrous was instilled into the test eyes of four New Zealand White rabbits at a dose of 0.10 g. The eyes of two rabbits remained unwashed while the eyes of the remaining two rabbits were gently washed with 100 mL of tap water approximately 20 - 30 seconds after treatment. Eyes were assessed for irritation using the method of Draize at 24, 48 and 72 hours after instillation.

Mild to severe conjunctivitis and slight to mild corneal opacities were noted during the study. In addition, white, brown and hemorrhagic areas were noted on the conjunctivae. All irritation resolved by study day 16, at which the test was terminated. Washing the eyes with tap water shortly after exposure increased the severity of the irritation observed. One rabbit (with washed eyes) developed significantly higher scores regarding cornea opacity (2), conjunctival redness (2.33) and chemosis (3.67) compared to the other three animals. Due to the facts it can not be totally excluded that lithium bromide is irritating.

Considering the results of this study, lithium bromide anhydrous is considered to be irritating to the eyes of New Zealand White rabbits. (FMC, 1988)

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1997-01-22

Reliability:

other: Study itself has a reliability of 1, but was considered as disregarded since a 52 % solution was tested.

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 24th 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 29th 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HRP, Inc., Denver, PA, USA
- Age at study initiation: young adults
- Weight at study initiation: 2.51 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Purina High Fiber Rabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68
- Humidity (%): 48 - 49
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

water

Controls:

other: The adjacent eye served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Number of animals or in vitro replicates:

one animal

Details on study design:

TOOL USED TO ASSESS SCORE: fluorescein

Irritant / corrosive response data:

Immediately upon dosing, the animal appeared to be in pain and the conjunctivae appeared hemorrhaged. The rabbit was immediately euthanized because of animal welfare reasons.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on this eye irritation study lithium bromide solution showed severely irritating effects to the eye of one New Zealand White rabbit.

Executive summary:

In preparation for the definitive eye irritation study, lithium bromide solution was instilled into the right eye of one anesthetized New Zealand White rabbit (a local anesthetic was also administered to the eye to minimize the pain). Immediately upon dosing, the animal appeared to be in pain and the conjunctivae appeared hemorrhaged. The definitive study was not conducted. The material should be considered severely irritating to eyes. ( FMC, 1997)

This study is disregarded due to the fact that lithium bromide anhydrous is going to be registered under REACH Registration 1906/2007 and not a 52 % solution.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation study in vivo

In the most appropriate in vivo skin irritating study (key study) with 0.5 g lithium bromide anhydrous (in solid form), three New Zealand White rabbits were treated topically on each of two test sites which were previously clipped free of hair according to OECD guideline 404. The test sites were covered with gauze patches and the trunk of each animal was wrapped with a sheet of cheesecloth. The test material was in contact with the skin for 4 hours, after which the animals were unwrapped and the test material removed. Approximately 30 minutes after the end of the exposure period, the test sites were scored for irritation using the method of Draize. The test sites were scored daily thereafter for 14 days. Slight to severe erythema and slight to severe edema were noted on the test sites during the study. One rabbit also exhibited eschar, exfoliation and appeared to be burned on the test sites. Irritation on two of the rabbits had not resolved by day 14 of the study. The primary irritation index was 2.1 (out of 8). Under the conditions of this study and based on the primary irritation index, the test material was evaluated to be irritating to intact skin when applied topically to New Zealand White rabbits.

The result of the in vivo study might be explained as follows: Sweat is produced during the 4 hour wrapping of the animals. During solving of lithium bromide in the sweat the heat of the reaction can lead to irritations as mentioned above. Furthermore the pH changed from slightly acid to slightly basic (9 - 10.5), which is the normal pH of lithium bromide solution. (FMC, 1988)

This result is supported by an in vitro skin corrosion study (Corrositex). Lithium bromide anhydrous did not cause any corrosive effects in this study. (FMC, 1999)

Eye irritation study in vivo

An eye irritation study was conducted with lithium bromide anhydrous according to a non-definitive eye irritation protocol from FMC. Lithium bromide anhydrous was instilled into the test eyes of four New Zealand White rabbits at a dose of 0.10 g. The eyes of two rabbits remained unwashed while the eyes of the remaining two rabbits were gently washed with 100 mL of tap water approximately 20 - 30 seconds after treatment. Eyes were assessed for irritation using the method of Draize at 24, 48 and 72 hours after instillation.

Mild to severe conjunctivitis and slight to mild corneal opacities were noted during the study. In addition, white, brown and hemorrhagic areas were noted on the conjunctivae. All irritation resolved by study day 16, at which the test was terminated. Washing the eyes with tap water shortly after exposure increased the severity of the irritation observed. One rabbit (with washed eyes) developed significantly higher scores regarding cornea opacity (2), conjunctival redness (2.33) and chemosis (3.67) compared to the other three animals. Due to this fact, it cannot be completely excluded that lithium bromide is irritating, therefore lithium bromide anhydrous is considered to be irritating to the eyes of New Zealand White rabbits. (FMC, 1988)

disregarded studies

Two studies (in vivo skin study from 1997 and in vivo eye study from 1997) have been marked as disregarded. Both studies used a 52 - 54 % lithium bromide solution and resulted in severe injuries of the animals with irreversible damage of tissue in both eye and skin. In both studies a pH value of 7.4 is stated for the lithium bromide solution. The published pH value of 55 % solutions of lithium bromide in water is between 9 - 10.5. This is slightly basic just like customary soap. In the eye irritation study from 1988 (FMC), the eyes of two animals were washed with water after 30 sec of exposure. This had increased the severity of the irritation, but all irritations were resolved by study day 16. Thus, lithium bromide solution is irritating to both eye and skin. The two studies were marked as disregarded as solid lithium bromide (not the solution) is registered.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin irritation/corrosion and eye irritation, the test item has to be classified and labelled as skin irrit. cat. 2, H315 (Causes skin irritation) and eye irrit. cat. 2A, H319 (causes serious eye irritation) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.