Lithium sulphate

Endpoint summary

Description of key information

Under the conditions of the skin irritation study, lithium carbonate is not irritating to intact skin of New Zealand White rabbits when brought into contact with the skin for four hours. This study that was used for read-across
Lithium sulfate anhydrous and its monohydrate were also tested for corrosive properties in the Corrositex TM Assay which is used for assigning the packaging group according to UN Dangerous Goods Transport Regulations. Both substances were found to be not corrosive. 
Under the conditions of the eye irritation study, lithium carbonate is irritating to eyes. The study was used for read-across.

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:

1988-01-21 to 1988-01-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

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
- Age at study initiation: Young adult
- Weight at study initiation: 3.19 kg to 3.33 kg
- Housing: individually in stainless steel cages
- Diet: ad libitum, Purina High Fiber Rabbit Chow 5326
- Water:ad libitum, fresh tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21.7
- Humidity (%): 36 - 48
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

physiological 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:

The animals were weighed once on the day before dosing. Clinical signs were recorded as noted. Approximately 30 minutes after unwrapping, the test sites of each rabbit were scored for irritation using the method of Draize.

Number of animals:

3 (2 male, 1 female)

Details on study design:

TEST SITE
- Area of exposure: The clipped area extended from the scapular to the pelvic region. One test site was located on each side of the spinal column.
- Type of wrap: semi-occlusive cheesecloth bandage

REMOVAL OF TEST SUBSTANCE
- Washing: The test sites were wiped with clean gauze moistened with methanol, then rinsed with tap water.

SCORING SYSTEM: Approximately 30 minutes after unwrapping, the test sites of each rabbit were scored for irritation using the method of Draize. The sites were evaluated daily thereafter for 5 days.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

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

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All animals remained healthy throughout the study.
One rabbit had slight erythema on study days 1-4. All irritation had resolved by study day 5 at which time the test was terminated.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Under the conditions of this study , the lithium carbonate is not irritating to intact skin of New Zealand White rabbits after 4 hours of exposure.

Executive summary:

An acute skin irritation/corrosion study in New Zealand White rabbits was performed in accordance with OECD Guideline 404. 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 Carbonate Technical Grade 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, 24, 48, 72 hours after the end of the exposure period, the test sites were scored for irritation using the method of Draize. Irritation observed in one of the three animals (scored 1 for erythema) had resolved by the end of the study (day 5). Under the conditions of this study, the test material is not irritating to intact skin of New Zealand White rabbits when brought into contact with the skin for four hours. The used scores of the test system (US scheme) were adapted to the EU scheme.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2001-08-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable, scientific valid study in order to assess eventual corrosive potential.

Qualifier:

no guideline available

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

Species:

other: not applicable

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:

other: other: corrosivity

Value:

> 60

Remarks on result:

other:

Remarks:

Basis: other: mean of breakthrough time of 4 replicates. Time point: > 60 minutes. Remarks: When results of > 60 minutes are obtained, the substance is consequently categorized to be non-corrosive.. (migrated information)

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 sulfate anhydrous has not to be classified as corrosive according to the UN Dangerous Goods Transport Regulations.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: UN Dangerous Goods Transport Regulations

Conclusions:

Lithium sulfate anhydrous 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 sulfate anhydrous was found in this test to be not corrosive.

Executive summary:

Lithium sulfate anhydrous 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 lithium sulfate anhydrous was not considered to be corrosive.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2001-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable, scientific valid study in order to assess eventual corrosive potential.

Qualifier:

no guideline available

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

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:

other: other: corrosivity

Value:

> 60

Remarks on result:

other:

Remarks:

Basis: other: mean of breakthrough time of 4 replicates. Time point: > 60 minutes. Remarks: When results of > 60 minutes are obtained, the substance is consequently categorized to be non-corrosive. (migrated information)

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 sulfate monohydrate has not to be classified as corrosive according to the UN Dangerous Goods Transport Regulations.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: UN Dangerous Goods Transport Regulations

Conclusions:

Lithium sulfate monohydrate 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 sulfate monohydrate was found in this test to be not corrosive.

Executive summary:

Lithium sulfate monohydrate 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 lithium sulfate monohydrate was not considered to be corrosive.

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:

1988-01-21 to 1988-01-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

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
- Age at study initiation: Young adult
- Weight at study initiation: 2.83 kg to 3.15 kg
- Housing: individually in stainless steel cages
- Diet: ad libitum, Purina High Fiber Rabbit Chow 5326
- Water:ad libitum, fresh tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21.7
- Humidity (%): 33 - 48
- 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): 0.1 g per test eye

Duration of treatment / exposure:

The test material was tapped off a piece of weighing paper into the lower conjunctival sac which was formed when the lower eyelid was pulled away from the test eye. The upper and lower lids were then brought together and held closed for one second and released. The eyes of two of the rabbits remained unwashed and the eyes of the remaining two rabbits were gently washed with 100 ml of tap water approximately 20 - 30 sec after treatment.

Observation period (in vivo):

The animals were weighed once on the day before dosing. Clinical signs were recorded as noted.

Number of animals or in vitro replicates:

4 (3 male, 1 female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of two of the rabbits remained unwashed and the eyes of the remaining two rabbits were gently washed with 100 ml of tap water approximately 20 - 30 sec after treatment. The rate of application of the wash water was approximately 100 ml/min.
- Time after start of exposure: 20 - 30 sec

SCORING SYSTEM: The eyes were scored for irritation potential at 1, 24, 48 and 72 hours and on day 4 and 7 using the method of Draize.

TOOL USED TO ASSESS SCORE: After the 24 hour examination with a penlight type light, the eyes were examined with the aid of 2 % sodium fluorescein dye.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: day 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: day 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: day 4

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

All animals remained healthy throughout the study.
One hour after dosing, unwashed eyes had mild corneal opacities, iritis, moderate conjunctivitis and white and hemorrhagic areas on the conjunctivae. Washed eyes had slight corneal opacities and slight conjunctivitis. At the 24-hour scoring, both washed and unwashed eyes had mild corneal opacities and moderate conjunctivitis. Irritation gradually resolved; washed eyes recovered by day 4, and unwashed eyes recovered by day 7. Washing the eyes with tap water shortly after exposure decreased both the severity and duration of the irritation observed.

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of this study, the test material is irritating to eyes.

Executive summary:

An acute eye irritation/corrosion study in New Zealand White rabbits was performed in accordance with OECD Guideline 405. Lithium carbonate Technical Grade was instilled into the test eyes of 4 New Zealand White rabbits at a dose of 0.1 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 1, 24, 48 and 72 hours after installation, as well as on days 4 and 7. Slight to mild corneal opacities, iritis and slight to moderate conjunctivitis were noted in all eyes. Unwashed eyes also had hemorrhages and white areas on the conjunctivae. Washing the eyes with tap water shortly after exposure decreased both the severity and the duration of the irritation observed. Irritation gradually resolved; washed eyes recovered by day 4 and unwashed eyes recovered by day 7. Based on the results obtained with unwashed eyes, lithium carbonate has to be classified as irritating to the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

An acute eye and skin irritation/corrosion study was not available for lithium sulfate and its monohydrate. Consequently, read-across was applied using study results obtained from lithium carbonate as a characteristically similar compound. The study on skin irritation is supported by two in vitro Corrositex studies performed with lithium sulfate anhydrous and its corresponding monohydrate.

skin irritation/corrosion

An acute skin irritation/corrosion study in New Zealand White rabbits was performed in accordance with OECD Guideline 404. 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 Carbonate Technical Grade 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, 24, 48, 72 hours after the end of the exposure period, the test sites were scored for irritation using the method of Draize. Irritation observed in one of the three animals (scored 1 for erythema) had resolved by the end of the study (day 5). Under the conditions of this study, the test material is not irritating to intact skin of New Zealand White rabbits when brought into contact with the skin for four hours. The used scores of the test system (US scheme) were adapted to the EU scheme. (FMC, 1988)

Corrositex Assays with lithium sulfate and the corresponding monohydrate

Lithium sulfate anhydrous and its monohydrate were 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 both substances were not considered to be corrosive. (FMC, 2001)

eye irritation

An acute eye irritation/corrosion study in New Zealand White rabbits was performed in accordance with OECD Guideline 405. Lithium carbonate Technical Grade was instilled into the test eyes of 4 New Zealand White rabbits at a dose of 0.1 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 1, 24, 48 and 72 hours after installation, as well as on days 4 and 7. Slight to mild corneal opacities, iritis and slight to moderate conjunctivitis were noted in all eyes. Unwashed eyes also had hemorrhages and white areas on the conjunctivae. Washing the eyes with tap water shortly after exposure decreased both the severity and the duration of the irritation observed. Irritation gradually resolved; washed eyes recovered by day 4 and unwashed eyes recovered by day 7. Based on the results obtained with unwashed eyes, lithium carbonate has to be classified as irritating to the eyes. (FMC, 1988)

Justification for classification or non-classification

In conclusion, lithium sulfate and its monohydrate are not to be classified according to Regulation (EC) No 1272/2008 (CLP) with regard to skin irritation. With respect to eye irritation, both have to be classified into Cat. 2B (H319) according to the Regulation (EC) No 1272/2008 (CLP).