Registration Dossier

Administrative data

Description of key information

The test substance lithium nitrate was considered to be not irritating to the skin based on the results obtained in an in vivo skin irritation study with New Zealand White rabbits. Lithium nitrate is judged to be irritating to the intact eyes of New Zealand White rabbits in an acute eye irritation study.

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:
1999-03-18 to 1999-04-19
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:
July 17th 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
January 1993
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance, Denver, PA
- Age at study initiation: young adult
- Weight at study initiation: 2.2-2.6 kg
- Housing: individually housed in stainless steel cages
- Diet (e.g. ad libitum): Purina High FiberRabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-67
- Humidity (%): 53-54
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
other: test site was clipped free of fur
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g

VEHICLE
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 animals per sex
Details on study design:
TEST SITE
- Area of exposure: scapular to pelvic region
- Type of wrap: plastic wrap

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

SCORING SYSTEM: according to method of Draize
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
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:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

Edema scores for each of the 6 animals at observation time 24, 48 or 72 hours were 0. Erythema scores for each of the animals at observation times 48 or 72 hours were 0. Only at observation time 24 hours 2 / 6 animals had an erythema score of 1 while the rest of the animals 4 / 6 had each a score of 0.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance lithium nitrate is not irritating to the skin of New Zealand White rabbits.
Executive summary:

An acute dermal irritation study has been performed with lithium nitrate according to OECD guideline 404 and EU method B.4. One-half gram of lithium nitrate was topically applied to 3 male and 3 female New Zealand White rabbits for 4 hours under a plastic wrap. Sixty minutes after the end of the exposure period, each test site was scored for irritation using the Draize method. Each test site was scored again 24, 48 and 72 hours after exposure. The irritation scores are as follows:

Edema scores for each of the 6 animals at observation time 24, 48 or 72 hours were 0. Erythema scores for each of the animals at observation times 48 or 72 hours were 0. Only at observation time 24 hours 2 / 6 animals had an erythema score of 1 while the rest of the animals 4 / 6 had each a score of 0.

During the first hour slight to mild erythema and slight edema were noted. At the 24-hour scoring, only slight erythema was observed on two test sites. All irritation resolved by the 48-hour scoring interval and the study was terminated following the 72-hour scoring. Based on the results of the study the test material was considered to be not irritating when topically applied to New Zealand White rabbits. (FMC, 1999)

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:
1999-03-25 until 1999-04-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Feb. 24 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Jan. 1993
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
Aug. 1999
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance, Denver, PA, U.S.A
- Weight at study initiation: 2.52-2.73 kg
- Housing: animals were individually housed in stainless steel cages
- Diet: Purina High Fiber Rabbit Chow 5326 was provided ad libitum
- Water: Fresh tap water, ad libitum
- Acclimation period: 5 days prior to study start

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 66-68
- Humidity (%): 52-57
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each animal (left eye) was used as a control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Duration of exposure is the duration of study as the eyes were not washed after test item application
Observation period (in vivo):
1, 24 , 48, 72 hours after application and 7 days after application
Number of animals or in vitro replicates:
6 animals, 3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not done

SCORING SYSTEM: Draize scoring

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
At the 1 hour scoring, slight to mild corneal opacities, slight conjunctival redness, slight to mild chemosis, severe discharge, and gray areas on the conjunctivae were noted. Additionally, three rabbits had miosis. During the 24-hour scoring, slight corneal opacities, iritis, moderate conjunctivitis, and a positive reaction to fluorescein were observed. Irritation gradually resolved and all eyes had completely recovered by study day 7.

All animals remained healthy throughout the study. No changes were observed in necropsy.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Lithium nitrate is judged to be irritating to the intact eyes of New Zealand White rabbits in this acute eye irritation study.
Executive summary:

The eye irritating potential of lithium nitrate was assessed in this acute eye irritation study according to OECD guideline 405 and EU method B.5. One single anesthetized rabbit was dosed with lithium nitrate prior to the start of the definitive study to minimize pain. Since only moderate irritation was noted in this rabbit, six rabbits (3 males and 3 females, New Zealand White) were dosed in the following manner. Lithium nitrate was instilled into the right eye of each of the six rabbits at a dose of 0.10 mL dry volume measure. Eyes were assessed for irritation using the Draize method 1, 24, 48, and 72 hours post-dosing, and on day 7. At the 1 hour scoring, slight to mild corneal opacities, slight conjunctival redness, slight to mild chemosis, severe discharge and gray areas on the conjunctivae were noted. Additionally, three rabbits had miosis. During the 24-hour scoring slight corneal opacities, iritis, moderate conjunctivitis, and a positive reaction to fluorescein were observed. Irritation gradually resolved and all eyes had completely recovered by study day 7. Lithium nitrate is judged to be moderately irritating. (FMC, 1999)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

An acute dermal irritation study was performed with lithium nitrate according to OECD guideline 404 and EU method B.4. One-half gram of lithium nitrate was topically applied to 3 male and 3 female New Zealand White rabbits for 4 hours under a plastic wrap. Sixty minutes after the end of the exposure period, each test site was scored for irritation using the Draize method. Each test site was scored again 24, 48 and 72 hours after exposure. The irritation scores are as follows:

Edema scores for each of the 6 animals at observation time 24, 48 or 72 hours were 0. Erythema scores for each of the animals at observation time 48 or 72 hours were 0. Only at observation time 24 hours 2 / 6 animals had an erythema score of 1 while the rest of the animals 4 / 6 had each a score of 0.

During the first hour slight to mild erythema and slight edema were noted. At the 24-hour scoring, only slight erythema was observed on two test sites. All irritation resolved by the 48-hour scoring interval and the study was terminated following the 72-hour scoring. Based on the results of the study the test material was considered to be not irritating when topically applied to New Zealand White rabbits. (FMC, 1999)

Eye irritation

The eye irritating potential of lithium nitrate was assessed in this acute eye irritation study according to OECD guideline 405 and EU method B.5. One single anesthetized rabbit was dosed with lithium nitrate prior to the start of the definitive study to minimize pain. Since only moderate irritation was noted in this rabbit, six rabbits (3 males and 3 females, New Zealand White) were dosed in the following manner. Lithium nitrate was instilled into the right eye of each of the six rabbits at a dose of 0.10 mL dry volume measure. Eyes were assessed for irritation using the Draize method 1, 24, 48, and 72 hours post-dosing, and on day 7. At the 1 hour scoring, slight to mild corneal opacities, slight conjunctival redness, slight to mild chemosis, severe discharge and gray areas on the conjunctivae were noted. Additionally, three rabbits had miosis. During the 24-hour scoring slight corneal opacities, iritis, moderate conjunctivitis, and a positive reaction to fluorescein were observed. Irritation gradually resolved and all eyes had completely recovered by study day 7. Lithium nitrate is judged to be moderately irritating. (FMC, 1999)


Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study.

Effects on eye irritation: irritating

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 irritating properties, the test item needs to be classified as eye irritating cat. 2 (H319: may cause serious eye irritation) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.