Lithium bis[ethanedioato(2-)-κO1,κO2]difluorophosphate(1-)

Endpoint summary

Description of key information

Skin irritation:

The study was performed in accordance with OECD Guideline 404. The test material produced a mean erythema score of 2.83 and oedema score of 0.83. It was concluded that application of the test substance was moderately irritating by acute dermal irritation.

Eye irritation:

The study was performed in accordance with OECD Guideline 405. It was concluded that application of the test substance was severe irritating (rating 6) by acute eye irritation (unwashed test), was moderately irritating (rating 5) 4 s after instillation of the substance and was moderately irritating (rating 5) 30 s after instillation of the substance.

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:

key study

Study period:

From 2015-01-12 to 2015-02-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Remarks:

non GLP, but in compliance with China National Metrology Accreditation

Specific details on test material used for the study:

Batch No.: 141104
Purity: 95.4%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zhejiang Center of Laboratory Animals , Hangzhou, Zhejiang
- Weight at study initiation: About 2 kg
- Housing: Housed individually in suspended, wire bottom, stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12-hour light / dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

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

CONTROL
A single intact exposure site was selected as the test site, while the contralateral intact site served as a control site.

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

4 Males or female (nulliparous and non - pregnant)

Details on study design:

TEST SITE
- Area of exposure: At least 3 x 3 cm
- Type of wrap if used: Orthopedic stockinette

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin cleaned of residual test item using room temperature tap water
- Time after start of exposure: Four hours

OBSERVATION TIME POINTS
All animals should be examined for signs of erythema and oedema, and the responses scored at 24, 48 and 72 hours after patch removal. If there is damage to skin which cannot be recorded at 72 hours, observations rnay be needed until day 14 to determine the reversibility of the effects. If reversibility has been observed/ seen before 14 days, the experiment should be terminated at that time.

SCORING SYSTEM:
- Method of calculation: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.83

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.83

Max. score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Inidividual scores for dermal irritation:      

Number	Symptom	24 h	48 h	72 h	14 d
1	Erythema Edema	3 1	3 1	3 1	- -
2	Erythema Edema	3 1	4 1	4 1	- -
3	Erythema Edema	3 1	4 1	4 1	- -
4	Erythema Edema	1 1	1 0	1 0	- -

                                                                            

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material produced a mean erythema score of 2.83 and oedema score of 0.83. It was concluded that application of the test substance was moderately irritating by acute dermal irritation.

Executive summary:

The evaluation of acute dermal irritation/corrosion potential in white rabbits was conducted on the test substance according to OECD Guideline 404: Acute Dermal Irritationl Corrosion Test (Ministry of Environmental Protection of the People's Republic of China, 2004).

There was one intact test site per animal. Each test animal was treated with 0.5g test substance and covered with a semi-permeable dressing. The test substance was maintained in contact with the skin for 4 hours. Observations for dermal irritation and defects were made up to 14 days after removal of the dressings, or until reversibility was seen.

Both erythema and edema were observed in the skin of New Zealand white rabbits after the patch removal, the test was end on the 11th day. Therefore, the maximum primary irritation index of the test substance was calculated to be 3.75.

Based on the results, it was concluded that the application of the test substance was moderately irritating by acute dermal irritation.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Justification for type of information:

An in vivo skin irritation study is available, which was performed in order to satisfy the China new chemical notification scheme.

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:

From 2015-01-12 to 2015-02-16

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:

no

Remarks:

non GLP, but in compliance with China National Metrology Accreditation

Specific details on test material used for the study:

Batch No.: 141104
Purity: 95.4%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Zhejiang Center of Laboratory Animals, Hangzhou, Zhejiang
- Weight at study initiation: about 2 kg
- Housing: housed individually in suspended, wire bottom, stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7/8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%): 30% to 70%
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12-hour light / dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

4 s, 30 s

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

11 Males or female (nulIiparous and non - pregnant)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Six additional New Zealand white rabbits were used for washed test. 4 s after instillation, three eyes of the rabbits were washed for 30 s, using 0.9% saline water. 30 s after instillation, another three eyes of rabbits were washed for 30 s, using 0.9% saline water.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Inidividual scores for ocular irritation (unwashed test):

Animal	Symptom	Observation	1 h	24 h	48 h	72 h	21 d
1	Cornea	Degree	-	1	1	1	0
	Iris		1	1	1	1	0
	Conjunctivae	Redness	2	3	3	3	0
	Conjunctivae	Swelling	2	4	4	4	0

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

It was concluded that application of the test substance was severe irritating (rating 6) by acute eye irritation (unwashed test), was moderately irritating (rating 5) 4 s after instillation of the substance and was moderately irritating (rating 5) 30 s after instillation of the substance.

Executive summary:

The evaluation of acute eye irritation / corrosion potential in white rabbits was conducted on the test substance according to the Guidelines for the Testing of Chemicals: Test No. 405: Acute Eye Irritation / Corrosion Test (Ministry of Environmental Protection of the People's Republic of China, 2004).

0.1 g of the test substance was placed into the conjunctival sac of the right eye of each animal selected for testing. All treated eyes were then gently washed with 0.9% saline water, for 24 hours after instillation of the test substance. Parameters measured during the observation period included the conjunctivae, cornea and iris. Six additional New Zealand white rabbits were used for washed test. 4 s after instillation, three eyes of the rabbits were washed for 30 s, using 0.9% saline water. 30 s after instillation, another three eyes of rabbits were washed for 30 s, using 0.9% saline water.

Observation results of eye reaction after the application were shown as diffuse, crimson colour, individual vessels not easily discernible, obvious swelling, with partial eversion of lids, increased secretions accompanied by wet eyelid and eyelashes, corneal damage, iris hyperemia. The highest average of total score until 4 d after instillation was 45.0. Duration of irritation reaction was the average of total score on 7 d >20. All the signs were restored on the 21th day. Observation was finished on the 21th day.

Observation results of eye reaction (washed test, 4 s after instillation) were shown as diffuse, swelling, with lids about half closed, increased secretions, accompanied by wet eyelid and eyelashes. The highest average of total score until 4 d after instillation was 29.33. Duration of irritation reaction was the average of total score on the 7th day ≤ 20, more than half of animals ≤ 10.

Observation results of eye reaction (washed test, 30 s after instillation) were shown as diffuse beefy red, swelling, with lids about half closed, increased secretions, accompanied by eyelids, eyelashes and a large area around the eyes moist. The highest average of total score until 4d after instillation was 40.67. Duration of irritation reaction was the average of total score on the 7th day ≤ 10, more than half of animals ≤ 10.

It was concluded that application of the test substance was severe irritating (rating 6) by acute eye irritation (unwashed test), was moderately irritating (rating 5) 4 s after instillation of the substance and was moderately irritating (rating 5) 30 s after instillation of the substance.

Reference 2

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

Justification for type of information:

An in vivo eye irritation study is available, which was performed in order to satisfy the China new chemical notification scheme.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The evaluation of acute dermal irritation/corrosion potential in white rabbits was conducted on the test substance according to OECD Guideline 404: Acute Dermal Irritationl Corrosion Test (Ministry of Environmental Protection of the People's Republic of China, 2004).

There was one intact test site per animal. Each test animal was treated with 0.5g test substance and covered with a semi-permeable dressing. The test substance was maintained in contact with the skin for 4 hours. Observations for dermal irritation and defects were made up to 14 days after removal of the dressings, or until reversibility was seen.

Both erythema and edema were observed in the skin of New Zealand white rabbits after the patch removal, the test was end on the 11th day. Therefore, the maximum primary irritation index of the test substance was calculated to be 3.75.

Based on the results, it was concluded that the application of the test substance was moderately irritating by acute dermal irritation.

Eye irritation:

The evaluation of acute eye irritation / corrosion potential in white rabbits was conducted on the test substance according to the Guidelines for the Testing of Chemicals: Test No. 405: Acute Eye Irritation / Corrosion Test (Ministry of Environmental Protection of the People's Republic of China, 2004).

0.1 g of the test substance was placed into the conjunctival sac of the right eye of each animal selected for testing. All treated eyes were then gently washed with 0.9% saline water, for 24 hours after instillation of the test substance. Parameters measured during the observation period included the conjunctivae, cornea and iris.Six additional New Zealand white rabbits were used for washed test. 4 s after instillation, three eyes of the rabbits were washed for 30 s, using 0.9% saline water. 30 s after instillation, another three eyes of rabbits were washed for 30 s, using 0.9% saline water.

Observation results of eye reaction after the application were shown as diffuse, crimson colour, individual vessels not easily discernible, obvious swelling, with partial eversion of lids, increased secretions accompanied by wet eyelid and eyelashes, corneal damage, iris hyperemia. The highest average of total score until 4 d after instillation was 45.0. Duration of irritation reaction was the average of total score on 7 d >20. All the signs were restored on the 21th day. Observation was finished on the 21th day.

Observation results of eye reaction (washed test, 4 s after instillation) were shown as diffuse, swelling, with lids about half closed, increased secretions, accompanied by wet eyelid and eyelashes. The highest average of total score until 4 d after instillation was 29.33. Duration of irritation reaction was the average of total score on the 7th day ≤ 20, more than half of animals ≤ 10.

Observation results of eye reaction (washed test, 30 s after instillation) were shown as diffuse beefy red, swelling, with lids about half closed, increased secretions, accompanied by eyelids, eyelashes and a large area around the eyes moist. The highest average of total score until 4d after instillation was 40.67. Duration of irritation reaction was the average of total score on the 7th day ≤ 10, more than half of animals ≤ 10.

It was concluded that application of the test substance was severe irritating (rating 6) by acute eye irritation (unwashed test), was moderately irritating (rating 5) 4 s after instillation of the substance and was moderately irritating (rating 5) 30 s after instillation of the substance.

Justification for classification or non-classification

Skin irritation/corrosion:

In accordance with Regulation (EC) No. 1272/2008 Table 3.2.2, substance can be classified as Category 2: Irritant when mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions.

As mean scores at 24, 48 & 72 hours for erythema were 3.25, 3, 3 for 4 test animals, respectively; mean scores at 24, 48 & 72 hours for edema were 1, 0.75, 0.75 for 4 test animals, respectively; and irritating was seen to be fully reversible within 14 days, therefore this substance should be classified as Category 2 for the Skin irritation/corrosion endpoint.

 

Serious eye damage/eye irritation:

In accordance with Regulation (EC) No. 1272/2008 Table 3.3.2, substance that have the potential to induce reversible eye irritation are classified in Category 2 when mean scores at 24, 48 & 72 hours for corneal opacity were ≥ 1 and/or for iris were ≥ 1 and/or for conjunctival redness were ≥ 2 and/or for conjunctival oedema (chemosis) were ≥ 2 in at least 2 of 3 tested animals.

As mean scores of cornea opacity, iris, conjunctivae redness and conjunctival swelling were 1, 1, 3, 4 at 24, 48 and 72 hours after administrations and irritating was seen to be fully reversible within 21 days, therefore this substance should be classified Category 2 for the Serious eye damage/eye irritation endpoint.