Lithium bis(oxalato)borate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-11-02 to 2010-11-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24th 2002

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium bis(oxalato)borate

EC Number:

456-990-3

EC Name:

Lithium bis(oxalato)borate

Cas Number:

244761-29-3

Molecular formula:

C4BLiO8 (Hill Empirical Formula) C4BO8.Li (CAS Empirical Formula)

IUPAC Name:

boron(3+) lithium(1+) dioxalate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Myrtle´s Rabbitry, Inc., Thompsons Station, TN, USA
- Age at study initiation: ca. 4 months old (born on 2010-07-20)
- Weight at study initiation: ca. 2.7 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): PMI Rabbit Chow (Diet# 5321), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
- animal room was temperature controlled.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The contralateral eye served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 83.2 mg (0.1 mL equivalent)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 (one male, two females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: washing was not done.

TYPE AND FREQUENCY OF OBSERVATIONS
Using a Mini-Maglite flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours and again on days 7, 14 and 21 postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval up to day 21. The eye was examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.
Body weights were recorded pretest and at termination.
Observations for toxicity and pharmacological effects were recorded at each ocular observation period and mortality observations were performed daily. All animals were humanely sacrificed using CO2 following study termination.

ANALYSIS OF DATA
The primary eye irritation score for each rabbit was calculated from the weighted Draize scale.

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

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #1

Time point:

24 h

Score:

22

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 2

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #1

Time point:

48 h

Score:

98

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 3

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #1

Time point:

72 h

Score:

98

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 4

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #2

Time point:

24 h

Score:

40

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 5

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #2

Time point:

48 h

Score:

98

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 6

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #2

Time point:

72 h

Score:

98

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 7

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #3

Time point:

24 h

Score:

73

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 8

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #3

Time point:

48 h

Score:

71

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 9

Irritation parameter:

overall irritation score

Remarks:

sum of cornea, iris and conjunctiva score

Basis:

animal #3

Time point:

72 h

Score:

71

Max. score:

110

Reversibility:

not fully reversible within: 21 days of observation period.

Results 10

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 11

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 12

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 13

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Corneal opacity, iritis and conjunctival irritation, noted in 3/3 eyes, persisted to day 21.

Other effects:

There were no abnormal physical signs noted during the observation period. Body weight increases were normal.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Based on the results of this in vivo eye irritation study on three New Zealand White rabbits, lithium bis(oxalato) borate causes irreversible effects to the eyes.

Executive summary:

An eye irritation study has been conducted with lithium bis(oxalato)borate in accordance with OECD guideline 405. Three healthy New Zealand White rabbits, free from evidence of ocular irritation and corneal abnormalities, were dosed with lithium bis(oxalato)borate. The test article (0.1 mL equivalent (83.2 mg)) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pretest and scored by Draize technique at 1, 24, 48 and 72 hours and again on days 7, 14 and 21 postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24 -hour observation interval up to day 21. Observations for toxicity and pharmacological effects were recorded at each ocular observation period and mortality observations were performed daily. Body weights were recorded pretest and at termination. Corneal opacity, iritis and conjunctival irritation, noted in 3/3 eyes, persisted to day 21. There were no abnormal physical signs noted during the observation period. Body weight increases were normal.

Lithium bis(oxalato)borate causes irreversible effects to the healthy eye of New Zealand White rabbits. (MB Research Laboratories, 2010)