Disulfiram

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 May - 25 May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2021

Deviations:

yes

Remarks:

Limited information on the scoring system.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disulfiram

EC Number:

202-607-8

EC Name:

Disulfiram

Cas Number:

97-77-8

Molecular formula:

C10H20N2S4

IUPAC Name:

disulfiram

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Isaac’s Farm, Litchfield, Illinois
- Age at study initiation: young adult
- Weight at study initiation: 2.16 - 2.37 kg
- Housing: one per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A mass of 32 ± 1 mg, determined to occupy a volume of 0.1 mL of test material

Duration of treatment / exposure:

single eye instillation

Observation period (in vivo):

24, 48, 72 hours and 7 day

Number of animals or in vitro replicates:

6 animals (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No washing

SCORING SYSTEM: The method of Draize (1944)

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

4.2

Max. score:

110

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 tested animals and mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Iris values according to current EU classification criteria

Results 4

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Iris values according to current EU classification criteria

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

of the remaining 4 tested animals and mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

6.67

Max. score:

20

Reversibility:

fully reversible within: 7 days

Remarks:

the scores were 16 after 24 h, and 2 after 48 and 72 h

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

2.66

Max. score:

20

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

4

Max. score:

20

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #4

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

3.33

Max. score:

20

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #5

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

2.66

Max. score:

20

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #6

Remarks:

mean of readings at

Time point:

24/48/72 h

Score:

2.66

Max. score:

20

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max. score as a sum of redness, chemosis and discharge

Irritant / corrosive response data:

Only one out of 6 tested animals showed stronger irritation of conjunctivae. No data on chemosis was available as it was used for the calculation of the conjunctivae score:

Iris Values were given as total scores x 5

Conjunctivae values were given as total results from (A+B+C) x 2 with a total maximum of 20 (A = Redness, B = Chemosis and C = Discharge)

As can be seen in the table entered in "Any other information on results incl. tables", the iris score was 5 for 2 animals on observation Day 1 (corresponding to total scores of 1 for each animal). For conjunctivae, no single scores can be calculated. However, according to the scoring system of Draize in combination with the scoring system of Kay and Calandra (1962), information on classification can be gained by calculating the overall irritation score. Therefore, the scores for conjunctivae, iris and cornea for each animal at each time point are added together and the mean calculated. An overall irritation score of 4.2 on a scale of 0 to 110 is considered a mild irritant, if the overall irritation scoe is >0 at the 48 h time point.

Reference: Kay JH, Calandra JC. 1962. Interpretation of eye irritation tests. J Soc Cosmet Chem 13:281–289

Any other information on results incl. tables

Table 1: Ethyl Thiurad: Primary Eye Irritation to Rabbits - Individual Irritation Scores*

Animal #	Obs. Day	Cornea	Iris	Conjunctivae	Total	Average of 24, 48 and 72 h
1	1	0	5	16	21	8.33
	2	0	0	2	2
	3	0	0	2	2
	7	0	0	0	0
2	1	0	0	8	8	2.66
	2	0	0	0	0
	3	0	0	0	0
3	1	0	5	8	13	5.66
	2	0	0	2	2
	3	0	0	2	2
	7	0	0	0	0
4	1	0	0	8	8	3.33
	2	0	0	2	2
	3	0	0	0	0
5	1	0	0	6	6	2.66
	2	0	0	2	2
	3	0	0	0	0
6	1	0	0	6	6	2.66
	2	0	0	2	2
	3	0	0	0	0

* Scores according to Draize, J.H. et al., 1944, J. Pharmacol. Exp. Therap. 82: 377-390.

Iris Values were given as total scores x 5

Conjunctivae values were given as total results from (A+B+C) x 2 with a total maximum of 20 (A = Redness, B = Chemosis and C = Discharge)

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU criteria not met

Conclusions:

The study was conducted similar to OECD guidelines and under GLP conditions. Under the conditions of the test, the test substance was a mild eye irritant.