Diquat dibromide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Aug 1996 to 5 Sep 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diquat dibromide

EC Number:

201-579-4

EC Name:

Diquat dibromide

Cas Number:

85-00-7

Molecular formula:

C12H12N2.2Br

IUPAC Name:

1,1'-ethylene 2,2'-bipyridyldiylium dibromide

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 3021 - 3077 g
- Housing: Individually in aluminium sheet cage
- Diet: Diet (STANRAB SQC), ad libitum
- Water: Mains water, ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): approximately 25 - 30
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 21 Aug 1996 To: 5Sep 1996

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

Technical solution

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3 females

Details on study design:

PREPARATION AND SELECTION OF ANIMALS
The eyes of the animals were examined one day prior to test item administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.

INSTILLATION
Initially, the test substance (0.1 mL) was instilled into the conjunctival sac of the left eye of one rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for 1 - 2 seconds after which the animal was released. The other eye was untreated (control eye). Immediately after the instillation of the test substance, an assessment of initial pain was made on a 6 point scale.

CAGE SIDE OBERVATIONS
When the eye irritation potential had been fully assessed in the first animal, the test eye of the remaining two animals was assessed. Animals were observed frequently on the day of dosing and daily throughout the remainder of the study.

OCULAR SCORING
The eyes were examined for up to 8 days, to assess the grade of ocular reaction. Irritation was scored by the method of Draize 1959, to assess the grade of ocular reaction approximately one hour and 1, 2 and 3 days after instillation and then at intervals for up to 8 days. In addition, as an aid in the assessment of corneal damage, fluorescein staining was used at all readings from 1 day after instillation. A modified form of the Kay and Calandra (1962) system was used to interpret and classify the numerical scores. This scoring table is derived fom the Draize scoring table, which is included in the "Any other information on materials and methods incl. tables" field. This table will be used to interpret the results from this study.

BODY WEIGHT
The animals were weighed prior to the start of the study.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Instillation into the eye caused slight initial pain (class 2 on a 0 - 5 scale). No corneal or iridial effects were observed. Conjunctival effects included slight to moderate redness, slight chemosis and slight to moderate discharge. The area around the eye of two of the animals was stained brown or brown/red by the test material. Additional signs of irritation included mucoid and Harderian discharge and erythema and thickening of the eyelids. All effects had completely regressed by day 8.

Other effects:

MORTALITY
No deaths occurred.

CLINICAL SIGNS
No systemic signs of toxicity were noted during the study

BODY WEIGHT:
The body weights of the rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Table 1: Eye irritation scores of the test substance according to the Draize scheme

Time		Cornea			Iris			Conjunctiva
								Redness			Chemosis
Animal number		#1	#2	#3	#1	#2	#3	#1	#2	#3	#1	#2	#3
after approx. 1 hour		0	0	0	0	0	0	1 m, st	1 m	1 m, st	1	1	1
after 24 hours		0	0	0	0	0	0	2 m, d, st	2 e	2 m, r, st	1	1	1
after 48 hours		0	0	0	0	0	0	2 m, st	2 e, d, r	2 d, r, st,	1	0	0
after 72 hours		0	0	0	0	0	0	1 st	1 e, d, r	1 d, r, st	0	0	0
mean scores 24 - 72h		0	0	0	0	0	0	1.7	1.7	1.7	0.7	0.3	0.3
after 4 days		0	0	0	0	0	0	1 st	1 d	1 d, st	0	0	0
after 7 days		0	0	0	0	0	0	0	1	0 st	0	0	0
after 8 days		-	0	-	-	0	-	-	0	-	-	0	-

d – Harderian discharge; m – mucoid discharge; st – staining of peri orbital area; e – eyelids thickened; r – erythema of the upper/lower eyelid

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance is a mild irritant to the rabbit eye.

Executive summary:

In a primary eye irritation study following OECD TG 405 and in compliance with GLP, 0.1 mL of test substance was instilled into the conjunctival sac of the left eye of each of 3, young adult female, New Zealand White rabbits. Immediately after the instillation of the test substance, an assessment of initial pain was made. The eyes were examined for up to 8 days, to assess the grade of ocular reaction. Irritation was scored by the method of Draize 1959.

Instillation into the eye caused slight initial pain (class 2 on a 0 - 5 scale). No corneal or iridial effects were observed. Conjunctival effects included slight to moderate redness, slight chemosis and slight to moderate discharge.  The area around the eye of two of the animals was stained brown or brown/red by the test material. Additional signs of irritation included mucoid and Harderian discharge and erythema and thickening of the eyelids. All effects had completely regressed by day 8.

The test substance is a mild irritant to the rabbit eye.