Diquat dibromide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Aug 1996 to 12 Sep 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal 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

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 2305 - 3020 g
- Housing: Individually in aluminium sheet cage
- 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 20 Aug 1996 To:12 Sep 1996

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

Technical solution

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

23 days

Number of animals:

3 females

Details on study design:

APPLICATION OF TEST SUBSTANCE
Approximately 24 hours prior to application of the test substance, the hair was removed with a pair of veterinary clippers from an area approximately 7 cm x 13 cm on the left flank of each animal. The undiluted test substance (0.5 mL) was applied, using a sterile disposable polypropylene syringe, to the test site (approximate size 2.5 cm x 2.5 cm) on the left flank of each rabbit. The treated area was covered with a piece of 4-ply surgical gauze (approximate size 2.5 cm x 2.5 cm), which was secured by two strips of surgical tape (approximate size 1 cm x 8 cm). This was covered by a piece of impermeable rubber sheeting (approximate size 35 cm x 13 cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape. The dressings were left in position for approximately four hours. After this time each dressing was carefully removed and discarded. The application site was gently cleansed free of any residual test substance using clean swabs of absorbent cotton wool soaked in 3 % teepol in water and was then dried gently with clean tissue paper.

IRRITATION RESPONSE
The animals were assessed daily for up to 23 days for any signs of skin irritation. Irritation was scored by the method of Draize, to assess the degree of erythema and oedema at the application sites approximately 30 - 60 minutes and 1, 2 and 3 days after removal of the dressings and then at intervals for up to 23 days. Any other signs of skin irritation were also noted.

BODY WEIGHTS
The body weight of each animal was recorded at the start of the study.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Very slight or well-defined erythema was seen in two animals for up to 7 days and in one animal for up to 17 days. Very slight or slight erythema was seen in all animals for up to 2 or 7 days. There were no additional signs of irritation in one animal. Additional signs seen in the remaining two animals included desquamation, thickening and development of new skin with the associated sparse hair growth. All signs of irritation had completely regressed by day 23 in both animals.

Other effects:

There were no signs of ill-health in any animal during the study.

Any other information on results incl. tables

Table 1: Individual and mean skin irritation scores of test substance according to the Draize scheme

Time	Erythema			Oedema
Animal number	#1	#2	#3	#1	#2	#3
after 30 - 60 minutes	1	1	0	1	1	0
after 1 day	1	1	1	1	1	1
after 2 day	1	1	1	1	0	1
after 3 days	1	1	1	1	0	2
mean score 24 - 72 h	1.0	1.0	1.0	1.0	0.3	1.3
after 4 days	2	1	1	1	0	2
after 7 days	0 d, n, t	0	1 d, t	0	0	0
after 10 days	-	-	1 d, t	-	-	0
after 11 days	0 d, n, t	-	-	0	-	-
after 14 days	0	-	1 d,	0	-	0
after 17 days	-	-	0 d, n, sp	-	-	0
after 21 days	-	-	0 n	-	-	0
after 23 days	-	-	0	-	-	0

  d – desquamation;  n – new skin;    t – thickening;   sp – sparse hair growth

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test substance is a moderate to severe irritant following a single four-hour application to rabbit skin.

Executive summary:

In a primary dermal irritation study in accordance with OECD 404 and in compliance with GLP, 3 young adult female New Zealand White albino rabbits were dermally exposed to 0.5 mL of test substance to an area (approximately 2.5 cm x 2.5 cm) of the shorn flank for 4 hours. The animals were assessed for up to 23 days for any signs of skin irritation. Irritation was scored by the method of Draize.

Very slight or well-defined erythema was seen in two animals for up to 7 days and in one animal for up to 17 days. Very slight or slight oedema was seen in all animals for up to 2 or 7 days. There were no additional signs of irritation in one animal. Additional signs seen in the remaining two animals included desquamation, thickening and development of new skin with associated sparse hair growth. All signs of irritation had completely regressed by day 23 in both animals. The test substance is a moderate to severe irritant following a single four-hour application to rabbit skin.