Chlorothalonil

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Dec 1999 to 16 Jan 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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 OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chlorothalonil

EC Number:

217-588-1

EC Name:

Chlorothalonil

Cas Number:

1897-45-6

Molecular formula:

C8Cl4N2

IUPAC Name:

tetrachlorobenzene-1,3-dicarbonitrile

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 2519 to 2976 g
- Housing: The rabbits were housed individually in cages suitable for animals of this strain and the weight range expected during the course of the study
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): A minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 Dec 1999, To: 16 Jan 2000

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

(deionised)

Controls:

no

Amount / concentration applied:

VEHICLE
- Amount applied: 0.5 to 0.6 mL

Duration of treatment / exposure:

4 hours

Observation period:

10 days

Number of animals:

3 males

Details on study design:

DOSE ADMINISTRATION
On the day 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 test substance (approximately 500 mg) was moistened to a dry paste with a small amount (0.5 - 0.6 mL) of deionised water to allow good skin contact and, using a metal spatula, was applied 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 cut (using blunt-tipped scissors), removed and discarded. The application site was gently cleansed free of any residual test substance using clean swabs of absorbent cotton wool soaked in clean warm water and was then dried gently with clean tissue paper. The application site was identified using a black waterproof marker-pen.

CLINICAL OBSERVATIONS
Prior to the start of the study, all rabbits were examined to ensure that they were physically normal and exhibited normal activity. Throughout the study, the animals were observed daily for general signs of well-being. All animals were removed from the study at the end of the observation period.

IRRITATION RESPONSE
The Draize scale (see "Any other information on materials and methods incl. tables) was used to assess the degree of erythema and oedema at the application sites approximately 1 hour and 1, 2 and 3 days after removal of the dressings and then at intervals for up to 10 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:

0

Max. score:

4

Remarks on result:

no indication of irritation

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:

2.3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 4 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

Very slight erythema was seen in two animals for 1 hour or 5 days, and very slight to moderate/severe erythema was seen in one animal for 7 days. Very slight oedema was seen in one animal for 2 days and very slight to slight oedema was seen in another animal for 3 days. Additional signs of irritation comprised desquamation, thickening, scabbing and wrinkling. All signs of irritation had completely resolved 10 days after application.

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 according to the Draize scheme

Time	Erythema			Oedema
Animal number	#1	#2	#3	#1	#2	#3
after 1 hour	1	1	2	0	0	1
after 24 hours	0	1	2	0	1	2
after 48 hours	0	1t	3tw	0	1	2
after 72 hours	0	1t	2ts	0	0	1
mean score 24-72 h	0	1.0	2.3	0	0.7	1.7
after 4 days	-	1dt	2ts	-	0	0
after 5 days	-	1d	2dts	-	0	0
after 7 days	-	0d	1dt	-	0	0
after 10 days	-	0	0	-	0	0

- Animal removed from study, d desquamation, t thickening, s scabbing, w wrinkling

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this study the test substance is considered to be a mild irritant following a single four-hour application to rabbit skin, however not sufficient for classification under CLP.

Executive summary:

The skin irritation potential of the test substance was determined in vivo according to the OECD 404 test guideline and GLP principles. A group of 3 male rabbits received a single four-hour application of 500 mg test substance to the shorn flank. The animals were assessed for up to 10 days for any signs of skin irritation.

Very slight erythema was seen in two animals for 1 hour or 5 days, and very slight to moderate/severe erythema was seen in one animal for 7 days. Very slight oedema was seen in one animal for 2 days and very slight to slight oedema was seen in another animal for 3 days. Additional signs of irritation comprised desquamation, thickening, scabbing and wrinkling. All signs of irritation had completely resolved 10 days after application.

In conclusion, the test substance is considered to be a mild irritant following a single four-hour application to rabbit skin, however not sufficient for classification under CLP.