Chlorothalonil

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Jan 2000 to 27 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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: Males: 352-393 g. Females: 211-249 g
- Housing: The rats 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): 22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): A minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 Jan 2000 To: 27 Jan 2000

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The day prior to application of the test substance, the hair was removed with a pair of veterinary clippers from an area, at least 7 cm x 7 cm, on the dorso-lumbar region of each animal. The appropriate amount of the test substance was weighed onto a plastic weighing boat and, to allow good skin contact, was moistened to a dry paste with a small amount (0.9 - 1.3 mL) of water. The amount applied was calculated for each animal according to its weight at the time of dosing. The estimated amount applied per unit area of skin exposed was 47.9 - 53.5 mg/cm2 for males and 28.6 - 33.8 mg/cm2 for females.
The test substance was applied to the shorn back of each animal and was kept in contact with the skin for approximately 24 hours using an occlusive dressing wrapped around the trunk of the animal. Each dressing consisted of a foil backed gauze patch to cover the treated area and was held in position by a cohesive bandage secured with two pieces of surgical tape.
At the end of the 24-hour contact period, the dressings were carefully cut, using blunt tipped scissors, removed and discarded. The skin, at the site of application, was 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.

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw/day

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

CLINICAL OBSERVATIONS
Prior to the start of the study, all rats were examined to ensure that they were physically normal and exhibited normal activity. The animals were observed twice following dosing on day 1 (only gross abnormalities were noted at this time as the presence of the dressings may have affected the behaviour and movement of the rats). Subsequent observations for signs of systemic toxicity and skin irritation were made once daily up to day 15.

BODY WEIGHTS
The animals were weighed immediately before dosing (day 1) and on days 8 and 15.

TERMINATION
All rats were killed by exsanguination under terminal anaesthesia induced by halothane vapour.

MACROSCOPIC EXAMINATION
All animals were examined post mortem. This involved an external observation and a careful examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.

Statistics:

The acute dermal median lethal dose was estimated from the mortality data.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

None of the animals died and there were no significant signs of systemic toxicity.

Clinical signs:

other: Slight or moderate skin irritation was seen in all animals. Signs of skin irritation had resolved in all the females by day 14, but was still apparent in four of the males at the end of the study.

Gross pathology:

At examination post mortem, compound-related abnormalities comprised scabs at the application site of two males. One male had stained nares. This is considered to be a non-specific finding which is incidental to treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this study, the acute dermal median lethal dose of the test substance is estimated to be in excess of 5000 mg/kg to male and female rats.

Executive summary:

A group of five male and five female Alpk:APfSD (Wistar-derived) rats received a single 24 hour dermal application of 5000 mg/kg of the test substance (OECD 402, GLP). The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. At the end of the study all the animals were killed and subjected to a macroscopic examination post mortem.

None of the animals died and there were no significant signs of systemic toxicity. All except one animal showed an overall body weight gain during the study. At examination post mortem, compound-related abnormalities comprised scabs at the application site of two males. Slight or moderate skin irritation was seen in all animals. Signs of skin irritation had resolved in all the females by day 14, but was still apparent in four of the males at the end of the study.

In conclusion, the acute dermal median lethal dose of the test substance is estimated to be in excess of 5000 mg/kg to male and female rats.