Reaction mass of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9RS)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide and of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9SR)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide; isopyrazam

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 2014 to 06 Feb 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

632-619-2

EC Number:

632-619-2

Cas Number:

881685-58-1

Molecular formula:

C20 H23 F2 N3 O

IUPAC Name:

632-619-2

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan:(WIST) (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 208 g and 253 g
- Housing: Individual caging
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance. Ad libitum
- Water: Tap water. Ad libitum
- Acclimatisation period: 6 and 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.9 – 22.8 °C
- Humidity : 27 – 55 %
- Air changes: 15-20 air exchanges per hour
- Photoperiod: 12/12 hours light/dark

IN-LIFE DATES: From: 21 Jan 2014 To: 06 Feb 2014

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- Pre-treatment: Approximately 24 hours before treatment an area on the back of the rat was shaven with an electric clipper.
- % coverage: Approximately 10 % area of the total body surface
- Type of wrap if used: Sterile gauze pads, a patch with adhesive hypoallergenic plaster and semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours, the dressing was removed and the treated area was washed using body temperature water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration: 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes. All animals were subjected to gross macroscopic examination. All animals were anaesthetised and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. Any gross macroscopic findings were recorded.

Statistics:

- From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no adverse clinical signs noted in any animals throughout the study.

Gross pathology:

There was no evidence of macroscopic observations in animals terminated on day 14.

Other findings:

No treatment related skin irritation was observed in any animal throughout the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median LD50 of the test material after a single dermal administration was > 2000 mg/kg bw in male and female RccHan:(WIST) rats.

Executive summary:

Ten (5 male and 5 female) RccHan:(WIST) rats were treated with a single semi-occlusive dermal application of test material at the limit dose of 2000 mg/kg bw in a study according to OECD TG 402 and GLP principles. Sufficient water was used to dampen the test material to ensure good contact with the skin. The application period was 24 hours, followed by a 14-day observation period. Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. All animals were examined macroscopically at the end of the study.

No mortality occurred during the study. No adverse clinical signs were observed after treatment with the test material or during the 14 day observation period and no effects were observed at the site of application. There were no treatment related effects on body weight or body weight gain during the observation period. There was no evidence of necropsy.

The median LD50 of test material after a single dermal administration was > 2000 mg/kg bw in male and female RccHan:(WIST) rats.