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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 2014 to 26 Jan 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

GLP compliance:

yes (incl. QA statement)

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Male
- Age at study initiation: ~11 weeks
- Weight at study initiation: 2668 g – 2988 g
- Housing: Animals were housed individually in AAALAC approved metal wire rabbit cages. Cages are of an open wire structure and cages are placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: UNI diet for rabbits. Ad libitum
- Water: Tap water. Ad libitum
- Acclimatisation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17.7 – 21.7 °C
- Humidity: 23 – 58 %
- Air changes: 15-20 air exchanges/hour
- Photoperiod: 12/12 hours light/dark

IN-LIFE DATES: From: 21 Jan 2014 To: 26 Jan 2014

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g of the test material

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

PRE-STUDY EXAMINATION
- The test was performed on 3 male rabbits, checked for normal skin conditions.

TEST SITE
- Area of exposure: An area of 10 x 10 cm on the back and flanks of the rabbits was clipped with an electric clipper 24 hours before the treatment.
- Type of wrap if used: A surgical gauze pad (ca. 2.5 x 2.5 cm) was applied to the intact skin of the clipped area and was kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunk of the animals was than wrapped with plastic wrap held in place with an elastic stocking.

REMOVAL OF TEST SUBSTANCE
- Washing: The dressing was then removed and the skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS : 1, 24, 48 72 hours after the end of exposure

SCORING SYSTEM:
- Method of calculation: The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004 which was based on the Draize scoring system. For criteria, see 'Any other information on materials and methods incl. tables'.

OTHER OBSERVATIONS
- Clinical signs, including viability/mortality, were recorded daily from the day of application of the animals to the termination of the test.
- Body weights were recorded on the day of application and the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

8

Irritant / corrosive response data:

The primary irritation index was 0.00 (out of a maximum score of 8.0). No corrosive effects were noted on the treated skin of any animal at any of the observation intervals. No local dermal signs were observed in the treated animals throughout the study.

Other effects:

CLINICAL OBSERVATIONS
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The application of the test material did not result in any signs of skin irritation.

Executive summary:

Three young adult male New Zealand White rabbits were treated by topical, semi-occlusive application of 0.5 g test material to their intact shaved flanks in a study according to OECD TG 404 and GLP principles. The test material was moistened with water to ensure good skin contact. The duration of treatment was 4 hours. The scoring of skin reactions was performed at 1, 24, 48 and 72 hours after removal of the dressing. The primary irritation index (P.I.I.) was calculated.

The mean average erythema and oedema scores of all animals over 24, 48 and 72 hours were 0. The P.I.I was 0. No local dermal signs were observed in the treated animals throughout the study. No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation. The body weights of all rabbits were considered to be within the normal range of variability.

The application of the test material did not result in any signs of skin irritation.