benzovindiflupyr (ISO); N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 January 2010 to 08 January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-[11-(dichloromethylidene)tricyclo[6.2.1.0²,⁷]undeca-2,4,6-trien-3-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide

EC Number:

691-719-4

Cas Number:

1072957-71-1

Molecular formula:

C18H15Cl2F2N3O

IUPAC Name:

N-[11-(dichloromethylidene)tricyclo[6.2.1.0²,⁷]undeca-2,4,6-trien-3-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide

Details on test material:

- Name of test material (as cited in study report): SYN545192 tech.
- Physical state: Beige powder
- Analytical purity: 97.0% (by HPLC)
- Purity test date: 25 February 2009
- Expiration date of the lot/batch: End February 2013
- Storage condition of test material: <30°C

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: 3606-3667 g
- Housing: Individually in metal wire rabbit cages (65 x 65 x 45 cm)
- Diet: Purina Base – Lap gr. diet ad libitum
- Water: Municipal tap water ad libitum
- Acclimation period: 32 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17.0-20.5°C
- Humidity: 36-68%
- Air changes: 15-20 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 05 January 2010 To: 08 January 2010

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm on back and flank
- Type of wrap if used: Surgical gauze patch kept in contact with skin by a patch with a surrounding hypoallergenic plaster. Entire trunk then wrapped with plastic wrap held in place with an elastic stocking

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004 which was based on the Draize scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

1

Max. score:

1

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hours

Score:

0.3

Max. score:

1

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 hours

Score:

0

Max. score:

0

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 hour

Score:

0

Max. score:

0

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

0

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hours

Score:

0

Max. score:

0

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Results 9

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.11

Irritant / corrosive response data:

After 1 hour, very slight erythema (score 1) was observed in all animals. No oedema was observed in any animal.
After 24 hours, very slight erythema (score 1) was observed in 1 animal. No oedema was observed in any animal.
After 48 and 72 hours, no erythema or oedema was observed in any animal.

Other effects:

None

Any other information on results incl. tables

Table 1: Individual and mean skin irritation scores of SYN545192

Time	Erythema			Oedema
Animal number	597	595	582	597	595	582
after 1 hour	1	1	1	0	0	0
after 24 hours	1	0	0	0	0	0
after 48 hours	0	0	0	0	0	0
after 72 hours	0	0	0	0	0	0
mean score 24-72 hours	0.3	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The application of SYN545192 did not result in any significant signs of skin irritation. According to the Draize classification criteria SYN545192 is considered to be a “mild irritant” to rabbit skin (P.I.I. = 0.11).

Executive summary:

The primary skin irritation potential of SYN545192 was investigated according to the OECD Test Guideline no. 404. The animals were treated by topical semi-occlusive application of 0.5 g to the intact shaved flank of 3 young adult New Zealand White rabbits. The duration of treatment was 4 hours. The primary irritation index was 0.11 and according to the Draize classification criteria SYN545192 is considered to be a "mild irritant" to rabbit skin.