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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2011-05-05 to 2011-05-25 (experimental phase)

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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment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

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted April 24, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

from May 30, 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

from August 1998

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:

- Physical state: Beige powder
- Stability under test conditions: not reported
- Reanalysis date of the lot/batch: End of February 2013
- Storage condition of test material: At room temperature (20 ± 5 °C), light protected
- Safety Precautions: Routine hygienic procedures (gloves, goggles, face mask)

Test animals / tissue source

Species:

rabbit

Strain:

other: New Zealand White Rabbit, SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 14 weeks (male), 14 – 15 weeks (females)
- Weight at study initiation: 2612 g (male), 2886 g – 3066 g (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. A piece of wood and a haystick were provided for environmental enrichment.
- Diet (e.g. ad libitum): Pelleted Teklad Global Rabbit diet 2031C ad libitum
- Water (e.g. ad libitum): Community tap water, ad libitum.
- Acclimation period: 5-6 days, under laboratory conditions after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Single administration into the eye

Observation period (in vivo):

10 days
Viability/mortality and clinical signs: assessed daily from acclimatization to termination of the test.
Eye reactions: assessed at approximately 1, 24, 48 and 72 hours as well as 7 and 10 days after treatment.
Body weights: recorded at acclimatization, on the day of treatment and on the last day of observation.
Fluorescein staining: employed at least 24 hours prior to instillation of the test item and 24, 48 and 72 hours as well as 7 days post dose after the standard observations had been made

Number of animals or in vitro replicates:

1 male, 2 female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Numerical evaluation (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49). Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C (1962), J. Soc. Cosmet. Chem. 13, 281 289 was used to classify the ocular irritancy potential of the test material.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp. To assess for the presence of corneal damage, instillation of a 0.5% fluorescein solution was performed directly onto the cornea of both eyes and assessment was made with a hand slit lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: conjunctivae redness

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: conjuntivae redness

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: conjunctivae redness

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: corneal opacity

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 7

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 hours after application

Score:

2.67

Max. score:

110

Remarks on result:

other: Scoring according to Kay and Calandra

Irritant / corrosive response data:

- No corrosion was observed at any of the measuring intervals.
- Slight reddening of the sclera was observed in two animals 1 hour after treatment.
- Test item remnants were observed in two animals 1 hour after treatment.
- Positive corneal fluorescence was observed in all animals 24 hours after treatment and persisted until 72 hours after treatment. Corneal fluorescence was negative 7 days after treatment.

Other effects:

- No staining of the treated eyes by the test item was noted.
- No clinical signs were observed.
- The test item did not induce irreversible damage to the rabbit eye.

Any other information on results incl. tables

Eye Irritation Scores

Animal number	Sex	Evaluation Interval	Corneal Opacity	Area of Corneal Opacity	Iris light reflex	Conjunctivae		Sclera	Test Item Remnants
						Redness	Chemosis
61	M	1 hour	0	0	0	2	0	1	1
62	F		0	0	0	1	0	0	0
63	F		0	0	0	1	0	1	1
61	M	24 hours	0	0	0	1	0	0	0
62	F		0	0	0	1	0	0	0
63	F		0	0	0	1	0	0	0
61	M	48 hours	0	0	0	1	0	0	0
62	F		0	0	0	1	0	0	0
63	F		0	0	0	1	0	0	0
61	M	72 hours	0	0	0	1	0	0	0
62	F		0	0	0	1	0	0	0
63	F		0	0	0	1	0	0	0
61	M	7 days	0	0	0	0	0	0	0
62	F		0	0	0	1	0	0	0
63	F		0	0	0	0	0	0	0
61	M	10 days	0	0	0	0	0	0	0
62	F		0	0	0	0	0	0	0
63	F		0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the Kay and Calandra classification criteria, the test item is considered to be "moderately irritating" to the rabbit eye (maximum average score = 2.67; not all scores were zero at the 72 hour reading). The study is regarded to be adequate and reliable.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD TG 405 in a valid GLP study. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7 and 10 days after test item instillation.

The instillation of the test item into the eye resulted in slight to moderate reddening of the conjunctivae in all animals and slight reddening of the sclera in two animals. Test item remnants were observed in two animals. These eye reactions were reversible and were no longer evident 7 days (two animals) or 10 days (one animal) after treatment, the end of the observation period for all animals. Positive corneal fluorescence was observed in all animals 24 hours after treatment and persisted until 72 hours after treatment. No abnormal findings were observed in the iris of any animal at any of the observations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was noted. Furthermore, no clinical signs were observed. The test item did not induce irreversible damage to the rabbit eye. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00 for reddening and 0.00 for chemosis for all animals. Based on the Kay and Calandra interpretation, the mean of the cumulative scores for eye irritation was 2.67 at 1 hour, 2.00 at 24, 48 and 72 hours, 0.67 after 7 days and 0.00 after 10 days.

Based upon the Kay and Calandra classification criteria, the test item is considered to be “moderately irritating” to the rabbit eye (maximum average score = 2.67; not all scores were zero at the 72 hour reading).