3,3'-[(4-{(E)-[2-bromo-4-nitro-6-(trifluoromethyl)phenyl]diazenyl}phenyl)imino]dipropanenitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 14-MAR-2000 to 18-MAY-2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guidance test with GLP compliance

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:

other: Directive 92/69 EEC, B.5. “Acute Toxicity - Eye Irritation” July 31, 1992.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT41'029/A
Batch number: ARL 123/PP 1/99 UL
Purity: approx. 98 %
Color / Physical form: orange red to brown powder
Stability of test article: Stable under storage conditions
Expiry date: 04-NOV-2005
Storage conditions: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST SYSTEM
Test system: New Zealand White Rabbit, SPF
Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
Number of animals: 1 male and 2 females
Age at start of treatment: 15 weeks (male); 14 (no.38) and 15 (no.39) weeks (females)
Body weights at start of treatment: 2.7-2.8 kg
Acclimatization: Six days under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

HUSBANDRY
Conditions
Standard Laboratory Conditions:
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a range for room temperature of 22±3 °C, and for relative humidity between 30-70 %. The animals were provided with a 12-hour light, 12-hour dark cycle. Music was played during the light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclaved wood and haysticks for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum.
Water: Community tap-water.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

one second

Observation period (in vivo):

Viability/Mortality: Daily from delivery of the animals to the termination of test.
Clinical signs: Daily from delivery of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 2 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 4

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.11

Max. score:

13

Reversibility:

fully reversible

Irritant / corrosive response data:

A slight corneal opacity was seen in one animal at the 1-hour examination. Slight to moderate conjunctival redness was observed in all animals at the first hour and persisted in only one animal 24 hours later. Slight conjunctival swelling was noted in one animal at the 1-hour examination. A slightly reddened sclera was observed in two animals at the first hour, persisted in one animal at the 24 hours, disappeared in the second one and appeared in the third animal. All eye reactions were clear within 48 hours after treatment.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and observation period, and no mortality occurred.
Red-brown remnants of the test article in eye or conjunctival sac were observed in the female animals one hour after treatment.
The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FAT41'029/A is considered to be not irritating to the rabbit eye.

Executive summary:

The primary irritation potential of FAT41'029/A was investigated by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of data points. The primary irritation score was 0.11 (max. 13). The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris,grade 0.11 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae.

A slight corneal opacity was seen in one animal at the 1- hour examination. Slight to moderate conjunctival redness was observed in all animals at the first hour and persisted in only one animal 24 hours later. Slight conjunctival swelling was noted in one animal at the 1-hour examination. A slightly reddened sclera was observed in two animals at the first hour, persisted in one animal at the 24 hours, disappeared in the second one and appeared in the third animal. All eye reactions were clear within 48 hours after treatment.Red-brown remnants of the test article in eye or conjunctival sac were observed in the female animals one hour after treatment. No corrosion was observed at any of the measuring intervals.

Thus, FAT41'029/A is considered to be not irritating to the rabbit eye.