N-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)-phenyl-aminocarbonyl]-2,6-difluorobenzamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Feb 1998 to 12 Feb 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Feb 1987

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)-phenyl-aminocarbonyl]-2,6-difluorobenzamide

EC Number:

410-690-9

EC Name:

N-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)-phenyl-aminocarbonyl]-2,6-difluorobenzamide

Cas Number:

103055-07-8

Molecular formula:

C17 H8 Cl2 F8 N2 O3

IUPAC Name:

1-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

KFM-NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2410 - 2640 g
- Housing: The animals were housed individually in metal cages.
- Diet: standard rabbit pellet, ad libitum (analysed for nutritive ingredients and contaminants)
- Water: Ad libitum.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 Feb 1998 To 12 Feb 1988

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- 0.1 mL (70 mg)

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males

Details on study design:

INSTILLATION
The test substance was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The right eye remained untreated and served as a control.

OCULAR SCORING
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of the test substance according to the OECD scoring system (see Table 1 at ‘Any other information on methods and materials incl. tables’). A slit-lamp was used to facilitate the evaluation.
The irritant/corrosive potency of test substance was classified according to the EC Commission Directive No. 83/467, 1983. Ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours and correspond to the following values determined on the rabbit according to the eye irritation method:
- The mean value of the scores for each type of lesion, calculated over all the animals tested, is one of the following:
(1) cornea opacity two or more
(2) iris lesion one or more
(3) redness of conjunctivae 2.5 or more
(4) oedema of conjunctivae
(5) (chemosis) two or more
- or, in the case where the Annex V test has been completed using three animals, either cornea opacity, iris lesion, redness of conjunctivae or oedema of conjunctivae (chemosis) equivalent to a mean value such as is quoted above, but calculated for each animal separately, has been observed in two or more animals.
In both cases all scores at each of the reading times (24, 48, and 72 hours) and for an effect should be used in calculating the respective means values.

CAGE SIDE OBERVATIONS
The animals were checked daily for systemic symptoms and mortality..

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance induced reactions in the cornea (score 1), iris (score 1) and conjunctiva (redness score 1 and/or chemosis score 1) in all 3 animals at the 1-hour reading. At the 24-hour reading, only 1 animal still exhibited redness of the conjunctiva (score 1). The eye reactions observed were reversible until the end of the observation period on day 3.

Other effects:

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

Any other information on results incl. tables

Table 2 Scores of eye irritation after instillation of test substance

	Cornea	Iris	Conjunctiva
			redness	chemosis
score (3 animals investigated)	0 -4	0 - 2	0 - 3	0 - 4
60 min	1/1/1	1/1/1	1/1/1	1/0/1
24 hours	0/0/0	0/0/0	0/0/1	0/0/0
48 hours	0/0/0	0/0/0	0/0/0	0/0/0
72 hours	0/0/0	0/0/0	0/0/0	0/0/0
average 24h, 48h, 72h	0/0/0	0/0/0	0/0/0.33	0/0/0
Reversibility*	c	c	c	c
time for reversion	24 h	24 h	48 h	24 h

* c : completely reversible

Table 3 Body weight

Animal no.	#1	#2	#3
At start of test	2410	2630	2640
After 3 days (end)	2460	2710	2670

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this study, it was concluded that test substance was considered to be not irritating to the eyes of rabbits.

Executive summary:

In a primary eye irritation study performed in accordance with OECD TG 405 following GLP principles. An amount of 0.1 mL (70 mg) of the undiluted test substance into the conjunctival sac of the left eye of each the 3 males albino New Zealand White rabbits (KFM-NZW), after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The right eye remained untreated and served as a control. The animals were checked daily for systemic symptoms and mortality. The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of test article. A slit-lamp was used to facilitate the evaluation. The animals were checked daily for systemic symptoms and mortality.

The test substance induced reactions in the cornea (score 1), iris (score 1) and conjunctiva (redness score 1 and/or chemosis score 1) in all 3 animals at the 1-hour reading. At the 24-hour reading, only 1 animal still exhibited redness of the conjunctiva (score 1). The eye reactions observed were reversible until the end of the observation period on day 3. The body weights of all rabbits were considered to be within the normal range of variability.

Under the conditions of this study, the test substance was considered to be not irritating to the eyes of rabbits.