2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 24 2002 - April 27 2002.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

EC Number:

264-980-3

EC Name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Cas Number:

64628-44-0

Molecular formula:

C15H10ClF3N2O3

IUPAC Name:

3-(2-chlorobenzoyl)-1-[4-(trifluoromethoxy)phenyl]urea

Test material form:

solid: particulate/powder

Remarks:

White powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Age: Young adult

Source: Received from Davidson’s Mill Farm, South Brunswick, NJ on April 19, 2002.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.

Photoperiod: 12 hour light/dark cycle.

Acclimation Period: 5 days.

Food: Pelleted Purina Rabbit Chow #5326

Water: Filtered tap water was supplied ad libitum by automatic water dispensing system.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study.

Test system

Vehicle:

physiological saline

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of one-tenth of a milliliter (0.08-0.10 g) of the test substance, as received, was instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

Not applicable: treated eyes were not rinsed after exposure

Observation period (in vivo):

1, 24, 48 and 72 hours post-instillation

Number of animals or in vitro replicates:

3 (2 males and 1 female)

Details on study design:

Preparation and selection of animals: Prior to instillation, both eyes of a number of animals were examined using a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein. Using a Spectroline® Lamp (compact 4-watt UV Lamp), the eyes were checked for gross abnormalities according to the "Scale for Scoring Ocular Lesions". Only healthy animals without preexisting ocular irritation were selected for test.


Ocular scoring: Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with the Draize method. The fluorescein dye evaluation procedure was used at 24 hours to verify the absence of corneal damage. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted.

Cage-Side Observations: The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The incidence, severity and reversibility of irritation are detailed below (Table 1 and 2).

Other effects:

All animals appeared active and healthy. Apart from the eye irritation noted below, there were no other signs of gross toxicity.

Any other information on results incl. tables

Table 1: Time post instillation and incidence of irritation (corneal opacity, iritis, conjunctivitis).

Time Post Instillation	Corneal Opacity	Iritis	Conjunctivitis
1 hour	0/3	0/3	3/3 (score 1 each)
24 hours	0/3	0/3	1/3 (score 1)
48 hours	0/3	0/3	0/3
72 hours	0/3	0/3	0/3

 

Table 2: Time post instillation and severity of irritation- mean score. 

Time Post Instillation	Severity of Irritation – Mean Score
1 hour	4
24 hours	0.7
48 hours	0
72 hours	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Triflumuron was found to be a minimal and reversible eye irritant under the conditions of this study and does not require classification for eye irritation according to the CLP criteria.

Executive summary:

A primary eye irritation test was conducted with New Zealand albino rabbits to determine the potential for triflumuron to produce irritation from a single instillation via the ocular route. Under the conditions of this study, the test substance is classified as minimally irritating to the eye. A volume of one-tenth of a milliliter (0.08-0.10 g) of the test substance, as received, was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize.  No corneal opacity or iritis was observed during the study. One hour following instillation, all three treated eyes exhibited conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 48 hours.  Triflumuron was found to be a minimal and reversible eye irritant under the conditions of this study and does not require classification for eye irritation according to the CLP criteria.