1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-03-14 to 1990-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

See Principles of method if other than guideline.

Principles of method if other than guideline:

The study was conducted in accordance with "OECD Guideline for Testing of Chemicals No. 405.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

EC Number:

266-096-3

EC Name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Cas Number:

66063-05-6

Molecular formula:

C19H21ClN2O

IUPAC Name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species and Species Justification
The study was performed using rabbits, an animal species recommended in the test guidelines. Healthy, adult albino rabbits (strain: HC:NZW) were used (bred by INTERFAUNA UK LTD.). The state of health of the breed was routinely tested for the most significant specific infective pathogens. If females were used, they were nulliparous and nonpregnant.

Experimental Animal Care
The rabbits were housed in individual cages under standardized conventional conditions (Type III wire cages, tall). Feces pans containing low-dust wood shavings (Type S 8/15; SSNIFF, in Soest, FRB) were located below the cages. These wood shavings were routinely analyzed for contaminants by the Central Office for Experimental Animal Concerns.
Identification of the Animals; The rabbits were identified by individual ear markings (tattooing) and cage I.D. cards.
Acclimatization; 1 day prior to application, the rabbits were examined to determine whether those scheduled for treatment were biologically normal. At least 14 days prior to treatment, the rabbits were clinically examined for diseases and acclimatized in the quarantine station. Shortly after arrival of the animals, feces samples were collected and examined for oocysts of coccidia.
Animal Quarters; All animals of this study were placed in one animal room. For reasons of capacity, rabbits treated with other test substances were also housed in the same animal room. Mix-ups with other animals were avoided by adequate spacing and separation, unambiguous cage and animal identification, and an appropriate scheduling of work.

Climatic Conditions in the Animal Room;
Conditions were adjusted as follows:
Room Temperature: 20° ± 3°C
Relative Humidity: approx. 50%
Light/Dark Cycle: 12 hours, artificial illumination from 6:00 a.m. to 6:00 p.m. MEZ [Middle European Time]
Illumination: approx. 27 watts/m^2 floor area
Air Exchange Rate: approx. 10 times per hour

The humidity and temperature in the animal quarters were recorded continuously using a calibrated thermohygrograph. There were occasional deviations from these conditions, e.g. as a result of the cleaning of the animal room. They had no detectable effect on the outcome of the study.

Cleaning. Disinfection, and Pest Control; All surface areas in the animal quarters were cleaned at least once per month and disinfected with Zephirol (1% in water); the floor in the animal quarters was cleaned and disinfected once per week. In so doing, contamination of the feed and contact with the experimental animals were avoided. No pest control was performed in the animal quarters. The water dispensers were cleaned once per week.

Diet;
Feed: standard diet (approx. 100 g to 120 g per animal per day; animals fed once per day in the morning).
Water: Tap water was available to the rabbits ad libitum between 7:00 a.m. and 7:00 p.m.
At the request of the Central Office for Experimental Animal Concerns, the nutrient composition and the contaminant content of the standard diet were checked routinely by taking random samples and analyzing them. These records are archived at the Central Office for Experimental Animal Concerns. The tap water was of drinking water quality (Drinking Water Ordinance dated May 22, 1986, Bundesqesetzblatt [Federal Law Bazettel, Part I, page 760). Results of the analyses of feed and water are archived at BAYER A6. These data provided no evidence of an effect on the study objective. Either approximately 750-ml polycarbonate bottles or automatic water dispensers were used to provide water.

Body Weights
The rabbits were weighed immediately prior to application of the test substance.

State of Health
Only healthy animals that were free of signs were used for the study. No vaccination or treatment of the animals with antibiotics was performed either prior to receipt of the animals or during the acclimatization period or the experimental period.

Test system

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 µl of test substance (bulk volume) were applied in the conjunctival sac of one eyelid of each of 3 adult rabbits. This is equivalent to an applied weight of about 50 mg of the test substance.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

Following application, the lids were gently held together for approximately 1 second.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline solution
- Time after start of exposure: 24 hours

SCORING SYSTEM:
In evaluating the results, only those findings which persisted for 24 hours or longer are used. The results were classified on the basis of the DRAIZE scores by calculating a primary eye irritation index for the cornea (degree of opacity) and iris as well as for the redness and swelling (chemosis) of the conjunctivae observed at approx. 24, 48 and 72 hours after application and averaging these scores.

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:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Pencycuron was found to be non-irritant under the conditions of this study and does not require classification under CLP for serious eye damage or serious eye irritation.

Executive summary:

Pencycuron (NTN 19701 Technical) was tested for eye irritation potential in the rabbit in a study performed to OECD 405. 0.1 g of the test material was instilled into one eye of three rabbits. Ocular reactions were scored at 1, 24, 48 and 72 hours; and at 7 days following patch removal, using the Draize scale. No signs of irritation were seen in any rabbit at any time point. Pencycuron was found to be non-irritant under the conditions of this study and does not require classification under CLP for serious eye damage or serious eye irritation.