4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

EC Number:

277-874-7

EC Name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Cas Number:

74441-06-8

Molecular formula:

C14H13N3O2

IUPAC Name:

4-amino-N-(4-carbamoylphenyl)benzamide

Details on test material:

- Name of test material (as cited in study report): p-Aminobenzoylaminobenzamid TF

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test Animals:
Animals: Young Adult New Zealand White Rabbit, SPF
Breeder: Harlan France, ZI Le Malcourlet, 03800 Gannat / France
Number of Animals per Test: 3 (Animals of both sexes were used)
Age (when treated): 12 weeks (male), 14 weeks (females)
Body Weight Range (when treated): 2597 g (male), 2754 – 2951 g (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.


Environmental Conditions:
Temperature: 17-23 °C and for
Relative humidity: 30-70% (values above 70% during cleaning process possible)
Light cycle of 12 hours light and 12 hours dark
Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
Water: Community tap water from Füllinsdorf ad libitum

Test system

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

0.1 g of p-Aminobenzoylaminobenzamid TF was placed in the conjunctival sac of the left eye of each animal. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.

Duration of treatment / exposure:

Single application, the treated eyes were not rinsed after instillation.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

Purpose:
The purpose of this primary eye irritation study was to assess the possible irritation potential when a single dose of p-Aminobenzoylaminobenzamid TF is placed in the conjunctival sac of rabbit eyes. This study should provide a rational basis for risk assessment in man as ocular contact is one of
the possible routes of human exposure.

Preparation of Dose Formulations:
0.1 g (per animal) of p-Aminobenzoylaminobenzamid TF was weighed and applied undiluted as it was delivered by the Sponsor. The pH of a 1% (w/w) solution was measured for Harlan Laboratories Study C57806 (skin irritation with p-Aminobenzoylaminobenzamid TF) and was found to be 5-6.
According to Commission Regulation (EC) No 440/2008, B.4. and OECD Guidelines 405, a test item does not need to be tested if the pH-value is less than 2 or greater than 11.5, owing to its predictable corrosive properties.

Observations:
Viability / Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical Signs (systemic): Daily from acclimatization of the animals to the termination of test.
Body Weights: At start of acclimatization, on the day of application and at termination of observation.

Determination of Eye Irritating Potential:
Observation and Scoring: The eye reactions were assessed according to the numerical scoring system listed in the Commission Regulation (EC) No 440/2008, B.5, at approximately 1, 24, 48, 72 hours after administration. Scleral reddening and ocular discharge were also assessed. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland). Data were summarized in tabular form, showing for each individual animal the irritation scores for the designated observation time, a description of the degree and nature of irritation, the presence of serious lesions and non-ocular effects. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values (with the exception of the sclerae) for each type of lesion. The evaluation of the results was performed according to the classification criteria of the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no signs of irritation (cornea) at any time

Results 2

Irritation parameter:

iris score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

2

Reversibility:

other: no signs of irritation (iris) at any time

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

3

Reversibility:

other: no signs of irritation (redness) at any time

Results 4

Irritation parameter:

chemosis score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no signs of irritation (chemosis) at any time

Irritant / corrosive response data:

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. All individual mean scores were 0.00 for all three animals.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

No corrosion was observed at any of the measuring intervals.

One hour after test item instillation, slight reddening of the sclerae was noted in one female. In the treated eyes of all animals, beige test item remnants were still observed. No abnormal findings were observed in the treated eye of any animal 24 hours after treatment until the end of the observation period after 72 hours.

Other effects:

No other effects

Any other information on results incl. tables

Viability / Mortality:

No mortality occurred.

Clinical Signs:

No clinical signs were observed during the course of the study.

Body Weights:

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

Coloration:

No staining produced by the test item of the treated eye was observed.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Based upon the classification criteria according to the Commission Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, p-Aminobenzoylaminobenzamid TF is not classified with respect to eye irritation.

Executive summary:

The primary eye irritation potential of p-Aminobenzoylaminobenzamid TF was investigated according to OECD test guideline no. 405. 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 after test item instillation.

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. All individual mean scores were 0.00 for all three animals.

The instillation of p-Aminobenzoylaminobenzamid TF into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the sclerae in 1/3 animals. This effect was reversible and was no longer evident 24 hours after treatment. No abnormal findings were observed in the cornea or iris or the conjunctivae of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed.Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Based upon the classification criteria according to the Regulation Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, p-Aminobenzoylaminobenzamid TF is not classified with respect to eye irritation.