N-(2-oxo-1,2-dihydropyrimidin-4-yl)benzamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date: 27 November 2012. Experimental end date: 04 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N4-Benzoylcytosine

EC Number:

628-907-2

Cas Number:

26661-13-2

Molecular formula:

C11H9N3O2

IUPAC Name:

N4-Benzoylcytosine

Specific details on test material used for the study:

Sponsor's identification: N-Benzoyl Cytosine
Description: off white powder
Batch number: NBC-5-11001
Purity: not supplied
Date received: 09 July 2012
Expiry date: not supplied
Storage conditions: room temperature in the dark over silica gel

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals and Animal Husbandry
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.55 to 2.70 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

For the purpose of the study the test item was used as supplied. The absorption of the test item was not determined.
0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar
formation preventing grading of erythema 4

Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined
by definite raising) 2
Moderate oedema (raised approximately
1 millimetre) 3
Severe oedema (raised more than 1 millimetre
and extending beyond the area of exposure) 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
An additional observation was made on Day 7 to assess the reversibility of skin reactions.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Skin Reactions
Very slight erythema was noted at all treated skin sites at the 24, 48 and 72-Hour observations.
All treated skin sites appeared normal at the 7-Day observation.

Bodyweight
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Individual Skin Reactions

Skin Reaction	Observation Time (following patch removal)	Individual Scores — Rabbit Number and Sex			Total
		72739 Male	72740 Male	72741 Male
Erythema/Eschar Formation	Immediately	0	0	0	[0]
	1 hour	0	0	0	[0]
	24 hours	1	1	1	3
	48 hours	1	1	1	3
	72 hours	1	1	1	3
	7 days	0	0	0	[0]
Oedema Formation	Immediately	0	0	0	[0]
	1 hour	0	0	0	[0]
	24 hours	0	0	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
	7 days	0	0	0	[0]

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a mean erythema value of 1 and mean oedema value of 0 as such was not classified as irritant to rabbit skin according to CLP. No corrosive effects were noted.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test itemto the skin of the New Zealand White rabbit. The method was designed to be compatiblewith the following:

OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002)

Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC)No. 440/2008

Results

A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight erythema. All treated skin sites appeared normal at the 7-Day observation.

Conclusion

The test item produced a mean erythema value of 1 and mean oedema value of 0 as such was not classified as irritant to rabbit skin according to CLP. No corrosive effects were noted.