Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 5 December 1991 to 8 December 1991.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
84/449/EEC
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Test material: CYDI ((1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide)
Description: Off-white powder
Storage: In original container at room temperature
Molecular formula: C5H4N4O2
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Description: off-white powder
- Sponsor's identification: CYDI

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Container: white plastic jar (x2)
- Data relating to the identity, purity and stability of the test material are the responsibility of the sponsor.


Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.28 - 2.43 kg
- Housing: individual housing in suspended metal cages
- Diet (e.g. ad libitum): Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol; free access was allowed throughout the study
- Water (e.g. ad libitum): Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol; free access was allowed throughout the study
- Acclimation period: five days each animal

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 37-47%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): continuous 12 hours light and 12 hours of darkness

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
A quantity of 0.5g of the test material, moistened with 0.6 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape.
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure:
2.5 cm x 2.5 cm
- Type of wrap if used:
The patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure:
4 hours

OBSERVATION TIME POINTS
- Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation

SCORING SYSTEM:
- Method of calculation: according to the scale from Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics". See Table 1.

INTERPRETATION OF THE RESULTS:
- The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by 6 to give the primary irritation index of the test material. The test material was classified according to the sceme displayed in Table 2 below.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
4
Reversibility:
other: not relevant in absence of reaction
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No adverse dermal reactions were noted during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material was classified as non-irritant to rabbit skin according to EEC labelling regulations.
Executive summary:

A study was performed to assess the irritancy potential of the test material (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide to the skin of the New Zealand white rabbit. The method used followed that described in the OECD guideline no. 404 and Method B4 in Commission Directive 84/449/EEC. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no adverse dermal reactions. The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material was also classified as non-irritant according to EEC labelling regulations.