Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Toxi-Coop ZRT.

Test material

Constituent 1
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Thymidine

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult rabbits
- Weight at study initiation: 2844 - 3085 g
- Housing: Animals were housed individually in metal cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES:
- From: 15 Jan. 2013
- To: 19 Jan. 2013

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: The test item was used in pure state, in a single dose of 0.5 g test item
Duration of treatment / exposure:
In the first step an initial test was performed using one animal. One hour after application of the test item to the sentinel animal, the application site was examined. Severe irritation or corrosive effect was not observed in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). 4 hours after the application the rest of the test item was removed using body temperature water. Two additional animals were treated comparably for this study.
Observation period:
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes, 24, 48 and 72 hours after the patch removal.
Number of animals:
Three animals
Details on study design:
TEST SITE
- Area of exposure: Approximately 6 cm² area of intact skin
- Type of wrap if used: Sterile gauze pads (10 x10cm) were placed on the skin of rabbits. These gauze patches were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunks of the animals were wrapped with plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: 4 hours after the application the rest of the test item was removed using body temperature water.
- Time after start of exposure: 4 hours

SCORING SYSTEM
- The dermal irritation scores were evaluated according to the scoring system by Draize (1959) shown in the Appendix III. The animals were observed for 72 hours, the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours after treatment
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours after treatment
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours after treatment
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours after treatment
Score:
0
Max. score:
0
Irritant / corrosive response data:
1 hour after the patch removal well defined erythema (score 2) was observed in two animals (No.: 1, 2) and very slight erythema (score 1) occurred in animal No.: 3. Oedema was not observed in animals during the study.
24 hours after the patch removal well defined erythema (score 2) was recorded in animal No.: 1 and very slight erythema (score 1) was detected in two animals (No.: 2, 3).
48 hours after the patch removal very slight erythema (score 1) was observed in animal No.: 1. Two animals (No.: 2, 3) became free of symptoms.
72 hours after the treatment the study was terminated, since there were no primary irritation symptoms.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) were as follows:
- erythema: 1.00, 0.33, 0.33
- oedema: 0.00, 0.00, 0.00
There were no signs of corrosion. During the study the behaviour and general state of animals were normal. There were no notable body weight changes during the contact and observation period and no signs of systemic toxicity.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Test item treatment caused mild irritation. There were no signs of corrosion. The behavior and general state of animals was normal. No changes to body weight and no systemic toxicity were observed.
Executive summary:

An acute skin irritation study was performed in New Zealand White rabbits according to EU Method B.4, OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and OPPTS 870.2500. The irritation effects of the test item were evaluated according to the Draize (1959) method.

The test item was administered in pure state, in a single dose of 0.5 g to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control. After 4 hours the rest of the test item was removed with water of body temperature.

The animals were examined at 1, 24, 48 and 72 hours after the patch removal. 1 hour after the patch removal very slight to well defined erythema was observed in animals. 48 hours after the patch removal very slight erythema was found in one animal and two animals became free of symptoms. 72 hours after the treatment the study was terminated, since there were no primary irritation symptoms.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) were as follows:

- erythema: 1.00, 0.33, 0.33

- oedema: 0.00, 0.00, 0.00

There were no signs of corrosion. During the study the behaviour and general state of animals were normal. There were no notable body weight changes during the contact and observation period and no signs of systemic toxicity.