Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: recent study conducted in accordance with GLP guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test article, E2932.01 (TMPD) was provided by the sponsor as a white solid compound, the expiry date of which was 12/87. Just prior to administration, a representative sample of the test article was ground in a mortar and then passed through a 40 mesh sieve.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Six New Zealand White rabbits (3 males and 3 females) were used in this study. They were selected on the basis of their health status. From a supernumerary lot of animals purchased from Conelli Arona, only animals with healthy skin were used. Upon arrival, the rabbits were about 3 months old and weighte 2.00 - 3.00 Kg. During the acclimation period (about 1 week) they were housed in the same room (G15) in which treatment would be performed.

The rabbits were individually housed in stainless steel cages measuring 38x49x34h cm. Each cage was suspended in a metal rack over an automatic cleaning sluce which periodically rinses waste away. Teh ambient conditions were the following: about 10-12 air changes per hour, temperature 20 degrees C, with controlled humidity and natural lighting.

The rabbits received a pelleted feed coded CBB 15 produced by the Charles River Italina, sfeed licensee Italiana Mangini, Sertimo Milanese. The diet was available to the animals "ad libitum". Filtered tap-water was distributed "ad libitum" by means of an automatic watering valve system. Periodically the drinking water is analyzed for microbiologic count, heavy metals and other chemical and physical characteristics expected to be present either in the diet or in the tap water.

Each rabbit was identified with an individual number which was borne on an ear tag. The 6 rabbits allocated to the experiment had the following identification numbers: 31M, 32M, 33F, 34F, 35F and 36M. Each cage was identified with a label bearing indelible indications fo experiment number, number and sex of the animal, and date of treatment.

Test system

Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
not specified
Amount / concentration applied:
A dose of 0.5 g of the test artice was placed directly onto the gauze patch (non-adherent dressing, Smith and Nephew, Brussels, Belgium) which was loosely held in contact with the skin by an impermeably, hypoallergenic non-irritant tape (Blenderm, 3M ITALIA, Milano).
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
Approximately 24 hours before the test, fur was removed by clipping the dorsal area of the trun of each animal. Only animals with healthy intact skin were used. Immediately before the treatment, the clipped skin of three rabbits (males no 31 and 32, and female no. 33) was abraded by making four epidermal incisions (two perpendicular to the other ina "tic-tac-toe" pattern and spaced 2 cm) with a disposable sterile needly. Incisions were sufficiently deep to penetrate the stratum corneum but no to disturb the derma or to produce bleeding. The other three rabbits (females no. 34 and 35, and male no 36) served as intact skin group. The test site was a amall area of skin (approximately 5 square cm) of the trunk of the rabbits.
Animals were not restrained and were returned to their cages during the exposure period. After the 4-hour exposure period, the patch was removed and residual test substance wiped off using water. At study termination, animals were sacrificed by an intracardiac administration of Tanag (Hoechst AG).

The rabbits were observed daily for clinical signs and behaviour alterations. The skin was observed for signs of erythem and edema at 4.5, 24, 48, and 72 hours after treatment start. Dermal irritation was scored and recorded accoring to the grades reported below:

EVALUATION OF SKIN REACTION VALUE

Erythema and eschar formation

No erythema 0
very slight erytema (barely perceptible) 1
well-defined erythema 2
moderate to severe erythema 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Highest possible erythema score 4

Edema formation

no edema 0
very slight edema (barely perceptible) 1
slight edema (edges of area well defined by definite raising) 2
moderate edema (raised approximately 1 mm) 3
severe edema (raised more than 1 mm and extending beyond area of exposure 4

highest possible edema score 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No local changes were oberved in 5 of 6 rabbits throughout the study. In only one rabbit, in the intact skin group showed very slight erythema (score 1) at the 24 hour reading, which fully resolved by the 48 hour reading. No other local changes were observed in this rabbit at other times during the study. The calculated primary irritation index for ths rabbit was 0.05.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test article (E2932.01) was determined to be non irritating for rabbit skin.
Executive summary:

The test material (E2932.01; TMPD) was applied to intact or abraided skin of 3 New Zealand White rabbits. No local changes were oberved in 5 of 6 rabbits throughout the study. In only one rabbit, in the intact skin group showed very slight erythema (score 1) at the 24 hour reading, which fully resolved by the 48 hour reading. No other local changes were observed in this rabbit at other times during the study. The calculated primary irritation index was 0.05. These data indicate that the test article is non-irritating to rabbit skin.