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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21-June-2011 to 03 July 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The study integrity was not adversely affected by the deviations
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Yellow powder (determined at NOTOX)

Test animals

Species:
rabbit
Strain:
New Zealand White

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Amount / concentration applied:
0.5 grams of 9-Aminominocycline
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
3 males
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 9 days later, after considering the degree of skin irritation observed in the first animal.

Treatment
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.6 mL of the vehicle and applied to the skin of one flank, using a metalline patch# of 2x3 cm. The patch was mounted on Micropore tape#, which was wrapped around the abdomen and secured with Coban elastic bandage#. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

After the final observation, animal nos.76 and 97 were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands). Animal no. 95 was used for internal research purposes, procedures/results of which did not form part of this project and hence were reported nor retained in the study raw data.

Observations
Mortality/Viability Twice daily.

Toxicity At least once daily.

Body Weight Day of treatment (prior to application) and after the final observation.

Necropsy No necropsy was performed according to protocol. Irritation The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

The irritation was assessed according to the following numerical scoring system.
Interpretation
The results were evaluated according to: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), - Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Other effects:
Irritation and corrosion
Four hours exposure to 0.5 g of 9-Aminominocycline resulted in very slight erythema in the treated skin areas of the three rabbits. The skin irritation resolved within 24 hours after exposure in all animals.

Coloration / Remnants
Yellow-green staining of the treated skin by the test substance was observed throughout the observation period, which did not hamper the scoring of the skin reactions.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results 9-Aminominocycline does not have to be classified and has no obligatory labelling requirement for skin irritation according to the: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Primary skin irritation/corrosion study with 9-Aminominocycline in the rabbit (4-hour semi-occlusive application).

The study was carried out based on the guidelines described in:  OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)  EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion" US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation   JMAFF Guidelines (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of 9-Aminominocycline, moistened with water by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

Exposure to 9-Aminominocycline resulted in very slight erythema in the treated skin areas of the rabbits, which had resolved within 24 hours.  

Yellow-green staining of the treated skin by the test substance was observed  throughout the observation period, which did not hamper the scoring of the skin reactions.

Based on these results 9-Aminominocycline does not have to be classified and has no obligatory labelling requirement for skin irritation according to the: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.