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Acute Toxicity: dermal

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acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2007
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 402 (Acute Dermal Toxicity)
according to
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Test material form:
solid: particulate/powder

Test animals

other: CRL: CD (SD) BR
Details on test animals and environmental conditions:
Species, strain Rats, CRL: CD (SD) BR (outbred, SPF-Quality).
Supplier Charles River Laboratories, D-97633 Sulzfeld.
Number of animals and sex 5 males and 5 females.
Females were nulliparous and non-pregnant.
Age Young adult animals, approximately 8 weeks (males) and 12 weeks (females) at the time of administration.

A health inspection was performed prior to the commencement of treatment to ensure, that the animals were in a good state of health.
Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Hygienic status Optimal hygienic conditions.
Room number EH1-23.
Room temperature Average of 22.0 °C (continuous control and recording).
Relative humidity Average of 51.7 % (continuous control and recording).
Air exchange 12 per hour.
Light Artificial light from 6 a.m. to 6 p.m.
Cages Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm).
Wire mesh lids. Sanitation of cages once a week.
Bedding material Aspen wood chips, type "ABEDD", (Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach), autoclaved. Bedding material was changed
weekly. Samples of the bedding material are checked periodically for contaminants by the supplier.
Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material,
(same source and material as the bedding material), were offered to
the animals once a week.
Feed Ssniff R/M-H maintenance diet for rats and mice (item V1534-3 ) ad
libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest,
Germany. Analysis of the feed for ingredients and contaminants is
performed randomly by Ssniff.
Water Tap water, acidified with HCl to pH ≥3, from an automatic watering
system, ad libitum. Random samples of the water are analysed by
the "AGES", 1226 Vienna, Austria, to check, if the water fulfils the
requirements for drinking water for humans (exception: the pH).
Identification Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation 5 days under laboratory conditions.

Administration / exposure

Type of coverage:
soaked with deionised water
Details on dermal exposure:
A single dermal administration was performed by spreading the undiluted test substance on an area of at least 10 % of the estimated body surface:
The body surface was calculated using the formula: body surface (cm²) = 10 x body weight (g)2/3 E.g.: a rat of 250 g body weight has therefore a body surface of at least 400 cm2.
The test site was located on the dorsal thoracal region. An area of 6.5 cm x 8 cm (52 cm2) was marked on a relaxed animal.
The hair of the dorsal trunk was clipped with an electrical hair clipper (Aesculap GH, 0.1 mm cutterhead) one day before application of the test substance.
The individual amounts of the test substance were calculated using the body weights determined on the day of the administration.
A cellulose patch (Pehazell, Hartmann AG) with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape (Blenderm Wundpflaster, 3M).
Patch and tape were covered semi-occlusively by a dressing (Fixomull Stretch, Fa. Beiersdorf).
The duration of exposure was 24 hours.
Duration of exposure:
24 h
Due to available data of a former acute oral toxicity study (LD50, rats > 2000 mg/kg), it seemed appropriate to perform a limit-test with the dose of 2000 mg per kg body weight.
No. of animals per sex per dose:
Animal Nos. Sex Dose(mg / kg b.w.)
5 male 2000
5 female 2000
Control animals:
Details on study design:
Observations were performed 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No toxic signs were observed.
Body weight:
All animals gained weight in both weeks
Gross pathology:
Effects on organs:
No toxic signs were observed.
Other findings:
Signs of toxicity (local):
No toxic signs were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Migrated information Criteria used for interpretation of results: EU
No test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight.