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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2012-2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and valid testing guidance, therefore it is considered relevant, adequate and reliable for classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: Males (at dosing): 227–254 g; Females (at dosing): 201-226 g
- Fasting period before study: Approx. 16 hours before administration; only tap water was then available ad libitum
- Housing: During the 141-day observation period the animals were kept singly in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maximum range)
- Humidity (%): 55% ± 15% (maximum range)
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 7,2012 To: September 11, 2012

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Aqua ad iniectabilia
Details on dermal exposure:
TEST SITE
- Area of exposure: intact dorsal skin on the animals back between the fore and hind extremities ; an area of at least 5 cm x 6 cm
- % coverage: approx. 1/10 of body surface
- Type of wrap if used: The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips on the application site for 24 hours.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw (a correction factor of 1.05 was used)
- Concentration (if solution): 2.1 g/ g water
- Constant volume or concentration used: constant concentration, different volume (3.1 g/kg bw of the test item preparation)
- For solids, paste formed:


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations were performed before and immediately, 5, 15, 60 and 60 minutes, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days. During the follow-up period (two weeks), changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern, were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study.
Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
None of the animals died prematurely.
Clinical signs:
A very slight erythema (barely perceptible) on the application site was observed in all 5 of 5 male and 5 of 5 female animals on test days 2 and 3.
Body weight:
All animals gained the expected body weight throughout the whole experimental period.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item (>95% purity) requires no labelling (as LD50 > 2000 mg/kg bw).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute dermal toxicity.
Executive summary:

In this experiment, the test item (>95% purity) was examined for acute toxicity after a single dermal application to rats at one dose level of 2000 mg act. ingr./kg bw. The test item was applied once for 24 hours on the shaved intact dorsal skin of rats (5 cm x 6 cm, approx. 1/10 of body surface). This treatment was followed by an observation period of 2 weeks. Under the present test conditions, a single dermal administration of 2000 mg/kg bw to rats revealed no signs of toxicity and no deaths. A very slight erythema (barely perceptible) on the application site was observed in all 5 of 5 male and 5 of 5 female animals on test days 2 and 3. All animals gained the expected body weight throughout the whole experimental period. No macroscopic findings were observed at necropsy.