Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 18, 2013 - January 13, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: solid
- Colour: colourless
- Storage condition of test material: dry, at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males: 9 - 10 weeks old; females: 12 - 13 weeks old
- Weight at study initiation: males: 258 – 269 g; females: 205 – 230 g
- Housing: full barrier in an air-conditioned room
- Diet (e.g. ad libitum): free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0801)
- Water (e.g. ad libitum): free access to tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): artificial light, sequence being 12 hours light, 12 hours dark

Administration / exposure

Type of coverage:
other: gauze-dressing and non-irritating tape
Vehicle:
cotton seed oil
Details on dermal exposure:
TEST SITE
- Area of exposure: uniformly over an area which was approximately 10% of the total body surface
- Type of wrap if used: dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed using cottonseed oil
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): single dose of 2000 mg/kg body weight
- For solids, paste formed: no

VEHICLE
- Lot/batch no. (if required): Sigma, lot no. MKBN8713V, expiry date: 31/01/2014
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: on day 1 (prior to the application) and on days 8 and 15
- Frequency of clinical examination: several times on day of dosing, thereafter once daily until end of observation period
- Necropsy of survivors performed: yes, gross necropsy

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No treatment-related signs of systemic toxicity or effects on organs were observed.

Erythema grade 1 was observed in all animals. Oedema grade 1 was observed in 1 of 5 male animals. In all animals, green spots were observed at the application site 1 day post-application, together with necrosis. Necrosis and eschar were observed in all animals.
Erythema and oedema were reversible by day 7 in the male animals and by day 9 in the female animals. Eschar was reversible by day 11 in the male animals and by day 9 in the female animals. Necrosis was not reversible in any animal within the observation period.
Body weight:
A slight weight loss was recorded for 1 out of 5 male animal during the first week, but all of the animals showed weight gain during the second week. The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot be clearly concluded.
The female animals showed weight gain during the first and the second week of the observation period.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which was due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, single dermal application of the test item to rats up at a dose of 2000 mg/kg body weight was associated with no mortality but signs of irritation. The dermal LD50 was determined to be > 2000 mg/kg body weight.
In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item has no obligatory labelling requirement for percutaneous toxicity.
According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for percutaneous toxicity and is unclassified.
According to GHS (Globally Harmonized Classification System) the test item has no obligatory labelling requirement for percutaneous toxicity.