Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 19, 2010 - January 12, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 402 (1987), EU Method B.3 ( 2008), EPA OPPTS 870.1200 (1998) and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
(1998)
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: crystalline
Details on test material:
- Name of test material (as cited in study report): F10Fine
- Physical state: colourless solid

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation:
Males: 7-8 weeks
Females: 14 weeks
- Weight on the day of administration:
Males: 237-295 g
Females: 224-234 g
- Housing: Individually in IVC cages, type III H, polysulphone
- Diet: ad libitum (Altromin 1324)
- Water: ad libitum (tap water, sulphur acidified to a pH value of approx. 2.8)
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
(aqua ad injectionem (B. Braun Melsungen, lot no. 0195A191, expiry date: 04/2013))
Details on dermal exposure:
TEST SITE
- Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper.
- Area of exposure: approx. 10% of the total body surface
- Dressing: gauze and non-irritating tape, which was fixed with an additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing: yes, using water
- Time after start of exposure: 24 hours

VEHICLE AND WATER USED FOR REMOVAL OF TEST SUBSTANCE
Aqua ad injectionem (B. Braun Melsungen, lot no. 0195A191, expiry date: 04/2013)
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 weighing: The animals were weighed on day 1 (prior to the application) and on days 8 and 15
- Frequency of observations: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes
- Other: Signs of erythema and oedema were assessed using the scoring system laid down in OECD 404 (2002)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities and no clinical signs of toxicity occurred
Mortality:
No mortalities occurred
Clinical signs:
No clinical signs of toxicity occurred
Body weight:
A slight weight loss was recorded in 2 females during the first week.
Gross pathology:
Macroscopic examination of the animals did not reveal any abnormalities.
Other findings:
Eschar was observed in 2 females, during day 3 to 7/9

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed in accordance with OECD 402 (1987), EU Method B.3 ( 2008), EPA OPPTS 870.1200 (1998) and according to GLP principles, a LD50 of >2000 mg/kg bw was determined.
Executive summary:

The acute dermal toxicity of the substance was determined in the rat, in accordance with OECD 402 (1987), EU Method B.3 ( 2008), EPA OPPTS 870.1200 (1998) and according to GLP principles. The substance was administered to five Wistar rats of each sex by a single dermal application of 2000 mg/kg bw for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality and no clinical signs of toxicity occurred. A slight weight loss was recorded in 2 females during the first week. Macroscopic examination of the animals did not reveal any abnormalities. The dermal LD50 value of the substance in Wistar rats was established to be >2000 mg/kg bw.