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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 November 1998 to 02 December 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to EU & OECD test guidance in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

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

Test material

Constituent 1
Details on test material:
Name: Reaktiv-Orange DYPR 1410
Certificate of analysis: NB 208 of December 15, 1998
Content: 73 % (w/w) + 2 %
Appearance: orange powder approx.
Solubility: 350 g/l in water
Batch number: DYPR 1410
Date of production: August 17, 1998
Date of receiving: August 26, 1998
Date of expiry: August 2003
Storage conditions: darkness at approximately 5°C in a refrigerator

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Sprague Dawley rat
Strain: HSD: Sprague Dawley SD
Origin: HARLAN WINKELMANN Gartenstr. 27, 33178 Borchen SPF breeding colony
Body weight at start of study
male animals: mean = 231g (=100%)
s = ±2.7g
min = 228g (-1.3%)
max = 234g (+1.3%)
n 5
female animals: mean = 202g (=100%)
s = ±4.7g
min = 198g (-2.0%)
max = 210g (+4.0%)
n 5
Age at the start of the study: 6-10 weeks
Randomization: Randomization schemes 98.0611 and 98.0703 as per the laboratory protocol.
Animal maintenance: in fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate, one animal per cage
Room temperature: 22 ± 3°C
Relative humidity: 50 ± 20 %
Lighting time: 12 hours daily
Acclimatization: at least seven days
Food: ssnifT R/M-H (V 1534), ad libitum
Water: tap water in plastic bottles, ad libitum
Animal identification: cage numbering

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: deionized water
Details on dermal exposure:
To check the suitability of the vehicle 0.5 g Reaktiv-Orange DYPR 1410 was moistened with 0.3 ml deionized water.

Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximately 30 cm.

The appropriate amount of the test substance was moistened on an aluminium foil (6 x 8 cm) and distributed as uniformly as possible. Together with the foil the test substance was administered to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body (Fixomull and Elastoplast, 8 cm in width, both manufactured by Beiersdorf Aktiengesellschaft).
At the end of the dermal exposure period of 24 hours the bandage was removed and the treated skin area washed with warm water in order to remove any unabsorbed remnants of the test substance.
Duration of exposure:
24 h
Doses:
The acute dermal toxicity of Reaktiv-Orange DYPR 1410 was tested only at a dose level of 2000 mg/kg body weight.
If no compound-related mortality is produced in this limit test according to the guidelines no full study has to be carried out.
No. of animals per sex per dose:
10 - 5 male, 5 female.
Control animals:
no
Details on study design:
The observation period after the dermal administration lasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study
Clinical signs:
other: No symptoms were observed after administration of 2000 mg/kg body weight.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Other findings:
Two days after administration up to the end of the study the animals showed orange discoloured skin.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of Reaktiv-Orange DYPR 1410 for the male and female rat is greater than 2000 mg/kg body weight.
Executive summary:

Testing for acute dermal toxicity provides information on health risks resulting from acute dermal exposure and serves as a basis for classification and labelling. It permits the selection of optimum dose levels for repeated dermal toxicity testing and gives the first indications on the percutaneous resorptive properties of a substance. The rat has proved to be a suitable species for acute dermal toxicity testing with many different substances.

 

The study was conducted in compliance with EEC-Guideline B.3. "Acute Dermal Toxicity" of the Directive 92/69/EEC andOECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxicity". This study was conducted in compliance with the Principles of Good Laboratory Practice.

 

Acute dermal toxicity testing of Reaktiv-Orange DYPR 1410 in the rat yielded a median lethal dose above 2000 mg/kg body weight in both male and female animals. After administration of 2000 mg/kg b.w. neither deaths nor symptoms occurred.

 

Two days after administration up to the end of the study the animals showed orange discolored skin.

 

Development of body weight was not impaired, with exception of one female animal which showed a decrease from day 1 to day 6.

 

The animals killed at the end of the observation period showed no macroscopically visible changes.