Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted in accordance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Purity 99.7%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young adult animals
(male animals approx. 8 - 16 weeks
female animals approx. 9 - 16 weeks)
Animal weights at start of Animals of comparable weight (200 g - 300 g ± 20% of the the study: mean weight)
Source: Charles River Laboratories, Sulzfeld, Germany

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Tylose CB 30.000
Details on dermal exposure:
The test substance was prepared in 0.5% aqueous Tylose® and was applied to a skin area of about 50 cm2 (10% of body surface) under semi occlusive conditions for 24 hours.The test substance concentration in the vehicle was 80g/100 ml (w/v) and the application volume was 2.5 ml/kg
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:
Five male and five female Wistar rats were treated with 2000 mg/kg bw test substance.The test substance was prepared in 0.5% aqueous Tylose® and was applied to a skin area of about 50 cm2 under semi-occlusive conditions for 24 hours.The test substance concentration in the vehicle was 80g/100 ml (w/v) and the application volume was 2.5 ml/kg. After 24 hours of exposure the treated skin was cleaned with water. The animals were checked for mortality twice each working day and once on Saturday, Sundays or holidays. They were observed for clinical symptoms of toxicity several times on the day of treatment and once daily thereafter. Body weights were recorded prior test start, weekly thereafter, and at the end of the observation period. The skin was examined 30 to 60 minutes following removal of the dressing, weekly thereafter, and at the end of the observation period. All rats that died and the surviving rats at the end of the study (18 days observation period) were subjected to necropsy and examined for gross pathology.Analytical determinations of the test substance preparation with respect to stability in the vehicle were performed prior to starting the toxicological study.
The assessment of skin findings was based on Draize JH (Appraisal of the safety of chemicals in food, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas, 1959).
Statistics:
Binomial test according to SNEDECOR GW (“Statistical methods”, 8th ed., Iowa State University Press/Ames, 1989).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
The animals of both sexes displayed poor general state, dyspnoea and apathy as clinical symptoms; these symptoms lasted until day 1 of observation.Local effects at the application sites were seen in both, males and females and included white discoloration of the skin, erythema, edema, eczematoid skin change, scaling and crust formation.These effects lasted until the end of the observation period.
Body weight:
Body weights were inconspicuous.
Sex BW on Day 0 BW on Day 7 BW on Day 13
Males 246 g 247 g 263 g
Females 220 g 219 g 221 g
Gross pathology:
Excepted for incrustation and full thickness necrosis seen at the application site in 4/5 males and 5/5 females, pathological examination at necropsy revealed no further abnormalities.

Applicant's summary and conclusion