Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 October 1997 - 13 November 1997
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
yes
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
Details on test material:
- Name of test material (as cited in study report): Epyrron
- Physical state: Off white powder
- Composition of test material, percentage of components: Main component 55%; Other 22% & 18%
- Lot/batch No.: GV-1458 K1
- Expiration date of the lot/batch: 24 September 1998
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, sulzfed, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: Males (average): 369 grams; Females (average) 235 grams
- Fasting period before study: No
- Housing: Individually in polycarbonated cages
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, OUd-Turnhout, Belgium).
- Water (e.g. ad libitum): Free access tap-water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 10% of total body surface
- Type of wrap if used: Gauze patch, fixed successively to aluminium foil and Coban elastic bandage; in addition micropore tape was used.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Tap-water moistened tissue
- Time after start of exposure: 24 hours after application
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males;
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice Daily; Body Weights - Day 1 (pre-administration), day 8 and day 15; Clinical Signs - periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Internal macroscopic abnormalities

Results and discussion

Preliminary study:
Since the 2000 mg/kg body weight limit test resulted in no adverse effects, or mortalities in the study group, no additional dose levels were required.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality reported.
Clinical signs:
General or focal erythema, scales and scabs on the back or flank were reported in one male and two females. By day 8 the females recovered from symptoms, however scabs persisted in the male at termination of study.
Yellow staining of the skin by the test substance was noted in all animals during the study period.
Body weight:
Body weight changes in males and females were within the range expected for rats used in this type of study and were therefore not considered indicative of toxicity.
Gross pathology:
No treatment related abnormalities were reported at the macroscopic level.
Pelvic dilation of the kidneys were found in one male, however this is a common occurrence among rats of this age and strain and was not considered toxicologically related.

Any other information on results incl. tables

Clinical Signs - Males                                    
   
Test day     1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time after treatment Hours   0 2 4                            
   
Animal No. Signs Max Grade  
1 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
2 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1  -  -  -  -
3 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
4 Skin/Fur/Plumage/Erythema Focal (Back) 4  -  -  - 2 2 2 1 1 1 1 1 1  -  -  -  -  -
Scabs (Back) 3  -  -  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1
Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
5 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Clinical Signs - Females                                    
   
Test day     1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time after treatment Hours   0 2 4                            
   
Animal No. Signs Max Grade  
6 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
7 Skin/Fur/Plumage/General Erythema (Back) 4  -  -  - 2 2 2 1 1 1  -  -  -  -  -  -  -  -
Scales (Back) 3  -  -  -  -  - 1  -  -  -  -  -  -  -  -  -  -  -
Skin Yellow (Flank Left) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
8 Skin/Fur/Plumage/General Erythema (Back) 4  -  -  - 2 2 2  -  -  -  -  -  -  -  -  -  -  -
Erythemal Focal (Flank Right) 4  -  -  -  -  -  - 2 2 1  -  -  -  -  -  -  -  -
Scales (Back) 3  -  -  -  -  - 1  -  -  -  -  -  -  -  -  -  -  -
Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1  -  -  -  -
Skin Yellow (Flank Left) 1  -  -  -  -  -  -  -  -  -  -  -  -  - 1 1 1 1
9 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
10 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance, when administered as supplied to 5 male and female Wistar rats, appears to have an acute dermal LD50 greater than 2000 mg/kg
Executive summary:

The dermal LD50 value of the test substance in rats was established as exceeding 2000 mg/kg body weight.