Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-guideline and GLP-compliant study

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain as stated in the report: Hanlbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 9 weeks (males), 12 weeks (females)
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding. During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 3433 rat maintenance diet, ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3°C
- Humidity (%):40-70% (values above 70% during cleaning process possible).
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10 % of the total body surface

REMOVAL OF TEST SUBSTANCE
- Washing: 24 h after application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels

TEST MATERIAL
- Amount applied: 4.0 ml/kg bw
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations for mortality and clinical symptoms: 4-times on first day, afterwards once daily
- Frequency of weighing: On first day, day 8 and day 15
- Necropsy of survivors performed: yes, all animals were sacrified and subjected to gross pathology
Statistics:
No statistical analysis was used as no deaths occurred.

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: None of the treated animals died. No clinical signs were observed.
Mortality:
No deaths occurred during the study.
Clinical signs:
No systemic or local signs of toxicity were observed during the study period.
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age (details table 1).
Gross pathology:
No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Body weight of male and female rats after dermal treatment with 2000 mg/kg bw of test article

Body weight in grams:

Sex

Animal No.

Day of treatment

Day 8

Day 15

Male

1

235.8

259.5

281.6

2

235.1

252.8

269.6

3

231.3

258.2

279.8

4

247.3

277.4

300.5

5

240.1

262.1

278.6

female

6

201.4

207.7

216.2

7

223.5

230.0

227.4

8

207.9

226.7

228.9

9

199.1

203.3

212.0

10

205.7

207.5

223.4

 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After dermal application of 2000 mg/kg bw test article to female and male rats for 24 h under semi-occlusive conditions according to OECD 402 (1987) no mortality was observed. Thus, the LD50 was above 2000 mg/kg bw for both sexes.