Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
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 material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
other: Rat Ico : OFA.SD. (IOPS Caw.)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO (L'Arbresle Cedex, France)
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: 200 - 300 g
- Fasting period before study: no
- Housing: individually in polycarbonate cages type FI
- Diet (e.g. ad libitum): pelleted complete diet (Diet reference A04 C10, Usine d'Alimentation Rationelle, Epinay s/Orge, France), ad libitum
- Water (e.g. ad libitum): softened and filtered mains drinking water, ad libitum
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40-70%
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
- Preparation of the animals:
The day before the acclimatisation of the test article, the back and the flanks of each animal were carefully clipped, to expose an area of skin which was not less than 10'% of the total body surface area. At the time of aplication, only those animals showing perfectly healthy skin and with no sign of macroscopic irritation, were kept for the test.

- Method of administration:
The powder was prepared as a paste, moistened with water for injection. The test item was held in contact with the skin by a semi-occlusive bandage. This bandage covered fully the treated area, in order to prevent ingestion of the test item. At the end of the 24 hour period, the binders were removed and the skin wiped clean of residual test article using water.
Duration of exposure:
24 h
Doses:
Preliminary study:
1000 or 2000 mg/kg bw
Main study:
2000 mg/kg bw
No. of animals per sex per dose:
Preliminary study:
2
Main study:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration:
14 days
- Frequency of observations and weighing:
Examinations for mortality and abnormal clinical signs were performed 15 min after application, then at 1, 2 and 4 hours and then daily for the 14 day study period. All animals were weighed immediately before application of the test item (day 1), on days 8 and 15, as well as at time of death from day 2 onwards.
- Necropsy of survivors performed:
yes
- Other examinations performed:
cutaneous examinations were performed from day 2 to 15.
Statistics:
- Body weight: analysis of variance and Student's t test
- Mortality: calculated as percentage to determine the innocuity or degree of toxicity
- LD50: expressed in mg/kg bw with a 95% confidence limit interval evaluated according to Bliss and Litchfield & Wilcoxon's methods

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Main study
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
- Mortality:
One male was found dead on day 2

-Clinical signs:
There were no abnormal clinical signs in any of the treated animals during the observation
Body weight:
Body weight changes in the treated animals were not influenced by treatment.
Gross pathology:
There were no macrosocpic findings that could be associated with the treatment.
Other findings:
The local tolerance of the test item was good: no cutaneous lesions (erythema or oedema) was noted to the application site of the test item during the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the results obtained under the conditions of this OECD 402 dermal toxcity study the LD50 greater than 2000 mg/kg bw.
Executive summary:

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation. The dermal LD50 was determined to be > 2000 mg / kg body weight.