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: study conducted according to GLP and OECD Guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: aqueous solution

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Ohio, USA
- Age at study initiation: young adult
- Weight at study initiation: 2.14-2.99 kg


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount applied: 0, 172, 337, 660 mg a.s./kg bw





No vehicle used.
Duration of exposure:
24 h
Doses:
0, 172, 337, 660 mg a.s./kg bw
No. of animals per sex per dose:
5, control: 3
Control animals:
other: control animals were treated with deionized water
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweights were recorded on days 0, 7 and 14, the animals were examined for clinical signs 1, 3 and 4 hours after treatment and daily afterwards
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Dose-effects were evaluated using the method developed by Litchfield and Wilcoxon.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
429 mg/kg bw
Based on:
act. ingr.
95% CL:
264 - 627
Mortality:
Mortality occurred in males from the 337 mg/kg bw dose group onwards (two males were found dead). In the highest dose group, 4 males and 3 females died.
Clinical signs:
Decreased defecation was observed in all dose groups. Lethargy, ataxia, decreased respiration rate were observed in the 337 and 660 mg/kg bw dose groups. In the highest dose groups, clear nasal discharge, purulent nasal discharge and a clear wet matting around the mouth were also recorded and one animal appeared emaciated.
Body weight:
During the observation period body weight losses were observed in one animal each from the 337 and the 660 mg/kg bw dose groups.
Gross pathology:
At necropsy the application sites of the rabbits found dead during the observation period was thickened, blanched and subcutaneously haemorrhagic. In some of the animals the brain appeared haemorrhagic and dark red areas and red foci were found in the stomachs. Eschar formation on the skin was observed in the animals of the highest dose group. These animals also exhibited a haemorrhagic thymus. A pale and soft liver as well as soft, spongy and dark reddened kidneys were found in one animal of the highest dose group.
The surviving animals also exhibited a thickened application site and eschar formation. Pale, reddened and pitted kidneys were recorded, but pale kidneys were also observed in the control group. One of the three surviving animals of the highest dose group was found to have white nodules in the lungs and red foci in the stomach.

Applicant's summary and conclusion