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: GLP-guideline study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
1/ Clinical observation: On one day, observations were only recorded once, and on two other days, they were not recorded. 2/ Test conducted at 2000 mg/kg instead of 5000 mg/kg. Both protocol deviations were not considered to adversely affect study results
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ETHYL THIURAD
- Physical state: off-white powder
- Purity: 98.6%
- Lot/batch No.: 5394

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Isaacs’ Rabbitry, Litchfield, Illinois
- Age at study initiation: Young adult
- Weight at study initiation: 2.27-2.64 kilograms
- Housing: one per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10-30% of total body surface
- Type of wrap if used: wrap of latex rubber


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the excess material was wiped from the animal
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
one group of 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made three times during the first eight hours following test material administration and routinely twice daily (morning and afternoon) thereafter until sacrifice. On one day, observations were only recorded once, and on two other days, they were not recorded. These protocol deviations were not considered to adversely affect study results.
Body weights were recorded on days 0 (day of exposure), 7, and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Clinical signs:
Erythema in the exposed area was observed in one female and two male animals on the day after dosing and in the same female rabbit on the following day. No other clinical abnormalities were observed.
Gross pathology:
At necropsy, one male and two female animals had off-white fibrous tissue in and/or a marbled appearance of all hepatic lobes. Two of these same animals had numerous hard, yellow foci on all lobes of the liver, and one also had an area of green, necrotic hepatic tissue. All three of these animals also had tapeworm cysts in the mesentery. Pale renal coloration was observed in each of two animals, one of which also had kidneys with pitted exteriors. No abnormalities were observed in the remaining five rabbits.

Applicant's summary and conclusion