Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 21 - June 10, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented pre-guideline study without GLP, testing protocol similar to OECD 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
pre-guideline and pre-GLP study
Principles of method if other than guideline:
According to: Noakes, D.N. and Sanderson, D.M. (1969). A method for determining the dermal toxicity of pesticides. Brit. J. Indust. Med. 26, pp 59-64.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Substance type: organic
- Physical state: liquid
- Storage condition of test material: In refrigerator (2-8°C) in the dark

Test animals

Species:
rat
Strain:
other: Tif:RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
Healthy random bred Rats of 8-9 weeks age were raised on the premises and kept at room temperature of 22 + 2 deg. C, at relatie humidity of 55 +/- 10% and on a 10 hour light cylce day. They received ad libitum rat food (supplier: NAFAG, Gossau, Switzerland) and water. They were adapted to the laboratory for a minimum of 4 days before treatment. During treatment and observation period the animals were housed individually in Macrolon cages type 2.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours before treatement an area of approximately 60 square centimeters was shaved with an electric clipper. For the treatment the test material was evenly dispersed on the skin with a syringe and was covered with an occlusive dressing which was fastened around the trunk with an adhesive elastic bandage. After 24 hours the dressing was removed, the skin was cleaned with lukewarm water and the reaction of the skin was appraised.
Duration of exposure:
24 hours
Doses:
0 - 3000 - 3500 - 4000 mg/kg bw Treatment with higher doses was not possible

No. of animals per sex per dose:
5 males and 5 females

Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: 1 / hour for the first 5 hours, thereafter at least 1 / day. Body weight determination 1 / week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:
not required

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed during the observation period of 14 days following treatment
Clinical signs:
Animals treated with 4000 mg/kg bw showed a moderate skin erithema (days 2-8) and a slight skin erythema on day 9.
Slight effects recorded are sedation (days 1-5), dyspnea (days 1-6), exophthalmos (days 1-7), ruffled fur (days 1-8) and curved body position (days 1-6).

Animals treated with 3500 mg/kg bw showed a moderate skin erithema (days 2-7) and a slight skin erythem(days 8-9).
Slight effects recorded are sedation (days 1-5), dyspnea (days 1-6), exophthalmos (days 1-7), ruffled fur (days 1-8) and curved body position (days 1-6).

Animals treated with 3000 mg/kg bw showed a moderate skin erithema (days 2-7) and a slight skin erythema (days 8-9).
Slight effects recorded are sedation (days 1-2), dyspnea (days 1-6), exophthalmos (days 1-7), ruffled fur (days 1-8) and curved body position (days 1-6).
Body weight:
The following body weight changes were recorded :

Control 3000 mg/kg 3500 mg/kg 4000 mg/kg
males 1st week 12% 4% 5% -1%
2nd week 19% 9% 21% 21%

Control 3000 mg/kg 3500 mg/kg 4000 mg/kg
females 1st week 3% -1% -1% -4%
2nd week 7% 13% 10% 11%
Gross pathology:
No substance related gross organ changes were seen.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity is similar for males and females. The acute dermal toxicity is >4000 mg/kg bw.
Executive summary:

The acute dermal toxicity has been investigated in a pre-guideline and pre-GLP study performed and recorded similarly to the later standards. The doses selected were 4000, 3500 and 3000 mg/kg bw. Each 5 male and 5 female animals were treated on the shaved skin (60 cm2) and received an occlusive patch . There was no mortality in all dose groups. At all doses there were the usual clinical symptoms in animals of both sexes. The LD50 derived is >4000 mg/kg.