Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The information on this study is in the form of a letter report. It was conducted prior to international guidelines and good laboratory practice standards. The study appears to be robust.

Data source

Reference
Reference Type:
other: Letter Report
Title:
Unnamed
Year:
1964

Materials and methods

Principles of method if other than guideline:
Conducted generally as modern studies - a single dermal dose to four groups of rabbits with observation for 15 days followed by sacrifice with gross necropsies.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
not specified
Details on test animals and environmental conditions:
The animals were housed individually in metal cages elevated above the droppings. Food (Purina Rabbit Pellets) and water were available at all times.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The test material was applied to the skin of four groups of albino rabbits each (1344 – 2310 g). The test material was applied moistened with sufficient water to form a paste. The sample was applied to the intact abdominal skin area from which the fur had been removed with electric clippers. The sample was applied under a binder of rubber dental damming which was placed around the trunk of the animal. The trunk was wrapped securely with gauze and adhesive tape to keep the binder and test material in contact with the skin and to prevent ingestion. After 24 hr, the binders were removed and any unabsorbed material was removed by gentle sponging with a moistened towel.
Duration of exposure:
24 hr
Doses:
1000, 2150, 4640, 10000 mg/kg bw.
No. of animals per sex per dose:
4/dose
Control animals:
no
Details on study design:
The test material was applied to the skin of four groups of albino rabbits each (1344 – 2310 g). The test material was applied moistened with sufficient water to form a paste. The dosage levels were 1000, 2150, 4640, 10000 mg/kg bw. The sample was applied to the intact abdominal skin area from which the fur had been removed with electric clippers. The sample was applied under a binder of rubber dental damming which was placed around the trunk of the animal. The trunk was wrapped securely with gauze and adhesive tape to keep the binder and test material in contact with the skin and to prevent ingestion. After 24 hr, the binders were removed and any unabsorbed material was removed by gentle sponging with a moistened towel. The rabbits were observed for gross signs of systemic toxicity at several intervals during the day of application and for gross signs of dermal irritation and systemic toxicity daily thereafter for a total of 15 days. A gross necropsy was performed on animals dieing on-test. At the end of the 15-d observation, all rabbits were weighed, sacrificed by air embolism, and a gross necropsy performed.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
None due to test article. Four rabbits died from enteritis. See remarks.
Clinical signs:
Rabbits at the highest dose level appeared depressed after application of test material. Thereafter, these animals appeared normal. Rabbits at the 3 lower doses showed no clinical signs during dosing. No skin irritation was observed at removal of the test article.
Body weight:
Eleven of the 12 surviving rabbits showed overall weight gains of 100 - 500 grams. The remaining rabbit maintained its starting weight. Transient diarrhea was noted in 8 of these rabbits.
Gross pathology:
Gross necropies on the four animals that died on test were hampered by autolytic changes. Gross necropsies at scheduled sacrifice showed no gross lesions.

Any other information on results incl. tables

Four rabbits died between the 10th and 13thday of the study: 1 in the 1000 and 4640 mg/kg groups and 2 in the 2150 mg/kg group. Death was preceded by body weight loss and diarrhea, and attributed to enteritis, a common syndrome in laboratory rabbits. There were no other mortalities. The LD50 was determined to be > 10000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment