Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 1980 to April 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed under GLP conditions with only 3 days observation.
Cross-reference
Reason / purpose:
reference to same study

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The procedure involved the application of undiluted test material (at three dose levels) to the intact skin of sexually mature male rabbits. Ten animals, randomly selected, were used in each group. A fourth group of rabbits served as the sham control. Animals were exposed to the test material (0.5, 1.5 and 4.5 mL/kg bw) for 24 hours. They were sacrificed 72 hrs after initial application. Tissues that were collected during necropsy were evaluated histologically on a blind basis. Complete blood count was determined and evalated statistically.
GLP compliance:
yes (incl. certificate)
Test type:
other: Multi-dose acute percutaneous toxicity in rabbits

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
I.D. Number: J0165.01
Storage conditions: room temperature in glass bottle
Characteristics: Colorless liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
The animal maintenance was according to DHEW Standards in a USDA registered, AAALAC accredited facility.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The appropriate amount of test material was applied to a pre-cut patch (pad with Blenderm backing) and placed on the clipped back of each rabbit. dental dam was placed over the entire test site and held in place by several wrappings of Elastoplast tape. The animals were placed in Newmann harness and returned to their cages for 24 hours. After 24 hours , the harness and wrapping were removed. The test site were rinsed off under a sink with tepid water for 25-30 seconds and were blotted with paper towels. Approximately 30 minutes after the test sites were dry, teh test sites were evaluated for skin irritation.
Duration of exposure:
24 hopurs
Doses:
Group I: Control
Group II: 4.5 mL/kg
Group III: 1.5 mL/kg
Group IV: 0.5 mL/kg
No. of animals per sex per dose:
10 male animals per test group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 3 days after dosing
- Frequency of observations: Skins were graded 30 minutes aftre removal of the patches and again 3 days aftre dosing. Body weight at start and end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, skin reaction, hematology
Statistics:
Where appropriate, the results were compared statistically using the method of analysis of variance at <= 0.05 (G.W. Snedecor and W.G. Cochran in statistical Methods, P.258, Iowa State U. Press, 1978).

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD0
Effect level:
>= 4.5 mL/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the course of the study.
Clinical signs:
No test article related changes in normal behavior or physiological processes were observed during the study.
Body weight:
The body weights of the animals in the four groups were not significantly different either before the study started or at the 3-day weighing.
Gross pathology:
No test article related gross lesions were observed at necropsy.
Other findings:
Only slight irritation was observed at 24 hours, and moderate irritation was reported after 72 hours in all treated groups. Immediately prior to sacrifice, blood was collected from the vena cava of each animal and checked for Hgb, Hct, WBC, RBC, and differential leukocyte counts. Organ weights were determined for testes with and without epididymis, and for liver, heart, kidneys and brain. The testes, epididymis, ductus deferens, seminal vesicles, prostate and heart were further subjected to histopathological examination. There were no compoundrelated effects on body weight, organ weights, and blood morphology, and no adverse effects observed at gross necropsy or histopathological examinations

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on the sudy results, the dermal LD50 in rabbits is considered to be greater than 4.5 mL/kg (equivalent to 4000 mg/kg)
Executive summary:

Sexually mature male New Zealand albino rabbits were exposed dermally to doses of alkyl (Cl2-C14) glycidyl ether, ranging from 0.5 to 4.5 ml/kg (equivalent to 4 g/kg). The test material was applied undiluted. There was no mortality. Only slight irritation was observed at 24 hours, and moderate irritation was reported after 72 hours in all treated groups. Immediately prior to sacrifice, blood was collected from the vena cava of each animal and checked for Hgb, Hct, WBC, RBC, and differential leukocyte counts. Organ weights were determined for testes with and without epididymis, and for liver, heart, kidneys and brain. The testes, epididymis, ductus deferens, seminal vesicles, prostate and heart were further subjected to histopathological examination. There were no compoundrelated effects on body weight, organ weights, and blood morphology, and no adverse effects observed at gross necropsy or histopathological examinations.