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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No guideline stated, however study appears to have been well conducted and appears to be similar to OECD 402. The study predates GLP. No details on test material.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1962
Report Date:
1962

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Principles of method if other than guideline:
- Only 4 animals with intact skin were used per dose.
- Occlusive dressings were used.
GLP compliance:
no
Remarks:
pre-dates GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rabbit
Strain:
other: Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.4 - 2.3 kilograms
- Housing: Throughout the observation period the animals were housed individually in metal cages with wire mesh floors elevated above the droppings
- Diet/water: Feed and water were available at all times.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: Undiluted test material was applied under rubber dental damming. The trunks of the animals were wrapped securely with gauze and adhesive tape binders to prevent ingestion of the applied material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Abdominal skin areas were sponged with Wesson Oil to remove any residue.
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
The dosage levels tested were 10.3, 15.4, 20.5, and 25.6 g/kg of body weight.
No. of animals per sex per dose:
4 with intact skin and 4 with abraded skin per dose level.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for gross signs of systemic toxicity daily for a period of 14 days. At the end of the observation period, the animals were weighed.
- Necropsy of survivors performed: yes
- Other examinations performed: At the end of the observation period, the animals were sacrificed by air embolism and gross autopsies were performed.
Statistics:
nda

Results and discussion

Preliminary study:
n/a
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 25 600 mg/kg bw
Based on:
test mat.
Mortality:
There were no fatalities at any dosage level tested.
Clinical signs:
The animals at all dosage levels tested exhibited normal behavior during the day of application of the test material and daily thereafter, throughout the study.
Body weight:
The animals maintained or showed an increase over their respective initial body weights for the 14-day interval.
Gross pathology:
Gross autopsies performed upon each of the animals at termination of the study revealed normal internal organs and body cavities.
Other findings:
The 24-hour exposure to the test compound produced a moderate degree of dermal irritation characterized by severe erythema and edema. These signs, in general, had subsided within nine or 10 days following removal of the binders. Beginning at this time however, the treated skin areas showed drying, and desquamation was observed which persisted throughout the remainder of the observation period.

Any other information on results incl. tables

The study also tested the Dermal Application of abraded Skin, however it should be noted that these results are not suitable for classification according to recognised guidelines. The results are as follows:

No fatalities attributable to the test compound occurred at any dosage level tested. A single fatality which occurred at the 10.3 g/kg level within 12 to 24 hours following dosage was attributed to a previously contracted gastro-intestinal disorder. The acute dermal LD50 of the test material when applied to the abraded skin of rabbits is therefore greater than 25.6 g/kg of body weight.

With the exception of the fatality at the low level, each of the animals exhibited normal behavior during the day of application of the test material and daily thereafter throughout the 14-day observation period. In addition, each of the animals maintained or showed an increase over its respective initial body weight.

The 24-hour exposure to the test compound produced on the abraded rabbits a moderate degree of skin irritation characterized by severe edema and erythema. In addition, the abrasions showed purulent exudates. The exudates had dried and the abrasions had begun to heal within an additional two or three days. The erythema and edema had in general subsided within nine or 10 days. At this time, however, the treated skin areas showed appreciable drying accompanied by desquamation; these signs persisted thereafter.

Gross autopsies performed upon each of the animals at termination of the study revealed normal internal organs and body cavities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of the test material when applied to the intact skin of rabbits is greater than 25.6 g/kg of body weight.

Executive summary:

Eight groups of four albino rabbits of either sex, weighing between 1.4 and 2.3 kilograms (kg) were used to evaluate the dermal toxicity of the test material. Four dosage levels were administered; each level was administered to a group of four animals whose closely clipped abdominal skin was left intact and to a corresponding abraded group. The dosage levels tested were 10.3, 15.4, 20.5, and 25.6 g/kg of body weight. The sites were occluded for 24 hours and then the dressings were removed and the sites washed with Wesson oil.

For the intact skin doses there were no deaths, signs of toxicity, weight loss or gross abnormalities at any dose level tested.

The acute dermal LD50 of the test material when applied to the intact skin of rabbits is greater than 25.6 g/kg of body weight.

The test material is dermally non-toxic within the meaning of the Federal Hazardous Substances Labeling Act.