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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 indicated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well-documented non-GLP study performed according to guideline similar to OECD Guideline 402. Only 2 animals per sex per dose level are used (instead of 5). Skin was abraded in half of the animals.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 2 instead of 5 animals per sex per dose level are used. Skin was abraded in half of the animals.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- State of aggregation : liquid
- Appearance : colourless to yellow brown
Specific details on test material used for the study:
OTHER SPECIFICS:
- Name of test material (as cited in study report): Aus 0213 4236-14-4 Alkaline Corrosive Liquid N2 Pad Urethane Catalyst
- Appearance: orange liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Pel-Freez, Inc., USDA No. 71-B-16, Rogers, Arkansas 72756
- Age at study initiation: young adult albino rabbits: approximately 10 - 13 weeks of age
- Housing: The rabbits were housed in suspended, wire-bottomed steel cages
- Diet (e.g. ad libitum): The rabbit were maintained on a standard laboratory diet: Purina Rabbit Chow Special, 5340, Ralston Purina Company, St. Louis, Missouri, 63188
- Water (e.g. ad libitum): Water was offered ad libitum
- Acclimation period: All rabbits were kept under observation in the laboratory for at least 7 days prior to testing

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- 24 hours prior to the dermal applications, the backs of the rabbits were clipped free of hair with electric clippers. The animals were then returned to their cages to await testing on the following day. The 24-hour waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close-clipping procedure and permitted healing of any microscopic abrasians possibly produced during the process. At the end of the 24-hour recovery period, just prior to the application of the test material, the clipped test skin site of one half of the animals was abraded (with a slightly bent tip of a hypodermic needle) by making a series of parallel, epidermal abrasions, every 2 or 3 centimeters longitudinally. These abrasions were made sufficiently deep to penetrate the stratum corneum, but not to disturb the derma.
- Area of exposure: backs of the rabbits
- % coverage: 30% of the total body surface area
- Type of wrap if used: The test site was covered by wrapping the trunk of each animal with an impervious plastic sleeve which was securely taped in place. This plastic wrap insured close contact of the epidermis and the test material. To prevent oral ingestion of the test material, each animal was fitted with a lightweight, flexible plastic collar which was worn throughout the observation period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test material remained in contact with the skin for 24 hours. At the end of this period, the plastic sheeting was taken off and all removable residual test material was washed off with warm tap water.
Duration of exposure:
24 hours
Doses:
1350, 2025, 3038 and 4556 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
One hour after test material removal, the test skin sites were examined for local skin reactions. Observations for mortality and behavioral abnormalities were made daily for a total of 14 days following the dermal exposure. Initial, 7- and 14-day body weights were recorded. In addition, local skin reactions were evaluated at 7 and 14 days. A necropsy examination was conducted on all animals.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 038 mg/kg bw
Based on:
test mat.
Remarks on result:
other: SD = +/- 356.4 mg/kg
Mortality:
1350 mg/kg group: 0/4 dead
2025 mg/kg group: 0/4 dead
3038 mg/kg group: 2/4 dead (both exposed to intact skin)
4556 mg/kg group: 4/4 dead
Clinical signs:
Adverse body effects, varying in degree of severity, were noted in several of the animals at 7 and 14 days. The test material was slightly irritating to the skin of the albino rabbit. Skin reactions at 24 hours were characterized by barely perceptible to pale red erythema and slight edema. Desquamation was observed at the test skin sites of most of the surviving animals at 7 and 14 days.
Hypoactivity was observed in the 1350, 2025 and 4556 mg/kg dose group
Hyperirritability was observed in all dose groups
Diarrhea, slight miosis, hindquarter paralysis and emaciation were observed in the 3038 mg/kg dose group
Loss of righting and tremors were observed in the 4556 mg/kg dose group
Body weight:
No data
Gross pathology:
1350 mg/kg dose group: jejunum distended with gas; perineum stained with urine in one male
2025 mg/kg dose group: perineum stained with feces in one male
3038 mg/kg dose group: moderate postmortem autolysis in one male and perineum stained with feces; emaciation; moderate postmortem autolysis
4556 mg/kg dose group: Diffuse yellow discoloration of all lobes of the liver; hemorrhagic-like foci (1 mm) within mucosa of glandular region of the stomach in one male and hemorrhagic-like foci (1-3 mm) within the mucosa of the stomach in one female.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In this study an acute dermal LD50 value of 3038 mg/kg bw was determined in rabbits after exposure to the test substance. Therefore, the substance is considered not to be classified.