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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-compliant near-guideline study, no restrictions, fully adequate for assessment. However, no analytical purity of the tested ETBE sample was reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Ethyl-tert-Butyl Ether (ETBE), identification no. LF-9072, was purchased from Aldrich Chemical Company (Milwaukee, WI; Lot No. 00423HW) and received July 12, 1989; it was stored refrigerated (approximately 4°C) and was a clear, colorless liquid.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
New Zealand albino rabbits were purchased from Johnson Rabbit Ranch (Wilkinson, IN) for use in this study. Upon arrival (5/24/89), the rabbits were held in quarantine for approximately twelve weeks and examined carefully to ensure their health and suitability as test subjects.
Each rabbit was provided approximately 150 g of Purina Lab Rabbit Chow HF #5326 (Ralston Purina Co., St. Louis, MO) daily. Reverseosmosis- purified water was provided ad libitum by means of an automatic watering system.
The rabbits were housed individually in stainless steel cages measuring 61.0 x 45.5 x 41.0 cm. Poly pads (12 ply, Shepherd Specialty Papers, Kalamazoo, Ml) were placed in the pan below the stainless steel mesh floor of each animal cage to absorb liquids. Air-conditioned animal rooms were maintained at approximately 22°C and 60% relative humidity. Fluorescent lighting was provided for 12 hours followed by 12 hours of darkness.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours prior to study initiation, fur was clipped from an area of approximately 240 cm2 on the back of each rabbit and the skin was examined for abnormalities. Care was taken to avoid abrading the rabbits' backs.
ETBE (undiluted, equivalent to 2 g/kg bw) was applied uniformly to the shaved dorsum of each rabbit, covered with a surgical dressing under plastic film (occlusion) and held in place by elastic adhesive bandage for 24 hr. The application site was cleaned with light mineral oil and towel dried on removal of the patch.



Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
All test rabbits were observed approximately 1/2, 1-1/2, 2-1/4, 3-3/4 and 5 hours after dosing and at least once per day for 14 days after removal of the wrappings.
Body weights recorded pre-test, weekly and at termination.
The treatment site was observed for signs of dermal irritation on 1, 7 and 14 d after post-dosing.
All rabbits were euthanized by anesthetic overdose at the end of the observation period (8/30/89) and necropsied.
Statistics:
Statistical analyses were used to analyse the results: calculation of standard deviations.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
Dermal irritation (i.e., edema and erythema) was observed within the application sites of all rabbits following removal of the wrappings. Eschar formation was observed at the application site of most rabbits within 5 to 7 days after test article administration and was ultimately noted in all study animals. Hair growth eventually masked the application sites of some of the rabbits. Complete recovery from all signs of dermal irritation was not evident in any rabbit at study termination.
A transient increase in respiration was observed in three male and four female rabbits 30 minutes after test article administration, but not at subsequent observation times.
Body weight:
The initial mean body weights of the male and female rabbits were 3.73 kg and 4.02 kg, respectively. Mean body weights increased slightly during the study.
Gross pathology:
Gross pathological findings were within normal limits in seven rabbits. Three females had multiple red foci on the lungs at necropsy, but this was not considered to be treatment related.

Applicant's summary and conclusion