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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study conducted prior to development of GLP and OECD guideline, however methodology is comparable to current guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Conducted prior to development of GLP
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-formyl-2-methoxyphenyl isobutyrate
EC Number:
243-956-6
EC Name:
4-formyl-2-methoxyphenyl isobutyrate
Cas Number:
20665-85-4
Molecular formula:
C12H14O4
IUPAC Name:
4-formyl-2-methoxyphenyl isobutyrate
Test material form:
other: liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Isobutavan Y-09607
- Physical state: clear colourless liquid
- Received at laboratory on December17, 1982

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Young adult, SPF bred, albino rats (Cpb:WU; Wistar random) were used. The body weights of the males varied from 92-115g, those of the females from 82-90g. The rats were acclimatized to the laboratory conditions for at least 5 days prior to the test. The rats were housed in groups of five, males and females separated in stainless steel cages with grid bottom and front in a well ventilated room, maintained at 23°C.

Relative humidity was between 30 and 70%, lighting was artifical with a sequence of 12 hours lights and 12 hours dark. Tap water was freely availiable at all times, and they recieved stock diet ad libitum, except for the overnight period before treatment, when food was withheld.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered undiluted by gavage
Doses:
The test substance was administered in one single dose of 5.0 mL/kg body weight (equivalent to approximately 5000 mg/kg bw)
No. of animals per sex per dose:
Five male and female rats were used
Control animals:
no
Details on study design:
After treatment, the rats were observed frequently for signs of intoxication during the first 4 hours post treatment and thereafter at least once daily throughout the 14 day observation. The indiviual body weights were determined on day 0, 7 and 14. At the end of the observation period the survivors were killed and necropsied.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 40% mortality at the limit dose
Mortality:
Two males and two females died between 6 hours and 2 days after treatment.
Clinical signs:
Clinical observations during the first 4 post treatment hours revealed sluggishness and rough coats. Later on, encrustations around eyes and nostrils, signs of emaciation and coma were frequently observed. The survivors were reported to recover gradually and appeared healthy by study termination.
Body weight:
The Individual body weights on day 7 and 14 indicated normal growth.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute oral LD50 of isobutavan was found to be greater than 5000 mg/kg bw in rats.
Executive summary:

The acute oral toxicity of isobutavan was evaluated in 5 male and 5 female Wistar rats. The test substance was administered undiluted by gavage, at a dose of 5 mL/kg bw, equivalent to appoximately 5000 mg/kg bw. The rats were observed for mortality and signs of toxicity for 14 days after dosing. Necropsies were performed on survivors at study termination. Clinical signs of toxicity observed in the first 4 hours after administration included sluggishness and rough coats. Later, encrustations around the eyes and nostrils, emaciation and coma were frequently observed. Two males and two females died between 6 hours and 2 days after treatment. Individual bodyweights of survivors increased during the observation period. No abnormalities were detected at gross necropsy of survivors. Under the conditions of the study, the acute oral LD50 of isobutavan was found to be greater than 5000 mg/kg bw in rats.