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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Oct. 2000 - Febr. 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The accordance of the study with its protocol, the OECD Guideline 401 and the Principles of Good Laboratory Practice (GLP) is guaranteed.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate
EC Number:
296-417-2
EC Name:
1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate
Cas Number:
92671-67-5
Molecular formula:
C14H19NO4
IUPAC Name:
8-methyl-3-(propan-2-yl)-1H,3H,5H-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate
Details on test material:

- Substance type: Intermediate
- Physical state: solid
- Analytical purity: not stated
- Impurities (identity and concentrations): not specified
- Lot/batch No.:
- Expiration date of the lot/batch: not stated

- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Other:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Gartenstr. 27, D-33178 Borchen
- Fasting period before study: food was withheld overnight before the day of administration
- Housing: the rats housed individually in Makrolon cages (800 cm^2, height 17 cm)
- Diet (e.g. ad libitum): twice, 8 g daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: 5 days

Administration / exposure

Route of administration:
other: diluted in vehicle
Vehicle:
ethanol
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg



Doses:
Group I (10 rats, 5 males and 5 females) 2000 mg/kg applied
Group II (5 rats, 5 females) 1333 mg/kg applied
Group III (5 rats, 5 females) 890 mg/kg applied
Group IV (5 rats, 5 females) 590 mg/kg applied
Group V (5 rats, 5 males) 1333 mg/kg applied
No. of animals per sex per dose:
see above - doses
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 15 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not relevant

Results and discussion

Preliminary study:
no preliminary study
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 850 mg/kg bw
Mortality:
The following times of death after administration of Isobutyralacetat were recorded:
2000 mg/kg: 4 of 10
1333 mg/kg: 0 of 10
890 mg/kg: 2 of 5
590 mg/kg: 1 of 5
Clinical signs:
disturbance of coordination with hyperactivity,
lateral position, strong spasm, pain screaming, therefore euthanasia for human reasons,
ruffled fur, hard breathing, diarrhoea, severe apathy, hunched posture
Body weight:
no specific findings
Gross pathology:
The post-mortem findings did not show any macroscopic organ changes
Other findings:
no other findings

Any other information on results incl. tables

no additional remarks

Applicant's summary and conclusion

Interpretation of results:
other: categorie V GHS
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Isobutyralacetate needs not to be classified neighter according to 67/548/EEC nor 1272/2008/EEC. Category 5 has to be selected according to OECD GHS
Executive summary:

The test substance dissolved in diluted absolute ethanol was administered orally in two doses within less than 3 hours to five groups of Sprague Dawley rats:

Group I (l0 rats, 5 males and 5 females) 2000 mg/kg applied

Group II (5 rats, 5 females) 1333 mg/kg applied

Group III (5 rats, 5 females) 890 mg/kg applied

Group IV (5 rats, 5 females) 590 mglkg applied

Group V (5 rats, 5 males) 1333 mg/kg applied

Isobutyralacetat, a solid, was dissolved immediately prior to administration in pure ethanol. Therefore, Group VI demonstrates the inoffensiveness of administrating ethanol: Group VI (4 rats, 2 males and 2 females)

Acute toxicological synlptoms attributed to the exposure to Isobutyralacetat could be observed in 4

out of ten rats dosed with 2000 mg/kg, in 0 rats out of 10 dosed with 1333 mg/kg, in 2 out of 5 rats

dosed with 890 mg/kg and in 1 out of 5 rats dosed with 590 mg/kg. The post-mortem findings did

not show any macroscopic organ changes. The LD50 value of Isobutyralacetat was determined to

2824 mg/kg for the female sex according to Probit Analysis.