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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-11-14 to 1994-11-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DIBK (Diisobutyl Ketone)
- Physical state: Clear liquid
- Analytical purity: 95.6%
- Lot/batch No.: 02264 00010

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Barriered Animal Breeding Unit, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: 7 weeks
- Weight at study initiation: Males weighed 241-255g and the females weighed 180-182g
- Fasting period before study: Overnight prior dosing
- Housing: In suspended cages (26.5cm x 50.0cm x 20.7cm). The cages were made of stainless steel, with one solid sheet side and a mesh front, floor, rear and remaining side. The sexes were housed separately with a maximum of five rats per cage.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 45±15
- Air changes (per hr): 25-30/h
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of systemic toxicity once within 2 hours of dosing and again between 4 and 7 hours after dosing. Subsequent observations were made once daily, or twice daily whenever there were significant signs of toxicity, up to day 15. The animals were weighed on the day before dosing (day -1), the day of dosing (day 1) and days 3, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities
Clinical signs:
Signs of slight and non-specific systemic toxicity including piloerection, sides pinched in (slight indentation in the sides of the abdomen) and urinary incontinence were observed in female rats. No signs of systemic toxicity were evident in male rats.
Body weight:
All animals gained weight consistently after an initial weight loss due to the overnight fast.
Gross pathology:
Pelvic dilatation of the kidney was observed in one male and pale areas of the lung was observed in one female. These are common spontaneous findings in rats of this age and strain and and are considered not to be treatment related.

Any other information on results incl. tables

The acute oral median lethal dose LD50 of Diisobutyl Ketone (DIBK) was estimated to be in excess of 2000mg/kg to male and female rats. According to DSD and CLP, DIBK has not to be classified.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of DIBK in rats is greater than 2000 mg/kg. Hence, no classification for acute oral toxicity is required according to EU criteria.