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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:
1994-11-14 to 1994-11-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline 402

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 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive dressing according to former guideline
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: males 7 weeks, females 9 weeks
- Weight at study initiation: Males weighed 248-268g and the females weighed 232-281g
- Fasting period before study: Overnight prior dosing
- Housing: Individually 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.
- 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
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10x5cm on dorso lumbar region
- Type of wrap if used: Each dressing consisted of a gauze patch (approximately 4cm x 6cm x 4-ply) to cover the treated area, which was covered by a patch of plastic film (7.5cm x 5cm) and was held in position using adhesive bandage (approximately 25cm x 5cm). This was secured by two pieces of PVC tape (approximately 2.5cm x 20cm) wrapped around the animal.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with clean swabs of absorbent cotton wool soaked in clean warm water
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw
- Concentration (if solution): 95.6%


Duration of exposure:
24h
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 between one and four hours after application on the day of dosing and then once daily for systemic toxicity and skin irritation, up to day 15. The animals were weighed immediately before application of the test sample (day 1), and on 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:
There were no signs of systemic toxicity. Signs of slight skin irritation were observed in all animals including erythema, oedema and desquamation. All signs of irritation had completely regressed by day 8.
Body weight:
The majority of animals lost weight initially but all animals had exceeded their initial bodyweight by the end of the study.
Gross pathology:
Pelvic dilatation of the kidney was observed in one male and a reddened cervical lymph node was observed in one female. These are common spontaneous findings in rats of this age and strain and are considered not to be treatment related.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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