Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-01-09 to 1985-04-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conduction and documentation of study very acceptable. Study report available.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985
Reference Type:
publication
Title:
The acute toxicity and primary irri-tancy of 2,4-pentanedione
Author:
Ballantyne, B., Dodd, D.E., Myers R.C., Nachreiner, D.J.
Year:
1986
Bibliographic source:
Drug and Chemical Toxicology, 9, 133-146

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as reported in test report
Deviations:
no
Principles of method if other than guideline:
undiluted TS applied on the shaved dorsal skin (25 cm2) of 3-5  male or female New Zealand White rabbits/group; occlusive contact for 24  h; 14 d post application period; 5 doses tested.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,4-Pentanedione
- Substance type: industrial chemical
- Physical state: liquid
- Analytical purity: > 99%
- Impurities (identity and concentrations): not reported
- Lot/batch No.: 496500
- Expiration date of the lot/batch: not given
- Stability under test conditions: stable
- Storage condition of test material: not given

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 to 3.0 kg
- Fasting period before study: no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm2

REMOVAL OF TEST SUBSTANCE
- Washing (if done): removal of excess fluid
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2, 1 and 0.5 ml/kg bw
- Constant volume or concentration used: yes


VEHICLE not used
Duration of exposure:
24 h
Doses:
2, 1 and 0.5 ml/kg bw
No. of animals per sex per dose:
5 per sex and does
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: one hour, 7 and 14 days after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Moving average method of Thompson

Results and discussion

Preliminary study:
not reported
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
790 mg/kg bw
Based on:
test mat.
95% CL:
560 - 980
Sex:
male
Dose descriptor:
LD50
Effect level:
1 370 mg/kg bw
Based on:
test mat.
95% CL:
770 - 2 100
Mortality:
death occurred within 1-24 h  after application; 
Clinical signs:
signs of toxicity at 970 mg/kg or more: dilated   pupils, salivation and convulsions (high dose); local erythema, edema and  necrosis (persisted for 1-7 d) and scab formation at day 14; 
Body weight:
normal body weight gain; no effect on  body weight in survivors
Gross pathology:
dead animals showed red mottled lungs, patchy congestion of tracheal mucosa, and a few stomachs with superficial black  foci at necropsy.
Other findings:
- Organ weights: not affected by study

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Substance is harmful in contact with skin under the conditions used.
Executive summary:

Acetylacetone (2,4 -Pentanedione) was administered to groups of 5 male and 5 female New Zealand White Rabbits. The rabbits received the test material (1.41 and 0.812 ml/kg bw respectively) by retaining the material under impervious sheeting on the clipped intact skin of the trunk.

The LD50 for male rabbits receiving 2,4 -Pentanedione were 790 mg/kg bw for males and 1370 mg/kg bw for females. Erythema,. edema and a few instances of necrosis and scab formation were observed at the dose sites. Signas of toxicity included dilated pupils, bloody discharge from the mouth, salviation abd in one animal convulsions. Time to death ranged from 45 min to one day. Gross pathologic examination revealed mottled and red lungs, a few tracheas with red patches and a few stomache with black foci on the surface. The test substance is harmful in contact with skin under the conditions used.