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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:
November 14 - December 13, 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline and GLP. No CoA included in the report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
- a maximum dose volume of 20 ml/kg was used for a non aqueous solution, 10 ml/kg is recommended.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: Ca-Acetylacetonate
Batch No.: 106002
Physical state: Powder
Purity: 98%

No CoA included in the report.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Zentralinstitut fur verzuchstierzucht GmbH
- Age at study initiation: no data
- Weight at study initiation: m: 239-271g f: 150-180g
- Fasting period before study: yes, from 16 hours before until 3-4 hours after the study
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon typy III)
- Diet (e.g. ad libitum): ad libitum, Ssniff Spezialdiaten GmbH
- Water (e.g. ad libitum): ad libitum, drinking water as for human consumption
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: November 14 - December 13, 1991

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5% and 7.5% suspension
- Amount of vehicle (if gavage): 20 ml/kg
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg
Doses:
Range finding: 2000, 1500, 1000 mg/kg bw
Final study: 1500, 1000 mg/kg bw
No. of animals per sex per dose:
Range finding: 2 females
Final study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined at the following post-treatment intervals 10 min., 30 min., 1, 2, 6, 24 hoours and daily thereafter once daily up to day 14. The body weights were recorded immedialtly before treatment (day 0) and surviving animals were reweighed on day 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
LD50 values were calculated accoring to methods of linear regression.

Results and discussion

Preliminary study:
There were 4 deaths in the preliminary study. 0 at 1000 mg/kg bw, 2 at 1500 mg/kg bw and 2 at 2000 mg/kg bw.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 417 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 250 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died at 1000 mg/kg bw. All males died at 1500 mg/kg bw and 3 females died at 1500 mg/kg bw.
Clinical signs:
Severe abonormal clinical intoxication signs were observed up to 24h p.a. The most frequent findings were reduced activity, abnormal body posture, decreased body and abdominal tone, impaired respiration, tremor, tonic and clonic convulsions.
Body weight:
Weight gains were normal in all surviving animals.
Gross pathology:
Surviving animals showed no abnormalities at necropsy. Animals found dead showed; redness and swelling of the gastric mucous membrane, congestion in liver and lung, urinary retention, dicoloration of the renal pelvis and spleen.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 male 1250 mg/kg, females 1417 mg/kg.
Executive summary:

The acute oral toxicity of Ca-Acetylacetonate was investigated in 2 groups of Wistar rats, each containing 5 males and 5 females. On the basis of the range finding results, the animals were given a single oral administration at doses of 1000 mg/kg and 1500 mg/kg. Clinical observations were conducted at regular intervals during the 14 -day observation period. Body weights were measured 0, 7 and 14 days p.a. Gross pathological examinations were performed immediatly on animals found dead or killed in extremis and at termination on surviving animals.

None of the animals died at 1000 mg/kg bw. All males died at 1500 mg/kg bw and 3 females died at 1500 mg/kg bw. Severe abonormal clinical intoxication signs were observed up to 24h p.a. The most frequent findings were reduced activity, abnormal body posture, decreased body and abdominal tone, impaired respiration, tremor, tonic and clonic convulsions. Weight gains were normal in all surviving animals. Surviving animals showed no abnormalities at necropsy. Animals found dead showed; redness and swelling of the gastric mucous membrane, congestion in liver and lung, urinary retention, dicoloration of the renal pelvis and spleen.

The LD50 for males is 1250 mg/kg and for females is 1417 mg/kg .