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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
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.
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
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
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.
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.
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.
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 .

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 250 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and documented study, fully adequate for assessment. Performed guideline conform and according to GLP in a recognised contract research organisation.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt., 1103 Budapest, Hungary
- Age at study initiation: 9 - 10 weeks
- Fasting period before study: not reported
- Diet : ad libitum
- Water (tap water) : ad libitum
- Acclimation period: 6 days to lab conditions plus 7 - 9 days to the test apparatus


ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: 30 - 70%
- Room air change: 10 - 15 times per hour
- Light/dark cycle: 12/12 h
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
The animals were exposed to an atmosphere of the test item generated according to the system and flow rates determined during the technical trials, for a single, four-hour period. The four-hour exposure period was not started until theoretical chamber concentration equilibration of 0.5 minutes, calculated according to Silver S. D. (1946) has been reached. Based on the experience gained in the trial runs 5 minutes were let for equilibration. The periods when exposures were interrupted to re-fill the dust generator and for cleaning of the exposure system from deposited test item were also not taken into account as part of the four-hour exposure. In order to achieve the required concentration during exposure the test item input rate was adjusted according to the actual concentration level indicated by the monitoring system.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Aerosol Light Scattering Photometer calibrated by gravimetry of samples obtained on aerosol filters
Duration of exposure:
4 h
Concentrations:
5470 mg/m³
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: observations for morbidity/mortality twice daily; body weights on days 0, 1, 3, 7, and 14
- Necropsy of survivors performed: yes, complete examination of abdominal and thoracic cavities
- Other examinations performed: clinical signs : behaviour, mucous membranes, respiratory system
Statistics:
not reported
Preliminary study:
In a pre-test with each one male and one female rat a 4 hour exposure at 4.33 mg/l air did not cause mortality or severe clinical signs. Accordingly, a limit test was performed.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.47 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
no mortality
Clinical signs:
other: directly after exposure animals showed slight dyspnea. One day after exposure until the end of the observation period there were no clinical signs observed.
Body weight:
In all male and female animals body weight loss was observed on day 1 after exposure. Body weight recovered in the following days and after 14 days all animals had higher body weights than prior to treatment.
Gross pathology:
no findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and documented study, fully adequate for assessment. Performed guideline conform and according to GLP in a recognised contract research organisation.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
small deviations without effect on study performance and result.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 170 - 256 g; females: 246 - 287 g
- Fasting period before study: no
- Diet (pelleted): ad libitum
- Water (tap water): ad libitum
- Temperature: 22 +/- 2°C
- Humidity: 45 - 65%
- Room air change: approx. 10 times per hour
- Light/dark cycle: 12/12 h
Type of coverage:
occlusive
Vehicle:
other: powder was moistened with water
Details on dermal exposure:
TEST SITE
- Area of exposure: > 10% of body surface; the dorsal area of the trunk was shaven prior to application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): removal of remnants on the skin with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex and dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: 8 days before application, on the day of application, 8 and 15 days after application
- Frequency of observations: 4 times on the day of treatment, once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
dose selection was based on LD50 values determined with the read-across substance 2,4-pentanedione.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
No test item related clinical findings were noted during application and until the end of the observation period.
Body weight:
Normal body weight gain.
Gross pathology:
In females no macroscopic findings were noted during necropsy. Application sites were without any findings, as well as subcutaneous tissue.
In males macroscopic findings were assumed to have been incidental and not test item related. Application sites were without any findings, as well as subcutaneous tissue.
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50 in rats > 2000 mg/kg body weight
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

The studies performed on the acute toxicity of the substance after administration by the oral route show that bis(pentane-2,4-dionato)calcium has to be regarded harmful if swallowed, cat. 4. Based on the results of the studies for dermal and inhalation acute toxicity no classification is required.