Bis(pentane-2,4-dionato)calcium

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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

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 or test system 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:

other: 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.

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

Link to relevant study records

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

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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

Link to relevant study records

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

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

small deviations without effect on study performance and result.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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:

other: No test item related clinical findings were noted during application and until the end of the observation period.

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

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.