Bis(pentane-2,4-dionato-O,O')zinc

Endpoint summary

Description of key information

After oral application of 2000 mg/kg bw of the test substance 1 of 3 animals died.

Thus the LD50 oral can be determined as > 2000 mg/kg bw.

In a read-across approach an inhalative toxicity study with bis(pentane-2,4 -dionate)calcium is used for classification.

It can be stated that the LC50 inhalative is higher than 5.47 mg/L.

In a read-across approach an dermal toxicity study with bis(pentane-2,4 -dionate)calcium is used for classification.

It can be stated that the LD50 dermal is higher than 2000 mg/kg bw.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Three test animals were purchased from Harlan Winkelmann GmbH, 33178 Borchen, Germany

Route of administration:

oral: gavage

Vehicle:

other: 2 mL of sesame oil

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

temperature: 19 - 24 °C
humidity: 30 - 70 %
light/dark: 12/12 h
acclimatization time: 5 days

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1 of 3 animals died at day 1 after application. 2 animals survived the test period of 15 days.

Interpretation of results:

GHS criteria not met

Conclusions:

After application of 2000 mg/kg bw of the test substance 1 of 3 animals died.
Thus the LD50 can be determined as > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

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.

Key result

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

Conclusions:

It can be stated that the LC50 inhalative is higher than 5.47 mg/L.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

Based on the structural similarities, a read-across to bis(pentane-2,4-dionato) calcium is acceptable.

Reason / purpose for cross-reference:

read-across source

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.

Key result

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

Conclusions:

It can be stated that the LC50 inhalative is higher than 5.47 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

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:

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:

It can be stated that the LD50 dermal is higher than 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

Based on the structural similarities, a read-across to bis(pentane-2,4-dionato) calcium is acceptable.

Reason / purpose for cross-reference:

read-across source

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:

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:

It can be stated that the LD50 dermal is higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed