Tetrakis(pentane-2,4-dionato-O,O')zirconium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Feb 2020 - 10 Apr 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

November 2000, including the most recent revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrakis(pentane-2,4-dionato-O,O')zirconium

EC Number:

241-510-5

EC Name:

Tetrakis(pentane-2,4-dionato-O,O')zirconium

Cas Number:

17501-44-9

Molecular formula:

C20H28O8Zr

IUPAC Name:

2,4,8,8,10,10,13,15-octamethyl-1λ³,5λ³,7λ³,7λ³,11λ³,11λ³,12λ³,16λ³-octaoxa-6-zirconadispiro[5.5⁶.5⁶.5⁶]henicosa-1,4,7,7,10,10,12,15-octaene-6,6,6,6-tetrakis(ylium)-3,9,9,14-tetraide

Test material form:

solid: particulate/powder

Details on test material:

- Identification: Zirconium (IV) acetylacetonate (Zr-acac)
- Description: White to off-white powder
- Storage conditions: At room temperature

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8-9 weeks old
- Weight at study initiation: 149 to 179 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: ad libitum, municipal tap-water
- Acclimation period: at least 5 days
- Microbiological status: SPF-Quality

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 36-53
- Air changes (per hr): ≥10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 Mar 2020 To: 10 Apr 2020

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION:
Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
An adjustment was made for specific gravity of the vehicle (specific gravidity propylene glycol: 1.036). No correction was made for the purity/composition of the test item.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose level was selected based on available toxicity data of the test item.

Doses:

The first group was treated at a dose level of 300 mg/kg. Based on the results, two additional groups were dosed, one at 2000 mg/kg and one at 300 mg/kg.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes, descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Not performed

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, all animals were found dead on Day 1 post-treatment.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: At 2000 mg/kg hunched posture, erected fur, moderate salivation, abnormal respiratory rate, lying on the side and decreased activity was noted for all animals on day 1. At 300 mg/kg hunched posture and erected fur was noted for all six animals on Day 1 an

Gross pathology:

No test item related abnormalities were found at macroscopic post mortem examination of the animals. Abnormalities of the kidney (dilatation bilateral) and the thymus (focus dark red multifocal) were found in one animal that died during the study, however, these findings are more often seen in rats of this strain in this type of study and therefore no toxicological relevance was attached to these findings.

Applicant's summary and conclusion

Interpretation of results:

other: acute tox. 4

Remarks:

according to Regulation (EC) No 1272/2008

Conclusions:

In an acute oral toxicity study in Wistar Han rats according to OECD TG 423 the oral LD50 value of Zirconium (IV) acetylacetonate (Zr-acac) was established to be within the range of 300-2000 mg/kg body weight.

Executive summary:

An acute oral toxicity study was performed in rat according to OECD TG 423 and in accordance with GLP principles. Initially, Zirconium (IV) acetylacetonate (Zr-acac) was administered by oral gavage to three

female Wistar Han rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed, one at 2000 mg/kg and one at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 15).

At 2000 mg/kg, all animals were found dead on Day 1 post-treatment. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, erected fur, moderate salivation, abnormal respiratory rate, lying on the side and decreased activity was noted for all animals on day 1. At 300 mg/kg, hunched posture and erected fur was noted for all six animals on day 1 and for three animals also between days 2 and 4. The body weight gain shown by the surviving animals over the study period was considered

to be similar to that expected for normal untreated animals of the same age and strain. No test item related abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Zirconium (IV) acetylacetonate (Zr-acac) in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight.

According to OECD TG 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.