Carbonyl(pentane-2,4-dionato-O,O')(triphenylphosphine)rhodium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 July 2020 - 12 August 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 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17 Dec 2001

Deviations:

yes

Remarks:

temperature in animal room was 20 - 26°C instead of 20 - 24°C for several hours on several days due to insufficient capacity of the air conditioning system during a summer heat wave. This deviation does not affect the validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

30 May 2008

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carbonyl(pentane-2,4-dionato-O.O')(triphenylphosphine)rhodium

IUPAC Name:

Carbonyl(pentane-2,4-dionato-O.O')(triphenylphosphine)rhodium

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Acetylacetonatocarbonyl(triphenylphosphine) Rhodium (I)
- Molecular weight (if other than submission substance): 492.32 g/mol
- Physical state: Yellow solid
- Analytical purity: Not reported

Specific details on test material used for the study:

purity: 100%

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar Han

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Janvier Labs CS4105 Le Genest Saint Isle 53941 Saint Berthevin Cedex / France
Females were nulliparous and non-pregnant, Age (beginning of treatment) 8 - 12 weeks
At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.
Housing: groups of one to five rats (of the same sex and dose group)
Cage Type: Makrolon Type IV, with wire mesh top
Bedding: granulated soft wood bedding
Feed: 2018C Teklad Global 18% protein rodent diet
(certified), ad libitum
(except for overnight fasting prior to dosing; diet was returned immediately after dosing was complete)
Water: tap water, ad libitum
Environment: temperature 22 + 2°C (except for deviations)
relative humidity approx. 45-65%
(with the aim of 50 – 60%)
artificial light 6.00 a.m. - 6.00 p.m.
ventilation: at least eight air changes per hour
Environmental enrichment: provided throughout the study period (e.g., wooden chew blocks, fun tunnels or suitable nesting material)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The different test item concentrations were prepared individually. Homogeneity of the test item in vehicle was maintained during treatment using a magnetic stirrer.
The test item was formulated at a concentration of 30 and 200 mg/mL in the vehicle and administered at a constant dose volume of 10 mL/kg body weight. Grinding of the test item in a mortar was used to formulate the test item.
Test substance formulations were freshly prepared on the day of dosing, issued at room temperature and administered as soon as possible (within 4 hours of preparation). The formulations were assumed to be stable for this period unless specified otherwise by the Sponsor.
Samples of test substance formulations were not taken for analysis and consequently the homogeneity, concentration and stability of the test item were not determined.

Doses:

Dose administration was once orally by gavage (feeding needle). The volume administered did not exceed 10 mL/kg b.w.
In the absence of data regarding the toxicity of the test item 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.
Two single animals were treated as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
300 30 10 1
2000 200 10 1

In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
2000 200 10 4

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

No. of animals per sex per dose:

4 females at the maximum tolerated dose

Control animals:

no

Details on study design:

Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days. All animals were observed for 14 days after dosing.
The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation for all individual animals. If applicable, the time of death/humane kill was recorded as precisely as possible. Observations included changes in the skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Animals were sacrificed by carbon dioxide asphyxiation followed by cervical dislocation.
Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14, or (if applicable) at death (unscheduled).
A gross necropsy was performed on all animals that died or were humanely killed during the study (if applicable) and at the end of the in-life part. Any macroscopic abnormalities were recorded. Routinely no organs or tissues were retained.

Statistics:

The test item is classified according to Annex 3 of the OECD Guidelines for Testing of Chemicals No. 420 ‘Acute Oral Toxicity – Fixed Dose Procedure’ (adopted 17 December 2001) as shown in the Flow Chart in Annex 2.
Evaluation of data includes the identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of toxic effects of evident toxicity are described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were identified.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:

In the absence of data regarding the toxicity of the test item 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.
 
Two single animals were treated as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
300 30 10 1
2000 200 10 1

In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
2000 200 10 4

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

300 mg/kg: Enlarged mesenteric lymphnodes were noted for this animal.
2000 mg/kg: In one animal (animal numer 2) increased fat tissue in the abdomen was noted. No abnormalities were noted in any other animal at the macroscopic examination.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of Carbonyl(pentane-2,4-dionato-O,O’) (triphenylphosphine)rhodium was demonstrated to be greater than 2000 mg/kg body weight. The substance does not need to a classification for acute toxicity under EU CLP.

Executive summary:

A study was performed to assess the acute oral toxicity of Carbonyl(pentane-2,4-dionato-O,O’) (triphenylphosphine)rhodium to the rat.

Following a sighting test at dose levels of 300 mg/kg b.w. and 2000 mg/kg b.w. in one female rat per dose group, a further group of four fasted females was given a single oral dose of Carbonyl(pentane-2,4-dionato-O,O’) (triphenylphosphine)rhodium, as a suspension in corn oil, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity noted in the animals.

Body Weight:All animals showed expected gains in body weight.

Necropsy:In the animal treated with 300 mg/kg b.w. enlarged mesenteric lymphnodes were noted and in one animal treated with 2000 mg/kg b.w. increased fat tissue in the abdomen was noted. No abnormalities were noted in the remaining animals.

The acute median lethal oral dose (LD₅₀) to rats of Carbonyl(pentane-2,4-dionato-O,O’) (triphenylphosphine)rhodium was demonstrated to be greater than 2000 mg/kg body weight. Carbonyl(pentane-2,4-dionato-O,O’) (triphenylphosphine)rhodium is not classified under EU CLP.