Carbonylhydrotris(triphenylphosphine)rhodium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carbonylhydrotris(triphenylphosphine)rhodium

EC Number:

241-230-3

EC Name:

Carbonylhydrotris(triphenylphosphine)rhodium

Cas Number:

17185-29-4

Molecular formula:

C55H46OP3Rh

IUPAC Name:

carbonylhydrotris(triphenylphosphine)rhodium

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Carbonylhydridotris(triphenylphosphane)-rhodium(I)
- Substance type: yellow powder
- Physical state: solid
- Analytical purity: >99%
- Impurities (identity and concentrations): not stated
- Composition of test material, percentage of components: not stated
- Isomers composition: not stated
- Purity test date: not stated
- Lot/batch No.: FM 36/4/90
- Expiration date of the lot/batch: not stated
- Stability under test conditions: stable
- Storage condition of test material: in a closed container at room temperature
- Other:
- Purity test method: gravimetric Rh-analysis
- Solubility: insoluble in water and n-hexane; soluble in chloroform (1 g/60 ml); soluble in acetone (1 g/100 ml)
- pH: ~7

Test animals

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG.

- Age at study initiation: males 8 weeks, females 9 weeks

- Weight at study initiation: males 144-171 g, females 130-156 g

- Fasting period before study: 16 hours

- Housing: Macrolon cages, type 2, with animal bedding chips; 1/cage

- Diet (e.g. ad libitum): Standard diet, Ssniff R, special diet for rats; ad libitum

- Water (e.g. ad libitum): municipal water supply, using an automatic drinking water system with drinking nipples; ad libitum

- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-23.0

- Humidity (%): 40-65

- Air changes (per hr): not stated

- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Not stated, but QA inspections on 19-Feb-1991 21-Feb-1991 during the experimental phase

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 46.4, 100 and 215 mg/ml

- Amount of vehicle (if gavage): 21.5 ml/kg bw

- Justification for choice of vehicle: not stated

- Lot/batch no. (if required): Tylose® (Tylopur® C 1000 P batch E 084 4357) supplied by Hoechst AG

- Purity: not stated; used at 1% (aqueous)

MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg bw

DOSAGE PREPARATION (if unusual): suspended in vehicle immediately before dosing using a homogenizer

CLASS METHOD (if applicable): not applicable

Doses:

1000, 2150 and 4640 mg/kg bw

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:
- Behaviour, general condition, clinical symptoms: continuous for 4-6 hours after dosing, then once daily
- Mortality: twice daily in working days, once daily otherwise
- Body weight: days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs-yes, body weight-yes, organ weights-no, histopathology-yes (liver and kidney), other-no

Statistics:

LD50 calculated for each sex and for both sexes together with 95% confidence limits by probit analysis

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 206 mg/kg bw

95% CL:

1 580 - 3 089

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2 390 mg/kg bw

95% CL:

1 156 - 5 676

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

2 118 mg/kg bw

95% CL:

1 054 - 4 226

Mortality:

Males: 1000 mg/kg bw - 0/5; 2150 mg/kg bw - 3/5 on days 2 and 3; 4640 mg/kg bw - 4/5 on day 2
Females: 1000 mg/kg bw - 0/5; 2150 and 4640 mg/kg bw - 3/5 on days 2 and 3; 4640 mg/kg bw - 5/5 on day 2

Clinical signs:

Males: 1000 mg/kg bw - slight hypokinesia, staggered/restrained gait, diarrhoea, sunken sides; 2150 and 4640 mg/kg bw - slight to severe hypokinesia, staggered/restrained gait, moderate clonic convulsions, decreased muscle tone, loss of righting reflex, loss of corneal reflex, mydriasis, salivation, diarrhoea/soft faces, piloerection, strenuous respiration, sunken sides (2150 mg/kg bw only), ataxia, stiff legs (4640 mg/kg bw only), opisthotonus (2150 mg/kg bw only), low body surface temperature;
Females: 1000 mg/kg bw - restrained gait, sunken sides; 2150 and 4640 mg/kg bw - slight to moderate hypokinesia, staggered/restrained/stilted gait, moderate clonic convulsions, decreased muscle tone, loss of righting reflex, mydriasis (4640 mg/kg bw only), salivation (4640 mg/kg bw only), diarrhoea (2150 mg/kg bw only), piloerection, strenuous respiration (4640 mg/kg bw only), sunken sides, ataxia, stiff legs (4640 mg/kg bw only), low body surface temperature, green urine (2150 mg/kg bw only)

Body weight:

Males and females: 1000 mg/kg bw - gained weight during the observation period; 2150 and 4640 mg/kg bw - survivors gained weight during the study; animals that died had lost weight

Gross pathology:

1000 mg/kg bw: no changes in any organs
2150 and 4640 mg/kg bw: stomach - yellow/black contents, black staining and white red discolouration of glandular stomach mucosa, fusion of pyloric stomach/first part of duodenum to liver (1 high dose male only); liver - prominent lobular patter, yellow discolouration of lobus caudatus, pale and soft; kidney (females only) - reddened papillae or cortex/medulla border; bladder - greenish/black discoloured urine

Other findings:

- Organ weights: not recorded

- Histopathology:
- Males - 1000 mg/kg bw: liver - minimal to mild centrolobular hypertrophy;
- Males - 2150 mg/kg bw: liver - minimal to mild centrolobular hypertrophy (surviving animals), mild to marked periportal hepatocellular vacuolization/degeneration and chromatin abnormalities (animals that died); kidney - minimal to mild vacuolization/degeneration of proximal tubular epithelial cells and mild to moderate congestion of the medulla (animals that died);
- Males - 4640 mg/kg bw: liver - mild to marked periportal hepatocellular vacuolization/ degeneration and chromatin abnormalities (animals that died) ; kidney - minimal to mild vacuolization/degeneration of proximal tubular epithelial cells and mild to moderate congestion of the medulla (animals that died)

- Potential target organs: liver and kidney

- Other observations: none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of carbonylhydridotris(triphenylphosphane)-rhodium(I) in rats was established to be above 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of carbonylhydridotris(triphenylphosphane)-rhodium(I) was evaluated in an OECD Test Guideline 401 study, conducted according to GLP. Test substance was administered by oral stomach tube to rats (5/sex/dose) at a single oral gavage dose of 1000, 2150 or 4640 mg/kg bw in 1% carboxymethylcellulose and observed for up to 14 days.

 

LD50 values (with 95% confidence limits) were 2206 (1580-3089) mg/kg bw for both sexes together, 2390 (1156-5676) mg/kg bw for males and 2118 (1054-4226) mg/kg bw for females. A small number of clinical signs were apparent in all dose groups. No macroscopic changes in any organs were observed at 1000 mg/kg bw. At higher doses, there were effects in the stomach, liver and kidneys (females only). Males displayed liver histopathology at all doses and kidney effects at the top dose.

 

The acute oral LD50 of carbonylhydridotris(triphenylphosphane)-rhodium(I) in rats was therefore established to be above 2000 mg/kg bw.

 

Based on the results of this study, no classification for acute oral toxicity is required according to EU CLP criteria (EC 1272/2008).