Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 December 2002 - 22 January 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Conducted according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Rhodium(III) nitrate hydrate
EC Number:
603-842-2
Cas Number:
13465-43-5
Molecular formula:
H4N3O11Rh
IUPAC Name:
Rhodium(III) nitrate hydrate
Constituent 2
Reference substance name:
Rhodiumtrinitrate hydrate
IUPAC Name:
Rhodiumtrinitrate hydrate
Details on test material:
- Name of test material (as cited in study report): Rhodiumtrinitrate hydrate
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: Green-brown powder
- Analytical purity: Rhodium 35.7% +/-0.1%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: 2586/00-02
- Expiration date of the lot/batch: 21 October 2003
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material: at room temperature in the dark
- Other:

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR (Outbred, SPF-Quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals, approximately 8 weeks old
- Weight at study initiation: 161-258 g
- Fasting period before study: overnight (for a maximum of 20 hrs) prior to dosing until 3-4 hrs after administration of test substance
- Housing: 3 animals/sex/cage in Macrolon cages (type IV; height 18 cm)
- Diet (e.g. ad libitum): ad libitum standard pelleted laboratory animal diet (from Altromin, code VRF-1, Lage Germany)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3ºC
- Humidity (%): 30-70%
- Air changes (per hr): approx. 15 air changes/hr
- Photoperiod (hrs dark / hrs light): 12 hrs artificial fluorescent light and 12 hrs dark/day

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: selected based on trial formulations
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:
200 and 2000 mg/kg bw.
No. of animals per sex per dose:
Each dose group consisted of 3 animals/sex (females were nulliparous and non-pregnant).
Control animals:
no
Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality/viablility were made twice daily. Body weights were recorded the day before administration, and weekly after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic post mortem examination.

Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Mortality:
No male or female rats died over the study period at 200 mg/kg bw. At 2000 mg/kg bw all three female rats in the treatment group were killed in extremis on day 2 after treatment.
Clinical signs:
Females at 200 mg/kg bw dose level: hunched posture, piloerrection
Males at 200 mg/kg bw: hunched posture
Females at 2000 mg/kg bw: lethargy, hunched posture, uncoordinated movements, swelling, piloerection, yellow staining (genital region), yellow discolouration (urine), hypothermia, rales, pale, ptosis, laboured respiration, orange staining (lower mandible), orange staining (forelegs), salivation.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered by the author of the report to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were observed in the surviving male and female animals of the 200 mg/kg bw treatment groups. Examination of the three female rats treated at 2000 mg/kg bw revealed abnormalities of the stomach (hardened wall and content, dark red discolouration fore stomach, distended with gas).
Other findings:
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- Organ weights: no data
- Histopathology: no data
- Potential target organs:
- Other observations:

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline study, to GLP, the acute oral LD50 value of rhodium trinitrate hydrate was determined to range between 200 and 2000 mg/kg bw following gavage administration in rats.
Executive summary:

In an OECD Test Guideline 423 study, to GLP, rhodium trinitrate hydrate was studied for acute toxicity after single oral administration in Wistar rats. The test substance was administered by oral stomach tube at a dose of 200 mg/kg bw to groups of rats (3/sex). A further group of three females received a dose of 2000 mg/kg bw.

No mortality was observed at the 200 mg/kg bw dose level. The three females treated at 2000 mg/kg bw were killed in extremis one day following treatment. Hunched posture (males and females) and piloerection (females only) were observed at the lower dose. Numerous clinical signs were observed in the 2000 mg/kg bw treated females, including: lethargy, hunched posture, uncoordinated movements, swelling, piloerection, yellow staining (genital region), yellow discolouration (urine), hypothermia, rales, pale, ptosis, laboured respiration, orange staining (lower mandible), orange staining (forelegs), and salivation. Surviving animals recovered within one or two days of treatment. The growth shown by the surviving animals over the study period was considered by the author of the report to be normal. Macroscopic post mortem examination of the three female rats from the 2000 mg/kg bw treatment group revealed abnormalities of the stomach (hardened wall and content, dark red discolouration fore stomach, distended with gas). No abnormalities were observed at macroscopic post mortem examination of the surviving animals from the 200 mg/kg bw treatment groups.

An acute oral LD50 value of >200 and < 2000 mg/kg bw was determined in male and female rats (van Huygevoort, 2003a). This is considered to approximate to a discriminating dose of 300 mg/kg bw. The adverse signs were typical of severe local gastrointestinal effects, rather than of systemic toxicity.

Based on the results of this study, rhodium trinitrate hydrate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).