Dirhodium trioxide

Endpoint summary

Description of key information

Haferkorn (2018) is a GLP compliant study assessing the acute oral toxicity of dirhodium trioxide according OECD 425. No mortality or pathological changes were apparent at the limit dose of 2000 mg/kg bw following the 14-day observation period while growth was unaffected. It was concluded that dirhodium trioxide does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).

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

Study period:

28 September 2018 - 31 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Specific details on test material used for the study:

100% Rh2O3x0.67 H2O or 95.5% Rh2O3 (based on Rh content of 77.4 wt%)

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 183-200 g
- Fasting period before study: 16 hours
- Housing: Individually in MAKROLON cages (type III plus) with granulated textured wood bedding material
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany); discontinued approximately 16 hours before administration, food was withheld 3 - 4 hours post dosing.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): relative humidity 55 ± 10%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12, 150 lux at approx 1.5m room height)

IN-LIFE DATES: From: 28 September 2018 to 31 October 2018

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: solubility of dirhodium trioxide in suitable vehicles was assessed in a preliminary solubility test. The test item was insoluble in 0.8% aqueous hydroxypropyl methylcellulose (Methocel) and sesame oil, but formed a suspension in propylene glycol, which was considered acceptable for oral dosing.
- Lot/batch no. (if required): Batch no. MKBX0067V, SIGMA-ALDRICH Chemie GmbH, 82024 Taufkirchen, Germany
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg dirhodium trioxide/kg bw (limit dose)

No. of animals per sex per dose:

5 (A dose of 2000 mg dirhodium trioxide/kg b.w. was tested in 1 animal. As the animal survived, the test item was administered to additional 4 animals)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following dose administration, observations were made and recorded systematically with individual records being maintained for each animal. Clinical observations were recorded before and after dose administration: at 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration and then daily for a period of 14 days. During the follow-up period (two weeks), changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on mortality were made at least once daily to minimize loss of animals during the study.
Individual body weights were recorded before administration of the test item (day 1) and thereafter and on days 2, 4 and 8 and prior to sacrifice on day 15. Changes in weight were calculated if survival exceeds one day.
- Necropsy of survivors performed: yes (macroscopic)
- Other examinations performed: No histopathology was carried out as no macroscopic findings were noted at necropsy.

Statistics:

No statistical analysis was performed as the LD50 is greater than 2000 mg/kg b.w. and no main test was carried out.

Preliminary study:

The LD50 was greater than 2000 mg/kg bw therefore no main test was carried out.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No statistical analysis was performed as the LD50 is greater than 2000 mg/kg b.w. and no main test was carried out.

Mortality:

No animal died prematurely.

Clinical signs:

other: There were no clinical signs of toxicity.

Gross pathology:

No pathological findings were noted at necropsy.

Other findings:

Not applicable

Interpretation of results:

GHS criteria not met

Conclusions:

In an OECD guideline study, conducted to GLP, the acute oral LD50 of dirhodium trioxide was found to exceed 2000 mg/kg bw in female rats.

Executive summary:

The acute oral toxicity of dirhodium trioxide was assessed in female rats, in a study conducted according to OECD Test Guideline 425 and to GLP.

 

Initially, one female received a single (limit) dose of 2000 mg/kg bw by oral gavage. As the animal survived, the test item was administered to an additional four animals. No mortality or pathological changes were apparent at the limit dose following the 14-day observation period while growth was unaffected. The study authors conclude that the acute oral median lethal dose (LD50) of the test material in females rats exceeds 2000 mg/kg bw.

 

Based on the results of this study, dirhodium trioxide does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Dirhodium trioxide does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).