Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 April - 12 May 2014
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:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Diammonium Sodium Hexakis (nitrito-N) Rhodate
- Molecular formula (if other than submission substance): (NH4)2Rh(NO2)6
- Substance type: technical product
- Physical state: Pale yellow/green powder
- Analytical purity: Rh content 16.63 % w/w; sodium content 3.88% w/w
- Impurities (identity and concentrations): Trace amounts of precious metals (platinum, ruthenium, iridium, silver) and other metals (iron, nickel, copper, tellurium, bismuth, magnesium, chromium) reported on the certificate of analysis in the study report.
- Composition of test material, percentage of components: Total precious metals 16.77%; total metals 22.56%
- Purity test date: 01 April 2014
- Lot/batch No.: RHL 653
- Expiration date of the lot/batch: 03 June 2015
- Stability under test conditions: no data
- Storage condition of test material: Controlled Room Temperature (15-25 degrees C, below 70% relative humidity) and protected from light

Test animals

Species:
rat
Strain:
other: CRL:(WI) rats
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation:8-11 weeks
- Weight at study initiation: 202-231 g
- Fasting period before study: overnight prior to treatment
- Housing: Individual caging in Type II polypropylene/polycarbonate cages with Lignocel Bedding for Laboratory Animals and deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, from 500 ml bottles, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 – 23.3
- Humidity (%): 37-60
- Air changes (per hr): 15 – 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: various
- Amount of vehicle (if gavage): 1.0-1.2 ml/animal
- Justification for choice of vehicle: based on trial formulations with the test item
- Lot/batch no. (if required): 1D30012N13
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 1.2 ml/animal

- Rationale for the selection of the starting dose: The doses were selected from the sequence 1.75, 5.5, 17.5, 55, 175, 550, 2000 mg/kg bw. A starting dose of 175 mg/kg bw was selected after discussions between the Study Director and the Sponsor.
Doses:
175, 550, 2000 mg/kg bw
No. of animals per sex per dose:
1 (in lower two dose groups); 3 (in highest dose group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation after dosing at 30 minutes, then at 1, 2, 3, 4, and 6 hours, then once each day for 14 days thereafter. Weighing one day before and on the day of treatment (day 0), and on days 7 and 14 after treatment.
- Necropsy of survivors performed: yes
- Observations: these included the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsies: macroscopic examination of the external appearance and of the tissues and organs of the cranial, thoracic and abdominal cavities.
Statistics:
The Acute Oral Toxicity (OECD Test Guidelines 425) Statistical Programme (AOT 425 Stat Pgm) was used to evaluate data.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Mortality:
None
Clinical signs:
None
Body weight:
No indication of a treatment-related effect for body weight or body weight gain
Gross pathology:
No macroscopic observations
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an OECD guideline study, the acute oral LD50 value for diammonium sodium hexakis(nitrito-N)rhodate was determined to exceed 2000 mg/kg bw following gavage administration in female rats.
Executive summary:

The acute oral toxicity of diammonium sodium hexakis(nitrito-N)rhodate was assessed in female rats, in a study carried out in accordance with OECD guideline 425 and to GLP. Animals were treated by gavage with the test material (in 1% methyl cellulose) at doses of 175 (1 animal), 550 (1 animal) or 2000 (3 animals) mg/kg body weight. Macroscopic examination was conducted on surviving animals.

 

No mortality, clinical signs or effects on body weight/growth were apparent during the 14-day post-dose observation period, and there were no notable external or internal macroscopic findings upon necropsy. The study investigators concluded that the acute oral median lethal dose (LD50) of diammonium sodium hexakis(nitrito-N)rhodate was greater than 2000 mg/kg bw in female rats.

 

Based on the results of this study, diammonium sodium hexakis(nitrito-N)rhodate does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).