Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-09-15 to 2017-02-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Batch No.: 86888
- Colour: grey
- Density: 1300-1900 kg/m³
- Purity: > 99.4 %
- Expiry Date: 1 year after the date of delivery
- Storage Conditions: room temperature, dry conditions, container closed tightly
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: suspension in steril water (AlleMan Pharma, lot no. 511535, expiry date: 10/2018)
- Final dilution of a dissolved solid, stock liquid or gel: 0.2 g/mL

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: step 1: 165 - 177 g
step 2: 176-184 g
- Fasting period before study: 16 to 19 h (access to water was permitted)
- Housing: SPF, the animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): ad libitum; Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): ad libitum, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): AlleMan Pharma, lot no. 511535, expiry date: 10/2018

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight, as no toxicity was expected.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 females per step, 2 steps performed
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily, weighing on day 1 (prior administration), 8 and 15
- Necropsy of survivors performed: yes, sacrificed with an overdosage of phenobarbital. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.
- Other examinations performed: Cage-side observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
N.A.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
No specific findings in any test animal during the whole observation period
Body weight:
None of the animals showed weight loss during the observation period
Gross pathology:
No specific findings
Other findings:
N.A.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study in rats according to OECD 423, no adverse effects were observed for Chromium diboride at the limit dose of 2000 mg/kg bw. Hence, the LD50 value is determined to be greater than 2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), two groups of fasted, 8-10 weeks old, female Wistar rats (3 rats/group) were given a single oral dose of Chromium diboride (>99.4% purity) in sterile water at the limit dose of 2000 mg/kg bw and were observed for 14 days. All animals survived until the end of the study without showing any test item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Based on the results from this study, the oral LD50 in rats is considered to be greater than 2000 mg/kg bw.