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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2010-04-01 to 2010-04-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
, 2001-12-17
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
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): Strontium nitrate
- Molecular formula: Sr(NO3)2
- Molecular weight: 211.63
- Physical state: White crystals
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- pH (1% in water, indicative range): 6.4 - 7.0 (determined at NOTOX)
- Solubility in water (vehicle): Yes
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, germany
- Age at study initiation: Approx. 11-12 weeks old
- Weight at study initiation: 181 - 203 g
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.0 ± 3.0ºC (actual range: 19.9 – 21.7ºC)
- Relative humidity: 40-70% (actual range: 34 - 53%)
- Air changes: Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Water (Elix, Millipore S.A.S., molsheim, France) was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION: The formulations (w/) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
No further information on the oral exposure was stated.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Total: 6 female rats (Each dose group consisted of 3 animals.)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was observed twice daily. The time of death was recorded as precisely as possible. body weights were measured on Days 1 (pre-administration), 8 and 15. Clinical signs were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were
recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: Yes
The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
No further infromation on the study design was stated.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead within 4 hours post-treatment on Day 1. No further mortality occurred.
Clinical signs:
Lethargy, hunched posture, piloerection and/or ptosis were noted for all animals and the surviving animals had recovered from all symptoms on Day 4 or Day 6. In addition to these symptoms, flat posture and slow breathing were observed for the animal that was found dead on Day 1.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animal that was found dead on Day 1 revealed several dark red foci on the glandular mucosa of the stomach. No abnormalities were found at macroscopic post mortem examination of the animals that survived until termination.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of Strontium Nitrate in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.
According to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, strontium nitrate does not have to be classified and has no obligatory labeling requirement for oral toxicity.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic by the oral route.