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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2015-09-30 to 2015-10-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
adopted 2008-10-03
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2014-05-14
Test type:
up-and-down procedure
Limit test:
no

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 neodecanoate
- Molecular weight: 429.6 g/mol
- Physical state: cream/pale yellow granular solid
- Storage condition of test material: in a tightly closed container, in a dry, cool and well-ventilated place
- Water solubility: 45.07 g/L

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at dosing: approx. 8 weeks
- Weight at first dosing: 169 - 184 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum. Food was withheld to up to 3 - 4 hours post dosing.
- Housing: during the 14-day observation period the animals were kept individually in MAKROLON cages (type III plus); Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet: Commercial ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Source: SIGMA-ALDRICH Chemie GmbH, 82024 Taufkirchen, Germany
- Justification for choice of vehicle: the vehicle is known for its low toxicity and provided test item suspensions that could be administered orally.
- Lot/batch no.: BCBN5570V

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

DOSAGE PREPARATION:
Strontium neodecanoate was suspended to the appropriate concentration in the vehicle.

DOSING SEQUENCE.
1) Limit Test at 5000 mg/kg:
A dose of 5000 mg strontium neodecanoate/kg bw was tested in one animal. As this animal died prematurely the main test was conducted to determine the LD50.
2) Main test:
Dosing was initiated at 175 mg/kg bw and continued using a progression factor of approx. 3.2. The resulting sequence was 175, 550, 1750, 550, 1750, 550 and 1750 mg/kg bw. Each dose level was conducted with one female rat.
Doses:
175, 550, 1750, and 5000 mg/kg bw
No. of animals per sex per dose:
175 mg/kg bw: 1 female rat
550 mg/kg bw: 3 female rats
1750 mg/kg bw: 3 female rats
5000 mg/kg bw: 1 female rat
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed before and immediately, 5, 15, 30 and 60 minutes, as well as 3, 6 and 24 hours after administration.
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.
Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death. Changes in weight were calculated if survival exceeds one day.
- Necropsy of survivors performed: yes, at the end of the experiments, all surviving animals were sacrificed and inspected macroscopically. Necropsy and macroscopic inspection of animals which died prematurely were carried out as soon as possible after exitus.
Statistics:
The LD50 value and the confidence interval were calculated using the software “AOT425statpgm (Version:1.0)”.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
1 030 mg/kg bw
Based on:
test mat.
95% CL:
550 - 1 750
Mortality:
175 mg/kg bw: no animal died prematurely.
550 mg/kg bw: no animal died prematurely.
1750 mg/kg bw: all animals died prematurely within 3 hours after administration
5000 mg/kg bw: animal died prematurely within 24 hours after administration
Clinical signs:
175 mg/kg bw: no signs of toxicity
550 mg/kg bw: no signs of toxicity
1750 mg/kg bw: reduced motility, ataxia, reduced muscle tone, dyspnoea and dorsal or lateral position in all animals. Clinical signs occurred up to 60 minutes after administration.
5000 mg/kg bw: reduced motility, ataxia, reduced muscle tone, dyspnoea and an increased pinna reflex in the animal. Clinical signs occurred up to 6 hours after administration.
Body weight:
All surviving animals gained the expected body weight.
Gross pathology:
No pathological findings were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rats): 1030 mg/kg bw
According to the Directive 67/548/EEC and its subsequent amendments, the test substance is acutely toxic via the oral route (R22; Xn).
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is classified as acute toxic via the oral route (Category 4; H302).