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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 December 2021 - 21 December 2021
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2022
Report date:
2022

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Strontium bis(2-ethylhexanoate)
EC Number:
219-536-3
EC Name:
Strontium bis(2-ethylhexanoate)
Cas Number:
2457-02-5
Molecular formula:
C16H30O4Sr
IUPAC Name:
strontium bis(2-ethylhexanoate)
Test material form:
solid
Remarks:
powder lumps
Details on test material:
Supplier: ORGANOMETAL S.A.
CAS Number: 2457-02-5
Batch/Lot number: 3823121121
Appearance: solid powder lumping
Purity: min 94%
Metal content: 22% Sr
Expiry date: 12 November 2022

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Han:WIST rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt., H-1122 Budapest, Magyar Jakobinusok tere 4B
- Hygienic level at supplier: SPF
- Hygienic level during the study: Standard housing conditions
- Number of animals: 6 animals, 3 animals/group
- Sex: Female, nulliparous and non-pregnant animals
- Age of animals at dosing: Young adult rats, approx. 9-10 weeks old
- Body weight range at dosing: 189-207 g. The maximum difference of individual animal weights from the mean of the treatment group did not exceed 20%.
- Acclimatisation period: At least 19 days
- Animal health: Only healthy animals were used for the test. The health status was certified by the Veterinarian.
- Housing: Group caging (3 animals/cage)
- Cage type: T3H polycarbonate
- Bedding and nesting: “SAFE 3/4-S-FASERN” certified wooden chips and “Sizzle pet” nest material were available to animals during the study.
- Enrichment: Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Animals received standard laboratory rat diet, ad libitum, and tap water from the municipal supply, as for human consumption from drinking bottles designed for rodents, ad libitum.
- The night before treatment, the animals were fasted. Food, but not water, was withheld overnight. Animals were weighed before dosing. Food was replaced 3 hours after the treatment.

ENVIRONMENTAL CONDITIONS
- Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
- Temperature: 20 – 23 °C (target: 22 ± 3 °C)
- Relative humidity: 38 – 61 % (target: 30 – 70 %)
- Ventilation: 15-20 air exchanges/hour

IN-LIFE DATES: From 06 December 2021 to 21 December 2021

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
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: The powdered test item did not dissolve in distilled water, in 1% methyl cellulose solution and in PEG 400, but formed a homogenous suspension in corn oil after stirring with magnetic stirrer for approx. 30 minutes.
- Lot/batch no.: MKCM9808
- Manufacturer: Sigma-Aldrich
- Expiry date: 30 April 2026

DOSAGE PREPARATION: The test item was freshly formulated in the vehicle at the appropriate concentration (200 mg/mL), in the Pharmacy of NEXTREAT Laboratories on the day of administration. The formulations were stirred with magnetic stirrer up to finishing the treatment.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As starting dose level for acute toxicity study, a dose of 2000 mg/kg body weight (bw) has been selected based on the information published by ECHA.
- Initially three animals were treated at the starting dose of 2000 mg/kg bw (Group 1). As no mortality was observed in this group, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in this confirmatory dose group, therefore no further testing was required according to the criteria for termination given in Annex 2d of OECD Guideline No. 423.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (3 animals per group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: Following the end of the dosage, the animals were observed individually once during the first 30 minutes, at 1, 2, 3, 4 and 6 hours after the treatment and once daily for 14 consecutive days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The time of death was recorded as precisely as possible.
- Body weight: The body weight of the animals was recorded on Days 0 (prior to dosing), 7 and 14 (prior to necropsy), with a precision of 1 g.
- Necropsy: Animals were subjected to a necropsy and a macroscopic examination. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross macroscopic changes were recorded for each animal.
Statistics:
The method used was not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
Strontium bis(2-ethylhexanoate) did not cause mortality at 2000 mg/kg bw.
Clinical signs:
other:
Body weight:
lower than 10% body weight loss
Remarks:
There were no effects on body weight or body weight gain that could be attributed to treatment with the test item.
Gross pathology:
There were no macroscopic changes seen at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
The test substance is not classified according to Regulation (EC) No 1272/2008 (CLP)
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test item
Strontium bis(2-ethylhexanoate) was found to be above 2000 mg/kg bw in female
Han:WIST rats.
The LD50 cut-off value is 5000 mg/kg bw.
The study result triggers the following classification/labelling:
- Regulation (EC) No 1272/2008 (CLP): Unclassified
- GHS (rev. 7) 2017: Category 5