Dimethylbis(oleoyloxy)stannane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 May 2020 to 23 June 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000 (including the most recent revisions)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethylbis(oleoyloxy)stannane

EC Number:

223-384-3

EC Name:

Dimethylbis(oleoyloxy)stannane

Cas Number:

3865-34-7

Molecular formula:

C38H72O4Sn

IUPAC Name:

[dimethyl-[(Z)-octadec-9-enoyl]oxystannyl] (Z)-octadec-9-enoate

Test material form:

liquid

Details on test material:

- Appearance: Clear to slightly hazy pale yellow liquid
- Storage Conditions: At room temperature

Specific details on test material used for the study:

No purity/ correction factor required.
The test material was administered as received. The test material was stored in the refrigerator and was allowed to warm to room temperature for at least 30 minutes before dosing.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for species: the Wistar Han rat was chosen as the animal model for this study as recognised by international guidelines as a recommended test system.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (approximately 8-9 weeks old)
- Weight at study initiation: 133 to 172 g
- Fasting period before study: animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test material
- Housing: animals were housed in groups of up to 3 by sex in polycarbonate cages containing sterilised wooden fibers as bedding material, and equipped with water bottles. Animals were separated during designated procedures/activities.
For psychological/environmental enrichment, animals were provided with paper, except when interrupted by study procedures/activities.
- Diet: pelleted rodent diet, ad libitum (except during designated procedures)
- Water: municipal tap-water, ad libitum (via water bottles)
- Acclimation period: at least 5 days before the commencement of dosing
- Method of randomisation in assigning animals to test and control groups: animals were assigned to the study, with all animals within ± 20% of the sex mean body weights. Animals in poor health or at extremes of body weight range were not assigned to the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Humidity: 41 to 69%
- Air changes: Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms
- Photoperiod: 12 hour light/12 hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

TEST MATERIAL ADMINISTRATION
A single dose of (unchanged) test material was administered to the appropriate animals by oral gavage on Day 1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL) * purity correction factor.
The dosing formulations were stirred continuously during dose administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test material.
The test material was initially administered to three rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 2000 and 300 mg/kg body weight

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

Two groups of 3 females (300 mg/kg bw), One group of 3 females (2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Moribundity Checks: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.
Clinical Observations: Post-dose clinical observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.
ody Weights: Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanised moribund after Day 1.
- Necropsy of survivors performed: yes (all moribund animals and 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 were recorded)

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD50 cut-off value is considered to be 500 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The oral LD50 value of the test material is within the range of 300-2000 mg/kg bw

Mortality:

At 2000 mg/kg, all females were euthanised in moribund condition for animal welfare reasons on Day 5 post-treatment.
At 300 mg/kg, no mortality occurred.

Clinical signs:

At 2000 mg/kg, clinical signs consisted of moderate tremors, increased muscle tone, prostrate, hunched posture, erected fur, erected tail, moderate uncoordinated movements, hypersensitivity, cold to touch, abnormal gait, decreased activity and liquid faeces.
At 300 mg/kg, only hunched posture and erected fur were noted for the all animals between Days 1 and 4.

Body weight:

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

other: Acute 4 according to EU criteria

Conclusions:

Under the conditions of the study, the acute oral LD50 of the test material was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Executive summary:

The acute toxicity of the test material was investigated, via the oral route, according to the methods outlined in the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF, and under GLP conditions.

The study utilised the equential dosing scheme, as described by the Acute Toxic Class Method. Initially, the test material was administered by oral gavage to three female Wistar Han rats at 300 mg/kg bw. In a stepwise procedure two additional groups of three females were dosed at 2000 and 300 mg/kg bw. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15)

At 2000 mg/kg, all females were euthanised in moribund condition for animal welfare reasons on Day 5 post-dose. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, clinical signs consisted of tremors, increased muscle tone, prostrate, hunched posture, erected fur, erected tail, uncoordinated movements, hypersensitivity, cold to touch, abnormal gait, decreased activity and liquid faeces. At 300 mg/kg, only hunched posture and erected fur were noted for the all animals between Days 1 and 4.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

Under the conditions of the study, the acute oral LD50 of the test material was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be  500 mg/kg body weight.