[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 October 2020 to 17 November 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Acute oral toxicity (2-1-1),

Version / remarks:

2000

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid (H6Si2O7), ytterbium(3+) salt (1:2)

Cas Number:

13692-83-6

Molecular formula:

Yb2Si2O7H6

IUPAC Name:

Silicic acid (H6Si2O7), ytterbium(3+) salt (1:2)

Test material form:

solid: particulate/powder

Details on test material:

- Apperance: grey powder
- Storage conditions of lot/ batch: in darkness at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 152 to 169 g
- Fasting period before study: Overnight prior to and approximately four hours after dosing
- Housing: In groups up to four in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days
- Method of randomisation in assigning animals to test and control groups: The animals were allocated without conscious bias to cages within the treatment groups.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C
- Humidity (%): 40 to 70%
- Air changes: Periodic checks were made on the number of air changes in the animal rooms.
- Photoperiod: Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test material was ground using a pestle and mortar and formulated at concentrations of 30 and 200 mg/mL in the vehicle, by adding the vehicle to the test material and mixing. The test material formulations were prepared on the day of dosing.

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

1 animal was dosed at 300 mg/kg body weight
5 animals were dosed at 2000 mg/kg body weight

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities. Animals were also observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day. The weight of each rat was recorded on Days -1 (not reported), 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes. All animals were humanely killed on Day 15 by carbon dioxide asphyxiation and subsequently exsanguinated. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities.

Results and discussion

Preliminary study:

Two single animals were treated with a starting dose level of 300 mg/kg body weight and 2000 mg/kg body weight. In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of animals were treated at a dose level of 2000 mg/kg body weight.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality.

Clinical signs:

There were no clinical signs of reaction to treatment throughout the study.

Body weight:

Female number 36 (main study) was considered to have a low body weight gain between Day 8 and 15, however, achieved a satisfactory body weight gain between Day 1 and 8.
All other animals were considered to have achieved satisfactory body weight gains throughout the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the acute median lethal oral dose (LD50) to Wistar rats of the test material was demonstrated to be greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity potential of the test material to the rat was assessed according to the standardised guidelines OECD 420 and EU Method B1 bis under GLP conditions using the Fixed Dose Method.

Fasted female rats received a single oral gavage dose of the test material, formulated in 1% w/v aqueous methylcellulose. A sighting investigation was completed in which two animals received test material at dose levels of 300 and 2000 mg/kg body weight. Based on the results of the sighting investigations a further four fasted females were similarly dosed at 2000 mg/kg body weight. During the study, clinical condition, body weight and macropathology investigations were undertaken and all animals were observed for 14 days after dosing. There were no deaths during the study and no clinical signs of reaction to treatment throughout the study. Female number 36 (main study) was considered to have a low body weight gain between Day 8 and 15, however, achieved a satisfactory body weight gain between Day 1 and 8. All other animals were considered to have achieved satisfactory body weight gains throughout the study and no abnormalities were noted in any animal at the macroscopic examination at study termination.

Under the conditions of this study, the acute median lethal oral dose (LD50) to Wistar rats of the test material was demonstrated to be greater than 2000 mg/kg body weight.