Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity:

The study was performed (OECD No. 420) to assess the acute oral toxicity of Mg-SiO, to the rat.

Fasted female rats received a single oral gavage dose of the test item, formulated in 1% aqueous methyl cellulose, at the following dose levels:

Sighting investigations: 300 and 2000 mg/kg body weight

Main study: 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.

Results:

There were no deaths, clinical signs of reaction to treatment or macroscopic abnormalities noted in any animal dosed at 300 or 2000 mg/kg and all animals were considered to have achieved satisfactory body weight gains throughout the study.

Conclusion:

The acute median lethal oral dose (LD50) to rats of Mg-SiO was demonstrated to be greater than 2000 mg/kg body weight.

Mg-SiO is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 20 December 2018 and 31 January 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Test item: Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide
Alternative name: Mg-SiO
Reaction mass of MgSiO3, Si and SiO2
Appearance: Black powder
Storage conditions: Ambient temperature (10-30°C) in the dark
Supplier: Sponsor
Batch number: Y180510A
Expiry/Retest date: 31 May 2019
Purity: > 94%
Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST albino rats
Sex:
female
Details on test animals and environmental conditions:
Animal Information:
Healthy nulliparous and non-pregnant female RccHan™:WIST albino rats were obtained from Envigo RMS (UK) Ltd.
The animals were allocated without conscious bias to cages within the treatment groups.

They were housed in groups of one or four rats of the same sex.
Each animal was identified uniquely within the study by tail marking. Each cage label was color-coded and was identified uniquely with the study number, dose level and animal mark.

The animals were allowed to acclimatize to the conditions described below for at least 6 days before treatment. For those animals selected for this study, their body weights were in the range 154 to 172 g and they were approximately eight to twelve weeks of age prior to dosing (Day 1). The body weight variation did not exceed ± 20% of the mean body weight of any previously treated animals.

Animal Care and Husbandry:
Animals were housed inside a limited access rodent facility.

The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated. The temperature and relative humidity controls were set to maintain the range of 20 to 24°C and 40 to 70% respectively.
Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

Periodic checks were made on the number of air changes in the animal rooms. Temperature and humidity were monitored daily.

The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.

The animals were allowed free access to a standard rodent diet (Teklad 2014C Diet), except for overnight prior to and approximately four hours after dosing. This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.

Each cage of animals was provided with an Aspen chew blocks or balls for environmental enrichment. Chew blocks or balls were provided throughout the study and were replaced when necessary. Each cage of animals was provided with a plastic shelter for environmental enrichment, which was replaced at the same time as the cages.


Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1% aqueous methyl cellulose.
Details on oral exposure:
Test Item Preparation and Analysis:
The test item was formulated at concentrations of 30 and 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg body weight.
The test item formulations were prepared on the day of dosing.
The absorption of the test item was not determined.
Determination of the homogeneity, stability and purity of the test item or test item formulations were not undertaken as part of this study.

Study Design:
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Two single animals were treated as follows:
300 mg/kg dose level (1 female rat)
2000 mg/kg dose level (1 female rat)

In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
2000 mg/kg dose level (4 female rats).

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

Dose Administration:
The appropriate dose volume of the test item was administered to each rat by oral gavage using a plastic syringe and plastic catheter.
A record of the weight of each formulation dispensed and the amount remaining after dosing was made. The balance of these two weights was compared with the predicted usage as a check that the doses had been administered correctly.
Formulations were stirred before and throughout the dosing procedure.




Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg: 1 female
2000 mg/kg: 5 females
Control animals:
no
Details on study design:
Mortality:
Cages of rats were checked at least twice daily for any mortalities.

Clinical Observations:
Animals were observed soon after dosing and at frequent intervals (at least 0.5, 1, 2 and 4 hours after dosing) on Day 1. On subsequent days, animals were observed once in the
morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time
were recorded at each observation.

All animals were observed for 14 days after dosing.

Body Weight:
The weight of each rat was recorded on Days -1, 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.

Terminal Investigations:
Method of Kill:
All animals were humanely killed on Day 15 by carbon dioxide asphyxiation.

Macroscopic Pathology:
All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of the brain, cecum, duodenum, heart, kidneys, small and large intestine, liver, lungs and bronchi, spleen, stomach, subcutaneous tissue and urinary bladder was recorded.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical signs of reaction to treatment throughout the study.
Body weight:
All 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.

Individual and group mean body weight (g):

Dose (mg/kg)

Sex

Animal Number

Body weights (g) at Day

1*

8

15

Sighting investigations

300

Female

221

162

186

195

2000

Female

222

172

202

216

Main study

2000

Female

223

168

179

191

224

161

178

182

225

154

174

182

226

170

197

209

Mean

163

182

191

*             Prior to dosing

 

Individual body weight change (g)

Dose (mg/kg)

Sex

Animal Number

Body weight change (g) at Day

1-8

8-15

Sighting investigations

300

Female

221

24

9

2000

Female

222

30

14

Main study

2000

Female

223

11

12

224

17

4

225

20

8

226

27

12

Interpretation of results:
GHS criteria not met
Remarks:
EU CLP
Conclusions:
The acute median lethal oral dose (LD50) to rats of Mg-SiO was demonstrated to be greater than 2000 mg/kg body weight.

Mg-SiO is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).
Executive summary:

The study was performed to assess the acute oral toxicity of Mg-SiO, to the rat.

Fasted female rats received a single oral gavage dose of the test item, formulated in 1% aqueous methyl cellulose, at the following dose levels:

Sighting investigations: 300 and 2000 mg/kg body weight

Main study: 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.

Results:

There were no deaths, clinical signs of reaction to treatment or macroscopic abnormalities noted in any animal dosed at 300 or 2000 mg/kg and all animals were considered to have achieved satisfactory body weight gains throughout the study.

Conclusion:

The acute median lethal oral dose (LD50) to rats of Mg-SiO was demonstrated to be greater than 2000 mg/kg body weight.

Mg-SiO is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The substance does not meet the criteria for classification under the EU CLP regulations for acute toxicity via the oral route based on the result of an acute oral toxicity study, which gave a LD50 of > 2000 mg/kg bodyweight, which is above the classification cut-off value ( ≤2000 mg/kg bodyweight) for acute oral toxicity.