[No public or meaningful name is available]

Endpoint summary

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).

Acute inhalation toxicity:

The study was designed to investigate the acute inhalation toxicity of the test item and, if appropriate, allow the use of serial steps of Fixed Target Concentrations Procedure (FCP) to provide a ranking of test item toxicity. Data from this study was primarily used to classify and label the test item in accordance with the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Test item	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Test animals	RccHan^™;WIST rats
Study structure	1 test group, consisting of 5 males
Route of administration	Inhalation
Duration of exposure	Single 4-hour snout only exposure
Observation period	Fourteen days post exposure

Results

Exposure Levels

The mean average chamber concentration data are summarised as follows:

Group	Target aerosol concentration (mg/L)	Mean achieved aerosol concentration (mg/L)	Particle size
			MMAD (mm)	sg
2	5.0	5.05	3.6	2.12
MMAD Mass median aerodynamic diameter sg          Geometric standard deviation

The mean achieved concentration value was 101% of the target concentration of 5 mg/L. The MMAD was within the ideal range of 1-4 microns for an acute inhalation study, indicating that the aerosol was respirable to the rat.

There were no unscheduled deaths and no clinical signs related to treatment.

On the day following exposure, slight body weight losses were evident in the majority of animals. Body weight gains were observed on Day 4 for all animals and continued to increase thereafter for the remainder of the observation period.

The macroscopic examination performed after a single exposure and a 14-day observation period revealed no test item related findings. No abnormalities were observed.

 

Conclusion

Under the conditions of this study, the LC₅₀(4 hour) of Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is in excess of 5.05 mg/L for male rats.

Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is unclassified according to the Globally Harmonised System (GHS; UNITED NATIONS).

Acute Dermal Toxicity:

The study was performed to assess the acute dermal toxicity of Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide to the rat.

Methods:

Initially, one female animal was given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. Based on the preliminary results of the initial test, a further two female animals were similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results:

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: Animal 3 showed a small red spot and scratch on the skin and animals 2 and 3 showed patchy or no growth of fur, respectively. Stained fur and substance residuals were observed in all animals.

Body Weight: All animals showed expected gains in body weight.

Necropsy: Animal 2 showed orange spots in the half digested stomach content.

Conclusion:

The acute dermal median lethal dose (LD₅₀) to rats of Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide was found to be greater than 2000 mg/kg body weight.Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide 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

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

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. QA statement)

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 or test system 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:

other: There were no clinical signs of reaction to treatment 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

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 18 December 2018 and 12 February 2019.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)

Version / remarks:

Adopted 25 June 2018.

Deviations:

no

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

no

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: MgSiO
Intended use: Industrial Chemical
Appearance: Dark charcoal powder
Storage conditions: At ambient temperature (15 to 30ºC) protected from light
Supplier: Sponsor
Batch number: Y180510A
Expiry date: 31 May 2019
Supplier’s responsibilities: Characterisation of the test item and the documentation of the methods of synthesis, fabrication or derivation and stability.

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

Six male and one female RccHan™:WIST rats were received from Envigo RMS Limited in two consignments. The initial consignment consisted of one male and one female, and the second consignment consisted of five males. The rats were ordered at 64 to 70 days of age and within a weight range of 255 g to 285 g for males and 165 to 195 g for the female.
On arrival, the animals were removed from the transit boxes and allocated to study cages. Using the sequence of cages in the battery, one animal at a time was placed in each cage with the procedure being repeated until each cage held the appropriate number of animals.
Each animal was assigned a number and identified uniquely within the study by a microchip. Each cage label was color-coded according to group and was numbered uniquely with cage and study number, as well as the identity of the occupants.
The animals were allowed to acclimatize to the conditions described below for at least 5 days before treatment commenced. For those animals selected for this study, their age at the start of treatment was 69 to 75 days and their body weights were in the range of 280 to 305 g.

Animal Care and Husbandry
Animals were housed inside a restricted entry rodent facility (Building Y13, Room 008). The facility was designed and operated to minimize the entry of external biological and chemical agents and to minimize the transference of such agents between rooms. Before the study the room was cleaned and disinfected.
Each animal room was supplied with filtered fresh air, which was passed to atmosphere and not re-circulated. The temperature and relative humidity controls were maintained within 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.
Temperature and humidity were monitored continuously. Although conditions were occasionally outside the indicated ranges, these deviations were minor and/or of short duration and were not considered to have influenced the health of the animals and/or the outcome of the study.
Alarms were activated if there was any failure of the ventilation system, or temperature limits were exceeded. A stand-by electricity supply was available to be automatically brought into operation should the public supply fail.
The animals were housed one animal per cage during the sighting study and five animals per cage during the main study. The cages were made of a polycarbonate body with a stainless steel mesh lid. Wood shavings (Lignocel 3/4) were used as bedding and were sterilized by autoclaving and changed at appropriate intervals each week. Cages, food hoppers and water bottles were changed at appropriate intervals.
Whilst in the home cage, animals were allowed free access to a standard rodent diet (Teklad 2014C Diet). 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 block for environmental enrichment. Chew blocks 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.
Each batch of diet was analyzed routinely by the supplier for various nutritional components and chemical and microbiological contaminants. Supplier’s analytical certificates were scrutinized and approved before any batch of diet was released for use. The quality of the water supply is governed by regulations published by the Department for Environment, Food and Rural Affairs. Certificates of analysis were received routinely from the water supplier. Certificates of analysis were received routinely from the supplier of the wood shavings and Aspen chew blocks. Since the results of these various analyses did not provide evidence of contamination that might have prejudiced the study, they are not presented.
No other specific contaminants that were likely to have been present in the wood shavings, chew blocks, diet or water were analyzed, as none that may have interfered with or prejudiced the outcome of the study was known.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.6 µm

Geometric standard deviation (GSD):

2.12

Remark on MMAD/GSD:

The mean achieved concentration value was 101% of the target concentration of 5 mg/L. The MMAD was within the ideal range of 1-4 microns for an acute inhalation study, indicating that the aerosol was respirable to the rat.

Details on inhalation exposure:

See "Any other information on materials and methods" section

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.0 mg/L

No. of animals per sex per dose:

Sighting study:
1 male and 1 female at 5.0 mg/L

Main study:
5 males at 5.0 mg/L

Control animals:

no

Details on study design:

Serial Observations
Dated and signed records of all activities relating to the day by day running and maintenance of the study within the animal unit as well as to the group observations and examinations outlined in this experimental procedure were recorded.

Mortality
Throughout the study, all cages were checked at least twice daily, once in the morning and again towards the end of the normal working day, for dead or moribund animals.

Clinical Observations
A detailed weekly physical examination was performed on each animal to monitor general health.
Clinical signs were recorded prior to exposure, at hourly intervals during exposure, on return to home cage, 1 hour and 2 hours post-exposure and as late as possible in the working day.
During the observation period, the animals were observed once in the morning and once toward the end of the experimental day. On the day of study termination there was one observation (morning only).

Body Weight
The weight of each main study animal was recorded during the acclimatisation period and on Days 1 (prior to dosing) 2, 4, 8 and 15.

Terminal Investigations
Method of Kill
At the end of the scheduled observation period, animals were killed by an overdose of pentobarbitone sodium followed by exsanguination.

Macropathology
All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded. Tissues were discarded following necropsy.

Data Evaluation
In order to minimize the cumulative errors, which result from repeated rounding of numbers, some of the data in this report have been calculated continuously using unrounded numbers and only rounded for reporting. Consequently, any further calculation using these rounded numbers may include rounding errors in the last significant figure, possibly leading to small apparent discrepancies with other data in this report.
Throughout the report the following abbreviations are used:
M Male
N Number of animals
SD Standard deviation

Days of pretreatment relate to study days, as follows:
Phase day P5
Day of study -1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5.05 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths and no clinical signs related to treatment.

Clinical signs:

other: There were no unscheduled deaths and no clinical signs related to treatment.

Body weight:

On the day following exposure, slight body weight losses were evident in the majority of animals. Body weight gains were observed on Day 4 for all animals and continued to increase thereafter for the remainder of the observation period.

Gross pathology:

The macroscopic examination performed after a single exposure and a 14-day observation period revealed no test item related findings. No abnormalities were observed.

Body weight - group mean values (g)

	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Dose Group	2
Exposure level (mg/L)	5.05

  

Group		Day	Day						Change
/Sex		P5	1	2	4	8	15		1-15
2M	Mean	286	294	292	297	316	343		49
	SD	10.0	10.8	12.8	12.2	13.8	16.7		7.2
	N	5	5	5	5	5	5		5

Signs associated with dosing - individual observations (Day 1)

	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Dose Group	2
Exposure level (mg/L)	5.05

Group	Anim	al	Day of			Day(s) observed
/Sex	Numb	er	Death	Category	Observation	1 hour into exposure	2 hours into exposure	3 hours into exposure	4 hours into exposure	On return to home cage	1 hour after exposure	2 hours after exposure	As late as possible in the working day
2M	0071		15	Coat	Wet fur, Moderate			1	1	1
				Staining	Abnormal color, Black, Dorsal surface, Test item staining				1	1	1	1	1
					Abnormal color, Black, Head, Test item staining	1	1	1	1	1	1	1	1
	0072		15	Staining	Abnormal color, Black, Head, Test item staining	1	1	1	1	1	1	1	1
	0073		15	Staining	Abnormal color, Black, Dorsal surface, Test item staining			1	1	1	1	1	1
					Abnormal color, Black, Head, Test item staining			1	1	1	1	1	1
	0074		15	Staining	Abnormal color, Black, Head, Test item staining		1	1	1	1	1	1	1
	0075		15	Staining	Abnormal color, Black, Head, Test item staining		1	1	1	1	1	1	1

Only animals with observations are presented 

Signs associated with dosing - individual observations (Days 2 to 15)

	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Dose Group	2
Exposure level (mg/L)	5.05

Group	Anim	al	Day of			Day(s) observed
/Sex	Numb	er	Death	Category	Observation	AM check	As late as possible in the working day
2M	0071		15	Staining	Abnormal color, Black, Dorsal surface, Test item staining	2	2
					Abnormal color, Black, Head, Test item staining	2-3	2-3
	0072		15	Staining	Abnormal color, Black, Head, Test item staining	2-3	2
	0073		15	Staining	Abnormal color, Black, Head, Test item staining	2-3	2-3
	0075		15	Staining	Abnormal color, Black, Head, Test item staining	2-3	2-3

Only animals with observations are presented

Body weight - individual values (g)

	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Dose Group	2
Exposure level (mg/L)	5.05

Group	Anim	al	Day	Day
/Sex	Numb	er	P5	1	2	4	8	15
2M	0071		279	286	280	285	304	330
	0072		288	299	298	300	325	358
	0073		296	305	299	309	325	357
	0074		295	303	306	309	327	350
	0075		273	280	277	284	298	321

Macropathology - individual findings

	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Dose Group	2
Exposure level (mg/L)	5.05

Group	Anim	al	Day (Week)
/Sex	Numb	er	of Death	Phase	Tissue	Findings
2M	0071		15 (3)	Treatment 2	All tissues	No macropathology findings
	0072		15 (3)	Treatment 2	All tissues	No macropathology findings
	0073		15 (3)	Treatment 2	All tissues	No macropathology findings
	0074		15 (3)	Treatment 2	All tissues	No macropathology findings
	0075		15 (3)	Treatment 2	All tissues	No macropathology findings

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used: EU CLP

Conclusions:

Under the conditions of this study, the LC50 (4 hour) of Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is in excess of 5.05 mg/L for male rats.
Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is unclassified according to the Globally Harmonised System (GHS; UNITED NATIONS).

Executive summary:

The study was designed to investigate the acute inhalation toxicity of the test item and, if appropriate, allow the use of serial steps of Fixed Target Concentrations Procedure (FCP) to provide a ranking of test item toxicity. Data from this study was primarily used to classify and label the test item in accordance with the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Test item	Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide
Test animals	RccHan^™;WIST rats
Study structure	1 test group, consisting of 5 males
Route of administration	Inhalation
Duration of exposure	Single 4-hour snout only exposure
Observation period	Fourteen days post exposure

Results

Exposure Levels

The mean average chamber concentration data are summarised as follows:

Group	Target aerosol concentration (mg/L)	Mean achieved aerosol concentration (mg/L)	Particle size
			MMAD (mm)	og
2	5.0	5.05	3.6	2.12
MMAD Mass median aerodynamic diameter og          Geometric standard deviation

The mean achieved concentration value was 101% of the target concentration of 5 mg/L. The MMAS was within the ideal range of 1 - 4 microns for an acute inhalation study, indicating that the aerosol was respirable to the rat.

There were no unscheduled deaths and no clinical signs related to treatment.

On the day following exposure, slight body weight losses were evident in the majority of animals. Body weight gains were observed on Day 4 for all animals and continued to increase thereafter for the remainder of the observation period.

The macroscopic examination performed after a single exposure and a 14-day observation period revealed no test item related findings. No abnormalities were observed.

 

Conclusion

Under the conditions of this study, the LC₅₀(4 hour) of Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is in excess of 5.05 mg/L for male rats.

Reaction Mass of Crystalline Magnesium Silicate and Crystalline Silicon and Synthetic Amorphous Silicon Dioxide is unclassified according to the Globally Harmonised System (GHS; UNITED NATIONS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 050 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 24 April 2019 and 13 May 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Identification: Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide
Chemical Name: Reaction mass of Magnesium dioxide(oxo)silane and Silicon dioxide (MgSiO3, Si and SiO2)
Batch: E80-181130-11
Purity: 94 min wt%
Physical state, appearance: Black powder
Expiry Date: 30 November 2019
Storage Conditions: At room temperature, light protected
Stability in Solvent: Not indicated by the Sponsor

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information:
Species: Rat
Strain: Wistar Han TM
Source: Envigo RMS B.V., Inc
Sex: Female
Other: Females were nulliparous and non-pregnant
Number of animals for the pre-test: 1 female
Number of animals for the main study: 2 females
Age (beginning of treatment):
Pre-test: 10 - 11 weeks
Main study: 11 - 12 weeks
Bodyweight at Day 0: 201.5 - 243.1 g
Identification: The animals were distributed into the test groups at random. If possible, all animals belonging to the same experimental group were kept in one cage. The animals were individually marked by indelible ink markings on the tail. A colour-coded card was prepared for each project, giving details of the test type, project number, treatment start, dose level, sex and number of animals.
Acclimatization: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.

Husbandry:
Housing:
During the exposure period: single
During the acclimation phase and after the exposure period: groups of up to three rats (of the same sex and dose group)
Cage Type: Makrolon Type IV, with wire mesh top
Bedding: granulated soft wood bedding
Feed: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
Water: tap water, ad libitum
Environment:
temperature 22 + 2°C
relative humidity approx. 45-65 (except for deviation) (with the aim of 50 – 60%)
artificial light 6.00 a.m. - 6.00 p.m.
Environmental enrichment: provided throughout the study period (e.g., wooden chew blocks, fun tunnels or suitable nesting material)

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

Test Item Preparation and Analysis:
Formulation:
The different test item concentrations were prepared individually. Homogeneity of the test item in vehicle was maintained during treatment using a magnetic stirrer.
The test item was formulated at a concentration of 200 mg/mL in the vehicle and administered at a constant dose volume of 5 mL/kg body weight. Grinding of the test item in a mortar was used to formulate the test item.
Test item formulations were freshly prepared on the day of dosing, issued at room temperature and administered as soon as possible (within 4 hours of preparation). The formulations were assumed to be stable for this period unless specified otherwise by the Sponsor.
Samples of test substance formulations were not taken for analysis and consequently the homogeneity, concentration and stability of the test item were not determined.

Preparation of Animals:
The day before dose application, the fur was removed from the dorsal region and both flanks of each animal using veterinary clippers. Care was taken to avoid abrading the skin.
Prior to the start of the test the animals were weighed and the individual dose to be administered was adjusted to the animal’s body weight.

Dose Administration:
The test item was applied evenly to an area of clipped skin equivalent to approximately 10% of the total body surface area. The site of application was covered with a gauze dressing backed with semi-occlusive surgical tape.

Dose Levels:
Dose administration was once dermal (topical).
Based on available information on the toxicity of the test item, 2000 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.

One single animal was treated as follows:
Dose Level: 2000 mg/kg
Vehicle: Corn oil
Dose Volume: 5 mL/kg

In the absence of mortality or toxicity at a dose level of 2000 mg/kg, 2 additional animals were treated as follows:
Dose Level: 2000 mg/kg
Vehicle: Corn oil
Dose Volume: 5 mL/kg

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

Exposure Period:
The exposure period was twenty-four hours, then the dressings were carefully removed. Residual test item was removed by a cotton wool tissue soaked in corn oil to remove any residual test item.
After removal of the dressings and subsequently for 14 days, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth): 4

Edema Formation
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well-defined by definite raising): 2
Moderate edema (raised approximately 1 millimeter): 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure): 4

Any other skin reactions, if present were also recorded.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Morbidity/Mortality Inspection and Clinical Observations:
Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days.
All animals were observed for 14 days after dosing.
The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation for all individual animals. If applicable, the time of death/humane kill was recorded as precisely as possible. Observations included changes in the skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.

Determination of Body Weight:
Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14, or (if applicable) at death (unscheduled).

Terminal Investigations:
Necropsy:
At the end of the study the animals were killed by CO2 asphyxiation.
A gross necropsy was performed on all animals that died or were humanely killed during the study (if applicable) and at the scheduled end of the in-life part. This consisted of an external examination and opening of the abdominal and thoracic cavities. Any macroscopic abnormalities were 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:

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

Gross pathology:

In the stomach, one animal showed orange spots in the half digested food.

Other findings:

Dermal Reactions:
Animal 3 showed a small red spot and scratch on the skin and animal 2 and 3 showed patchy or no regrowth of fur, respectively. Stained fur and substance residuals were observed in all animals.

Individual Dermal Reactions – 2000 mg/kg b.w.

The Draize Scale was used for scoring primary skin irritation (erythema and edema).

Dose Level (mg/kg)	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	Fs Sr	Fs Sr	Fs Sr	Fs Sr	Fs Sr	Fs Sr	Fs Sr	0	0	0	0	0	0	0
	2 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	Fs Sr	Fs Sr	Fs Sr	Fs Sr	Fs	Fs	Fs	0	0	0	0	0	F	0
	3 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	Fs Sr	Fs Sr	Fs Sr	Fs Sr	Fs*	Fs**	0	0	0	0	0	0	F°	0

Fs stained fur
Sr substance residues
*red spot on skin
**small scratch
F fur grew back patchy
F° fur did not grow back

Interpretation of results:

GHS criteria not met

Remarks:

Not classified: EU CLP

Conclusions:

The acute median lethal oral dose (LD50) to rats of Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide was demonstrated to be greater than 2000 mg/kg body weight.
Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).

Executive summary:

Summary:

The study was performed to assess the acute dermal toxicity of Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide to the rat.

Methods:

Initially, one female animal was given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. Based on the preliminary results of the initial test, a further two female animals were similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results:

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: Animal 3 showed a small red spot and scratch on the skin and animals 2 and 3 showed patchy or no growth of fur, respectively. Stained fur and substance residuals were observed in all animals.

Body Weight: All animals showed expected gains in body weight.

Necropsy: Animal 2 showed orange spots in the half digested stomach content.

Conclusion:

The acute dermal median lethal dose (LD₅₀) to rats of Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide was found to be greater than 2000 mg/kg body weight. Reaction mass of crystalline magnesium silicate and crystalline silicon and synthetic amorphous silicon dioxide is included in Category 5/Unclassified according to the Globally Harmonised System (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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.

The substance does not meet the criteria for classification under the EU CLP regulations for acute toxicity via the inhalation route based on the result of an acute inhalation toxicity study, which gave a LC₅₀of > 5.05 mg/L, which is above the classification cut-off value (≤5.0 mg/L) for acute inhalation toxicity for dusts and mists.

The substance does not meet the criteria for classification under the EU CLP regulations for acute toxicity via the dermal route based on the result of an acute dermal toxicity study, which gave a LD₅₀of > 2000 mg/kg bodyweight, which is above the classification cut-off value ( ≤2000 mg/kg bodyweight) for acute dermal toxicity.