[No public or meaningful name is available]

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Silicon

EC Number:

231-130-8

EC Name:

Silicon

Cas Number:

7440-21-3

Molecular formula:

Si

IUPAC Name:

Silicon

Constituent 2

Reference substance name:

Magnesium silicate

EC Number:

237-413-2

EC Name:

Magnesium silicate

Cas Number:

13776-74-4

Molecular formula:

H2O3Si.Mg

IUPAC Name:

magnesium(2+) ion oxosilanebis(olate), crystalline

Constituent 3

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

Silicon dioxide, amorphous

Constituent 4

Reference substance name:

Dimagnesium silicate

EC Number:

233-112-5

EC Name:

Dimagnesium silicate

Cas Number:

10034-94-3

Molecular formula:

Mg2O4Si

IUPAC Name:

dimagnesium silicate

impurity 1

Reference substance name:

Carbon

EC Number:

231-153-3

EC Name:

Carbon

Cas Number:

7440-44-0

Molecular formula:

C

IUPAC Name:

Carbon

impurity 2

Reference substance name:

Metallic impurities (Na and S)

IUPAC Name:

Metallic impurities (Na and S)

Test material form:

solid: particulate/powder

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.

Test animals

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.

Administration / exposure

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

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).