Disodium metasilicate

Endpoint summary

Description of key information

oral: LD50 (rat) = 1152 - 1349 mg/kg bw
inhalation: LC50 (rat) > 2.06 g/m3
dermal: LD50 (rat) > 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to basic scientific principles, study report provides only summary of data, with no/very few tables with data from individual animals. There were discrepancies between the study report and the abstract (Ito, 1986).

Principles of method if other than guideline:

Standard acute oral toxicity

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: T23-48:ddy

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Source: Sankyo Laboratory Service 
- Age: 4 weeks

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

- Volume administered or concentration: 0.05-0.19 ml/10g for males, 0.05-0.14 ml/10g for females

Doses:

500-1920.8 mg/kg (males), 500-1372 mg/kg (females)

Control animals:

not specified

Details on study design:

- Post dose observation period: seven days

EXAMINATIONS: mortality, clinical symptoms, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

770 - 820 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

661.5 - 896.3 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

666.7 - 1 008.6 mg/kg bw

Remarks on result:

other: 66.7-1087.6 mg/kg is reported in Ito, 1986

MORTALITY: 
- Time of death: 4 hrs - 5 days

CLINICAL SIGNS:

2 minutes after administration males and females became lethargic and had a hunched posture. Tear flow increased with dose level. Surviving animals recovered within 2-4 days. The animals that died were lethargic, did
not react to external stimuli, had hanging eyelids, paralysis of hind legs, clonicity and tonic cramps, followed by cyanosis and respiratory paralysis.

NECROPSY FINDINGS: 

the following symptoms increased with increasing dose: localised bleeding in the mucous membranes of the "glandular stomach", duodenum, mucous membranes of the central part of the "small gut", capillary dilation,
rarefaction of the stomach lining, clear liver lobules, faded colour of the liver rim, redness of the gall. Animals
dosed 1372 mg/kg and above had bleeding and inflammation extending from the "glandular stomach"to the central part of
the "small gut". In surviving animals the liver lobules looked slightly clearer and the spleen showed slight rubefaction, compared to control group animals.

POTENTIAL TARGET ORGANS: stomach, liver, gut.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to basic scientific principles, study report provides only summary of data, with no/very few tables with data from individual animals.

Principles of method if other than guideline:

Standard acute oral toxicity

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Source: Nippon Kurea
- Age: 4 weeks

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

- Volume administered or concentration: 0.265-1 ml/100 g for males, 0.455-1.3 ml/100g for females

Doses:

538-2000 (males), 910-2600 (females)

No. of animals per sex per dose:

110 in total

Control animals:

not specified

Details on study design:

- Post dose observation period: seven days

EXAMINATIONS: mortality, clinical symptoms, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 152 - 1 349 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

1 189.6 - 1 530 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

994.7 - 1 335.9 mg/kg bw

MORTALITY:
- Time of death: 30 min - 96 h
 
CLINICAL SIGNS:

lethargy, increased breathing frequenc immediately after dosing, 20 minutes later the animals became lethargic, cyanosis and platycoria was observed. At 30 min the first animals developed clonicity and tonic
cramps, dying of respiratory paralysis. The symptoms increased in intensity, had an earlier onset, and were observed in a higher number of animals in the group with increasing dose level. 

NECROPSY FINDINGS:

the animals that died had localised bleeding at the rim of the "glandular stomach", which partly depended on the dose, and bleeding and rubefaction in the duodenum. Some animals in the high dosage group had
considerable stomach bleeding. Surviving animals had no significant changes.

POTENTIAL TARGET ORGANS: stomach

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Too little data available.

Principles of method if other than guideline:

Standard acute oral toxicity method

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male

Vehicle:

not specified

Doses:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

1 750 mg/kg bw

RS-Freetext:
MORTALITY:
- Time of death: from 3 hours up until 2 days after exposure
- Number of deaths at each dose: Not reported 
CLINICAL SIGNS: Apathy, staggering gait, dyspnoea,
piloerection and abdominal discomfort
NECROPSY FINDINGS: Not reported
POTENTIAL TARGET ORGANS: Not reported

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Too little data available.

Principles of method if other than guideline:

Standard acute oral toxicity test

GLP compliance:

no

Test type:

standard acute method

Species:

mouse

Sex:

male

Vehicle:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

1 200 - 1 700 mg/kg bw

RS-Freetext:
MORTALITY: Not reported
CLINICAL SIGNS: "uncharacteristic" according to the authors
of the study report
NECROPSY FINDINGS: Not reported
POTENTIAL TARGET ORGANS: Not reported

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only secondary literature available (review).

Principles of method if other than guideline:

Standard acute oral toxicity

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Dose descriptor:

LD50

Effect level:

800 mg/kg bw

RS-Freetext:
MORTALITY: Not reported
CLINICAL SIGNS: Not reported
NECROPSY FINDINGS: Not reported
POTENTIAL TARGET ORGANS: Not reported 
SEX-SPECIFIC DIFFERENCES: Not reported

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only secondary literature available (review).

Principles of method if other than guideline:

Standard acute oral toxicity

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Dose descriptor:

LD50

Effect level:

600 mg/kg bw

RS-Freetext:
MORTALITY: Not reported
CLINICAL SIGNS: Not reported
NECROPSY FINDINGS: Not reported
POTENTIAL TARGET ORGANS: Not reported 
SEX-SPECIFIC DIFFERENCES: Not reported

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:

19 Oct 2004 - 16 Dec 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets national standard methods; GLP

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

Product Safety Laboratories

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley derived albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 255 - 285 g (males) and 180 - 205 g (females)
- Housing: singly in stainless steeel cages
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): tap wter
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 21 Oct To: 4 Nov 2004

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: filtered air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole body plexiglas chamber
- Exposure chamber volume: 150 L
- Method of holding animals in test chamber: cages
- Source and rate of air: air compressor, total airflow 45.7 L per minute
- System of generating particulates/aerosols: The test atmosphere was generated using a 1/4 inch JCO atomizer, FC3 fluid cap and 70SS air cap. Compressed air was supplied. The test substance was metered to tthe atomization nozzle through size 14 tygon tubing using a peristaltic pump.
- Method of particle size determination: eight stage Andersen cascade impactor
- Temperature, humidity, pressure in air chamber:


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were collected with filter papers which were wighed before and after collection to determine the mass collected. This value was devided by the total vlume of air sampled to determine the chamber concentration. Sample airflows were measured using a Mass Flowmeter.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 9 µM: 4%, 5.8 µm: 8.3%, 4.7 µm: 11.1%, 3.3 µm: 12%, 2.1 µm: 32%, 1.1 µm: 22.6%, 0.7 µm: 7.4%, 0.4 µm: 2.6%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.7 µm/1.96

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above

Duration of exposure:

4.4 h

Concentrations:

2.06 ± 0.19 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: in chamber animal observations and at least daily following exposure; body weights were recorded prior to exposure and again on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.06 mg/L air (analytical)

Exp. duration:

4 h

During exposure, animals showed hunched posture and hypoactivity. All animals recovered from the above clinical signs upon removal from the exposure chamber and appeared healthy and active over the 14 -day observation period. All animals survived exposure to the test atmosphere and gained body weight over the 14 -day period. No gross abnormalities were noted for any of the animals at terminal necropsy.

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:

19 Oct 2004 - 16 Dec 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets national standard methods; GLP

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

Product Safety Laboratories

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley derived albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals Inc., Boyertown
- Age at study initiation: 8 -9 weeks
- Weight at study initiation: 251 - 280 g (males) and 175 - 210 g (females)
- Housing: sngly in stainless steel cages
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 20 Oct To: 3 Nov 2004

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area and the trunk
- % coverage: 10 (2 inches x 3 inches)
- Type of wrap if used: Durapore tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test sites were gently cleansed
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.71 - 1.1 mL depending on body weight
- Concentration (if solution): 30%

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently during the first sevral hours after application and at least once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

All animals survived, gained body weight and appeared healthy and active. Apart from the dermal irritation (erythema) and alopecia noted at the application site of five animals (4 females and 1 male) between days 1 and 8, there were no other signs of toxicity. No gross lesions were observed at final necropsy in any animal.

Additional information

Various concentrations (10 ¿ 99%) of disodium metasilicates have been tested using oral administration in rats and mice. The majority of test results are cited as secondary literature only (Schleyer and Blumberg, 1982), but several study reports are available, although in limited detail (Ito et al. 1986, Saiwai et al. 1980, Gloxhuber 1973, Gloxhuber and Potokar 1971). Clinical symptoms observed in a dose-dependent manner consisted of apathy, ataxia and respiratory paralysis. Histopathology revealed acute gastro-enteritis, mottled livers as well as chemical irritation and/or corrosion of the viscera. All symptoms are indicative of effects due to high alkalinity.

Limit tests were performed with potassium silicate for the inhalative and dermal exposure route. No deaths occurred. Only clinical signs caused by irritation (hunched posture, hypoactivity and erythema), which were all reversible, were observed.

Justification for classification or non-classification

Disodium metasilicate is not classified as harmful if swallowed. All symptoms of acute toxicity are due to high alkalinity.