Silicon tetrachloride

Endpoint summary

Description of key information

In the key acute oral toxicity study, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and pre-GLP, an LD50 for silicon tetrachloride was concluded to be 238 mg/kg bw in rats (Younger Laboratories, 1967).

In the key acute inhalation toxicity study, conducted according to a protocol similar to OECD Test Guideline 403 and in compliance with GLP, an LC50 value of 1312 ppm (equivalent to 9117 mg/m3 based on MW of 169.9 g/mol) was concluded (Dow Corning Corporation, 1997).

In the key acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 but pre-GLP, no mortalities occurred and an LD50 of >10,000 mg/kg bw was concluded (Younger Laboratories, 1967).

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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Test conducted prior to guideline adoption

Deviations:

yes

Remarks:

No test substance or animal environmental condition details.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 % in corn oil
- Amount of vehicle: No data
- Justification for choice of vehicle: No data
- Purity: No data

Doses:

158, 200, 251 and 316 mg/kg bw

No. of animals per sex per dose:

Five animals per dose (some doses had two male and three female, others had three male and two female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: At least 8 days (animals died up to day 8, but no other information).
- Frequency of observations and weighing: Observations for clinical signs of toxicity were made - no further details given.
- Necropsy of survivors performed: no
- Other examinations performed: macroscopic examination of animals that died.

Statistics:

Mortality data was used for calculation of the LD50 and was done according to modification of the method of EJ de Beer.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

238 mg/kg bw

95% CL:

> 205 - < 275

Mortality:

There were 0, 1, 4 and 4 deaths in the 158, 200, 251 and 316 mg/kg bw. Survival time was several hours to eight days with most deaths occurring in four to eight days.

Clinical signs:

other: Symptoms included prostration and dyspnea in 30 minutes. Severe diarrhea and loss of appetite were noted.

Gross pathology:

Severe inflammation of the gastric mucosa was noted. The intestinal tract was gaseous and irritated. Liver and renal congestion was noted.

Other findings:

No other findings reported

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In the acute oral toxicity study, conducted according to a protocol similar to the now-delete OECD Test Guideline 401 and pre-GLP, an LD50 for silicon tetrachloride was concluded to be 238 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

238 mg/kg bw

Quality of whole database:

Klimisch score of 2.

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:

25.09.1995 to 27.03.1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

1-hour exposure

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 182 +/- 25 grams (males) and 136 +/- 12 grams (females)
- Fasting period before study: No data
- Housing: Stainless steel, wire mesh bottomed cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: One week


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-78
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 12.10.1995 To: 27.10.1995

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Exposure duration: One hour plus six minutes (T99) using whole body exposure methods

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass whole body chamber
- Exposure chamber volume: 175 L
- Method of holding animals in test chamber: None
- Source and rate of air: 42-45 air changes per hour (from room air)
- Method of conditioning air: Filtered (HEPA and activated carbon)
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: 22 ± 2°C, 30-50%, under slight negative pressure.


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatograph and mass spectrometer
- Samples taken from breathing zone: No data, but four samples were collected for each exposure period.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

1209, 1497 and 3051 ppm (nominal) and 202, 307 and 777 ppm (actual mean)

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for clinical signs of toxicity: daily. Body weights: Prior to exposure and on Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross pathology.

Statistics:

The inhalation median lethal nominal concentration (LC50), 95% fiducial limits, approximate slope of the dose-response curve were calculated using SAS/STAT Probit program. Mean body weights and standard deviations were also calculated.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 312 ppm

95% CL:

> 1 006 - < 1 529

Exp. duration:

1 h

Remarks on result:

other: equivalent to 9117 mg/m3 based on MW of 169.9 g/mol.

Mortality:

All animals died at the highest concentration. Three animals died (1 male and 2 females) at the nominal concentration of 1209 ppm and 8 died (5 males and 3 females) at the concentration of 1497 ppm.

Clinical signs:

other: In the following summation, the study day or range of study days of onset is presented parenthetically after each clinical sign, with the day of exposure being study day 1. Clinical signs noted in a majority of the 1209 ppm rats included difficulty breath

Body weight:

Body weights were initially reduced at one week post-exposure, but surviving animals were gaining weight by the end of the observation period.

Gross pathology:

Among the 10 rats that survived to the scheduled necropsy, missing, misshapen and/or shrunken extremities were noted for nine, as was discoloration of the extremities. Uni- or bilateral corneal opacity was seen in six rats that survived to the scheduled necropsy. Obstructed nostrils were present for the two 1497 ppm rats that survived and various external staining was seen in two 1209 ppm rats that survived. A total of 21 rats died on the study. Findings seen at necropsy in approximately one-half or more of these rats included various external staining (N = 20), discoloration of the extremities (N = 17), liver congestion (N = 17), pulmonary haemorrhage, congestion and/or consolidation (N = 16), unilateral or bilateral corneal opacity (N = 15), obstructed nostrils (N = 15), pulmonary ectasia (N = 11), decreased or absent body fat (N = 11), blood in the gastrointestinal lumen (N = 10) and dehydration. In addition, missing, misshapen and/or shrunken extremities and gaseous distension of the gastrointestinal tract were each seen in six rats that died.

Other findings:

Potential target organs: None specifically identified in the report, however, clinical signs and necropsy findings were consistent with the respiratory tract and eyes being target organs. Responses were generally consistent between males and females.

Number of deaths at each dose level:

Sex	Dose level (ppm)	No. Deaths	Days to Death
Males	1209	1	14
	1497	5	6, 7, 7 ,8 ,8
	3051	5	1, 1, 1, 1, 2
Females	1209	2	9, 11
	1497	3	7, 11, 12
	3051	5	2, 2, 2, 3, 3

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In the acute inhalation toxicity study, conducted according to a protocol similar to OECD Test Guideline 403 and in compliance with GLP, an LC50 value of 1312 ppm (equivalent to 9117 mg/m3 based on MW of 169.9 g/mol) was concluded.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

9 117 mg/m³ air

Quality of whole database:

Klimisch score of 1.

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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Test was conducted prior to adoption of test guideline

Deviations:

yes

Remarks:

One animal per dose, used to measure minimum lethal dose rather than LD50, no necropsy as no animals died, no test substance or animal environmental condition details.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data given

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: Occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1000, 1580, 2510, 3980, 6310, 10000 mg/kg bw

Duration of exposure:

24 hours

Doses:

1000, 1580, 2510, 3980, 6310, 10000 mg/kg bw

No. of animals per sex per dose:

1 animal/dose (both male and female animals were used)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No
- Other examinations performed: None

Statistics:

No statistics performed

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 10 000 mg/kg bw

Mortality:

The highest application of 10000 mg/kg was not found to be lethal by dermal exposure.

Clinical signs:

other: Symptoms included marked discomfort and moderate weakness at the higher dosage levels. 

Gross pathology:

None conducted

Other findings:

None reported

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 but pre-GLP, no mortalities occurred and an LD50 of >10,000 mg/kg bw was concluded.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Klimisch score of 2

Additional information

In the key acute oral toxicity study for silicon tetrachloride, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and pre-GLP, an LD50 value was concluded to be 238 mg/kg bw. Five Sprague-Dawley rats per dose were given oral gavage dose of 158, 200, 251 and 316 mg/kg bw silicon tetrachloride in corn oil. Thereafter, the animals were observed for mortality and clinical signs of toxicity for at least 8 days. Animals that died were examined macroscopically. There were 0 out of 5 (0/5), 1/5, 4/5 and 4/5 deaths in the 158, 200, 251 and 316 mg/kg bw, respectively. Most deaths occurred in four to eight days after dosing. Clinical signs included prostration and dyspnoea within 30 minutes, severe diarrhoea and loss of appetite. At necropsy, severe inflammation of the gastric mucosa, liver and renal congestion were observed as well as gaseous and irritated intestinal tract (Younger Laboratories, 1967).

In the key acute inhalation toxicity study for silicon tetrachloride, conducted according to a protocol similar to OECD Test Guideline 403 and in compliance with GLP, an LC50 value of 1312 ppm (equivalent to 9117 mg/m3 based on MW of 169.9 g/mol) was concluded. Fischer 344 male and female rats, 5 per sex and per dose, were exposed to the vapours of silicon tetrachloride for one hour in whole body inhalation chambers. Following exposure, the animals were observed for 14 days. At the highest concentration (3051 ppm), all animals died. At 1497 ppm, 5/5 males and 3/5 females died and at 1209 ppm, 1/5 male and 2/5 females died. In total, 21 rats died prior to the scheduled necropsy. In the majority of the 3051 ppm group, clinical signs included difficulty breathing, closed eyes, ocular discharge, swollen nose, wet fur, discharge/drainage on fur and red and swollen paws. Additionally, rales, decreased activity, eye opacities, lacrimation and drainage from the nose and/or mouth were observed. In the 1497 ppm group, clinical signs included difficulty breathing, necrosis of the nose, ocular discharge, wet fur, red and swollen paws, decreased activity, ataxia, rales, emaciation, distended abdomen, hunched posture, drainage from the nose and mouth, swollen and/or red nose, necrosis of paw, eye opacities, eyes that appeared small, eyes closed, rough fur and piloerection. Other clinical sign in this group were lacrimation and black faeces. No surviving rats returned to a fully normal clinical condition prior to the scheduled necropsy. In general, the clinical signs listed above and/or their sequelae were present until death/scheduled necropsy. Body weights were initially reduced at one week post-exposure, however, surviving animals were gaining weight by the end of the observation period.

Nine of ten surviving animals were noted to have missing, misshapen and/or shrunken extremities as well as discolouration of the extremities. Furthermore, uni- or bilateral corneal opacity was observed in six rats that survived to the scheduled necropsy. Obstructed nostrils were present for the two 1497 ppm rats that survived and various external staining was seen in two 1209 ppm rats that survived. Additional necropsy findings included pulmonary haemorrhage, congestion and/or consolidation, obstructed nostrils, pulmonary ectasia, decreased or absent body fat, blood in the gastrointestinal lumen and dehydration (Dow Corning Corporation, 1997).

In a limited IUCLID 2000 summary of an acute inhalation toxicity study, conducted prior to the adoption of OECD Test Guidelines and GLP, the LD0 for silicon tetrachloride was 15 mg/l in mice. No further details are available (Unknown, 1969).

In a very limited IUCLID 2000 summary of an acute inhalation toxicity study, conducted prior to the adoption of OECD Test Guidelines and GLP, the LD50 for silicon tetrachloride was 8000 ppm in rats. No further details are available (Carpenter et al., 1949).

In a very limited summary of an acute inhalation study (reliability score 4), conducted prior to the adoption of OECD Test Guidelines and pre-GLP, 8000 ppm of silicon tetrachloride killed 2/6, 3/6 or 4/6 rats. An LC50 was not determined. No further details are available (Younger Laboratories, 1967).

In an acute inhalation toxicity study, conducted prior to the adoption of the OECD Test Guideline and GLP, an LC100 was determined to 488.3 mg/L. Six male rats were exposed to silicon tetrachloride for 15 minutes. There was a heavy fog in the chamber during the exposure and only one dose was tested (488.3 mg/L). Signs of toxicity observed during the exposure included roughened fur, ocular discharge, salivation, extreme laboured breathing, collapse and death. Gross macroscopic examination revealed severe lung congestion and ocular opacity suggestive of a corrosive effect (Younger Laboratories, 1978).

In a very limited summary of an acute inhalation toxicity study (reliability score 4), conducted prior to OECD Test Guidelines and GLP, the one-hour LC50 for silicon tetrachloride in rats was not determined. The LC0 and LC100 were 23400 and 46800 ppm, respectively (Mellon Institute, 1951).

In the key acute dermal toxicity study for silicon tetrachloride, conducted according to a protocol similar to OECD Test Guideline 402 but pre-GLP, an LD50 of >10,000 mg/kg bw was concluded. Undiluted silicon tetrachloride was applied to the clipped, intact skin of New Zealand white rabbits (one male or female per dose) at doses of 1000, 1580, 2510, 3980, 6310 or 10,000 mg/kg bw for 24 hours under occlusive dressing. The animals were observed for 5 days. Clinical signs included marked discomfort and moderate weakness at the higher dosage levels. At 3980 mg/kg bw, there was no body weight increase within five days after exposure. However, at doses of 6310 and 10 000 mg/kg bw, the animals lost 200 grams within the five days after exposure. No mortality occurred and therefore, necropsies were not performed. It was concluded that the test substance is not lethal up to a dermal dose of 10,000 mg/kg bw in rabbits (Younger Laboratories, 1967).

Justification for classification or non-classification

Based on the available information, silicon tetrachloride requires classification for acute oral toxicity Category 3, H301: “Toxic if swallowed” and acute inhalation toxicity (vapour) Category 3, H331: “Toxic if inhaled” according to Regulation EC (No) 1272/2008. No classification is required for acute dermal toxicity.