Registration Dossier

Administrative data

Description of key information

No data are available for the repeated dose oral toxicity of trichlorosilane therefore, good quality data for the precipitated hydrolysis product, synthetic amorphous silica (SAS) have been used to address the potential for systemic toxicity.

In a repeat dose 90-day oral toxicity study (Kim et al., 2014) with Sprague-Dawley rats, two forms of synthetic amorphous silica (SAS and NM-202; differing in particle size and specific surface area) were administered (vehicle: water) by oral gavage for 90 consecutive days at a dose of 500, 1000 or 2000 mg/kg bw/day (10 animals/sex/group). The particles were described as either 20 or 100 nm in diameter. Extra animals were included in the control (received water only) and highest dose groups to allow for a two-week post-exposure recovery period. Observations were made according to OECD Test Guideline 408. For 20 and 100 nm silica samples the findings were sporadic and without a dose-response, so were concluded by the study authors to be not treatment-related. The NOAEL for both particle sizes was therefore concluded to be ≥2000 mg/kg bw/day.

Since the local corrosive effects of chlorosilanes are significant, valid inhalation studies according to the relevant guidelines are technically not feasible. It is also unlikely that any systemic effects would be observed at doses made sufficiently low to prevent the known corrosive effects and/or distress in the test species. Indeed, ECHA’s Executive Director made the following statement in his decision (No. ED/49/2015) for trichlorosilane “ECHA notes that the Contested Decision should not have provided the option of carrying out the PNDT study on the registered substance, which is corrosive and consequently can only be tested at very low concentrations. In a PNDT study, which normally requires high systematic availability of the tested substance, the very low concentrations would almost certainly lead to a negative result”.

To support this conclusion, a 28-day inhalation study with another chlorosilane, dichloro(dimethyl)silane (CAS 75-78-5, WIL, 2014) is used to demonstrate that local effects are dominated by generation of the hydrolysis product, HCl, and that there are no adverse systemic effects.

For local effects, a good quality study on hydrogen chloride is available. In a 90-day repeated dose inhalation study in rats and mice (Toxigenics, 1984), 31 males and 21 females of each species/strain were exposed to test concentrations of 0, 10, 20 and 50 ppm hydrogen chloride gas (HCl). Treatment was whole-body exposure for six hours per day, 5 days per week. No serious adverse systemic effects were observed in rats and mice exposed up to 50 ppm (approximately 70 mg/m3) for 6 hours per day, 5 days per week. The only significant adverse finding relating to systemic toxicity was decreased body weight at the highest dose level. The No Observed Adverse Effect Concentration (NOAEC) for systemic effects was determined to be 20 ppm (approximately 30 mg/m3) based on decreased body weight following exposure to 50 ppm. Local effects on the nasal turbinates of mice were observed at all dose levels tested (10, 20 and 50 ppm). No NOAEC for local effects was established as irritant/corrosive effects were observed at all dose levels tested. Therefore, a LOAEC of 10 ppm was concluded.

No suitable dermal data are available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orient Bio, Korea
- Age at study initiation: 6 weeks old at purchase
- Weight at study initiation: 187.9-205.3 grams for males and 143.3-167.1 grams for females
- Fasting period before study: No
- Housing: Two animals per cage were housed in stainless steel wire cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-23.3°C
- Humidity (%): 42.0-51.4 %
- Air changes (per hr): 10-15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: No data
Route of administration:
oral: gavage
Vehicle:
other: Distilled water
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: Colloidal silica NPs with 20 nm and 100 nm diameters were diluted in distilled water and each of the tested doses were formulated by dilution of the highest dose with distilled water. Working samples of each dose formulation were prepared daily during the study. The formulated test particles were homogenised by vortexing just prior to administration.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Remarks:
20 nm synthetic amorphous silica particles
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Remarks:
20 nm synthetic amorphous silica particles
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
Remarks:
20 nm synthetic amorphous silica particles
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Remarks:
100 nm synthetic amorphous silica particles
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Remarks:
100 nm synthetic amorphous silica particles
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
Remarks:
100 nm synthetic amorphous silica particles
No. of animals per sex per dose:
Control and 2000 mg/kg bw/day: 15 (includes 5 animals for the recovery group);
500 and 1000 mg/kg bw/day: 10
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: A 14-day dose range-finding study was conducted where 5 male and 5 female rats were randomly distributed to each dose groups so the final mean body weight was approximately equal. The highest dose was selected to 2000 mg/kg bw/day, middle dose to 1000 mg/kg bw/day and the low dose to 500 mg/kg bw/day. A negative control group was included where the animals received distilled water. Clinical signs and body weight were monitored throughout the study whereas gross pathology was examined on the scheduled necropsy day. No toxicity was observed at the highest dose tested, therefore, the main study used the same highest dose of 2000 mg/kg bw/day.
- Post-exposure recovery period in satellite groups: Control and highest dose group had 5 extra animals each, which were observed for a recovery period of two weeks following the 90-day treatment period.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed once daily after treatment for well-being, mortality and clinical signs of toxicity (no further detail).

DETAILED CLINICAL OBSERVATIONS: It is not clear how detailed the observations were as it was not described in the publication.

BODY WEIGHT: Yes
- Time schedule for examinations: Prior to the administration of the test substance and thereafter, once a week.

FOOD CONSUMPTION: Yes
g food per rat was calculated.

FOOD EFFICIENCY: No

WATER CONSUMPTION: Yes
- Time schedule for examinations: Daily, calculated by difference between supplied amounts and remaining amounts measured the next day.

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Last week of 90-day treatment period
- Dose groups that were examined: Control and highest dose groups

HAEMATOLOGY: Yes
- Time schedule for collection of blood: The night before scheduled necropsy
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: The night before scheduled necropsy
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: For five animals per group of each sex during the last week of the 90-day treatment period. Total urine volume was calculated from the urine collected over a 24-h period.
- Metabolism cages used for collection of urine: Yes, for five animals from the control and highest dose group over a 3-h sampling period.
- Animals fasted: No data
- Parameters checked in Table 1 were examined.

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (see Table 2), on moribund or dead animals, and on all animals at the end of the 90-day exposure period.
HISTOPATHOLOGY: Yes (see Table 2), tissues from the control and highest dose group were examined histopathologically.
Statistics:
Body weight values, feed and water consumption data, haematological data, blood biochemistry data, and organ weight values were analysed for homogeneity of variance using Levene’s test. One-way analysis of variance was performed to evaluate the significance of differences. If the variance was homogeneous and a significant difference was identified, Scheffe’s multiple comparison test was performed as a post hoc test. If the variance was not homogeneous, the data were analysed using Dunnett’s T3 test. Analysis of data from the recovery groups was performed using the Student’s t-test. All analyses were performed using Statistical Package for the Social Sciences version 19.0 software (SPSS Inc, Chicago, IL, USA).
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
Irrespective of particle size, no treatment-related clinical signs occurred during the experimental period for rats of either sex. A few occurrences of salivation, loss of fur and wound scratching were observed in the 2000 mg/kg bw/day group for 20 nm silica. However, due to the sporadic nature and no dose-dependency, the study authors concluded that these observations were not related to treatment.
Mortality:
no mortality observed
Description (incidence):
No mortality occurred in any dose groups.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Regardless of SiO2 particle size, there were no statistically significant differences in body weight between treated rats and their respective control groups for either males or females.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
There were sporadic increases in food consumption for 20 nm silica and sporadic increases in food consumption for 100 nm silica. However, these differences were not considered as treatment-related.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
effects observed, non-treatment-related
Description (incidence and severity):
There were sporadic decreases in water consumption for 20 nm and 100 nm silica, however, these were not considered to be treatment-related.
Ophthalmological findings:
not specified
Description (incidence and severity):
The results were not reported although ophthalmoscopic examination was performed.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
In the high dose recovery group for 20 nm silica, a statistically significant increase in lymphocyte counts was observed compared to the control recovery group. There were no findings for the groups treated with 100 nm silica and therefore, the findings were not considered as treatment-related.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
No differences between treated and control animals were observed for 20 nm silica. For females of the high dose recovery group treated with 100 nm silica, aspartate aminotransferase and creatine kinase concentrations were statistically significantly decreased compared with the controls.
Urinalysis findings:
no effects observed
Description (incidence and severity):
There were no statistically significant differences in urinalysis parameters in any treated group compared with the respective control groups for either 20 nm or 100 nm silica.
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Relative liver weight was statistically significantly decreased whereas the absolute and relative lung weights were statistically significantly increased in males of the 2000 mg/kg bw/day dose group exposed to 20 nm silica compared to the control group. A statistically significantly increase in absolute weights of kidney, lung and submandibular glands and a statistically significant increase in the relative weights of kidneys and lungs were observed in the male 2000 mg/kg bw/day recovery group exposed to 100 nm silica. Females in the high dose recovery group had statistically significantly decreased absolute and relative ovary weights. The study authors concluded that due to the sporadic nature of the organ weight findings, the observations were not treatment related. No further details are available.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Pale yellowish discoloration on the posterior surface of the left lateral lobe of the liver was observed in one male animal from the 20 nm silica 500 mg/kg bw/day group. With regard to 100 nm silica, a small-sized right testis and epididymis were observed in one male from the 500 mg/kg group. A light yellow discoloration of the left lateral lobe of the liver (about 1 mm diameter), and a light yellow-coloured cyst with adjacent fat near the right kidney were also observed in another male in the 1000 mg/kg group. In addition, a small-sized left ovary was observed in one female from the 2000 mg/kg recovery group. However, no dose-dependency occurred and the effects were not considered to be related to treatment.
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Granulomatous inflammation was observed in one male rat from the 1000 mg/kg bw/day group and two from the 2000 mg/kg bw/day group treated with 20 nm silica. Chronic bronchioalveolar inflammation was observed in one male rat from the 2000 mg/kg bw/day group treated with 20 nm silica. There were no adverse findings from the groups treated with 100nm silica. These lesions were observed in four cases in total and were minimal to mild in severity.
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse observed effects were observed
Critical effects observed:
no

Table 1 - Organ weights and organ weight to body weight ratios of male rats in the 90-day gavage study (main group) of 20 nm SiO2 nanoparticles*

   0 (vehicle control)  500 mg/kg bw/day  1000 mg/kg bw/day  2000 mg/kg bw/day
 Number of animals  10  10  10  10
 Male        
Necropsy body weight

565.9±43.4

553.7±45.1

529.1±48.4

 

526.6±48.9

 
  Liver        
  Absolute (g)  

14.70±1.90

 

13.65±1.26

 

13.11±1.94

 

12.59±1.71

  Relative (%)  

2.59±0.18

 

2.47±0.14

 

2.47±0.16

 

2.38±0.11a

*Organ (absolute) weights and body weights are given in grams: organ weight to body (relative) weights are given as mg organ weight/g body weight (mean ± standard deviation); aP<0.05 significantly different from control, by Scheffe’s test.

Table 2 - Organ weights and organ weight to body weight ratios for the recovery group in the 90-day gavage study of SiO2 nanoparticles*

   0 (vehicle control)  2000 mg/kg bw/day
 Number of animals  5  5
 SiO2 (20 nm)    
 Male    
  Necropsy body weight  

569.8±38.4

 

545.9±35.0

  Lung    
  Absolute (g)  

1.61±0.07

 

1.81±0.12a

  Relative (%)  

0.28±0.02

0.33±0.02a

 
  SiO2 (100 nm)    
 Male    
 Necropsy body weight  

577.4±60.5

 

603.3±22.0

 Kidney    
  Absolute (g)  

3.27±0.21

 

3.69±0.21a

Relative (%)   

0.57±0.03

 

0.61±0.02a

 Lung    
  Absolute (g)  

1.62±0.09

1.93±0.08a

 
  Relative (%)  

0.28±0.02

0.32±0.02a

 
 Submaxillary gland    
  Absolute (g)  

0.78±0.04

0.96±0.12a

 
  Relative (%)  

0.14±0.01

0.16±0.02

 Female    
 Necropsy body weight  

303.9±47.8

304.9±16.9

 Ovary    
  Absolute  

0.094±0.009

 

0.066±0.022a

  Relative  

0.0314±0.0040

0.0217±0.0069a

 

*Organ (absolute) weights and body weights are given in grams: organ weight to body (relative) weights are given as mg organ weights/g body weight (mean ± standard deviation); aP<0.05, significantly different from control by Scheffe’s test.

Conclusions:
In a 90-day oral repeated dose toxicity study, conducted according to OECD Test Guideline 408 and in compliance with GLP, the NOAEL for 20 nm and 100 nm colloidal silica particles were concluded to be ≥2000 mg/kg bw/day in Sprague-Dawley rats based on no adverse effects observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch score of 1

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 May 1983 to 18 August 1983
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 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Limit test:
no
Species:
other: rat and mouse
Strain:
other: Sprague-Dawley rats, Fischer-344 rats, and B6C3F1 mice
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No
- Housing: Individually housed in 8 cubic meter stainless steel and glass inhalation chambers.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Data could not be found in report supplied
- Humidity (%): Data could not be found in report supplied
- Air changes (per hr): Data could not be found in report supplied
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 September 1984 To: 20 December 1984
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals were housed and exposed in 8 cubic meter stainless steel and glass inhalation chambers.
The test substance was first passed through a regulator and was maintained at a pressure of 50 psig. It was then passed through a flowmeter which measured the flow rate. The gas was then mixed with a supply of filtered, dry air, introduced at the top of the inhalation chamber and exhausted at the bottom. The negative pressure of each test chamber was maintained at 0.1 inches of water. The control chamber was maintained at a positive pressure of 0.02 inches of water.

TEST ATMOSPHERE
- Brief description of analytical method used: Analyses of chamber scrub samples were performed throughout the study by a method involving the titration of dissolved chlorides with a dilute solution of mercuric nitrate in the presence of a mixed diphenylcarbazone-bromophenol blue indicator. Each test chamber was sampled approximately once per hour. The control chamber was sampled once daily.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analyses of chamber scrub samples were performed throughout the study by a method involving the titration of dissolved chlorides with a dilute solution of mercuric nitrate in the presence of a mixed diphenylcarbazone-bromophenol blue indicator. Each test chamber was sampled approximately once per hour. The control chamber was sampled once daily.
Duration of treatment / exposure:
90 days
Frequency of treatment:
six hours, five days per week
Dose / conc.:
10 ppm
Remarks:
target concentration
Dose / conc.:
20 ppm
Remarks:
target concentration
Dose / conc.:
50 ppm
Remarks:
target concentration
No. of animals per sex per dose:
31 males and 21 females of each species/strain
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: No data
- Rationale for selecting satellite groups: Interim sacrifice group of 15 males and 10 females sacrificed after the fourth exposure.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice daily for mortality and clinical signs of toxicity.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly

BODY WEIGHT: Yes
- Time schedule for examinations: All animals: just prior to the first exposure (day 1), then weekly, and a final fasted body weight measurement was obtained prior to the 90-day sacrifice.

FOOD CONSUMPTION:
- Just prior to the first exposure (day 1), then weekly for each animal.

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 90 days.
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes, for approximately 12 hours.
- How many animals: 10 males and 10 females
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 90 days.
- Animals fasted: Yes, for approximately 12 hours.
- How many animals: 10 males and 10 females
- Parameters checked in table 1 were examined.

URINALYSIS: Yes, in 10 males and 10 females.
- Time schedule for collection of urine: At 90 days.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes, for approximately 12 hours.
- Parameters checked in table 1 were examined.

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
15 males and 10 females per group per strain/species were sacrificed the day following the fourth exposure for pathological examination. After 90 days of exposure 10 males and 10 females per group per strain/species (same animals as those for clinical pathology) were sacrificed for pathological examination.

At the day 5 interim sacrifice the nasal turbinates, trachea, lung and gross lesions were examined microscopically. Organs and tissues examined microscopically at 90 days are summarised in Table 2.
Statistics:
Parametric data such as body weight and food consumption were analysed using an analysis of variance (ANOVA). Statistically significant differences that were noted were further studied by either Tukey's (equal populations) or Scheffe's (unequal populations) Test of Multiple Comparison. Non-parametric data such as organ weight ratios were analysed using a Kruskal-Wallis ANOVA and a Test of Multiple Comparison. Discontinuous data such as appropriate incidences of histopathological findings were compared using CHI-SQUARE or Fischer's Exact Probability Test.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs were consistent with the irritant/corrosive properties of HCl (appendage, tail or lip injury in the form of toe missing/swollen/open/gelatinous, scabbed/deformed/lesion, crusty nose, tissue mass, mouth injury, scabbed nose, crusty muzzle, red stained fur, nasal discharge, crusty eye, poor coat quality.
Mortality:
mortality observed, treatment-related
Description (incidence):
One female high dose mouse was found dead on study day 12, and four low dose male mice were found dead on study day 92. In addition, one high dose female mouse was sacrificed in extremis on study day 20. One high dose female Sprague-Dawley rat was found dead on study day 4. However, the study authors noted that the deaths did not appear to be related to exposure to HCl.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
50 ppm HCl resulted in decreased body weights in all four strains after four exposures. Following 90 days of exposure B6C3F1 male and female mice and male Sprague-Dawley rats exposed to 50 ppm had biologically significant decreases in body weight.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
After four days of exposure there were statistically significant decreases in food consumption for high dose male Sprague-Dawley rats and male Fischer 344 rats. After 90 days high dose mice had the largest reduction in food consumption. The rats did not show a consistent reduction in food consumption that could be deemed exposure-related.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Decrease liver weight in high dose male and female mice and Fischer 344 female rats. The authors noted that this might have been due to the overall reduced body weights.
Gross pathological findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Animals exposed to all concentrations of HCl had minimal to mild rhinitis, which occurred in the anterior portion of the nasal cavity and was dose and time related. Mice also developed varying degrees of cheilitis with accumulations of haemosiderin-laden macrophages involving the perioral tissues at 50 ppm. At all exposure concentrations mice developed oesinophilic globules in epithelial cells lining the nasal turbinates after 90 days of exposure.
Histopathological findings: neoplastic:
not examined
Dose descriptor:
NOAEC
Effect level:
20 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Systemic NOAEC based on reduced body weights at 50 ppm.
Dose descriptor:
LOAEC
Effect level:
10 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Local LOAEC based on irritant/corrosive effects seen at all dose levels tested in mice.
Critical effects observed:
no
Conclusions:
In a well conducted 90-day gas inhalation study (reliability score 1) the systemic NOAEC for hydrogen chloride was 20 ppm based on decreased body weight following exposure to 50 ppm (6 hours/day, 5 days/week) in rats and mice. The main adverse findings related to irritant/corrosive effects on the nasal turbinates in mice.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 May 1983 to 18 August 1983
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 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Limit test:
no
Species:
other: rat and mouse
Strain:
other: Sprague-Dawley rats, Fischer-344 rats, and B6C3F1 mice
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No
- Housing: Individually housed in 8 cubic meter stainless steel and glass inhalation chambers.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Data could not be found in report supplied
- Humidity (%): Data could not be found in report supplied
- Air changes (per hr): Data could not be found in report supplied
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 September 1984 To: 20 December 1984
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals were housed and exposed in 8 cubic meter stainless steel and glass inhalation chambers.
The test substance was first passed through a regulator and was maintained at a pressure of 50 psig. It was then passed through a flowmeter which measured the flow rate. The gas was then mixed with a supply of filtered, dry air, introduced at the top of the inhalation chamber and exhausted at the bottom. The negative pressure of each test chamber was maintained at 0.1 inches of water. The control chamber was maintained at a positive pressure of 0.02 inches of water.

TEST ATMOSPHERE
- Brief description of analytical method used: Analyses of chamber scrub samples were performed throughout the study by a method involving the titration of dissolved chlorides with a dilute solution of mercuric nitrate in the presence of a mixed diphenylcarbazone-bromophenol blue indicator. Each test chamber was sampled approximately once per hour. The control chamber was sampled once daily.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analyses of chamber scrub samples were performed throughout the study by a method involving the titration of dissolved chlorides with a dilute solution of mercuric nitrate in the presence of a mixed diphenylcarbazone-bromophenol blue indicator. Each test chamber was sampled approximately once per hour. The control chamber was sampled once daily.
Duration of treatment / exposure:
90 days
Frequency of treatment:
six hours, five days per week
Dose / conc.:
10 ppm
Remarks:
target concentration
Dose / conc.:
20 ppm
Remarks:
target concentration
Dose / conc.:
50 ppm
Remarks:
target concentration
No. of animals per sex per dose:
31 males and 21 females of each species/strain
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: No data
- Rationale for selecting satellite groups: Interim sacrifice group of 15 males and 10 females sacrificed after the fourth exposure.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice daily for mortality and clinical signs of toxicity.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly

BODY WEIGHT: Yes
- Time schedule for examinations: All animals: just prior to the first exposure (day 1), then weekly, and a final fasted body weight measurement was obtained prior to the 90-day sacrifice.

FOOD CONSUMPTION:
- Just prior to the first exposure (day 1), then weekly for each animal.

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 90 days.
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes, for approximately 12 hours.
- How many animals: 10 males and 10 females
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 90 days.
- Animals fasted: Yes, for approximately 12 hours.
- How many animals: 10 males and 10 females
- Parameters checked in table 1 were examined.

URINALYSIS: Yes, in 10 males and 10 females.
- Time schedule for collection of urine: At 90 days.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes, for approximately 12 hours.
- Parameters checked in table 1 were examined.

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
15 males and 10 females per group per strain/species were sacrificed the day following the fourth exposure for pathological examination. After 90 days of exposure 10 males and 10 females per group per strain/species (same animals as those for clinical pathology) were sacrificed for pathological examination.

At the day 5 interim sacrifice the nasal turbinates, trachea, lung and gross lesions were examined microscopically. Organs and tissues examined microscopically at 90 days are summarised in Table 2.
Statistics:
Parametric data such as body weight and food consumption were analysed using an analysis of variance (ANOVA). Statistically significant differences that were noted were further studied by either Tukey's (equal populations) or Scheffe's (unequal populations) Test of Multiple Comparison. Non-parametric data such as organ weight ratios were analysed using a Kruskal-Wallis ANOVA and a Test of Multiple Comparison. Discontinuous data such as appropriate incidences of histopathological findings were compared using CHI-SQUARE or Fischer's Exact Probability Test.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs were consistent with the irritant/corrosive properties of HCl (appendage, tail or lip injury in the form of toe missing/swollen/open/gelatinous, scabbed/deformed/lesion, crusty nose, tissue mass, mouth injury, scabbed nose, crusty muzzle, red stained fur, nasal discharge, crusty eye, poor coat quality.
Mortality:
mortality observed, treatment-related
Description (incidence):
One female high dose mouse was found dead on study day 12, and four low dose male mice were found dead on study day 92. In addition, one high dose female mouse was sacrificed in extremis on study day 20. One high dose female Sprague-Dawley rat was found dead on study day 4. However, the study authors noted that the deaths did not appear to be related to exposure to HCl.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
50 ppm HCl resulted in decreased body weights in all four strains after four exposures. Following 90 days of exposure B6C3F1 male and female mice and male Sprague-Dawley rats exposed to 50 ppm had biologically significant decreases in body weight.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
After four days of exposure there were statistically significant decreases in food consumption for high dose male Sprague-Dawley rats and male Fischer 344 rats. After 90 days high dose mice had the largest reduction in food consumption. The rats did not show a consistent reduction in food consumption that could be deemed exposure-related.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Decrease liver weight in high dose male and female mice and Fischer 344 female rats. The authors noted that this might have been due to the overall reduced body weights.
Gross pathological findings:
no effects observed
Description (incidence and severity):
There were no treatment-related effects.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Animals exposed to all concentrations of HCl had minimal to mild rhinitis, which occurred in the anterior portion of the nasal cavity and was dose and time related. Mice also developed varying degrees of cheilitis with accumulations of haemosiderin-laden macrophages involving the perioral tissues at 50 ppm. At all exposure concentrations mice developed oesinophilic globules in epithelial cells lining the nasal turbinates after 90 days of exposure.
Histopathological findings: neoplastic:
not examined
Dose descriptor:
NOAEC
Effect level:
20 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Systemic NOAEC based on reduced body weights at 50 ppm.
Dose descriptor:
LOAEC
Effect level:
10 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Local LOAEC based on irritant/corrosive effects seen at all dose levels tested in mice.
Critical effects observed:
no
Conclusions:
In a well conducted 90-day gas inhalation study (reliability score 1) the systemic NOAEC for hydrogen chloride was 20 ppm based on decreased body weight following exposure to 50 ppm (6 hours/day, 5 days/week) in rats and mice. The main adverse findings related to irritant/corrosive effects on the nasal turbinates in mice.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
15 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch score of 2

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no adequate long-term repeated dose toxicity data on trichlorosilane so good quality data for the hydrolysis products polysilicic acid (equivalent to synthetic amorphous silica) and hydrogen chloride have been used to assess the potential for adverse effects following exposure to trichlorosilane.

Overview

It is considered not to be either ethical or technically feasible to perform repeated dose toxicity testing with trichlorosilane by any route of exposure due to its known corrosive properties, which dominate the toxicity profile of this substance. Following repeated oral dosing, the corrosive nature of the product could affect the lining of the stomach, giving rise to hyperplasia and a subsequent reduced food intake. This would confound the interpretation of any systemically driven effects. A guideline-compliant repeated-dose inhalation study should elicit systemic toxicity at the highest test concentration. Since the local corrosive effects of trichlorosilane would be significant, a valid inhalation study according to the relevant guidelines is technically not feasible. It is also unlikely that any systemic effects would be seen at dose levels made sufficiently low to prevent the known corrosive effects and/or distress in the test species. This has been confirmed in a 28-day inhalation study with another chlorosilane, dichloro(dimethyl)silane (WIL, 2014) in which there were no effects of treatment on clinical signs, body weight or food consumption that would indicate a systemic effect. Furthermore, the histopathology in the study indicated that the effects in the upper respiratory tract were similar to HCl. It is therefore concluded that HCl will dominate the inhalation toxicity profile of trichlorosilane.

With regard to the dermal and inhalation routes, due to the known corrosive effects of trichlorosilane, appropriate H-phrases and P-statements are included in the labelling, meaning that repeated skin and inhalation exposure is not expected. Any accidental skin contact or inhalation exposure could cause severe local effects but would be unlikely to cause any systemic effects.

There are no adequate long term repeated dose toxicity data on trichlorosilane so good quality data for the hydrolysis products polysilicic acid (equivalent to synthetic amorphous silica) and hydrogen chloride have been used to assess the potential for adverse effects following exposure to trichlorosilane.

ORAL ROUTE

SYSTEMIC EFFECTS

There are no adequate repeat-dose toxicity data on trichlorosilane, however, good quality data for synthetic amorphous silica (CAS 112926-00-8) have been used to assess the general systemic oral toxicity of trichlorosilane. Local effects from the hydrolysis product, hydrogen chloride (HCl) are not addressed by these data (see section on local effects below).

Trichlorosilane, like all inorganic chlorosilanes, is a severely corrosive substance that is decomposed by water, producing silicic acid and HCl. The reaction is highly exothermic (Merck, 2013). Hydrolysis half-life is approximately <0.3 minutes at 1.5°C and pH 4, 7 and 9. The initial products of hydrolysis are hydrogen chloride and silanetriol. The silanetriol is expected to react rapidly to produce hydrogen and monosilicic acid. Hydrogen would be released to the atmosphere.  

Monosilicic acid condenses to insoluble polysilicic acid [equivalent to synthetic amorphous silica (SAS)] at concentrations higher than 100-150 mg/l ‘SiO2equivalent’ in water (Holleman-Wiberg, 2001). At very high concentration, polysilicic acid can condense to silicon dioxide (SiO2). The hydrolysis products of hydrochloric acid and (poly) silicic acid are significant for the chemical safety assessment (CSR).

Monosilicic acid and polysilicic acid are naturally occurring substances which are ubiquitous in the environment. Soluble monosilicic acid is the major bioavailable form of silicon and plays an important role in the biogeochemical cycle of silicon (ECETOC, 2006). Typical background concentrations of monosilicic acid in the environment are up to 75 mg/l ‘SiO2equivalent’ in river water and up to 14 mg/l ‘SiO2equivalent’ in seawater (Iler, 1979).

The literature gives various values for the solubility of silicic acid, determined indirectly as ‘SiO2equivalent’ because the soluble species cannot be directly measured:

The solubility of monosilicic acid according to Alexander et al. (1954) at 25 °C:

·   150 mg/l ‘SiO2 equivalent’ at pH 2.0 and pH 3.0

·   130 mg/l ‘SiO2 equivalent’ at pH 4.2

·   110 mg/l ‘SiO2 equivalent’ at pH 5.7

·   100 mg/l ‘SiO2 equivalent’ at pH 7.7

·   490 mg/l ‘SiO2 equivalent’ at pH 10.3

·   1120 mg/l ‘SiO2 equivalent’ at pH 10.6

 

The solubility of monosilicic acid according to Goto and Okura (1953) at 25 °C:

·   120 mg/l ‘SiO2 equivalent’ at pH 2.0

·   150 mg/l ‘SiO2 equivalent’ at pH 7.0

 

The solubility of monosilicic acid according to Elmer and Nordberg (1958) at neutral pH:

·   170 mg/l ‘SiO2 equivalent’ at 35 °C

·   270 mg/l ‘SiO2 equivalent’ at 65 °C

·   465 mg/l ‘SiO2 equivalent’ at 95 °C

Due to the properties of trichlorosilane, particularly, the corrosive nature of the substance, it is impossible to conduct 90-day repeated dose toxicity studies in experimental animals. Additionally, it is impossible to isolate the hydrolysis product, monosilicic acid and thereby, it cannot be tested. However, based on physicochemical properties, it is known that an initial rapid hydrolysis to soluble monosilic acid will occur and the monomer will start to condense to form insoluble polysilicic acid (equivalent to SAS) following ingestion of trichlorosilane. This condensation will start to occur when the concentration of monosilicic acid reaches approximately 100-150 mg/l in the gastric juice.

Monosilicic acid (soluble silica) undergoes condensation reactions in solution at about 100 -150 mg/l ‘SiO2 equivalent’. The solubility of monosilicic acid in water is 150 mg/l ‘SiO2 equivalent'.

Following dosing by oral gavage, partitioning will occur between the dose vehicle and the aqueous environment in the stomach.

Mass dosed (in mg/day) = Body weight (in kg) x dose level (in mg/kg bw/day)

Dose concentration (in mg/l) = mass dosed (in mg/day) ÷ volume (in l)

So, the dose level (mg/kg bw/day) required to reach the dose concentration of 150 mg/l 'SiO2 equivalent', the estimated (conservative) maximum concentration of silicic acid that can occur in the stomach before condensation to insoluble polysilicic acid (equivalent to SAS) begins is calculated as follows:

Body weight of rat = 0.3 kg

Dose level = X                                                        

Estimated aqueous volume = 0.0015 l                                                                      

Dose concentration = 150 mg/l

150 mg/l = 0.3 kg x dose level (mg/kg bw/day) ÷ 0.0015l

Dose level = 0.75 mg/kg bw/day 'SiO2 equivalent'

Therefore, based on a condensation limit of 150 mg/l, the maximum dose level that could be used in practice to ensure exposure mainly to monosilicic acid in the stomach of experimental animals is approximately 0.75 mg/kg bw/day or less of 'SiO2 equivalent'.

A correction for molecular weight gives a maximum dose level for trichlorosilane:

Mr [trichlorosilane] = 135.45 g/mol

Mr [silicon dioxide] = 60.08 g/mol

Dose level [trichlorosilane] = [Dose level [silicon dioxide] x Mr [trichlorosilane]] / Mr [silicon dioxide]                

                                                = (0.75 mg/kg bw/day) x (135.45 g/mol) / (60.08 g/mol)

                                                = 1.69 mg/kg bw/day

Therefore, based on a condensation limit of 150 mg/l the maximum dose level of trichlorosilane that could theoretically be dosed to ensure exposure mainly to monosilicic acid is approximately 1.7 mg/kg bw/day.

For comparison purposes, using the above calculation, the following shows the dose concentrations for the dose levels typically used in experimental animal studies (100, 300 and 1000 mg/kg bw/day).

Body weight                               = 0.3 kg

Total amount dosed                    = 30 mg

Estimated aqueous volume          = 1.5 ml

Dose concentration                     = 20,000 mg/l

Body weight                               = 0.3 kg

Total amount dosed                    = 90 mg

Estimated aqueous volume          = 1.5 ml

Dose concentration                    = 60,000 mg/l

Body weight                                = 0.3 kg

Total amount dosed                     = 300 mg

Estimated aqueous volume          = 1.5 ml

Dose concentration                      = 200,000 mg/l

Therefore, dosing at these dose levels clearly gives a dose concentration in the stomach that far exceeds the dose at which condensation to polysilicic acid (equivalent to SAS) starts to occur. Consequently, the majority of the dose in the stomach will be present as insoluble polysilicic acid (equivalent to SAS). In all cases only approximately 150 mg/l will be present as soluble monosilicic acid.

Overall, it can be concluded that trichlorosilane at gavage doses unlikely to cause local corrosive effects and at doses that give mainly soluble monosilicic acid (2 mg/kg bw/day or less) would be unethical based on animal usage. However, since the vast majority of a gavage dose will rapidly condense to insoluble polysilicic acid, it is appropriate to use toxicology data on SAS to address the potential for oral toxicity of trichlorosilane.

In the key 90-day oral repeated dose toxicity study, conducted according to OECD Test Guideline 408 and in compliance with GLP, Sprague-Dawley rats were exposed daily to 20 or 100 nm of two forms of synthetic amorphous silica (described as SAS and NM-202; differing in particle size and specific surface area) in doses of 500, 1000 or 2000 mg/kg bw/day, respectively. Control animals received the vehicle distilled water only. Satellite groups included the control group and the highest dose groups and were observed for 14 days following the initial 90 days of exposure. Irrespective of particle size, no treatment-related clinical signs occurred during the experimental period for rats of either sex. A few occurrences of salivation loss of fur and wound scratching occurred in the 2000 mg/kg bw/day group for 20 nm silica in mouse. However, there were no dose-dependency and the findings occurred spontaneously and therefore, was not considered as treatment related. No treatment-related differences in mortality, body-weight changes, food or water consumption, haematological findings, clinical biochemistry, urinalysis were observed. Relative liver weight was statistically significantly decreased whereas the absolute and relative lung weights were statistically significantly increased in males of the 2000 mg/kg bw/day dose group exposed to 20 nm silica compared to the control group. A statistically significantly increase in absolute weights of kidney, lung and submandibular glands and a statistically significant increase in the relative weights of kidneys and lungs were observed in the male 2000 mg/kg bw/day recovery group exposed to 100 nm silica. Females in the high dose recovery group had statistically significantly decreased absolute and relative ovary weights. The study authors concluded that due to the sporadic nature of the organ weight findings, the observations were not treatment related.

Pale yellowish discolouration on the posterior surface of the left lateral lobe of the liver was observed in one male animal from the 20 nm silica 500 mg/kg bw/day group. With regard to 100 nm silica, a small sized right testis and epididymis were observed in one male from the 500 mg/kg group. A light yellow discoloration of the left lateral lobe of the liver (about 1 mm diameter) and a light yellow-coloured cyst with adjacent fat near the right kidney were also noted in another male in the 1000 mg/kg bw/day group. In addition, a small-sized left ovary was observed in one female from the 2000 mg/kg recovery group. However, no dose-dependency occurred and the effects were therefore not considered to be related to treatment. The histopathology examination revealed granulomatous inflammation in one male rat from the 1000 mg/kg bw/day group and two from the 2000 mg/kg bw/day group treated with 20 nm silica. Chronic bronchioalveolar inflamma tion was observed in one male rat from the 2000 mg/kg bw/day group treated with 20 nm silica. There were no adverse findings from the groups treated with 100nm silica. These lesions were observed in four cases in total and were minimal to mild in severity. It is concluded that there were no observed adverse effects and therefore, a NOAEL for 20 nm and 100 nm colloidal silica particles were concluded to be ≥2000 mg/kg bw/day in Sprague-Dawley rats (Kim et al., 2014).

In a supporting sub-chronic oral toxicity study, not conducted according to any OECD guideline and not specified if in compliance with GLP, Sprague-Dawley rats were dosed with two forms of synthetic amorphous silica (SAS and NM-202; differing in particle size and specific surface area) for 28 or 84 days. After 84 days of exposure to NM-202, an increased incidence of liver fibrosis was observed. Additionally, a moderate, although statistically significant increase in the expression of fibrosis-related genes in liver samples of this group occurred. Concentrations of biochemical and immunological markers in blood and isolated cells did not indicate toxicity. Therefore, the conservative NOAEL for NM-202 was 500 mg/kg bw/day and the NOAEL for SAS was ≥2500 mg/kg bw/day. Noteworthy, the limit dose of 1000 mg/kg bw/day was not tested for NM-202 (van de Zande et al., 2014).

INHALATION ROUTE

LOCAL EFFECTS

As has already been described above, trichlorosilane is a severely corrosive substance that is decomposed by water, producing silicic acid, HCl and hydrogen. Hydrogen is immediately exhaled. For local effects it is appropriate to use results of a 90-day inhalation toxicity study on HCl, which demonstrates the severe corrosive effects of HCl in the respiratory tract and a 4-week dichloro(dimethyl)silane study (WIL, 2014).

Hydrogen chloride

In the key 90-day inhalation toxicity study, conducted according to OECD Test Guideline 413 and in compliance with GLP, hydrogen chloride was tested in Sprague-Dawley rats, Fischer-344 rats and B6C3F1 mice. The exposure was whole-body exposure for 6 hours per day, 5 days a week in concentrations of 10, 20 or 50 ppm. Fifteen males and 10 females from each group were sacrificed after four exposures and the nasal turbinates, trachea, lung and gross lesions were examined microscopically. In general, all animals in the high dose group showed adverse findings after 4 days of exposure.

Clinical signs included appendage, tail or lip injury in the form of toe missing / swollen / open / gelatinous, scabbed / deformed/ lesion, crusty nose, tissue mass, mouth injury, scabbed nose, crusty muzzle, red stained fur, nasal discharge, crusty eye and poor coat quality. These findings were consistent with the irritant/corrosive properties of HCl.

One 50 ppm female B6C3F1 mouse was found dead on study day 12 and four 10 ppm male BC3F1 mice were found dead on study day 92. One 50 ppm female B6C3F1 mouse was sacrificed in extremis on study day 20. One 50 ppm female Sprague-Dawley CD rat was found on study day 4, however, the study authors noted that the deaths did not appear to be directly related to exposure to gaseous HCl. No Fischer-344 (CDF) rats died during the 90-day study. At the sacrifice, a statistically significant decrease of the body weight was evident for B6C3F1 male and T-III mice, T-III CD male rats as well as T-III CDF male and female rats in the 50 ppm exposure groups. These decreases were considered to be due to the exposure of gaseous HCl and therefore treatment-related. A statistically decreased liver weight occurred in B6C3F1 T-III male and female mice as well as in C DF T-III female rats. The decrease was in conjunction with the body weight data for these animals and therefore, considered as treatment-related. A statistically significant increase in CD T-II heart weight was observed. A statistically significant decrease of liver weight occurred in T-III B6C3F1 male mice. Furthermore, various organ ratios in all strains were statistically different compared to the untreated control groups. This variance depends on decreased body weights and/or changes, although, not statistically significant, in the organ weights themselves. The changes include a decrease in liver weights among T-III male and female B6C3F1 mice and female CDF rats.  

Following 90 days exposure, CDF rats at T-I, T-II and T-III levels was associated with minimal to mild rhinitis in all dose groups. The lesion occurred in the anterior portion of the nasal cavity and was dose and time related. Similar effects were observed in CD rats. In 50 ppm B6C3F1 mice, varying degrees of cheilitis with accumulations of haemosiderin-laden macrophages involving the perioral tissues at TIII occurred. Moreover, at all exposure levels, B6C3F1 mice (at T-I, T-II and T-III) developed eosinophilic globules in epithelial cells lining the nasal turbinated following 90 days exposure. A systemic NOAEC for hydrogen chloride was concluded to be 20 ppm based on decreased body weight. The main adverse findings related to irritant/corrosive effects on the nasal turbinates in mice. A local LOAEC was concluded to be 10 ppm (equivalent to 15 mg/m3) based on the irritant/corrosive effects observed at all dose levels tested in mice (Toxicogenics, 1984).

Dichloro(dimethyl)silane

In a supporting short-term repeated dose inhalation toxicity study, conducted in a similar manner to OECD Test Guideline 412 and in compliance with GLP, dichloro(dimethyl)silane was tested at concentrations of 5.3 ppm, 25 ppm and hydrogen chloride was tested at a concentration of 50 ppm for 5 days per week for 4 weeks. A NOAEC could not be determined depending on subacute inflammation, hyperplasia and/or hyperkeratosis of the squamous epithelium and mucous cell hyperplasia of the respiratory epithelium in the anterior nasal cavity with a clear dose-relationship in incidence and severity between the 5 and 25 ppm dichloro(dimethyl)silane groups for the majority of findings. Similar findings were recorded for 50 ppm HCl which were generally comparable in incidence and severity to 25 ppm dichloro(dimethyl)silane (WIL, 2014).

Trichlorosilane

In a two-week repeated inhalation toxicity study with trichlorosilane, not conducted according to OECD Test Guideline but in compliance with GLP, rats were exposed to 10 ppm of trichlorosilane and 30 ppm of HCl. A LOAEC for females was concluded to be 10 ppm based on mineralization in the kidneys in females. A NOAEC for males was concluded to be 10 ppm based on no adverse effects observed (Dow Corning Corporation, 1993).

In a 9-day repeated inhalation toxicity study (reliability score 4) with trichlorosilane, conducted to a protocol similar to OECD Test Guideline 412 and in compliance with GLP, a LOAEC of 25 ppm was determined based on respiratory irritancy, body weight reduction, upper respiratory tract rhinitis, haemorrhage and necrosis in all exposure groups. Increased lung weight was noted at the 50 ppm exposure group. The toxicity was attributed primarily to the hydrolysis products (Union Carbide Corporation, 1989).

Justification for classification or non-classification

Based on the available data from the hydrolysis products insoluble polysilicic acid [equivalent to synthetic amorphous silica (SAS)] and hydrogen chloride, trichlorosilane does not require classification for specific target organ toxicity following repeated administration according to Regulation (EC) No 1272/2008.