Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The key study for acute oral toxicity, conducted according to a guideline similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of greater than 5000 mg/kg bw/day (Toxicon Corporation, 1994).

The key study for acute inhalation toxicity, conducted according to OECD Test Guideline 403 and in compliance with GLP, reports an LC50 value of 500 mg/m³ (0.5 mg/l air) after a 4-hour exposure of rat to an atmosphere of aerosol of the test material (Dow Corning Corporation, 2000).

The key study for acute dermal toxicity, conducted according to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >2000 mg/kg bw in rabbit (Dow Corning Corporation, 1997).

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:
1994-09-07 to 1994-09-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
other: TSCA 40 CFR Pt 798.1175
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, United States
- Age at study initiation: 49 - 74 days old
- Weight at study initiation: 200 - 300 g
- Fasting period before study: food was withheld on the night prior to dosing
- Housing: The animals were housed in groups in polycarbonate cages.
- Diet: commercial rodent ration, ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature: 68±30°F
- Humidity (%): 30-70 %
- Air changes (per hr): 10 to 13 air changes/ hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: The volume dosed did not exceed 1 ml/100 g bw

Doses:
5 g/kg bw administered in three fractional doses within 24 hours.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations; test animals were weighed on days 7 and 14 prior to sacrifice
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
No evidence of toxicity at >=5000 mg/kg bw
Mortality:
No mortality was observed during the 14-day study period.
Clinical signs:
other: No signs of toxicity were noted in any of the animals during the observation period.
Gross pathology:
No unusual lesions were noted in any of the animals at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral study the reported LD50 value for 1,1,5,5,5-hexamethyl-3-phenyl-3-[(trimethylsilyl)oxy]trisiloxane was > 5000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 March 2000 to 21 September 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The restrictions were: non-compliance with test guideline with respect to group sizes and exposure concentrations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(the guideline was not followed with respect to group size or exposure concentrations)
GLP compliance:
yes
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:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 8 weeks
- Weight at study initiation:Group 1 (5 mg/L): males 269 g and females 201 g; Group 2 (0.5 mg/L): males 283 g and females 204 g.
- Fasting period before study: No
- Housing: individually-housed in suspended, stainless steel, wire mesh cages during non-exposure periods; individually-housed in whole-body cages contained within a 100 litre glass and plexiglass exposure chamber during exposure periods
- Diet (e.g. ad libitum): Certified Rodent Diet, #5002 (meal), ad libitum(except during exposure)
- Water (e.g. ad libitum): ad libitum (except during exposure)
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Group 1 (5 mg/L): 23-25; Group 2 (0.5 mg/L): 24-25
- Humidity (%): Group 1 (5 mg/l): 38-65%; Group 2 (0.5 mg/l): 43-54%
- Air changes (per hr): measured twice and recorded at 10.3 and 11.0 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: Group 1 (5 mg/L) From: 4 April 2000 To: 5 April 2000. Group 2 (0.5 mg/L): From 7 April 2000 to 21 April 2000.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass and plexiglass exposure chamber
- Exposure chamber volume: 100 liters
- Method of holding animals in test chamber: whole-body cages
- Source and rate of air: house-supply air
- Method of conditioning air: regulator and backpressure gauge, via 1/4" tubing, to a metering valve
- System of generating particulates/aerosols: Baxter Syringe Pump Model #A540A.
- Method of particle size determination: ITP 7-Stage cascade impactor Model 2977 with stainless steel slides and glass fiber filter paper, type CF/F size 2.5 cm, Lot #182505 (Whatman)
- Treatment of exhaust air: the chamber was exhausted via 1" tubing through a system consisting of a coarse filter, a HEPA filter and activated charcoal bed
- Temperature, humidity, pressure in air chamber:
- Temperature: Group 1 (5 mg/L): 24.4°C; Group 2 (0.5 mg/L): 24.9°C.
- Humidity: Group 1 (5 mg/L): 47.7%; Group 2 (0.5 mg/L): 49.9%.
- Pressure in air chamber: slight positive pressure

TEST ATMOSPHERE
- Brief description of analytical method used: sample concentration was determined gravimetrically
- Samples taken from breathing zone: yes, hourly at a rate of 2.00 Lpm for 1 minute for Group 1 (5 mg/L) and for 5 minutes for Group 2 (0.5 mg/L).

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- Group I (5 mg/L): 18.16% <= 1 µm, 76.77% <=4 µm, 96.56% <= 10 µm
- Group II (0.5 mg/L): 19.57% <=1 µm, 85.69% <= 4µm, <=98.98% <=10 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Group I (5 mg/L) 2.165 / 2.316, Group 2 (0.5 mg/L) 1.857 / 2.060
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal: 5 and 0.5 mg/L
Gravimetric concentration: 5.393 and 0.4670 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 for Group 2 animals
- Frequency of observations and weighing: daily observations; weighed on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, examination of the external surface and all orifices, external surfaces of the brain and spinal cord, organs and tissues of the cranial, thoratic, abdominal and pelvic cavities and neck, and the remainder of the carcass, microscopic evaluation of respiratory tracts (group 2)
Statistics:
Means and standard deviations were calculated and reported for the following parameters: chamber concentration and environment data,
particle size determinations, body w eight and body w eight change data.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 0.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 5/10 deaths at 0.5 mg/L; 10/10 deaths at 5 mg/L
Mortality:
Group I (5 mg/L): males 5/5, females 5/5
Group II (0.5 mg/L): males 1/5, females 4/5
Clinical signs:
other: Group I (5 mg/L): laboured breathing (5/10), eye closure (8/10), one prostrated and another in poor condition, lacrimation, nasal discharge (red or clear), excessive salivation, laboured breathing, moist rales, decreased activity and irregular gait were o
Body weight:
All surviving animals gained weight during both weeks of the 14-day post-exposure observation period.
Gross pathology:
Group I (5 mg/L): fluid in the lungs of one male.
Group II (0.5 mg/L): fluid was found in the lungs and trachea of the 5 animals (1/5 males, 4/5 females) found dead. Evidence of agonal haemorrhages commonly seen in this strain and age of rats were considered not to be treatment related. Slight to moderate oedema and acute inflammation characterized by perivascular, interstitial and alveolar neurotphilic infiltrates.
Other findings:
- Organ weights: not examined
- Histopathology: not examined (except lungs - see below)
- Potential target organs: lung, trachea; slight to moderate oedema and inflammation were present in the lungs of the rats found dead following exposure to 0.5 mg/L
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
In a GLP study, conducted to OECD test guideline 403, rats were exposed by inhalation to silsesquioxanes, Ph at 5 and 0.5 mg/ml for 4 hours. An LC50 of 0.5 mg/L was determined.
Executive summary:

In a GLP study, conducted to OECD test guideline 403, silsesquioxanes, phenyl was tested for its potential to induce acute inhalation toxicity in rats.

Groups of 5/sex were exposed to the test material as an aerosol at 5.0 and 0.5 mg/L (nominal) (5.393 and 0.467 mg/L, gravimetric)

for 4 hours by whole-body exposure. All surviving animals were sacrificed 14 days post-exposure and macroscopic examinations were performed on various tissue with and histological examination of the respiratory tract. All rats in the 5.0 mg/L and half of those in the 0.5 mg/L exposure group died within 24 hours of exposure. Fluid was present in the lung of one animal exposed at 5 mg/L, and at 0.5 mg/L slight to moderate oedema and inflammation were present in the lungs of the 5 (1 male and 4 female) rats found dead. No other effects were considered treatment related.

The LC50was 0.5 mg/L.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
500 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 August 1995 to 30 September 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The restrictions were minor deviations from the guideline.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(occlusive coverage (semi-occlusive recommended), humidity slightly above recommended range for a short time)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbit Ranch
- Age at study initiation: 3.5 months
- Weight at study initiation: females 2.89 kg, males 2.70 kg
- Housing: stainless steel cages with mesh floors, 61.0 x 45.5 x 41.0 cm
- Diet (e.g. ad libitum): 150 g/day, Purina Lab Rabbit Chow HF #5326
- Water (e.g. ad libitum): ad libitum, reverse osmosis-purified water
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 33-72
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: 7 to 21 September 1995
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: not stated but a 147 cm2 dressing covered the site (shaved area 240 cm2, ~10% of the dorsal skin surface)
- % coverage: no data
- Type of wrap if used: 12.8 x 11.5 surgical dressing pad, covered with plastic film, then secured by lint-free cloth and an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with mineral oil
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): undiluted

Duration of exposure:
24 hours
Doses:
2000 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: observed twice daily on weekdays and once daily on weekends and holidays for mortality; observed at frequent intervals on the day of dosing and at least once daily on days 2-14 for signs of toxicity; animals were weighed immediately prior to dosing, 1 week following application of test material and at 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations following unwrapping included the examination of the application site skin for signs of dermal irritation
Statistics:
Group mean and standard deviation for body weight and body weight change
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No evidence of toxicity at >=2000 mg/kg bw
Mortality:
No deaths
Clinical signs:
other: No adverse signs were observed in any animal at any time during the study
Gross pathology:
Within normal limits
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In the acute dermal toxicity study, which was conducted according to OECD Test Guideline 402 and in compliance with GLP, there was no evidence of toxicity following 24-hour covered contact of rabbit skin with the test material at a dose of 2000 mg/kg bw.
Executive summary:

In a GLP study, performed to OECD Test Guideline 402 (acute dermal toxicity), the test material was tested for its acute dermal toxicity in rabbits.

The test material was applied undiluted to the shaved skin of 5 male and 5 female rabbits at a dose of 2000 mg/kg bw and covered for 24 hours. The animals were observed for 14 days, weighed at the beginning and end of the study, and a gross necropsy examination was performed.

No evidence of toxicity was observed.

Under the conditions of the test, the acute dermal LD50 for the test matrial was >2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The key study for acute oral toxicity, conducted according to a guideline similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of greater than 5000 mg/kg bw/day (Toxicon Corporation, 1994). In the study 5000 mg/kg bw were administered in three fractional doses within 24 hours to 5 male and 5 female rats. The animals were observed for signs of toxicity for 14 days. Body weights were measured on a regular basis. At the end of the 14-day study period, the animals were sacrificed and subject to gross pathological evaluation. No mortality was observed during the 14-day study period. No signs of toxicity were noted in any of the animals during the observation period. All animals gained weight during the observation period. No unusual lesions were noted in any of the animals at necropsy.

The key study for acute inhalation toxicity, conducted according to OECD Test Guideline 403 and in compliance with GLP, reports an LC50 value of 500 mg/m³ (0.5 mg/l air) (Dow Corning Corporation, 2000). There was a deviation from the test guideline in group size and exposure concentrations. In the study 5 male and 5 female rats were exposed via whole body inhalation to the nominal concentrations of 5000 and 500 mg/m³ (5 and 0.5 mg/L) phenyl silsesquioxanes for 4 hours. The animals were observed for signs of toxicity for 14 days. Body weights were measured on a regular basis. At the end of the 14-day study period, the animals were sacrificed and subject to gross pathological evaluation. All rats in the 5000 mg/m³ (5.0 mg/l) and half of those in the 500 mg/m³ (0.5 mg/l) exposure group died within 24 hours of exposure. Clinical signs included laboured breathing, red nasal discharge, eye closure, one prostrated and another in poor condition, lacrimation, nasal discharge (red or clear), excessive salivation, laboured breathing, moist rales, yellow anogenital staining, decreased activity and irregular gait after exposure. Among surviving animals, decreased faecal volume and decreased feed were noted in the first week. Fluid was present in the lung of one animal exposed at 5000 mg/m³ (5 mg/L), and at 500 mg/m³ (0.5 mg/L) slight to moderate oedema and inflammation were present in the lungs of the 5 (1 male and 4 female) rats found dead. No other effects were considered treatment related.

The key study for acute dermal toxicity, conducted according to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >2000 mg/kg bw in rabbit (Dow Corning Corporation, 1997). There was a deviation from the test guideline in that occlusive coverage instead of recommended semi-occlusive was used, and the humidity was slightly above recommended range for a short time. In the study 2000 mg/kg bw phenyl silsesquioxanes were applied onto the skin of 5 male and 5 female rats under occlusive dressing for 24 hours. The animals were observed for signs of toxicity for 14 days. Body weights were measured on a regular basis. At the end of the 14-day study period, the animals were sacrificed and subject to gross pathological evaluation. No mortality was observed during the 14-day study period. No adverse signs were observed in any animal at any time during the study. All of the animals gained weight during the study. There were no lesions at pathology evaluation.


Justification for classification or non-classification

Based on the available data on acute oral and dermal toxicity, no classification is required for phenyl silsesquioxanes. However, classification for acute inhalation toxicity (aerosol) as Category 2; H330 'Fatal if inhaled' is required in accordance with Regulation (EC) No 1272/2008.