Reaction mass of 1,1,1,5,5,5-hexamethyl-3-phenyl-3-((trimethylsilyl)oxy)trisiloxane and 1,1,1,7,7,7-hexamethyl-3,5-diphenyl-3,5-bis[(trimethylsilyl)oxy]tetrasiloxane and 1,1,1,9,9,9-hexamethyl-3,5,7-triphenyl-3,5,7-tris((trimethylsilyl)oxy)pentasiloxane

Acute Toxicity: inhalation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

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

Applicant's summary and conclusion

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.