Reaction mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane

Endpoint summary

Description of key information

There are no available acute toxicity data for the registered substance "Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane". Therefore, data have been read-across from its constituents, HMDS, L3, L4 and L5.

Oral:

In the acute oral toxicity study for HMDS (Bushy Run Research Center, 1982), the LD50 was determined to be >16.0 ml/kg (equivalent to 12.16 g/kg bw) for male and female rats.  

The acute oral toxicity study for L3 determined the LD50 value of >2000 mg/kg in a reliability 1 study (Dow Corning 2004), conducted according to an appropriate test protocol, and in compliance with GLP.

Inhalation:

The acute inhalation study for HMDS (Dow Corning Corporation, 1997) determined a LC50 of 15956 ppm (approximately 106 mg/L) in rats.

In the acute inhalation toxicity study for L3 rats were exposed to a test atmosphere of vapour and a LC50 value of >22.6 mg/L (analytical) was determined in a reliability 1 study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2004).

Dermal:

In the acute dermal toxicity study for HMDS (Institut Francais de Recherches et Essais Biologiques, 1982), the LD50 for male and female rats was determiend to be >2000 mg/kg.

The acute dermal toxicity study for L3 determined an LD50 value of >2000 mg/kg in a reliability 1 study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009).

The acute dermal toxicity study for L4 determined an LD50 value of >2000 mg/kg in a reliability 1 study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 2009a).

Data for acute dermal toxicity for L5 was available. In a GLP reliability 1 study conducted according to OECD Test Guideline 402, the LD50 value was determined to be >2000 mg/kg bw (Dow Corning, 2009).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

CLP compliance not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Hilltop-Wistar albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

weighing between 200 and 300 g

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: Not applicable

MAXIMUM DOSE VOLUME APPLIED: Not stated

Doses:

8.0 and 16.0 ml/kg

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

Hilltop-Wistar albino rats, weighing between 200 and 300 g, received the test material by stomach intubation with a ball-end stainless steel needle.  The sample was injected through the needle by means of a syringe and doses were varied by adjusting the volume of the test material.  The rats were fasted overnight before dosing.  Five males and 5 females were included on each level (16.0 and 8.0 ml/kg).  The animals were maintained on appropriate commercial diet and municipal water.  Both were available ad libitum except during period of fasting, manipulation or restraint.   Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice).  At death or sacrifice, each animal was subjected to gross pathological evaluation.

Statistics:

 LD50s were calculated by the moving average method (Thompson WR.: Use of moving averages and interpolation to estimate median effective dose. Bact. Rev., 11, 115-145, 1947) and were based on a 14-day observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Remarks on result:

other: corresponding to >12.16 g/kg

Mortality:

MALES:
 16.0 ml/kg Dead/Dosed: 0/5
8.0 ml/kg Dead/dosed: 1/5

FEMALES:
 16.0 ml/kg Dead/Dosed: 0/5
8.0 ml/kg Dead/Dosed: 0/5

Clinical signs:

other: MALES: 16.0 ml/kg  None noted.  8.0 ml/kg: In the animal that died, sluggishness, unsteady gait at 4 min; death at 15 min.  In survivors, none noted. FEMALES:  16.0 ml/kg None noted. 8.0 ml/kg  None noted.

Gross pathology:

MALES:
 16.0 ml/kg : Nothing remarkable.
 8.0 ml/kg  In animal that died, lungs with dark spots; liver dark; stomach liquid-filled, injected; intestines and kidneys red.  In survivors, nothing remarkable.

FEMALES:
 16.0 ml/kg : Nothing remarkable.
8.0 ml/kg  Nothing remarkable.

Other findings:

No other findings reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 was determined to be >16.0 ml/kg (corresponding to >12.16 g/kg), dosed as received, in both male and female rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CD (SD) IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: ca. 11 weeks
- Weight at study initiation: 220-241 g
- Fasting period before study: over night
- Housing: Individually housed in suspended wire mesh cages
- Diet: Lab diet 5002 Certified Rodent Diet, ad libitum, except the night prior to dosing and approximately 4 hours post-dosing
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 -22.2
- Humidity (%): 46-65
- Air changes (per hr): 10.2-11.3
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

3F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical abnormalities immediately after dosing and then approximately 30 minutes, 90 minutes, four hours post dose and daily thereafter. The animals were examined for a minimum of the following changes in the skin and fur, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, motor activity and behaviour pattern. The body weights were recorded on study day 0 prior to dosing, on study day 7 and on study day 14 prior to terminal sacrifice.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The gross necropsy included examination of the external surface, all orifices of the body and the cranial, thoracic and abdominal cavities and their contents.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: All animals appeared normal throughout the study.

Gross pathology:

No significant macroscopic findings were noted.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

The mean actual exposure concentrations were significantly higher than OECD limit test guideline of 5 mg/l.

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, Raleigh, NC

- Age at study initiation:Males approximately 8 weeks and females approximately 10 weeks old when exposed.

- Weight at study initiation: 126 - 150 g

- Housing: Individually in stainless steel, wire mesh-bottom cages

- Diet: Purina rodent chow ad libitum except during exposure

- Water: Ad libitum

- Acclimation period: One week

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 2

- Humidity (%): 30 - 70

- Air changes (per hr): Not stated

- Photoperiod (12 hrs dark /12 hrs light):

IN-LIFE DATES: From: 15th February 1994 To: 3rd March 1994

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: Stainless steel and glass exposure chambers

- Exposure chamber volume: 120 litre

- Method of holding animals in test chamber:

- Source and rate of air: Ambient air; 10-15 air changes per hour (20.4 - 20.5 litres per minute)

- Method of conditioning air: HEPA and charcoal filters

- System of generating particulates/aerosols: Not applicable

- Method of particle size determination: Not applicable

- Treatment of exhaust air: HEPA and charcoal filters then passed through water scrubber

- Temperature, humidity in chamber: 22.9 - 23.9 °C; 52.0 - 61.2% humidity

TEST ATMOSPHERE

- Brief description of analytical method used: Gas chromatography

- Samples taken from breathing zone: Yes

VEHICLE

Not applicable

TEST ATMOSPHERE
- Particle size distribution: Not applicable

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Not applicable

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC

Duration of exposure:

4 h

Concentrations:

11,000; 14,000 and 18,000 (nominal); 10,067; 14,050 and 16,659 ppm (as measured by gas chromatography)

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, gross pathology

Statistics:

No statistical analysis included.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

15 956 ppm

Based on:

test mat.

95% CL:

> 14.024 - < 34.045

Exp. duration:

4 h

Mortality:

See Table 1.

One animal in the mid-dose group was sacrificed for human reasons on Day 2. This was not included in the statistical analysis.

Clinical signs:

other: During the 4-hour exposure, some of the animals exposed to concentrations of 14,050 and 16,659 ppm test material experienced prostration and convulsions. Ataxia was also observed in the high exposure group. The primary clinical sign after the exposure was

Body weight:

No apparent effects on body weight gains were observed.

Gross pathology:

In animals that died, congestion and/or haemorrhage of various lobes of the lung were observed in males and females. Congestion of the lungs was also noted in one female from each of the two higher exposure groups at the final sacrifice of the animals that survived exposure.

Other findings:

- Potential target organs: Lung

- Other observations: Response was generally consistent between males and females.

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated

Nominal Conc. (ppm)	Analytical Conc. (ppm)	Number dead/Number exposed
		Males	Females	Combined
11000	10067	0/5	0/5	0/10
14000	14050	1/5	1/5	2/10
18000	16659	3/5	3/5	6/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

An acute inhalation LC50 of 15,956 ppm with (95% confidence limits of 14,024-34,045) (equivalent to ca. 106 mg/L) was determined for male and female rats in an reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 April 2004 - 23 June 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Mass median aerodynamic diameter / Geometric st. dev. not reported.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Age at study initiation: 9 weeks at experimental start
- Weight at study initiation: females 199.4-208.2 g, males 295-310 g
- Housing: wire-mesh cages
- Diet: certified rodent chow, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: 450 litres
- Method of holding animals in test chamber: The animals were positioned within stainless steel exposure caging specifically designed for use in the 450 litre chamber (two levels of 10 wire mesh cages).
- Source and rate of air: Nash Air Compressor (Model/Size: AL-574), air sourced from building air supply
- Method of conditioning air: Conditioned building air was passed through HEPA and activated charcoal filters before delivery to the chamber. The compressed air was passed through a series of filters to remove contaminants (Matheson model: 460/461 and Balston model 100-18-DX and 100-18-BX) prior to use in test atmosphere. Chamber atmosphere consisted of a dilution air stream and an octamethyltrisiloxane vapour/carrier stream. The dilution air stream was building-conditioned air (i.e. warmed and humidified) passed through activated carbon and HEPA filters. The carrier air stream was compressed air passed through a series of particulate filters prior to use in vapour generation.
- System of generating particulates/aerosols: Generation of test article vapour concentration was performed using a heated stainless steel J-tube containing a column of stainless steel beads. Test article was metered from a reservoir into the J-tube using a pump. Compressed air flowed through the J-tube at a controlled rate of 34.8 l/minute. The carrier/vapour mixture passed from the J-tube to the inlet port at the top of the exposure chamber. Just prior to entering the exposure chamber, the carrier/vapour mixture combined with chamber supply air (dilution air) and was diluted to the target chamber concentration as it enters the exposure chamber.
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: The exposure chamber was operated under dynamic conditions with regard to airflow, temperature, relative humidity and pressure. Chamber temperature was maintained within the range of 22.1-25.8°C. Chamber relative humidity was maintained within the range of 31.7%-46.6%, Chamber airflow, temperature and percent relative humidity were monitored continuously and recorded at approximately thirty-minute intervals.

TEST ATMOSPHERE
- Brief description of analytical method used: Test atmosphere oxygen content was measured once during the exposure period. The test article reservoir weight was determined pre- and post-exposure. These data, along with the chamber airflow rate and the vapour generation time, were used to calculate a nominal chamber concentration of test article. Chamber atmosphere was analysed using a Varian 3400 gas chromatograph equipped with a flame ionization detector (GC/ID) to determine the actual chamber concentration of test article. The concentration of test article in the chamber atmosphere during exposure period was evaluated approximately every 30 minutes. A continuously purged sample line was used to transfer a sample of the chamber atmosphere to the GC/FID for analysis.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

plus one 20 minute chamber equilibration time

Concentrations:

Measured 2350 ppm (22.6 mg/l)
Nominal 2448 ppm (23.5 mg/l)

No. of animals per sex per dose:

5 male, 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Mortality and morbidity were observed twice daily during the week and once daily on weekends. Following the exposure, animals were evaluated once daily for clinical signs. Individual body weights were collected prior to exposure for randomization. Following randomization, body weights were recorded on day 1 (prior to exposure), day 8, and day 15 (prior to terminal sacrifice).

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Complete gross pathology was carried out, no tissues were saved.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22.6 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no mortalities.

Clinical signs:

other: There were no clinical signs.

Body weight:

All body weights and weight gains were considered normal for both sexes.

Gross pathology:

There were no macroscopic abnormalities.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LC50 value of >22.6 mg/l (analytical) was determined in a reliablility 1 study conducted according to an appropriate test protocol, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

22 600 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Not compliant with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

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: IFFA CREDO

- Weight at study initiation: 180-200g

- Housing: in individual cages (37.5x17x15 cm)

- Diet: IFFARAT feed, ad libitum

- Water: ad libitum



ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 +/- 1

- Humidity (%): 50 +/- 10

- Air changes (per hr): 8

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE

- Area of exposure: shaved dorsal skin

- Type of wrap if used: an aluminium sheet, held in place with adhesive tape


REMOVAL OF TEST SUBSTANCE

- Washing (if done): not rinsed



TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 2.62 ml/kg

Duration of exposure:

Single application, not rinsed

Doses:

2000 mg/kg

No. of animals per sex per dose:

5M, 5F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

No statistical analysis reported in the study report.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the study.

Clinical signs:

other: No skin reactions were noted during the exposure or over the 14 day observation period.

Gross pathology:

Not reported.

Other findings:

Not reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute dermal LD50 value of >2000 mg/kg was determined for male and female rats in a reliability 1 study conducted according to an appropriate test protocol. Not conducted according to GLP.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 2009 - 10 Feb 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

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
- Age at study initiation: males 9 weeks, females 11 weeks
- Weight at study initiation: 232.8 - 322.3 g
- Housing: During acclimation in groups of 5 per sex in Makrolon type - 4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet.
- Water: Community tap water
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light):

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the back
- % coverage: 10
- Type of wrap if used: The test item was applied evenly on the intact skin with a syringe and covered with a surgical gauze pad, held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water after the removal of the dressing and dapped off with disposable paper towels
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.44 ml

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male, 5 female.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs during the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.

- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical or local signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

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
- Age at study initiation: 9 weeks (male), 11 weeks (female)
- Weight at study initiation: 224.6-325.9g
- Housing: Five per sex per cage during acclimatization, one per sex per cage during treatment and observation
- Diet: Pelleted standard rat/mouse maintenance diet
- Water: Community tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10
- Type of wrap if used: Surgical gauze held in contact with adhesive hypoallergenic aerated semi-occlusive dressing and elastic adhesive restrainer bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.35mL
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

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: Viability/Mortality - Daily during acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Clinical signs - Daily during acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15. Local dermal signs - Once daily during days 2-15. Body weight - days 1, 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute dermal LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Reference 4

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 January 2009 to 10 February 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(all male rats exceeded 300 g in body weight (mean 312.4) at time of dosing, humidity was noted to possibly exceed 70% during cleaning process)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal 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: Harlan Laboratories
- Age at study initiation: 9 weeks (males), 11 weeks (females)
- Weight at study initiation: 229.5 to 330.1 g
- Fasting period before study: no data available
- Housing: in groups of 5/sex (acclimation period), then individually (study)
- Diet (e.g. ad libitum): standard pellet diet [presumably ad libitum]
- Water (e.g. ad libitum): tap water [presumably ad libitum]
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 to 70% (values above 70% possible during cleaning process)
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 January 2009 To: 10 February 2009

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ~ 5 x 5 cm
- % coverage: ~10
- Type of wrap if used: gauze pad with semi-occlusive dressing and an elastic adhesive restrainer bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.3 ml/kg bw (2000 mg/kg bw)
- Constant volume or concentration used: no

Duration of exposure:

24 h

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 (administered on day 1, observed until day 15)
- Frequency of observations and weighing: weighed on test days 1 (prior to administration), 8 and 15. Observed for clinical signs and mortality 30 mins, 1, 2, 3 and 5 hours, and twice daily during days 2 to 15. Dermal signs checked daily from days 2 to 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

No statistical analysis performed

Preliminary study:

None performed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no signs of toxicity/mortality at this dose

Mortality:

No deaths occurred during the study

Clinical signs:

other: No clinical signs were observed during the study

Gross pathology:

No macroscopic findings reported at necropsy

Other findings:

No local signs were observed during the study

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Test Guideline 402, no toxic effects were observed when dodecamethylpentasiloxane (L5) was applied to the skin of rats for 24 hours at 2000 mg/kg bw. The LD50 value was determined to be greater than 2000 mg/kg bw.

Executive summary:

In a GLP study conducted according to OECD Test Guideline 402 (acute dermal toxicity), five male and five female Sprague-Dawley rats were treated with 2000 mg/kg bw undiluted dodecamethylpentasiloxane (L5), under semi-occlusive dressing, for 24 hours.

Rats were observed for 14 days after treatment for changes in body weight, clinical signs of toxicity, and signs of local toxicity at the site of application. At the end of this period of observation, rats were sacrificed and necropsy was performed to identify any gross pathological changes.

There were no signs of toxicity or mortality over the period of this study.

The acute dermal LD50 was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

There are no available acute toxicity data for the registered substance "Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane". Therefore, data have been read-across from its four constituents:

1) HMDS: hexamethyldisiloxane (CAS 107-46-0)

2) L3: octamethyltrisiloxane (CAS 107-51-7)

3) L4: decamethyltetrasiloxane (CAS 141-62-8)

4) L5: dodecamethylpentasiloxane (CAS 141-63-9

Oral:

In the acute oral toxicity study for HMDS (Bushy Run Research Center, 1982) rats (5 animals/sex/dose) were administered 8 or 16 ml/kg bw of HMDS by oral gavage then observed for 14 days. The only death that occured was a male in the low dose group, which showed sluggishness and unsteady gait at 4 minutes and death at 15 minutes. Necropsy revealed lungs with dark spots, dark liver, liquid-filled, injected stomach, and red intestines and kidneys. There were no adverse findings in the animals that survived. The LD50 was >16 ml/kg bw (equivalent to 12160 mg/kg bw).

In the acute oral toxicity study for L3 conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 2004a), there were no mortalities and no clinical signs or macroscopic abnormalities reported at necropsy. The LD50 value of >2000 mg/kg is reported.

Inhalation:

In the acute inhalation toxicity study for HMDS (Dow Corning Corporation, 1997) rats (5 animals/sex/dose) were exposed to HMDS at concentrations of 10067; 14050 and 16659 ppm for 4 hours then observed for 14 days. Animals exposed to concentrations of 14050 and 16659 ppm experienced prostration and convulsions. Ataxia was also observed in the high exposure group. The primary clinical sign after the exposure was porphyrin staining of the eyes and face; this was evident in some of the animals of the two higher exposure groups for the entire observation period. In animals that died, congestion and/or hemorrhage of various lobes of the lung were observed in males and females. Congestion of the lungs was also noted in one female from each of the two higher exposure groups at the final sacrifice of the animals that survived exposure. The LC50 was 15,956 ppm with (95% confidence limits of 14,024-34,045).

The reported acute inhalation LC50 value in the acute inhalation toxicity study for L3 is >22.6 mg/L. The study was conducted according to an appropriate OECD test guideline and in compliance with GLP (Dow Corning Corporation, 2004b). Rats (5 animals/sex/dose) were exposed to octamethyltrisiloxane at a single concentration of 22.6 mg/L for 4 hours then observed for 14 days. There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy. Furthermore, all body weight gains were considered normal for both sexes.

Dermal:

In the acute dermal toxicity study conducted according to an appropriate test protocol but not according to GLP for HMDS (Institut Francais de Recherches et Essais Biologiques, 1982), rats (5 animals/sex) had HDMS applied to their skin under occlusive conditions at a dose of 2000 mg/kg bw, the skin was not rinsed and the animals were then observed for 14 days. There were no mortalities, clinical signs of toxicity, adverse necropsy findings or indications of local skin irritation. The LD50 value of >2000 mg/kg is reported in this study.

In the acute dermal toxicity study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009), rats (5 animals/sex/dose) were exposed to octamethyltrisiloxane (CAS 107-51-7) at a single concentration of 2000 mg/kg bw and observed for 14 days. There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy. The LD50 value of >2000 mg/kg is reported in this study.

The acute dermal toxicity study for L4 reports an LD50 value of >2000 mg/kg in a reliable, GLP compliant study (Dow Corning Corporation, 2009a). Rats (5 animals/sex/dose) were exposed to decamethyltetrasiloxane (CAS 141-62-8) at a single concentration of 2000 mg/kg bw and observed for 14 days. There were no mortalities, clinical signs or remarkable findings at necropsy.

Data for acute dermal toxicity for L5 was available. In a GLP study conducted according to OECD Test Guideline 402, no toxic effects were observed when the test material was applied to the skin of rats for 24 hours at 2000 mg/kg bw. The LD50 value was determined to be >2000 mg/kg bw (Dow Corning, 2009). There were no mortalities, all animals appeared normal throughout the study, no significant macroscopic findings were noted.

Read-across justification

A detailed read-across explanation is available in Section 7.5.

Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane (EC No 946-797-7) belongs to the structural class of siloxanes. Acute toxicity studies by the oral, dermal and inhalation routes are available for some or all of its constituents.

The available studies, as well as key physicochemical properties, are summarised in the table below. There is no evidence from any of the available studies that the substances in this group have any potential for acute toxicity (in terms of either lethality or adverse clinical effects) by any route up to and exceeding the maximum dose levels tested according to current OECD guidelines. It is therefore valid to read-across the lack of acute toxicity between the members of the group where there are data gaps. The most recent and reliable studies for the substance’s constituents were chosen for weight of evidence.

Table 1: Summary of key acute toxicity data for linear siloxanes

Substance	HMDS	L3	L4	L5
Chemical name	Hexamethyl disiloxane	Octamethyl trisiloxane	Decamethyl tetrasiloxane	Dodecamethyl pentasiloxane
CAS number	107-46-0	107-51-7	141-62-8	141-63-9
Water solubility (mg/l)	0.93	0.034	6.7E-03	7.5E-05
Log Kow	5.1	6.6	8.1	9.4
Acute oral toxicity (LD50,mg/kg bw)	>12,000 (BRRC, 1982)	>2000 (Dow Corning Corporation, 2004a)	-	-
Acute dermal toxicity (LD50,mg/kg bw)	>2000 (IFREB, 1982)	>2000 (Dow Corning Corporation, 2004b)	>2000 (Dow Corning Corporation, 2009c)	>2000 (Dow Corning Corporation, 2009a)
Acute inhalation toxicity (LC50,mg/l)	ca. 106 (Dow Corning Corporation, 1997)	>22.6 (Dow Corning Corporation, 2004c)	-	-

Justification for classification or non-classification

Based on the available data for Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane constituents, no classification is required for acute toxicity according to Regulation (EC) No 1272/2008.