Registration Dossier

Administrative data

Description of key information

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the acute oral and inhalation toxicity endpoint. There are key acute dermal toxicity data available for L5, therefore data for the other linear siloxanes have been included as supporting for consistency and to support read across justifications.

Acute oral toxicity

HMDS: In the acute oral study toxicity with HMDS (hexamethyldisiloxane, CAS 107-46-0) in rats (Bushy Run Research Center, 1982) , conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and without information about GLP compliance, the LD50 was determined to be > 16.0 ml/kg (12.16 g/kg bw) for males and females. 

L3: In the acute oral toxicity study with L3 (octamethyltrisiloxane, CAS 107-51-7), conducted according to an appropriate OECD Test Guideline 423 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg was concluded (Dow Corning Corporation, 2004a).

L4: There are no acute oral toxicity data with L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5: There are no acute oral toxicity data with L5 (dodecamethylsiloxane, CAS 141-63-9).

Acute inhalation toxicity

HMDS: The acute inhalation toxicity study with HMDS (hexamethyldisiloxane, CAS 107-46-0), conducted according to OECD Test Guideline 403 and in compliance with GLP (Dow Corning Corporation, 1997), concluded an LC50 of 15956 ppm (ca. 106 mg/l).

L3: The acute inhalation toxicity study with L3 (octamethyltrisiloxane, CAS 107-51-7), conducted according to OECD Test Guideline 403 and in compliance with GLP, exposed rats to a test atmosphere of vapour and determined an LC50 value of greater than 22.6 mg/l (analytical) (Dow Corning Corporation, 2004b).

L4: There are no reliable acute inhalation toxicity data with L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5: There are no acute inhalation toxicity data with L5 (dodecamethylsiloxane, CAS 141-63-9).

Acute dermal toxicity

L5: In the key acute dermal toxicity study with L5 ( dodecamethylpentasiloxane, CAS 141-63-9), conducted according to OECD Test Guideline 402 and in compliance with GLP, an LD50 value was determined to be greater than 2000 mg/kg bw (Dow Corning Corporation, 2009a).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
All animals appeared normal throughout the study.
Body weight:
All animals gained weight from study day 0 to 14.
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:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
not in compliance with GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
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). 
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 pathologic evaluation.
Statistics:
 LD50s were calculated by the moving average method (Thompson, 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:
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.
Body weight:
MALES:
16.0 ml/kg Weight change (g) at 7 days: 64 to 60 (mean = 67); Weight change (g) at 14 days: 101 to 121 (mean = 113)
8.0 ml/kg Weight change (g) at 7 days: 72 to 81 (mean = 76); Weight change (g) at 14 days: 96 to 107 (mean = 102)

FEMALES:
 16.0 ml/kg Weight change (g) at 7 days: 30 to 42 (mean = 36) Weight change (g) at 14 days: 35 to 59 (mean = 49)
8.0 ml/kg Weight change (g) at 7 days: 24 to 39 (mean = 33) Weight change (g) at 14 days: 33 to 43 (mean = 38)
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, dosed as received, in both male and female rats.
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

Referenceopen allclose all

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.
Exp. duration:
4 h
Remarks on result:
other: 95% CL = 14,024-34,045
Sex:
male/female
Dose descriptor:
other: NOEL
Effect level:
10 067 ppm
Based on:
test mat.
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) was determined for male and female rats in an reliable study conducted according to an appropriate test protocol, and in compliance with GLP. This is equivalent to ca. 106 mg/l.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
9 April 2004 - 23 June 2004
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:
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 (if not tabulated)
- 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 reliable 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

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:
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 °C
- 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:
No clinical signs were observed during the study
Body weight:
Body weight was within the normal range
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

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the acute toxicity endpoint. There are key acute dermal toxicity data available for L5, therefore data for the other linear siloxanes have been included as supporting for consistency and to support read across justifications.

Acute oral toxicity

HMDS: In the acute oral study (Bushy Run Research Center, 1982), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and without information about GLP compliance, Hilltop-Wistar rats (5 animals/sex/dose) were administered 8 or 16 ml/kg bw of HMDS by oral gavage and observed for 14 days. Animal weights were recorded at 0 days (before dosing), 7 days and 14 days (just prior to sacrifice). At death or sacrifice, each animal was subjected to gross pathologic evaluation. The only death 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 concluded to be greater than 16 ml/kg bw (equivalent to 12160 mg/kg bw).

L3: In the acute oral toxicity study with L5 (octamethyltrisiloxane, CAS 107-51-7), conducted according to an appropriate OECD Test Guideline 423 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg was concluded (Dow Corning Corporation, 2004a). There were no mortalities. All animals appeared normal throughout the study. All animals gained weight from study day 0 to 14. No significant macroscopic findings were noted.

L4:There are no acute oral toxicity datawith L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5:There are no acute oral toxicity datawith L5 (dodecamethylsiloxane, CAS 141-63-9).

Acute inhalation toxicity 

HMDS: In the acute inhalation toxicity study (Dow Corning Corporation, 1997), conducted according to OECD Test Guideline 403 and in compliance with GLP, Sprague-Dawley 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. At death or sacrifice, each animal was subjected to gross pathologic evaluation. 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 as 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 on 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).

L3: The acute inhalation toxicity study with L3 (octamethyltrisiloxane, CAS 107-51-7), conducted according to OECD Test Guideline 403 and in compliance with GLP, exposed rats to a test atmosphere of vapour and determined an LC50 value of greater than 22.6 mg/l (analytical) (Dow Corning Corporation, 2004b). There were no mortalities. There were no clinical signs. All body weights and weight gains were considered normal for both sexes. There were no macroscopic abnormalities.

L4: There are no reliable acute inhalation toxicity data with L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5:There are no acute inhalation toxicity data with L5 (dodecamethylsiloxane, CAS 141-63-9).

 

Acute dermal toxicity

L5: In the key acute dermal toxicity study with L5 (dodecamethylpentasiloxane, CAS 141-63-9), conducted according to OECD Test Guideline 402 and in compliance with GLP, 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 greater than 2000 mg/kg bw (Dow Corning Corporation, 2009a). There were no mortalities, all animals appeared normal throughout the study, no significant macroscopic findings were noted.

HMDS: In the acute dermal toxicity study with HMDS (hexamethyldisiloxane, CAS 107-46-0) (Institut Francais de Recherches et Essais Biologiques, 1982), conducted according to OECD Test Guideline 402 and in compliance with GLP, HMDS was applied onto the skin of Sprague-Dawley rats (5 animals/sex) 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 for male and female rats was concluded to be greater than 2000 mg/kg bw.

L3: The acute dermal toxicity study with L3 (octamethyltrisiloxane, CAS 107-51-7), conducted according to OECD Test Guideline 402 and in compliance with GLP, determined an LD50 value of greater than 2000 mg/kg bw (Dow Corning Corporation, 2009). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy.

L4: The acute dermal toxicity study with L4 (decamethyltetrasiloxane, CAS 141-62-8), conducted according to OECD Test Guideline 402 and in compliance with GLP, determined an LD50 value of greater than 2000 mg/kg bw (Dow Corning Corporation, 2009). There were no mortalities, clinical signs or remarkable findings at necropsy.

Justification for classification or non-classification

Based on the available information for the registration substance and read across from the structurally analogous substances hexamethyldisiloxane (HMDS; CAS 107-46-0), octamethyltrisiloxane (L3; CAS 107-51-7) and decamethyltetrasiloxane (L4; CAS 141-62-8), no classification is required for dodecamethylpentasiloxane for acute toxicity, in accordance with Regulation (EC) No 1272/2008.