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Administrative data

Description of key information

The key read-across study for acute oral toxicity determined an LD50 value of >2000 mg/kg in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 2004a).

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

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:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl: CD (SD) IGS BR
Sex:
female
Details on test animals 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 a 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 conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 occurred during the study.
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The most recent and reliable studies for the most closely related substances in terms of chemical structure and physiochemical properties were chosen as key.

The key study for acute oral toxicity was read across from the structurally analogous substance octamethyltrisiloxane (CAS 107-51-7) reporting an LD50 value of >2000 mg/kg. There were no mortalities, clinical signs or significant macroscopic findings reported (Dow Corning 2004a). The read across study was conducted according to the appropriate OECD guideline, and in compliance with GLP, and is considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified; the read across are considered to be reliability 2.

The key study for acute dermal toxicity reports an LD50 value of >2000 mg/kg in a reliable, GLP compliant study (Dow Corning Corporation, 2009a). There were no mortalities, clinical signs or remarkable findings at necropsy.

A reliability 2, non-standard supporting study for acute inhalation was also available, conducted with the registered substance (Dow Corning Corporation, 2006b). The study was designed to investigate the anti-estrogenic activity of decamethyltetrasiloxane (L4). Groups of animals were injected with either 17alpha-ethinyl estradiol or corn oil and exposed by inhalation to L4 at 400 ppm or air for 6 hours/day on 3 consecutive days. Estrogenic activity was assessed by evaluation of the uterus after the final exposure.

No substance-related clinical signs were noted and all animals survived the experimental period. No changes in the weight or histology of the uterus were seen at necropsy after the 3rd 6-hour inhalation exposure to L4 compared with inhalation of air.

Read-across justification

Decamethyltetrasiloxane (L4) belongs to the structural class of siloxanes (alkyl, vinyl, aryl or hydrogen substituted). The substances all have high log Kow (increasing with increasing chain length) and low water solubility. Acute toxicity studies by the oral, dermal and inhalation routes are available for a number of these substances. For the registration substance itself, the only available acute toxicity study is for the dermal route (Dow Corning Corporation, 2009d).

The available studies for the linear siloxanes from this analogue group, as well as key physicochemical properties, are summarised in Table 5.2.4. The results of the acute toxicity studies for this analogue group are in agreement: 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.

Table 5.2.4. Summary of key acute toxicity data for linear siloxanes

Substance

L2

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, 2009a)

>2000 (Dow Corning Corporation, 2009d)

>2000 (Dow Corning Corporation, 2009a)

Acute inhalation toxicity (LC50,mg/l)

ca. 106 (Dow Corning Corporation, 1997)

>22.6 (Dow Corning Corporation, 2004b)

-

-

 

In the case of the registration substance, the low order of acute toxicity is further supported by the absence of mortalities or clinical effects at dose levels up to 1000 mg/kg bw/day in a sub-acute oral toxicity study in rats (Dow Corning Corporation, 2010a), described in Section 5.6.

 


Justification for classification or non-classification

Based on the available information, decamethyltetrasiloxane does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.