Tetradecamethylhexasiloxane

Endpoint summary

Description of key information

The key study for acute oral toxicity is read across from the structurally analogous substance octamethyltrisiloxane (CAS 107-51-8). Based on the available information an LD50 value of >2000 mg/kg was determined. The study was conducted according to an appropriate OECD test protocol, and in compliance with GLP (Dow Corning Corporation, 2004a). The key study for acute dermal toxicity is read across from the structurally analogous substance dodecamethylpentasiloxane (CAS 141-63-6). Based on the available information an LD50 value of >2000 mg/kg was determined. The study was conducted according to an appropriate OECD test protocol, and in compliance with GLP (Dow Corning Corporation, 2009).

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:

March 30 2014 to May 20, 2014

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

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:

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:

no

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:

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

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 is read across from the structurally analogous substance octamethyltrisiloxane (L3, CAS 107-51-8). Based on the available information an LD50 value of >2000 mg/kg bw was determined. The study was conducted according to an appropriate OECD test protocol, and in compliance with GLP (Dow Corning Corporation, 2004a). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy.

The key study for acute dermal toxicity is read across from the structurally analogous substance dodecamethylpentasiloxane (L4, CAS 141-63-9). Based on the available information an LD50 value of >2000 mg/kg bw was determined. The study was conducted according to an appropriate OECD test protocol, and in compliance with GLP (Dow Corning Corporation, 2009). There were no mortalities, clinical signs or remarkable findings at necropsy.

The key data are supported by an acute dermal toxicity study for the structural analogue decamethyltetrasiloxane (L5, CAS 141-62-8), which was also conducted according to an appropriate OECD guideline and in compliance with GLP. There were no mortalities, clinical signs or remarkable finding at necropsy, and the LD50 was >2000 mg/kg bw. The study for the closest structural analogue was selected as key.

Read-across justification

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint.  In the case of acute toxicity relevant properties are structural similarity as well as physical-chemical and basic toxicological parameters in the same range. In the following paragraphs the read-across approach for tetradecamethylhexasiloxane is evaluated point by point. Further information can be found in the supporting report (PFA, 2013u) attached in Section 13 of the IUCLID 6 dossier. 

 

Read-across hypothesis

The read-across hypothesis is that the linear siloxanes have similar physicochemical properties and are structurally similar so have similar toxicological properties.

a) Structural similarity

Tetradecamethylhexasiloxane (L6) is a methyl-substituted linear siloxane, with six silicon atoms connected by five oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. Dodecamethylpentasiloxane (L5), decamethyltetrasiloxane (L4) and octamethyltrisiloxane (L3) are also methyl substituted linear siloxanes, with five, four or three silicon atoms and four, three or two oxygen atoms, respectively.

b) Similar physicochemical properties

The linear siloxanes all have high log K_ow (increasing with increasing chain length) and low water solubility.

c) Similar results from acute toxicity studies

Acute toxicity studies by the oral, dermal and inhalation routes are available for a number of these substances. There are no acute toxicity studies available for the registration substance itself, so data are read-across from structural analogues.

The available studies for the linear siloxanes from this analogue group, as well as key physicochemical properties, are summarised in Table 5.2.3. 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.

Summary of key acute toxicity data for linear siloxanes

Substance	L2	L3	L4	L5	L6
Chemical name	Hexamethyldisiloxane	Octamethyltrisiloxane	Decamethyltetrasiloxane	Dodecamethylpentasiloxane	Tetradecamethylhexasiloxane
CAS number	107-46-0	107-51-7	141-62-8	141-63-9	107-52-8
Water solubility (mg/l)	0.93 at 23°C	0.034 at 23°C	6.7E-03 at 23°C	7.0E-05 at 23°C	2.3E-06 at 20°C
Log Kow	5.06 (measured) at 20°C	6.6 (measured) at 25.3°C	8.21 (measured) at 25.1°C	9.41 (measured) at 25°C	>9.41 (read-across from L5) at 25°C
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, 2009d)	>2000 (Dow Corning Corporation, 2009c)	>2000 (Dow Corning Corporation, 2009e)	-
Acute inhalation toxicity (LC50,mg/l)	approximately 106 (Dow Corning Corporation, 1997)	>22.6 (Dow Corning Corporation, 2004b)	-	-	-

References

BRRC (1982). Silicone Fluid Y-4081: Acute Toxicity and Primary Irritancy Studies. Bushy Run Research Center. Testing laboratory: Bushy Run Research Center. Report no.: Project Report 44-108. Report date: 1982-04-30.

Dow Corning Corporation (1997). An acute whole body vapour inhalation toxicity study with Hexamethyldisiloxane in albino rats. Dow Corning Corporation. Testing laboratory: Dow Corning Corporation, Health and Environmental Sciences, 2200 W. Salzburg rd., Midland, Michigan 48686-0994. Report no.: 1996-I0000-41477. Study number: 8116. Report date: 1997-01-17.

Dow Corning Corporation (2004b). An acute whole body inhalation toxicity study of octamethyltrisiloxane in rats. Testing laboratory: Health and Environmental Sciences, Dow Corning Corporation, 2200 West Salzburg Road, Auburn MI 48611. Report no.: 2004-I0000-54030. Owner company: Dow Corning. Report date: 2004-06-23.

Dow Corning Corporation (2009b). Octamethyltrisiloxane (L3): Acute dermal toxicity study in rats. Testing laboratory: Dow Corning Corporation, Health and Environmental Sciences. Report no.: 2009-I0000-60383. Report date: 2009-03-10.

Dow Corning Corporation (2009c) Decamethyltetrasiloxane (L4): Acute Dermal Toxicity Study in Rats.Testing laboratory:Dow Corning Corporation, Health and Environmental Sciences., USA. Owner company: Dow Corning CorporationReport no.: 2009-10000-60384.Report date: 2009-03-11.

Dow Corning Corporation (2009d). Dodecamethylpentasiloxane (L5): acute dermal toxicity study in rats.Testing laboratory: Dow Corning Corporation, Health and Environmental Sciences, USA. Owner company: Dow Corning Corporation. Report no.:2009-I0000-60385.Report date: 2009-03-11.

IFREB (1982). Hexamethyldisiloxane (M2) Etude de toxicite aigue par voie percutanee chez le rat.Testing laboratory: Institut Francais de Recherches et Essais Biologiques. Report no.: 202212. Report date: 1982-02-10.

PFA, 2013u, Peter Fisk Associates, Analogue report - mammalian toxicity of linear and branched siloxanes, PFA.300.002.008

Justification for classification or non-classification

Based on the available data on the read across substances, octamethyltrisiloxane (CAS 107-51-8) and dodecamethylpentasiloxane (CAS 141-63-9), no classification for acute toxicity is required for the registered substance according to Regulation (EC) No 1272/2008.