Registration Dossier

Administrative data

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 dodecamethyltetrasiloxane (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

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

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 Kow (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.