Tetradecamethylhexasiloxane

Endpoint summary

Description of key information

The key study for skin irritation is read across from structurally analogous substance dodecamethylpentasiloxane (CAS 141-63-9). The study, conducted according to OECD TG 404 and in compliance with GLP, reports the test substance, dodecamethylpentasiloxane (CAS 141-63-9), to be not irritating to skin (Dow Corning Corporation, 2009). The key study for eye irritation is read across from structurally analogous substance decamethyltetrasiloxane (CAS 141-62-8). The study, conducted according to EPA OPPTS 870.2400 (Acute Eye Irritation) guideline, and in compliance with GLP, reports the test material, decamethyltetrasiloxane (CAS 141-62-8), to be not irritating to the eyes (Dow Corning Corporation, 2000).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Jan 2009 - 03 Mar 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 2819-2840 kg
- Housing: Individually housed in cages with suspended metal slat floors elevated above fecal pans.
- Diet: Certified Rabbit HF (PMI Nutrition International), Lab Diet 5325
- Water: municipal water, further purified by reverse osmosis, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 40-70
- Air changes (per hr): 14.7
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal area
- Type of wrap if used: elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any remaining material was wiped from the skin using gauze moistened with reverse-osmosis water followed by dry gauze.
- Time after start of exposure: 4 hours

SCORING SYSTEM: EEC Primary Irritation Index was calculated per EEC and EPA guidelines.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48,72h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48,72h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of dermal irritation, erythema and oedema were seen at any scoring interval throughout the study on any animal. There were also no notable lesions or any additional dermal findings noted during experimental phase.

Other effects:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The skin irritation study for dodecamethylpentasiloxane reports the test material to be not irritating to skin. The study was conducted according to OECD TG 404 and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 October 1998 to 10 February 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research, Kalamazoo, MI
- Age at study initiation: at least 11 weeks
- Weight at study initiation: 2081 to 2664 g
- Housing: housed individually in suspended metal cages with perforated floors measuring 45.5 cm high, 76 cm wide and 60.5 cm deep (floor area 4598 cm2). The cage size is in compliance with animal welfare guidelines. Absorbent cage liners were placed in the pan below the metal mesh floor of the animal cages to absorb liquids
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days (screen animal), 27 days (additional two animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-22.5
- Humidity (%): 43-78
- Air changes (per hr): ~18
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

Three days (i.e. no washing)

Observation period (in vivo):

Three days

Number of animals or in vitro replicates:

Three females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing


SCORING SYSTEM: Draize JH Appraisal of the Safety of Chemicals in Foods, Drugs & Cosmetics, Assoc. Food & Drug Officials of the USA, Austin, TX; 1959 (see attached document for more details)


TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: One hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: redness (transient hyperaemia of blood vessels)

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: all (1 hour, 1,2 and 3 days)

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

other: no signs of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: One hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: redness (transient hyperaemia of blood vessels)

Irritation parameter:

iris score

Basis:

mean

Time point:

other: all (1 hour, 1, 2 and 3 days)

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: no signs of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: all (1 hour, 1, 2 and 3 days)

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no signs of irritation

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: all (1 hour, 1, 2 and 3 days)

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: very slight conjunctival irritation

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

other: all (1 hour, 1, 2 and 3 days)

Score:

0

Max. score:

110

Reversibility:

other: not applicable

Remarks on result:

other: no signs of irritation

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

other: all (1 hour, 1, 2 and 3 days)

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: very slight conjunctival irritation

Irritant / corrosive response data:

A single instillation of 0.1 ml Dow Corning 200 (R) Fluid 1.5 cSt, into the eye of the rabbit elicited transient hyperaemia of the blood vessels of the conjunctivae in two animals. Ocular reactions had resolved completely in both animals by one day after instillation. There were no signs of irritation in the third animal.

Other effects:

No deaths occurred during the study. No clinical signs of systemic reaction to treatment were observed.

Interpretation of results:

not irritating

Conclusions:

Under the conditions of this study, conducted according to EPA OPPTS guideline 870.2400 (Acute Eye Irritation) and to GLP, 0.1 ml Dow Corning 200(R) Fluid 1.5 cSt instilled into the eyes of rabbits elicited very slight transient conjunctival irritation in two of three animals. The test material was considered to be not irritating to eyes.

Executive summary:

In a GLP study conducted according to US EPA Health Effects Test Guideline OPPTS 870.2400 (Acute Eye Irritation), 0.1 ml Dow Corning 200® Fluid, 1.5 cSt was administered to the lower lid of one eye of one female rabbit. This was performed in advance of the similar dosing of a further two females to ensure that if a severe response was produced, no further animals would be exposed. All animals were observed over three days, and scored for eye irritation at 1 hour, and 1,2 and 3 days after instillation.

There was no evidence of systemic toxicity in any of the animals following treatment. Transient hyperaemia of conjunctival blood vessels was observed in two rabbits, and resolved completely within 24 hours. No other signs of eye irritation were observed in any treated animal.

Under the conditions of this study, Dow Corning 200® Fluid, 1.5 cSt was non-irritating to the eyes of rabbits according to EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation is read across from structurally analogous substance dodecamethylpentasiloxane (CAS 141-63-9). The study, conducted according to OECD TG 404 and in compliance with GLP, reports the test substance, dodecamethylpentasiloxane (CAS 141-63-9), to be not irritating to skin (Dow Corning Corporation, 2009).

Following a 4 -hour application of 0.5 ml of undiluted test material onto the skin of 3 rabbits, no signs of dermal irritation, erythema or oedema were seen at any scoring interval (24, 48 and 72 hours) throughout the study on any animal. There were also no notable lesions or any additional dermal findings noted during experimental phase.

The key study for eye irritation is read across from structurally analogous substance decamethyltetrasiloxane (CAS 141-62-8). The study, conducted according to EPA OPPTS 870.2400 (Acute Eye Irritation) guideline, and in compliance with GLP, reports the test material, decamethyltetrasiloxane (CAS 141-62-8), to be not irritating to the eyes (Dow Corning Corporation, 2000).

Following a single instillation of 0.1 ml of the test material, into the eyes of three rabbits, transient hyperaemia of the blood vessels of the conjunctivae in two animals was observed. Ocular reactions had resolved completely in both animals by one day after instillation. There were no signs of irritation in the third animal. No deaths occurred during the study. No clinical signs of systemic reaction to treatment were observed.

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 irritation relevant properties are structural similarity, hydrolysis rate and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across is discussed.

Further information can be found in the supporting report (PFA, 2013u) attached in Section 13 of the IUCLID 6 dossier. 

Read-across hypothesis

The hypothesis is that the target (registered) source substance and the (read-across) substances have similar toxicological properties because they are linear siloxanes with similar physicochemical properties and are structurally similar with similar hydrolysis rates so have similar toxicological properties.

Read-across justification

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) and decamethyltetrasiloxane are also methyl substituted linear siloxanes, with five or four silicon atoms and four or three oxygen atoms.

b) Similar physicochemical properties

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

c) Similar hydrolysis rates

The linear siloxanes all hydrolyse slowly at neutral pH.

Summary of key irritation 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
Skin irritation result	Not irritant (Dow Corning Corporation, 1996)	Not irritant (Dow Corning Corporation, 1999)	Not irritant (Dow Corning Corporation, 2009e)	Not irritant (Dow Corning Corporation, 2009b)
Eye irritation result	Not irritant (Stauffer, 1973)	-	Not irritant (Dow Corning Corporation, 2000)	-

Reference

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 information from the read across substances, dodecamethylpentasiloxane (CAS 141-63-9) and decamethyltetrasiloxane (CAS 141-62-8), no classification for skin or eye irritation/corrosion is required for the registered substance according to Regulation (EC) No 1272/2008.