Octamethyltrisiloxane

Endpoint summary

Description of key information

The key study for skin irritation found the test material not irritating to rabbit skin in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 1999). The key study for eye irritation is read across from the structurally analogous decamethyltetrasiloxane (CAS 141-62-8). Very slight transient irritation was evident in two out of the three test animals which did not meet the EU criteria for classification for irritation (Dow Corning 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:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not stated
- Age at study initiation: not states
- Weight at study initiation: 2253-2685g
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 11

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-17.5
- Humidity (%): 54-76
- Air changes (per hr): ca. 18
- 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:

single application

Observation period:

72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorso-lumbar skin
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No dermal irritation was observed.

Other effects:

There was no evidence of systemic response to treatment. No dermal irritation was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was found not irritating in a reliable study conducted according to an appropriate test protocol, 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:

guideline study

Remarks:

The study was conducted according to an appropriate EPA OPPTS guideline 870.2400, and in compliance with GLP, and was considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified; the read across is considered to be reliability 2.The study was conducted according to and in compliance with GLP.

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: removed from report
- 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:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication 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

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of 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:

GHS criteria not met

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 was a reliable 4 hour, semi-occlusive study, conducted in compliance with GLP (Dow Corning 1999).

No dermal irritation was observed and there was no evidence of systemic response to treatment.

The available supporting data for skin irritation reports no irritant effects in any of the test animals in response to a 4 hour, semi-occlusive application. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Both the erythema and edema scores were 0 at 24, 48 and 72 hours (RCC 1999).

The key study for eye irritation is read across from the structurally analogous decamethyltetrasiloxane (CAS 141-62-8) (Dow Corning 2000). The study was conducted according to an appropriate EPA OPPTS guideline 870.2400, and in compliance with GLP, and was considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified. The study was conducted according to and in compliance with GLP. A single instillation of the test substance, 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. The test material was considered to be not irritating to eyes.

READ-ACROSS JUSTIFICATION

Octamethyltrisiloxane (L3) belongs to the structural class of siloxanes (alkyl, vinyl, aryl or hydrogen substituted). The substances all have high log K_ow (increasing with increasing chain length) and low water solubility. In vivo skin and eye irritation studies are available for a number of these substances. For the registration substance itself, only skin irritation studies are available (Dow Corning Corporation, 1999; RCC, 1999).

The available studies for the linear siloxanes from this analogue group, as well as key physicochemical properties, are summarised in the table below. The results of the irritation 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 skin or eye irritation. It is therefore valid to read-across the lack of irritation between the members of the group where there are data gaps.

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, 2009d)	Not irritant (Dow Corning Corporation, 2009e)
Eye irritation result	Not irritant (Stauffer, 1973)	-	Not irritant (Dow Corning Corporation, 2000)	-

Justification for classification or non-classification

Based on the available information on the registered substance, L3 is not classified for skin or eye irritation according to Regulation (EC) No 1272/2008.