Reaction mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane

Endpoint summary

Description of key information

There are no available skin or eye irritation data for the registered substance "Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane". Therefore, data have been read-across from its constituents, HMDS, L3, L4 and L5.

Skin irritation:

In the reliable skin irritation study for HMDS conducted in accordance with a suitable test guideline and in compliance with GLP (Dow Corning Corporation, 1996), repeated 24 hour occluded contact with HMDS caused slight to well defined erythema and moist exfoliation. Semi-occluded and open contacts did not cause test material-related irritation to the skin of albino rabbits.

The skin irritation study for L3 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).

In the reliable skin irritation study for L4 performed according to an appropriate test protocol and in compliance with GLP, found L4 non-irritating to the skin of three rabbits (Dow Corning Corporation, 2009b).

The skin irritation study for L5 reports the test material to be a non-irritant determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009b).

Eye irritation:

In the key eye irritation study for HMDS (Stauffer Chemical Company, 1973) HMDS was not irritating to the eyes of rabbits.

The eye irritation study for L4 conducted according an appropriate test protocol and in compliance with GLP, showed very slight transient conjunctival irritation in two of three animals. The test material was considered to be not irritating to eyes (Dow Corning Corporation, 2000).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1994/05/12 - 1996/04/11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: modified methods of CTFA Safety Testing Guidelines, published by the Cosmetic, Toiletry and Fragrancy Association on September 27, 1985, and Preclinical Safety Evaluation of Materials used in Medical Devices HIMA Report 85-1.

Deviations:

yes

Remarks:

The water contained Trihalomethane (162 μg/l) that was above the EPA recommended level of 100 μg/l.

GLP compliance:

yes

Species:

guinea pig

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: not stated

- Age at study initiation: ca. 3 months

- Weight at study initiation: 2.31-2.59 kg

- Housing: individual housing, in conventional design stainless steel cages

- Diet: Purina 5325 Certified High Fiber Rabbit Chow, ad libitum

- Water: ad libitum

- Acclimation period: 7 day quarantine


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 61-70

- Humidity (%): 40-60

- Air changes (per hr): 10-15

- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

other: occluded, semi-occluded or open

Preparation of test site:

other: intact and abraded

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:

10 applications over 14 days

Observation period:

14 days

Number of animals:

3/group

Details on study design:

TEST SITE

- Area of exposure: the back

- Type of wrap if used: For occlusive application; a cotton gauze patch covered with a piece of SARAN plastic wrap, held in place by a cotton cloth bandage taped to their hair for 24 hours. Semi-occlusive wrap; a cotton gauze patch, held in place by a cotton cloth bandage taped to the hair for 24 hours. For unocculuded applicaiton, no wrap was used.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): not reported


SCORING SYSTEM: The skin responses were cored on a 0-4 scale, 0 representing no reaction and 4 representing a severe reaction.

Irritation parameter:

other: Occluded application

Basis:

other: Repeated application

Time point:

other: Repeated 14 day exposure

Max. score:

2

Remarks on result:

other: Very slight to well defined erythema. See Table 1 for complete mean values.

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:

Occlusive group: very slight to well defined erythema and moist exfoliation was observed in all animals in this group by the fourth day of testing and continued throughout the study (abraded sites were healed by the fourth test day). A difference between intact and abraded sites showed a persistence of exfoliation at the abraded sites (exfoliation was present days 4 through 6 at intact sites and days 4 through 10 at abraded sites).

Semi-occlusive group: no test material - related irritation was observed in these animals during the study (abraded sites were healed by the fourth test day). No differences were observed between the intact and abraded sites.

Unoccluded group: No irritation was observed in animals during the course of the study (abraded sites were healed by the fourth day). No differences were seen between the intact and abraded sites.

Other effects:

There were no apparent test material-related effects on clinical signs, food consumption or body weight gains. The occluded wrapped animals gained less weight than the other groups. This equivocal result was possibly due to the occlusive wrappings.

Table 1: Mean Skin irritation scores at various intervals (30 minutes scoring)

Method	Skin Response	Score after application number*
		1	2	3	4	5	6	7	8	9	10
Occlusive	ErythemaMax. score: 4	0/0	0/0	0/0	2/2	2/2	1.3/1.3	0/1	0.7/1.7	1/1.7	0/1
	Edema     Max. score: 4	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0
Semi-occlusive	ErythemaMax. score: 4	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0
	Edema     Max. score: 2	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0
Unoccluded	ErythemaMax. score: 4	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0
	Edema     Max. score: 2	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0

 *intact/abraded

Interpretation of results:

GHS criteria not met

Conclusions:

In a test that was conducted in accordance with a suitable test guideline and in compliance with GLP, HMDS did not meet the criteria for classification as a skin irritant in the EU. The study involved repeated applications over 14 days and as such exceeds the requirements of the OECD 404 skin irritation study.

Reference 2

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 with L3. No dermal irritation was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material (L3) was found not irritating in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 January 2009 to 3 March 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)

Deviations:

no

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: no data available
- Age at study initiation: approximately 4 months
- Weight at study initiation: 2660 to 2789 g
- Housing: individually
- Diet (e.g. ad libitum): standard diet, provided as recommended by animal vendor
- Water (e.g. ad libitum): purified municipal water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 20.6
- Humidity (%): 51 to 62
- Air changes (per hr): 13.1
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 January 2009 To: 30 January 2009

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%

Duration of treatment / exposure:

Pilot study: 3 min, 1 hour, 4 hours (1 animal, three sites)
Confirmatory study: 4 hours (2 animals, 1 site/animal)

Observation period:

Pilot study: for 3-minute and 1-hour treatments, observation at 0 hours after patch removal; for 4-hour treatment, observations at 60 ± 5 min, 24 ± 2 hours, 48 ± 2 hours and 72 ± 2 hours after patch removal.
Confirmatory study: for 4-hour treatment, observations at 60 ± 5 min, 24 ± 2 hours, 48 ± 2 hours and 72 ± 2 hours after patch removal.

Number of animals:

1 male (pilot study)
2 males (confirmatory study)

Details on study design:

TEST SITE
- Area of exposure: no data available
- % coverage: no data available
- Type of wrap if used: coverlet wrapped by a layer of gauze bandage followed by a layer of elastic wrap (Elastoplast (R)). Animals were fitted with Elizabethan collars for at least 24 hours to prevent removal of bandaging.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance removed following exposure period with water-moistened gauze, and dry gauze
- Time after start of exposure: presumably 3 mins, 1 hour or 4 hours

SCORING SYSTEM: EEC Primary Irritation Index (PII); EPA Primary Irritation Index (PII)

Irritation parameter:

erythema score

Remarks:

EEC

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

EEC

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: overall

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

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 signs of dermal irritation (erythema or oedema) were seen at any observation time point in any animal.

Other effects:

No dermal lesions or additional dermal findings were noted during the experimental phase. No remarkable changes in body weight were observed (mean body weight change of 30.7 with standard deviation 7.77). No animals died during the course of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study performed according to OECD Test Guideline 404, L4 was non-irritating to the skin of three rabbits when applied undiluted semi-occluded for 4 hours.

Executive summary:

In an acute dermal irritation/corrosion study carried out to GLP and according to OECD Test Guideline 404, rabbits were exposed dermally to L4.

In a pilot study, 0.5 ml of the undiluted test substance was applied under occlusion to the shaved, intact skin of one male rabbit for three minutes or one hour. The test site was scored immediately after patch removal. The confirmatory study involved the treatment of the same animal, and two additional males, with the undiluted test substance under occlusion for four hours. Animals were observed at approximately 1, 24, 48 and 72 hours after patch removal.

No signs of dermal irritation or any other toxic effect were seen over the course of the study.

Under these experimental conditions, undiluted L4 was non-irritating to the skin of rabbits when applied for up to four hours.

Reference 4

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 slatted 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:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

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:

0

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 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 L5 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

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

It was not compliant with GLP.

Qualifier:

according to guideline

Guideline:

other: CFR 191.12 Ch Title 21

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 1.6-2.1 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye.

Amount / concentration applied:

TEST MATERIAL

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

Duration of treatment / exposure:

Single instillation, not rinsed.

Observation period (in vivo):

Eyes were observed at 24, 48 and 72 hours and scored for irritation.

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Eye irritation was determined according to the method outlined in the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances" (Total possible score 110). If at the end of 72 hours ocular damage appears to be remissable (reversible), the animal is observed for additional 4-7 days before final scoring is possible.

Irritation parameter:

other: Ocular irritation.

Basis:

other: not specified

Time point:

other: 24/48/72h

Score:

0

Remarks on result:

other: Not irritating

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:

cornea opacity score

Basis:

animal #4

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 #5

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 #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

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:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

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:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of 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

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of eye irritation were observed.

Other effects:

None reported.

No apparent signs of eye irritation were observed. The test animals appeared normal when necropsied 14 days after treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was found not irritating as determined in a reliable study conducted according to generally accepted scientific principles.

Reference 2

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

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:

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

Reversibility:

other: not applicable

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

Reversibility:

other: not applicable

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:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

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:

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:

no indication 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

There are no available skin or eye irritation data for the registered substance "Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane". Therefore, data have been read-across from its following four constituents:

1) HMDS: hexamethyldisiloxane (CAS 107-46-0)

2) L3: octamethyltrisiloxane (CAS 107-51-7)

3) L4: decamethyltetrasiloxane (CAS 141-62-8)

4) L5: dodecamethylpentasiloxane (CAS 141-63-9

Skin irritation:

In the skin irritation study for HMDS (Dow Corning Corporation, 1996), intact and abraded skin of NZW rabbits (3 animals/group) were exposed to HMDS under occlusive, semi-occlusive or open conditions for ten 24 hour periods over 14 days. There were no apparent test substance-related effects on clinical signs, food consumption or body weight gains. The occluded wrapped animals gained less weight than the other groups. This equivocal result was possibly due to the occlusive wrappings. Under the test conditions, repeated 24-hour occluded contacts with the test substance caused slight to well defined erythema and moist exfoliation. Semi-occluded and non-occluded contacts did not cause test substance-related irritation to the skin of albino rabbits.

The skin irritation study for L3 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 skin irritation study for L4 reported no signs of dermal irritation (erythema or oedema) at any observation time point in any animal when L4 was applied undiluted semi-occluded for 4 hours (Dow Corning Corporation, 2009c). No clinical signs, dermal lesions or remarkable changes in body weight were reported.

The skin irritation study for L5 reports the test material to be a non-irritant determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009b). 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.

Eye irritation:

In the eye irritation study for HMDS (Stauffer Chemical Company, 1973) the eyes of NZW rabbits (6 animals) were exposed to a single dose of HMDS and irritation graded after 24, 48 and 72 hours. No apparent signs of eye irritation were observed. The eyes also appeared normal when necropsied 14 days after treatment. Therefore HMDS was concluded not to be irritating to eyes.

The eye irritation study for L4 reported no evidence of systemic toxicity in any of the animals following treatment. L4 (0.1 ml) instilled into the eyes of rabbits elicited transient hyperaemia of conjunctival blood vessels in two rabbits, and resolved completely within 24 hours. No other signs of eye irritation were observed in any treated animal (Dow Corning Corporation, 2000).

Read-across from substance's constituents justification

A detailed read-across explanation is available in Section 7.5.

The registered substance "Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane (EC No 946-797-7)" belongs to the structural class of siloxanes. All the substances have high log Kow (increasing with increasing chain length) and low water solubility. In vivo skin and eye irritation studies are available for a number of these substances.

The available studies for the linear siloxanes from this analogue group, as well as key physicochemical properties, are summarised in the table below. 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. The most recent and reliable studies for the substance’s constituents were chosen for weight of evidence.

Summary of key irritation data for linear siloxanes

Substance	HMDS	L3	L4	L5
Chemical name	Hexamethyldisiloxane	Octamethyltrisiloxane	Decamethyltetrasiloxane	Dodecamethylpentasiloxane
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)	-

Justification for classification or non-classification

Based on the available data for Reaction Mass of decamethyltetrasiloxane; dodecamethylpentasiloxane; hexamethyldisiloxane; octamethyltrisiloxane constituents, no classification is required for skin and eye irritation according to Regulation (EC) No 1272/2008.