Registration Dossier

Administrative data

Description of key information

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the eye irritation endpoint. There are key skin irritation data available for L5, therefore data for the other linear siloxanes have been included as supporting for consistency and to support read across justifications.

Skin irritation

L5: The key study for skin irritation with L5 (dodecamethylpentasiloxane, CAS 141-63-9), conducted according to OECD Test Guideline 404 and in compliance with GLP, reports the test material to be not irritating to skin (Dow Corning Corporation, 2009b).

Eye irritation

HMDS: In the eye irritation study with HMDS (hexamethyldisiloxane, CAS 107-46-0), conducted according to a guideline similar to OECD Test Guideline 405 but not in compliance with GLP (Stauffer Chemical Company, 1973), HMDS was not irritating to the eyes of rabbits.

L3: There are no eye irritation data for L3 (octamethyltrisiloxane, CAS 107-51-7).

L4: In the eye irritation study with L4 (decamethyltetrasiloxane, CAS 141-62-8) conducted according to EPA OPPTS guideline 870.2400 (Acute Eye Irritation) and in compliance with GLP, the test material was concluded to be not irritating to eyes (Dow Corning Corporation, 2000).

L5: There are no eye irritation data for L5 (dodecamethylpentasiloxane, CAS 141-63-9).

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:
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 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

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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: 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:
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:
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:
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 test material, 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 test material 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 testt material 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, the test material was non-irritating to the eyes of rabbits according to EU criteria.

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:
4
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the eye irritation endpoint. There are key skin irritation data available for L5, therefore data for the other linear siloxanes have been included as supporting for consistency and to support read across justifications.

Skin irritation

L5: The key skin irritation study for L5 (dodecamethylpentasiloxane, CAS 141-63-9), conducted according to OECD Test Guideline 404 and in compliance with GLP, reports the test material to be not irritating to skin (Dow Corning Corporation, 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.

HMDS: In the skin irritation study with HMDS (hexamethyldisiloxane, CAS 107-46-0), conducted according to a guideline similar to OECD Test Guideline 404 and in compliance with GLP (Dow Corning Corporation, 1996), intact and abraded skin of New Zealand white 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 observed minor irritation did not meet the criteria for classification.

L3: The skin irritation study with L3 (octamethyltrisiloxane, CAS 107-51-7), conducted according to a protocol similar to OECD Test Guideline 404 and in compliance with GLP, found the test material to be not irritating to rabbit skin (Dow Corning Corporation, 1999). In the study the test material was applied onto rabbit skin for 4 hours under semi-occlusive dressing. No dermal irritation was observed and there was no evidence of systemic response to treatment.

L4: The skin irritation study with L4 (decamethyltetrasiloxane, CAS 141-62-8), conducted according to OECD Test Guideline 404 and in compliance with GLP, found the test material to be not irritating to the skin of three rabbits (Dow Corning Corporation, 2009). The study reported no signs of dermal irritation (erythema or oedema) at any observation time point in any animal when L4 was applied undiluted under semi-occlusive dressing for 4 hours. No clinical signs, dermal lesions or remarkable changes in body weight were reported.

Eye irritation

HMDS: In the eye irritation study with HMDS (hexamethyldisiloxane, CAS 107-46-0), conducted according to a guideline similar to OECD Test Guideline 405 but not in compliance with GLP (Stauffer Chemical Company, 1973), the eyes of New Zealand white 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.

L3: There are no eye irritation data forL3 (octamethyltrisiloxane, CAS 107-51-7).

L4: In the eye irritation study with L4 (decamethyltetrasiloxane, CAS 141-62-8) conducted according to EPA OPPTS guideline 870.2400 (Acute Eye Irritation) and in compliance with GLP, the test material was concluded to be not irritating to eyes (Dow Corning Corporation, 2000). Following instillation of 0.1 ml of L4 into the eyes of rabbits, there was no evidence of systemic toxicity in any of the animals. 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.

L5: There are no eye irritation data for L5 (dodecamethylpentasiloxane, CAS 141-63-9).

Justification for classification or non-classification

Based on the available information for the registration substance and read across from the structurally analogous substances hexamethyldisiloxane (HMDS; CAS 107-46-0), octamethyltrisiloxane (L3; CAS 107-51-7) and decamethyltetrasiloxane (L4; CAS 141-62-8), no classification is required for dodecamethylpentasiloxane for skin or eye irritation, in accordance with Regulation (EC) No 1272/2008.