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Diss Factsheets

Administrative data

Description of key information

There are no reliable skin and eye irritation data available for hexamethylcyclotrisiloxane (D3; CAS 541-05-9; EC No. 208-765-4

), therefore new in vitro skin and eye irritation tests will be conducted.

As an interim measure to support the limited study on D3, available key skin and eye irritation data for other cyclic siloxanes (octamethylcyclotetrasiloxane (D4; CAS No. 556-67-2; EC No. 209-136-7); decamethylcyclopentasiloxane (D5; CAS No. 541-02-6; EC No. 208-764-9); dodecamethylcyclohexasiloxane (D6; CAS No. 540-97-6; EC No. 208-762-8)) have been read across as a weight of evidence.

In the key skin irritation study (Laboratoires de Recherches de la Societe des Usines, 1971), D4 was not irritating to rabbit skin.

In the key eye irritation study (Dow Corning Corporation, 1997e) D4 was not irritating to the eyes of rabbits.  

In the key skin and eye irritation studies (Toxikon Corporation, 1990b and c, respectively), which were conducted using protocols comparable with OECD 404 and 405, respectively, and to GLP, it was concluded that D5 was not irritating to the skin or eyes of rabbits.

The key skin irritation/corrosion study with dodecamethylcyclohexasiloxane (D6) (NOTOX, 1999c), conducted according to OECD Test Guideline 404 and in compliance with GLP, concluded that D6 was not irritating to skin.

The key eye irritation/corrosion study with dodecamethylcyclohexasiloxane (D6) (NOTOX, 1999d), conducted according to OECD Test Guideline 405 and in compliance with GLP, concluded that D6 was not irritating to eyes.  

In the in vivo skin irritation study, not conducted according to OECD Test Guideline or in compliance with GLP (Dow Corning Corporation 1980), 10-day repeated application of hexamethylcyclotrisiloxane onto the intact or abraded rabbit skin produced only slight redness, which was not concluded to be sufficient evidence for irritation.

In the in vivo eye irritation study, not conducted according to OECD Test Guideline or in compliance with GLP (Dow Corning Corporation 1980), no eye irritation was observed and the test material was concluded to be not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The study did not meet the criteria of current guidelines for skin irritation testing.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test involved repeated application of 0.5 g undiluted test substance to shaved rabbit skin for 10 days (excluding weekends).
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No detail available.
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): 0.5g

- Concentration (if solution): undiluted

Duration of treatment / exposure:
The test material was applied daily for 10 days (excluding weekends)
Observation period:
Data not available.
Number of animals:
1
Details on study design:
TEST SITE

- Area of exposure: abdomen

- Type of wrap if used: The application sites were then covered with a semi-occlusive dressing.

- The abdomen of the rabbit was prepared for testing by shaving the application site. One side of the abdomen was manually abraded while the skin on the opposite was not.  
Irritation parameter:
overall irritation score
Remarks on result:
other: The test material produced slight redness only.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility.
Irritant / corrosive response data:
The test material produced slight redness only.
Other effects:
No data available.
Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo skin irritation study, not conducted according to OECD Test Guideline or in compliance with GLP, 10-day repeated application of hexamethylcyclotrisiloxane onto the intact or abraded rabbit skin produced only slight redness, which was not concluded to be sufficient evidence for irritation.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study report lacked many details regarding the test animals and environmental conditions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Not stated

- Age at study initiation: Not stated

- Weight at study initiation: 2.3 - 2.8 kg

- Housing: Not stated

- Diet (e.g. ad libitum): Not stated

- Water (e.g. ad libitum): Not stated

- Acclimation period: Not stated

ENVIRONMENTAL CONDITIONS

- Temperature (°C): Not stated

- Humidity (%): Not stated

- Air changes (per hr): Not stated

- Photoperiod (hrs dark / hrs light): Not stated
Type of coverage:
not specified
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 to intact and abraded skin
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE

- Area of exposure: 4cm diameter

SCORING SYSTEM: Draize
Irritation parameter:
overall irritation score
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: No skin reactions were observed at any time for intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours.
Irritation parameter:
erythema score
Remarks:
intact skin
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
Remarks:
intact skin
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
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
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
Remarks:
intact skin
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
Remarks:
intact skin
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
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Other effects:
No data

No skin reactions were observed at any time for intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours.

Interpretation of results:
GHS criteria not met
Conclusions:
In a study that pre-dates GLP but was similar to OECD 404, D4 produced to skin reactions in intact with of rabbits. It is therefore not irritant according to EU criteria.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Federal Hazardous Substance Act Regulations - Consumer Product Safety Commission, 16 CFR, Part 1500, Chapter II, Subpart C, Section 1500.41, 1988.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Eastern Rabbit Breeding Industry, Taunton, MA

- Age at study initiation: 11 weeks

- Weight at study initiation: 2-3kg

- Housing: Individually housed in suspended stainless steel cages, with hardwood chips as non-contact bedding under the cages.

- Diet: commercial rabbit ration, ad libitum

- Water: municipal water, ad libitum

- Acclimation period: upon receipt, animals were placed in quarantine for 3 days.


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 +/- 3

- Humidity (%): 30-70

- Air changes (per hr): minimum 10-13

- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: shaved and abraded sites tested independently
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its own control.
Amount / concentration applied:
TEST MATERIAL

- Concentration (if solution): Undiluted

Duration of treatment / exposure:
24 hour(s)
Observation period:
The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance.
Number of animals:
3M, 3F
Details on study design:
TEST SITE

- Area of exposure: dorsal skin

- Type of wrap if used: gauze patch, which was held in place with Vetrap bandaging. the patches were applied to one intact site and one abraded site per animal.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The skin was wiped and rinsed with USP water for injection following the exposure period to remove remaining test article.

- Time after start of exposure: 24 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72h
Score:
0
Max. score:
0
Reversibility:
other: no effects
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:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
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
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema 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 overt signs of toxicity were evident in any of the animals during the course of the study. No signs of erythema or edema formation were evident on the test (or control) sites of any animal at any of the observation periods, whether the skin was abraded or intact.
Other effects:
All of the test animals exhibited a gain in body weight during the study.

The test article is considered non-irritating to the skin of the test animals.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to not be irritating to rabbit skin in a reliable study conducted according to an appropriate test protocol.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999/06/09-1999/06/12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Charles River Nederland, The Netherlands

- Age at study initiation: at least 6 weeks

- Weight at study initiation: <3.5kg

- Housing: Individually housed in labelled cages with perforated floors.

- Diet: Standard laboratory rabbit diet, ca. 100g/day

- Water: tap water, ad libitum

- Acclimation period: min. 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C):21

- Humidity (%): 50

- Air changes (per hr): ca.15

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

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.5ml

- Concentration (if solution): undiluted


Duration of treatment / exposure:
4 hour(s)
Observation period:
Observations were made 1, 24, 48, and 72 hours after exposure.
Observations performed: The animals were observed for mortality/viability twice daily. Signs of toxicity were recorded at least once daily. Body weights were recorded on the day of treatment (prior to application).
Number of animals:
3
Details on study design:
TEST SITE

- Area of exposure: skin of flank

- Type of wrap if used: The test substance on the skin was covered with a Metalline patch of 2x3cm, mounted on with Micropore tape which was wrapped around the abdomen and secured with Coban elastic bandage.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): Skin was cleaned of residual test substance using water.

- Time after start of exposure: 4 hours


SCORING SYSTEM: According to guideline
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
0
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:
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:
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:
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:
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 #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation was observed by 4 hours exposure to the test substance.
Other effects:
There was no evidence of corrosive effect on the skin. No staining of the treated skin by the test material was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
The skin irritation/corrosion study with dodecamethylcyclohexasiloxane (D6), conducted according to OECD Test Guideline 404 and in compliance with GLP, concluded D6 to be not irritating to skin.

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:
key study
Study period:
1980
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The study did not meet the criteria of current guidelines for eye irritation testing.
Qualifier:
no guideline followed
Principles of method if other than guideline:
0.1 ml undiluted hexamethylcyclotrisiloxane were instilled onto both eyes of one rabbit, after which one eye was washed and the other was not. The eyes were observed at 1, 2, 24, 48 and 168 hours.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data available.
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL

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

- Concentration (if solution): undiluted


Duration of treatment / exposure:
Single instillation into both eyes, after which one eye was washed and the other was not.
Observation period (in vivo):
The eyes were observed for 1, 2, 24, 48 and 168 hours.
Number of animals or in vitro replicates:
1
Details on study design:
No data available.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: not stated
Score:
0
Max. score:
4
Remarks on result:
other: No eye irritation was observed. The test material was not an eye irritant.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual irritation scores were not available.
Irritant / corrosive response data:
Individual irritation scores were not available. No eye irritation was observed. The test material was not an eye irritant.
Other effects:
No data available.
Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo eye irritation study, not conducted according to OECD Test Guideline or in compliance with GLP, no eye irritation was observed and the test material was concluded to be not irritating to eyes.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995/08/21 - 1997/09/30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3F
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:
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:
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:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Remarks on result:
other: Mean scores ranged from 0 to 0.3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Remarks on result:
other: Mean scores ranged from 0 to 0.3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Remarks on result:
other: Mean scores ranged from 0 to 0.3
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1h
Score:
5.3
Other effects:
No deaths occurred during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined not irritating in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Federal Hazardous Substance Act Regulations - Consumer Product Safety Commission, 16 CFR, Part 1500, Chapter II, Subpart C, Section 1500.42, 1988
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Source: Eastern Rabbit Breeding Industry, Taunton, MA

- Age at study initiation: young adults

- Weight at study initiation: 2-3kg

- Housing: Individually housed in suspended stainless steel cages, with hardwood chips as non-contact bedding under the cages.

- Diet: commercial rabbit ration, ad libitum

- Water: municipal water, ad libitum

- Acclimation period: upon receipt, animals were placed in quarantine for 7 days.


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 +/- 3

- Humidity (%): 30-70

- Air changes (per hr): minimum 10-13

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


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:
24 hour(s)
Observation period (in vivo):
Eyes were examined at 24, 48 and 72 hours after treatment.
Number of animals or in vitro replicates:
3M, 3F
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): not rinsed


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
0
Reversibility:
other: no effects
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 overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any observation points.
Other effects:
All animals exhibited an increase in body weight during the course of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to not be irritating in a reliable study conducted according to an appropriate test protocol and in compliance with GLP.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999/06/21 - 1999/06/24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Source: Charles River Nederland, The Netherlands

- Age at study initiation: at least 6 weeks old

- Weight at study initiation: 1223g, 1559g, 1569g (each)

- Housing: Individually housed in labelled cages with perforated floors.

- Diet: standard laboratory rabbit diet, ca. 100g/day

- Water: tap water, ad libitum

- Acclimation period: min. 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 21

- Humidity (%): 50

- Air changes (per hr): ca.15

- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye.
Amount / concentration applied:
TEST MATERIAL

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

- Concentration (if solution): undiluted


Duration of treatment / exposure:
Single instillation.
Observation period (in vivo):
Observations were made after 1, 24, 48 and 72 hours after instillation.
Number of animals or in vitro replicates:
3M
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): solution of 2% fluorescein in water was instilled in both eyes of each animal to quantitatively determine corneal damage

- Time after start of exposure: 24h


SCORING SYSTEM: According to guideline.


TOOL USED TO ASSESS SCORE: fluorescein/ophthalmic examination lamp
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
0
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
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:
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
Irritant / corrosive response data:
Instillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness. The irritation had completely resolved within 24 hours in all animals. No iridial irritation, corneal epithelial damage or corneal opacity were observed in any of the animals.
Other effects:
There was no evidence of ocular corrosion, no staining or peri-ocular tissues by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
The eye irritation/corrosion study with dodecamethylcyclohexasiloxane (D6), conducted according to OECD Test Guideline 405 and in compliance with GLP, concluded D6 to be not irritating to eyes.  
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no reliable skin and eye irritation data available for hexamethylcyclotrisiloxane (D3; CAS 541 -05 -9), therefore new skin and eye irritation tests will be conducted. As an interim measure to support the limited study on D3, available key skin and eye irritation data for cyclic (octamethylcyclotetrasiloxane; decamethylcyclopentasiloxane; dodecamethylcyclohexasiloxane) analogue siloxanes have been read-across as a weight of evidence.

In the key skin irritation study (Laboratoires de Recherches de la Societe des Usines, 1971) 0.5 ml of undiluted D4 was applied to the shaved skin (intact and abraded) of 6 albino rabbits for 24 hours. There was no information on the type of dressing used to hold the D4 in place. The animals were then observed for 72 hours for skin reactions and signs of toxicity. Skin reactions were scored according to the scoring system of Draize. No skin reactions were observed at any time in intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours. Therefore, D4 was not irritating to the skin under the conditions of this study.

In the key eye irritation study (Dow Corning Corporation, 1997e) 0.1 ml of undiluted D4 was administrated into the right eye of each of three New Zealand white rabbits. The eyes were rinsed with lukewarm water 24 hours after instillation, and were then scored for irritation at 1, 24, 48 and 72 hours following test substance administration. D4 was determined to not be irritating to eyes under the conditions of this study.

The key skin irritation study was conducted according to OECD test guideline 404. New Zealand white rabbits (3 animals/sex) were dermally exposed to undiluted D5 under a semi-occlusive dressing for 24 hours. On each animal there was one intact application site and one abraded site. The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance. Throughout the test, animals were observed for signs of toxicity. Skin reactions were graded according to the Draize grading system. There were no signs of toxicity or irritation and animals gained weight as expected.

The key eye irritation study was conducted according to OECD test guideline 405. New Zealand white rabbits (3 animals/sex) had 0.1 ml undiluted D5 instilled into one of their eyes. Eyes were examined at 24, 48 and 72 hours after treatment. Animals were also observed for signs of toxicity throughout the test. No overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any of the observation points.

In the key skin irritation/corrosion study with dodecamethylcyclohexasiloxane (D6) (NOTOX, 1999c), conducted according to OECD Test Guideline 404 and in compliance with GLP, 0.5 ml of undiluted test material was applied onto the skin of 3 rabbits for 4 hours under semiocclusive dressing. Skin observations were made at 1, 24, 48, and 72 hours after exposure. The animals were observed for mortality/viability twice daily. Signs of toxicity were recorded at least once daily. Body weights were recorded on the day of treatment (prior to application). There was no evidence of irritant or corrosive effects on the skin. No staining of the treated skin by the test material was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. D6 was concluded to be not irritating to skin.

In the key eye irritation/corrosion study with dodecamethylcyclohexasiloxane (D6) (NOTOX, 1999d), conducted according to OECD Test Guideline 405 and in compliance with GLP, 0.1 ml of undiluted test material was instilled into the eyes of 3 rabbits. Observations were made at 1, 24, 48, and 72 hours after exposure. At 24 hours following exposure, solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal damage. Mortality and viability of the test animals were checked twice daily. Signs of toxicity were evaluated at least once daily. Body weight was recorded on the day of treatment prior to instillation. Instillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness. The irritation had completely resolved within 24 hours in all animals. No iridial irritation, corneal epithelial damage or corneal opacity were observed in any of the animals. There was no evidence of ocular corrosion. No staining of peri-ocular tissues by the test substance was observed. No symptoms of systemic toxicity were observed in any of the animals during the test period and no mortality occurred. D6 was concluded to be not irritating to eyes.

In the in vivo skin irritation study, not conducted according to OECD Test Guideline or in compliance with GLP (Dow Corning Corporation 1980), 0.5 g undiluted hexamethylcyclotrisiloxane were applied onto the shaved intact or abraded abdominal skin of one rabbit, repeatedly for 10 days. The application sites were then covered with a semi-occlusive dressing. Application was not performed on weekends. The report did not provide individual animal data including the severity score for skin irritation reactions or the time of its onset and reversibility. The study results demonstrated that a 10-day repeated application of hexamethylcyclotrisiloxane onto the intact or abraded rabbit skin produced only slight redness, which was not concluded to be sufficient evidence for irritation.

In the in vivo eye irritation study, not conducted according to OECD Test Guideline or in compliance with GLP (Dow Corning Corporation 1980), 0.1 ml undiluted hexamethylcyclotrisiloxane were instilled onto both eyes of one rabbit, after which one eye was washed and the other was not. The eyes were observed at 1, 2, 24, 48 and 168 hours. The report did not provide individual animal data for eye irritation reactions. No eye irritation was observed and the test material was concluded to be not irritating to eyes.

Justification for classification or non-classification

Based on the available data, hexamethylcyclotrisiloxane does not require classification for skin and eye irritation according to Regulation (EC) No 1272/2007.