Reaction products of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and triacetoxyvinylsilane.

Endpoint summary

Description of key information

The key study for skin irritation, conducted according to OECD Test Guideline 404 and in compliance with GLP, reported elicited well-defined, persistent dermal irritation in rabbits; although, the irritancy score did not meet the criteria for irritation. However, desquamation evident in two test animals at study termination on Day 14 indicates that classification as Skin Irritant Category 2 is appropriate (Dow Corning Corporation, 2000c).

In the key study for eye irritation, conducted according to OECD Test Guideline 405 and in compliance with GLP, corneal lesions, iridial and conjunctival inflammation were evident. All animals were sacrificed on humane grounds (Dow Corning Corporation, 2000d).

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:

June to April 1999

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: Information removed from report
- Age at study initiation: minimum 12 weeks
- Weight at study initiation: 2489 to 2671 g
- Housing: Individually housed in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 -23
- Humidity (%): 33-56
- Air changes (per hr):minimum 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

Single dose, 4 hour exposure

Observation period:

The treated skin was examined on Day 1 and on days 2, 3 and 4 (24, 48 and 72 hours after removal of the dressings) and additional observations made on days 5 through 14 for all animals.

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: dorso lumbar region
- % coverage: 10
- Type of wrap if used: porous gauze pad was covered with 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:

2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

The single application of test material elicited a persistent well-defined dermal irritation in all animals with resolution complete by Day 14. The irritant response was associated with desquamation of the stratum corneum (characterised with dryness and sloughing) notable in all animals with skin thickening in two animals during the observation period with desquamation still evident at study termination. The primary irritation index was calculated to be 4.1.

Other effects:

No deaths occurred during the study. There was no evidence of systemic toxicity to treatment.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

In the skin irritation study, conducted according to OECD 404 and in compliance with GLP, the test material elicited well-defined persistent dermal irritation in rabbits; although, the irritancy score did not meet the criteria for irritation. However, desquamation evident in two test animals at study termination on Day 14 indicates that the test material is a skin irritant (Category 2).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June - September 1999

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: Information removed from study report
- Age at study initiation: 13 weeks
- Weight at study initiation: 2678 to 2841 g
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 33 to 53
- Air changes (per hr): ca. 18
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

14 day observation period

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed

SCORING SYSTEM: Draize, 1959

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: Unable to assess reaction due to excessive swelling

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: Unable to assess reaction due to excessive swelling

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

other: experiment terminated early due to animal welfare considerations

Irritant / corrosive response data:

The test material elicited primarily conjunctival irritation in the pilot animal, although Grade 1 corneal opacity was also evident 48 and 72 hours after instillation. Two more animals were treated based on the findings in the first animal. Corneal lesions, iridial and conjunctival inflammation quickly exceeded that previously observed in the pilot animal and within 48 hours the animals were sacrificed on humane grounds. Due to the severity of these ocular lesions in the two animals, it was not possible to determine their reversibility.

Other effects:

There was no evidence of systemic toxicity to treatment.

Under the conditions of this study the test material elicited corneal opacification, iridial inflammation and well-defined conjunctival irritation and is considered an eye irritant with the potential to cause serious damage to the eyes.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In the key study for eye irritation, conducted according to OECD Test Guideline 405 and in compliance with GLP, the test material is concluded to be corrosive, based on corneal lesions, and thereafter iridial and conjunctival inflammation. The animals were sacrificed on humane grounds within 48 hours and therefore, it was not possible to determine the reversibility of the effect.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation was conducted according to a relevant guideline and in compliance with GLP. The single application of test material elicited persistent well-defined dermal irritation in all animals with resolution complete by Day 14. The irritant response was associated with desquamation of the stratum corneum notable in all animals with skin thickening in two animals during the observation period with desquamation still evident at study termination. No deaths occurred during the study. There was no evidence of systemic toxicity to treatment. Despite the well-defined persistent dermal irritation reported in the study, the irritancy score did not meet the criteria for irritation. However, desquamation evident in two test animals at study termination on Day 14 indicates the test substance causes skin irritation (Category 2) (Dow Corning Corporation, 2000c).

In the key study for eye irritation, conducted according to OECD Test Guideline 405 and in compliance with GLP,

the test material elicited primarily conjunctival irritation in the pilot animal, with Grade 1 corneal opacity being evident at 48 and 72 hours after instillation. Two more animals were treated based on the findings in the first animal. Corneal lesions, iridial and conjunctival inflammation quickly exceeded the previously observed effect in the pilot animal. Due to the severity of these ocular lesions in the two further animals, the animals were sacrificed on humane grounds within 48 hours and it was not possible to determine the reversibility of the effect. No evidence of systemic toxicity following treatment of the test material was observed (Dow Corning Corporation, 2000d).

Justification for classification or non-classification

Based on the available in vivo data, the registered substance is classified for skin irritation, Category 2: Irritant, H315: causes skin irritation and Irreversible effects on the eye, Category 1, H318: Causes serious eye damage, in accordance with Regulation (EC) No. 1272/2008.

The registered substance may contain acetic anhydride (CAS 108-24-7) at concentrations <10% w/w. In accordance with the harmonised entry in Annex VI of Regulation (EC) No 1272/2008 (specific concentration limits), acetic anhydride concentrations ≥5% should carry the additional classification STOT SE 3; H335: May cause respiratory irritation. In the absence of measured data for the inhalation route to override this limit, the additional classification is applied to the registration substance.