acrylic acid, 3-(trimethoxysilyl)propyl ester

Endpoint summary

Description of key information

In the key in vivo skin irritation study, conducted according to EPA OPP 81-5 (Acute Dermal Irritation, similar to OECD Test Guideline 404) and in compliance with GLP (reliability score 1, SafePharm Laboratories Limited, 1995d), the study authors concluded that 3-(trimethoxysilyl)propyl acrylate (CAS No. 4369-14-6, EC No. 419-560-6) causes severe skin irritation to rabbit skin following 4-hour semi-occluded dermal application. However, the study reviewer considers that the observed effects indicate the test substance causes skin corrosion based on the dermal effects still evident at the last (day 7) observation timepoint. The corrosion interpretation is consistent with Annex VI of Regulation (EC) No. 1272/2008.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

1984

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-20 weeks old
- Weight at study initiation: 2.25-2.82 kg
- Housing: Individually
- Diet (e.g. ad libitum): STANRAB SQC Rabbit Diet, ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Humidity (%): 50-69
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

Up to 7 days

Number of animals:

3M, 3F

Details on study design:

TEST SITE
- Area of exposure: Dorsal/flank area
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: Surgical adhesive tape wrapped in an elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test item was removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirits
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
At 1 hour following the removal of the patches and approximately at 24, 48 and 72 hours after patch removal, the test site was examined for primary irritation.

SCORING SYSTEM:
- Method of calculation: Draize system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks:

Noting, at this timepoint, crust formation and desquamation were noted at all treated skin sites. These reactions extended up to 6 cm at all treatment sites.

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Well-defined erythema (all animals) and slight (1 female) to severe oedema (3 animals at 1 hour, 5 animals at 24 hours) were noted in animals at 1 and 24 hours after patch removal. Well-defined (5 aninimals) to severe (1 female) erthema and very slight (one female) or severe (other 5 animals) edema were observed at 48 hours. Very slight (1 female) to severe (1 female) erythema and very slight (1 female) to severe ( 1 male and 1 female) oedema were seen at the 72-hour observation. The erythema extended up to 4 cm beyond all treatment sites at 1 hour after patch removal. The erythema extended up to 6 cm beyond for 5 treatment sites at the 24-hour observation, and 4 treatment sites at the 48-hour and 72-hour observations.

Haemorrhage of the dermal capillaries was noted at 1 treated skin site at 1 hour after patch removal and at the 24, 48 and 72-hour observations. Blanching of the skin around the edge of treatment site was noted at one treated skin site at the 24 and 48-hour observations. Light brown discolouration of the epidermis was noted at two treated skin sites at the 24, 48 and 72-hour observations. Skin reactions noted in all treated skin sites at the 7-day observation were crust formation or desquamation, with these reactions extending up to 6 cm beyond all treatment sites at this timepoint.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

Annex VI of Regulation (EC) No. 1272/2008 considers the classification to be Category 1B (corrosive), with this classification implemented for the registered substance.

Conclusions:

In the in vivo skin irritation study, conducted according to EPA OPP 81-5 (Acute Dermal Irritation) and in compliance with GLP, the study authors stated that 3-(trimethoxysilyl)propyl acrylate causes severe skin irritation to rabbit skin following 4-hour semi-occluded dermal application. However, the study reviewer concludes that the test substance causes skin corrosion based on the dermal effects still evident at the day 7 observation timepoint. Annex VI of (EC) No. 1272/2008 considers 3-(trimethoxysilyl)propyl acrylate to be corrosive/]h]]]

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key in vivo skin irritation study, conducted according to EPA OPP 81-5 (Acute Dermal Irritation) and in compliance with GLP (reliability score 1, SafePharm Laboratories Limited, 1995d), 0.5 ml of undiluted 3-(trimethoxysilyl)propyl acrylate was applied onto the clipped dorsal area of 6 rabbits under semi-occlusive dressing for 4 hours. Following patch removal, any residual test item was removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirits and skin irritation reactions were assessed at 1, 24, 48 and 72 hours and up to day 7.

 

Well-defined erythema and slight to severe oedema were noted in animals at 1 and 24 hours after patch removal. Well-defined to severe erythema and very slight or severe oedema were observed at 48 hours. Very slight to severe erythema and very slight to severe oedema were seen at the 72-hour observation. The erythema extended up to 4 cm beyond all treatment sites at 1 hour after patch removal. The erythema extended up to 6 cm beyond for 5 treatment sites at the 24-hour observation, and 4 treatment sites at the 48-hour and 72-hour observations.

 

Haemorrhage of the dermal capillaries was noted at one treated skin site at 1 hour after patch removal and at the 24, 48 and 72-hour observations. Blanching of the skin around the edge of treatment site was noted at one treated skin site at the 24 and 48-hour observations. Light brown discolouration of the epidermis was noted at two treated skin sites at the 24, 48 and 72-hour observations. Skin reactions noted in all treated skin sites at the day 7 observation were crust formation or desquamation, with these reactions extending up to 6 cm beyond all sites at this timepoint.

 

The study authors concluded that 3-(trimethoxysilyl)propyl acrylate causes severe skin irritation to rabbit skin following 4-hour semi-occluded dermal application. However, the study reviewer concludes the test substance causes skin corrosion based on the dermal effects still evident at the last (day 7) observation timepoint.

 

Based on the current classification criteria, the reviewer concludes the data indicate classification as Skin Corrosion Category 1C. However, in the absence of further information, the harmonised classification of Skin Corrosion Category 1B is implemented for the registered substance and is consistent with the Annex VI of Regulation (EC) No. 1272/2008.

Justification for classification or non-classification

3-(Trimethoxysilyl)propyl acrylate is classified for skin corrosion Category 1B, H314: "Causes severe skin burns and eye damage" according to Annex VI of Regulation (EC) No. 1272/2008, with the eye Category 1 classification triggered by the harmonised skin classification.