[No public or meaningful name is available]

Endpoint summary

Description of key information

Skin Irritation:
REACH_not irritating | EpiDerm | OECD 439 | #key study#
REACH_not corrosive | EpiDerm | OECD 431 | #key study#

 

Eye irritation:
REACH_not irritating | BCOP | OECD 437 | #key study#
REACH_not irritating | EpiOcular | OECD 492 | #key study#

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Remarks:

EpiDerm

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

foreskin from a single donor

Justification for test system used:

This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.

Vehicle:

unchanged (no vehicle)

Details on test system:

The test was carried out with the reconstituted three-dimensional human skin model EpiDerm (MatTek). This skin model consists of normal human epidermal keratinocytes (NHEK) which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. The NHEK are cultured on chemically modified, collagen-coated cell culture inserts (Millicell). The EpiDerm epidermis model exhibits in vivo-like morphological and growth characteristics which are uniform and highly reproducible. It consists of organised basal, spinous and granular layers and a multi-layered stratum corneum analogous to patterns found in vivo.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

- Negative control 30 μL DPBS
- Positive control 30 μL 5% SDS solution
- Test Item Liquids: 30 μL (undiluted)

Duration of treatment / exposure:

60 min

Duration of post-treatment incubation (if applicable):

42 h

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

test item

Value:

92.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

100.0

Positive controls validity:

valid

Remarks:

4.4

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

The controls confirmed the validity of the study.
The mean absolute OD570 of the three negative control tissues was >= 0.8 and <= 2.8 (1.724). The mean relative tissue viability (% negative control) of the positive control was < 20% (4.4%). Standard deviation of viability of replicate tissues of all dose groups was <= 18% (0.5% - 17.6%).

The mixture of 30 μL test item per 1 mL MTT medium showed reduction of MTT compared to the solvent. The mixture turned blue/purple.

For quantitative correction of results, two killed tissues were treated with 30 μL of the test item (KT) and two killed tissues were left untreated as a control (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NC) according to the following formula:

NSMTT [%] = [(ODKT - ODKU)/ODNC] * 100 = -8.7%

Mean ODKT = 0.109

Mean ODKU = 0.241

Mean ODNC = 1.518

NSMTT was ≤ 30% (-8.7%) relative to the negative control of living epidermis, the true MTT metabolic conversion (TODTT) of the test item treated living tissues TM was therefore corrected according to the following formula:

TODTT = ODTM – (ODKT – ODKU) = 1.685

The mixture of 30 μL of the test item per 300 μl aqua dest. and per 300 μL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSC equaled 0%.

The test item showed non-specific reduction of MTT, but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (100.4%, NSMTT-corrected) after 60 min treatment and 42 h post-incubation.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study under the given conditions the test item showed no irritant effects. The relative mean tissue viability after 60 min of exposure and 42 h post-incubation was > 50%. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.

Executive summary:

In the present study the skin irritant potential of

2-Propenoic acid,2-[[3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5(or 6)-yl]oxy]ethyl ester; EC Name: Reaction mass of 2-(3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-5-yloxy)ethyl acrylate and 2-(3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-6-yloxy)ethyl acrylate was analysed. The EpiDerm™-Standard Model (EPI-200™), a reconstituted three-dimensional human epidermis model, was used as a replacement for the Draize Skin Irritation Test (OECD TG 404) to distinguish between UN GHS “Category 2” skin irritating test substances and not categorized test substances (“No Category”) which may be considered as non-irritant. Hereby, the test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 60 min exposure and 42 h post-incubation period and compared to those of the concurrent negative controls.

The mixture of 30 μL test item per 1 mL MTT medium showed reduction of MTT compared to the solvent. The mixture turned blue/purple.

For quantitative correction of results, two killed tissues were treated with 30 μL of the test item (KT) and two killed tissues were left untreated as a control (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NC).

NSMTT was ≤ 30% (-8.7%) relative to the negative control of living epidermis, the true MTT metabolic conversion (TODTT) of the test item treated living tissues TM was therefore corrected according to the following formula: TODTT = ODTM – (ODKT – ODKU) = 1.685

The mixture of 30 μL of the test item per 300 μl aqua dest. and per 300 μL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSC equaled 0%. The test item showed non-specific reduction of MTT, but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (100.4%, NSMTT-corrected) after 60 min treatment and 42 h post-incubation.

Conclusion

In this study under the given conditions the test item showed no irritant effects. The relative mean tissue viability after 60 min of exposure and 42 h post-incubation was > 50%. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Version / remarks:

June 2018

Qualifier:

according to guideline

Guideline:

other: Council Regulation 440/2008, Method B.40 BIS: “In Vitro Skin Corrosion: Human Skin Model Test”

Version / remarks:

May 30, 2008

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Remarks:

EpiDerm

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

foreskin from a single donor

Justification for test system used:

The EpiDerm Skin Model is a well-established organotypic, three-dimensional model of the human epidermis and is used for in vitro experiments since many years. It is known for its similarity to human skin.

Vehicle:

unchanged (no vehicle)

Details on test system:

The test was carried out with the reconstituted three-dimensional human skin model EpiDerm (MatTek). This skin model consists of normal (non-cancerous), human-derived epidermal
keratinocytes (NHEK) which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. The NHEK are cultured on chemically modified, collagen-coated cell culture inserts (Millicell). The EpiDerm skin model exhibits in vivo-like morphological and growth characteristics which are uniform and highly reproducible. It consists of organised basal, spinous,
granular and cornified layers analogous to those found in vivo.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

- Negative control 50 μL distilled water
- Positive control 50 μL 8 N KOH
- Test Item 50 μL (undiluted)

Duration of treatment / exposure:

3 min / 60 min

Duration of post-treatment incubation (if applicable):

3 h MTT incubation

Number of replicates:

duplicate

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

3 min experiment

Value:

105.9

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

100.0

Positive controls validity:

valid

Remarks:

18.0

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

60 min experiment

Value:

94.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

100.0

Positive controls validity:

valid

Remarks:

4.3

Other effects / acceptance of results:

The controls confirmed the validity of the study.
The mean OD570nm of the two negative control tissues was >= 0.8 and <= 2.8 for each exposure period (1.765, 1.955).
The mean relative tissue viability (% negative control) of the positive control was <= 15% (4.3%) after 60 min treatment.
The coefficient of variation (CV) (in the range of 20 – 100% viability) of replicate tissues of all dose groups was <= 30% (0.1% - 10.1%).

Corrosivity potential of the test item was predicted from the relative mean tissue viabilities obtained after both treatment periods had been compared to the corresponding negative control tissues.

The mixture of 50 μL test item per 1 mL MTT medium showed reduction of MTT as compared to the solvent. The mixture turned blue/purple.

For quantitative correction of results, the part of absorption due to the non-specific reduction of MTT (NSMTT) was determined by using killed tissues. Therefore, two tissues per treatment period were treated with the test item (KT) or left untreated (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NC) per treatment period according to the following formula:

NSMTT (3min) = [(ODKT - ODKU)/ODNC] * 100 = [(0.076 - 0.062)/ 1.720] *100 = 0.8%

NSMTT (60 min) = [(ODKT - ODKU)/ODNC] * 100 = [(0.076 - 0.066)/ 1.910] *100 = 0.5%

NSMTT was ≤ 30% relative to the negative control of living epidermis. In the 3 min experiment NSMTT was 0.8%, in the 60 min experiment 0.5%. This means that the test item was washed away almost completely before the addition of the MTT solution. The true MTT metabolic conversion (TODTT) of the test item treated living tissues (TM) was corrected for each treatment period according to the follwing formula:

TODTT (3 min) = ODTM - (ODKT - ODKU) = 1.822 – (0.076 - 0.062) = 1.809

TODTT (60 min) = ODTM - (ODKT - ODKU) = 1.811 – (0.076 - 0.066) = 1.801

The mixture of 50 μL test item per 300 μL Aqua dest. and per 300 μL isopropanol showed no colouring as compared to the solvent. Therefore, NSC equalled 0%.

The test item showed non-specific reduction of MTT, but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed non-specific MTT-reducing potential. Therefore, additional killed tissue controls were treated with the test item to determine the non-specific reduction of MTT (NSMTT) and the results were corrected to the true MTT metabolic conversion (TODTT). The test item showed no water colouring potential.

The test item showed no corrosive effects. The mean relative tissue viability (% negative control) was >= 50% (105.1%, NSMTT-corrected) after 3 min treatment and >= 15% (94.3%, NSMTT-corrected) after 60 min treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study under the given conditions the test item showed no corrosive effects. The test item is classified as “non-corrosive“.

Executive summary:

In the present study the skin corrosivity potential of 2-Propenoic acid,2-[[3a,4,5,6,7,7a-hexahydro-4,7 -methano-1H-inden-5(or 6)-yl]oxy]ethyl ester was analysed. Since corrosive chemicals are cytotoxic after a short time exposure to the stratum corneum of the epidermis the cytotoxic effects of the test item on EpiDerm, a reconstituted three-dimensional human epidermis model, were determined. Hereby, the test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 3 min and 60 min exposure period and compared to those of the concurrent negative controls.

The mixture of 50 μL test item per 1 mL MTT medium showed reduction of MTT as compared to the solvent. The mixture turned blue/purple.

For quantitative correction of results, the part of absorption due to the non-specific reduction of MTT (NSMTT) was determined by using killed tissues. Therefore, two tissues per treatment period were treated with the test item (KT) or left untreated (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NC) per treatment period. NSMTT was ≤ 30% relative to the negative control of living epidermis. In the 3 min experiment NSMTT was 0.8%, in the 60 min experiment 0.5%. This means that the test item was washed away almost completely before the addition of the MTT solution. The true MTT metabolic conversion (TODTT) of the test item treated living tissues (TM) was corrected for each treatment period.

The mixture of 50 μL test item per 300 μL Aqua dest. and per 300 μL isopropanol showed no colouring as compared to the solvent. Therefore, NSC equalled 0%.

The test item showed non-specific reduction of MTT, but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed no corrosive effects. The mean relative tissue viability (% negative control) was >= 50% (105.1%, NSMTT-corrected) after 3 min treatment and >= 15% (94.3%, NSMTT-corrected) after 60 min treatment.

Conclusion

In this study under the given conditions the test item showed no corrosive effects. The test item is classified as “non-corrosive“.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Qualifier:

according to guideline

Guideline:

other: EURL ECVAM DB-ALM Method Summary No. 164: EpiOcular™ Eye Irritation Test

Version / remarks:

22 July 2015

GLP compliance:

yes (incl. QA statement)

Species:

human

Strain:

other: normal epidermal keratinocytes

Details on test animals or tissues and environmental conditions:

The test was carried out with the EpiOcular™ reconstructed human cornea-line epithelium (RhCE) model (MatTek). The model consists of normal, human-derived epidermal keratinocytes which have
been cultured to form a stratified, highly differentiated squamous epithelium morphologically similar to that found in a human cornea. The EpiOcular™ RhCE tissue construct consists of at least 3 viable
layers of cells and a non-keratinized surface, showing a cornea-like structure analogous to that found in vivo.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

- Negative Control 50 μL Aqua dest.
- Positive Control 50 μL methyl acetate
- Test Item 50 μL (undiluted)

Duration of treatment / exposure:

30 min

Duration of post- treatment incubation (in vitro):

- Post-treatment incubation 12 min (RT) + 120 min (37°C)
- MTT incubation 3 h

Number of animals or in vitro replicates:

duplicate

Details on study design:

The test item was applied topically to the EpiOcular tissue. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) after a 30 min exposure period and 120 min post-treatment period and compared to those of the concurrent negative controls.

Irritation parameter:

in vitro irritation score

Remarks:

Mean Relative Tissue Viability [%]

Run / experiment:

test item

Value:

80.17

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

100.0

Positive controls validity:

valid

Remarks:

36.0

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

The controls confirmed the validity of the study.
The mean absolute OD570 of the two negative control tissues was > 0.8 and < 2.8 (2.058).
The mean relative tissue viability (% negative control) of the positive control was < 50% (36.0%).
The maximum inter tissue difference of replicate tissues of all dose groups was < 20% (7.9%).

Ocular irritation potential of the test item was predicted from the relative mean tissue viabilities compared to the negative control tissues concurrently treated with Aqua dest.

The mixture of 50 μL test item per 1 mL MTT medium showed reduction of MTT as compared to the solvent. The mixture turned blue/purple. Since the mean relative tissue viability of the test item treated tissues (TM) was above the 60% threshold value killed tissue controls were performed for quantitative correction of results.

NSMTT [%] = [(ODKT - ODKU)/ODNC] * 100 = -0.356%

Difference of NSMTT of the two duplicate tissues must be < 20%, otherwise not accepted.

NSMTT1 [%] = [(meanODKT1 - ODKU)/ODNC] * 100 = [(0.030 – 0.035)/2.010] = -0.25%

NSMTT2 [%] = [meanODKT2 - ODKU)/ODNC] * 100 = [(0.026 – 0.035)/2.010] = -0.45%

NSMTT1 - NSMTT2 = ± 0.2%

NSMTT was ≤ 60% (-0.4% relative to the negative control of living epidermis and could therefore be used for determination of the killed control corrected viability (KCCV) according to the following formula:

KCCV [%] = 80.17% – (-0.356%) = ~ 80.52%

The mixture of 50 μL test item per 1 mL Aqua dest. and per 2 mL isopropanol showed no colouring as compared to the solvent. Therefore, NSCliving equalled 0%.

The test item showed non-specific reduction of MTT but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 60% (80.52% NSMTT- corrected).

Interpretation of results:

GHS criteria not met

Conclusions:

In this study under the given conditions the test item showed no irritant effects. The test item is classified as “non-irritant“ in accordance with UN GHS “No Category”

Executive summary:

In the present study the eye irritating potential of 2-Propenoic acid,2-[[3a,4,5,6,7,7a-hexahydro-4,7 -methano-1H-inden-5(or 6)-yl]oxy]ethyl ester; EC Name: Reaction mass of 2-(3a,4,5,6,7,7ahexahydro-1H-4,7-methanoinden-5-yloxy)ethyl acrylate and 2-(3a,4,5,6,7,7a-hexahydro-1H-4,7 -methanoinden-6-yloxy)ethyl acrylate was analysed. Since irritant substances are cytotoxic to the corneal epithelium after a short time exposure the cytotoxic effects of the test item on EpiOcular, a reconstituted three-dimensional human corneal epithelium model, were determined. Hereby, the test item was applied topically to the EpiOcular tissue. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) after a 30 min exposure period and 120 min post-treatment period and compared to those of the concurrent negative controls.

The mixture of 50 μL test item per 1 mL MTT medium showed reduction of MTT as compared to the solvent. The mixture turned blue/purple. Since the mean relative tissue viability of the test item treated tissues (TM) was above the 60% threshold value killed tissue controls were performed for quantitative correction of results.

NSMTT [%] = [(ODKT - ODKU)/ODNC] * 100 = -0.356%

Difference of NSMTT of the two duplicate tissues must be < 20%, otherwise not accepted.

NSMTT1 [%] = [(meanODKT1 - ODKU)/ODNC] * 100 = [(0.030 – 0.035)/2.010] = -0.25%

NSMTT2 [%] = [meanODKT2 - ODKU)/ODNC] * 100 = [(0.026 – 0.035)/2.010] = -0.45%

NSMTT1 - NSMTT2 = ± 0.2%

NSMTT was ≤ 60% (-0.4% relative to the negative control of living epidermis and could therefore be used for determination of the killed control corrected viability (KCCV) according to the following formula:

KCCV [%] = 80.17% – (-0.356%) = ~ 80.52%

The mixture of 50 μL test item per 1 mL Aqua dest. and per 2 mL isopropanol showed no colouring as compared to the solvent. Therefore, NSCliving equalled 0%.

The test item showed non-specific reduction of MTT but no relevant colouring potential after mixture with aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false negative results were necessary.

The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 60% (80.52% NSMTT-corrected).

Conclusion

In this study under the given conditions the test item showed no irritant effects. The test item is classified as “non-irritant“ in accordance with UN GHS “No Category”

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

adopted: 26 June 2020

GLP compliance:

yes (incl. QA statement)

Species:

cattle

Strain:

not specified

Remarks:

isolated corneas

Details on test animals or tissues and environmental conditions:

The assay uses isolated corneas obtained as a by-product from animals freshly slaughtered at the abattoir A. Moksel AG, Buchloe, Germany.
On the test day, fresh eyes were collected from the slaughterhouse and were transported in HBSS containing Pen/Strep on ice to the laboratories. Immediately after arrival of the eyes, cornea
preparation was initiated.
The eyes were carefully examined for defects and any defective eyes were discarded.
The tissue surrounding the eyeball was carefully pulled away and the cornea was excised leaving a 2 to 3 mm rim of sclera. The isolated corneas were stored in a petri dish containing HBSS. Before the corneas were mounted in corneal holders (Duratec GmbH) with the endothelial side against the O-ring of the posterior chamber, they had been visually examined for defects and any defective cornea had been discarded. The anterior chamber was then positioned on top of the cornea and tightened with screws. The chambers of the corneal holder were then filled with RPMI 1640 medium (without phenol red) containing 1% FBS and 2 mM L-glutamine (complete RPMI 1640 medium). The posterior chamber was always filled first. The corneas were incubated for one hour at 32 +/- 1 °C.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

750 µL

Duration of treatment / exposure:

10 min

Duration of post- treatment incubation (in vitro):

- 2 h before illuminance measurement
- 90 min before determination of optical density

Number of animals or in vitro replicates:

3

Irritation parameter:

in vitro irritation score

Remarks:

BCOP

Run / experiment:

Test item (mean)

Value:

1.39

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

-0.29

Positive controls validity:

valid

Remarks:

52.15

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

Corrected Opacity Value

Run / experiment:

Test item (mean)

Value:

1.15

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks:

25.24

Irritation parameter:

other: OD490

Remarks:

Permeability

Run / experiment:

Test item (mean)

Value:

0.027

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

0.011

Positive controls validity:

valid

Remarks:

1.794

None of the corneas treated with the test item showed any opacity of the tissue.

The following mean in vitro irritation score was calculated: 1.39

Therefore the test item was classified into UN GHS No Category.

The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.

The negative control responses should result in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control.

Interpretation of results:

GHS criteria not met

Conclusions:

According to the evaluation criteria the test item is classified into UN GHS: No Category.

Executive summary:

The eye irritancy potential of 2-Propenoic acid,2-[[3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5(or 6)-yl]oxy]ethyl ester was investigated in the bovine corneal opacity and permeability assay.

- Preparation of the test item: The test item was tested as provided by the sponsor.

- Visual observation after treatment: None of the corneas treated with the test item showed any opacity of the tissue.

- Mean in vitro irritation score: 1.39

- Classification: UN GHS: No Category

The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.

The negative control responses resulted in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control.

Conclusion

According to the evaluation criteria the test item is classified into UN GHS: No Category.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Eye Irritation
The test substance was investigated in the bovine corneal opacity and permeability assay according to OECD Test Guideline 437. A mean in vitro irritation score of 1.39 was established, which is below the cut-off for classification as eye irritant. In addition, an OECD 492 study was executed using the reconstructed human Cornea-like epithelium EpiOcular. After treatment with the test item the mean tissue viability was 80.52%, consequently the test item is considered not irritant.

 

Skin Irritation
In an OECD 431 for skin corrosivity the test item was topically applied onto the three-dimensional human skin model EpiDerm. The mean relative tissue viability was 105.1% after 3 minutes and 94.3% after 60 minutes of treatment, respectively. The test item is therefore considered as non-corrosive. In addition, a skin irritation study according to OECD 439 was performed. The mean relative tissue viability was 100.4% after 60 minutes of treatment. Consequently, the test item does not require classification.

 

Based on the available data reaction mass of 2-(3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-5-yloxy)ethyl acrylate and 2-(3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-6-yloxy)ethyl acrylate is not irritant to skin and eyes and does therefore not require classification.