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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ethyl 2-cyanoacrylate was tested in bacterial reverse mutation assays, in a mammalian chromosome aberration test (chromosome aberration) according to OECD TG 473 (human lymphoblastoid cells (TK6) with and without metabolic activation), and in a mouse lymphoma test according to OECD TG 476 (L5178Y cells, with and without metabolic activation). Based on the test results, ethyl 2 -cyanoacrylate is assessed as non-genotoxic.

Link to relevant study records

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Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study and GLP
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
no data
Species / strain / cell type:
human lymphoblastoid cells (TK6)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
320, 640 and 1280 µg/ml culture medium
Vehicle / solvent:
- Vehicle/solvent used: acetone
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Mitomycin C without S9, Cyclophosphamide with S9
Details on test system and experimental conditions:
Test system:
Cultured peripheral human lymphocytes were used as test system. Blood was collected from healthy adult, non-smoking, male volunteers. The Average Generation time (AGT) of the cells and the age of the donor at the time the AGt was determined (December 2009) are presented below:
- First dose range finding study: age 27, AGT = 14.3 h
- Second range finding study: age 33, AGT = 14.4 h
- First cytogenetic assay: age 33, AGT = 14.4 h
- Second cytogenetic assay: age 39, AGT = 14.0 h

All incubations were carried out in a controlled envrionment in the dark, in which optimal conditions were a humid atmosphere of 80-100%, containing 5.0 +/- 0.5% CO2 in air, at a temperature of 37.0 +/- 1.0°C.

Key result
Species / strain:
human lymphoblastoid cells (TK6)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
No effects of ethyl-2-cyanoacrylate on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both i n the absence and presence of S9 -mix. Therefore it can be concluded that ethyl-2-cyanoacrylate does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations under the experimental conditions described in this report.
Executive summary:

This study was performed to investigate the potential of ethyl-2-cyanoacrylate to induce chromosome aberrations in cultured peripheral human lymphocytes. The study were based on the most recent OECD and EC guidelines.

This report describes the effect of ethyl-2-cyanoacrylate on the number of chromosome aberrations in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system (phenobarbital and naphthoflavone induced rat liver S9 -mix). The possible clastogenicity of ethyl-2-cyanoacrylate was tested in two independent experiments.

A stock solution of 512 mg/ml and 611 mg/ml ethyl-2-cyanoacrylate was prepared in acetone for the use in the absence and presence of S9 -mix, respectively. Subsequent dilutions in culture medium resulted in the formation of precipiates.

In the first cytogentic assay, ethyl-2-cyanoacrylate was tested up to a loading rate of 1280 µg/ml (ca.0.01 M) for a 3 h exposure time with a 24 h fixation time in the absence and presence of 1.8% (v/v) S9 -fraction.

In the second cytogenetic assy, ethyl-2-cyanoacrylate was again tested up to a loading rate of 1280 µg/ml for a 24 h and 48 h continuous exposure timewith a 24 h and 48 fixation time in the absence of S9 mix. in the presence of S9 mix ethyl-2-cyanoacrylate was tested at the same concnetration range for a 3 h exposure time with a 48 h fixation time.

The number of cells with chromosome aberrations found in the negative, solvent and hydroquinone control cultures was within the laboratory historical control data range. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9 -mix) functioned properly.

ethyl-2-cyanoacrylate did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9 -mix, in either of the two independently repeated experiments.

No effects of ethyl-2-cyanoacrylate on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both i n the absence and presence of S9 -mix. Therefore it can be concluded that ethyl-2-cyanoacrylate does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations under the experimental conditions described in this report.

Finally, it is concluded that this test is valid and that ethyl-2-cyanoacrylate is not clastogenic in human lymphocytes under experimental conditions described in this report.

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study and GLP
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Qualifier:
according to
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
no data
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
Experiment 1: 10, 20, 40, 80, 160, 320, 640 and 1280 µg/ml
Experiment 2: 20, 40, 80, 160, 320, 640, 850 and 850 µg/ml
Vehicle / solvent:
- Vehicle/solvent used: acetone
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Methylmethanesulfonate without S9, Cyclophosphamide with S9
Details on test system and experimental conditions:
All incubations were carried out in a controlled environment in the dark, in which optimal conditions were a humid atmosphere of 80 – 100% (actual range 71 – 94%), containing 5.0 ± 0.5% CO2 in air, at a temperature of 37.0 ± 1.0°C (actual range 34.6 – 37.8°C). Temperature and humidity were continuously monitored throughout the experiment. The CO2 percentage was monitored once on each working day. Temporary deviations from the temperature (in the range of 35.1 - 36.0°C), humidity (with a maximum of 6%) and CO2 percentage (with a maximum of 1%) occurred that were caused by opening and closing of the incubator door, but the time of these deviations did not exceed 1 hour. Based on laboratory historical data these deviations are considered not to affect the study integrity.
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The spontaneous mutation frequencies in the negative and solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay.
Mutation frequencies in cultures treated with positive control chemicals were increased by 11- and 6.1-fold for MMS in the absence of S9-mix, and by 11- and 8.7-fold for CP in the presence of
S9-mix. It was therefore concluded that the test conditions, both in the absence and presence of S9-mix, were appropriate and that the metabolic activation system (S9-mix) functioned properly.

The additional control substance, hydroquinone, did not induce a significant increase in the mutation frequency after a 3 hours treatment period in the absence and presence of S9-mix. However, hydroquinone induced a 2.6-fold increase in the mutation frequency at the prolonged treatment period of 24 hours in the absence of S9-mix.

In the absence of S9-mix after a 3 hours treatment period, Ethyl 2-cyanoacrylate did not induce a significant increase in the mutation frequency. However, Ethyl 2-cyanoacrylate induced a 2.5-fold increase in the mutation frequency at the prolonged treatment period of 24 hours. The mutation frequency was above the global evaluation factor plus mutation frequency of the negative controls (GEF + MF(controls): 257 x 10-6). The increase observed was above the GEF and outside the historical control data range. Therefore this increase is considered biologically relevant and the tested sample of Ethyl 2-cyanoacrylate, containing nearly 0.1% hydroquinone, did exhibit a mutagenic response.
However, hydroquinone induced the same increase in the mutation frequency of 2.6-fold, when tested as additional control. Hydroquinone is present in the tested sample of Ethyl 2-cyanoacrylate (<0.1%) at the same concentration as it was tested in parallel solitarily. Hydroquinone is known to induce positive responses in gene mutation tests in vitro at comparable concentrations. Thus, it is very likely that the increase in the mutation rate observed at the highest concentration in the experiment without S9-mix at the 24-hour treatment is caused by the hydroquinone content in the test compound.

In the presence of S9-mix, Ethyl 2-cyanoacrylate did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. Also, hydroquinone did not induce increased mutation frequencies in the presence of S9-mix at the tested concentration.
Conclusions:
Based on the results of this study, it is concluded that the tested sample of Ethyl 2-cyanoacrylate, (containing nearly 0.1% hydroquinone) has shown a mutagenic response in the mouse lymphoma L5178Y test system under the experimental conditions described in this report. The mutagenicity was confined only to incubations without metabolic activation at the prolonged treatment period.
Due to the pattern of the identical response to an equivalent concentration of hydroquinone as such under the test conditions performed, hydroquinone is asumed to exert the detected mutagenic activity, and the observed effect should not be attributed to ethyl 2-cyanoacrylate.
Therefore, ethyl-2-cyanoacrylate was concluded to be not mutagenic.
Executive summary:

Evaluation of the mutagenic activity of Ethyl-2-cyanoacrylate in an in vitro mammalian cell gene mutation test with L5178Y mouse lymphoma cells (with independent repeat).

 

This report describes the effects of ethyl-2-cyanoacrylate on the induction of forward mutations at the thymidine-kinase locus (TK-locus) in L5178Y mouse lymphoma cells. The test was performed in two independent experiments in the absence and presence of S9-mix (rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone).  

 

The study procedures described in this report were based on the most recent versions of the guidelines OECD 476 and EC B.17.

 

Hydroquinone was tested in parallel as additional control at a concentration of 1.28 µg/ml, representing the concentration of hydroquinone in the test system at the highest tested initial concentration (load rate) of the test substance. The content of hydroquinone in the tested sample of Ethyl-2-cyanoacrylate according to the specification is in the range of just below 1000 ppm (equal to approx. 0.1%).

 

Batch L2PF090240 of Ethyl-2-cyanoacrylate was a clear colourless liquid with a purity of 99.7%. Stock solutions of 640 mg/ml and 762 mg/ml Ethyl-2-cyanoacrylate were prepared in acetone for the use in the absence and presence of S9-mix, respectively. The dilution in culture medium at a ratio of 1: 500 resulted in a concentration of the test substance of 1280 µg/ml as highest tested concentration. The dilution in culture medium resulted in the formation of precipitates. The precipitates were removed by centrifugation, thus the cells were exposed to the remaining soluble and non-separated parts of the test substance. This test solution, derived from the initial concentration of 1280 µg/ml and subsequent dilutions thereof were designated as corresponding “load rates”.

 

In the first experiment, Ethyl-2-cyanoacrylate was tested at load rates of 10 to 1280 µg/ml (at 1:2 dilution steps) in the absence and presence of 8% (v/v) S9-mix. The incubation time was 3 hours. Ethyl-2-cyanoacrylate was tested up to a cytotoxic level of 46% in the absence of S9-mix. No toxicity was observed in the presence of S9-mix.

 

In the second experiment, Ethyl-2-cyanoacrylate was tested at load rates of 20 to 1100 µg/ml and 10 to 1280 µg/ml in the absence and presence of 12% (v/v) S9-mix, respectively. The incubation times were 24 hours in the absence of S9-mix and 3 hours for incubations in the presence of S9-mix. Ethyl-2-cyanoacrylate was tested up to a cytotoxic level of 87% in the absence of S9-mix. No toxicity was observed in the presence of S9-mix.

 

The spontaneous mutation frequencies in the negative and solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay.

 

Mutation frequencies in cultures treated with positive control chemicals were increased by 11- and 6.1-fold forin the absence of S9-mix, and by 11- and 8.7-fold for CP in the presence of

S9-mix. It was therefore concluded that the test conditions, both in the absence and presence of S9-mix, were appropriate and that the metabolic activation system (S9-mix) functioned properly.

 

The additional control substance, hydroquinone did not induce a significant increase in the mutation frequency after a 3 hours treatment period in the absence and presence of S9-mix. However, hydroquinone induced a 2.6-fold increase in the mutation frequency at the prolonged treatment period of 24 hours in the absence of S9-mix.

 

In the absence of S9-mix after a 3 hours treatment period, Ethyl 2-cyanoacrylate did not induce a significant increase in the mutation frequency. However, Ethyl-2-cyanoacrylate induced a 2.5-fold increase in the mutation frequency at the prolonged treatment period of 24 hours. The mutation frequency was above the global evaluation factor plus mutation frequency of the negative controls (GEF + MF(controls): 257 x 10-6). Theincrease observed was above the GEF and outside the historical control data range. Therefore, this increase is considered biologically relevant and the tested sample of Ethyl-2-cyanoacrylate, containing nearly 0.1% hydroquinone, did exhibit a mutagenic response. However, hydroquinone induced the same increase in themutation frequencyof 2.6-fold, when tested as additional control. Hydroquinone is present in the tested sample of Ethyl-2-cyanoacrylate (<0.1%) at the same concentration as it was tested in parallel solitarily. Hydroquinone is known to induce positive responses in gene mutation testsin vitroat comparable concentrations. Thus, it is very likely that the increase in the mutation rate observed at the highest concentration in the experiment without S9-mix at the 24-hour treatment is caused by the hydroquinone content in the test compound.

 

In the presence of S9-mix, Ethyl-2-cyanoacrylate did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. Also, hydroquinone did not induce increased mutation frequencies in the presence of S9-mix at the tested concentration.

 

Based on the results of this study, it is concluded that the tested sample of Ethyl 2-cyanoacrylate, (containing nearly 0.1% hydroquinone) has shown a mutagenic response in the mouse lymphoma L5178Y test system under the experimental conditions described in this report. The mutagenicity was confined only to incubations without metabolic activation at the prolonged treatment period.

Due to the pattern of the identical response of hydroquinone under the test conditions performed, at an equivalent concentration as hydroquinone was present via the test sample, it has to be assumed that hydroquinone is the agent responsible for the detected mutagenic activity. The observed effect should therefore not be attributed to ethyl-2-cyanoacrylate as substance.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
TA1537: his C 3076; rfa; uvrB- frame shift mutations
TA 98: his D 3052; rfa; uvrB- (pKM101) frame shift mutations
TA 1538: his D 3052; rfa; uvrB- frame shift mutations
TA1535: his G 46; rfa; uvrB- base-pair substitutions
TA 100: his G 46; rfa; uvrB (pKM101) base-pair substitutions
Species / strain / cell type:
S. typhimurium, other: TA1535, TA1537, TA 1538, TA98, TA100
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
The test substance was dissolved in acetone and 100 µl aliquots containing from 10 to 4000 µg of ethyl-2-cyanoacrylate were delivered into the top agar.
Vehicle / solvent:
Acetone
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Details on test system and experimental conditions:
For the spot test the test substance was dissolved in acetone and 100 µl aliquots containing from 10 to 4000 µg of Ethyl 2-cyanoacrylate were delivered into the top agar. After incubatingthe plates for 48 h in the dark at 37°C, the number of revertant colonies was counted manually.
The spot test for volatile compounds was carried out only with TA100 with and without S9 mix. As soon as the agar overlay had hardened, a sterile polyethylenecover slip was placed in the middle of the plate. Hereafter a 5µl and 20 µl drop of the test substnace waas pipetted onto the cover slip To stop vapors from escaping, the petri dishes were then sealed with tape.
Key result
Species / strain:
S. typhimurium, other: TA1535, TA1537, TA1538, TA98, TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Ethyl 2-cyanoacrylate revealed toxic effects to the bacteria at higher amounts tested (>2000 µg/plate).
Conclusions:
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article did not induce gene mutations by base pair changes or frame shifts in the genome of the strains used with and without S9 mix.
Therefore, ethyl-2-cyanoacrylate is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.
Executive summary:

This study was performed to investigate the potential of ethyl-2-cyanoacrylate to induce gene mutations according to the Spot Tests using Salmonela typhiimurium strans TA 1535, TA 1537, TA 1538, TA 98, TA 100.

Therefore, ethyl-2-cyanoacrylate is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.

The Spot Tests were carried out with and without S9 mix. The test substance was dissolved in acetone and 100 µl aliquots containing from 10 to 4000 µg of ethyl-2-cyanoacrylate were delivered into the top agar.

The spot test for volatile compounds was carried out only with TA100 with and without S9 mix. As soon as the agar overlay had hardened, a sterile polyethylenecover slip was placed in the middle of the plate. Hereafter a 5µl and 20 µl drop of the test substnace waas pipetted onto the cover slip To stop vapors from escaping, the petri dishes were then sealed with tape.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with ethyl-2-cyanoacrylate at any dose level, neither in the presence nor absence of metabolic activation (S9 mix).

Therefore, ethyl-2-cyanoacrylate is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.

 

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
TA 98: his D 3052; rfa; uvrB- (pKM101) frame shift mutations
TA 1538: his D 3052; rfa; uvrB- frame shift mutations
TA1535: his G 46; rfa; uvrB- base-pair substitutions
TA 100: his G 46; rfa; uvrB (pKM101) base-pair substitutions
Species / strain / cell type:
S. typhimurium, other: TA100, TA1535, TA98, TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
Spot Test: 5, 10 and 20 mg ethyl 2-cyanoacetate
Spot Test for volatile compounds: 5, 10 and 20 mg ethyl 2-cyanoacetate
Plate incorporation assay: amounts from 0.1 to 5.0 mg etyl 2-cyanoacrylate per plate
Vehicle / solvent:
no
Details on test system and experimental conditions:
Spot Test: 5, 10 and 20 mg of etyhl-2-cyanoacrylate was placed directly on the agar surface. The plates were incubated at 37°C for 2 days.
Spot Test for volatile compounds: As soon as the agar overlay with bacteria and S9 mix had hardened, a sterile microscope glass cover slip (22 mm diameter) was placed in the middle of the plate. 5, 10 and 20 mg of the test substance was placed on the cover slip. to stop vapors from escaping, the petri dishes were then sealed with tape.
Plate incorporation assay: It was carried out with the test strain TA100 and without S9 mix. Ethyl-2-cyanoacrylate was dissolved in 100 µl acetone and incorporated into the agar overlay. Amounts from 0.1 to 5.0 mg of the test substance per plate was tested.
Key result
Species / strain:
S. typhimurium, other: TA100, TA1535, TA98, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
not examined
Untreated negative controls validity:
not examined
Positive controls validity:
not examined
Conclusions:
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article did not induce gene mutations by base pair changes or frame shifts in the genome of the strains used with and without S9 mix.
Therefore, ethyl-2-cyanoacrylate is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.
Executive summary:

This study was performed to investigate the potential of ethyl-2-cyanoacrylate to induce gene mutations according to the Spot Tests and the plate incorporation assay using the Salmonella typhimurium strains TA 1535, TA 1538, TA 98 and TA 100.

The Spot Tests were carried out with and without S9 mix. The test article was tested at the following concentrations: 5, 10 and 20 µg/plate.

The plate incorporation assay was carried out with the test strain TA100 and without S9 mix. Ethyl-2-cyanoacrylate was dissolved in 100 µl acetone and incorporated into the agar overlay. Amounts from 0.1 to 5.0 mg of the test substance per plate were tested.

No substantial increase in revertant colony numbers of any of the 4 tester strains was observed following treatment with ethyl 2-cyanoacrylate at any dose level, neither in the presence nor absence of metabolic activation (S9 mix).

Therefore, ethyl-2-cyanoacrylate is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Ethyl 2-cyanoacrylate was tested in bacterial reverse mutation assays, in a mammalian chromosome aberration test (chromosome aberration) according to OECD TG 473 (human lymphoblastoid cells (TK6) with and without metabolic activation), and in a mouse lymphoma test according to OECD TG 476 (L5178Y cells, with and without metabolic activation). Based on the test results, ethyl 2 -cyanoacrylate is assessed as non-genotoxic.

In the tests, polymerisation and precipitation of ethyl-2-cyanoacrylate after contact to moisture is observed (inherent property of ethyl-2-cyanoacrylate based instant glues). Based on this, exposure to monomeric ethyl 2 -cyanoacrylate in humans is considered negligible.

Justification for classification or non-classification

Based on the results of several in vitro tests, ethyl 2 -cyanoacrylate is considered non-genotoxic. Hence, ethyl 2 -cyanoacrylate is not classification for genotoxic properties.