Vinyl chloroacetate

Endpoint summary

Description of key information

The toxicity of VCA following short-term repeated oral exposure was assessed based on the toxicokinetics behaviour of the substance and the available information on the repeated-dose toxicity of its degradation products acetaldehyde and chloroacetic acid.

The short-term repeated dose toxicity of acetaldehyde by the oral route was investigated and allowed to derive a NOAEL of 125 mg/kg bw/d (equivalent to an ingestion of 341.25 mg/kg bw/d of VCA).

The repeated dose toxicity of chloroacetic acid by the oral route was investigated and a NOAEL of 3.5 mg/kg bw/d (equivalent to an ingestion of 4.48 mg/kg bw/d mg/kg bw/d of VCA) from a chronic toxicity study was identified. This value is considered as conservative in order to assess the short-term (4 weeks) repeated dose toxicity of VCA.

 It can be expected from these results that the short-term repeated-dose toxicity of VCA following an oral exposure will be driven by its degradation product chloroacetic acid as it was shown to be more hazardous than acetaldehyde following a repeated exposure. Therefore the NOAEL of 4.48 mg/kg bw/d derived from a chronic toxicity study shall be used for the short-term repeated-dose toxicity of VCA. This value is conservative and considered to cover the adverse effects induced by the two main degradation products of VCA.

In accordance with Annex VIII of REACH, Column 2, testing by the inhalation and dermal routes is only appropriate if exposure of humans via these routes is likely. Vinyl Chloroacetate is not made available on the EU market as a monomer and is imported already polymerised. Therefore no exposure of humans via the dermal and inhalation routes is expected.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

other: Expert assessment

Adequacy of study:

weight of evidence

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Expert assessment based on literature data on the degradation products of VCA

Justification for type of information:

An experimental study to determine the toxicity of VCA following a repeated oral exposure was not considered necessary, nor scientifically justified, since the registered substance is expected to undergo rapid degradation following an oral exposure. Therefore this assessment was based on the degradation products of VCA.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert assessment based on literature data on the degradation products of VCA

GLP compliance:

no

Limit test:

no

Key result

Dose descriptor:

NOAEL

Effect level:

4.48 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

organ weights and organ / body weight ratios

Critical effects observed:

no

Conclusions:

The short-term repeated-dose toxicity of VCA following an oral exposure is expected to be driven by its degradation product chloroacetic acid as it was shown to be more hazardous than acetaldehyde following a repeated exposure by the oral route. Therefore the NOAEL of 4.48 mg/kg bw/d derived from a chronic toxicity study shall be used for the short-term repeated-dose toxicity of VCA. This value is conservative and considered to cover the adverse effects induced by the two main degradation products of VCA.

Executive summary:

The toxicity of VCA following short-term repeated oral exposure was assessed based on the toxicokinetics behaviour of the substance and the available information on the repeated-dose toxicity of its degradation products acetaldehyde and chloroacetic acid.

The short-term repeated dose toxicity of acetaldehyde by the oral route was investigated and allowed to derive a NOAEL of 125 mg/kg bw/d (equivalent to an ingestion of 341.25 mg/kg bw/d of VCA). The

The repeated dose toxicity of chloroacetic acid by the oral route was investigated and a NOAEL of 3.5 mg/kg bw/d (equivalent to an ingestion of 4.48 mg/kg bw/d mg/kg bw/d of VCA) from a chronic toxicity study was identified. This value is considered as conservative in order to assess the short-term (4 weeks) repeated dose toxicity of VCA.

 

It can be expected from these results that the short-term repeated-dose toxicity of VCA following an oral exposure will be driven by its degradation product chloroacetic acid as it was shown to be more hazardous than acetaldehyde following a repeated exposure. Therefore the NOAEL of 4.48 mg/kg bw/d derived from a chronic toxicity study shall be used for the short-term repeated-dose toxicity of VCA. This value is conservative and considered to cover the adverse effects induced by the two main degradation products of VCA.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

4.48 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Expert assessment based on literature data on the degradation products of VCA

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII of REACH, Column 2, testing by inhalation route is appropriate if exposure of humans via inhalation is likely. Vinyl Chloroacetate is not made available on the EU market as a monomer and is imported already polymerised. Therefore no exposure of humans via inhalation is expected.

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII of REACH, Column 2, testing by inhalation route is appropriate if exposure of humans via inhalation is likely. Vinyl Chloroacetate is not made available on the EU market as a monomer and is imported already polymerised. Therefore no exposure of humans via inhalation is expected.

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII of REACH, Column 2, testing by the dermal route is appropriate if exposure of humans via this route is likely. Vinyl Chloroacetate is not made available on the EU market as a monomer and is imported already polymerised. Therefore no exposure of humans via the dermal route is expected.

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII of REACH, Column 2, testing by the dermal route is appropriate if exposure of humans via this route is likely. Vinyl Chloroacetate is not made available on the EU market as a monomer and is imported already polymerised. Therefore no exposure of humans via the dermal route is expected.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

VCA is expected to degrade rapidly following an oral exposure. The toxicity of VCA following short-term repeated oral exposure was therefore assessed based on the available information on the repeated-dose toxicity of its degradation products acetaldehyde and chloroacetic acid. None of these degradation products are classified as toxic to specific target organs following a repeated exposure based on the available information of these substances. As a result VCA shall not be classified as toxic to specific target organs.