Allyl acetoacetate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Analytical verification of doses or concentrations:

no

Dose descriptor:

other: "Effect LOEL"

Effect level:

1 689.051 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: "effect LOEL"
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((("a" and "b" ) and ("c" and ( not "d") ) ) and ("e" and "f" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(CC(C)=O)OCC=C
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Similarity boundary:Target: C(=O)(CC(C)=O)OCC=C
Threshold=60%,
Dice(Atom pairs)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Protein Binding Potency

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as 2-Alken-1-als (MA) OR Acrylates (MA) OR Alkyl 2-alkenoates (MA) OR Alkyl 4-chloroacetoacetates (SN2) OR Extremely reactive (GSH) OR Highly reactive (GSH) OR Miscellaneous alpha-halogenated ketones (SN2) OR Moderately reactive (GSH) OR Substituted 1-Alken-3-ones (MA) by Protein Binding Potency

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0016

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.403

Conclusions:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in a study on rat was observed at a dose concentration of 1689.051 mg/kg bw/day by the oral route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the oral route below the above mentioned dose

Executive summary:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in a study on rat was observed at a dose concentration of 1689.051 mg/kg bw/day by the oral route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the oral route below the above mentioned dose

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Dose descriptor:

other: "Effect LOEL"

Effect level:

710.535 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: "effect LOEL"
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((("a" and ("b" and ( not "c") ) ) and ("d" and ( not "e") ) ) and ("f" and "g" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(CC(C)=O)OCC=C
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic tertiary amines OR Alkyl phenols OR Alpha, beta- unsaturated esters OR Aromatic nitro OR Epoxides OR Furans OR Hydroquinones OR Isocyanates OR MA: Direct Acting Epoxides and related OR MA: Direct Acting Schiff Base Formers OR MA: Iminium Ion Formation OR MA: Isocyanates and Isothiocyanates OR MA: Nitrenium Ion Formation OR MA: P450 Mediated Activation of Heterocyclic Ring Systems OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR MA: Polarised Alkenes_Michael addition OR Mechanistic Domain: Acyalation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: Schiff base OR Mechanistic Domain: SN1 OR Mechanistic Domain: SN2 OR Mono aldehydes by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Protein Binding Potency

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as 3-Alken-2-ones (MA) OR Alkyl 2-alkenoates (MA) OR alpha-bromo and chloro alkyl/aryl ketones (SN2) OR Extremely reactive (GSH) OR Highly reactive (GSH) OR Miscellaneous alpha-halogenated ketones (SN2) OR Moderately reactive (GSH) OR Substituted 1-Alken-3-ones (MA) by Protein Binding Potency

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.483

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.874

Conclusions:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in rat was observed at a dose concentration of 710.5355 mg/kg bw/day by the inhalative route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the inhalative route below the above mentioned dose.

Executive summary:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in rat was observed at a dose concentration of 710.5355 mg/kg bw/day by the inhalative route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the inhalative route below the above mentioned dose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from European Union Risk assesment Report.

GLP compliance:

not specified

Species:

other: human

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Dose descriptor:

dose level:

Effect level:

420 other: mg/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: It suggests that systemic health risks due to repeated dermal exposure are not expected

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

In a study on ethyl acetoacetate, repeated dermal exposure of 420 mg/day suggested that systemic health risks due to repeated dermal exposure are not expected.

Executive summary:

In a study on ethyl acetoacetate, repeated dermal exposure of 420 mg/day suggested that systemic health risks due to repeated dermal exposure are not expected.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

420

Study duration:

subchronic

Species:

other: human

Quality of whole database:

The data is from European Union Risk assessment report

Additional information

Repeated dose toxicity : oral route and inhalation route

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in weight of evidence studies are summarised below..

Sr.No	Study on	End point name	Species	Effect level
1	Repeated dose toxicity : oral	Effect LOEL	Rat	1689.051mg/kg bw/day
2		Effect LOEL	Rat	883.5547 mg/kg bw/day
3		Effect LOEL	Rat	1563.982 mg/kg bw/day
1	Repeated dose toxicity: inhalation	Effect LOEL	Rat	710.5355 mg/kg bw/day

The studies indicate that allyl acetoacetate shall not exhibit toxic effect to rat by the oral and inhalative route below the above mentioned doses.

Repeated dose toxicity dermal :

The study on ethyl acetoacetate ,repeated dermal exposure of 420 mg/day suggests that systemic health risks due to repeated dermal exposure are not expected.

Sr.No	End point	Effect level	Species	Basis for effect
1	dose level:	420mg/day	Human	It suggests that systemic health risks due to repeated dermal exposure are not expected.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in a study on  rat was observed at a dose concentration of 1689.051 mg/kg bw/day by the oral route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the oral route below the above mentioned dose

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

The repeated dose toxicity LOEL (Lowest observed effect level) of allyl acetoacetate in rat was observed at a dose concentration of 710.5355 mg/kg bw/day by the inhalative route.This indicates that allyl acetoacetate shall not exhibit toxic effect to rat by the inhalative route below the above mentioned dose.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

The study on ethyl acetoacetate ,repeated dermal exposure of 420 mg/day suggests that systemic health risks due to repeated dermal exposure arenot expected. The data is from European Union Risk assessment report and hence considered reliable.

Justification for classification or non-classification

Using various sources of information (QSAR model as well as data from other sources) in a weight of evidence approach, it can be concluded that allyl acetoacetate is not likely to exhibit repeated dose toxicity within the concentration thresholds as mentioned in the studies.