Ethyl N-hydroxyacetimidate

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of Ethyl N-hydroxyacetimidate (10576-12-2) was predicted based on OECD QSAR toolbox 2901 mg/kg bw and different studies available on structurally similar read across substance Acetohydroxamic acid (546-88-3) 4800 mg/kg bw and closely related read across substance Ethyl vinyl ether (109-92-2) 8160 (7030 - 9480) mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) of Ethyl N-hydroxyacetimidate (10576-12-2) was predicted based on OECD QSAR toolbox 32.2 mg/L air (32200 mg/m3), and different studies available for closely related read across substance 2-methoxy-2-methylpropane (1634-04-4) 23576 ppm (23576000 mg/m3). All these studies concluded that the LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for Ethyl N-hydroxyacetimidate (10576-12-2) was predicted based on OECD QSAR toolbox 4125 mg/kg bwand differentstudies available on closely related read across substances Ethyl vinyl ether (109-92-2) >20000 mg/kg bw and Dibutyl ether (142-96-1) 10080 (4410–23040) mg/kg. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: Ethyl N-hydroxyacetimidate
SMILES:CCOC(C)=NO
InChI:1S/C4H9NO2/c1-3-7-4(2)5-6/h6H,3H2,1-2H3
Molecular Weight: 103.12 g/mole
Molecular Formula: C4H9NO2

Species:

rat

Strain:

other: CRL: CD (SD) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

2901 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 901 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Azomethine, aliphatic attach [-N=C] AND Hydroxy, nitrogen attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxime, aliphatic attach [-CH=N-OH]  AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "p"

Similarity boundary:Target: CCOC(C)=NO
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: CCOC(C)=NO
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Enamine form by Tautomers unstable

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkoxy propanol derivatives OR Di-substituted hydrocarbons (24a) OR Di-substituted hydrocarbons (24b) OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "v"

Similarity boundary:Target: CCOC(C)=NO
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.153

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.41

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2901 mg/kg bw, when CRL: CD (SD) BR male and female rats were treated with Ethyl N-hydroxyacetimidate (10576-12-2) via oral gavage route.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-hydroxyacetimidate (10576-12-2). The LD50 was estimated to be 2901 mg/kg bw, when CRL: CD (SD) BR male and female rats were treated with Ethyl N-hydroxyacetimidate (10576-12-2) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 901 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: Ethyl N-hydroxyacetimidate
SMILES:CCOC(C)=NO
InChI:1S/C4H9NO2/c1-3-7-4(2)5-6/h6H,3H2,1-2H3
Molecular Weight: 103.12 g/mole
Molecular Formula: C4H9NO2

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

32.2 mg/L air

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

32.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Azomethine, aliphatic attach [-N=C] AND Hydroxy, nitrogen attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxime, aliphatic attach [-CH=N-OH]  AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Ketoxime derivatives OR No functional group found by Organic Functional groups

Domain logical expression index: "p"

Similarity boundary:Target: CCOC(C)=NO
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.15

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.83

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was estimated to be 32.2 mg/L air, when Sprague-Dawley male and female rats were exposed with Ethyl N-hydroxyacetimidate (10576-12-2) for 4 h of exposure period by inhalation route.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for Ethyl N-hydroxyacetimidate (10576-12-2). The LC50 was estimated to be 32.2 mg/L air, when Sprague-Dawley male and female rats were exposed with Ethyl N-hydroxyacetimidate for 4 h of exposure period by inhalation route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

32 200 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and QSAR toolbox 3.3.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: Ethyl N-hydroxyacetimidate
SMILES:CCOC(C)=NO
InChI:1S/C4H9NO2/c1-3-7-4(2)5-6/h6H,3H2,1-2H3
Molecular Weight: 103.12 g/mole
Molecular Formula: C4H9NO2

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 h

Doses:

4125 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

4 125 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Azomethine, aliphatic attach [-N=C] AND Hydroxy, nitrogen attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxime, aliphatic attach [-CH=N-OH]  AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Azomethyme type compounds  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Di-substituted hydrocarbons (24b) OR Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Ethylenglycolethers OR Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids by Groups of elements

Domain logical expression index: "r"

Similarity boundary:Target: CCOC(C)=NO
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Oximes (Hemolytic anemia with methemoglobinemia) Rank B by Repeated dose (HESS)

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.604

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.01

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 4125 mg/kg bw, when New Zealand White male rabbit was treated with Ethyl N-hydroxyacetimidate (10576-12-2) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Ethyl N-hydroxyacetimidate (10576-12-2). The LD50 was estimated to be 4125 mg/kg bw, when New Zealand White male rabbit was treated with Ethyl N-hydroxyacetimidate (10576-12-2) for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 125 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute oral toxicity:

In different studies, Ethyl N-hydroxyacetimidate (10576-12-2) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Ethyl N-hydroxyacetimidate along with the study available on structurally similar read across substance Acetohydroxamic acid (546-88-3) and closely related read across substance Ethyl vinyl ether (109-92-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-hydroxyacetimidate (10576-12-2). The LD50 was estimated to be 2901 mg/kg bw, when CRL: CD (SD) BR male and female rats were treated with Ethyl N-hydroxyacetimidate (10576-12-2) via oral gavage route.

The above study is supported by HSDB (Hazardous Substances Data Bank), US national Library of Medicine (2017), for the structurally similar read across substance Acetohydroxamic acid (546-88-3).In an acute oral toxicity study, rats were treated at the concentration of 4800mg/kg bworally. 50% mortality was observed in treated rats at 4800 mg/kg bw. Therefore, LD50 was considered to be 4800 mg/kg bw, when rats was treated with Acetohydroxamic acid via oral route.

This study is further supported by Henry et al. (American Industrial Hygiene Association Journal, Volume 30, 1969 - Issue 5, Pages 470-476), for the closely related read across substance Ethyl vinyl ether (109-92-2).In an acute oral toxicity study, rats were treated at the concentration of 8160mg/kg bw orally. 50 % mortality was observed in treated rats at 8160 mg/kg bw. Therefore, LD50 was considered to be 8160 mg/kg bw with confidential limit of 7030 - 9480 mg/kg, when rats was treated with Ethyl vinyl ether via oral route.

Thus, based on the above studies on Ethyl N-hydroxyacetimidate (10576-12-2) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute oral toxicity.

Acute Inhalation toxicity: 

In different studies, Ethyl N-hydroxyacetimidate (10576-12-2) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Ethyl N-hydroxyacetimidate along with the study available on structurally similar read across substance 2-butanone oxime (96-29-7) and closely related read across substance 2-methoxy-2-methylpropane (1634-04-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for Ethyl N-hydroxyacetimidate (10576-12-2). The LC50 was estimated to be 32.2 mg/L air, when Sprague-Dawley male and female rats were exposed with Ethyl N-hydroxyacetimidate for 4 h of exposure period by inhalation route.

The above study is supported by Richard J. Lewis, Sr. (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012) and U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance 2-methoxy-2-methylpropane (1634-04-4).The acute inhalation toxicity study was conducted in rat at the concentration of 23576 ppm.50% mortality was observed at 23576 ppm, when exposed for 4 hours. Therefore, LC50 was considered to be 23576 ppm (23576000 mg/m3), when rat was treated with 2-methoxy-2-methylpropane by inhalation.

Thus, based on the above studies on Ethyl N-hydroxyacetimidate (10576-12-2) and it’s read across substances, it can be concluded that LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, Ethyl N-hydroxyacetimidate (10576-12-2) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for Ethyl N-hydroxyacetimidate along with the study available on closely related read across substances Ethyl vinyl ether (109-92-2) and Dibutyl ether (142-96-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Ethyl N-hydroxyacetimidate (10576-12-2). The LD50 was estimated to be 4125 mg/kg bw, when New Zealand White male rabbit was treated with Ethyl N-hydroxyacetimidate (10576-12-2) for 24 hours by dermal application occlusively.

This study is supported by Henry et al. (American Industrial Hygiene Association Journal, Volume 30, 1969 - Issue 5, Pages 470-476), for the closely related read across substance Ethyl vinyl ether (109-92-2).In an acute dermal toxicity study, rabbits were treated at the concentration of 20000mg/kg bw. No mortality was observed at 20000 mg/kg bw. Therefore, LD50 was considered to be >20000 mg/kg bw, when rabbits were treated with Ethyl vinyl ether by dermal application.

The above study is further supported by John Wiley & Sons (Patty's Industrial Hygiene and Toxicology, 2005), for the closely related read across substance Dibutyl ether (142-96-1).Acute Dermal toxicity study was conducted in rabbits at the concentration of 10080 mg/kg bw. 50% Mortality observed at 10080mg/kg bw. Therefore, LD50 was considered to be 10080 mg/kg with confidential limit of 4410–23040 mg/kg bw, when rabbits were treated with Dibutyl ether by dermal application.

Thus, based on the above studies on Ethyl N-hydroxyacetimidate (10576-12-2) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Ethyl N-hydroxyacetimidate (10576-12-2) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw for acute oral and dermal toxicity. LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, Ethyl N-hydroxyacetimidate can be classified as category V for acute oral, dermal and inhalation toxicity.