6-chlorohexan-2-one

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)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

no

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily, 5 days/week

Remarks:

Doses / Concentrations:
not reported
Basis:
no data

No. of animals per sex per dose:

10

Control animals:

yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Organ weight findings including organ / body weight ratios:

no effects observed

Dose descriptor:

NOEL

Effect level:

1 348.251 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects on organ weights

Critical effects observed:

not specified

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl halide AND Ketone by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl halide AND Ketone 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 Carbonyl, aliphatic attach [-C(=O)-] AND Chlorine, aliphatic attach [-Cl] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkyl chloride AND Alkyl halide AND Carbonyl compound AND Halogen derivative AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR SN1 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 >> Fused-Ring 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes 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: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Chloroacetamides (SN2) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments 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 Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Griseofulvin (Hepatotoxicity) Alert OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A OR Pirprofen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0775

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.62

Conclusions:

The NOEL value of 6-chlorohexan-2-one was estimated to be 1348.25 mg/kg bw/day in B6C3F1 mice in a 13 week study.

Executive summary:

The repeated dose toxicity of 6-chlorohexan-2-one by oral route was predicted using QSAR Toolbox version 3.3.

The NOEL value of 6-chlorohexan-2-one was estimated to be 1348.25 mg/kg bw/day in B6C3F1 mice in a 13 week study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 348.25 mg/kg bw/day

Study duration:

subchronic

Species:

mouse

Quality of whole database:

Data is predicted using QSAR Toolbox version 3.3

Additional information

Repeated dose toxicity: Oral route

The repeated dose toxicity of 6-chlorohexan-2-one by oral route was predicted using QSAR Toolbox version 3.3.

The NOEL value of 6-chlorohexan-2-one was estimated to be 1348.25 mg/kg bw/day in B6C3F1 mice in a 13 week study whereas it was 762.84 mg/kg bw/day in SD rats in a 28 day study.

The studies conducted on the similar substance (CAS: 821 -55 -6), indicate the NOAEL of 1000 mg/kg bw/day and LOAEL of 2000 mg/kg bw/day in 3 week as well as 90 day studies.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The repeated dose toxicity of 6-chlorohexan-2-one by oral route was predicted using QSAR Toolbox version 3.3.
The NOEL value of 6-chlorohexan-2-one was estimated to be 1348.25 mg/kg bw/day in B6C3F1 mice in a 13 week study.