(±)-menthone

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

The supporting QMRF report has been attached

Data source

Reference

Reference Type:

other: Predicted data

Title:

Estimation for NOAEL for CAS 1074-95-9

Author:

Sustainability Support Services (Europe) AB

Year:

2017

Bibliographic source:

OECD QSAR Toolbox version 3.4

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Data is predicted by OECD QSAR Toolbox version 3.4.

GLP compliance:

not specified

Justification for study design:

Predicted data

Test material

Test material information

Constituent 1

Reference substance name:

(±)-menthone

EC Number:

214-049-2

EC Name:

(±)-menthone

Cas Number:

1074-95-9

Molecular formula:

C10H18O

IUPAC Name:

2-isopropyl-5-methylcyclohexanone

Test material form:

liquid

Details on test material:

- Name of test material: 2-isopropyl-5-methylcyclohexanone
- Molecular formula: C10 H18 O
- Molecular weight: 154.2512g/mol
- Smiles notation: C1([C@@H](CC[C@@H](C1)C)C(C)C)=O
- InChl: 1S/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3
- Substance type: Organic
- Physical state: liquid

Specific details on test material used for the study:

- Name of test material: (±)-menthone
- Molecular formula: C10H18O
- Molecular weight: 154.2512 g/mol
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: gavage

Remarks on MMAD:

No data

Vehicle:

not specified

Details on exposure:

No data

Details on mating procedure:

No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

No data

Frequency of treatment:

No data

Details on study schedule:

No data

Doses / concentrations

Remarks:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Positive control:

No data

Examinations

Parental animals: Observations and examinations:

No data

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

No data

Litter observations:

No data

Postmortem examinations (parental animals):

No data

Postmortem examinations (offspring):

No data

Statistics:

No data

Reproductive indices:

No data

Offspring viability indices:

No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Details on results (P0)

No data

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

425.292 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

reproductive performance

Remarks on result:

other: other details not specified

Target system / organ toxicity (P0)

Critical effects observed:

not specified

Results: F1 generation

Effect levels (F1)

Remarks on result:

other: Not specified

Target system / organ toxicity (F1)

Critical effects observed:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential AND Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives 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 by DNA binding by OASIS v.1.4

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 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, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Strong 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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

Similarity boundary:Target: CC(C)C1CCC(C)CC1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: CC(C)C1CCC(C)CC1=O
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.18

Applicant's summary and conclusion

Conclusions:

Since no compound related effects on rats are observed, the no observed adverse effect level (NOAEL) relating to reproductive toxicity for the given test material 2-isopropyl-5-methylcyclohexanone is estimated to be 425.29 mg/kg/day via oral route of administration.

Executive summary:

The reproductive toxicity of 2-isopropyl-5-methylcyclohexanone to rats was estimated using QSAR Toolboox version 3.4. Since no compound related effects on rats are observed, the no observed adverse effect level (NOAEL) relating to reproductive toxicity for the given test material 2-isopropyl-5-methylcyclohexanone is estimated to be 425.29 mg/kg/day via oral route of administration.