Bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titanium

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

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:

Data is predicted by QSAR toolbox version 2.3

GLP compliance:

no

Species:

rat

Strain:

Brown Norway

Sex:

not specified

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Remarks:

Doses / Concentrations:
10 to 500 mg/kg/day
Basis:
no data

Remarks on result:

not measured/tested

Histopathological findings:

effects observed, treatment-related

Dose descriptor:

LOEL

Generation:

F2

Effect level:

306.58 other: mg/kg/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Histopathological effect-Neoplastic lesions observed in organs.

Critical effects observed:

not specified

Reproductive effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: LOEL
Estimation method: Taking 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 ("h" and "i" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alcohol AND Alkene AND Allyl AND Enol AND Ketone AND Methyl by Organic functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Allyl AND Enol AND Ketone by Organic functional groups (nested)

Domain logical expression index: "c"

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 Carbonyl, olefinic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anion by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acetates OR Allyl acetates and related chemicals OR MA: Direct Acylation Involving a Leaving group OR MA: Polarised Alkenes OR MA: SN2 reaction at a sp2 carbon atom OR MA: SN2 reaction at sp3 carbon atom OR Mechanistic Domain: Acylation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN2 OR Polarised alkene - ketones OR Polarised alkenes with a halogen leaving group by Protein binding by OECD

Domain logical expression index: "g"

Similarity boundary:Target: C(C)(=O)(.[Ti])C={t}C(C)O{-}.C(C)(=O)C={t}C(C)O{-}.C(C)(C)O{-}.C(C)(C)O{-}
Threshold=40%,
Dice(Atom pairs)

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of logP Multicase which is >= -0.617

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of logP Multicase which is <= 2.02

Conclusions:

The two generation reproductive toxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titanium in Rattus norvegicus was observed at a dose concentration of 306.5797 mg/kg/day.

Executive summary:

The two generation reproductive toxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titanium in Rattus norvegicus was observed at a dose concentration of 306.5797 mg/kg/day.This dose level do not exibit that the substance will have any toxic effect to reproduction in animals and so will not be considered for classification.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

306.58 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

K2 level data obtained by QSAR estimation study

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The two generation reproductive toxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis (propan-2-olato)titanium in Rattus norvegicus was observed at a dose concentration of 306.5797 mg/kg/day.This dose level do not exibit that the substance will have any toxic effect to reproduction in animals and so will not be considered for classification.

Short description of key information:

The target substance for not have toxicity effect to reproduction.

Justification for selection of Effect on fertility via oral route:

The two generation reproductive toxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titanium in Rattus norvegicus was observed at a dose concentration of 306.5797 mg/kg/day.

Effects on developmental toxicity

Description of key information

The fetotoxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titaniumin in rabbit by oral exposure was observed at a dose concentration of 55.55463 mg/kg/day . This indicates that bis(pentane-2,4-dionato-O,O') bis(propan-2-olato)titanium shall not exhibit toxic effect to rabbit by the oral route below the above mention dose.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

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:

Data is predicted by QSAR toolbox version 2.3

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Route of administration:

oral: drinking water

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Duration of treatment: Days 7-19 (post mating)
Post exposure period: 9 days

Duration of test:

28 days

Remarks:

Doses / Concentrations:
0, 12.2, 36.6 and 58.7 mg /kg/day
Basis:
no data

No. of animals per sex per dose:

17

Maternal examinations:

yes

Fetal examinations:

yes

Remarks on result:

not measured/tested

Abnormalities:

not specified

Dose descriptor:

LOEL

Effect level:

55.555 other: mg/kg/day

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: LOEL
Estimation method: Taking 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" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alcohol AND Alkene AND Allyl AND Enol AND Ketone AND Methyl by Organic functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Allyl AND Enol AND Ketone by Organic functional groups (nested)

Domain logical expression index: "c"

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 Carbonyl, olefinic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anion by Organic functional groups, Norbert Haider (checkmol)

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 Aliphatic tertiary amines OR Aromatic nitro OR MA: Iminium Ion Formation OR MA: Nitrenium Ion Formation OR MA: Quinones and Quinone-type Chemicals OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 OR Quinones 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, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of logP Multicase which is >= -0.373

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of logP Multicase which is <= 1.07

Conclusions:

The fetotoxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titaniumin in rabbit by oral exposure was observed at a dose concentration of 55.55463 mg/kg/day . This indicates that bis(pentane-2,4-dionato-O,O') bis(propan-2-olato)titanium shall not exhibit toxic effect to rabbit by the oral route below the above mention dose.

Executive summary:

The fetotoxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titaniumin in rabbit by oral exposure was observed at a dose concentration of 55.55463 mg/kg/day . This indicates that bis(pentane-2,4-dionato-O,O') bis(propan-2-olato)titanium shall not exhibit toxic effect to rabbit by the oral route below the above mention dose.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

55.554 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

K2 level data obtained by QSAR estimation study

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The fetotoxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titaniumin in rabbit by oral exposure was observed at a dose concentration of 55.55463 mg/kg/day . This indicates that bis(pentane-2,4-dionato-O,O') bis(propan-2-olato)titanium shall not exhibit toxic effect to rabbit by the oral route below the above mention dose.

Justification for selection of Effect on developmental toxicity: via oral route:

The fetotoxicity LOEL (Lowest observed effect level) of bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titaniumin in rabbit by oral exposure was observed at a dose concentration of 55.55463 mg/kg/day . This indicates that bis(pentane-2,4-dionato-O,O') bis(propan-2-olato)titanium shall not exhibit toxic effect to rabbit by the oral route below the above mention dose.

Justification for classification or non-classification

It has been estimated that the target substance, bis(pentane-2,4-dionato-O,O')bis(propan-2-olato)titanium, do not show any toxicity effect to reproductive and teratogenic level and so cannot be considered for further classification.