4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one

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:

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3

GLP compliance:

no

Species:

other: Rattus norvegicus

Strain:

not specified

Sex:

male/female

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Duration of treatment / exposure:

10 weeks

Details on study schedule:

Reproduction study in which 25 male and female rats were dosed with 5, 10 and 25 mg/kg/day of the test material for 10 weeks premating for 2 generations.

Remarks:

Doses / Concentrations:
5, 10 and 25 mg/kg/day
Basis:
no data

No. of animals per sex per dose:

25 male and female rats

Control animals:

not specified

Remarks on result:

not measured/tested

Critical effects observed:

not specified

Dose descriptor:

LOEL

Generation:

F2

Effect level:

129.019 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

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" and "b" ) and ("c" and "d" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C1(C)(C)C(C=CC(C)=O)=C(C)CCC1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Similarity boundary:Target: C1(C)(C)C(C=CC(C)=O)=C(C)CCC1
Threshold=60%,
Dice(Atom pairs)

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.37

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Conclusions:

Toxicity to reproduction to male and female Rattus norvegicus by the oral route by 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one gave an estimated LOEL as 129.0195 mg/kg bw/day from QSAR in two generation prediction. This value suggests that this chemical is unlikely to exhibit reproductive toxicity to Rattus norvegicus

Executive summary:

Toxicity to reproduction to male and female Rattus norvegicus by the oral route by 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one gave an estimated LOEL as 129.0195 mg/kg bw/day from QSAR in two generation prediction. This value suggests that this chemical is unlikely to exhibit reproductive toxicity to Rattus norvegicus

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

129.019 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data isa category 2 data as the same has been predicted by SSS using the recommendated QSAR tool

Additional information

Toxicity to reproduction to male and female Rattus norvegicus by the oral route by 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one gave an estimated LOEL as 129.0195 mg/kg bw/day from QSAR in two generation prediction. This value suggests that this chemical is unlikely to exhibit reproductive toxicity to Rattus norvegicus

Short description of key information:

Toxicity to reproduction to male and female Rattus norvegicus by the oral route by 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one gave an estimated LOEL as 129.0195 mg/kg bw/day from QSAR in two generation prediction. This value suggests that this chemical is unlikely to exhibit reproductive toxicity to Rattus norvegicus

Justification for selection of Effect on fertility via oral route:

This study was selected since it predicted a two generational reprotoxic study over a period of 10 weeks using 25 Rats of both the sexes nd over a concentration range of 5, 10 and 25 mg/kg/day. Thus the prediction can be considered to be reliable.

Effects on developmental toxicity

Description of key information

In the prediction of Developmental Toxicity(Fetotoxicity) using QSAR,the  low observed effect level (LOEL) for 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one was estimated to be 232.1587 mg/kg bw/day. This value is suggestive of the chemical not exhibiting developmental toxicity/teratogenecity.

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:

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3

GLP compliance:

no

Species:

other: Oryctolagus cuniculus

Strain:

not specified

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Frequency of treatment:

On Gestation Day 6-15

Duration of test:

10 days

Remarks:

Doses / Concentrations:
5, 10 and 25 mg/kg/day
Basis:
no data

No. of animals per sex per dose:

25 female rats

Control animals:

not specified

Details on study design:

Developmental Study in which 25 female rats were dosed with 5, 10 and 25 mg/kg/day of the test material on GD 6-15, 10 days

Remarks on result:

not measured/tested

Abnormalities:

not specified

Dose descriptor:

LOEL

Effect level:

232.159 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: fetotoxicity

Remarks on result:

other: not specified

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" and "b" ) and ("c" and "d" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C1(C)(C)C(C=CC(C)=O)=C(C)CCC1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Similarity boundary:Target: C1(C)(C)C(C=CC(C)=O)=C(C)CCC1
Threshold=60%,
Dice(Atom pairs)

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.37

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Conclusions:

In the prediction of Developmental Toxicity(Fetotoxicity) using QSAR,the low observed effect level (LOEL) for 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one was estimated to be 232.1587 mg/kg bw/day. This value is suggestive of the chemical not exhibiting developmental toxicity/teratogenecity.

Executive summary:

In the prediction of Developmental Toxicity(Fetotoxicity) using QSAR,the low observed effect level (LOEL) for 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one was estimated to be 232.1587 mg/kg bw/day. This value is suggestive of the chemical not exhibiting developmental toxicity/teratogenecity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

232.159 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Quality of whole database:

The data isa category 2 data as the same has been predicted by SSS using the recommendated QSAR tool

Additional information

In the prediction of Developmental Toxicity(Fetotoxicity) using QSAR,the low observed effect level (LOEL) for 4-(2,6,6-trimethylcyclohex-1-ene-1-yl)-but-3-ene-2-one was estimated to be 232.1587 mg/kg bw/day. This value is suggestive of the chemical not exhibiting developmental toxicity/teratogenecity.

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

This study was selected since it predicted developmental toxicity in which 25 female rats were dosed with 5, 10 and 25 mg/kg/day of the test material on GD 6-15 for a period of 10 days. Thus the prediction can be considered to be reliable.