1,4-diethylbenzene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Results of an study conducted in accordance with generally accepted scientific principles. Possible deficiencies in the reporting of the endopoint do not affect the quality of relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: slc:SD

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

Male: 44 days including 14 days before mating.
Female: from 14 days before mating to day 3 of lactation.
Premating exposure period: male, 14 days; female, 14 days

Frequency of treatment:

7 days/week

Remarks:

Doses / Concentrations:
0 mg/kg
Basis:
no data

Remarks:

Doses / Concentrations:
30 mg/kg
Basis:
no data

Remarks:

Doses / Concentrations:
150 mg/kg
Basis:
no data

Remarks:

Doses / Concentrations:
750 mg/kg
Basis:
no data

No. of animals per sex per dose:

12 animals/sex/group

Control animals:

yes, concurrent vehicle

Reproductive function: oestrous cycle:

no effects observed

The results observed in mating, fertility and estrous cycle did not reveal any effects attributable to the administration of test substance.
Observation of delivery, all gestation animals delivered of pups normally, and there were not a treatment-related effect throughout the lactation period.

Dose descriptor:

NOEL

Effect level:

750 mg/kg bw/day

Based on:

not specified

Sex:

male/female

Mortality / viability:

no mortality observed

Description (incidence and severity):

The external examination of pups revealed no effects attributable to the administration of test substance.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The body weights of fetuses showed the favorably growths until Day 4 of lactation.

The necropsy of stillborn, dead pups until day 4 of lactation and newborns at day 4 of lactation did not reveal any effects attributable to the administration of test substance.

Dose descriptor:

NOEL

Generation:

F1

Effect level:

750 mg/kg bw/day

Based on:

not specified

Sex:

male/female

Reproductive effects observed:

not specified

Conclusions:

The influences of test substance on reproductive and developmental toxicity were not observed in both male and female rats receiving 750 mg/kg/day, therefore maximum NOELs were considered to be 750 mg/kg/day in both sexes.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A reproductive/developmental screening study was conducted in rats at 0, 30, 150 and 750 mg/kg bw/day (by gavage) to investigate potential adverse effect of 1,4-diethylbenzene on reproductive performance, including mating, fertility and oestrus cycle and also for dams during the pregnancy and lactation period, according to OECD Guideline 422. Under the conditions of this study, no test substance-related effects were observed on reproductive performance at any dosage level. Based on these results, 750 mg/kg bw/day was considered to be the NOAEL for reproductive toxicity.

Justification for selection of Effect on fertility via oral route:
Only one study available. The study is a combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

Effects on developmental toxicity

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Results of an study conducted in accordance with generally accepted scientific principles. Possible deficiencies in the reporting of the endopoint do not affect the quality of relevant results.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD 422

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

Male: 44 days including 14 days before mating.
Female: from 14 days before mating to day 3 of lactation.
Premating exposure period: male, 14 days; female, 14 days

Remarks:

Doses / Concentrations:
0
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
30
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
150
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
750
Basis:
nominal in diet

Maternal examinations:

All gestation animals delivered pups normally.

Fetal examinations:

The body weight of fetuses showed the favorably growths until day 4 of lactation.

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
The results observed in mating, fertility and estrous cycle did not reveal any effects attributable to the administration of test substance.
Observation of delivery, all gestation animals delivered of pups normally, and there were not a treatment-related effect throughout the lactation period.

Dose descriptor:

NOAEL

Effect level:

750 mg/kg bw/day

Based on:

no data

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The necropsy of stillborn, dead pups until day 4 of lactation and newborns at day 4 of lactation did not reveal any effects attributable to the administration of the test substance.

Dose descriptor:

NOAEL

Effect level:

750 mg/kg bw/day

Based on:

no data

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

Under the conditions of this screening study, no test substance-related effects were observed on the general physical condition of F1 pups at any dosage level. As such, a dosage level of 750 mg/kg bw/day was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and teratogenic toxicity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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

A reproductive/developmental screening study was conducted in rats at 0, 30, 150 and 750 mg/kg bw/day (by gavage) to investigate potential adverse effect of 1,4-diethylbenzene on reproductive performance, including mating, fertility and oestrus cycle and also for dams during the pregnancy and lactation period, according to OECD Guideline 422. Under the conditions of this study, no test substance-related effects were observed on reproductive performance at any dosage level. In the absence of any effects on the general physical condition of the F1 pups, the NOAEL for neonatal toxicity (F1 offspring) was set to 750 mg/kg bw/day.

The (Q)SAR prediction as "non-toxic" is considered valid and supports the results observed in the test according to OECD 422.

The prediction determines the presence or absence of toxicity (indicated as Tox Index +1 and -1) based on modelling compared with a training set. 1,4 -diethylbenzene falls into the applicability domain of the model. The predicted value is "non-toxic".Due to the specific nature of the dataset, it being comprised of experimental data for different species, including human data, the dose limits for each particular species cannot be directly extracted from the prediction. However, most commonly available comparison would be data for rats, where the corresponding NOAEL limits can be estimated to be in the range of 500 – 750 mg/kg/day as reported in this Chemical Safety Report.

Justification for selection of Effect on developmental toxicity: via oral route:
Only one study available. The study is a combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

Justification for classification or non-classification

The reproductive/developmental screening study was conducted in rats to investigate the potential adverse effect of 1,4-diethylbenzene on reproduction, including embryo/foetal development. No adverse effects on reproductive/developmental parameters were noted at doses up to 750 mg/kg bw/day. Also, there were no effects on the general physical condition of the F1 pups at any dose. As a conclusion 1,4 -diethylbenzene is not classified as hazardous for these endpoints.