Registration Dossier

Administrative data

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:
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:
reference to same study
Qualifier:
according to
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.