Diethylbenzene

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Only short abstract available; GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-diethylbenzene

EC Number:

203-265-2

EC Name:

1,4-diethylbenzene

Cas Number:

105-05-5

Molecular formula:

C10H14

IUPAC Name:

1,4-diethylbenzene

Details on test material:

IUCLID4 Test substance: other TS: 1,4-DEB

Identity: 1,4-Diethylbenzene (CAS No. 105-05-5)
Purity:97.2%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Male: 44 days including 14 days before mating; Female: up to 52 days including 14 days before mating to lactation day 3

Frequency of treatment:

Frequency of treatment: 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

30 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

150 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

750 mg/kg bw/day (nominal)

No. of animals per sex per dose:

12 rats/sex/group

Control animals:

other: T27-03:Concurrent

Details on study design:

Control group and treatment:  Concurrent Postexposure observation period:  None
Terminal Kill: Male, day 45; Female, day 4 of lactation

Positive control:

No data

Examinations

Statistics:

Not stated

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

There were no deaths or abnormal clinical signs attributable to the treatment in males or females of any group throughout the dosing period. Body weights decreased in both males and females given 750 mg/kg. Food consumption decreased in males given 750 mg/kg until Day 8 and increased from Day 29.

There were no observed effects due to the test substance in the hematological findings for the treated males. Blood chemical examination revealed increases in levels of BUN and GPT in males given 150 and 750 mg/kg, and increases in levels of total protein, albumin, creatinine and total bilirubin and a decrease in the glucose level in the 750 mg/kg dose males. Absolute and relative kidney weights were elevated in the 150- and 750 mg/kg dose males. Moreover, absolute and relative weights of the liver were elevated in the 750 mg/kg-dose males and females. Necropsy revealed brown colored and enlarged livers in males given 750 mg/kg. Histopathological examination showed swelling of the liver cells in these animals.

NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for males and 150 mg/kg/day for females.



NOAEL: 150 mg/kg/day

Toxic response/effects: Male and female copulation and fertility indices, pregnancy rates, and implantation sites were comparable among groups. The  number of live and dead pups, the number of litters with live offspring,  the mean litter size, and the male-to-female ratio were comparable among  the groups on lactation day 0. 

Duration of gestation was  slightly, but statistically significantly, increased in the 750 mg/kg  group and there was a statistically significant decrease in pup survival  on day 4 in the 750 mg/kg group;  however, the investigators did not consider these findings treatment-related.

Effect levels (P0)

1

Dose descriptor:

NOAEL

Remarks:

Parental

Effect level:

30 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Absolute Organ weight changes (liver and kidney) and clinical chemistry parameters.

2

Dose descriptor:

NOEL

Remarks:

parental

Effect level:

150 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Based on absolute and relative weights of the liver.

Results: F1 generation

Details on results (F1)

There were no differences in mean pup  weights across groups. No differences were found in external  observations; and no remarkable findings were
observed at necropsy in  pups found dead prior to lactation day 4. 

Effect levels (F1)

Dose descriptor:

NOAEL

Remarks:

Reprodutive/developmental

Generation:

F1

Effect level:

> 750 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No treatment related reproductive toxicity observed

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

1,4-Diethylbenzene (105-05-5) does not appear to be a reproductive toxicant, although a slight effect was observed on duration of gestation.