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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

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)
Version / remarks:
1992
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
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
Test material form:
not specified
Details on test material:
Commercial, purity 97.2%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration of treatment / exposure:
Male: 44 days including 14 days before mating.
Female: form 14 days before mating to day 3 of lactation.
Premating exposure period: 14 days (male and female)
Frequency of treatment:
7 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
750 mg/kg
Basis:
no data
Remarks:
Doses / Concentrations:
150 mg/kg
Basis:
no data
Remarks:
Doses / Concentrations:
30 mg/kg
Basis:
no data
Remarks:
Doses / Concentrations:
0 mg/kg
Basis:
no data
No. of animals per sex per dose:
12 animals/sex/group
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
The results in clinical observations did not reveal any effects atributable to the administration of test substance and there were no mortality in all groups.
Mortality:
no mortality observed
Description (incidence):
The results in clinical observations did not reveal any effects atributable to the administration of test substance and there were no mortality in all groups.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Depression of body weight gain observed in both males and female rats receiving 750 mg/kg/day.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Food consumption of male rats receiving 750 mg/kg/day was less than those of control until day 7 and thereafter, increases in food consumption were observed in them from day 28.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
As a result of hematology, there were no essential effects of test substance.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Blood examination: increases in the BUN and GPT were observed in male rats (150 mg/kg/day and 750 mg/kg/day), and increases in total protein, albumin, creatinine and total bilirubin and decrease of glucose were observed in male rats (750 mg/kg/day)
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increases in liver weights were observed in both male and female rats receiving 750 mg/kg/day, moreover increases in kidneys weights were observed in male rats receiving 150 mg/kg/day or more groups.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Increase in incidence of brown coloured livers or enlargement of the livers were observed in male rats receiving 750 mg/kg/day
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
swelling of liver cells observed in livers of male rats receiving 750 mg/kg/day
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: see 'Remark'
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Increase in liver weights at 750 mg/kg/day
Dose descriptor:
dose level:
Effect level:
750 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Dose descriptor:
dose level:
Effect level:
150 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Dose descriptor:
NOEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LOEL
Effect level:
150 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The results described above led to a conclusion that effects of repeated dose toxicity study were considered to appear at 150 mg/kg/day or more in male rats and at 750 mg/kg/day in female rats (MHW, Japan, 1993b). The NOAEL for repeated dose toxicity in rats is considered 30 mg/kg/day in males and 150 mg/kg/day in female rats.
Executive summary:

1,4 -diethylbenzene was tested in 28 day repeated dose oral toxicity study in rats according to OECD Guideline 422 at doses of 30, 150, 500 and 750 mg/kg bw/day.  The effects observed in male rats have been increased BUN and GPT at 150 & 750 mg/kg; increases in total protein albumin, creatinine and total bilirubin, decrease in glucose at doses of 750 mg/kg/day and increase in kidney weight at 150 and 750 mg/kg/day; brown coloured livers and swelling of liver cells at 750 mg/kg bw. In male and female rats the effects observed were increase in liver weights at 750 mg/kg/day .