Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
not specified
Principles of method if other than guideline:
no data
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 75, 125, or 250 mg/kg/day
Basis:
nominal in diet
No. of animals per sex per dose:
20/sex/group
Control animals:
yes

Examinations

Sacrifice and pathology:
The toxicological parameters examined in this study included body weight changes, food consumption, mortality, clinical pathological evaluations of major organs and tissues, and hematology and serum chemistry. Nephropathy, characterized by the presence of multiple foci of renal tubular regeneration, often accompanied by interstitial lymphocytic infiltrates and/or foci of interstitial fibrosis, was present in 4, 1, 1, and 9 male mice in the control, low-, medium-, and high-dose groups, respectively. Similar lesions were seen in 2, 3, 7, and 10 female mice in the 0, 75, 125, and 250 mg/kg treatment groups. The kidney lesions were described as minimal or mild in all dose groups. Relative and absolute kidney weights were reduced in the two higher dosage groups.

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 75 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
ca. 125 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

Male and female CD-1 mice (20/sex/group) were gavaged with 0, 75, 125, or 250 mg/kg/day pyrene in corn oil for 13 weeks. The toxicological parameters examined in this study included body weight changes, food consumption, mortality, clinical pathological evaluations of major organs and tissues, and hematology and serum chemistry. Nephropathy, characterized by the presence of multiple foci of renal tubular regeneration, often accompanied by interstitial lymphocytic infiltrates and/or foci of interstitial fibrosis, was present in 4, 1, 1, and 9 male mice in the control, low-, medium-, and high-dose groups, respectively. Similar lesions were seen in 2, 3, 7, and 10 female mice in the 0, 75, 125, and 250 mg/kg treatment groups. The kidney lesions were described as minimal or mild in all dose groups. Relative and absolute kidney weights were reduced in the two higher dosage groups. Based on the results of this study, the low dose (75 mg/kg/day) was considered the NOAEL and 125 mg/kg/day the LOAEL for nephropathy and decreased kidney weights.