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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Draft available, according to national guideline, peer-reviewed data, acceptable for assessment (Study conducted by Hazelton Laboratories, Inc., for the Office of Solid Waste, Washington, DC)

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Acenaphthene - IRIS Summary
Author:
US EPA
Year:
1994
Bibliographic source:
http://www.epa.gov/ncea/iris/subst/0442.htm
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 82-1 (90-Day Oral Toxicity)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
PHYSICO-CHEMICAL PROPERTIES
- Vapour pressure: ~ 0.3 Pa (25 °C)
- Water solubility (under test conditions): ~ 3.9 mg/L (25 °C)
- log Pow: ~ 3.9

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
--
Duration of treatment / exposure:
90 d
Frequency of treatment:
1x/d
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 175, 350 and 700 mg/(kg bw*d)
Basis:
actual ingested
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: no data
- Rationale for selecting satellite groups: no sattelite groups
Positive control:
none

Examinations

Observations and examinations performed and frequency:
The toxicological evaluations of this study included body weight changes, food consumption, mortality, clinical pathological evaluations (includings hematology and clinical chemistry), organ weights and histopathological evaluations of target organs.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
--

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
high-dose males and mid- and high-dose females showed significant increases in cholesterol levels
Urinalysis findings:
not specified
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Liver weight increase in mid- and high-dose animals
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
hepatocellular hypertrophy
Histopathological findings: neoplastic:
not examined
Details on results:
see above

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
(90 d, oral)
Effect level:
175 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Clinical chemistry; organ weight; histopathology
Dose descriptor:
LOAEL
Remarks:
(90 d,oral)
Effect level:
350 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Clinical chemistry; organ weight; histopathology
Dose descriptor:
other: RfD (Reference dose, US EPA IRIS)
Effect level:
0.06 other: mg/kg bw/d (lifelong for any human)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: non-neoplastic effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:
Four groups of CD-1 mice (20/sex/group) were gavaged daily with 0, 175, 350, or 700 mg/kg/day acenaphthene for 90 days. The toxicological evaluations of this study included body weight changes, food consumption, mortality, clinical pathological evaluations (includings hematology and clinical chemistry), organ weights and histopathological evaluations of target organs. The results of this study indicated no treatment-related effects on survival, clinical signs, body weight changes, total food intake, and ophthalmological alterations. Liver weight changes accompanied by microscopic alterations (cellular hypertrophy) were noted in both mid- and high-dose animals and seemed to be dose-dependent. Additionally, high-dose males and mid- and high-dose females showed significant increases in cholesterol levels. Although increased liver weights, without accompanying microscopic alterations or increased cholesterol levels, were also observed at the low dose, this change was considered to be adaptive and was not considered adverse. The LOAEL is 350 mg/kg/day based on hepatotoxicity); the NOAEL is 175 mg/kg/day.