Creosote oil, acenaphthene fraction

Repeated dose toxicity: oral

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

Reference

Reference 1

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 2

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 82-1 (90-Day Oral Toxicity)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Acenaphthene

EC Number:

201-469-6

EC Name:

Acenaphthene

Cas Number:

83-32-9

Molecular formula:

C12H10

IUPAC Name:

1,2-dihydroacenaphthylene

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 or test system 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

1

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

2

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

3

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.