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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
evaluated by OECD SIDS (2004) as good quality supporting study

Data source

Reference
Reference Type:
secondary source
Title:
Subchronic toxicity investigation of ethyl alcohol: a test for lowest effective dose (led) to be used in a long term bioassay for carcinogenicity
Author:
Holmberg, B., Kronevi, T., Ekner, A.
Year:
1986
Bibliographic source:
National Board of Occupational safety and Health, Solna, Sweden; cited in OECD SIDS (2004) for Ethanol

Materials and methods

Principles of method if other than guideline:
other: not specified in OECD SIDS
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Age at study start: 43 days

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
ethanol in liquid diet
Vehicle:
water
Details on oral exposure:
Ethanol supplied in nutritionally balanced liquid diet.
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
1 other: %
Remarks:
w/w in liquid diet
Dose / conc.:
2 other: %
Remarks:
w/w in liquid diet; calculated to be equivalent to 2400 mg/kg bw/d
Dose / conc.:
3 other: %
Remarks:
w/w in liquid diet
Dose / conc.:
4 other: %
Remarks:
w/w in liquid diet
Dose / conc.:
5 other: %
Remarks:
w/w in liquid diet
Dose / conc.:
10 other: %
Remarks:
w/w in liquid diet
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Examinations

Statistics:
No statistical tests for significance were used.

Results and discussion

Results of examinations

Details on results:
Bodyweight: All groups gained weight though final weights decreased with dose.
Food/water consumption: Consumption in the 10% group was reduced relative to controls (182 ml diet/kg-d versus 195 ml diet/kg-d).
Clinical signs: No adverse signs were observed
Ophthalmology, haematology: Not examined.
Clinical biochemistry: Serum liver enzymes were not affected by treatment and kidney findings were minimal.
Mortality and time to death: No deaths occurred.
Gross pathology: Liver yellowing, dosage-related.
Histopathology: Hepatic centrilobular steatosis increased in severity with dose as did the frequency and severity of Mallory bodies (hyaline) and acidophilic degeneration and necrosis. Most liver findings were absent or mild at 2% w/w ethanol but became more significant at 3% and higher dose. Reticulo-endothelial cell proliferation was slight at 1 and 2%. A few kidney casts were noted in animals from the 1-3% dose groups and there were a few calcifications in the 3-5% groups. Slight tubular fatty change occurred in all groups.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 400 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:
yes
Lowest effective dose / conc.:
2 400 mg/kg bw/day (nominal)
System:
hepatobiliary
Organ:
liver
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Executive summary:

This study was selected from a larger set of repeated dose studies with ethanol, as this study was selected by OECD SIDS (2004) as good quality supporting study with the lowest reliable NOAEL.