Ethyl methacrylate

Repeated dose toxicity: oral

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

Test material information

1

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

C2H6O

IUPAC Name:

ethanol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

1 other: %

Remarks:

w/w in liquid diet

Doses / concentrations 2

Dose / conc.:

2 other: %

Remarks:

w/w in liquid diet; calculated to be equivalent to 2400 mg/kg bw/d

Doses / concentrations 3

Dose / conc.:

3 other: %

Remarks:

w/w in liquid diet

Doses / concentrations 4

Dose / conc.:

4 other: %

Remarks:

w/w in liquid diet

Doses / concentrations 5

Dose / conc.:

5 other: %

Remarks:

w/w in liquid diet

Doses / concentrations 6

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.