Sodium ethanolate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable study, meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

The effects of long-term oral administration of ethanol on Sprague-Dawley rats - a condensed report

Author:

Holmberg B and Ekstrom T

Year:

1994

Bibliographic source:

Toxicology 96 (1995) 133-145

Materials and methods

Principles of method if other than guideline:

2-year bioassay of ethyl alcohol in a semisynthetic liquid diet given to Sprague-Dawley rats

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

C2H6O

IUPAC Name:

ethanol

Details on test material:

test substance: ethanol
- Supplier: Kemetyl AB, Stockholm.
- Analytical purity: 99.5% spectroscopically pure
- Impurities (identity and concentrations): < 100 mg methanol/l, < 1 mg cyclohexane/l, and maximum 1 mg fusel/l

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ALAB AB, Sollentuna, Sweden
- Age at study initiation: 6 and 7 weeks of age
- Housing: individually
- Diet (e.g. ad libitum): liquid diet adapted for rat nutritional purposes based upon a semisynthetic liquid human parenteral diet, Nutrauxile (Kabi Vitrum AB, Stockholm).; ad libitum
- Water (e.g. ad libitum): water; ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 45 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Ethyl alcohol - 1% (w/w) or 3% (w/w) - was added to the liquid diet and 20.2 g or 62.0 g glucose diet was added to serve as equicaloric controls

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 3% w/w ethanol
Basis:
nominal in diet

No. of animals per sex per dose:

50

Control animals:

other: diet with additional glucose content (high and low)

Details on study design:

- Dose selection rationale: based on data of a 13-week dose-range finding study (Holmberg et al., 1986)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: every week during the first 13 weeks, then every second week thereafter

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: end of study

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data


NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
The median survivals for males were 105 weeks for low glucose, 104 weeks for high glucose, 110 weeks for low ethanol, and 105 weeks for high ethanol males. For females the corresponding figures were: low glucose 103 weeks, high glucose 94 weeks, low ethanol 101 weeks and high ethanol 109 weeks.

BODY WEIGHT AND WEIGHT GAIN
Low ethanol males had a similar body weight development as the corresponding control. High ethanol males had lower body weights (P < 0.005) from week 13 than had the high glucose males. Low ethanol females had a body weight development, which was similar to the low glucose females. For high ethanol females there was a statistically significant lower (P < 0.05) body weight from week 69 than in the controls.

DIET CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
The total diet consumption of low ethanol diet was higher than for low glucose among males, but not statistically significant. The consumption of high ethanol diet among males was lower (P < 0.05) than the consumption of the high glucose diet. For females, the total diet consumption among low ethanol animals was slightly higher than for the low glucose controls. For high ethanol females the diet consumption was significantly higher (P < 0.01) than for the high glucose control.

ORGAN WEIGHTS
There were no statistically significant differences in liver or kidney weights between the groups compared.

HISTOPATHOLOGY:
For male rats no neoplastic lesions were observed to be related to ethanol exposure.
For females, when liquid diet individual group comparisons were made, an increase in mammary gland tumors was seen for females receiving the low ethanol containing diet. Liver and bile duct injury was seen among males. Inflammatory reactions were among males in pancreas and for females in the clitoral gland. Hyperplasia was observed in the thyroid gland in both sexes and in the adrenal glands among females. Peripheral nerve degeneration was common in both sexes. Unlike males, females had centrilobular hepatic necrosis in a certain fraction of the animals (this was not a significant difference).

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

> 3 other: %

Sex:

male/female

Basis for effect level:

other: body weight; histopathology

2

Dose descriptor:

LOAEL

Effect level:

3 other: %

Sex:

male/female

Basis for effect level:

other: body weight; histopathology

3

Dose descriptor:

NOAEL

Effect level:

> 3 600 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: body weight; histopathology

Target system / organ toxicity

Critical effects observed:

not specified