Ethanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Critical study for SIDS endpoint Acceptable, study with sufficient basic documentation to demonstrate that study meets basic scientific principles and contains enough detail to be able to judge the results reliable as a contribution to the understanding of the acute toxicity of this substance.

Data source

Reference

Reference Type:

publication

Title:

Comparative lethality of methanol, ethanol and mixtures in female rats.

Author:

Youssef, A., Madkour, K., Cox, C., Weiss, B.

Year:

1992

Bibliographic source:

J. Appl. Toxicol. 12(3):193-197.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

mortality only recorded over 24 hours

Principles of method if other than guideline:

Based on the method of Litchfield and Wilcoxon (Exp Ther J, 96, 99, 1949). The purpose of the study was to assess the acute toxicity of ethanol, methanol and mixtures of the two (as typically found in denatured ethanol products). Only the information relating to ethanol is reported here.

GLP compliance:

not specified

Test type:

standard acute method

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:

- Name of test material (as cited in study report): ethanol
- Source: El Nasr Co, Cairo
- Analytical purity: Test substance was 99.8% ethanol and 0.1% methanol.

Test animals

Species:

rat

Strain:

other: Ratus Norvegicus, albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Research Centre, Egypt
- Age at study initiation: Adults
- Weight at study initiation: 180 g +/-3g.
- Fasting period before study: 16hrs
- Diet: ad libitum (ex El Dabba Trade Co, Egypt)
- Water: ad libitum
- Other: virgin females

ENVIRONMENTAL CONDITIONS
- Temperature: 22 -26°C
- Photoperiod: 12 hour light/12 hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: no data but assumed undiluted.

Details on oral exposure:

Ethanol gavage was preceded by gum acacia gavage given 10 mins before dosing to reduce local irritation in stomach.

MAXIMUM DOSE VOLUME APPLIED: One dose per time period
- Exposure duration: not applicable.

Doses:

16, 17, 18, 19, 20, 21 and 22 ml/kg (selected on the basis of published information to range from non fatal in all animals to fatal in all animals)

No. of animals per sex per dose:

8. Larger number used to improve precision.

Details on study design:

- Duration of observation period following administration: 24 hours
- Frequency of observations and weighing:
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

15 010 mg/kg bw

95% CL:

> 14 450 - < 15 560

Mortality:

Individual times of death not given.

Clinical signs:

other: Clinical obserbations ranged from inebriation to gait disturbance and dose-related decrease in resonse to painful stimuli, respiratory depression and coma. Deaths were due to cardiorespiratory failure preceded by coma.

Gross pathology:

Gross and histopathological examination showed gastric mucosa with diffuse congestion and dilation of blood vessels but no hemorrhage or ulceration. All other tissues appeared normal.

Other findings:

- Potential target organs: Not reported
- Necropsy findings: Diffuse congestion of the gastric mucosa without gross haemorrhage or ulceration.
- Sex Comparison: not applicable.

Any other information on results incl. tables

Mortality

Dose (ml)	Mortality
16	0/8
17	0/8
18	2/8
19	4/8
20	6/8
21	8/8
22	8/8

19 ml/kg converts to 15.01 g/kg bw. SD=0.23

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In an acute toxicity study in female rats using a relatively large number of animals over 7 closely spaced doses, an LD50 value of 14500 -15500mg/kg was obtained. Animals were only observed for a period of 24 hours, although it is unlikely that significant deaths would have occurred after this point due to the known toxicokinetics of metabolism. Those animals that died showed severe CNS effects with death due to cardiorespiratory failure that was preceded by coma.