Fusel oil

Specific investigations: other studies

Administrative data

Endpoint:

behavioural effects

Type of information:

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

Adequacy of study:

other information

Study period:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Results only presented as small graphs. Small number of animals used. Otherwise, acceptably documented study which meets basic scientific principles and contains sufficient detail to be able to judge the results reliable as a contribution to the understanding of the toxicity of this substance.

Data source

Reference

Reference Type:

publication

Title:

Behavioral effects of ethanol inhalation in rats.

Author:

Ghosh TK, Copeland JR, Alex PK, Pradhan SN

Year:

1991

Bibliographic source:

Pharmacol Biochem Behav 38, 699-704

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

Behavioral effects of ethanol inhalation were studied on two fixed-ratio (FR) liquid-reinforced schedules and a continuous reinforcement (CRF) schedule intracranial self-stimulation (SS) in rats. Exposure regimes ranged from short to long in one day then repeated short exposures for 5 days.

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

acute toxicity: inhalation

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:

CH3CH2OH

IUPAC Name:

ethanol

Details on test material:

- Name of test material (as cited in study report): Other TS
- Analytical purity: 100% anydrous ethanol
- Other: sourced from US Industrials Co.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 180-210g
- Housing: housed individually, stainless steel cages
- Food: controlled, see details of method.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 1°C
- Humidity: 55 ± 5%
- Photoperiod: 12hr light/12hr dark

Administration / exposure

Route of administration:

inhalation

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation behavioural chamber ex Pradhan & Copeland. Glass chamber over a grid floor fitted with a metal plate accommodating a lever and liquid dipper. Individual animals exposed to multiple concentrations. Laboratory air was mixed with ethanol vapour generated from an evaporating flask then cooled back to ambient before entering the test chamber.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

15 minute sampling of chamber atmosphere. Samples analysed by gas chromatography.

Duration of treatment / exposure:

1x2 hour, 1x5 hour and 5x2 hour over 5 days. Not all tests were used for all exposure regimes.

Frequency of treatment:

one exposure per day

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2 hour exposures: 140, 161, 202 and 398ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
five hour exposure: 140ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2 hrx5 exposure: 206ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
2 hour exposures: 130, 373, 603, 1287ppm
Basis:
analytical conc.
used for self stimulationbehaviour study.

No. of animals per sex per dose:

6

Control animals:

other: animal response on previous day in air.

Details on study design:

See other information below.

Results and discussion

Any other information on results incl. tables

FR behaviour:  reinforcement behaviour dropped by a small but statistically significantly amount in the 15 minute exposure periods from 45mins  onward and for exposures of 202ppm and above.  There was no cumulative effect (exposure for 5 hours did not produce any effects not seen in the  2hr exposure.).   In the daily repeat exposure, effects declined showing a  developing tolerance to ethanol. SS: there was a decline in self stimulation behaviour at exposures of  600ppm and above but these were not statistically significant.

Blood ethanol concentrations following 2 hr exposure: 393ug/ml after  600ppm, 545ug/ml after 1200ppm. Data from the other exposures was presented graphically. The author of this summary fitted a curve to this data . Over this data range a polynomial of form BEC=-0.0002C^2 + 0.7335C fits with an correlation co-efficient R=0.9989 and where BEC is the blood ethanol concentration (mg/l) and C the inhalation concentration (ppm). A linear equation with slope 0.5237 fits with R=0.9816.

Applicant's summary and conclusion

Conclusions:

Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule. Ethanol inhalation can produce adequate blood concentrations in the rat so as to produce behavioral effects but these are transient.

Executive summary:

Behavioral effects of ethanol vapour inhalation were studied on two fixed-ratio (FR) liquid feed-reinforced schedules and a continuous reinforcement schedule intracranial self-stimulation (SS) in rats.  Exposure regimes were 2 and 5 hours and daily 2 hour exposures over 5 days. . In the FR-50 schedule , small but significant decreases of the rate (around 20% reduction) were observed at 202 ppm and above.  However, these effects did not increase with increased exposure time and when repeated daily, they disappeared after 3 days showing a developing tolerance to ethanol.   In the SS behavior study, there was a decline in self stimulation behaviour at exposures of  600ppm and above but these were not statistically significant.  Blood ethanol concentrations were measured to be 393 micrograms/ml and 545 micrograms/ml after exposure to 600 ppm and 1200 ppm of ethanol respectively. Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule, leading to the conclusion that inhalation can produce adequate blood concentrations in the rat so as to produce some behavioral effects but these are transient, even if exposure is continued.