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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This well-designed study with intention for use in forensic studies gave consistent respiratory uptake values and fractional uptake values across all 11 volunteers and values close to previously published data. There was robust support for the conclusion that inspired ethanol can be considered as a source of elevation of blood alcohol concentration.

Data source

Reference
Reference Type:
publication
Title:
Handling of inspired vapourized ethanol in the airways and lungs (with comments on forensic aspects).
Author:
Kruhoffer, P.W.
Year:
1983
Bibliographic source:
Forensic Sci Int. 21:1-17.

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study to determine the fraction of inspired ethanol vapour that is taken up by human volunteers by measuring the ethanol concentration in inspired and expired air and monitoring resultant blood ethanol concentrations. A number of experiments were performed to hold constant variables such as ethanol concentration, tidal volume, work rate and respiratory frequency.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data
Radiolabelling:
no

Test animals

Species:
human
Sex:
male
Details on test animals and environmental conditions:
Normal adults. Ages 24-66, weights 63-82kg

Administration / exposure

Route of administration:
other: oral drink in orange juice followed by prolonged inhalation
Vehicle:
other: inspired air
Details on exposure:
INHALATION: TYPE OF INHALATION EXPOSURE: mouth only
GENERATION OF TEST ATMOSPHERE
- Exposure apparatus: Ethanol pumped at a controlled rate (0.61g/min) into a heated column packed with glass wool, glass marbles and filter paper through which compressed air was passed. The ethanol/air mixture was held in a 6 litre Douglas bag as a gas depot. This was connected to a mouthpiece fitted with an infinitely variable sliding valve to allow admission of either air or the air/ethanol mixture. The whole apparatus, up to and including the mouthpiece was in a temperature controlled chamber at 37C. The air/ethanol supply tube had a sampling point from which samples could be taken for ethanol concentration determination.
- Treatment of exhaust air: The expiration tube of the mouthpiece was connected to a T-valve to allow expired air to be directed into a 90l Douglas bage (all within the 37C environment.

ORAL:
Ethanol dose taken in 250ml orange juice 1.5-2hr after a light breakfast followed by periodic light exercise.
Duration and frequency of treatment / exposure:
INHALATION: 1 hour(s)
ORAL: Monitored for 4.3 hours.
Doses / concentrations
Remarks:
Doses / Concentrations:
INHALATION: 10-12mg/l (approximately 6000ppm after taking into account temperature of 28C and pressure of 760Torr.
ORAL: 0.7g/kg
No. of animals per sex per dose:
INHALATION EXPERIMENT: 11
ORAL DOSE EXPERIMENT: 6
Control animals:
no
Details on dosing and sampling:
ORAL: Four blood samples taken during last 2 hours of observation.

Results and discussion

Preliminary studies:
Test with a single subject at 14mg/l (7000ppm) and 26l/min produced feelings of warmth in the URT and an occasional sensation of not wanting to continue to breath the atmosphere. Concentrations of 18-19mg/l (9500-10000ppm) produced a marked urge to cough. The selected concentration for the main experiment was the highest bearable concentration without significant adverse subjective effects.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The fractional absorption was typically around 55% (variation less than 10% within and between individuals) and was found to be not detectably affected by variations in tidal volume, breathing frequency nor the existing blood ethanol concentration. The concentration of ethanol in expired air did not fall below 30%.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

Results varied from 52 -59% for a single subject exposed only to ethanol vapour over different experiments with different tidal volumes (0.58 -2.32/l) and different respiratory frequencies (9 -32/min).

In the larger experiment which looked at ethanol inhalation uptake after an oral dose, again aa range of 50 -56% of ethanol in air was absorbed by adult volunteers and fractional absorption was not affected by variations in tidal volume (0.7 to 2.1 litres), nor by the presence of systemic blood levels up to 50 times higher than that of inspired air. Absorption fractions were about 0.55 and the concentration in end expiratory air did not fall below some 30% of the inspired air. Respiratory uptakes were 8.3 -11.6g/hr (range of means across the 11 volunteer studies).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: study not suitable for deriving bioaccumulation potential.
Inspired ethanol is a significant contributor to elevations of blood alcohol concentration.
Executive summary:

In a study to determine the fractional uptake of ethanol during inhalation exposure, human volunteers were exposed to ethanol vapour concentrations of 10 -12mg/l (6000ppm) for periods of 1 hour. Experiments were done with and without a prior dose of ethanol by the oral route. The fractional absorption was typically around 55% (variation less than 10% within and between individuals) and was found to be not detectably affected by variations in tidal volume, breathing frequency nor the existing blood ethanol concentration. The concentration of ethanol in expired air did not fall below 30%.