Magnesium diethyl dicarbonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, study with sufficient documentation which meets basic scientific principles and contains enough detail to be able to judge the results reliable as a contribution to the understanding of the toxicokinetics of this substance.

Data source

Reference

Reference Type:

publication

Title:

Disappearance Rate of Ethanol from the Blood of Human Subjects: Implications in Forensic Toxicology.

Author:

Jones, A.W., Andersson, L.

Year:

1993

Bibliographic source:

J Forensic Sci, JFSCA 1993;38(1):104-118.

Materials and methods

Objective of study:

absorption

excretion

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

This publication details the results of a large number of controlled experiments examining the rate of ethanol elimination from humans against a large number of variables. This study also describes a specific set of experiments which specifically followed the elimination of ethanol following an oral dose in human volunteers. One part of this study relevant for the evaluation of the toxicokinetics is summarised here.

GLP compliance:

not specified

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:

no data

Radiolabelling:

no

Test animals

Species:

human

Sex:

male

Details on test animals or test system and environmental conditions:

Aged 20-60. Body weights 60-109kg
Subjects fasted overnight (8-10hrs) before experiment and ingested ethanol between 8:00 and 9:00am the following morning.

Administration / exposure

Route of administration:

other: drinking

Vehicle:

other: orange juice

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Justification for use and choice of vehicle (if other than water): More palatable. Note that in some experiments ethanol in the form of pure whisky was used.
- Concentration (if solution): 15-20% strength solution of ethanol

Doses / concentrations

Remarks:

Doses / Concentrations:
0.35, 0.51. 0.68, 0.85, 1.05g/kg

No. of animals per sex per dose / concentration:

150

Control animals:

no

Details on dosing and sampling:

Blood specimens were obtained by finger prick or indwelling venous catheter. For the former samples, ethanol was assayed by an automated enzymatic procedure. Venous blood samples were assayed by GC.

Statistics:

Mean and standard deviation. Error of GC method 1%, error or enzymatic method 3.2%.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Elimination rates obtained (whisky consumption):

Ethanol doseg/kg	N	Peak blood ethanol (mg/dl)	Mean slope of elimination curve('beta') mg/dl/hr	Standard deviationof 'beta'
0.51	16	75	11.4	0.75
0.68	48	91	12.6	1.2
0.85	16	131	14.6	0.9

The rate of elimination increased significantly with the dose.

The mean blood alcohol levels for driving under the influence (DUI) suspects was 1.88 +/- 0.748 mg/ml in males and 1.86 +/- 0.702 for females. The overall mean rate of alcohol elimination from DUI suspects was 0.191 +/- 0.049 mg/ml/hr with 95% limits spanning from 0.09 to 0.29 mg/ml/h.

The slowest rate of ethanol disappearance was in a healthy male who ingested 0.68 g ethanol per kg bodyweight after an 8 hr fast; the beta-slope was 9 mg/dL/h.  The fastest rate of disappearance was observed in a male chronic alcoholic during detoxification; the beta-slope was 36 mg/dL/h. 

The drugs that inhibited gastric secretion had no significant impact on ethanol metabolism/elimination.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results

Executive summary:

In a study which both contained original data and the results of other published studies, human volunteers were given varying oral doses of ethanol and the elimination rate followed by measuring decaying blood ethanol concentration. Ethanol was found to be rapidly eliminated with a typical elimination rate constant of 11 -15mg/dl/hr over the range of doses examined (0.5 -0.8g/kg). It was noted that the elimination rate increase slightly but significantly with dose and that the range of rate constants varied by a factor of 3 from 8 -13mg/dl/hr in the relatively large number of subjects studied.