reaction mass of sodium acetate, monoethylene glycol and diethylene glycol

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well reported published study with sufficient information to judge it as reliable

Data source

Reference

Reference Type:

publication

Title:

Kinetic aspects of acetate metabolism in healthy humans

Author:

Pouteau E, Poloquet H, Maugeais P, Champ M, Dumon H, Nguyen P, Krempf M

Year:

1996

Bibliographic source:

Am J Physiol 271 (1 part 1) E58-64

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Human volunteer study to assess kinetics of plasma acetate in humans

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium acetate

EC Number:

204-823-8

EC Name:

Sodium acetate

Cas Number:

127-09-3

Molecular formula:

C2H4O2.Na

IUPAC Name:

sodium acetate

Details on test material:

Radio labelled (1-C13), 99% enriched supplied by Tracer Technologies, Somerville, MA, USA)

Method

Type of population:

other: young, healthy adults

Subjects:

- Number of subjects exposed: 11 (6 study one, 5 study 2)
- Sex: male and female
- Age: 20-28 years
- Known diseases: disease free and not on medication.
- Other: Body mass indices: 20.5 +/-0.9

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

other: intravenous

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

STUDY 1: Catheter in vein of one arm for infusion. Prime was 19.25umol/kg followed by an infusion of 0.57 +/- 0.02umol/kg/min for 3 hours. The bicarbonate pool was also primed with 40umol/kg of NaH[13]CO3.
STUDY 2: Via enteral feeding tube into stomach for 3 hours followed by intravenous infusion as above.

Examinations:

BOTH STUDIES:
- Venous blood sampled from catheter in wrist of same arm receiving infusion. Arterial blood collected from catheter in wrist of other arm (hand heated to 55C on electric pad.)
- Expired air samples assessed.

SAMPLING TIMES:
-Study 1: 0, 90, 120, 135, 150, 165 minutes.
-Study 2: 0, 90, 120, 135, 150, 165, 240 ,270, 300, 315, 330, 345, 360 minutes.

Results and discussion

Results of examinations:

No differences were found between the arterialised and venous tracer enrichments from the arm although arterialised acetate concentrations were soewhat higher (74 +/-12 versus 59 +/-14 umol/l). Total body flux of acetate was 8.4umol/kg/min of which 69 +/-5% was oxidised. In the second study first pass removal within the splanchic bed was 60 +/-7%.

Any other information on results incl. tables

The authors noted that acetate contributes significantly to the energy supply of the body and is mainly used by the liver when produced (or present) in the gut. Clearly acetate is an important endogenous substance.

Applicant's summary and conclusion

Executive summary:

In a study to assess the kinetic aspects of acetate metabolism in humans, volunteers were exposed to acetate either by intravenous and/or gastric infusion. No differences were found between the arterialised and venous tracer enrichments from the arm although arterialised acetate concentrations were somewhat higher (74 +/-12 versus 59 +/-14 umol/l) (suggesting that the hand muscles used but did not produce acetate). Total body flux of acetate was 8.4umol/kg/min of which 69 +/-5% was oxidised. In the gastric dosing study first pass removal within the splanchic bed was 60 +/-7%. Acetate contributes significantly to the energy supply of the body and is mainly used by the liver when produced (or present) in the gut. Clearly acetate is an important endogenous substance.