Acetic anhydride

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non-guideline, human experimental study, published in peer reviewed literature, minor restrictions in design but otherwise adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Sodium acetate induces a metabolic alkalosis but not the increase in fatty acid oxidation observed following bicarbonate ingestion in humans

Author:

Smith GI, Jeukendrup AE and Ball D

Year:

2007

Bibliographic source:

J. Nutr. 137:1750-1756

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:

The rate of oxidation of exogenous acetate was determined in human volunteers.

GLP compliance:

not specified

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:

- Name of test materials (as cited in study report):
Sodium acetate / NaAc (trihydrate)
- Physical state: not reported
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
- Lot/batch No.: not reported
- Radiochemical purity (if radiolabelling): not reported
- 13C labelling: 2 mg[1,2-13C]NaAc/kg bw added to NaAc drink giving enrichments of 707.6±69.2δ/1000 vs. PDB determined by elemental analyser-isotope ratio mass spectrophotometry. NaH13CO3 at 0.064 mg/kg bw was infused immediately before drinking NaAc to prime the bicarbonate pool.

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 8
- Sex: 6 male and 2 female
- Age: 29±3 years
- Height: 1.76±0.03 m
- Body weight: 71.62±5.29 kg
- Known diseases: none (healthy volunteers)

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

other: oral: Sodium acetate... (see attached file)

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

In a randomised, crossover, single-blind experiment, on two occasions, at least 1 week apart, each volunteer drank 500 mL low-energy cordial (42 kJ/500 mL; 2.5 g carbohydrate/500 mL) which contained either NaAc (trihydrate) or NaHCo3 at 2 mmol/kg bw. The volunteers rested for at least 1 hour prior to drinking. The volunteers minimised 13C glycogen stores by at least 1 hour intense exercise 5 days prior to each visit. Volunteers' dietary intake was identical for each 5 day period prior to each experiment. During the experiment, volunteers avoided eating food derived from carbohydrates from C4 plants. Volunteers fasted overnight prior to experiment and drank 500 mL tap water prior to experiments.

Examinations:

BREATH SAMPLES:
-collection times: 2 consecutive pre-ingestion respiratory gas samples collected followed by samples every 30 minutes for 3 hours
- parameters measured: 13C content (continuous flow isotope ratio MS), % oxygen and % carbon dioxide (gas analyser), volume (dry gas meter), temperature (thermocouple within dry gas meter).
URINE SAMPLES:
-collection times: 1 pre-ingestion sample and one after 3 hours (complete voiding of bladder)
- parameters measured: volume, pH, partial pressure CO2, urinary bicarbonate concentration (calculated) and acetate concentration.
BLOOD SAMPLES:
-collection times: 1 pre-ingestion sample followed by samples every 30 minutes for 3 hours
- parameters measured: pH, base excess, O2 % saturation of haemoglobin, partial pressure of CO2, blood bicarbonate concentration, lactate, glycerol, FFA, acetate and haemoglobin concentrations

Results and discussion

Clinical signs:

Sodium acetate induced mild alkalosis, increased energy expenditure (p <0.05) but had no effect on fat or carbohydrate utilisation.

Results of examinations:

Ingestion of sodium acetate (2 mmol/kg bodyweight) resulted in a transient increase in plasma and urinary acetate concentrations. 80.1 ± 2.3% of the administered acetate was oxidized to CO2 and exhaled within 3h, 0.60 ± 0.09% was excreted unchanged in urine i.e. ~0.5 mg/kg bw acetate is removed per minute via the citric acid cycle.

Applicant's summary and conclusion

Conclusions:

Following ingestion of 2 mmol/kg bw of acetate, 80.1% of dose was oxidised over the subsequent 3 hours.