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Propionic acid occurs naturally in foods, and together with other short-chain fatty acids, it can be ubiquitous found in the gastrointestinal tract of humans and other mammals as endproducts of microbial digestion (Mellon 2000). Propionic acid occurs physiologically as an intermediate in breakdown of odd-numbered fatty acids, cholesterol and amino acids (valine, isoleucine, norleucin, methionine, and threonine). Up to four percent of volatile fatty acids in blood of humans (0.28-0.32 mmol/l) can be attributed to propionic acid (Baessler 1959).

The metabolism of propionic acid has been thoroughly studied. Propionic acid is readily absorbed in the gastrointestinal tract and metabolized in mammals rapidly and entirely. In rats, the rate of absorption in the intestines is similar to that of acetates. Irrespective of the route of exposure, parent propionic acid is not identified in urine even after dosing with high doses (Baessler 1959). Studies with radioactively (C11) labelled propionic acid indicated that up to 54% of the carbon atoms in propionic acid end up in exhaled carbondioxide. The rest ends up in glucose, glycogen, lipids, amino acids, and proteins (Buchanan 1943; Eckstein 1933; Deuel 1935). Small to marked increases in liver glycogen has been reported in white rats 4 -7 hours post oral exposure to propionates (Eckstein 1933; Deuel et al 1943). Besides the liver, which is the main organ for metabolism, propionic acid metabolism also occurs in the kidneys, heart, muscles and adipose tissues (Baessler 1959). The hepatic metabolic rate of propionic acid for a 70 kg man was roughly estimated by Baessler (1959) on the working assumption that the metabolisation rate of the human liver equals that of the rat. Mitochondria from 1 g of rat liver have a turnover at 38°C of 31.5 μmol 14 CO3- per hour. For a 70 kg man with a liver weight of 1925 g, this corresponds to turnover of 4.5 g propionic acid per hour.

The metabolism of propionic acid starts with the catalytic conjugation with Coenzyme A to propionyl-CoA. The conjugation step is catalysed by acetate thiokinase with the consumption ATP. In the next step catalysed by the propionyl carboxylase, activated CO2 (carbonyl phosphate) is incorporated in propionyl-CoA to form methylmalonyl-CoA. In the subsequent rate determining transcarboxylisation step, catalysed by the Vit B-dependent methylmalonylmutase, methylmalonyl-CoA is converted to succinyl -CoA. After deacylation, succinate is released which can be incorporated in the citric acid cycle.

  

In ruminants, as well as in the adipose tissue of rats, propionic acid may also be metabolized after the activating condensation with Coenzyme A via condensation with acetyl-CoA to beta-Ketovalerianyl- CoA. Beta-Ketovalerianyl- CoA can eventually be incorporated in the lipid cycle (Baessler 1959).

 

Propionic acid inhibits the production of acetyl CoA in vitro. Propionic acid metabolism eventually leads to increased supply of oxalacetate. Oxalacetate conjugates with acetic acid thus preventing the recondensation of C2 fragments to acetoacetate. Another plausible mechanism may be via the competition of propionic acid with acetic acid for Coenzyme A. Furthermore, the metabolic activation processes for propionic acid and acetic acid may compete for the catalyzing enzyme acetate thiokinase. In vivo, however, it is not expected that extrinsicly added propionic acid would significantly interfere in the supply of acetic-CoA since the turn over of acetyl CoA in vivo is very high and propionic acid is readily and quickly metabolised such that systemically high concentrations of propionic acid capable of competing with acetic acid system are not attainable.