Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans

Abstract

The mycotoxin ochratoxin A (OTA) is a rodent carcinogen produced by species of the ubiquitous fungal genera Aspergillus and Penicillium. OTA is found in a variety of food items and as a consequence is also found in human plasma (average concentrations found in this study: 0.1±1 ng OTA/ml plasma). To improve the scienti®c basis for cancer risk assessment the toxicokinetic pro®le of OTA was studied in one human volunteer following ingestion of 395 ng 3 H-labeled OTA (3.8 lCi). A two-compartment open model consisting of a central compartment was found to best describe the in vivo data. This two-compartment model consisted of a fast elimination and distribution phase (T 1/2 about 20 h) followed by a slow elimination phase (renal clearance about 0.11 ml/min.) and a calculated plasma half-life of 35.55 days. This half-life was approximately eight times longer than that determined previously in rats. In addition, the intraindividual¯uctuation of OTA plasma levels was investigated in eight individuals over a period of 2 months. The concentrations determined ranged between 0.2 and 0.9 ng OTA/ml plasma. The plasma levels in some individuals remained nearly constant over time, while others varied considerably (e.g. increase of 0.4 ng/ml within 3 days, decrease of 0.3 ng/ml within 5 days) during the observation period. This intraindividual¯uctuation in OTA plasma levels, which may represent di erences in OTA exposure and/or metabolism, as well as the large di erence in plasma half-life in humans compared to rats must be taken into consideration when the results of rat cancer study data are extrapolated to humans for risk assessment purposes.

Biomarkers of human exposure to ochratoxin A

“…This contributes to the unreliability of correlations of dietary intake and serum levels. Part of the variation would be due to expected decreases in plasma concentrations after OTA is received in the food; plasma half life determined in one person was about 20 h during the first 6 days and 35.6 days from day 6 onwards (Studer-Rohr et al 2000). Considerable variation of serum levels of OTA over three years was observed in 20 persons in a city in Germany, with extreme variations in two people of 0.3-1.2 and 0.3-1.3 ng ml À1 (Märtlbauer et al 1996).…”

“…1N citric acid and 1M acetic acid were considered adequate (Solti et al 1997, Hassen et al 2004. Acidification of plasma with phosphoric acid followed by chloroform extraction as an efficient analytical procedure was demonstrated with plasma obtained from a human volunteer who ingested tritium labelled OTA (Studer-Rohr et al 2000). No significant radioactivity was found in the aqueous phase and >80% of the administered dose, identified as unchanged OTA after immunoaffinity column cleanup and liquid chromatography (LC), was found in the plasma 8 h after digestion, showing the overall analytical method was reliable for plasma analysis.…”

Ochratoxin A contamination of cereal grains and coffee in Hungary in the year 2001

“…StuderRohr et al (2000) found that orally administered OTA doses had a half-life of 840 hours in humans, which is much longer than the half-lives found in any other species. OTA could be detected in the blood even 240 days after a single intake of a high dose (Studer-Rohr et al, 2000;Petzinger and Ziegler, 2000). This unique kinetics of OTA may lead to increased accumulation of this mycotoxin in the human organism.…”

Ochratoxin A is not detectable in renal and testicular tumours

“…28 OTA half-life was only examined in 1 human volunteer and was reported to be 840 hours or 35.55 days. 29 OTA may have induced some DNA adducts in exposed patients; this may have induced malignant tumours years later after the initial OTA has been cleared. The absence of OTA in tissues may also be explained by the fact that animal carcinogens might not necessarily have the same effects and pathogenesis on humans.…”