Toxicokinetics of ochratoxin A in several species and its plasma‐binding properties

Hagelberg, Sigrid; Hult, Karl; Fuchs, Radovan

doi:10.1002/jat.2550090204

Cited by 244 publications

(205 citation statements)

References 13 publications

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“…The bioavailability of OTA would be expected to be much lower when it is ingested as a food contaminant. Indeed, considerable species di erences in the bioavailability and gastrointestinal absorption of orally administered OTA have been reported by Hagelberg et al (1989), who found, in comparison with OTA administered i.v. dissolved in 51 mM NaHCO 3 , only 97%, 44% and 57% of orally administered OTA in the blood of mice, rats and monkeys, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…2). OTA reabsorption in the kidney was also suggested by the fact that the overall clearance for OTA was much lower than clearance of freely ®lterable nonreabsorbable inulin (Hagelberg et al 1989). …”

Section: Discussionmentioning

confidence: 99%

“…This observation may be explained by a stabilizing e ect of proteins on the OTA molecule, which otherwise degrades in alkaline medium and in the presence of water (T.J. Jansen, Vicam, USA; R. Dick, Swiss Federal O ce of Public Health, Switzerland; personal communications). OTA has also been demonstrated to bind to human plasma proteins (Hagelberg et al 1989). It was therefore assumed that human plasma proteins would stabilize the radiolabeled OTA in a comparable fashion as determined with BSA in vitro.…”

Section: Methodsmentioning

confidence: 99%

“…However, at present human cancer risk evaluation based on extrapolation from animal data is di cult, as large species di erences are known to exist; for example, plasma halflives determined in various species range from 0.68 h in ®sh to 510 h in monkeys (Hagelberg et al 1989;Li et al 1997). One of the main factors in¯uencing plasma halflife is the capacity of OTA to bind to plasma proteins, which appears to di er among species (Chang and Chu 1977;Galtier et al 1979;Hagelberg et al 1989).…”

Section: Introductionmentioning

confidence: 99%

“…One of the main factors in¯uencing plasma halflife is the capacity of OTA to bind to plasma proteins, which appears to di er among species (Chang and Chu 1977;Galtier et al 1979;Hagelberg et al 1989). Consequently the values for renal clearance may also di er considerably (Hagelberg et al 1989;Li et al 1997).…”

Section: Introductionmentioning

confidence: 99%

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

Studer-Rohr

Schlatter

Dietrich

2000

Archives of Toxicology

220

139

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Studer-Rohr

Schlatter

Dietrich

2000

Archives of Toxicology

220

139

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Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother

Petkova-Bocharova¹,

Stoichev²,

Chernozemsky³

et al. 1998

Environ. Mol. Mutagen.

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Placental and lactational transfer of ochratoxin A in rats

Hallén

Breitholtz‐Emanuelsson

Hult

et al. 1998

Nat. Toxins

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The placental and lactational transfer of ochratoxin A (OA) was investigated in a cross‐fostering study in rats. Dams were given 50 μg OA−1 kg body weight by gastric intubations 5 times a week for 2 weeks before mating, during gestation and then 7 days a week during lactation. Neonates from OA‐treated dams were cross‐fostered at birth to control dams treated with only vehicle. In the same way, neonates from control dams were cross‐fostered to OA‐treated dams. Treatment with OA did not result in any effects on birth weight or growth development of the pups during the first 21 days of life. There were no effects on milk quality as measured by milk lipids, protein or lactose concentrations, or on milk production, assessed by the mammary gland content of RNA and DNA. A mean milk:blood ratio of approximately 0.6 was found. The dose of OA from milk to the suckling pup at 14 days of age can be calculated to about 50 μg kg−1 body weight−1 day, which is similar to the dose given to the dams. Pups exposed to OA only via milk had blood and kidney levels of OA approximately 3 times higher than their dams, indicating a high absorption and/or a low excretion of OA in the sucklings. At 14 days of age the highest blood and kidney levels of OA were found in offspring exposed both via placenta and milk, with the highest contribution from milk. Offspring exposed only via milk had about 4–5 times higher levels of OA in blood and kidney compared to offspring exposed only via placenta. As milk could be a significant source of OA exposure in newborns, adverse health effects resulting from postnatal exposure should be studied and evaluated in the risk assessment of OA. Copyright © 1998 John Wiley & Sons, Ltd.

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Toxicokinetics of ochratoxin A in several species and its plasma‐binding properties

Cited by 244 publications

References 13 publications

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

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

Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother

Placental and lactational transfer of ochratoxin A in rats

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