Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats

Li, S.; Marquardt, R. R.; Frohlich, A. A.; Vitti, Trieste G.; Crow, G. H.

doi:10.1006/taap.1997.8155

Cited by 124 publications

(105 citation statements)

References 29 publications

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“…The far weaker bondage of OTα to blood serum proteins and therefore faster excretion is generally considered to be another key feature for its much lower toxicity compared with OTA [138,139]. …”

Section: Systemic Occurrence and Excretion Of Ota In Ruminantsmentioning

confidence: 99%

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

Mobashar

Hummel

Blank

et al. 2010

Toxins

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Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2–6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant.

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Section: Systemic Occurrence and Excretion Of Ota In Ruminantsmentioning

confidence: 99%

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

Mobashar

Hummel

Blank

et al. 2010

Toxins

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“…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%

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

Studer-Rohr

Schlatter

Dietrich

2000

Archives of Toxicology

225

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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“…However, very few analytical techniques have been specifically validated for application in biological samples obtained from rats . In many cases, the entire validation data has not been reported or the methods have been developed and validated in other animal species, such as a pig, or even in food commodities, and then applied to rat samples (Alvarez et al, 2004;Aoudia et al, 2008;Domijan et al, 2005;Kerkadi et al, 1998;Li et al, 1997;Mantle, 2008;Miljkovic et al, 2003). This could be acceptable for some objectives but, as reported in the S3A ICH Guideline for drugs (ICH S3A), the analytical technique method used in kinetic studies should always be validated in each type of sample and in each animal species in order to investigate possible interferences by endogenous components.…”

Section: Analytical Techniques For Ochratoxin a Toxicokinetic Studiesmentioning

confidence: 99%

“…In the main rat kinetic studies performed to date with HPLC-FLD or HPLC-MS, complete data from the validation for each matrix is not given or the extraction and/or detection methods were developed for other species (Li et al, 1997;Mantle et al, 2008;. In some kinetic studies in which a specifically validated method was used, only plasma, kidney and liver levels were measured (Vettorazzi et al, 2009(Vettorazzi et al, , 2010(Vettorazzi et al, , 2011.…”

Section: Analytical Techniques For Ochratoxin a Toxicokinetic Studiesmentioning

confidence: 99%

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

Vettorazzi

González-Peñas

Ceráin

2014

Food and Chemical Toxicology

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Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety of foodstuffs. It is nephrotoxic in all of the mammalian species tested, being the pig the most sensitive one; among rodents, rats are the most susceptible to OTA carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism and excretion of xenobiotics, is an important tool for the extrapolation of animal toxicity data. The most important kinetic studies performed with OTA in rats have been reviewed, together with the different methods used for OTA quantification in biological matrices. Thirteen studies in Wistar, Sprague-Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or HPLC-MS have been summarized. Very often methods validated for food have been directly applied to tissues. Strain, sex and age differences have been detected but the interpretation is difficult due to the different experimental conditions, and the connection of the several factors that may account for these differences.

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Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats

Cited by 124 publications

References 29 publications

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

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

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

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