Renal tumourigenesis in male rats in response to chronic dietary ochratoxin A
Peter Mantle1, Elena Kulinskaya, Sandra Nestler
1Department of Environmental Science and Technology, Imperial College London, UK. p.mantle@imperial.ac.uk
Abstract:
The potency of ochratoxin A (OTA) as a renal carcinogen in the rat in response to lifetime administration by oral gavage is a basis of current concern about possible human risk from dietary exposure to the mycotoxin. In this study, dietary delivery of OTA was chosen as the mode of administration, since this mimics human intake of OTA-contaminated food more accurately than gastric intubation. Young male Fischer rats were given approximately 300 microg OTA/kg body weight (bwt) daily until they reached 333 g; thereafter their daily intake was held at about 100 microg. Renal tumours, mostly unilateral carcinomas, were first discovered at week 75 and total incidence reached 25%. Statistical comparison of total carcinoma incidence (20%) in this study with that of the classic US NTP study suggested that OTA was significantly less carcinogenic when administered in feed than when given by oral gavage. The finding may moderate perceptions of a putative risk of trace amounts of OTA in some foodstuffs to human health.
Insights
Ochratoxin A (OTA) is a kidney carcinogen. When administered through diet, OTA showed less carcinogenic potential in rats compared to oral gavage, potentially lowering human health risk concerns from contaminated food.
Area of Science:
- Toxicology
- Carcinogenesis
- Food Safety
Background:
- Ochratoxin A (OTA) is a mycotoxin with known renal carcinogenicity in rats via oral gavage.
- Dietary exposure is a more relevant route for assessing human risk from OTA-contaminated food.
- Previous studies established OTA's carcinogenic potential through specific administration methods.
Purpose of the Study:
- To evaluate the carcinogenic potency of Ochratoxin A (OTA) when administered via diet in rats.
- To compare the dietary route's carcinogenicity with the established oral gavage method.
- To reassess the potential human health risks associated with dietary exposure to OTA.
Main Methods:
- Young male Fischer rats were administered OTA daily through their diet.
- Dosage was adjusted based on body weight: ~300 microg/kg bwt until 333 g, then ~100 microg/kg bwt.
- Tumor incidence was monitored over time, with statistical comparison to historical oral gavage data.
Main Results:
- Renal tumors, primarily unilateral carcinomas, were observed starting at week 75.
- The overall incidence of renal tumors reached 25% in the study population.
- A statistically significant lower incidence of total carcinomas (20%) was noted compared to oral gavage studies.
Conclusions:
- Dietary administration of Ochratoxin A (OTA) in rats resulted in a lower incidence of renal carcinomas than oral gavage.
- OTA appears to be significantly less carcinogenic when delivered via feed compared to oral gavage.
- These findings may moderate concerns regarding the human health risks posed by trace amounts of dietary OTA.
