Lifetime, low-dose ochratoxin A dietary study on renal carcinogenesis in male Fischer rats

Abstract

Carcinoma arising from male rat renal parenchyma is an aspect of the nephrotoxicity of ochratoxin A (OTA) and is a factor in considering application of animal data to human health risk assessment. We present experimental data to complement already published and to complete dose–response findings for dietary OTA. From 34 rats, only four unilateral renal carcinomas (12%) developed during a 2-year exposure to dietary OTA, contaminated to give the same weekly overall dosage as in the 50 µg kg⁻¹ gavage-dosing regimen of an NTP study (30%). Statistical analysis included adjustment for premature leukaemia deaths, resulting in the carcinoma incidence of 35% (10–81%), and showed no significant difference from NTP (incidence of 43% (23–49%)) due to the smaller number of animals. However, absence of microscopic neoplastic renal lesions in premature decedents argues for minimal effect of the 47% leukaemia on carcinoma expression in the present experiment. This would fit with previously published findings showing significantly less carcinoma expression from a regimen administering an OTA dose in feed than was achieved by a lower dose by gavage as in the NTP study. It is concluded that chronic gavage administration of OTA to male rats may optimise carcinoma incidence for toxicological purposes, but that the dietary mode gives data more applicable to assessing putative health risk for humans.

Keywords:

• toxicology
• in vivo
• ochratoxin A

Acknowledgements

We gratefully acknowledge the skilled animal husbandry from staff of Imperial College Central Biomedical Services; histological preparation at the Breast Pathology Laboratory, Guy's Hospital, London, and the European Union for part-funding (Contract No. QLK1-CT-2001-011614).