Minimum tolerable exposure period and maximum threshold dietary intake of ochratoxin A for causing renal cancer in male Dark Agouti rats

Food Chem Toxicol. 2009 Oct;47(10):2419-24. doi: 10.1016/j.fct.2009.05.043. Epub 2009 Jul 3.

Abstract

In rats fed dietary ochratoxin A (5 ppm for 3, 6 or 9 months) no renal tumours occurred throughout natural life of the group treated for 3 months, during which the ochratoxin dose was 3 times that in the high dose group of the NTP study. Bilateral renal carcinoma occurred in one rat in the 6 month group. Four rats treated for 9 months developed unilateral renal carcinoma. Overall latency between ceasing toxin exposure and discovering tumours was 35-97 weeks. Experimental verification of a 'no observable effect level' was made for feed containing 400 ppb, equivalent to approximately 7 microg ochratoxin A/day for Dark Agouti rats for up to 2 years, during which mean daily dose commenced at approximately 50 microg/kg, but later for adults was in the range 30-20 microg/kg. This data doubles the daily in vivo threshold dose from the NTP study ( approximately 15 microg/kg), and could influence human risk assessment. An at least 3 month threshold period for exposure to exceptionally high daily OTA intake (90 microg; 640-450 microg/kg) raises doubts over interpretation of experimental molecular data for OTA exposure at lower dose for up to 3 months in studies aimed at understanding carcinogenic mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced*
  • Adenocarcinoma / pathology
  • Animal Feed
  • Animals
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Diet
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Kidney Neoplasms / chemically induced*
  • Kidney Neoplasms / pathology
  • Longevity / drug effects
  • Male
  • Mycotoxins / administration & dosage
  • Mycotoxins / toxicity*
  • Ochratoxins / administration & dosage
  • Ochratoxins / toxicity*
  • Rats
  • Rats, Inbred Strains
  • Time Factors

Substances

  • Carcinogens
  • Mycotoxins
  • Ochratoxins
  • ochratoxin A