Minimum tolerable exposure period and maximum threshold dietary intake of ochratoxin A for causing renal cancer in male Dark Agouti rats.
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.
Mantle
Peter G
PG
Centre for Environmental Policy, Imperial College London, South Kensington, London SW7 2AZ, UK. p.mantle@imperial.ac.uk
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000821:Animal Feed; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009793:Ochratoxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A