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.
|
Authors | Peter G Mantle |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 47
Issue 10
Pg. 2419-24
(Oct 2009)
ISSN: 1873-6351 [Electronic] England |
PMID | 19577606
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Carcinogens
- Mycotoxins
- Ochratoxins
- ochratoxin A
|
Topics |
- Adenocarcinoma
(chemically induced, pathology)
- Animal Feed
- Animals
- Carcinogens
(administration & dosage, toxicity)
- Diet
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Kidney Neoplasms
(chemically induced, pathology)
- Longevity
(drug effects)
- Male
- Mycotoxins
(administration & dosage, toxicity)
- Ochratoxins
(administration & dosage, toxicity)
- Rats
- Rats, Inbred Strains
- Time Factors
|