Minimum tolerable exposure period and maximum threshold dietary intake of ochratoxin A for causing renal cancer in male Dark Agouti rats |
| |
Authors: | Peter G Mantle |
| |
Institution: | aCentre for Environmental Policy, Imperial College London, South Kensington, London SW7 2AZ, UK |
| |
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 7 μg ochratoxin A/day for Dark Agouti rats for up to 2 years, during which mean daily dose commenced at 50 μg/kg, but later for adults was in the range 30–20 μg/kg. This data doubles the daily in vivo threshold dose from the NTP study ( 15 μg/kg), and could influence human risk assessment. An at least 3 month threshold period for exposure to exceptionally high daily OTA intake (90 μg; 640–450 μg/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. |
| |
Keywords: | Latency Threshold Renal carcinoma Dietary ochratoxin A Dark Agouti rat Carcinogenesis |
本文献已被 ScienceDirect 等数据库收录! |
|