Ochratoxin A

Executive Summary

Abstract

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment on ochratoxin A (hereinafter referred to as OTA) as a self-tasking risk assessment. OTA is a mycotoxin produced by fungal species such as Aspergillus ochraceus and Penicilium verrucosum, which occur mainly in stored foods. Food contamination with OTA has been reported in various food commodities including cereal, coffee, cocoa, beer and wine. Nephrotoxicity was observed in all the animal species examined in the subacute toxicity studies. Pathological changes observed in the studies are karyomegaly and cytomegaly as well as tubular atrophy and degeneration in proximal tubules at the outer zone of renal medulla. The dose- and treatment period-dependent changes were observed in kidneys in rats and pigs. In chronic toxicity/carcinogenicity studies with oral administration, tumor induction was observed at the outer zone of renal medulla in rodents, mainly in male rats. Chromosome aberration was observed both in in vitro and in vivo genotoxicity studies, but gene point mutation was not detected. After reviewing the results of various toxicological studies, FSCJ considered that OTA is a non-genotoxic carcinogen acting indirectly on DNA, and that tolerable daily intake (TDI) is able to be specified for OTA. Regarding non-carcinogenic toxicity of OTA, the effects observed at the lowest dose in various studies were decreased ability to concentrate urine and degenerative changes in epithelial cells of the tubules observed in a 120-day subacute toxicity study in pigs. The lowest-observed-adverse-effect level (LOAEL) in these studies was set at 8 µg/kg bw/day. FSCJ specified the TDI of 16 ng/kg bw/day, applying an uncertainty factor of 500 (10 for species difference, 10 for individual difference and 5 for the use of LOAEL based on irreversible renal failure indices) to the LOAEL. Regarding carcinogenicity of OTA, FSCJ specified the TDI of 15 ng/kg bw/day, applying an uncertainty factor of 1000 (10 for species difference, 10 for individual difference and 10 for carcinogenicity) to the no-observed-adverse-effect level (NOAEL) of 15 µg/kg bw/day, which was derived from a two-year carcinogenicity study in rats (administered 5 times a week at 21 µg/kg bw) performed by the National Toxicology Program (NTP). The estimated exposure levels of OTA in Japan for average (the 50th percentile) and high risk consumers (the 95th percentile) are 0.14 ng/kg bw/day and 2.21 ng/kg bw/day, respectively. These estimations suggest the intake of OTA to be below the TDI even in the high risk consumers. Therefore, FSCJ considers that no apparent adverse effect is expected in Japan from the current risk estimate. OTA-producing fungi grow in agricultural products and food under different environmental conditions. OTA contamination in these products varies depending on environmental conditions such as climate. Therefore, the risk management organizations are encouraged to monitor OTA contamination in foods continuously. The monitoring is a key importance to consider the necessity of the regulation for OTA.