Ochratoxin A: previous risk assessments and issues arising.
Ochratoxin A (OTA) causes nephropathy in all species tested with large sex and species differences in potency, pigs being most sensitive. It has been linked to Balkan endemic nephropathy (BEN) in humans. Embryotoxicity, teratogenicity, and immunotoxicity occur only at doses higher than those causing nephrotoxicity. OTA has long serum half-lives in various species including humans. OTA produced renal tumours in mice and rats. The male rat was most sensitive, renal carcinomas occurring after 70 microg/kg bw per day but not 21 microg/kg bw per day. OTA was not mutagenic in most studies in bacteria and mammalian cells, but produced DNA damage and chromosomal aberrations in mammalian cells in vitro, and in mice in vivo. DNA adducts found in the kidneys of mice and rats dosed with OTA, did not contain fragments of OTA. OTA in food has been evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and by the EC Scientific Committee on Food (SCF). JECFA established a provisional tolerable weekly intake (PTWI) of 100 ng/kg bw based on the LOEL for renal effects in pigs. Conversely, SCF recommended reducing exposure to OTA as much as possible, e.g. below 5 ng/kg bw per day. Both committees recommended further studies to clarify the mechanism by which OTA induces nephrotoxicity and carcinogenicity.
Walker
Ron
R
School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK. profronwalker@aol.com
Larsen
John Christian
JC
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005506:Food Contamination; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D051379:Mice; D009793:Ochratoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment / Q000379:methods; D013045:Species Specificity; D013552:Swine
D002273:Carcinogens; D009793:Ochratoxins; C025589:ochratoxin A