Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic: example: CAS No: 105650-23-5 PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine).
PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is a heterocyclic amine and genotoxic carcinogen contaminant that occurs during the grilling and frying of meat and fish, through an interaction between sugars and creatine via the Maillard reaction. PhIP causes cancers of the prostate, mammary gland and colon in rodents. Dose-response modelling of the data for these three tumour types gives BMDL10 values of 0.48 mg/kg/day for the prostate tumours, 0.74 mg/kg/day for mammary tumours and 2.71 mg/kg/day for colon tumours. The lowest MOEs for prostate, mammary and colon tumours were 20,000, 40,000 and 150,000, respectively.
Carthew
Philip
P
Unilever Research, UK. publications@ilsieurope.be
DiNovi
Michael
M
Setzer
R Woodrow
RW
D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D003296:Cooking; D003627:Data Interpretation, Statistical; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D005506:Food Contamination / Q000032:analysis*; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D051379:Mice; D015233:Models, Statistical; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D051381:Rats
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine