PhIP is formed at high temperatures from the reaction between creatine or creatinine (found in muscle meats), amino acids, and sugar.

Different cooking methods for meat (broiling, grilling, frying, roasting, pan drippings) all contribute to formation of PhIP.

Studies examining the amount of PhIP in cooked meats have shown that high levels of exposure are possible.

One method used is a Food Frequency Questionaries (FFQ) which surveys a population on their estimated consumption of cooked meats.

[16] An in vivo study found mice injected with 5, 10, 12, 18, 20, 24, 28, 32, or 36 mg/kg bw showed a strong correlation between consumption of PhIP and genetic damage.

Therefore, a margin of exposure (MOE) based on the benchmark lower confidence limit (BMDL) reference has been developed for PhIP in relation to prostate and mammary carcinomas.

[18] Numerous in vivo and in vitro studies have demonstrated that PhIP is a potent mutagen and can induce tumors of multiple sites in animal models.

PhIP was positive in bacterial (Ames) test and induced chromosomal abnormalities in human and Chinese hamster cells in vitro.

[19] Also, an increasing number of epidemiological studies have evaluated the association of well-done meat intake and HCA exposure with cancer risk in humans.

In humans receiving a dose of PhIP equivalent to that found in very well-done chicken, DNA and protein adducts were formed in the colon and blood.