acramer's version from 2018-02-27 22:06


Question Answer
how do OTA and ROS (reactive oxygen species) relate?inc doses of OTA lead to inc doses of ROS. ROS causes DNA damage. If we add an antioxidant (Vit E aka alpha-tocopherol), we see less ROS formation. ROS are one of the ways OTA leads to mutagenicity. (kirks notes said; See GSH (intracellular antioxidant glutathione) depletion in different cell lines)
list of problems OTA causesProximal tubule damage (the primary target), Karyomegaly, Desquamation (skin peeling), focal degeneration, Focal peri-tubular fibrosis
Risk assessment: so we know OTA causes renal damage and tumors etc. so how do you determine how bad these things are in a quantifiable way?need to look at NOEL and LOAEL. Then figure out a uncertainty factor. So if sthing comes up positive on the AMES test or some of the other tests, then we DRASTICALLY inc the uncertainty effect (remember how anything above a 100 was iffy? well for OTA they made it 450). so with a bunch of other calculations they came up with a provisional tolerable weekly intake (meaning we should prolly be ok with an intake of whatever that PTWI was determined to be)
Conclusions of OTA risk assessment..what are the conclusions they came to after all the testing they did?(1) OTA is a frequently occurring food and feed contaminant (2) Intoxications in farm animals are reported in pigs and poultry (3) Toxicological testing indicated a specific renal toxicity, driven by the accumulation of the compound in proximal tubular cells followed by tubular injury (4) A typical pathological marker is karyomegaly in proximal tubular cells (5) Genotoxicity and carcinogenicity testing revealed genotoxic and epigenetic toxic mechanisms (6) A recent rodent bioassay confirmed the induction of renal cells carcinomas (7) The ADI/TDI/TWI derived from previous rodent studies amounts to 100 ng/kg bw (8) Exposure assessment indicates that children may exceed this PTWI (provisional tolerable weekly intake) - the uncertainty is increased because OTA is also excreted with breast milk
what is a typical pathological marker of OTA tox?karyomegaly in proximal tubular cells