Scope High‐level exposure to aflatoxin B1 (AFB1) is known to cause acute liver damage and fatality in animals and humans. The intakes actually causing this acute toxicity have so far been estimated based on AFB1 levels in contaminated foods or biomarkers in serum. The aim of the present study is to predict the doses causing acute liver toxicity of AFB1 in rats and humans by an in vitro–in silico testing strategy. Methods and results Physiologically based kinetic (PBK) models for AFB1 in rats and humans are developed. The models are used to translate in vitro concentration–response curves for cytotoxicity in primary rat and human hepatocytes to in vivo dose–response curves using reverse dosimetry. From these data, the dose levels at which toxicity would be expected are obtained and compared to toxic dose levels from available rat and human case studies on AFB1 toxicity. The results show that the in vitro–in silico testing strategy can predict dose levels causing acute toxicity of AFB1 in rats and human. Conclusions Quantitative in vitro in vivo extrapolation (QIVIVE) using PBK modeling‐based reverse dosimetry can predict AFB1 doses that cause acute liver toxicity in rats and human.

No abstract

Fumonisins (FB1+FB2) and deoxynivalenol (DON) are mycotoxins produced by Fusarium species that might be present in maize and maize products. Knowledge on their occurrence in nixtamalized maize from Mexico together with an accompanying risk assessment are scarce, while nixtamalized maize is an important food in Mexico. This study presents the occurrence of FB1 + FB2 and DON in nixtamalized maize samples collected in Mexico City and analyses their distribution and resulting estimated daily intake for Mexican consumers by a probabilistic approach using a two-dimensional Monte-Carlo simulation. The results obtained reveal that for FB1 + FB2, 47% of the Mexican men and 30% of the Mexican women might exceed the provisional tolerable daily intake (PMTDI) of 2 µg/kg bw/day for fumonisins and for DON, 9% of men and 5% of women would be exceeding the PMTDI of 1 µg/kg bw/day, corresponding to the high consumers. The results raise a flag for risk managers in Mexico, to consider regulations and interventions that lower mycotoxin levels in nixtamalized maize for human consumption.

The presence of mycotoxins in nixtamalized maize products from Mexico requires risk management actions. (this thesis) 2. Estimation of a point of departure for risk assessment on induction of acute liver toxicity by aflatoxin B1 in humans requires physiological based kinetic (PBK) modeling. (this thesis) 3. Recommending alcoholic beverage consumption for its health benefits reflects a science failure. 4. Artificial intelligence and big data analysis will uncover complex models, hidden to intuitive human intelligence. 5. A scientific education and career should be accessible to everyone. 6. Diet and lifestyle changes are a collective task requiring political actions.Propositions belonging to this thesis, entitled:'Mode-of-action based risk assessment of exposure to mycotoxins in nixtamalized maize products from Mexico City'