Dietary intake of methylmercury from fish was estimated via Monte Carlo simulation using data for methylmercury concentrations in 210 fish samples and data regarding fish consumption extracted from the Japanese National Health and Nutrition Survey. The fish analyzed were classified into 5 groups according to categories used in the survey. The distribution of consumption of fish from each group was used without fitting to statistical distributions. A log-normal distribution was fitted to the distribution of methylmercury concentration in each fish group. Two random numbers that followed these distributions were generated, and a trial value was calculated by multiplying these random numbers. The trial value was divided by the body weight (50 kg) to arrive at an estimate of dietary methylmercury intake. A total of 100,000 Monte Carlo simulation iterations were performed. The estimated mean daily intake of methylmercury was 0.093 µg/kg body weight (bw)/day. This value is well below the tolerable daily intake of 0.292 µg/kg bw/day calculated from the tolerable weekly intake (2.0 µg/kg bw/week) established by the Food Safety Commission of Japan. The probability that the daily intake of methylmercury exceeds the tolerable daily intake was 7.6%. As there are no data regarding fish consumption for consecutive days, estimation of the weekly intake of methylmercury is a subject for future studies.
Cytochrome P450 (CYP)-mediated metabolisms are often associated with biological and toxicological events of chemicals. A major hepatic enzyme, CYP3A4, showed clear distinctions on their catalyses even among ligands having resemble structures. To better understand mechanisms of their distinct catalyses, possible associations of ligand interactions at specific parts of CYP3A4 residues were investigated using CYP3A4-Template system developed (DMPK 2019 and 2020). A placement was available selectively for CYP3A4-mediated R-thalidomide 5-oxidation on Template, but not for the 5’-oxidation and the S-isomer oxidations. Similar placements were generated for pomalidomide (4-amino-thalidomide), but not for a poor ligand, lenalidomide (3-deoxy-pomalidomide). The latter ligand took placements lacking IJK-Interaction or sticking the 4-amino part beyond the facial-side wall on Template. A placement was available for the tert-butyl oxidation of terfenadine, but not for an analog, ebastine. Their interactions with upper-Cavity-2 residue were expected to differ at their sites of oxygen substituents. Some phenolic antioxidants behave distinctly toward biological oxidations in vitro and in vivo. Butylated hydroxytoluene is oxidized to the peroxy-derivative in vitro, but solely to the oxidized metabolites at the benzyl and tert-butyl methyl positions in vivo. Involvement of CYP3A4 were suggested for all the three reactions from the placements on Template. Tocopherols were also applied on Template for the oxidations for chroman and side-chain terminals. The primary placement was suggested to undergo the futile-recycling through formation of the peroxide intermediate subsequently to lead the substantial lack of the CYP3A4-mediated oxidation. These data suggest the effectiveness of CYP3A4-Template assessment to understand the causal basis of poor oxidations and also to verify the in vivo contribution of CYP3A4-mediated peroxidative reactions.
The Food Safety Commission of Japan (FSCJ) updated a risk assessment on antimicrobial-resistant bacteria arising from the use of a veterinary medicinal product, colistin sulfate, in cattle and pigs, according to the “Assessment Guideline for the Effect of Food on Human Health Regarding Antimicrobial-Resistant Bacteria Selected by Antimicrobial Use in Food-producing Animals” (FSCJ, September 30, 2004). Both Escherichia coli (E. coli) and Salmonella enterica subsp. enterica (Salmonella) were potential antimicrobial-resistant bacteria. In cases of occurrences of human infectious diseases due to the bacteria in foods derived from livestock, these resistant bacteria could be responsible for reduction or loss of the antibiotic treatment efficacy. FSCJ thus conducted a risk assessment of E. coli and Salmonella as identified hazards. FSCJ judged to be low on the occurrence probability and extent of selection of drug-resistant E. coli and Salmonella, due to the use of colistin sulfate in cattle and pigs, unless otherwise the use of colistin increases. The chance and extent of human exposure to the resistant bacteria were evaluated low via livestock products including pigs and cattle, as long as proper cooking practice is implemented. The degree of possible reduction or loss of clinical effectiveness against E. coli and Salmonella was evaluated as moderate. The overall estimation of the risk regarding reduction or loss of clinical effectiveness of antimicrobials in humans was low. It is necessary to keep up with the latest scientific findings and information.