Food safety (Tokyo, Japan)最新文献

{"title":"Multi-omics Analyses of Non-GM Tomato Scion Engrafted on GM Rootstocks.","authors":"Takumi Ogawa,&nbsp;Kanae Kato,&nbsp;Harue Asuka,&nbsp;Yumi Sugioka,&nbsp;Tomofumi Mochizuki,&nbsp;Takumi Nishiuchi,&nbsp;Taira Miyahara,&nbsp;Hiroaki Kodama,&nbsp;Daisaku Ohta","doi":"10.14252/foodsafetyfscj.D-23-00005","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-23-00005","url":null,"abstract":"<p><p>Grafting has been widely applied in agricultural production in order to utilize agriculturally valuable traits. The use of genetically modified (GM) plants for grafting with non-GM crops will soon be implemented to generate chimeric plants (transgrafting)*, and the non-GM edible portions thus obtained could fall outside of the current legal regulations. A number of metabolites and macromolecules are reciprocally exchanged between scion and rootstock, affecting the crop properties as food. Accordingly, the potential risks associated with grafting, particularly those related to transgrafting with GM plants, should be carefully evaluated based on scientific evidence. In this study, we prepared a hetero-transgraft line composed of non-GM tomato scion and GM-tobacco rootstock expressing firefly luciferase. We also prepared a homograft line (both rootstock and scion are from non-GM tomato) and a heterograft line (non-GM tobacco rootstock and non-GM tomato scion). The non-GM tomato fruits were harvested from these grafted lines and subjected to comprehensive characterization by multi-omics analysis. Proteomic analysis detected tobacco-derived proteins from both heterograft and hetero-transgraft lines, suggesting protein transfer from the tobacco rootstock to the tomato fruits. No allergenicity information is available for these two tobacco-derived proteins. The transcript levels of the genes encoding two allergenic tomato intrinsic proteins (Sola l 4.0101 and Sola l 4.0201) decreased in the heterograft and hetero-transgraft lines. Several differences were observed in the metabolic profiles, including α-tomatine and nicotine. The accumulation of tobacco-derived nicotine in the tomato fruits of both heterograft and hetero-transgraft lines indicated that the transfer of unfavorable metabolites from rootstock to scion should be assessed as a food safety concern. Further investigations are needed to clarify whether variable environmental conditions and growth periods may influence the qualities of the non-GM edible parts produced by such transgrafted plants.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 3","pages":"41-53"},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Valencene\" Produced Using <i>Rhodobacter Sphaeroides</i> 168 strain (Genetically Modified Foods and Feeds).","authors":"","doi":"10.14252/foodsafetyfscj.D-23-00003","DOIUrl":"10.14252/foodsafetyfscj.D-23-00003","url":null,"abstract":"<p><p>Food Safety Commission of Japan (FSCJ) conducted a safety assessment on a food additive: flavoring \"Valencene\", which is produced using <i>Rhodobacter sphaeroides</i> 168 strain based on documents mainly submitted by the applicant. Safety of the inserted genes including toxicity and allergenicity of the proteins produced from the inserted genes, recombinant and host protein residues, and others were evaluated based on the guideline. In the evaluations no risk due to use of recombinant technology was found in the bio-production of \"Valencene\". From the identified chemical structures, toxicological findings and also estimated intakes of non-active ingredients detected in \"Valencene\", none of safety issues were expected for them. From the above evaluations, FSCJ concluded that no concern relevant to human health is raised on the food additive, \"Valencene\" produced using <i>Rhodobacter sphaeroides</i> 168 strain.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 2","pages":"34-35"},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acrylamide in Cooked Sprouts of Mung Bean (<i>Vigna radiata</i>).","authors":"Kazuhiro Chiku,&nbsp;Ai Yamada,&nbsp;Yui Shibasaki,&nbsp;Yoshiki Makino,&nbsp;Taidoh Komatsuzaki,&nbsp;Mitsuru Yoshida","doi":"10.14252/foodsafetyfscj.D-23-00001","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-23-00001","url":null,"abstract":"<p><p>We investigated the time-dependent acrylamide formation in mung bean sprouts during stir-frying under high and medium heat conditions. The acrylamide concentration range detected using the 3-mercaptobenzoic acid derivatization LC-MS/MS method was from below 29 ng/g [limit of detection (LOD)] to 6,900 ng/g. We also investigated the acrylamide levels in mung bean sprouts cooked using four methods while retaining their fresh firm texture using the thiosalicyclic acid derivatization LC-MS/MS method. The acrylamide concentration in microwave oven-cooked sprouts was below 16 ng/g (LOD). The samples cooked by stir-frying, parching, or boiling contained an acrylamide concentration above the LOD but below 42 ng/g [limit of quantification (LOQ)], except for one replicate of a stir-fried sample, whose acrylamide concentration was 42 ng/g. Bean sprouts are popular affordable vegetables, and when stir-fried, their acrylamide concentration is assumed to strongly affect the exposure of the Japanese population to acrylamide. Because the acrylamide concentration range of fried bean sprouts is as broad as mentioned above, the selection of a representative concentration value is difficult. A precise survey and data about acrylamide formation in relation to the bean sprout components before heating, their changes occurring during storage, and the cooking methods and conditions used are needed to estimate the exposure of the Japanese to acrylamide. Here, we showed that rinsing the sprouts before frying and frying them for a short time while mixing them well, while retaining the fresh firm texture to avoid burning and shriveling the sprouts is effective in decreasing the amount of acrylamide formed.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 2","pages":"25-33"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9717184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimesulfazet (Pesticides).","authors":"","doi":"10.14252/foodsafetyfscj.D-23-00007","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-23-00007","url":null,"abstract":"<p><p>Food Safety Commission of Japan (FSCJ) conducted a risk assessment of a sulfonanilide herbicide, dimesulfazet (CAS No. 1215111-77-5), based on results from various studies. The data used in the assessment include the fate in plants (paddy rice), residues in crops, fate in animals (rats), subacute toxicity (rats, mice and dogs), chronic toxicity (dogs), combined chronic toxicity/carcinogenicity (rats), carcinogenicity (mice), acute neurotoxicity (rats), subacute neurotoxicity (rats), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), and genotoxicity. The major adverse effects of dimesulfazet from those test results were observed in body weight (suppressed body weight gain in all test results), kidneys (increased weight in rats) and urinary bladder (urothelial hyperplasia in mice and dogs). None of carcinogenicity, neurotoxicity and genotoxicity were observed. No obvious effects on fertility were detected. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 0.39 mg/kg bw per day in two-year combined chronic toxicity/carcinogenicity study in rats. On the basis of this value, FSCJ specified an acceptable daily intake (ADI) of 0.0039 mg/kg bw per day after applying a safety factor of 100 to the NOAEL. The lowest NOAEL for potential adverse effects after a single oral administration of dimesulfazet was 15 mg/kg bw per day in the developmental toxicity study in rabbits. FSCJ thus specified an acute reference dose (ARfD) of 0.15 mg/kg bw after applying a safety factor of 100 for women who are pregnant or might be pregnant. For the general population, an ARfD of 0.41 mg/kg bw after applying a safety factor of 300 (additional factor 3 by applying LOAEL of 125 mg/kg bw resulted from acute neurotoxicity study in rats).</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 2","pages":"36-39"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyridachlometyl (Pesticides).","authors":"","doi":"10.14252/foodsafetyfscj.D-23-00002","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-23-00002","url":null,"abstract":"<p><p>Food Safety Commission of Japan (FSCJ) conducted a risk assessment of pyridachlometyl (CAS No.1358061-55-8), a pyridazine fungicide, based on results from various studies. The data used in the assessment include the fate in plants (wheat, sugar beet and others), residues in crops, fate in livestock (goats and chickens), residues in livestock, fate in animals (rats), and tests of subacute toxicity (rats, mice and dogs), chronic toxicity (dogs), combined chronic toxicity/carcinogenicity (rats), carcinogenicity (mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), genotoxicity and others. The major adverse effects of pyridachlometyl in experimental animals were observed in body weight (suppressed body weight gain), thyroid (increased weight, hypertrophy of follicular epithelial cell: rats and mice) and liver (increased weight, hepatocellar hypertrophy). No adverse effects were observed in the tests of fertility, teratogenicity or genotoxicity. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 8 mg/kg bw per day in a two-year combined chronic toxicity/carcinogenicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.08 mg/kg bw per day by applying a safety factor of 100 to the NOAEL. It is unnecessary to specify an acute reference dose (ARfD) because of adverse effects not expected to occur via a single administration of pyridacholometyl.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 1","pages":"21-24"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics Profiles of Non-GM Tubers from Transgrafted Potato with a GM Scion.","authors":"Taira Miyahara,&nbsp;Takumi Nishiuchi,&nbsp;Nao Fujikawa,&nbsp;Taichi Oguchi,&nbsp;Akira Kikuchi,&nbsp;Ken-Ichiro Taoka,&nbsp;Takumi Ogawa,&nbsp;Karuna Honda,&nbsp;Yube Yamaguchi,&nbsp;Tomofumi Mochizuki,&nbsp;Daisaku Ohta,&nbsp;Hiroaki Kodama","doi":"10.14252/foodsafetyfscj.D-22-00010","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-22-00010","url":null,"abstract":"<p><p>\"Transgrafting\" is a grafting procedure whereby a transgenic plant body is grafted to a non-transgenic plant body. It is a novel plant breeding technology that allows non-transgenic plants to obtain benefits usually conferred to transgenic plants. Many plants regulate flowering by perceiving the day-length cycle via expression of <i>FLOWERING LOCUS T (FT)</i> in the leaves. The resulting FT protein is translocated to the shoot apical meristem via the phloem. In potato plants, FT is involved in the promotion of tuber formation. Here we investigated the effects of a genetically modified (GM) scion on the edible parts of the non-GM rootstock by using potato plants transformed with <i>StSP6A</i>, a novel potato homolog of the <i>FT</i> gene. Scions prepared from GM or control (wild-type) potato plants were grafted to non-GM potato rootstocks; these were designated as TN and NN plants, respectively. After tuber harvest, we observed no significant differences in potato yield between TN and NN plants. Transcriptomic analysis revealed that only one gene-with unknown function-was differentially expressed between TN and NN plants. Subsequent proteomic analysis indicated that several members of protease inhibitor families, known as anti-nutritional factors in potato, were slightly more abundant in TN plants. Metabolomic analysis revealed a slight increase in metabolite abundance in NN plants, but we observed no difference in the accumulation of steroid glycoalkaloids, toxic metabolites found in potato. Finally, we found that TN and NN plants did not differ in nutrient composition. Taken together, these results indicate that <i>FT</i> expression in scions had a limited effect on the metabolism of non-transgenic potato tubers.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"11 1","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of CYP1A2-Template System to Understand Metabolic Processes in the Safety Assessment.","authors":"Norie Murayama, Takashi Yamada, Yasushi Yamazoe","doi":"10.14252/foodsafetyfscj.D-22-00008","DOIUrl":"10.14252/foodsafetyfscj.D-22-00008","url":null,"abstract":"<p><p>Cytochrome P450 (CYP)-mediated metabolisms of four chemicals have been investigated to understand their unresolved phenomena of their metabolisms using human CYP-Template systems developed in our previous studies (Drug Metab Pharmacokinet 2019, 2021, 2022). Simulation experiments of a topoisomerase-targeting agent, amonafide, offered a possible new inhibitory-mechanism as Trigger-residue inactivation on human CYP1A2 Template. <i>N</i>-Acetylamonafide as well as amonafide would inactivate CYP1A2 through the interference of Trigger-residue movement with their dimethylaminoethyl parts. The mechanism was also supported on the inhibition/inactivation of two other drugs, DSP-1053 and binimetinib. Both the drugs, after other CYP-mediated slight structural alterations, were expected to interact with Trigger-residue for the intense inhibition on CYP1A2 Template. Possible formation of reactive intermediates of amonafide and 3-methylindole was also examined on CYP1A2 Template. Placements of amonafide suggested the scare <i>N</i>-oxidation of the arylamine part due to the Trigger-residue interaction. Placements of 3-methylindole suggested the formation of a reactive intermediate, 3-methyleneindolenine, rather selectively on rodent CYP1A2 than on human CYP1A2, in consistent with the experimental data. These results suggest that CYP Template systems developed are effective tools to warn an appearance of unstable reactive intermediates. Our CYP-Template systems would support confident judgements in safety assessments through offering the mechanistic understandings of the metabolism.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 4","pages":"129-139"},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10874718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japanese Regulatory Framework and Approach for Genome-edited Foods Based on Latest Scientific Findings.","authors":"Kazunari Kondo,&nbsp;Chie Taguchi","doi":"10.14252/foodsafetyfscj.D-21-00016","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-21-00016","url":null,"abstract":"<p><p>The food supply system is facing important challenges and its sustainability has to be considered. Genome-editing technology, which accelerates the development of new variety, could be used to achieve sustainable development goals, thereby protecting the environment and ensuring the stable production of food for an increasing global population. The most widely used genome-editing tool, CRISPR/Cas9, is easy to use, affordable, and versatile. Foods produced by genome-editing technologies have been developed worldwide to create novel traits. In the first half of the review, the latest scientific findings on genome-editing technologies are summarized, and the technical challenge in genome sequence analysis are clarified. CRISPR/Cas9 has versatile alternative techniques, such as base editor and prime editor. Genome sequencing technology has developed rapidly in recent years. However, it is still difficult to detect large deletions and structural variations. Long-read sequencing technology would solve this challenge. In the second part, regulatory framework and approach for genome-edited foods is introduced. The four government ministries, including the Ministry of Environment, the Ministry of Agriculture, Forestry and Fisheries, and the Ministry of Health, Labour and Welfare (MHLW), started to discuss how the regulation should be implemented in 2019. The SDN-1 technique is excluded from the current genetically modified organism (GMO) regulation. The Japanese regulatory framework includes pre-submission consultation and submission of notification form. In the last part of this review, transparency of regulatory framework and consumer confidence were described. Since maintaining consumer trust is vital, transparency of regulatory framework is a key to consumers. The information of notification process on approved genome-edited foods is made public immediately. This review will help regulators build regulatory frameworks, and lead to harmonization of the framework between the countries.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 4","pages":"113-128"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10874715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraquat (Pesticides).","authors":"","doi":"10.14252/foodsafetyfscj.D-22-00012","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-22-00012","url":null,"abstract":"<p><p>Food Safety Commission of Japan (FSCJ) conducted a risk assessment of a bipyridinium herbicide, paraquat (CAS No. 1910-42-5), based on results from various studies. Major adverse effects of paraquat in experimental animals were observed in body weight (suppressed weight gain), lungs (increased weight, alveolar epithelium hyperplasia, and pneumonia), kidneys (renal tubule dilatation) and eyes (cataract in rats and dogs). The effects on the lung were considered to be the most critical endpoints in the assessment. Neither carcinogenicity, effects on fertility, teratogenicity, genotoxicity, or immunotoxicity was observed. FSCJ reasonably concluded no obvious concern of paraquat-residue in foods to yield neurotoxicity through human dietary exposure, as long as paraquat is applied following the registered standard use of the pesticide. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 0.45 mg paraquat ion^*/kg bw per day in one-year chronic toxicity study in dogs. FSCJ specified an acceptable daily intake (ADI) of 0.0045 mg paraquat ion/kg bw per day by applying a safety factor of 100 to the NOAEL. FSCJ judged these effects also as the end-point of the acute reference dose (ARfD). The lowest NOAEL was 0.45 mg paraquat ion/kg bw per day in one-year chronic toxicity study in dogs. For potential adverse effects of a single oral administration of paraquat, FSCJ specified an ARfD to be 0.0045 mg paraquat ion/kg bw by applying a safety factor of 100 to the NOAEL.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 4","pages":"140-147"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Risk Assessment of Food-derived Coumarin with <i>in Silico</i> Approaches.","authors":"Takashi Yamada, Naruo Katsutani, Taeko Maruyama, Tomoko Kawamura, Hiroshi Yamazaki, Norie Murayama, Weida Tong, Yasushi Yamazoe, Akihiko Hirose","doi":"10.14252/foodsafetyfscj.D-21-00015","DOIUrl":"10.14252/foodsafetyfscj.D-21-00015","url":null,"abstract":"<p><p>Hepatotoxicity associated with food-derived coumarin occurs occasionally in humans. We have, herein, assessed the data of existing clinical and nonclinical studies as well as those of <i>in silico</i> models for humans in order to shed more light on this association. The average intakes of food-derived coumarin are estimated to be 1-3 mg/day, while a ten-times higher level is expected in the worst-case scenarios. These levels are close to or above the tolerable daily intake suggested by a chronic study in dogs. The human internal exposure levels were estimated by a physiologically-based pharmacokinetic model with the use of virtual doses of coumarin in the amounts expected to derive from foods. Our results suggest that: (i) coumarin can be cleared rapidly <i>via</i> 7-hydroxylation in humans, and (ii) the plasma levels of coumarin and of its metabolite, <i>o</i>-hydroxyphenylacetic acid associated with hepatotoxicity, are considerably lower than those yielding hepatotoxicity in rats. Pharmacokinetic data suggest a low or negligible concern regarding a coumarin-induced hepatotoxicity in humans exposed to an average intake from foods. Detoxification of coumarin through the 7-hydroxylation, however, might vary among individuals due to genetic polymorphisms in CYP2A6 enzyme. In addition, the CYP1A2- and CYP2E1-mediated activation of coumarin can fluctuate as a result of induction caused by environmental factors. Furthermore, the daily consumption of food-contained coumarin was implicated in the potential risk of hepatotoxicity by the drug-induced liver injury score model developed by the US Food and Drug Administration. These results support the idea of the existence of human subpopulations that are highly sensitive to coumarin; therefore, a more precise risk assessment is needed. The present study also highlights the usefulness of <i>in silico</i> approaches of pharmacokinetics with the liver injury score model as battery components of a risk assessment.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 3","pages":"73-82"},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}