Food safety (Tokyo, Japan)最新文献

{"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}

{"title":"Commentary on the Risk Assessment of Lead by the Food Safety Commission of Japan.","authors":"Fumi Irie","doi":"10.14252/foodsafetyfscj.D-22-00007","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-22-00007","url":null,"abstract":"<p><p>This article describes in detail the process of and the basis for the risk assessment of lead, started as a self-tasking assessment in April 2008 and finalized in June 2021 by the Food Safety Commission of Japan (FSCJ). Discussion points addressed in the working group set under the FSCJ in April 2019 are also presented in this commentary. To reflect the overall exposure to lead from various sources, blood lead level (BLL) was used as the basic metric for the assessment. For the evaluation of effects on human health, the approach of overall weight of evidence was taken, rather than selecting one critical endpoint, in consideration of the uncertainties inherent to epidemiological studies, particularly those examining the effects associated with low-level lead exposure. The overall evidence compiled for the assessment suggested that BLLs in the range of 1-2 μg/dL might be associated with some effects on human health. The representative value of BLL for the entire population was difficult to obtain due to the lack of a national population-based survey in Japan. Instead, the current average BLL of the Japanese population was estimated based on recent studies conducted in Japan. The estimated average exposure level was below or equal to 1 μg/dL and close to the levels at which some effects on human health might occur, as suggested by epidemiological studies. Hence, the continued enforcement of measures to reduce lead exposure is indispensable. Furthermore, a national human biomonitoring program to continuously assess the exposure status of the Japanese population, which can be ultimately used for assuring the effectiveness of control measures, is needed.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 3","pages":"102-111"},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511194","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":"Dietary Exposure of the Japanese General Population to Elements: Total Diet Study 2013-2018.","authors":"Takahiro Watanabe,&nbsp;Yohei Kataoka,&nbsp;Kyoko Hayashi,&nbsp;Rieko Matsuda,&nbsp;Chikako Uneyama","doi":"10.14252/foodsafetyfscj.D-22-00003","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-22-00003","url":null,"abstract":"<p><p>Some countries have conducted a total diet study (TDS) focused on the estimation of specific trace elements. Although some results of a Japanese TDS examining trace elements were published, there have been no reports of a nationwide TDS across Japan over a multi-year period to estimate the level of exposure to multiple elements. In the present study, a TDS using a market basket approach was performed to estimate the dietary exposure levels of the general population of Japan to 15 elements, including aluminum (Al), total arsenic (tAs), boron (B), barium (Ba), cadmium (Cd), cobalt (Co), chromium (Cr), total mercury (THg), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and uranium (U). Samples prepared in eight regions across Japan over a 6-year period were analyzed using validated methods. The robust mean exposure estimates for Al, tAs, B, Ba, Cd, Co, Cr, THg, Mo, Ni, Pb, Sb, Se, Sn, and U were 48, 4.2, 29, 8.6, 0.35, 0.17, 0.49, 0.14, 4.2, 2.8, 0.15, 0.022, 1.8, 0.10, and 0.021 μg/kg body weight/day, respectively. Although the variability in exposure estimates varied greatly from element to element, the relative standard deviations calculated from the robust means and robust standard deviations were ≤ 50% for all elements except Sn. Compared against the health-based guidance values, none of the robust and precise estimates obtained for the target elements would be associated with urgent health risk concern. In addition, the estimated exposure levels were generally in agreement with previously reported estimates, indicating that health risks associated with exposure to these elements have not changed markedly nationwide in Japan in recent years.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 3","pages":"83-101"},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511192","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":"Lead (Chemicals and Contaminants).","authors":"","doi":"10.14252/foodsafetyfscj.D-22-00004","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-22-00004","url":null,"abstract":"<p><p>Food Safety Commission of Japan (FSCJ) conducted risk assessment of lead (hereinafter referred to as Pb) as a Self-Tasking assessment. Risk assessments of Pb were initially requested from the Ministry of Health, Labour and Welfare in relation to revision of the standards for apparatus/container and packaging (ACP) and to revision of the standards for beverages. Considering the diverse modes and routes of human exposure to Pb, FSCJ judged that a comprehensive risk assessment of Pb is appropriate instead of specific risk assessment relating to ACP or beverages. To estimate the actual Pb exposure of the general population in Japan, the present Self-Tasking assessment working group started to inspect available data of blood Pb levels among children (12 years old boys and girls, n = 289, surveyed for 2015-2018) and among adults (pregnant women, n = 96,696, surveyed for 2011-2014)¹⁾. FSCJ concluded that average blood level of Pb of current Japan is about 1 µg/dL or less based on the data available at present. Comprehensive evaluation of the findings from the previous epidemiological studies suggested that even blood Pb at the level of 1-2 µg/dL potentially affected children's neuro-behavioral development or adult renal function. FSCJ, however, concluded that figuring out of a blood Pb level without adverse effects was difficult from the data of epidemiological studies. Pb level in current Japan as about 1 µg/dL or less. This value is close to the level potentially to have some effects, 1-2 µg/dL as suggested by epidemiological studies. Continuous implementation of measures to reduce Pb exposure is thus required. A close watch on the trend of blood Pb level by human biomonitoring is also necessary for verification of the efficacy of the measures to reduce Pb exposure.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 2","pages":"70-71"},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595388","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":"Focusing Points on FSCJ's Guideline Recently Established: Risk Assessment of Food Contact Materials.","authors":"Masahiro Nakamoto","doi":"10.14252/foodsafetyfscj.D-21-00029","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-21-00029","url":null,"abstract":"<p><p>In Japan, the Positive List (PL) system was introduced (Enforcement: June 1, 2020) in the regulative field of Food Apparatus, Containers, and Packaging (ACP) by the recent amendment of the Food Sanitation Act. Under this situation, continuous requests for the risk assessments from the Ministry of Health, Labour and Welfare (MHLW) to the Food Safety Commission of Japan (FSCJ) will be expected. To enhance fairness and transparency and to clarify the data required for the risk assessment, the FSCJ established its \"Guidelines for the Risk Assessment of Food Apparatus, Containers, and Packaging\" on May 28, 2019. The Guidelines apply to new Food Contact Materials or Substances (FCMs) after enforcement of the PL system (June 1, 2020). The subject material is synthetic resins, because the PL system was first introduced to them in Japan. In general, the substances that are migrated from ACP are not intended to migrate into foods, and their technological effects on foods are not expected. It can be supposed that the migration of these substances is generally very limited. Therefore, as adopted in the USA and the EU, the Guidelines also adopt the tiered approach for the toxicological data requirement that depend on the estimated migration levels (Tier of Dietary Concentration (Tier of DC)) on the subject substance. The greater the exposure to the substance through migration, the more toxicity test results will be needed. The risk assessment steps by the tiered approach in the Guidelines are (1) migration assessment, (2) toxicity assessment, (3) exposure assessment, and (4) risk characterization. These steps are aimed to harmonize with the general 4 steps of risk assessments: hazard identification, hazard characterization, exposure assessment, and risk characterization. In this review, we will introduce the overview of the Guidelines and details of the above 4 steps.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 2","pages":"57-69"},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595386","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":"Comparison of the Importance and Prioritization of Information Communicated to Consumers by Experts Regarding Food Safety.","authors":"Itsuko Horiguchi,&nbsp;Kazuo Koyama,&nbsp;Azusa Hirakawa,&nbsp;Mieko Shiomi,&nbsp;Kaoruko Tachibana,&nbsp;Katsuyuki Watanabe","doi":"10.14252/foodsafetyfscj.D-21-00010","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-21-00010","url":null,"abstract":"<p><p>Key topics related to risk communication and food safety were investigated by three different expert groups. In this study, the Delphi method was used to systematically and iteratively aggregate experts' opinions, and the topics to be communicated to consumers were expressed and prioritized. The opinions of three groups, consisting of 26 members of the expert committee (EC) from the Food Safety Commission of Japan (FSCJ), 29 local government officials (LGOs) from their respective food safety departments, and 25 food safety monitors (FSM) appointed by the FSCJ, were obtained in the period of June through September 2017. \"Safety and security concept\" was identified and ranked high in all groups. This topic identified \"Zero-risk\" demand of consumers without understanding risks as the reverse side of safety. The EC group prioritized additional issues, such as \"concept of risk\" and \"safety costs and relevant risk management\". The LGO and FSM groups prioritized specific hazard items for food poisoning and preventive measures. With regard to the so-called \"health foods\", the EC and LGO groups indicated insufficient transmission of scientific evidence from the government to consumers, and the FSM group indicated insufficient understanding by consumers of the food labeling system for health and nutrition. Because consumers do not fully understand all concepts of food safety, governments are encouraged to disseminate the probability of risk and the knowledge of risk reduction directly to the consumers by using simple and easy-to-understand terms.</p>","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 2","pages":"43-56"},"PeriodicalIF":0.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595387","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":"Inhibition of CYP3A-mediated Midazolam Metabolism by Kaempferia Parviflora","authors":"Yumika Kashiwabuchi, Y. Nishimura, N. Kurata, M. Iwase, Y. Kiuchi, K. Nobe","doi":"10.14252/foodsafetyfscj.D-21-00013","DOIUrl":"https://doi.org/10.14252/foodsafetyfscj.D-21-00013","url":null,"abstract":"Abstract Kaempferia parviflora (KP) extract has recently attracted attention in Japan as a dietary supplement; however, there is little information regarding food-drug interactions (FDIs). The current study was conducted to clarify the FDI of KP extract via inhibition of cytochrome P450 3A (CYP3A), a typical drug-metabolizing enzyme. The inhibitory effects of KP extract and its main ingredients, 5,7-dimethoxyflavone (5,7-DMF) and 3,5,7,3’,4’-pentamethoxyflavone (3,5,7,3’,4’-PMF), on CYP3A-mediated midazolam 1’-hydroxylation (MDZ 1’-OH) activity were investigated in human liver microsomes. In addition, the effect of a single oral treatment with KP extract (135 mg/kg) on oral MDZ (15 mg/kg) metabolism was investigated in rats. Serum MDZ concentration was analyzed and pharmacokinetic parameters were compared with the control group. KP extract competitively inhibited MDZ 1’-OH activity with an inhibition constant value of 78.14 µg/ml, which was lower than the estimated concentration in the small intestine after ingestion. Furthermore, KP extract, 5,7-DMF, and 3,5,7,3’,4’-PMF inhibited the activity in a time-, NADPH-, and concentration-dependent manner. In vivo study showed that administration of KP extract to rats 2 h before MDZ significantly increased the area under the serum concentration-time curve and the maximum concentration of MDZ significantly by 2.3- and 1.9- fold, respectively (p < 0.05). Conversely, administration of MDZ 18 h after KP extract treatment displayed a weaker effect. These results suggest that KP extract competitively inhibits CYP3A-mediated MDZ metabolism, and that this inhibition may be time-dependent but not irreversible. This work suggests an FDI through CYP3A inhibition by KP extract.","PeriodicalId":73044,"journal":{"name":"Food safety (Tokyo, Japan)","volume":"10 1","pages":"32 - 41"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42819005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}