Food Safety
Online ISSN : 2187-8404
ISSN-L : 2187-8404
最新号
選択された号の論文の3件中1~3を表示しています
Original Article
  • Takashi Yamada, Naruo Katsutani, Taeko Maruyama, Tomoko Kawamura, Hiro ...
    2022 年 10 巻 3 号 p. 73-82
    発行日: 2022年
    公開日: 2022/09/23
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    電子付録

    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 in silico 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 via 7-hydroxylation in humans, and (ii) the plasma levels of coumarin and of its metabolite, o-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 in silico approaches of pharmacokinetics with the liver injury score model as battery components of a risk assessment.

  • Takahiro Watanabe, Yohei Kataoka, Kyoko Hayashi, Rieko Matsuda, Chikak ...
    2022 年 10 巻 3 号 p. 83-101
    発行日: 2022年
    公開日: 2022/09/23
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    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.

Review
  • Fumi Irie
    2022 年 10 巻 3 号 p. 102-111
    発行日: 2022年
    公開日: 2022/09/23
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    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.

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