1.Establishment of Drug Risk Management System -the Promise of Safety Science Approaching from Non-Clinical Safety
Ichiro TSUNENARI ; Kyoko BARATA ; Naoki NAKAYAMA ; Shoichiro SUGAI ; Motomu TAN ; Shoji SASAKI ; Takashi UNNO ; Kazuhiko MATSUMOTO
Japanese Journal of Pharmacoepidemiology 2008;13(1):29-38
A questionnaire survey of risk management systems for medical products was conducted with the cooperation of domestic and foreign pharmaceutical companies. As for the foreign companies, it was revealed that specialized safety management teams and data-management committees are established to formulate risk management plans in order to create systems that assure consistent risk management for each company. In addition, it was revealed that toxicologists are incorporated in the central decision making organization. As for domestic companies, it turned out that no less than half of the respondents pay attention to consistent risk management from the development stage through the post marketing stage. From now on, it will be essential to consolidate safety data, improve the accessibility of centralized safety data from the relevant departments, and establish systems to provide consistent risk management from the development stage to the post marketing stage.
2.Negative results ofumu genotoxicity test of fluorotelomer alcohols and perfluorinated alkyl acids.
Yoshimitsu ODA ; Shoji NAKAYAMA ; Kouji H HARADA ; Akio KOIZUMI
Environmental Health and Preventive Medicine 2007;12(5):217-219
OBJECTIVESRecently, perfluorooctanoate (PFOA) has been ubiquitously detected in the environment as well as in human serum. Fluorotelomer alcohols (FTOHs), a precursor of PFOA, undergo biodegradation via several metabolic routes which leads to formation of various biodegradation products. The degradation of FTOHs produces an α,β-unsaturated aldehyde that seems possibly to be electrophilic and may react with cellular macromolecules including DNA.
METHODSWe investigated the genotoxicity of three FTOHs (6∶2 FTOH, 8∶2 FTOH and 10∶2 FTOH), PFOA and perfluorooctane sulfonate (PFOS) using theumu test.
RESULTSThe FTOHs, PFOA and PFOS showed no significant increases in β-galactosidase activity at 0-1000 μM in the absence of S9 mix. The results were unchanged by the metabolic activation with S9 mix.
CONCLUSIONThe genotoxicities of FTOHs, PFOA or PFOS are not detectable using the present method, suggesting that they are unlikely mutagens.
3.Exposure profile of mercury, lead, cadmium, arsenic, antimony, copper, selenium and zinc in maternal blood, cord blood and placenta: the Tohoku Study of Child Development in Japan.
Miyuki IWAI-SHIMADA ; Satomi KAMEO ; Kunihiko NAKAI ; Kozue YAGINUMA-SAKURAI ; Nozomi TATSUTA ; Naoyuki KUROKAWA ; Shoji F NAKAYAMA ; Hiroshi SATOH
Environmental Health and Preventive Medicine 2019;24(1):35-35
BACKGROUND:
The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594-650).
METHODS:
Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively.
RESULTS:
Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68-6.81), 1.18 (0.74-1.79), 10.8 (8.65-13.5), 0.2 (0.06-0.40) and 0.2 (0.1-0.38) ng mL and 5.42 (3.89-7.59) ng g, respectively. Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58-5.25), 0.53 (0.10-1.25), 9.89 (8.02-12.5), 0.39 (0.06-0.92) and 0.2 (0.2-0.38) ng mL and 9.96 (7.05-13.8) ng g, respectively.
CONCLUSIONS
THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.
Adult
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Female
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Fetal Blood
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chemistry
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Humans
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Japan
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Maternal Exposure
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statistics & numerical data
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Maternal-Fetal Exchange
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Metals
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blood
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Placenta
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chemistry
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Pregnancy
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blood
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Trace Elements
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blood
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Urban Health
4.Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan.
Basilua Andre MUZEMBO ; Miyuki IWAI-SHIMADA ; Tomohiko ISOBE ; Kokichi ARISAWA ; Masayuki SHIMA ; Tetsuhito FUKUSHIMA ; Shoji F NAKAYAMA
Environmental Health and Preventive Medicine 2019;24(1):6-6
BACKGROUND:
Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002-2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers.
METHODS:
From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit.
RESULTS:
The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8-9.9) pg TEQ/g lipid and 0.3 (0.2-0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011-2016 survey was found to have decreased by 41.3% compared to the 2002-2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake.
CONCLUSIONS
Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population.
Adult
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Aged
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Analysis of Variance
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Biomarkers
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blood
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Body Mass Index
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Cross-Sectional Studies
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Diet
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Dioxins
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analysis
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Environmental Exposure
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analysis
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Environmental Monitoring
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methods
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Female
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Food
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Food Analysis
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Food Contamination
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analysis
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Gas Chromatography-Mass Spectrometry
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Humans
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Japan
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Male
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Middle Aged
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Surveys and Questionnaires
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Young Adult
5.Dietary supplement use in elementary school children: a Japanese web-based survey.
Kazue ISHITSUKA ; Satoshi SASAKI ; Hidetoshi MEZAWA ; Mizuho KONISHI ; Maki IGARASHI ; Kiwako YAMAMOTO-HANADA ; Shoji F NAKAYAMA ; Yukihiro OHYA
Environmental Health and Preventive Medicine 2021;26(1):63-63
BACKGROUND:
A variety of dietary supplements are commercially available. However, the efficacy and safety of dietary supplement use in children are not well established. Understanding dietary supplement use is important for developing public health policy regarding dietary supplements. This study aimed to investigate the types of dietary supplements used and characteristics of dietary supplement users among Japanese elementary school children.
METHOD:
We conducted a cross-sectional web-based questionnaire study. Dietary supplement use, socio-demographics, and health-related behaviors were assessed through mother-reported questionnaire. Types of dietary supplements were identified based on ingredient using product barcodes and brand names. Multivariate logistic regression analysis was conducted to investigate the socio-demographics and health-related behaviors associated with supplement use.
RESULTS:
Among 4933 children, 333 (6.8%) were identified as dietary supplement users. The most common supplement was amino acids or protein (1.4%), followed by n-3 fatty acids or fish oil (1.0%), probiotics (1.0%), multivitamins (0.9%), multivitamin-minerals (0.8%), and botanicals (0.8%). Overall, any dietary supplement use was significantly associated with the highest frequency of sports participation (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.65-4.02), highest household income (OR, 1.87; 95% CI, 1.13-3.10), highest maternal educational level (OR, 1.82; 95% CI, 1.31-2.52), and male sex (OR, 1.38; 95% CI, 1.09-1.75). The highest frequency of sports participation was significantly associated with higher odds of use of amino acids or protein (OR, 6.06; 95% CI, 1.78-20.6) and multivitamins (OR, 3.56; 95% CI, 1.11-11.5), compared to the lowest frequency of sports participation.
CONCLUSION
This study showed that Japanese children primarily use non-vitamin, non-mineral supplements. Non-vitamin, non-mineral supplements should thus be included in future studies aimed at monitoring dietary supplement use. We also found that dietary supplement use in children was associated with sports participation. Guidelines for dietary supplement use for children, in particular sport participants, are needed.
6.Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.
Keisuke HIOKI ; Yuki ITO ; Naoko OYA ; Shoji F NAKAYAMA ; Tomohiko ISOBE ; Takeshi EBARA ; Kanemitsu SHIBATA ; Naomi NISHIKAWA ; Kunihiko NAKAI ; Tomota KAMIDA ; Jun UEYAMA ; Mayumi SUGIURA-OGASAWARA ; Michihiro KAMIJIMA
Environmental Health and Preventive Medicine 2019;24(1):7-7
BACKGROUND:
Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan.
METHODS:
Urine samples were collected from 62 non-smoking pregnant women (12-22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses.
RESULTS:
For all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points.
CONCLUSION
This study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.
Adult
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Chromatography, Liquid
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Creatinine
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urine
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Environmental Exposure
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analysis
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Environmental Monitoring
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methods
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Environmental Pollutants
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urine
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Female
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Humans
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Japan
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Mass Spectrometry
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Organophosphates
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urine
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Pesticides
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urine
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Pregnancy
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Pregnant Women
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Young Adult
7.Questionnaire results on exposure characteristics of pregnant women participating in the Japan Environment and Children Study (JECS).
Miyuki IWAI-SHIMADA ; Shoji F NAKAYAMA ; Tomohiko ISOBE ; Takehiro MICHIKAWA ; Shin YAMAZAKI ; Hiroshi NITTA ; Ayano TAKEUCHI ; Yayoi KOBAYASHI ; Kenji TAMURA ; Eiko SUDA ; Masaji ONO ; Junzo YONEMOTO ; Toshihiro KAWAMOTO ; Japan Environment and Children’s Study Group
Environmental Health and Preventive Medicine 2018;23(1):45-45
BACKGROUND:
The Japan Environment and Children's Study (JECS) is a nation-wide birth cohort study investigating environmental effects on children's health and development. In this study, the exposure characteristics of the JECS participating mothers were summarized using two questionnaires administered during pregnancy.
METHODS:
Women were recruited during the early period of their pregnancy. We intended to administer the questionnaire during the first trimester (MT1) and the second/third trimester (MT2). The total number of registered pregnancies was 103,099.
RESULTS:
The response rates of the MT1 and MT2 questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and 27.9 (6.5) weeks, respectively. The frequency of participants who reported "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1 and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31) about the occupational chemical use between MT1 and MT2 questionnaires. Most of the participants (80%) lived in either wooden detached houses or steel-frame collective housing. More than half of the questionnaire respondents answered that they had "mold growing somewhere in the house". Insect repellents and insecticides were used widely in households: about 60% used "moth repellent for clothes in the closet," whereas 32% applied "spray insecticide indoors" or "mosquito coil or an electric mosquito repellent mat."
CONCLUSIONS
We summarized the exposure characteristics of the JECS participants using two maternal questionnaires during pregnancy.
Adult
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Child Health
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Cohort Studies
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Female
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Gestational Age
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Humans
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Japan
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Maternal Exposure
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statistics & numerical data
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Mothers
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statistics & numerical data
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Pregnancy
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Surveys and Questionnaires
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Young Adult