Doping control analyses during the Tokyo 2020 Olympic and Paralympic Games.

The doping control analyses at the XXXII Olympic Games (July 23 to August 8, 2021) and the XVI Paralympic Games (August 24 to September 5, 2021) held in Tokyo, Japan, after a year of delay due to the COVID-19 pandemic are summarized in this paper. A new satellite facility at the existing World Anti-Doping Agency (WADA)-accredited Tokyo laboratory was established and fully operated by 278 staff, including 33 Tokyo laboratory staff, 49 international experts, and 196 Japanese temporary staff. The numbers of urine samples were 5081 (Olympics) and 1519 (Paralympics), and the numbers of blood samples were 1103 (Olympics) and 500 (Paralympics). The laboratory could prepare for analysis in advance using a paperless chain-of-custody system, allowing for faster turnaround time reporting. For the first time, a new polymerase chain reaction method for detecting erythropoietin (EPO) gene doping was used. The laboratory also analyzed blood samples for detecting steroid esters following the spotting of collected venous EDTA blood onto dried blood spot cards. Moreover, full-scan data acquisition using high-resolution mass spectrometers was performed for all urine samples, allowing for detecting traces of doping substances, which are not currently analyzed in the subsequent data processing. The presence of some prohibited substances was confirmed, resulting in 8 atypical findings (ATFs) and 11 adverse analytical findings (AAFs), including homologous blood transfusion (2 cases) and recombinant EPO in the blood (1 case), at the Olympics, whereas 2 ATFs and 10 AAFs were reported at the Paralympics.

Cumulative exposure assessment of neonicotinoids and an investigation into their intake-related factors in young children in Japan.

Exposure levels of neonicotinoids (NEO) in young children remain unknown, despite their widespread use and the plausible vulnerability of toddlers to environmental toxicants. Herein we aimed to clarify the exposure levels and sources of NEOs in young Japanese children. Disposable diapers were collected from 1036 children (16-23 months old) participating in an adjunct study of the Japan Environment and Children's Study between 2015 and 2016. Six NEOs and one metabolite in urine extracted from a diaper from each child were analyzed using high-performance liquid chromatography-tandem mass spectrometry. A relative potency factor approach was used to assess the cumulative exposure to NEOs equivalent to dinotefuran levels (DINRPF). The 95th percentile urinary concentration of DINRPF was 157 µg/L and 380 µg/g creatinine (Cr). Receiver operating characteristic curve analyses for the propensity scores of the possible exposure-related factors revealed that the discriminatory powers determining whether Cr-adjusted and Cr-unadjusted DINRPF concentrations exceeding the 95th percentile values were higher for the amount of each foodstuff ingested on the survey day (areas under the curve were 0.62 and 0.75, respectively) than for the exposure-related behaviors (0.60 and 0.71, respectively) or for mothers' attitudes toward food selection and preparation (0.54 and 0.57, respectively). Use of a mosquito coil, insect repellent, and mothproof net for a screen door, and playing on a lawn were associated with increased urinary NEO levels (odds ratio [OR]: 2.0-2.9), while care about the child's nutritional balance by mothers reduced urinary NEO levels (OR: 0.23-0.41). To the best of our knowledge, this is the first study that dealt with urinary concentrations and possible exposure sources of NEOs in a large number of young children. Attention to the children's behavior and diet might result in the reduction of a high exposure to NEOs in young children.

Biomonitoring method for neonicotinoid insecticides in urine of non-toilet-trained children using LC-MS/MS.

There is a growing appreciation of the importance of determining chemical exposure levels in early childhood, as well as in embryonic and foetal life, which are now widely believed to be essential for gaining insight into potential health risks associated with these chemicals. To facilitate the assessment of exposure to neonicotinoid insecticides (NEOs) in non-toilet-trained children, a new method using disposable diapers (nappies) was developed for the simultaneous determination of the NEOs acetamiprid and its metabolite N-desmethylacetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam (NEO biomarkers). The urine absorbed in disposable diapers was extracted with acetone (diaper urine) and was cleaned using a solid-phase extraction column, before analysis with LC-MS/MS. The absolute recoveries of NEO biomarkers were 19-50%. Good results were observed for the linearity of the matrix-matched calibration curves (r2 = 0.983-0.996; concentration range LOQ-20 µg L-1) and the precision of intra-day (% relative standard deviation (%RSD): 3.3-12.7%) and inter-day (%RSD: 4.3-19.5%) analyses. The lowest and highest limits of detection of the developed method were 0.07 µg L-1 for acetamiprid and 0.75 µg L-1 for clothianidin. The developed method was applied for the evaluation of fifty diapered three-year-old children in Japan. Importantly, the study revealed relatively high detection rates for dinotefuran and N-desmethylacetamiprid; 84% and 78% respectively. The highest geometric mean of dinotefuran urinary concentration was 2.01 µg L-1. Thus, a method for determining NEO biomarkers in urine extracted from disposable diapers was established. This is the first report on the simultaneous quantitative analysis of NEO biomarkers of diaper-absorbed urine samples.

Exposure levels of organophosphate pesticides in Japanese diapered children: Contributions of exposure-related behaviors and mothers' considerations of food selection and preparation.

Organophosphate (OP) pesticide exposure is a public health issue due to its potential link to neurodevelopmental problems in children. This study aimed to examine the exposure levels of OP pesticides in Japanese toddlers and explore the possible contributions of their exposure-related behaviors and their mothers' considerations of food selection and preparation to their exposure levels to OP pesticides. We recruited diapered children participating in the Japan Environment and Children's Study and collected used disposable diapers from 1037 children between June 2015 and August 2016. Six dialkylphosphates (DAPs) were measured in the urine extracted from the diapers. The geometric means of urinary creatinine (Cr)-unadjusted and Cr-adjusted concentrations of the sum of the six DAPs (ΣDAP) were 120 nmol/L and 243 nmol/g Cr, respectively. A receiver operating characteristic curve analysis for propensity scores of exposure-related factors revealed that discriminatory powers determining whether Cr-unadjusted and Cr-adjusted ΣDAP concentrations exceeded the 95th percentile values were lower for the exposure-related behaviors (areas under the curve, 0.72 and 0.69, respectively) and the mothers' considerations of food selection and preparation (0.55 and 0.57, respectively) than those for the foodstuffs ingested on the survey day (0.75 and 0.81, respectively). Some exposure-related behaviors, namely the use of insecticides, herbicides, and insect repellent sprays, were found to be associated with increased Cr-unadjusted ΣDAP concentrations (odds ratio, 2.0-2.6) via multivariate analysis. In contrast, only the use of a fragrance or deodorant was associated with increased Cr-adjusted ΣDAP concentrations (odds ratio, 2.3). This is the first report on the exposure levels of OP pesticides in a large number of Japanese toddlers. Some household chemical product use was related to OP common metabolite DAP levels. Japanese toddlers were widely exposed to OP pesticide.

Oxidized human serum albumin as a possible correlation factor for atherosclerosis in a rural Japanese population: the results of the Yakumo Study.

BACKGROUND: The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population. METHODS: We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA). RESULTS: We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized ß = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA). CONCLUSIONS: We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.

Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan.

BACKGROUND AND AIM: Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan. METHODS: We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children's Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations. RESULTS: The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (ΣDAP) were 3.6, 3.9, 0.9, 6.0, 0.6µg/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate. CONCLUSIONS: We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan.