BACKGROUND: Icaridin and DEET are common insect repellents widely used on human skin and clothing (skin-insect repellents [skin-IR]) to repel common pests, such as mosquitoes and biting flies. Novel analytical methods for urinary skin-IR exposure biomarkers that can be effectively applied in epidemiological studies and provide strong evidence related to risk assessment associated with daily exposure are required. In this study, we aimed to develop a method for analyzing the concentrations of icaridin, DEET, and two DEET metabolites N,N-diethyl-3-(hydroxymethyl) benzamide and 3-(diethylcarbamoyl) benzoic acid in human urine. METHODS: In this analysis, after formic acid-induced acidification of the urine sample, exposure biomarkers were extracted using solid-phase extraction composed of a modified polystyrenedivinylbenzene polymer for reversed phase (hydrophobic) retention. Subsequently, high-performance liquid chromatography-tandem mass spectrometry was performed within 10 min for a separation analysis. The present method was applied to five Japanese adults (aged 20-43 years) who used icaridin or DEET-containing products within a week. RESULTS: Limits of detection were 0.06-0.11 µg/L. Extraction recoveries were 74%-88%. The intraday and interday variations were 1.5-17.5 and 0.9-15.8% relative standard deviation, respectively. All exposure biomarkers were successfully detected in all five adults. Urinary concentrations of exposure biomarkers reached their maximum values within 15 h after starting to use skin-IR. CONCLUSIONS This method was successful in measuring urinary exposure biomarkers of skin-IR, including icaridin and DEET. Moreover, this study presents the first application of biomonitoring of urinary icaridin concentrations after using a commercial product.
Humans ; Solid Phase Extraction/methods* ; Tandem Mass Spectrometry/methods* ; Adult ; Insect Repellents/urine* ; DEET/urine* ; Young Adult ; Male ; Japan ; Female ; Chromatography, Liquid ; Biomarkers/urine* ; Chromatography, High Pressure Liquid ; East Asian People

BACKGROUND: Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries. METHODS: A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95^th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93), CONCLUSIONS This study represents the first comprehensive exposure assessment for DON, T2/HT2, and ZEN in Japanese adults using human biomonitoring methods. These data provide valuable information for a better understanding of mycotoxin exposure in Japan.
Humans ; Zearalenone/urine* ; Japan ; Male ; Female ; Trichothecenes/urine* ; T-2 Toxin/urine* ; Biological Monitoring ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Young Adult ; Mycotoxins/urine* ; Environmental Exposure/analysis* ; East Asian People

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH₂-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH₂-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH₂-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.
Agriculture ; Child, Preschool ; Environmental Exposure/analysis* ; Humans ; Infant ; Insecticides ; Japan ; Mass Spectrometry ; Pyrethrins/urine*

BACKGROUND: Glyphosate and its salt formulations are nonselective herbicides that have been extensively used worldwide, both for residential and agricultural purposes. The possible carcinogenicity and teratogenicity of glyphosate remain to be elucidated. We developed a sensitive and high-throughput analytical method for urinary glyphosate using liquid chromatography-tandem mass spectrometry with the aim of contributing to glyphosate exposure assessment in epidemiological studies. METHODS: After urine dilution (creatinine matching dilution to 0.05 g creatinine/L), glyphosate was extracted using two types of solid phase extraction columns (SCX and NH2) with automated sample preparation instruments. The eluate was dried and dissolved in the mobile phase, followed by liquid chromatography-tandem mass spectrometry analysis. The optimized method was applied to urine samples obtained from 54 Japanese adults and children. RESULTS: The results from the validation study demonstrated good recoveries (91.0-99.6%), within- and between-run precisions (< 15%), low detection limits (0.1 μg/L), and lower limit of quantification (0.3 μg/L). The detection frequency and median concentration of the urinary glyphosate in Japanese subjects were 59% and 0.25 μg/L (0.34 μg/g creatinine). CONCLUSIONS Our reliable determination method was successful in measuring urinary glyphosate concentration. Moreover, this is the first biomonitoring report of urinary glyphosate levels in the Japanese general population.
Adult ; Aged ; Chromatography, Liquid/methods* ; Female ; Glycine/urine* ; Humans ; Male ; Middle Aged ; Solid Phase Extraction/methods* ; Tandem Mass Spectrometry/methods*

BACKGROUND: We aimed to examine the association of exposure to environmental tobacco smoke with dental caries among preschool children. Exposure to environmental tobacco smoke was assessed in terms of urinary cotinine concentrations and pack-years of exposure to smoking by parents and other family members at home. METHODS: This cross-sectional study included 405 preschool children aged 3-6 years from two preschools in Japan in 2006. Information on the smoking habits of family members living with the child was obtained from parent-administered questionnaires. Dental examination was conducted to assess dental caries, that is, decayed and/or filled teeth. Urinary cotinine levels were measured using first-void morning urine samples. RESULTS: Overall, 31.1% of the children had dental caries, and 29.5% had decayed teeth. Exposure to current maternal and paternal smoking was positively associated with the presence of dental caries after controlling for covariates. More than three pack-years of exposure to maternal smoking and more than five pack-years of exposure to smoking by all family members were significantly associated with the presence of dental caries as compared with no exposure (odds ratio [OR] = 5.55, 95% confidence interval [CI] = 2.17-14.22, P for trend < 0.001 and OR = 2.00, 95% CI = 1.12-3.58, P for trend = 0.004, respectively). These exposure variables were similarly associated with the presence of decayed teeth (OR = 2.92, 95% CI = 1.23-6.96, P for trend = 0.01 and OR = 1.75, 95% CI = 0.96-3.20, P for trend = 0.03, respectively). As compared with lowest tertile of the urinary cotinine level, the highest tertile of the urinary cotinine level was significantly associated with the presence of dental caries as well as decayed teeth; the ORs for the highest vs. lowest tertile of urinary cotinine levels were 3.10 (95% CI = 1.71-5.63, P for trend = 0.012) and 2.02 (95% CI = 1.10-3.70, P for trend = 0.10), respectively. CONCLUSIONS These data suggest that exposure to tobacco smoke may have a dose-dependent influence on the development of caries.
Child ; Child, Preschool ; Cotinine ; urine ; Cross-Sectional Studies ; Dental Caries ; epidemiology ; etiology ; Female ; Humans ; Japan ; epidemiology ; Logistic Models ; Male ; Maternal Exposure ; adverse effects ; Parents ; Paternal Exposure ; adverse effects ; Risk Factors ; Surveys and Questionnaires ; Tobacco Smoke Pollution ; adverse effects ; Tobacco Smoking ; adverse effects ; epidemiology

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 ; Chromatography, Liquid ; Creatinine ; urine ; Environmental Exposure ; analysis ; Environmental Monitoring ; methods ; Environmental Pollutants ; urine ; Female ; Humans ; Japan ; Mass Spectrometry ; Organophosphates ; urine ; Pesticides ; urine ; Pregnancy ; Pregnant Women ; Young Adult

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 β = - 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.
Adult ; Aged ; Aged, 80 and over ; Atherosclerosis ; epidemiology ; etiology ; Biomarkers ; Carotid Intima-Media Thickness ; statistics & numerical data ; Cross-Sectional Studies ; Female ; Humans ; Japan ; epidemiology ; Male ; Middle Aged ; Oxidation-Reduction ; Risk Factors ; Serum Albumin ; metabolism ; Serum Albumin, Human ; metabolism

Primary cardiac myxofibrosarcoma is an extremely rare malignant tumor of the heart, which can be difficult to diagnose. We report such a case, which recurred 7 months after the initial heart surgery. A 63-year-old woman with progressive dyspnea was seen by a physician. A transthoracic echocardiography revealed a large mobile mass in the left atrium, causing severe mitral stenosis. The patient was referred to our hospital for an operation. The tumor, which arose from the anterior mitral annulus, was resected, and mitral and tricuspid annuloplasty were performed. The histopathological diagnosis was myxoma. The postoperative course was uneventful. Seven months later, the patient reported suffering from dyspnea and leg edema. The echocardiography showed multiple recurrences of tumor in the left atrium. A second operation was performed to reduce the mass volume as a palliative treatment because some large fragile tumors occupied the left atrium. The patient died 5 months after the second operation due to metastasis. The final diagnosis by histopathology was myxofibrosarcoma.

OBJECTIVESThe ingestion of pesticides in the daily diet is assumed to be the main modality of pesticide exposure for most people. A widely used class of pesticides in agricultural or residential settings is pyrethroid. We have examined the relationship between the intake frequency of selected items of vegetables and fruits and urinary metabolites of pyrethroid pesticides in a healthy general population.

METHODSA total of 535 residents (184 men and 351 women) who attended a healthcare checkup program conducted in a rural area of Hokkaido, Japan, in August 2005 provided informed consent for their spot urine samples to be used for the determination of 3-phenoxybenzoic acid (3-PBA) levels. They also completed a self-administered questionnaire regarding the intake frequency of 12 food items. The concentrations of creatinine-corrected 3-PBA were predicted by the intake frequency of each item, using analysis-of-covariance models to adjust for age, sex, body mass index, and drinking and smoking status.

RESULTSBoth a significant association between the 3-PBA concentration and the frequency of tomato consumption and a significant positive linear trend was found in female subjects. In contrast, no such association was found in the male subjects.

CONCLUSIONSThe frequency of tomato consumption was confirmed to strongly predict the urinary pyrethroid metabolite levels in the general population-presumably because tomatoes are most often consumed raw and unpeeled (more so than all other vegetables and fruits analyzed in the current study). However, it should be noted that the 3-PBA levels, even among those subjects with the highest consumption of tomatoes, were far below the levels of toxicological significance, although the health consequences from long-term low-level exposure to pyrethroid requires further exploration.

OBJECTIVESPolyamines have long been known to have an insulin-like action, but their antiglycating effect has only recently attracted the attention of researchers. The aim of our investigation was to determine the whole blood polyamine concentration in a healthy population in order to examine its relationship with glycemic profiles.

METHODSThe study cohort comprised 622 men aged 40-59 who participated in a health checkup program conducted in 1997, when they underwent measurements of fasting plasma glucose (FPG), insulin (FPI), and fructosamine as glycemic indices. Colorimetric assay methods using oat and barley seedling polyamine oxidase were used to determine total polyamine (spermidine + spermine) and spermine concentrations in the whole blood, respectively. Polyamine concentrations adjusted for hemoglobin were quartiled for the analysis of covariance to assess the association with glycemic indices.

RESULTSA significant association was demonstrated between the FPG and total polyamine concentrations. In the trend test, FPG and fructosamine levels increased in accordance with the shift of quartiles of total polyamine concentrations from low to high. In contrast, the association between the spermine and glycemic indices was not statistically significant based on the test for difference of multivariate-adjusted means or trend for linearity.

CONCLUSIONSThis is the first epidemiological study to reveal that the concentrations of blood polyamines are related with either FPG or fructosamine level in a healthy population. There may be some feedback mechanism for the elevation of circulating polyamines to quench the glycation reaction under hyperglycemic conditions. In addition, total polyamines, rather than spermine alone, seem to be a sensitive biomarker representing the antiglycation effect of polyamines.