Yayoi Suzuki

Foetal exposure to phthalate esters and anogenital distance in male newborns.

Phthalate esters, commonly used as plasticizers, show anti-androgenic activity and cause male reproductive malformation in experimental animals. However, the effects of prenatal exposure to phthalate esters in humans have not been extensively studied. The purpose of this study was to examine the relationship between prenatal exposure to phthalate esters and the anogenital distance (AGD) as a reproductive endpoint in human male newborns. Spot urine samples were collected from 111 Japanese pregnant women after obtaining their informed consent. Seven urinary phthalate ester metabolites were determined by high performance liquid chromatography-tandem mass spectrometry. Urinary isoflavones concentrations were measured as possible covariates because their oestrogenicities and high exposure levels among Japanese have the potential to affect male genital development. Birth outcomes and AGD, the distance from the centre of the anus to external genitalia, were measured for their male newborns. In a multiple regression model, the log-transformed mono-2-ethylhexyl phthalate concentration (specific gravity-corrected) was negatively significant, and maternal smoking status was positively significant, in explaining anogenital index (AGI) when potential covariates were controlled for. Urinary isoflavones did not significantly contribute to AGI in any models. Our results suggest that prenatal exposure to di(2-ethylhexyl) phthalate affects reproductive development in human males.

Prenatal exposure to phthalate esters and PAHs and birth outcomes

The purpose of this study was to investigate the relationship between the levels of prenatal exposure to phthalate ester and PAHs and birth outcomes among 149 Japanese pregnant women. Urinary concentrations of 9 phthalate ester metabolites, mono methyl phthalate (MMP), mono ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-iso-nonyl phthalate (MINP) and mono-n-octyl phthalate (MnOP) and PAHs metabolite (1-hydroxypyrene, 1-OHP) were analyzed in spot urine samples collected from pregnant women. Correlation analysis and multiple regression analysis were conducted between the concentrations of maternal urinary metabolites and birth outcomes such as birth weight, birth length, head circumference and gestational age. Creatinine-corrected concentration (geometric mean; microg/g cre) was 9.14 (MMP), 9.76 (MEP), 51.6 (MnBP), 5.62 (MBzP), 5.45 (MEHP), 10.6 (MEHHP), 11.3 (MEOHP), 0.031 (MINP), 0.025 (MnOP) and 0.121 (1-OHP). These concentrations are comparable with literature value. The relationships between prenatal exposure to phthalate esters and birth outcomes were not significant. Statistically significant negative correlation was observed between 1-OHP and birth weight, birth length and head circumstances although the correlation was insignificant when only non-smokers were included in multiple regression analysis. In conclusion, we found that prenatal exposure to phthalate esters or PAHs did not affect birth outcomes at the exposure level of the present subjects.

Maternal exposure to low-level heavy metals during pregnancy and birth size

We evaluated the effect of environmental, low-level exposure to heavy metals during pregnancy, as estimated by urine analysis, on birth size of the newborns. Spot urine samples were collected from unexposed 78 pregnant women in Tokyo during 2007 and 2008. The urinary concentrations of beryllium (Be), copper (Cu), arsenic (As), zinc (Zn), selenium (Se), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), and lead (Pb) were measured by ICP-MS. The birthweight (BW), length (BL) and head circumference (HC) of the newborns delivered to the subjects were measured and relationship with urinary metal concentration was examined. The geometric mean concentration of urinary Be, Cu, As, Zn, Se, Mo, Cd, Sn, Sb, and Pb were 0.031, 12.8, 393, 76.9, 37.6, 79.0, 0.766, 0.232, < 0.21, 0.483 μ g g-creatinine− 1, respectively. The mean birth size of the newborn was close to the national average value in Japan. Stepwise multiple regression analysis using birth size as a dependent variable and urinary metal concentrations and covariates as independent variables extracted urinary Cd with a significant negative standardized partial regression coefficient (β) for BW along with gestational age and maternal BMI. For HC, Sn was selected with a negative β. The present study suggested that even a low-level Cd body burden of general population has slight but significant negative effect on BW.

Urinary excretion of parabens in pregnant Japanese women.

Urinary excretion of free and total (free plus conjugated) forms of methyl, ethyl, n-propyl and n-butyl parabens (MP, EP, PP and BP, respectively) and their metabolite p-hydroxybenzoic acid were measured for 111 pregnant Japanese women. Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women. The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered. Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products. No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.

Endocrine disrupting chemicals in urine of Japanese male partners of subfertile couples: a pilot study on exposure and semen quality.

The concentrations of chemicals with suspected endocrine disrupting effect were measured in urine samples collected from 42 Japanese male partners of couples who had infertility consultation at a gynecology clinic in Tokyo. The urinary analytes included metabolites of 5 phthalate diesters, pyrethroid insecticide (3-phenoxybenzoic acid, 3-PBA) and soy isoflavones (daidzein and equol), and cadmium. The semen parameters (semen volume, concentration and motility) of the male subjects were examined at the clinic as a diagnostic screening. Multiple regression analysis using one of the semen parameters examined as dependent variable and urinary biomarkers with age, body mass index, abstinent period, alcohol drinking, smoking and consumption frequency of selected foods as independent variables. For sperm concentration, urinary mono-n-butyl phthalate was selected as a significant independent variable with positive beta, while urinary daidzein was with negative beta. Consumption frequency of coffee (negative) and fruits (positive) were also significant. For sperm motility, urinary 3-PBA was selected as significant with negative beta as well as detectability of equol and frequency of coffee consumption with negative beta while smoking was with positive beta. This pilot study suggested the pyrethroid exposure level and dietary habit (coffee and soy products) as a significant contributor to poorer semen quality.

Formation of mutagens from tryptophan by the reaction with nitrite

Summary Tryptophan treated with nitrite under acidic conditions was found to be mutagenic to Salmonella typhimurium tester strains TA 100 and TA 98 both in the presence and in the absence of S-9 mix. Tryptamine, glycyltryptophan and indole were also mutagenic when treated with nitrite, suggesting that the appearance of mutagenic activity from tryptophan was attributable to the reaction of nitrite with the indole ring. Nitrite-treated arginine and proline were not mutagenic in the presence of S-9 mix.

Sudden bilateral hearing loss due to gastric carcinoma and its histological evidence

Six temporal bones and a brain tissue sample removed at autopsy from four patients with bilateral sudden hearing loss related to gastric adenocarcinoma were histologically studied. The pathological remains suggest that the sudden hearing loss of these patients may have occurred via one of two different mechanisms: (1) metastasis to the internal auditory meatus damaging the auditory nerve or (2) inner ear haemorrhage damaging Cortis organ. These two mechanisms may cause bilateral sudden deafness in patients with gastric adenocarcinoma.

Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Birth Outcomes

The effect of prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) at the environmental level on birth size was examined. The concentration of 1-hydroxypyrene (1-OHP) in spot urine samples collected from 50 pregnant women in Tokyo was measured and was related to birth weight, length, and head circumference of the newborns the subjects delivered. Analysis of inter- and intra-individual variation in 1-OHP concentration in spot urine samples from non-smoking subjects revealed that single spot urine can represent the subjects exposure to PAHs over several weeks and utility of spot urine for assessing PAHs exposure level of non-smokers was indicated. Geometric mean urinary concentration of 1-OHP of the subjects was 0.056 μmol/mol creatinine, and smoking mothers (n = 7) excreted more 1-OHP (0.200 μmol/mol-cre) than non-smoking mothers (0.046 μmol/mol-cre). Multiple regression analysis using birth outcomes as the dependent variable and urinary 1-OHP and other covariates as independent variables revealed that urinary 1-OHP was not a significant variable to explain birth outcomes among non-smoking mothers.

Inter- and intra-individual variation in urinary excretion of daidzein and equol in female Japanese

Abstract Objective: To evaluate the representativeness of single measurement of urinary soy-isoflavone concentrations for the assessment of long-term intake levels. Methods: Five urine samples taken from 14 Japanese female subjects over 2–3 months were measured for daidzein and equol by gas chromatography-mass spectrometry (GC-MS). Results: Geometric mean daidzein and equol concentrations of 14 subjects were 582 and 2.66 μg/g creatinine, respectively. Intra-class correlation coefficients for daidzein and equol were 0.355 (95% CI: 0.130–0.649) and 0.741 (0.551–0.891), respectively. Conclusion: Single measurement of urinary equol is effective for the assessment of long-term equol status of Japanese subject while that of daidzein is not.

Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects

ABSTRACT Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg−1 day−1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL−1. Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.