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The occurrence of 70 pharmaceutical and personal care products (PPCPs) was investigated in the Tone River. The river has the largest basin in Japan, and the water is utilized not only for farming, but also as a source of water supply. One day in both January and October 2006, surface waters in the river and its tributaries and effluents from sewage treatment plants (STPs) directly discharging into the Tone River were collected, the location of which ranged over 150 km along the river. The 70 PPCPs in the samples were concentrated by solid phase cartridge and were measured by LC-MS/MS using three analytical methods. Fifty-seven PPCPs were detected in one or more samples. Bezafibrate, caffeine, carbamazepine, clarithromycin, crotamiton and sulpiride were frequently detected. Mass flow profiles of some PPCPs (e.g., crotamiton) were comparable to cumulative inhabitants in the basin, suggesting that these PPCPs could be markers of population. Total load of each PPCP into the basin from upstream, the tributaries, and the STPs were calculated. The contribution of selected PPCPs from the tributaries with lower sewerage system coverage was dominant compared to those from upstream and the STPs, suggesting the installation of sewerage systems is necessary to reduce the load of PPCPs in the Tone River basin. [ABSTRACT FROM AUTHOR]

Residual pharmaceutical products in sewage and other water environments have recently become a serious social problem in advanced countries. Among these pharmaceutical products, antibiotics have attracted special attention due to their serious impact on the ecosystem and connections to the emergence of drug-resistant bacteria. Our research intended to develop a new method to analyse the three antibiotics estimated to be released out of the body in large amounts in Japan; levofloxacin (LVFX), clarithromycin (CAM) and azithromycin (AZM), and survey the state of pollution in the sewerage. The concentrations of the water-phase antibiotics LVFX, CAM and AZM were measured in each process of activated sludge process in six wastewater treatment plants. Liquid chromatography tandem mass spectrometry (LC/MS/MS) was used to analyse solutions of the antibiotics after pretreatment with a solid phase extraction. The limits of quantification and the average recoveries for these antibiotics in the influent were 1.2 to 29 ng/L and 46 to 93%, respectively. In the influent, LVFX, CAM and AZM were detected at concentrations of 552, 647 and 260 ng/L, respectively, while their removal efficiencies were 42, 43 and 49%, respectively. Although the CAM and AZM concentrations decreased as the treatment progressed, it was shown that the LVFX concentration increased in activated sludge reactors in some cases. Despite differences in octanol-water partition coefficients among LVFX, CAM and AZM, their removal efficiency showed no major difference. This indicates that this removal phenomenon cannot be explained by simple adsorption by the activated sludge. [ABSTRACT FROM AUTHOR]

Estrogen-like substances have been suspected to cause feminization of wild fish in rivers in Japan. To elucidate the influence of estrogen-like substances on fish in river, we have started to develop the on-site continuous fish exposure system using medaka Oryzias latipes that were placed in water quality monitoring stations along a river. Adult male medaka were exposed to the river water in a glass exposure tank placed in the monitoring stations. Flow rate of water and water temperature were controlled at 30 L/hour and 26 °C respectively, and a light: dark cycle was maintained 16:8 hours. A commercial diet free from phytoestrogens was fed 4 times in a day using automatic feeder. After 2-week exposure, hepatic vitellogenin concentration of each male medaka was measured. The exposure tests were repeatedly performed at both the upstream and the downstream of sewage treatment plants along the River Tama which is a representative urbanized river in Japan. At the control site Haijimabashi monitoring station, vitellogenin was not detected in male medaka. On the other hand, at the Ishihara monitoring station which is the most downstream in this test area, every male medaka were produced vitellogenin in the test performed in the spring of 2004. As the results of the water quality analysis, it could be inferred that the estrone derived from effluents of sewage treatment plants caused the feminization of male medaka. The reason why the concentrations of the estrone and the estrogenic activity using DNA recombinant yeast varied in proportion to the electric conductivity of river water measured at the water quality monitoring station. Furthermore, after continuous 2-week exposure, the vitellogenin production of male medaka was reduced similar to the decrease of the concentrations of the estrone and the estrogenic activity of river water. [ABSTRACT FROM AUTHOR]

Background: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP., Methods: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis., Result: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed., Conclusion: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications., Competing Interests: Declaration of competing interest Hiroshi Mukae received lecture honoraria and research grants from KYORIN Pharmaceutical Co., Ltd. Outside of the submitted work., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF.

The contribution of specific precursors to N-nitrosodimethylamine formation potential (NDMA FP) upon chloramination depends not only on their NDMA molar yields but also on their concentrations in the actual environment. We investigated the seasonal and diurnal patterns of the NDMA precursor N,N-dimethylformamide (DMF) and NDMA FP in the Yodo River basin, Japan, by examining water samples taken from inside the basin's largest sewage treatment plant (STP) as well as samples from five final effluents from four STPs, two main stream sites, and two tributary sites in the same basin. DMF and NDMA FP were found to be high in influent (raw sewage), and were found to be mostly removed during the STP treatment processes (especially with biological treatment). Nevertheless, DMF was found in concentrations of 0.06 to 31.7 µg/L in chlorinated effluents and in receiving rivers, while NDMA FP was detected in concentrations of 3.57 to 306 ng/L. Thus, STPs were shown to be an important source of DMF and NDMA FP to rivers. A strong positive correlation between NDMA FP and DMF was confirmed in the receiving river (K-M), indicating that DMF was an important NDMA precursor in the Yodo River basin. The contribution of DMF to NDMA FP was 15.8±11.2% (n = 4) in summer and 82.1±10.2% (n = 4) in winter in the main stream (site K-M) of the river due to insufficient dilution of chlorinated effluents from the largest STP. From the viewpoint of NDMA and NDMA FP control at downstream sites, monitoring and control of DMF at upstream sites are important., Competing Interests: Declaration of Competing interest none, (Copyright © 2021. Published by Elsevier Ltd.)

Pharmaceuticals raise concerns for aquatic species owing to their biological activities. It is estimated that nearly 40% of marketed pharmaceuticals target G protein-coupled receptors (GPCRs). Using an in vitro transforming growth factor-α (TGFα) shedding assay, we previously detected antagonistic activities of GPCR-acting pharmaceuticals against angiotensin (AT1), dopamine (D2), acetylcholine (M1), adrenergic family members (β1), and histamine (H1) receptors at up to μg-antagonist-equivalent quantities/L in wastewater in England and Japan. However, which pharmaceuticals were responsible for biological activities in wastewater remained unclear. Here, we used (1) the consumption of GPCR-acting pharmaceuticals, particularly antagonists, as calculated from prescriptions, (2) their urinary excretion, and (3) their potency measured by the TGFα shedding assay to prioritize them for analysis in wastewater in England and Japan. We calculated predicted activities of 48 GPCR-acting pharmaceuticals in influents in England and Japan and identified which were mainly responsible for antagonistic activities in wastewater against each GPCR. Mixtures of pharmaceuticals tested in this study were confirmed to behave additively. The combination of consumption and potency is useful in prioritizing pharmaceuticals for environmental monitoring and toxicity testing.

While pharmaceuticals are now routinely detected in aquatic environments, we know little of the biological activity their presence might provoke. It is estimated that nearly 40% of all marketed pharmaceuticals are G protein-coupled receptors (GPCRs) acting pharmaceuticals. Here, we applied an in-vitro assay, called the TGFα shedding assay, to measure the biological activities of GPCRs-acting pharmaceuticals present in effluents from municipal wastewater treatment plants in the United Kingdom (UK) and Japan from 2014 to 2016. The results indicated that compounds were present in the wastewater with antagonistic activities against angiotensin (AT1), dopamine (D2), adrenergic (β1), acetylcholine (M1), and histamine (H1) receptors in both countries. The most consistent and powerful antagonistic activity was against the H1, D2, and AT1 receptors at up to microgram-antagonist-equivalent quantity/L. Chemical analysis of the same UK samples was also conducted in parallel. Comparing the results of the bioassay with the chemical analysis indicated (1) the existence of other D2 or M1 receptor antagonists besides sulpiride (D2 antagonist) or pirenzepine (M1 antagonist) in wastewater and (2) that there might be a mixture effect between agonist and antagonistic activities against β1 receptor. GPCR-acting pharmaceuticals should be paid more attention in the environmental monitoring and toxicity testing in future studies.

To reduce the risk of producing an anti-influenza drug-resistant virus from wildfowl, it is important to estimate the concentrations of anti-influenza drugs in river water during an influenza pandemic and to evaluate the concentrations that keep river basins safe. We first created a newly designed infectious disease transmission model based on the Susceptible-Infected-Recovered model. This model was then applied to replicate the transitional changes of three representative anti-influenza drugs, oseltamivir (OS), oseltamivir carboxylate (OC), and zanamivir (ZAN), in the urban area of the Yodo River system, which is one of the major basins in Japan with a population of 12 million; this region contains nearly 10% of the country's flu cases during the seasonal influenza outbreaks between 1999 and 2010. The results showed high correlations between the estimated number of influenza cases and the concentrations of the three investigated anti-influenza drugs with the reported values. We then extended the application of the model to estimate the concentration level of these anti-influenza drugs during the several influenza pandemics. The maximum estimated concentrations for OS, OC, and ZAN were known to be 260-450ng/L, 1500-2600ng/L and 40-70ng/L, respectively, at the peak of the influenza pandemic. These results suggest that it is possible that a drug-resistant influenza virus can originate from wild mallard when there is a large-scale influenza pandemic. However, ozonation before discharge at sewage treatment plants is known to significantly reduce the release of such drugs into the aquatic environment to reduce the risk of a drug-resistant virus outbreak. It was also suggested that further environmental risk could be reduced by decreasing these concentrations further in river water., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A simple model was set up to predict estrogen concentrations and endocrine disruption risk in the Yodo River, Japan. This catchment spans the conurbations of Kyoto and Osaka and is the main source of drinking water for Osaka City, Japan. From the river survey data (5 separate occasions between 2005 and 2008), a maximum of 32 g per day estrone (E1) load was observed in the most downstream site of the river. Predicted E1 concentrations were in reasonable agreement with the measurements taken at several points within the basin from a series of sampling campaigns. The predicted concentrations exceeded a net estradiol (E2) equivalent of 1 ng L(-1) on only a few occasions, suggesting that only limited endocrine disruption phenomena in fish along the Yodo River is likely. The model was then used to examine the impact on estrogen concentrations and endocrine disruption of a number of different scenarios. It was found that in-river biodegradation had little effect on predicted concentrations and the outcome of endocrine disruption along the catchment. However, reduced sewage treatment removal, as can be experienced in winter in Japan, led to levels of 3.1 ng L(-1) E2 equivalents being possible. The reduced river flow in winter in Japan exacerbates the situation as it offers less dilution. It was found that the application of the ozonation process as a tertiary sewage treatment in winter could prevent this higher risk endocrine disruption situation.

The fate and removal of 48 pharmaceuticals and personal care products (PPCPs) during anaerobic digestion of sewage sludge were investigated in four full-scale sewage treatment plants (STPs). We measured concentrations in both the liquid and solid phases of the sludge to compare the distribution ratios (Kd) between phases before and after digestion. The results showed changes in Kd values of PPCPs with carboxyl or amino functional groups, probably due to a shift of dissociation equilibrium with the increase in pH. Sulfamethoxazole and trimethoprim were almost completely degraded (>90%); triclosan, triclocarban, and ofloxacin were moderately degraded (around 30-50%); but carbamazepine was not eliminated. To our knowledge, this is the first report that shows (i) the occurrence and removal of several tens of PPCPs by anaerobic sludge digestion in full-scale municipal STPs and (ii) the change of distribution between the liquid and solid phases during digestion., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Despite the fact that some hydrophobic pharmaceuticals and personal care products (PPCPs) have been found to accumulate in river sediments, little is known about the contribution of these compounds to the toxicity of the whole sediment. We sampled river sediments from two urban creeks with an unsewered drainage area to investigate the toxicity for a benthic organism, Chironomus yoshimatsui. The concentrations of selected hydrophobic PPCPs, triclosan (TCS), triclocarban (TCC) and galaxolide (HHCB) were analysed using gas chromatographic mass spectroscopy or liquid chromatographic mass spectroscopy and were found to lie within the range 50 to 200 ng g(-1). The toxicity of the three individual contaminants for the chironomid was also determined. The toxicity of TCC was found to be the strongest, with an NOEC value of 2.5 microg g(-1). Combining the toxicity and measured environmental concentration, the ecological risk was assessed and the contribution of these contaminants to the whole sediment toxicity estimated, assuming additivity. The hazard quotient of all three compounds, determined without assessment factor, ranged between 0.01 and 0.1. The combined contribution of the three compounds to total sediment toxicity was as high as 8.2%, but other unknown factors may also make an important contribution.

N-nitrosamines are well known as carcinogens present in the environment. However, studies of the occurrence and fate of N-nitrosamines and their N-nitrosamine formation potential (FP) in wastewater treatment plants (WWTPs) are lacking. Therefore, the objectives of this study were to determine the occurrence of N-nitrosamines in WWTPs, the FP of N-nitrosamines on chloramination during wastewater treatment, and the efficiency of FPNH2Cl reduction by biological treatment. Also, the residual FPNH2Cl in the final discharge was investigated. The efficiencies of removal of N-nitrosamines ranged from 35 to 94% (WWTP O; residential area), from 58 to 98% (WWTP E; industrial area), and from 58% to >99% (WWTP N; industrial area). In WWTP O, the rates of production of N-nitrosodimethylamine (NDMA) (42%) and NDBA (58%) were the highest. In WWTP E, only NDBA (34%) was produced. In WWTP N, NPYR and NPIP (both >99%) were produced. NDMA FPNH2Cl values were very high in influent in all WWTPs. The efficiencies of removal of N-nitrosamine FPNH2Cl during biological treatment ranged from 20% to >99%, but there is no obvious explanation for this variability. Residual N-nitrosamine FPNH2Cl ranged from 2 to 22 ng L(-1). Thus, N-nitrosamines could be produced in water purification or reclamation plants using discharge from WWTPs.

Background and Aims: Molecular target therapy against L-type amino acid transporter 1 (LAT1) is unique and expected to be developed soon. LAT1 expression was investigated in pancreatic cancer as a prognostic predictor., Methods: Surgically resected pancreatic ductal adenocarcinomas (PDAC, n=66) were investigated using immunohistochemistry. For reference, intraductal papillary mucinous carcinomas (IPMC, including intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia or with an associated invasive carcinoma, n=13) and adenomas (IPMA, including IPMN with low- and intermediate-grade dysplasia, n=5) were also examined., Results: LAT1 expression scores increased from PDAC to IPMA to IPMC. Kaplan-Meier analysis showed significant differences between LAT1-high and -low scores in PDAC. Even in each Ki-67-labelling index (LI) low and high PDAC group (cut off 40%), high LAT1 expression could also predict poor prognosis. Multivariable analysis showed that LAT1 expression, Ki-67 LI, tumour differentiation and size were individual prognostic factors., Conclusions: LAT1 aberrant overexpression in PDAC predicts poor prognosis, independent of Ki-67 LI, and offers a potential target for future anticancer therapy with its inhibitors.

We report the results of a nationwide survey of commonly used human and veterinary antibiotics (7 sulfonamides, trimethoprim, and 4 macrolides) in 37 Japanese rivers. Concentrations of the sum of the 12 target antibiotics ranged from undetectable to 626 ng/L, with a median of 7.3 ng/L for the 37 rivers. Antibiotics concentrations were higher in urban rivers than in rural rivers and were correlated with those of molecular markers of sewage (crotamiton and carbamazepine). Macrolides were dominant over sulfonamides in urban rivers. Sulfonamides, especially sulfamethazine (used in animals), were dominant in a few rivers in whose catchment animal husbandry is active. However, these signals of veterinary antibiotics were overwhelmed by those of human antibiotics in lower reaches of most rivers. The analysis of the antibiotics in all 88 samples showed that the target antibiotics in Japanese rivers are derived mainly from urban sewage, even though larger amounts of antibiotics are used in livestock. Most of the livestock waste-derived antibiotics are unlikely to be readily discharged to surface waters., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A detailed study of the free and conjugated estrogen load discharged by the eight major sewage treatment plants into the Yodo River basin, Japan was carried out. Sampling campaigns were focused on the winter and autumn seasons from 2005 to 2008 and the free estrogens estrone(E1), 17β-estradiol(E2), estriol(E3), 17α-ethynylestradiol(EE2) as well as their conjugated (sulfate and glucuronide) forms. For both sewage effluent and river water E2 and E1 concentrations were greatest during the winter period (December-March). This coincides with the period of lowest rainfall and lowest temperatures in Japan. E1 was the dominant estrogenic component in effluent (means of 10-50 ng/L) followed by E2 (means of 0.5-3 ng/L). The estrogen sulfate conjugates were found intermittently in the 0.5-1.7 ng/L concentration range in the sewage effluents. The greatest estrogen exposure was found to be in the Katsura River tributary which exceeded 1 ng/L E2-equivalents during the winter period., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Oseltamivir phosphate (OP; Tamiflu) is a prodrug of the anti-influenza neuraminidase inhibitor oseltamivir carboxylate (OC) and has been developed for the treatment and prevention of both A and B strains of influenza. The recent increase in OP resistance in influenza A virus (H1N1; commonly called "swine flu") has raised questions about the widespread use of Tamiflu in seasonal epidemics and the potential ecotoxicologic risk associated with its use in the event of a pandemic., Objectives: The objectives of this study were to develop an analytical method for quantitative determination of OC in sewage treatment plant (STP) effluent and receiving river water, and to investigate the occurrence of OC in STP effluent and river water in Japan during a seasonal flu outbreak., Methods: We developed an analytical method based on solid-phase extraction followed by liquid chromatography-tandem mass spectrometry. Using this method, we analyzed samples from three sampling campaigns conducted during the 2008-2009 flu season in Kyoto City, Japan., Results: The highest concentration of OC detected in STP discharge was 293.3 ng/L from a conventional activated-sludge-based STP; however, we detected only 37.9 ng/L from an advanced STP with ozonation as a tertiary treatment. In the receiving river water samples, we detected 6.6-190.2 ng/L OC, during the peak of the flu season., Conclusion: OC is present in STP effluent and river water only during the flu season. Ozonation as tertiary treatment in STP will substantially reduce the OC load in STP effluent during an influenza epidemic or pandemic.

A nonlinear mixed-effect modeling (NONMEM) program was used to evaluate the effects of cytochrome P450 (CYP) 2C9 and CYP2C19 polymorphisms on the phenobarbital (PB) population clearance for Japanese epileptics. The pharmacokinetics of the 260 PB concentrations at a steady-state obtained from 79 patients was described with a one-compartment open pharmacokinetic model with first-order elimination. The covariates screened included the total body weight (BW), age, gender, PB daily dose, CYP2C9 and CYP2C19 genotypes, the coadministered antiepileptic drugs (AEDs), and complications. The final model of PB apparent clearance was as follows: CL = 0.23 x (BW/40)0.21 x 0.52CYP2C9*1/*3 x 0.68VPA x 0.85PHT x 0.85SMID x (1 + etaCL) where CL = the clearance of PB; CYP2C9*1/*3 = 1, otherwise 0; VPA = 1 if valproic acid is coadministered, otherwise 0; PHT = 1 if phenytoin is coadministered, otherwise 0; SMID = 1 if complications of severe or profound mental retardation with a significant behavior impairment are presented, otherwise 0; and etaCL = the independent random error distributed normally with the mean zero and variance equal to omegaP2. The total clearance of PB decreased by 48% in patients with CYP2C9*1/*3 genotype in comparison with those with CYP2C9*1/*1 genotype (P < 0.001). An effect of CYP2C19 polymorphisms was not detected. To our knowledge, this is the first report to demonstrate that the CYP2C9 genotype affects the PB metabolism in routine care, but the results should be further verified in other ethnic populations.

Objective: To clarify the association between the cytochrome P450 (CYP) 1A2 genotype with the CYP1A2 phenotype and to search for the CYP1A2*1K haplotype, which has been shown to decrease CYP1A2 inducibility and/or other functional polymorphisms in Japanese., Methods: Two polymorphisms, CYP1A2*1C and CYP1A2*1F, were genotyped in 126 patients receiving oral slow-release theophylline (TP) therapy and in 224 healthy volunteers. The CYP1A2 phenotype was assessed by the plasma [1-methyluric acid (1U)+3-methylxanthine (3X)]/TP ratio in the patients. The volunteers were given 150 mg caffeine, and the urine [1X+1U+5-acetylamino-6-amino-3-methyluracil (AAMU)]/17U ratio was used for CYP1A2 phenotyping. CYP1A2 intron 1 and six exons (exon 2-exon 7) were sequenced in the patients whose (1U+3X)/TP ratios were below the mean-2SD of those of all patients, and intron 1 was also sequenced in an additional 20 healthy volunteers exhibiting putative low CYP1A2 activities., Results: The individual (1U+3X)/TP ratios ranged from 0.007 to 0.21 (a 30-fold difference) in the patients, and the (1X+1U+AAMU)/17U ratios ranged from 1.6 to 112 (a 70-fold difference) in the healthy volunteers. The CYP1A2 activities were not significantly influenced by CYP1A2*1C or CYP1A2*1F. We found no functional polymorphisms by a sequencing analysis., Conclusion: These results suggest that the CYP1A2*1C and CYP1A2*1F genotypes are not crucial factors for the variability of CYP1A2 activity and that the CYP1A2*1K haplotype is either nil or only shows a very low frequency in Japanese.

The fates of anti-inflammatory drugs (e.g., ibuprofen, naproxen, mefenamic acid and ketoprofen), which are frequently detected in the discharges of wastewater treatment plants (WWTPs) and river water in Japan, were clarified in two WWTPs. The concentrations of ibuprofen, naproxen, mefenamic acid and ketoprofen were 69-1080, 179-305, 143-1580 and 160-1060 ng/L in the influent, and N.D. (< 40 ng/L), 74-166, 72-265, 64-107 ng/L in the effluent, respectively. The concentrations of the anti-inflammatory drugs analyzed were almost equal to or lower than those reported in foreign countries. High removal efficiencies of the drugs, except ibuprofen, were observed in the WWTP that has longer hydraulic retention time than that of the other WWTP. For ibuprofen, high removal efficiencies were observed in both WWTPs (84 to 98%). Disinfection by chlorination was not effective to remove the drugs surveyed. On the other hand, the effective removal of ketoprofen by ultraviolet (UV) radiation for disinfection was demonstrated, although the disinfection by-products were not identified.

For ecotoxicological risk assessment in a marine ecosystem, we constructed a coupled three-dimensional hydrodynamic and ecotoxicological model (EMT-3D), and applied it to Tokyo Bay. The model was calibrated with field data obtained in 2002. The results of sensitivity analysis for dissolved Bisphenol A showed that biodegradation rate was the most important factor for concentration change. Bioconcentration coefficient was the most important factor for Bisphenol A in phytoplankton. Therefore, the parameters must be carefully considered in the modeling. The mass balance results showed that standing stocks of Bisphenol A in water, in particulate organic carbon and in phytoplankton are 7.85 x 10(4), 1.78 x 10(2) and 3.44 x 10(-1) g, respectively. With respect to flux, biodegradation in the water column had the highest value of 1.06 x 10(3) g/day, and next were effluent to the open sea, partition to particulate organic carbon, and bioconcentration in phytoplankton.

Haptoglobin (Hp) subtypes have been determined in the Japanese population by polyacrylamide gel isoelectric focusing followed by immunoblotting and by two-dimensional polyacrylamide gel electrophoresis. In the present study, neuraminidase-treated plasma samples were used for subtyping of Hp, without prior purification. These samples were obtained from 372 unrelated healthy donors. Allelic frequencies were: Hp*1F = 0.0014; Hp*1S+ = 0.2688; Hp*2FF = 0.0000; Hp*2FS = 0.7284, and Hp*2SS = 0.0014. The phenotypic distribution was in good accordance with the Hardy-Weinberg equilibrium.