Oseltamivir Carboxylate, the Active Metabolite of Oseltamivir Phosphate (Tamiflu), Detected in Sewage Discharge and River Water in Japan

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; commonlly 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. Me t h o d s: 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. Res u l t s: 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. Co n c l u s i o n: 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. Key w o r d s: influenza, LC-MS/MS, oseltamivir carboxylate, river water, sewage discharge, Tamiflu. Environ Health Perspect 118:103–107 (2010). doi:10.1289/ehp.0900930 available vi

Learning from the past and considering the future of chemicals in the environment

Knowledge of the hazards and associated risks from chemicals discharged to the environment has grown considerably over the past 40 years. This improving awareness stems from advances in our ability to measure chemicals at low environmental concentrations, recognition of a range of effects on organisms, and a worldwide growth in expertise. Environmental scientists and companies have learned from the experiences of the past; in theory, the next generation of chemicals will cause less acute toxicity and be less environmentally persistent and bioaccumulative. However, researchers still struggle to establish whether the nonlethal effects associated with some modern chemicals and substances will have serious consequences for wildlife. Obtaining the resources to address issues associated with chemicals in the environment remains a challenge

Influence of hydraulic retention time, sludge retention time, and ozonation on the removal of free and conjugated estrogens in Japanese activated sludge treatment plants

This study describes the occurrence, fate, and removal of free estrogens (estrone (E1), 17 beta-estradiol (E2), estriol (E3), 17 alpha-ethynylestradiol (EE2)) and their glucuronide and sulfate conjugates (estrone-3-sulphate (E1-3S), 17 beta-estradiol-3-sulfate (E2-3S), estriol-3-sulfate (E3-3S), estrone-3-glucuronide (E1-3G), 17 beta-estradiol-3-glucuronide (E2-3G), and estriol-3-glucuronide (E3-3G)) in 12 sewage treatment plants in Japan. Glucuronide conjugates were only rarely detected in sewage influents and entirely eliminated within the treatment plants. E1 was found at 69 ng/L, E2 at 108 ng/L, E1-3S at 18 ng/L, and E2-3S at 78 ng/L in the sewage influents. The average removal efficiency for E1, E2, and sulfate conjugates was 88, 92, and 93%, respectively, following activated sludge treatment. The removal of E1 and E2 was improved with increasing the sludge retention time (SRT), with the highest removal typically found from 12 days SRT onward. The removal of sulfate conjugates was also related to SRT with highest removals found from eight days SRT onward. No correlation was found between the hydraulic retention time and the removal of any of the estrogens. The ozone dosage of 4-7 mg/L reduced E3 and E2-3S and E3-3S to below detection levels. Overall ozonation reduced the estrogenicity of the effluents as expressed as estradiol equivalents from 8.4 to 0.7 ng/L. The results suggest adequate river basin management of estrogens in Japan could be accomplished by a mixture of activated sludge plants with long SRT and where necessary, the addition of tertiary ozonation

The different fate of antibiotics in the Thames River, UK, and the Katsura River, Japan

Little is known about the mechanisms influencing the differences in attenuation of antibiotics between rivers. In this study, the natural attenuation of four antibiotics (azithromycin, clarithromycin, sulfapyridine, and sulfamethoxazole) during transport along the Thames River, UK, over a distance of 8.3 km, and the Katsura River, Japan, over a distance of 7.6 km was compared. To assist interpretation of the field data, the individual degradation and sorption characteristics of the antibiotics were estimated by laboratory experiments using surface water or sediment taken from the same rivers. Azithromycin, clarithromycin, and sulfapyridine were attenuated by 92, 48, and 11% in the Thames River stretch. The first-order decay constants of azithromycin and sulfapyridine were similar to those in the Katsura River, while that of clarithromycin was 4.4 times higher. For sulfamethoxazole, the attenuation was limited in both rivers. Loss of sulfapyridine was attributed to both direct and indirect photolysis in the Thames River, but to only direct photolysis in the Katsura River. Loss of azithromycin and clarithromycin was attributed to sorption to sediment in both rivers. The probable explanation behind the difference in loss rates of clarithromycin between the two rivers was considered to be sediment sorption capacity

Linking changes in antibiotic effluent concentrations to flow, removal and consumption in four different UK sewage treatment plants over four years

The arrival and discharge of seven antibiotics were monitored at two trickling filter sewage treatment plants of 6,000 and 11,000 population equivalents (PE) and two activated sludge plants of 33,000 and 162,000 PE in Southern England. The investigation consisted of 24 h composite samples taken on two separate days every summer from 2012 to 2015 and in the winter of 2015 (January) from influent and effluent. The average influent concentrations generally matched predictions based on England-wide prescription data for trimethoprim, sulfamethoxazole, azithromycin, oxytetracycline and levofloxacin (within 3-fold), but were 3-10 times less for clarithromycin, whilst tetracycline influent concentrations were 5-17 times greater than expected. Over the four years, effluent concentrations at a single sewage plant varied by up to 16-fold for clarithromycin, 10-fold for levofloxacin and sulfamethoxazole, 7-fold for oxytetracycline, 6-fold for tetracycline, 4-fold for azithromycin and 3-fold for trimethoprim. The study attempted to identify the principal reasons for this variation in effluent concentration. By measuring carbamazepine and using it as a conservative indicator of transport through the treatment process, it was found that flow and hence concentration could alter by up to 5-fold. Measuring influent and effluent concentrations allowed assessments to be made of removal efficiency. In the two activated sludge plants, antibiotic removal rates were similar for the tested antibiotics but could vary by several-fold at the trickling filter plants. However, for clarithromycin and levofloxacin the variations in effluent concentration were above that which could be explained by either flow and/or removal alone so here year on year changes in consumption are likely to have played a role

Assessing the population equivalent and performance of wastewater treatment through the ratios of pharmaceuticals and personal care products present in a river basin: application to the River Thames basin, UK

The quality of surface waters in lowland rivers is largely dependent on the efficiency of wastewater treatment. Even in the developed countries, there have been difficulties in evaluating the effectiveness of wastewater management and the proportion of wastewater content (WWC) in the river, as well as in estimating the contributing human population. This study aimed to develop a wastewater quality and quantity assessment based on the occurrence of pharmaceuticals in the receiving waters. A survey of 53 pharmaceuticals in 324 samples (river water and influent and effluent of sewage (wastewater) treatment plants) was carried out in southern England in the River Thames catchment over four years. Carbamazepine was selected as stable marker and from its concentration WWC in the rivers and cumulative human populations along the catchment were estimated. The estimated population had a strong relationship (R2=0.94) with that reported by the local water company. The concentration ratio of the labile marker caffeine to carbamazepine indicated the efficiency of wastewater treatment in the different treatment systems (i.e. trickling filter or activated sludge) and in the receiving waters. The ratio in some river samples revealed unexpected discharges of untreated or poorly treated wastewater, with a total concentration of the analytes (up to 20mug/L) five times higher than that in treated wastewater. Such information could be valuable to estimate the discharge or occurrence of not only non-targeted chemicals, but also pathogens within the basin

Quantification of pharmaceutical related biological activity in effluents from wastewater treatment plants in UK and Japan

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

Ubiquitous occurrence of sulfonamides in tropical Asian waters.

Seven sulfonamides, trimethoprim, five macrolides, lincomycin and three tetracyclines were measured in 150 water samples of sewage, livestock and aquaculture wastewater, and river and coastal waters, in five tropical Asian countries. The sum of the concentrations of the target antibiotics in sewage and heavily sewage-impacted waters were at sub- to low-ppb levels. The most abundant antibiotic was sulfamethoxazole (SMX), followed by lincomycin and sulfathiazole. The average concentration of SMX in sewage or heavily sewage-impacted waters was 1720 ng/L in Vietnam (Hanoi, Ho Chi Minh, Can Tho; n = 15), 802 ng/L in the Philippines (Manila; n = 4), 538 ng/L in India (Kolkata; n = 4), 282 ng/L in Indonesia (Jakarta; n = 10), and 76 ng/L in Malaysia (Kuala Lumpur; n = 6). These concentrations were higher than those in Japan, China, Europe, the US and Canada. A predominance of sulfonamides, especially SMX, is notable in these tropical countries. The higher average concentrations, and the predominance of SMX, can be ascribed to the lower cost of the antibiotics. Both the concentration and composition of antibiotics in livestock and aquaculture wastewater varied widely. In many cases, sulfamethazine (SMT), oxytetracycline (OTC), lincomycin, and SMX were predominant in livestock and aquaculture wastewater. Both human and animal antibiotics were widely distributed in the respective receiving waters (i.e., the Mekong River and Manila Bay). SMT/SMX ratios indicate a significant contribution from livestock wastewater to the Mekong River and nearby canals, with an estimated ~ 10% of river water SMX derived from such wastewater. Mass flow calculations estimate that 12 tons of SMX is discharged annually from the Mekong River into the South China Sea. Riverine inputs of antibiotics may significantly increase the concentration of such antibiotics in the coastal waters