Ikumi Tamura

Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments.

We selected eight pharmaceuticals with relatively high potential ecological risk and high consumption-namely, acetaminophen, atenolol, carbamazepine, ibuprofen, ifenprodil, indomethacin, mefenamic acid, and propranolol-and conducted laboratory experiments to examine the persistence and partitioning of these compounds in the aquatic environment. In the results of batch sunlight photolysis experiments, three out of eight pharmaceuticals-propranolol, indomethacin, and ifenprodil-were relatively easily photodegraded (i.e., half-life<24h), whereas the other five pharmaceuticals were relatively stable against sunlight. The results of batch biodegradation experiments using river water suggested relatively slow biodegradation (i.e., half-life>24h) for all eight pharmaceuticals, but the rate constant was dependent on sampling site and time. Batch sorption experiments were also conducted to determine the sorption coefficients to river sediments and a model soil sample. The determined coefficients (K(d) values) were much higher for three amines (atenolol, ifenprodil, and propranolol) than for neutral compounds or carboxylic acids; the K(d) values of the amines were comparable to those of a four-ring polycyclic aromatic hydrocarbon (PAH) pyrene. The coefficients were also higher for sediment/soil with higher organic content, and the organic carbon-based sorption coefficient (logK(oc)) showed a poor linear correlation with the octanol-water distribution coefficient (logD(ow)) at neutral pH. These results suggest other sorption mechanisms-such as electrochemical affinity, in addition to hydrophobic interaction-play an important role in sorption to sediment/soil at neutral pH.

Aquatic toxicity and ecological risk assessment of seven parabens: Individual and additive approach

In the present study, aquatic concentrations of seven parabens were determined in urban streams highly affected by treated or untreated domestic sewage in Tokushima and Osaka, Japan. The detected highest concentrations were 670, 207, and 163ngl(-1) for methylparaben, n-propylparaben, and n-butylparaben, respectively in sampling sites with watershed area of no sewer system in Tokushima. Conventional acute/chronic toxicity tests were conducted using medaka (Oryzias latipes), Daphnia magna, and Psuedokirchneriella subcapitata for four parabens, which was consistent with our previous study on three parabens, n-butylparaben, i-butylparaben, and benzylparaben. The aquatic toxicity on fish, daphnia, and algae was weaker for the parabens with a shorter alkyl chain than those with a longer alkyl chain as predicted by their hydrophobicity. Medaka vitellogenin assays and DNA microarray analysis were carried out for methylparaben and found induction of significant vitellogenin in male medaka at 630μgl(-1) of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10μgl(-1) of methylparaben. Measured environmental concentrations (MECs) of seven parabens in Tokushima and Osaka were divided by predicted no effect concentrations (PNECs) and hazard quotient (MEC/PNEC) was determined for individual parabens. The MEC/PNEC was highest for n-propylparaben and was 0.010 followed by n-butylparaben (max. of 0.0086) and methylparaben (max. of 0.0042). The sum of the MEC/PNEC for the seven parabens was 0.0049. Equivalence factors were assigned for each paraben on the basis of the toxicity of n-butylparaben for each species, and n-butylparaben equivalence was calculated for the measured environmental concentrations. The MEC/PNEC approach was also conducted for the n-butylparaben-based equivalence values. The maximum MEC/PNEC was 0.018, which is lower than the trigger level for further detailed study such as large-scale monitoring for chronic toxicity tests including full-life cycle tests for fish.

Ecotoxicity and screening level ecotoxicological risk assessment of five antimicrobial agents: triclosan, triclocarban, resorcinol, phenoxyethanol and p-thymol.

Acute and chronic (or sub‐chronic) toxicity of five selected antimicrobial agents, including triclosan (TCS), triclocarban (TCC), resorcinol, phenoxyethanol and p‐thymol, was investigated using the conventional three‐aquatic‐organism battery. These compounds are widely used in cosmetics and other personal care products and their ecological risk has recently become a significant concern. As results of toxicity tests, TCS was found to be most strongly toxic for green algae [e.g. 72 h no observed effect concentration (NOEC) of 0.50 µg l−1] among the selected compounds, followed by TCC, while TCC was more toxic or similar to TCS for Daphnia and fish (e.g. Daphnia 8 day NOEC of 1.9 µg l−1). Having compared the predicted no effect concentration (PNEC) determined from the toxicity data with measured environmental concentrations (MEC), the preliminary ecological risk assessment of these five antimicrobials was conducted. The MEC/PNEC ratios of TCS and TCC were over 1 for some monitoring data, especially in urban streams with watershed areas without sewage service coverage, and their potential risk for green algae and Daphnia might be at a level of concern, although the contribution of TCS/TCC on the total toxicity of the those sites needs to be further investigated. For the three other antimicrobials, the maximum MEC/PNEC ratio for resorcinol was 0.1–1, but those for phenoxyethanol and p‐thymol were <0.1 and their risk to aquatic organisms is limited, although the additive effects with TCS, TCC and other antimicrobial agents, such as parabens, need to be further examined in future studies. Copyright

Triclosan, an antibacterial agent, increases intracellular Zn2+ concentration in rat thymocytes: Its relation to oxidative stress

Triclosan is used as an antibacterial agent in household items and personal care products. Since this compound is found in maternal milk of humans and bodies of wild animals, there is growing concern among some consumer groups and scientific community that triclosan is adverse for humans and wild animals. In order to estimate adverse actions of triclosan, the effects of triclosan on intracellular Zn(2+) concentration and cellular thiol content were studied in rat thymocytes by the use of flow cytometer with appropriate fluorescent probes. Triclosan at 1-3 μM (sublethal concentrations) increased the intensity of FluoZin-3 fluorescence (intracellular Zn(2+) concentration) and decreased the intensity of 5-chloromethylfluorescein (5-CMF) fluorescence (cellular thiol content). Negative correlation (r=-0.985) between triclosan-induced changes in FluoZin-3 and 5-CMF fluorescences was found. Removal of external Zn(2+) did not significantly affect the triclosan-induced augmentation of FluoZin-3 fluorescence, suggesting an intracellular Zn(2+) release by triclosan. These actions of triclosan were similar to those of H(2)O(2) and triclosan significantly potentiated the cytotoxicity of H(2)O(2). Therefore, the results may suggest that triclosan at sublethal concentrations induces oxidative stress that decreases cellular thiol content, resulting in an increase in intracellular Zn(2+) concentration by Zn(2+) release from intracellular store(s). Since recent studies show many physiological roles of intracellular Zn(2+) in cellular functions, the triclosan-induced disturbance of cellular Zn(2+) homeostasis may induce adverse actions on the cells.

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action.

Ecological risk assessment of urban creek sediments contaminated by untreated domestic wastewater: potential contribution of antimicrobials and a musk fragrance.

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 μg 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.

Contribution of inorganic and organic components to sorption of neutral and ionizable pharmaceuticals by sediment/soil

Our previous study showed that the sorption coefficient of certain polar pharmaceuticals to river sediment, especially particular amines, was unexpectedly high. Thus, we conducted sorption experiments of selected polar pharmaceuticals and pyrene derivatives, including amines, carboxylic acids, and neutral compounds, to model clay minerals, i.e., montmorillonite and kaolin, in addition to silica sands and humic substances. The contribution of each component was roughly estimated by simple fractionation of the individual sorption coefficients. Relatively high sorption coefficients (Kd values) were found, especially for amines on clay minerals, which suggest that electrochemical affinity may play an important role. The estimated contribution percentage suggests a relatively large contribution from inorganic constituents, such as clay minerals, for silt loam soil; in contrast, organic components predominantly contribute for sandy river sediments. These findings could be the key to understanding not only the fate and transport but also bioavailability and environmental risks of pharmaceuticals, which are mostly polar and/or ionizable.