Other aspects of BSE issues in East Asian countries.

Scientific risk estimates of BSE can be the same internationally; however, socioeconomic backgrounds, such as food supply (e.g., beef import status) and dietary life, are different between East Asian countries (i.e., in this article, Japan, Korea, and Taiwan) and Western countries, which may account for differences in risk perception of people. Since political and social backgrounds also differ among these East Asian countries, they will also influence people's attitudes toward food safety. Psychological factors such as "dread" and the "unknown" are considered to be important in risk perception, but socioeconomic, and in some cases political, situations (e.g., attitudes of politicians and political pressures in trade) may strongly influence the perception and acceptance of various risks by citizens. With regard to the BSE issues, latter aspects may contribute a lot to risk perception, but have not been examined in depth until now. Although protection of health is the key element to food safety, sometimes business factors can overwhelm safety issues in international trade. Appropriate risk governance in food safety issues, such as BSE, can be attained not only through application of outputs of scientific assessment, but also through deliberation of various aspects, that may have strong influence on people's risk perception, and improved communication among stakeholders and also among countries.

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.

Low-dose effects of bisphenol A: a serious threat to human health?

The author tried to review and summarize low-dose effects of endocrine disrupting chemicals (EDCs) through an extensive literature survey of toxicological studies with bisphenol A (BPA), taking BPA as an example for which many studies were published. Data on low-dose effects with BPA, especially on neurobehavioral effects after fetal or early postnatal exposures, suggested that there would be new aspects to be considered. Specific mention for future tasks was made. Firstly, toxicity tests should be designed with more elaboration to ensure a sufficient number of animals with careful handling of litters to allow adequate statistical analysis and appropriate selection of dosages to obtain insight in dose-response relationship. Secondly, precise measurement of plasma levels in both humans and rodents and construction of relevant physiologically-based pharmacokinetic models would help obtain quantitative estimates of intake and target-organ exposure relationship. Thirdly, biological backgrounds, particularly differences and similarities in endocrinological, neurological and immunological aspects among species, should be revisited. Fourthly, mechanistic deliberations on the possibilities of epigenetic mechanism and examinations of putative neurobehavioral effects or a presumptive link of miscarriage with BPA exposures are requested. Finally, general public concerns must be addressed in a thoughtful way so that a simple precautionary approach is not pursued, but uncertainties of the new toxicological aspects should be carefully explained. Further researches and internationally concerted efforts on elucidating risk of low-dose effects by integrating knowledge will contribute to setting new directions in toxicology and improving chemical risk assessments.

The effects of pH on fluoxetine in Japanese medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish.

Recent detection of fluoxetine in the aquatic environment and fish suggests a possibly high accumulation of fluoxetine; however, no report is available on the bioaccumulation of fluoxetine in aquatic organisms. Since bioaccumulation of fluoxetine was probably dependent on pH near the pK(a) value of 10.1, experiments were conducted approximately at pH 7, 8, and 9. Distribution coefficients between 1-octanol and water (D(ow)), and those between synthetic membrane vesicles (liposomes) and water (D(lip-wat)) were determined at pH 7, 8, and 9. The D(ow) and D(lip-wat) values increased significantly with increasing pH. Acute toxicity tests were performed using Japanese medaka (Oryzias latipes) prior to the bioaccumulation test, and 96-h LC(50) values were 5.5, 1.3, and 0.20mgl(-1) at pH 7, 8, and 9, respectively. In the bioaccumulation test, concentrations of fluoxetine and its major metabolite, norfluoxetine, in the fish body and liver were measured. The bioconcentration factors (BCF) of fluoxetine for Japanese medaka were 8.8, 3.0x10, and 2.6x10(2) in the body and 3.3x10(2), 5.8x10(2), and 3.1x10(3) in the liver at pH 7, 8, and 9, respectively. The BCF values were lower at pH 7 and higher at pH 9 mainly because of the increase in nonionized species with significantly higher hydrophobicity than the ionized species at pH values closer to pK(a). A similar trend was obtained for the concentration of norfluoxetine in the fish but the pseudo-BCF values (the ratio of the norfluoxetine concentration in the fish and the fluoxetine concentration in test water) were higher than the BCF value of fluoxetine at all pH conditions.

Initial ecological risk assessment of eight selected human pharmaceuticals in Japan.

Eight pharmaceuticals were selected on the basis of their domestic consumption in Japan, the excretion ratio of the parent compound and the frequency of detection in the aquatic environment or wastewater treatment plant effluent. Toxicity tests on these pharmaceuticals were conducted using Japanese medaka (Oryzias latipes), daphnia (Daphnia magna), and green algae (Psuedokirchneriella subcapitata). Predicted no effect concentration (PNEC) was calculated using lethal or effect concentration 50 (LC50 or EC50) values and no effect concentration (NOEC) obtained in the toxicity tests for these compounds. Predicted environmental concentration (PEC) was also calculated from annual consumption, the excretion rate of the parent compound, and removal rate in the preliminary batch activated sludge treatment performed in this study. Maximum concentrations found in the aquatic environment or sewage effluent in Japan or foreign countries were also used for another calculation of PEC. Initial risk assessment on the selected pharmaceuticals was performed using the PEC/PNEC ratio. The results of initial risk assessment on the eight selected pharmaceuticals suggest neither urgent nor severe concern for the ecological risk of these compounds, but further study needs to be conducted using chronic toxicity tests, including reproduction inhibition and endocrine disruption assessments.

Preliminary ecological risk assessment of butylparaben and benzylparaben -1. Removal efficiency in wastewater treatment, acute/chronic toxicity for aquatic organisms, and effects on medaka gene expression.

Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been found to be weakly estrogenic. Batch activated-sludge treatment and batch chlorination were carried out to roughly determine the removal efficiency of a wastewater treatment plant. Combining the removal efficiency with the estimated annual consumption and the unaltered excretion ratio, the maximum predicted environmental concentration (PEC) was estimated. Conventional acute/chronic toxicity tests were conducted using Japanese medaka (Oryzias latipes), daphnia (Daphnia magna), and green algae (Pseudokirchneriella subcapitata) for n-butylparaben, i-butylparaben, and benzylparaben. Medaka vitellogenin assays were also conducted for the three compounds and DNA microarray analysis was carried out to examine the effects of benzylparaben on gene expression. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100, and 100 microg L(-1) n-butylparaben, i-butylparaben, and benzylparaben for 14 days, respectively, while the expression levels of genes encoding proteins such as p53, cytochrome P450 3A40, and choriogenin-L increased for concentrations higher than 4 microg L(-1) of benzylparaben. Furthermore, the predicted no-effect concentration (PNEC) was calculated using the lethal or effect concentration 50 (LC50 or EC50) values and no-effect concentrations (NOECs) obtained in the toxicity tests for these compounds. The maximum concentrations found in the aquatic environment or sewage effluent (MEC eff) were used to carry out preliminary environmental risk assessment. The calculated MEC/PNEC ratio suggests the necessity of further study such as a more detailed large-scale monitoring and chronic toxicity tests including reproduction inhibition and endocrine disruption.

Preliminary ecological risk assessment of butylparaben and benzylparaben -2. Fate and partitioning in aquatic environments.

Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been shown to be weakly estrogenic. Batch sunlight photolysis and river water biodegradation experiments were conducted to determine the persistence of these compounds in aquatic environments. As a result, benzylparaben was found to be moderately photodegradable whereas both n-butylparaben and i-butylparaben were highly stable against sunlight. Both benzylparaben and butylparabens were relatively biodegradable in the river water but the degradability was dependent on the sampling site and time. Batch sorption experiments were also conducted to determine the coefficients of sorption into river sediments and a model soil sample. The determined coefficients were slightly higher for benzylparaben than the two butylparabens and comparable to that of the natural estrogen 17beta-estradiol. The coefficients were also higher for sediment/soil with a higher organic content and the organic-carbon-based sorption coefficient (log K oc) shows a moderate linear correlation with the octanol-water partition coefficient (log K ow). These results suggest that hydrophobic interaction plays a predominant role in sorption at neutral pH.

A comparison between integrated risk assessment and classical health/environmental assessment: emerging beneficial properties.

Both humans and wildlife are exposed to various types of halogenated organic compounds such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), typically old chemicals, and tris(4-chlorophenyl) methane (TCPM) and brominated flame retardants, some new chemicals, simultaneously. Classical risk assessment has evaluated health and ecological risks independently by experts from different disciplines. Taking into considerations the recent concerns about endocrine disrupting chemicals and the progress of research in related areas, we integrated and assessed data on exposure and potential effects in humans and wildlife. Comparisons were made for organ concentrations, body burdens of several organochlorine compounds (OCs), metabolic capacities between humans and various wildlife. When we integrate the knowledge on effects and exposure in humans and in wildlife, new insights were suggested about similarities and/or differences in potential effects among various human populations living on different foods and having different body burdens. Combining existing information with emerging knowledge of mechanisms of actions on endocrine disrupting chemicals after exposure to above chemicals during early developmental stages will further elucidate potential risks from exposure to those chemicals.

An integrated framework for health and ecological risk assessment.

The World Health Organization's (WHO's) International Program for Chemical Safety has developed a framework for performing risk assessments that integrate the assessment of risks to human health and risks to nonhuman organisms and ecosystems. The WHO's framework recognizes that stakeholders and risk managers have their own processes that are parallel to the scientific process of risk assessment and may interact with the risk assessment at various points, depending on the context. Integration of health and ecology provides consistent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The advantage of the framework to toxicologists lies in the opportunity to use understanding of toxicokinetics and toxicodynamics to inform the integrated assessment of all exposed species.

Fate and partitioning of selected pharmaceuticals in aquatic environment.

Two nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and acetaminophen, a beta-blocker atenolol, and an antidepressant fluoxetine were selected, and their sorption coefficients (Koc values) on the basis of dissolved organic matter (DOM) and model sediments were determined. The highest values were found for fluoxetine for both DOM and sediments, followed by atenolol or ibuprofen. These Koc values were comparable to those of pyrene and 17beta-estradiol, a nonpolar four-ring polycyclic aromatic hydrocarbon and a polar natural estrogen, respectively. For these four pharmaceuticals, partition coefficients between synthetic membrane vesicles (liposomes) and water (Klipw values), and removal efficiencies for a simple batch activated sludge treatment were also determined. The highest Klipw values were again found for fluoxetine followed by atenolol. The removal efficiency for a 6-hour batch activated sludge treatment was over 90% for the two NSAIDs whereas that for atenolol was as low as 10%; both agreed with the results obtained in conventional studies, which showed the concentration in the influent and effluent of sewage treatment plants. The removal efficiency for fluoxetine was also over 90%, but it was sorbed by sludge and not biodegraded.