Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor

Metabolites of methoxychlor such as 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1-trichloroethane (mono-OH-MXC) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which the carbon atom bridging two benzene rings is the chiral centre. In previous studies the estrogenic activity of racemic mono-OH-MXC has been measured, and the activity of each enantiomer of this compound has not yet been elucidated. In this study, we evaluated the estrogen receptor-binding activity of each enantiomer of mono-OH-MXC to clarify the enantioselective recognition by the estrogen receptor. (S)-mono-OH-MXC showed 3-fold higher binding activity than that of the (R) enantiomer. The activity of bis-OH-MXC was only 1.7-fold higher than that of (S)-mono-OH-MXC. This result suggests that the one hydroxy group and the orientation of the CCl3 group of mono- and bis-OH-MXCs are important for the interaction with the estrogen receptor. The result also points out the estrogenic activity of methoxychlor after metabolic activation in vivo, which predominantly produces the (S)-mono-OH-MXC, may be higher than estimated from the in vitro activity of racemic mixtures.     

Residues of pharmaceutical products in recycled organic manure produced from sewage sludge and solid waste from livestock and relationship to their fermentation level

In recent years, sludge generated in sewage treatment plants (STPs) and solid waste from livestock being utilized is useful for circulation of nourishment in farmlands as recycled organic manure (ROM). In this study, we determined the residue levels and patterns of 12 pharmaceutical products generated by human activity in the ROMs produced from human waste sludge (HWS), sewage sludge (SS), cattle manure (CM), poultry manure (PM), swine manure (SM) and horse manure (HM).The kind and number of pharmaceutical products detected in ROMs were different. Fluoroquinolones (FQs) were detected at high levels in HWS and SS samples. In addition, the detection frequency and concentration levels of sulfonamides (SAs) in PM and SM were high. Moreover, high concentrations of chlortetracycline (CTC) were found in only SM. These differences reflect specific adherence adsorption of the pharmaceutical products to different livestock and humans. Moreover, it was found that the concentrations of pharmaceutical products and fermentation levels of ROMs had significant positive correlation (r = 0.41, p = 0.024).When the fermentation test of ROM was conducted in a rotary fermentor in a lab scale test, the residue levels of pharmaceutical products decreased effectively except carbamazepine (CBZ). The rates of decrease were in the case of tetracyclines (TCs): 85-92%, FQs: 81-100%, erythromycine: 67%, SAs: 79-95%, trimethoprim: 86% and CBZ: 37% by 30 d. Pharmaceutical products that can be decomposed by fermentation process at the lowest impact of residual antibiotic activities may therefore be considered as environmentally friendly medicines.     

Ecological fluid mechanics: interaction between living organisms and environments

Environmental Fluid Mechanics -     

Distribution and abundance of finless porpoise in the Inland Sea of Japan

Aerial sighting surveys were conducted in 2000 to evaluate the distribution and abundance of finless porpoise Neophocaena phocaenoides in the Inland Sea of Japan. We flew 60 north–south transects (2,218 km in total) at intervals of 6.43 km over the study area between 131°3′ and 134°59′ E. In total, 148 groups were detected by two observers. The average group size was 1.56 individuals. The effective strip half-width of each observer was estimated to be 107 m (coefficient of variation [CV] = 8.26%). Porpoise abundance was estimated at 7,572 individuals and the density was as low as 0.506 individuals/km² (CV = 17.3%). The sea is among the Japanese waters with the lowest density in spite of its favorable topographical conditions. In the western stratum of the study area, where the estimated density was 1.31 individuals/km², we observed a relatively regular distribution. In the central-eastern stratum, which had an estimated density of 0.208 individuals/km², we confirmed a clumped distribution that was restricted to inshore waters or near islands. No individuals were observed in waters between 132°51′ and 133°11′E, and between 133°43′ and 133°59′E, where sand dredging and other human activities have been active, suggesting that habitat fragmentation has occurred.     

Investigation of the hemolytic effects of various organophosphoric acid triesters (OPEs) and their structure‐activity relationship

The hemolytic effects of various organophosphonc acid triesters (OPEs) were investigated and they showed strong hemolyic toxicity except triethyl phosphate and tris(chloroethyl)phosphate. 2‐Ethylhexyl diphenyl phosphate (EHDP) showed the strongest toxicity. By quantitative structure‐activity relationship (QSAR) study, one‐parameter regression equation to estimate hemolysis was not obtained. But, two‐parameter regression equations were obtained which were enought to estimate EC₅₀ and EC₂₀. The correlation coefficients with the two‐parameter regression equations were 0.939 for log(l/EC₅₀) and 0.946 for log(l/EC₂₀).