Assessment of human exposure to di-isodecyl phthalate using oxidative metabolites as biomarkers

Di-isodecyl phthalate (DiDP), primarily used as a plasticiser, is a mixture of isomers with predominantly ten-carbon branched side chains. Assessment of DiDP exposure has not been conducted before because adequate biomarkers were lacking. In 129 adult volunteers with no known exposure to DiDP, the urinary concentrations of three oxidative metabolites of DiDP: monocarboxyisononyl phthalate (MCiNP), monooxoisodecyl phthalate (MOiDP) and monohydroxyisodecyl phthalate (MHiDP), previously identified in DiDP-dosed rats, were estimated by solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using the respective oxidative metabolites of di(2-ethylhexyl)phthalate since authentic standards of the DiDP oxidative metabolites were unavailable. Interestingly, the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), was not detected in any of the samples, while MCiNP, MHiDP and MOiDP were detected in 98%, 96% and 85%, respectively, of the samples tested. MCiNP was excreted predominantly in its free form, whereas MOiDP was excreted as its glucuronide. MCiNP, MHiDP and MOiDP eluted as clusters of multiple peaks from the HPLC column probably due to the presence of numerous structurally similar isomers present in commercial DiDP formulations. The urinary concentrations of these oxidative metabolites correlated significantly (p<0.0001) with each other, thus confirming a common precursor. The urinary concentrations of these DiDP oxidative metabolites also correlated significantly (p<0.0001) with oxidative metabolites of di-isononyl phthalate (DiNP) suggesting the potential presence of DiNP isomers in commercial DiDP or simultaneous use of DiDP and DiNP in consumer products. The concentrations presented are semiquantitative estimates and should be interpreted cautiously. Nevertheless, the higher frequency of detection and higher urinary concentrations of MCiNP, MHiDP and MOiDP than of MiDP suggest that these oxidative metabolites are better biomarkers for DiDP exposure assessment than MiDP. These data also suggest that unless oxidative metabolites are measured, the prevalence of exposure to DiDP will probably be underestimated.     

Antinociceptive effect of Nidularium procerum: a Bromeliaceae from the Brazilian coastal rain forest

Nidularium procerum, a common plant of the Brazilian flora, has not yet been studied for its pharmacological properties. We report here that extracts of N. procerum show both analgesic and anti-inflammatory properties. Oral (p.o.) or intraperitoneal (i.p.) administration of an aqueous crude extract from leaves of N. procerum (LAE) inhibited the writhing reaction induced by acetic acid (ED50 value = 0.2 mg/kg body weight, i.p.) in a dose-dependent manner. This analgesic property was confirmed in rats using two different models of bradykinin-induced hyperalgesia; there was 75% inhibition of pain in the modified Hargreaves assay, and 100% inhibition in the classical Hargreaves assay. This potent analgesic effect was not blocked by naloxone, nor was it observed in the hot plate model, indicating that the analgesic effect is not associated with the activation of opioid receptors in the central nervous system. By contrast, we found that LAE (0.02 microg/ml) selectively inhibited prostaglandin E2 production by cyclooxygenase (COX)-2, but not COX-1, which is a plausible mechanism for the analgesic effect. A crude methanol extract from the leaves also showed similar analgesic activity. An identical extract from the roots of N. procerum did not, however, block acetic acid-induced writhes, indicating that the analgesic compounds are concentrated in the leaves. Finally, we found that LAE inhibited an inflammatory reaction induced by lipopolysaccharide in the pleural cavity of mice.     

Septal fracture in Nautilus: implications for cephalopod paleobathymetry

Analysis of septal geometry, as embodied in the septal strength index model developed by Westermann (1973, Lethaia 6). , has become a prime avenue for estimating living depths of fossil cephalopods. We have examined the fracturing of Nautilus septa, and its bearing on strength index, by inducing septal rupture under the action of hydrostatic pressure. We found that: (1) septa which actually fail under pressure are not generally weakest as defined by their strength indices; (2) septal strength as defined by the strength index is not correlated with rupture pressure; and (3) most instances of septal failure originate in septal sutures, not in the septa. These results indicate that: (1) septal strength index does not yield wholly reliable strength or depth estimates; and (2) the shortcomings of the strength index model stem from its inability to account for complexities of mechanical failure in morphologically complex cephalopod shells.     

Mycobiota in Portuguese 'normal' and 'green' cork throughout the manufacturing process of stoppers

The compounds responsible for the so-called 'cork taint' include, among others, some microbial metabolites which can be produced by the microbial population colonizing the unprocessed cork and stoppers. This study was intended to obtain information on the mycobiota associated with Portuguese cork throughout the manufacturing process of stoppers. Samples of barks and stoppers of both 'normal' and 'green' cork were examined. Moulds were isolated from 'normal' and 'green' cork throughout the entire cork stopper manufacturing process. Yeasts were rarely detected in the corks. Fungal contamination was not detected in finished stoppers from the company under study.