Using a physiologically based pharmacokinetic model to link urinary biomarker concentrations to dietary exposure of perchlorate

Exposure to perchlorate is widespread in the United States and many studies have attempted to character the perchlorate exposure by estimating the average daily intakes of perchlorate. These approaches provided population-based estimates, but did not provide individual-level exposure estimates. Until recently, exposure activity database such as CSFII, TDS and NHANES become available and provide opportunities to evaluate the individual-level exposure to chemical using exposure surveillance dataset. In this study, we use perchlorate as an example to investigate the usefulness of urinary biomarker data for predicting exposures at the individual level. Specifically, two analyses were conducted: (1) using data from a controlled human study to examine the ability of a physiologically based pharmacokinetic (PBPK) model to predict perchlorate concentrations in single-spot and cumulative urine samples; and (2) using biomarker data from a population-based study and a PBPK model to demonstrate the challenges in linking urinary biomarker concentrations to intake doses for individuals. Results showed that the modeling approach was able to characterize the distribution of biomarker concentrations at the population level, but predicting the exposure-biomarker relationship for individuals was much more difficult. The type of information needed to reduce the uncertainty in estimating intake doses, for individuals, based on biomarker measurements is discussed.     

Cholinesterase characterization in Corbicula fluminea and effects of relevant environmental contaminants: a pesticide (chlorfenvinphos) and a detergent (SDS)

This study characterizes the cholinesterasic forms present in the bivalve Corbicula fluminea, through the analysis of differential affinity towards various substrates and inhibitors. This approach also permitted the validation of cholinesterase inhibition in the mentioned species for monitoring purposes by evaluating the inhibitory activity of a detergent (SDS) and a pesticide (chlorfenvinphos), both in vitro and in vivo. The cholinesterasic form present in the tissues of C. fluminea showed intermediate properties in terms of its relation with substrates and inhibitors. Furthermore, it was not inhibited by the detergent SDS under any of the test conditions, but was clearly inhibited by the selected organophosphate. The data show clearly that the main cholinesterasic form in C. fluminea is responsive to the organophosphate chlorfenvinphos, thus supporting the use of this biomarker for the environmental monitoring of specific contaminants such as anticholinesterasic pesticides. Despite not being commonly attained in the wild, the levels of chlorfenvinphos required to elicit a significant ChE inhibition were only one order of magnitude above actual values of aquatic contamination by this pesticide.     

Cholinesterase characterization in Corbicula fluminea and effects of relevant environmental contaminants: A pesticide (chlorfenvinphos) and a detergent (SDS)

This study characterizes the cholinesterasic forms present in the bivalve Corbicula fluminea, through the analysis of differential affinity towards various substrates and inhibitors. This approach also permitted the validation of cholinesterase inhibition in the mentioned species for monitoring purposes by evaluating the inhibitory activity of a detergent (SDS) and a pesticide (chlorfenvinphos), both in vitro and in vivo. The cholinesterasic form present in the tissues of C. fluminea showed intermediate properties in terms of its relation with substrates and inhibitors. Furthermore, it was not inhibited by the detergent SDS under any of the test conditions, but was clearly inhibited by the selected organophosphate. The data show clearly that the main cholinesterasic form in C. fluminea is responsive to the organophosphate chlorfenvinphos, thus supporting the use of this biomarker for the environmental monitoring of specific contaminants such as anticholinesterasic pesticides. Despite not being commonly attained in the wild, the levels of chlorfenvinphos required to elicit a significant ChE inhibition were only one order of magnitude above actual values of aquatic contamination by this pesticide.     

Multiplex biotoxin surface plasmon resonance method for marine biotoxins in algal and seawater samples

A multiplex surface plasmon resonance (SPR) biosensor method for the detection of paralytic shellfish poisoning (PSP) toxins, okadaic acid (and analogues) and domoic acid was developed. This method was compared to enzyme-linked immunosorbent assay (ELISA) methods. Seawater samples (n?=?256) from around Europe were collected by the consortia of an EU project MIcroarrays for the Detection of Toxic Algae (MIDTAL) and evaluated using each method. A simple sample preparation procedure was developed which involved lysing and releasing the toxins from the algal cells with glass beads followed by centrifugation and filtering the extract before testing for marine biotoxins by both multi-SPR and ELISA. Method detection limits based on IC₂₀ values for PSP, okadaic acid and domoic acid toxins were 0.82, 0.36 and 1.66 ng/ml, respectively, for the prototype multiplex SPR biosensor. Evaluation by SPR for seawater samples has shown that 47, 59 and 61 % of total seawater samples tested positive (result greater than the IC₂₀) for PSP, okadaic acid (and analogues) and domoic acid toxins, respectively. Toxic samples were received mainly from Spain and Ireland. This work has demonstrated the potential of multiplex analysis for marine biotoxins in algal and seawater samples with results available for 24 samples within a 7 h period for three groups of key marine biotoxins. Multiplex immunological methods could therefore be used as early warning monitoring tools for a variety of marine biotoxins in seawater samples.     

The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure - effects in reproductive organs

The dioxin/aryl hydrocarbon receptor (AhR) mediates most toxic effects of dioxins. In utero/lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fetal/neonatal development and the developing male reproductive tract are among the most sensitive tissues. TCDD causes antiestrogenic responses in rodent mammary gland and uterus and in human breast cancer cell lines in the presence of estrogen. Also, more recently an estrogen-like effect of TCDD/AhR has been suggested in the absence of estrogen. A transgenic mouse expressing a constitutively active AhR (CA-AhR) was developed as a model mimicking a situation of constant exposure to AhR agonists. Male and female reproductive tissues of CA-AhR mice were characterized for some of the effects commonly seen after dioxin exposure. Sexually mature CA-AhR female mice showed decreased uterus weight, while an uterotrophic assay in immature CA-AhR mice resulted in increased uterus weight. In immature mice, both TCDD-exposure and CA-AhR increased the expression of the estrogen receptor target gene Cathepsin D. When co-treated with 17β-estradiol no increase in Cathepsin D levels occurred in either TCDD-exposed or CA-AhR mice. In sexually mature male CA-AhR mice the weights of testis and ventral prostate were decreased and the epididymal sperm reserve was reduced. The results of the present study are in accordance with previous studies on dioxin-exposed rodents in that an activated AhR (here CA-AhR) leads to antiestrogenic effects in the presence of estrogen, but to estrogenic effects in the absence of estrogen. These results suggest the CA-AhR mouse model as a useful tool for studies of continuous low activity of the AhR from early development, resembling the human exposure situation.     

An Examination of Governance Arrangements at Kisakasaka Mangrove Reserve in Zanzibar

This study employs insights largely derived from critical reflections on the common pool resources (CPR) theory to examine the current governance arrangements in place to manage the mangrove forest at Kisakasaka, in Zanzibar, Tanzania. Kisakasaka was used as a site for a community-based management pilot project of forest resources in Zanzibar. After some initial success in setting up a local management structure and regulating access to the mangrove for mainly charcoal production, there are now clear indications that forest conditions have deteriorated dramatically with concomitant ongoing resource use problems for local villagers who have relied heavily on forest resources as a source of cash income. Extra-local factors, such as urban population increases and associated market pressures for charcoal, are also conjectured to overlay and interact with the institutional problems at Kisakasaka. As a result, over concern about the deterioration in the condition of the mangrove forest, the responsible government authority decided not to renew the community-based governance arrangements after an initial five-year pilot period. While revealing the inadequacies of existing governance arrangements and of its relationship to deteriorating forest conditions at Kisakasaka, this study concludes by suggesting an approach to more fully understand forces driving local resource management and use.     

Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47

In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study I; 18 or 36 mg/kg bw/day) or BDE-47 (Study II; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 microg sumPBDE/g lipid (Study I) or 421 microg BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100,000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison.     

From food aid to livelihoods support: rethinking the role of WFP in eastern Sudan

Despite more than 20 years of distribution of free emergency food in eastern Sudan (38 years in the case of refugees) Global Acute Malnutrition rates are currently the highest in the country. There has been no real improvement in the chronic livelihoods vulnerability that affects people in the region—particularly pastoralists. Food security must be seen from an informed livelihoods perspective. While food aid may still be required as part of transition, WFP must rethink its assistance strategy and advocate for complementarity in the efforts by development actors working across a range of sectors. Alternative models and interventions focused on the rehabilitation of markets and the development of' cargo nets' for the destitute, including cash transfers, must be developed and tested. Land tenure issues should be given particular attention. Food aid will probably remain an important element in the overall response, but its significance relative to other less developed forms of interventions should be reassessed.     

Global-scale vs. regional-scale scenario assumptions: implications for estimating future water withdrawals in the Elbe River basin

In this paper, we explore how scenarios of future water withdrawals in a river basin are influenced by scale-dependent quantifications of the driving forces for two global-scale storylines. Either global-scale information or region-specific information is used to do the quantifications. In addition, we analyze the impact of including or not some restricted regional-scale information in the employed water use model. To develop scenarios of water withdrawals in the German part of the Elbe River basin, we applied the modules for domestic, thermoelectric power and manufacturing water use of the global water model WaterGAP, using scale-dependent driving forces scenarios and other scale-dependent model input. In the global-scale quantitative interpretations of the storylines of the IPCC SRES scenarios A1 and B2, all major driving forces of water withdrawals in the basin—population, thermoelectric power production and industrial gross domestic product—show vigorous increases between 2000 and 2025, while from the regional perspective, smaller increases but mostly decreases appear to be plausible. These discrepancies are partly due to the fact that for the global-scale interpretations only the historic developments until 1990 were taken into account, and not until 2000 as in the regional case. The resulting scenarios of sectoral water withdrawals in 2025 differ strongly between the two scale-dependent interpretations of the storylines, with the global one leading to much higher absolute water withdrawals and much lower withdrawal decreases between 2000 and 2025. Therefore, for regional assessments of water withdrawals, we recommend to embed the scenario analysis in global-scale storylines by performing regional-scale quantifications of the global qualitative driving forces scenarios, based on a limited amount of region-specific information.     

Rhythmic vertical migration of the gastropod Cerithidea decollata in a Kenyan mangrove forest

In Mida Creek, Kenya (3°20′S, 40°5′E), at high water, the snail Cerithidea decollata dwells on the trunks of mangrove trees (Avicennia marina), while during low water it migrates to the ground, foraging at various distances from the trunk, where it aggregates again well before the incoming tide. Snails from the upper shore level are 150–200 m distant from those living at the lower shore level and they cluster at lower heights on trunks. In any case, sufficient height is usually attained to avoid being submersed. An experiment was designed (February and October 2005), exchanging individuals from different shore levels subject to different tide regimes, in order to test whether snails rely on internal information or on external, direct cues, to adapt their behaviour to local conditions. Results show that C. decollata mostly rely on internal information, presumably based on an internal clock. When individuals from upper and lower shore levels were exchanged, their internal clocks continued to govern when to ascend the home trunk and how high to climb for five to six successive tides, after which the behaviour was reset to the new local conditions.