Systematic selection of a dose metric for metal-based nanoparticles.

Mass is traditionally the unique measure of the administered dose in toxicity studies with conventional chemical substances. Because of the variety of specific physical properties of nanoparticles, other dose metrics such as the number of particles, their size, shape, surface area or volume may be more appropriate. Here we applied a systematic, unbiased approach to derive the most appropriate dose metric for nanoparticles from experimental data. The approach was exemplified for copper, zinc oxide, and silver nanoparticles with different diameters, coatings and shapes, combining experiments with six aquatic organisms, two mammalian and two piscine liver cell lines from different research groups. The nanoparticle diameter appeared to be a powerful estimator of metal oxide nanoparticle effects. Since effect concentrations were related to size to the power 3, it is indicated that volume (mass) is the appropriate dose metric for all tested species and toxicological endpoints and all tested metal oxide nanoparticles within the tested size range (25–500 nm). The new method enables extrapolation of test results from one type of metal oxide nanomaterial to another, thereby offering a powerful tool to improved efficiency in risk research and risk assessment of nanomaterials.Environmental Biolog

Revision of the Intervention value for lead; evaluation of the intervention values derived for soil/sediment and groundwater

This report documents the important aspects in deriving the intervention values for lead (Pb) for soil/sediment and groundwater as part of a current ongoing running evaluation of existing intervention values. Reported for lead are the physical-chemical properties, the ecotoxicological serious soil-contamination concentration (ECOTOX SCC), the human toxicological Maximal Tolerable Risk (human MTR), human toxicological serious soil contamination concentration (HUM-TOX SCC) and proposals for the intervention value for soil and groundwater. It is recommended to use an equation derived for field soils (with pH, organic matter and clay content)for the soil type correction of the intervention values derived. If it is decided to use only the organic-matter and clay content, we advise proceeding with the current correction of Van den Berg/Roels. Based on the current toxicological information, ECOTOX SCC is recalculated with the current soil type correction (490 mg/kg d.m.) and the proposed soil type correction with pH (450 mg/kg d.m.). If it is decided to use the 'added risk-approach', the ECOTOX SCC for lead will be 575 and 535 mg/kg d.m., respectively. The ECOTOX SCC calculated for sediments is much higher (64.000 mg/kg d.m.).The human-toxicological maximal tolerable risk (human MTR) is maintained at 3.6 microg/kg b.w./day, which is also supported by the World Health Organisation (WHO). The human exposure to lead is mainly determined by the ingestion of soil particles, the intake of contaminated crops and the bioavailability of lead from soil in the human body. Prior to completing the research on bioavailability in the human body, a relative bioavailability factor for lead in soil of 0.6 was deduced. An average of 100 mg of soil per day is proposed for soil ingestion by children (1 to 6), instead of the current 150 mg per day. The average crop consumption can be slightly reduced. If it is decided to use a general background, the background exposure for lead is estimated to be 25% of the human MTR. The recalculated HUMTOX EBVC is found between 450 and 670 mg/kg, depending on the choices made and the extent to which new data are used. Integration of the HUMTOX SCC value with that of ECOTOX SCC leads to a proposal for the intervention value soil/sediment of 450-575 mg/kg d.m. and 32-41 microg/l for groundwaterDit rapport behandelt de aspecten die van belang zijn voor de prioritaire evaluatie van de interventiewaarde bodemsanering voor lood als onderdeel van het lopende project Evaluatie Interventiewaarden. De partitie-coefficient en de bodemtypecorrectie voor lood kunnen gebaseerd worden op een vergelijking die voor veldbodem is afgeleid. Wanneer alleen gebruik gemaakt mag worden van humus- en lutumgehalten, wordt aanbevolen de huidige vergelijking van Van den Berg/Roels te handhaven. De bioconcentratiefactor van lood in bladgewas wordt gehandhaafd; voor knolgewas is deze verdubbeld. De ecotoxicologische ernstige bodemverontreinigings-concentratie (ECOTOX EBVC) is herberekend met actuele toxiciteitsgegevens voor bodem volgens de bestaande bodemtypecorrectie en volgens de voorgestelde bodemtypecorrectie met pH (resp. 490 en 450 mg/kg d.s.). Wanneer de 'toegevoegd risico' benadering wordt toegepast is de ECOTOX-EBVC berekend op resp. 575 en 535 mg/kg d.s.. De berekende risicogrens voor waterbodem is veel hoger (64.000 mg/kg). Het maximaal toelaatbaar risico voor de mens (MTR-humaan) blijft gehandhaafd op 3.6 microg/kg lichaamsgewicht/dag, welke ook door de WHO wordt aangehouden. De blootstelling van de mens door bodemverontreiniging wordt vooral bepaald door ingestie van grond en opname via verontreinigd gewas en biobeschikbaarheid van lood uit de grond in het lichaam. Voorafgaand aan de afronding van het onderzoek naar de biobeschikbaarheid van lood in het lichaam is een relatieve biobeschikbaarheidsfactor voor grond afgeleid van 0.6. In het kader van de Evaluatie als geheel wordt voorgesteld de grondingestie door kinderen terug te brengen tot 100 mg/dag (was 150 mg/dag). Indien beleidsmatig gewenst, kan de generieke achtergrondblootstelling van de mens voor lood gesteld worden op 25% van het MTR-humaan. Afhankelijk van de gemaakte keuzes ligt de herziene humaan-toxicologische ernstige bodemverontreinigingsconcentratie (HUMTOX EBVC) tussen 450 en 670 mg/kg. Integratie met de ECOTOX EBVC levert een voorstel voor een interventiewaarde grond tussen 450 en 575 mg/kg. Op basis van de bijgestelde partitiecoefficient wordt voorgesteld de interventiewaarde grondwater iets te verlagen tot 32-41 microg/l

Revision of the Intervention value for lead; evaluation of the intervention values derived for soil/sediment and groundwater

Dit rapport behandelt de aspecten die van belang zijn voor de prioritaire evaluatie van de interventiewaarde bodemsanering voor lood als onderdeel van het lopende project Evaluatie Interventiewaarden. De partitie-coefficient en de bodemtypecorrectie voor lood kunnen gebaseerd worden op een vergelijking die voor veldbodem is afgeleid. Wanneer alleen gebruik gemaakt mag worden van humus- en lutumgehalten, wordt aanbevolen de huidige vergelijking van Van den Berg/Roels te handhaven. De bioconcentratiefactor van lood in bladgewas wordt gehandhaafd; voor knolgewas is deze verdubbeld. De ecotoxicologische ernstige bodemverontreinigings-concentratie (ECOTOX EBVC) is herberekend met actuele toxiciteitsgegevens voor bodem volgens de bestaande bodemtypecorrectie en volgens de voorgestelde bodemtypecorrectie met pH (resp. 490 en 450 mg/kg d.s.). Wanneer de 'toegevoegd risico' benadering wordt toegepast is de ECOTOX-EBVC berekend op resp. 575 en 535 mg/kg d.s.. De berekende risicogrens voor waterbodem is veel hoger (64.000 mg/kg). Het maximaal toelaatbaar risico voor de mens (MTR-humaan) blijft gehandhaafd op 3.6 microg/kg lichaamsgewicht/dag, welke ook door de WHO wordt aangehouden. De blootstelling van de mens door bodemverontreiniging wordt vooral bepaald door ingestie van grond en opname via verontreinigd gewas en biobeschikbaarheid van lood uit de grond in het lichaam. Voorafgaand aan de afronding van het onderzoek naar de biobeschikbaarheid van lood in het lichaam is een relatieve biobeschikbaarheidsfactor voor grond afgeleid van 0.6. In het kader van de Evaluatie als geheel wordt voorgesteld de grondingestie door kinderen terug te brengen tot 100 mg/dag (was 150 mg/dag). Indien beleidsmatig gewenst, kan de generieke achtergrondblootstelling van de mens voor lood gesteld worden op 25% van het MTR-humaan. Afhankelijk van de gemaakte keuzes ligt de herziene humaan-toxicologische ernstige bodemverontreinigingsconcentratie (HUMTOX EBVC) tussen 450 en 670 mg/kg. Integratie met de ECOTOX EBVC levert een voorstel voor een interventiewaarde grond tussen 450 en 575 mg/kg. Op basis van de bijgestelde partitiecoefficient wordt voorgesteld de interventiewaarde grondwater iets te verlagen tot 32-41 microg/l.This report documents the important aspects in deriving the intervention values for lead (Pb) for soil/sediment and groundwater as part of a current ongoing running evaluation of existing intervention values. Reported for lead are the physical-chemical properties, the ecotoxicological serious soil-contamination concentration (ECOTOX SCC), the human toxicological Maximal Tolerable Risk (human MTR), human toxicological serious soil contamination concentration (HUM-TOX SCC) and proposals for the intervention value for soil and groundwater. It is recommended to use an equation derived for field soils (with pH, organic matter and clay content)for the soil type correction of the intervention values derived. If it is decided to use only the organic-matter and clay content, we advise proceeding with the current correction of Van den Berg/Roels. Based on the current toxicological information, ECOTOX SCC is recalculated with the current soil type correction (490 mg/kg d.m.) and the proposed soil type correction with pH (450 mg/kg d.m.). If it is decided to use the 'added risk-approach', the ECOTOX SCC for lead will be 575 and 535 mg/kg d.m., respectively. The ECOTOX SCC calculated for sediments is much higher (64.000 mg/kg d.m.).The human-toxicological maximal tolerable risk (human MTR) is maintained at 3.6 microg/kg b.w./day, which is also supported by the World Health Organisation (WHO). The human exposure to lead is mainly determined by the ingestion of soil particles, the intake of contaminated crops and the bioavailability of lead from soil in the human body. Prior to completing the research on bioavailability in the human body, a relative bioavailability factor for lead in soil of 0.6 was deduced. An average of 100 mg of soil per day is proposed for soil ingestion by children (1 to 6), instead of the current 150 mg per day. The average crop consumption can be slightly reduced. If it is decided to use a general background, the background exposure for lead is estimated to be 25% of the human MTR. The recalculated HUMTOX EBVC is found between 450 and 670 mg/kg, depending on the choices made and the extent to which new data are used. Integration of the HUMTOX SCC value with that of ECOTOX SCC leads to a proposal for the intervention value soil/sediment of 450-575 mg/kg d.m. and 32-41 microg/l for groundwaterDGM-Bode

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [I-123]-FP-CIT SPECT imaging: The [I-123]-FP-CIT study group

OBJECTIVE: To evaluate whether visual assessment of [I-123]-FP-CIT (DaTSCAN(TM), Nycomed Amersham, pie) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [I-123]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [I-123]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome

Intravascular lymphomatosis of the brain in a patient with myelodysplastic syndrome

Background. A 77-year-old retired research pharmacologist with a long-standing history of anemia and a recent pathologically confirmed diagnosis of myelodysplastic syndrome was referred to a stroke unit for evaluation of slowly progressive cognitive deterioration, confusion and paroxysmal stroke-like episodes. a previous neurological work-up had revealed no noteworthy abnormalities except for chronic bilateral caudate infarctions seen on MRI and CT examinations of the brain. Investigations. Physical examination, laboratory testing, brain MRI scanning, EEG, transesophageal echocardiography, cerebral angiography, CT scanning, and brain biopsy. Diagnosis. Intravascular lymphomatosis of the brain. Management. combined chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and rituximab