in vitro toxicity assessment of carbon nanomaterial dispersions
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Letters
S106 Abstracts / Toxicologysignificantly, however there was decrease in levels ofreduced glutathione (GSH), ferric reducing ability ofplasma (FRAP) and glutathione peroxidase (GPx) fol-lowing preterm cases as compared to full term cases.In a detailed study we have also established significantcorrelation between levels of organochlorine residuesand oxidative stress. These results indicate the possi-ble involvement of organochlorines pesticides in pretermbirth and altered levels of antioxidant markers. Hence,exposure to such organochlorine pesticides may increasethe risk preterm birth mediated through oxidative stress.
doi:10.1016/j.toxlet.2007.05.285
Q16Further development of an in vitro skin absorptionmethod to measure compartmental disposition andkinetics for chemicals in skin
Ruth Pendlington 1, Helen Minter 1, L. Stupart 2,Cameron MacKay 1, Clive Roper 2, David Sanders 1,Camilla Pease 1
1 Unilever, Bedford, United Kingdom; 2 Charles River
Laboratories, Edinburgh, United KingdomIn vitro skin absorption methodology has been designed(adapting OECD guideline 428) (OECD Guideline,
172S (2007) S1–S240
2004; Pendlington et al., 2007) and further tested togenerate stratum corneum(SC)/epidermis(E)/dermis(D)disposition and kinetic data. This method generatesprospectively useful skin compartment data for der-mal risk assessments today. Data from this methodmay also provide useful input into novel integratedapproaches for predicting skin sensitisation without ani-mals (Pease et al., 2007). Human split-thickness skin(200–400 �m) from several female donors was usedas the model in flow-through diffusion experiments.Twenty-five milligram per milliliter (2.5%, w/w) ofeither [14C]-cinnamic aldehyde or [14C]-cinnamic alco-hol in 4:1 acetone:olive oil was applied in a dose of25 �l/cm2. At each terminal time point (0.5, 1, 2, 4, 8 and24 h), samples were taken for mass balance calculations.Skin samples were tape stripped to remove the SC foranalysis and the E/D of the dosed area was separated byheat treatment. The time course design, with concomi-tant compartmentalisation of skin samples provides thenew methodological aspect. The figures below providean illustrative example of the type of data one can obtainusing radioactive scintillation counting in this method.Temporal profiles of material recovered from (a) SC, Eand D and (b) SC, using 10 individual tape strips areshown for cinnamaldehyde. Given the extensive natureof results obtained from these experiments, we presentan in silico approach to best interpret the data for use insubsequent predictive integrated modelling approaches.
Further evidence has thus been provided here to showthat standard in vitro skin absorption methodology canbe adapted to produce robust time course data on skincompartmental disposition and permeation kinetics.
References
OECD Guideline 428, 2004. Skin absorption: in vitro method.Pendlington, et al., 2007. OEESC Colorado, USA (POSTER and
ORAL).Pease, C.K., et al., 2007. See related Eurotox abstract.
doi:10.1016/j.toxlet.2007.05.286
Q17In vitro toxicity assessment of carbon nanomaterialdispersions
Thomas Peter, Uwe Vohrer, Heike Mertsching
Fraunhofer Institute for Interfacial Engineering and
Biotechnology (Fh-IGB), Stuttgart, GermanyBackground: Carbon nanotubes (CNT) may represent apotential health risk, because there are possible adsorb-tion pathways through skin and lung. In the blood they
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Abstracts / Toxicology
an agglomerate with lipophilic serum proteins and getn touch with many cell types and tissues, if proteinoated CNT agglomerates can penetrate endothelium.y their high surface as well as their residual concen-
ration at catalyst materials these possible bioactive andiopersistent particles have the potential to harm cellsy releasing inflammation reactions, oxidative stress andven necrosis and apoptosis.
Aim: For testing the biocompatibility according toIN ISO 10993-5 in BMBF-supported “TRACER”
Toxicology and health risk assessment of carbon nano-aterials), we examine different kinds of dispersive and
onverted CNT materials for possible cytotoxic charac-eristics.
Methods: Defined CNT-dispersions depending onarticle size and catalyst materials were character-zed with optical density and particle size distribution.ccording to reference material in vitro biocompatibil-
ty was measured with cell proliferation assays (WST-1),eactive oxygen species detection (ROS) and activationf immune cells (FACS) with relevant primary cells, cellines and 3D-testsystems (skin, trachea and vascularized
atrix) after incubation with CNT.Results: Investigations exhibit a changed prolifera-
ion attitude to CNT incubation concerning CNT kind,ize distribution and residual concentrations of catalystaterial. Although CNT exhibit proliferation in dose-
ependent way, acute toxicity compared to asbestos orarbon Black could not be observe.
Outlook: Cytotoxic assessment of CNT is facilitatedith a combination of exact material characterisation and
n vitro toxicological tests. After this, health risks coulde estimated and guidelines for employment protectionecommended.
oi:10.1016/j.toxlet.2007.05.287
18ercutaneous diffusion of uranium: What is the bestxperimental model for occupational riskssessment in the nuclear industry?
abrice Petitot 1, Stephanie Fages 1, Olivier Blanck 2,andrine Frelon 1, Francois Paquet 1
Institut de Radioprotection et de Surete Nucleaire,aboratoire de Radiotoxicologie Experimentale,ierrelatte, France; 2 Bayer Cropscience, Toxicologieecherche, Sophia Antipolis, France
ranium uptake represents an occupational risk in theuclear industry. Uranium intoxication can occur acci-entally by inhalation, ingestion, injection or absorption
172S (2007) S1–S240 S107
through intact or wounded skin. Intact skin route ofabsorption of uranium received little attention and exper-imental data are needed.
The aim of this work was to compare the percutaneousdiffusion of an uranyl nitrate solution (0.01 mol l−1)through hairless rat and human skin in vitro using Franz’sdiffusion cells and through hairless rat skin and nudemouse with human skin biopsy grafted onto its back invivo. Uranium absorption rate through skin and uraniumfraction retained in skin were calculated for each modelafter 24 h of topical exposure to uranyl nitrate.
No significant differences were observed betweenin vitro and in vivo hairless rat model concerninguranium absorption rate, respectively, 2.7 × 10−4 and2.1 × 10−4 cm−2 h−1. Rat models slightly overestimateuranium percutaneous diffusion data obtained throughhuman skin in vitro (1.4 × 10−4 cm−2 h−1). However,using the grafted nude mouse, uranium absorption ratewas higher, reaching 9.9 × 10−4 cm−2 h−1. Uraniumfraction retained in the human grafted skin was about1.8 times lower than the one retained in the skin from allother described models.
As a conclusion, the grafted nude mouse model seemsnot to be adapted to the study of kinetics of uraniumdiffusion. The assessment of kinetics of uranium percu-taneous diffusion will be made using human and hairlessrat skin in vitro. Hairless rat in vivo will be used toobtain data concerning biokinetics of uranium after top-ical exposure.
doi:10.1016/j.toxlet.2007.05.288
Q19A physiologically based biokinetic model forestragole in rats providing more detailed insight indose dependent bioactivation and detoxification
Ans Punt 1, Andreas Freidig 2, Thierry Delatour 3,Gabriele Scholz 3, Benoit Schilter 3, Peter vanBladeren 3, Ivonne Rietjens 1
1 Division of Toxicology, Wageningen University,Wageningen, Netherlands; 2 TNO Quality of Life,Zeist, Netherlands; 3 Nestle Research Centre,Lausanne, Switzerland
Estragole is a natural constituent of several herbs andspices. In mice and rats estragole was demonstratedto be hepatocarcinogenic when administered at high
doses. This carcinogenicity of estragole has been linkedto its metabolic conversion to 1′-sulfooxyestragole asthe proximate carcinogenic and genotoxic metabolite.In order to determine the safety of estragole at low dose