in vitro toxicity assessment of carbon nanomaterial dispersions

2
S106 Abstracts / Toxicology Letters 172S (2007) S1–S240 significantly, however there was decrease in levels of reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) and glutathione peroxidase (GPx) fol- lowing preterm cases as compared to full term cases. In a detailed study we have also established significant correlation between levels of organochlorine residues and oxidative stress. These results indicate the possi- ble involvement of organochlorines pesticides in preterm birth and altered levels of antioxidant markers. Hence, exposure to such organochlorine pesticides may increase the risk preterm birth mediated through oxidative stress. doi:10.1016/j.toxlet.2007.05.285 Q16 Further development of an in vitro skin absorption method to measure compartmental disposition and kinetics 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 Kingdom In vitro skin absorption methodology has been designed (adapting OECD guideline 428) (OECD Guideline, 2004; Pendlington et al., 2007) and further tested to generate stratum corneum(SC)/epidermis(E)/dermis(D) disposition and kinetic data. This method generates prospectively useful skin compartment data for der- mal risk assessments today. Data from this method may also provide useful input into novel integrated approaches for predicting skin sensitisation without ani- mals (Pease et al., 2007). Human split-thickness skin (200–400 m) from several female donors was used as the model in flow-through diffusion experiments. Twenty-five milligram per milliliter (2.5%, w/w) of either [ 14 C]-cinnamic aldehyde or [ 14 C]-cinnamic alco- hol in 4:1 acetone:olive oil was applied in a dose of 25 l/cm 2 . At each terminal time point (0.5, 1, 2, 4, 8 and 24 h), samples were taken for mass balance calculations. Skin samples were tape stripped to remove the SC for analysis and the E/D of the dosed area was separated by heat treatment. The time course design, with concomi- tant compartmentalisation of skin samples provides the new methodological aspect. The figures below provide an illustrative example of the type of data one can obtain using radioactive scintillation counting in this method. Temporal profiles of material recovered from (a) SC, E and D and (b) SC, using 10 individual tape strips are shown for cinnamaldehyde. Given the extensive nature of results obtained from these experiments, we present an in silico approach to best interpret the data for use in subsequent predictive integrated modelling approaches. Further evidence has thus been provided here to show that standard in vitro skin absorption methodology can be adapted to produce robust time course data on skin compartmental 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 Q17 In vitro toxicity assessment of carbon nanomaterial dispersions Thomas Peter , Uwe Vohrer, Heike Mertsching Fraunhofer Institute for Interfacial Engineering and Biotechnology (Fh-IGB), Stuttgart, Germany Background: Carbon nanotubes (CNT) may represent a potential health risk, because there are possible adsorb- tion pathways through skin and lung. In the blood they

Upload: thomas-peter

Post on 01-Dec-2016

216 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: In vitro toxicity assessment of carbon nanomaterial dispersions

Letters

S106 Abstracts / Toxicology

significantly, 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 Kingdom

In 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, Germany

Background: Carbon nanotubes (CNT) may represent apotential health risk, because there are possible adsorb-tion pathways through skin and lung. In the blood they

Page 2: In vitro toxicity assessment of carbon nanomaterial dispersions

Letters

cicBtbbe

D(mct

piAirolm

tsmdC

wibr

d

QPea

FS

1

LPR

Und

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