Stewart, J. D.

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EXCLI Journal 2010;9:156-158  ISSN 1611-2156 Received: October 14, 2010, published: October 15, 2010  156 Editorial:  IN VITRO TEST SYSTEMS IN TOXICOLOGY  J.D. Stewart  Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardey-strasse 67, 44139 Dortmund, Germany  E-mail: stewart@ifado.de, Telephone: +49 231-1084-406, Fax: +49 231-1084-403  In vitro test systems are becoming increasingly important within EU funding policy (Van-haecke et al., 2009). In the context of the new European Chemicals Legislation (REACH) it will be particularly important to establish improved and rapid in vitro toxicology assays (Lilienblum et al., 2008). However it is currently impossible to predict NOAELS (no observ-able adverse effect levels) only by in vitro tests. Therefore, a premature replacement of in vivo studies may lead to a loss of information required for adequate protection of human health. To give our readers an overview over this controversial topic we summarize key messages of recent publications on in vitro toxicity test systems (Table 1A), studies on endocrine disrup-tion and developmental toxicity (Table 1B) as well as nanoparticle and fibre research (Table 1C).   Table 1A: Recent studies in in vitro toxicity test systems  Key message Reference  An optimized 3D in vitro system with rat hepatocytes was established that shows similar gene expression alterations in response to methapyrilene compared to the in vivo situation in rat liver. Schug et al., 2008 Despite important advances in the field of in vitro systems one of the major limitations is that still no techniques are available allowing de-termination of NOAELs in vitro. Bolt and Hengstler, 2008  Thresholds for genotoxic carcinogens is still a controversially dis-cussed topic. Nevertheless, under certain circumstances „practical thresholds“ may be defined. Bolt, 2008  This review gives a comprehensive overview over the available in vitro tests and discusses if and to which degree they can replace animal experiments. Lilienblum et al., 2008  Ethanol may cause artefacts in cell culture. The amounts of ethanol used for disinfection that contaminates cell culture media may be underestimated. Pontes et al., 2008  Human gingival and pulpal fibroblast in vitro systems are applicable for toxicity evaluation of dental restorative materials. Reichl et al., 2008    EXCLI Journal 2010;9:156-158  ISSN 1611-2156 Received: October 14, 2010, published: October 15, 2010  157 Table 1B: Recent studies on endocrine disruption and developmental toxicity  Key message Reference  Diesel exhaust may compromise spermatogenesis in mouse off-spring. Ono et al., 2008  Methoxychlor, an organochlorine pesticide, transiently inhibits testicu-lar steroidogenesis in rats. Vaithinathan et al., 2008  Low doses of (137) caesium modify testicular and adrenal steroido-genic metabolism. Grignard et al., 2008  Perinatal coexposure to methylmercury and polychlorinated biphenyls produces no synergistic effects on neurobehavioral development in mice. Sugawara et al., 2008  NOELS for 4,4’-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol were derived in the uterotrophic assay in rats. Yamasaki et al., 2008  In utero and postnatal exposure of rats to a phytoestrogen-enriched diet did not protect but enhanced the extent of inflammation. Seibel et al., 2008    Table 1C: Nanoparticle and fibre research  Key message Reference  Eicosane, a component of nanoparticles in diesel exhaust may be related to dysfunction of surfactant. Kanno et al., 2008  An in vitro system for the analysis of mineral fiber biopersistence was established. Dika Nguea et al., 2008a  Alterations in gene expression patterns during mineral fiber degrada-tion by monozytes are presented. Dika Nguea et al., 2008b  Intravenous administration of low doses (5 mg/kg body weight) of titanium dioxide nanoparticles did not induce toxic effects in rats. Fabian et al., 2008     REFERENCES  Bolt HM. International symposium on genotoxic and carcinogenic thresholds. Arch Toxicol 2008;82:981-2.   Bolt HM, Hengstler JG. Most cited articles in the Archives of Toxicology: the debate about possibilities and limitations of in vi-tro toxicity tests and replacement of in vivo studies. Arch Toxicol 2008;82:881-3.  Dika Nguea H, de Reydellet A, Lehuédé P, de Méringo A, Robé A, Le Faou A, Rihn BH. A new in vitro cellular system for the analysis of mineral fiber biopersistence. Arch Toxicol 2008a;82:435-43.  Dika Nguea H, de Reydellet A, Lehuédé P, De Meringo A, Le Faou A, Marcocci L, Rihn BH. Gene expression profile in mono-cyte during in vitro mineral fiber degrada-tion. Arch Toxicol 2008b;82:355-62.   Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, van Ravenzwaay B. Tissue distribution and toxicity of intra-venously administered titanium dioxide nanoparticles in rats. Arch Toxicol 2008; 82:151-7.  Grignard E, Guéguen Y, Grison S, Lobac-caro JM, Gourmelon P, Souidi M. In vivo effects of chronic contamination with 137 cesium on testicular and adrenal steroido-genesis. Arch Toxicol 2008;82:583-9.  EXCLI Journal 2010;9:156-158  ISSN 1611-2156 Received: October 14, 2010, published: October 15, 2010  158 Kanno S, Furuyama A, Hirano S. Effects of eicosane, a component of nanoparticles in diesel exhaust, on surface activity of pul-monary surfactant monolayers. Arch Toxi-col 2008;82:841-50.   Lilienblum W, Dekant W, Foth H, Gebel T, Hengstler JG, Kahl R, Kramer PJ, Schwein-furth H, Wollin KM. Alternative methods to safety studies in experimental animals: role in the risk assessment of chemicals under the new European Chemicals Legis-lation (REACH). Arch Toxicol 2008;82: 211-36.  Ono N, Oshio S, Niwata Y, Yoshida S, Tsukue N, Sugawara I, Takano H, Takeda K. Detrimental effects of prenatal exposure to filtered diesel exhaust on mouse sper-matogenesis. Arch Toxicol 2008;82:851-9.  Pontes H, Carvalho M, de Pinho PG, Carmo H, Remião F, Carvalho F, Bastos ML. Ethanol, the forgotten artifact in cell culture. Arch Toxicol 2008;82:197-8.  Reichl FX, Seiss M, Marquardt W, Klein-sasser N, Schweikl H, Kehe K, Hickel R. Toxicity potentiation by H2O2 with com-ponents of dental restorative materials on human oral cells. Arch Toxicol 2008;82:21-8.  Schug M, Heise T, Bauer A, Storm D, Blaszkewicz M, Bedawy E, Brulport M, Geppert B, Hermes M, Föllmann W, Rapp K, Maccoux L, Schormann W, Appel KE, Oberemm A, Gundert-Remy U, Hengstler JG. Primary rat hepatocytes as in vitro sys-tem for gene expression studies: compari-son of sandwich, Matrigel and 2D cultures. Arch Toxicol 2008;82:923-31.   Seibel J, Molzberger AF, Hertrampf T, Laudenbach-Leschowski U, Degen GH, Diel P. In utero and postnatal exposure to a phytoestrogen-enriched diet increases pa-rameters of acute inflammation in a rat model of TNBS-induced colitis. Arch Toxi-col 2008;82:941-50.  Sugawara N, Ohba T, Nakai K, Kakita A, Nakamura T, Suzuki K, Kameo S, Shimada M, Kurokawa N, Satoh C, Satoh H. Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobe-havioral development in mice. Arch Toxi-col 2008;82:387-97.   Vaithinathan S, Saradha B, Mathur PP. Transient inhibitory effect of methoxychlor on testicular steroidogenesis in rat: an in vivo study. Arch Toxicol 2008;82:833-9.  Vanhaecke T, Snykers S, Rogiers V, Garthoff B, Castell JV, Hengstler JG: EU research activities in alternative testing strategies: current status and future perspec-tives. Arch Toxicol 2009;83:1037-42.  Yamasaki K, Miyata K, Shiraishi K, Muroi T, Higashihara N, Oshima H, Minobe Y. Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4'-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol, based on the OECD draft protocols. Arch Toxicol 2008;82:301-11.   

In vitro test systems in toxicology

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In vitro test systems in toxicology

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