Print Email Facebook Twitter The benchmark approach applied to a 28-day toxicity study with rhodorsil silane in rats: The impact of increasing the number of dose groups Title The benchmark approach applied to a 28-day toxicity study with rhodorsil silane in rats: The impact of increasing the number of dose groups Author Woutersen, R.A. Jonker, D. Stevenson, H. te Biesebeek, J.D. Slob, W. Instituut CIVO-Toxicologie en Voeding TNO Publication year 2001 Abstract The OECD study design, aimed at obtaining a no-observed-adverse-effect level (NOAEL), may be suboptimal for deriving a benchmark dose. Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design. Seven groups of 10 female rats each were intragastrically administered corn oil without (controls) or with 50, 150, 300, 450, 600 or 750 mg Rhodorsil Silane/kg body weight/day, once daily (7 days/week) for 4 weeks. From the complete dataset, two subsets were selected, one representing a study design with seven dose groups of five animals (7×5 design), the other representing a study design with four dose groups of 10 animals (4×10 design). Under the conditions of the present study, the NOAEL for Rhodorsil Silane 198 was assessed at 50 mg/kg body weight/day, based on the data of the 4×10 design. The benchmark approach resulted in a benchmark dose of 19 mg/kg body weight/day, based on the data of the 7×5 design. Comparison of the results demonstrated that the multiple dose (7×5) design led to a more reliable result than the OECD (4×10) design, despite the smaller total number of animals. The dose-response analysis showed that at "the NOAEL" the effect on relative spleen weight was larger than 10%, illustrating that at the NOAEL, adverse effects may occur. © 2001 Elsevier Science Ltd. Chemicals/CAS: Alanine Transaminase, EC 18.104.22.168; Aspartate Aminotransferases, EC 22.214.171.124; Hemoglobins; methyl 2-butoxyethyl silicate; Silanes; Silicates Subject NutritionAlanine TransaminaseAnimalsAspartate AminotransferasesDose-Response Relationship, DrugErythrocyte CountFemaleHematopoiesisHemoglobinsLiverNo-Observed-Adverse-Effect LevelOrgan SizeRatsRats, WistarResearch DesignSilanesSilicatesSpleenToxicity TestsAnimaliaZea mays To reference this document use: http://resolver.tudelft.nl/uuid:a4cd196b-081c-473b-ae37-19dbd169be16 DOI https://doi.org/10.1016/s0278-6915(01)00015-1 TNO identifier 57110 ISSN 0278-6915 Source Food and Chemical Toxicology, 39 (7), 697-707 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.