LACK OF DISTINCTIVE SURFACE ANTIGEN ON CELLS TRANSFORMED BY MURINE SARCOMA VIRUS

Some murine sarcoma virus (MSV)-transformed mouse 3T3 cells contain the MSV genome in the absence of infectious helper murine leukemia virus (MuLV) and MSV production. These cells, designated S+L- (sarcoma positive, leukemia negative), were analyzed for the presence of a possible MSV-determined membrane antigen by the mixed hemadsorption test and in vitro lymphocyte cytotoxicity assay. Two different serological approaches were used: (a) isoantibody-free sera were obtained by immunizing with MSV of syngeneic origin or by allowing primary, autologous MSV sarcomas to regress, or (b) alloantisera obtained by immunizing C57BL mice with S+L- cells were absorbed with the corresponding nontransformed 3T3 cells until all activity against 3T3 had been removed. While MuLV-superinfected S+L- cells and a culture line of an MSV sarcoma known to produce both MSV and MLV were highly reactive, normal 3T3 and S+L- cells were negative. Similarly, lymph node cells from MSV immune mice or rats did not kill S+L- cells, although they were cytotoxic against target cells known to carry MuLV-associated antigens. Thus, the present study gives no positive evidence for the existence of any MSV-induced new surface antigen in the transformed target cell, known to carry the viral genome

Grouping of nanomaterials to read-across hazard endpoints: from data collection to assessment of the grouping hypothesis by application of chemoinformatic techniques

An increasing number of manufactured nanomaterials (NMs) are being used in industrial products and need to be registered under the REACH legislation. The hazard characterisation of all these forms is not only technically challenging but resource and time demanding. The use of non-testing strategies like read-across is deemed essential to assure the assessment of all NMs in due time and at lower cost. The fact that read-across is based on the structural similarity of substances represents an additional difficulty for NMs as in general their structure is not unequivocally defined. In such a scenario, the identification of physicochemical properties affecting the hazard potential of NMs is crucial to define a grouping hypothesis and predict the toxicological hazards of similar NMs. In order to promote the read-across of NMs, ECHA has recently published “Recommendations for nanomaterials applicable to the guidance on QSARs and Grouping”, but no practical examples were provided in the document. Due to the lack of publicly available data and the inherent difficulties of reading-across NMs, only a few examples of read-across of NMs can be found in the literature. This manuscript presents the first case study of the practical process of grouping and read-across of NMs following the workflow proposed by ECHA. The workflow proposed by ECHA was used and slightly modified to present the read-across case study. The Read-Across Assessment Framework (RAAF) was used to evaluate the uncertainties of a read-across within NMs. Chemoinformatic techniques were used to support the grouping hypothesis and identify key physicochemical properties. A dataset of 6 nanoforms of TiO2 with more than 100 physicochemical properties each was collected. In vitro comet assay result was selected as the endpoint to read-across due to data availability. A correlation between the presence of coating or large amounts of impurities and negative comet assay results was observed. The workflow proposed by ECHA to read-across NMs was applied successfully. Chemoinformatic techniques were shown to provide key evidence for the assessment of the grouping hypothesis and the definition of similar NMs. The RAAF was found to be applicable to NMs