{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T05:45:22Z","timestamp":1740980722573,"version":"3.38.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[1996,9,1]],"date-time":"1996-09-01T00:00:00Z","timestamp":841536000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Ind Health"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p> Currently, most neurotoxicological investigations are still conducted using various animal models (e.g. chickens, rodents). In this report, alternative strategies of testing were examined to detect the neurotoxic potency of foreign compounds. Primary neuronal cell cultures from fetal rats are already an accepted model for mechanistic and pharmacological studies in drug research. Their suitability for neurotoxicological studies was examined by using industrial model compounds, which are well-known inductors of neuropathies: acrylamide, hexachlorophene, paraquat, n-hexane, and its neurotoxic metabolites acetylaceton and 2,5-hexandione. As a control compound, the nonneurotoxic solvent n-heptane was used. General cytotoxicity and the intracellular content of glial fibrillary acid protein, neuron-specific enolase, and neurofilaments were measured. <\/jats:p><jats:p> n-Heptane induced an acute cytotoxicity and acrylamide and 2,5-hexandione produced a delayed cytotoxicity in primary neuronal cells, whereas the others showed no cytotoxic potency in the tested concentration range. These results were in agreement with the quantification of neurons by neuron-specific enolase. In contrast, with the exception of acetylaceton, glia cells were significantly affected by all neurotoxins at the later time. Signs of axonopathies were demonstrated for acrylamide, n-hexane and its metabolites, as well as for hexachlorophene and paraquat in vitro, by determining the intracellular neurofilament level. Therefore, the determination of cell-specific end points is necessary to detect the neurotoxic potency and quality of a compound, whereas the cytotoxicity assay limited the tested concentration range. <\/jats:p>","DOI":"10.1177\/074823379601200507","type":"journal-article","created":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T22:40:01Z","timestamp":1378766401000},"page":"683-696","source":"Crossref","is-referenced-by-count":15,"title":["An in Vitro Model for Toxicological Investigations of Environmental Neurotoxins in Primary Neuronal Cell Cultures"],"prefix":"10.1177","volume":"12","author":[{"given":"Gabriele","family":"Schmuck","sequence":"first","affiliation":[{"name":"BAYER Pharma Research Center Research Toxicology Wuppertal, Germany"}]},{"given":"Gerhard","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"BAYER Pharma Research Center Research Toxicology Wuppertal, Germany"}]}],"member":"179","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"key":"atypb1","first-page":"358","volume":"22","author":"Abou-Donia, M.B.","year":"1995","journal-title":"Physiol"},{"key":"atypb2","unstructured":"Andreas, K. (1994). Nervensystem. In: Lehrbuch der Toxicologie (H. Marquardt and S.G. Sch\u00e4fer, eds.) Wissenschaftsverlag, Mannheim and Leipzig, Germany. pp. 291-312."},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00580957"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1982.tb00300.x"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90679-6"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(91)90020-F"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880050406"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(86)90447-7"},{"key":"atypb9","first-page":"178","volume":"33","author":"Dumuis, A.","year":"1987","journal-title":"Mol. Pharmacol."},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1991.tb00700.x"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.9.3454"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1038\/327620a0"},{"key":"atypb13","unstructured":"Grcevic', N., Gardro-Santel, D., and Jukic', S. (1977). \"Cerebral changes in paraquat poisoning.\" In: Neurotoxicol. (L. Roizin, H. Shiraki, and N. Grcevic ', eds.). Raven Press, New York, NY. pp. 469-484."},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1007\/BF00967658"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(88)90008-1"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-008301-5.50015-7"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1016\/0887-2333(92)90022-J"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(76)90119-8"},{"key":"atypb19","unstructured":"Le Quesne, P.M. (1980). \"Acrylamide in industrial neuropathies.\" In: Neurotoxicology. (L. Roizin, H. Shiraki, and N. Grcevic' , eds.). Raven Press, New York, NY pp. 309-325."},{"key":"atypb20","first-page":"58a","volume":"111","author":"Maccoubrey, C.","year":"1990","journal-title":"J. Cell Biol."},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)91168-3"},{"key":"atypb22","unstructured":"Powell, H.C. and Lampert, P.W. (1977). \"Hexachlorophene neurotoxicity.\" In: Neurotoxicology. (Roizin, L., H. Shiraki, and N. Grcevic' , eds.) Raven Press, New York, NY. pp. 381-389."},{"key":"atypb23","first-page":"R26","volume":"351","author":"Schmuck, G.","year":"1995","journal-title":"Naunyn Schmiedeberg's Arch. Pharmacol. Suppl."},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1982.tb03772.x"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1007\/BF00964098"},{"key":"atypb26","unstructured":"Schousboe, A., Meier, E., Drejer, J., and Herz, L. (1989). \"Preparation of primary cultures of mouse (rat) cerebellar granule cells.\" In: A Dissection and Tissue Culture of the Nervous System. (A. Shahar, J. de Vellis, A. Vernadakis , B. Haber, (eds.). Alan R. Liss, Inc., New York, NY. pp. 203-207."},{"key":"atypb27","first-page":"768","volume":"37","author":"Selkoe, D.J.","year":"1978","journal-title":"Exp. Neurol."},{"key":"atypb28","unstructured":"Spencer, P.S. and Schaumburg, H.H. (1977). \"Industrial neuropathies .\" In: Neurotoxicology. ( L. Roizin, H. Shiraki, and N. Grcevic', eds.). Raven Press, New York, NY. pp. 427-430."},{"key":"atypb29","unstructured":"Spencer, P.S., Couri, D., and Schaumburg, H.H. (1980). \"n-Hexane and n-methyl butyl ketone.\" In: Experimental and Clinical Neurotoxicology . (P.S. Spencer and H.H. Schaumburg, eds.). Williams and Wilkins , Baltimore, MD. pp. 456-475."},{"key":"atypb30","unstructured":"Towfighi, J. (1980). \"Hexachlorophene.\" In: Experimental and Clinical Neurotoxicology. (P.S. Spencer and H.H. Schaumburg, eds.). Williams and Wilkins, Baltimore, MD. pp. 440-455."},{"key":"atypb31","unstructured":"Watanabe, I. (1980). \"Organotins (Triethyltin).\" In: Experimental and Clinical Neurotoxicology. ( P.S. Spencer and H.H. Schaumburg, eds.). Williams and Wilkins, Baltimore, MD. pp. 545-557."},{"key":"atypb32","doi-asserted-by":"crossref","unstructured":"Weiss, D.G. (1986). \"The mechanism of axonal transport.\" In: Axonal Transport. (Z. Iqbal, ed.). CRL Press, Inc. 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