title: Models of neurotoxicity: extrapolation of benchmark doses in vitro.
abstract: In risk assessment, no observed exposure level (NOAEL) and benchmark dose (BMD) are usually derived either from epidemiological studies in humans or from animal experiments. In many in vitro studies, concentration-effect/response curves have been analyzed using different mathematical models finalized to the identification of EC50. In the present article, we propose a model to fit dose-response curves in vitro. The BMD approach has been used to compare the cell viability (MIT assay) of different rat (C6 and PC12, glial and neuronal, respectively) and human cell lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-hour exposure to the following neurotoxic substances: manganese chloride (MnCl2), methyl-mercury (Me-Hg), and the enantiomers of styrene oxide (SO). For all rat and human cell lines, the potency of the examined compounds was: MnCl2 < S-SO < R-SO < Me-Hg. A preliminary comparison with in vivo toxicity data for these substances gave rise to consistent results. Whereas a reasonable agreement between in vitro and in vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has been reported for Me-Hg and these appear to be either much higher or lower than the BMD for the MIT assay we observed in vitro.
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Vettori
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.forename: Andrea
authors.initials: A
authors.lastname: Caglieri
authors.forename: Sandra
authors.initials: S
authors.lastname: Ceccatelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D017895:Manganese Compounds / Q000008:administration & dosage; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity; D008954:Models, Biological; D009498:Neurotoxins / Q000008:administration & dosage* / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D018570:Risk Assessment; D013237:Stereoisomerism
chemical_list: D002712:Chlorides; D004852:Epoxy Compounds; D017895:Manganese Compounds; D008767:Methylmercury Compounds; D009498:Neurotoxins; C013690:styrene oxide; C025340:manganese chloride