title: Classification of phthalates based on an in vitro neurosphere assay using rat mesencephalic neural stem cells.
abstract: Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental programming, we previously established an in vitro neurosphere assay system using rat mesencephalic neural stem cells that can be used to evaluate. Here, we extended the assay system to examine the neurodevelopmental toxicity of the endocrine disruptors butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, diethyl phthalate, di(2-ethyl hexyl) phthalate, di-n-pentyl phthalate, and dihexyl phthalate at a range of concentrations (0-100 μM). All phthalates tested inhibited cell migration with a linear or non-linear range of concentrations when comparing migration distance to the logarithm of the phthalate concentrations. On the other hand, some, but not all, phthalates decreased the number of proliferating cells. Apoptotic cells were not observed upon phthalate exposure under any of the conditions tested, whereas the dopaminergic toxin rotenone induced significant apoptosis. Thus, we were able to classify phthalate toxicity based on cell migration and cell proliferation using the in vitro neurosphere assay.
authors.affiliation: Center for Environmental Risk Research, National Institute for Environmental Studies.
authors.forename: Masami
authors.initials: M
authors.lastname: Ishido
authors.forename: Junko
authors.initials: J
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology*; D010795:Phthalic Acids / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D051381:Rats; D012402:Rotenone / Q000633:toxicity; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D052244:Endocrine Disruptors; D010795:Phthalic Acids; D012402:Rotenone; C032279:phthalic acid