title: Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos.
abstract: Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia. In another group of conscious animals, auditory startle reflex (ASR) was evaluated followed, after euthanasia, with measurements of plasma B-esterases, and genotoxicity with the alkaline comet assay (ACA) at the same CPF doses. The results indicated a CPF dose related inhibition of B-esterases. Enhanced inhibition of the ASR by a subthreshold pre-pulse was observed at all doses and ACA showed a significant higher DNA damage than vehicle controls in animals exposed to 10mg/kg CPF. A trend to higher frequencies of EEGp and an increase in amplitude of the first negative wave of the SEP were found at all doses. The first positive wave of the SEP decreased at the CPF dose of 10mg/kg. In summary, a shift to higher EEG frequencies and alterations of somatosensory and auditory input to the central nervous system were sensitive manifestations of CPF toxicity, associated with depression of B-esterases. The changes in electrical activity of the cerebral cortex and DNA damage observed at doses that do not elicit overt toxicity may be useful in the detection of CPF exposure before clinical signs appear.
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
authors.forename: Mariel
authors.initials: M
authors.lastname: Muller
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Hess
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
authors.forename: Agostina
authors.initials: A
authors.lastname: Tardivo
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lajmanovich
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina.
authors.forename: Andres
authors.initials: A
authors.lastname: Attademo
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina.
authors.forename: Gisela
authors.initials: G
authors.lastname: Poletta
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe, Argentina.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Simoniello
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Yodice
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
authors.forename: Simona
authors.initials: S
authors.lastname: Lavarello
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina.
authors.forename: Dante
authors.initials: D
authors.lastname: Chialvo
authors.affiliation: PROFISIO, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina; Greater Los Angeles VA Healthcare System and David Geffen School of Medicine at UCLA, 11301 Wilshire Building, Los Angeles, CA 90073, USA. Electronic address: oscremin@ucla.edu.
authors.forename: Oscar
authors.initials: O
authors.lastname: Scremin
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000161:Acoustic Stimulation; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002091:Butyrylcholinesterase / Q000097:blood; D043182:Carboxylesterase / Q000097:blood; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology*; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004950:Esterases / Q000097:blood / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D065808:Prepulse Inhibition / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*
chemical_list: D002800:Cholinesterase Inhibitors; D004950:Esterases; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D004390:Chlorpyrifos
keywords: Acetylcholinesterase inhibitors; Auditory startle; Comet assay; EEG; Evoked potentials