title: Assessing biomarkers and neuropsychological outcomes in rural populations exposed to organophosphate pesticides in Chile--study design and protocol.
abstract: BACKGROUND
  Health effects of pesticides are easily diagnosed when acute poisonings occurs, nevertheless, consequences from chronic exposure can only be observed when neuropsychiatric, neurodegenerative or oncologic pathologies appear. Therefore, early monitoring of this type of exposure is especially relevant to avoid the consequences of pathologies previously described; especially concerning workers exposed to pesticides on the job. For acute organophosphate pesticides (OPP) exposure, two biomarkers have been validated: plasma cholinesterase (ChE) and acetylcholinesterase (AChE) from erythrocytes. These enzymes become inhibited when people are exposed to high doses of organophosphate pesticides, along with clear signs and symptoms of acute poisoning; therefore, they do not serve to identify risk from chronic exposure. This study aims to assess a novel biomarker that could reflect neuropsychological deterioration associated with long-term exposure to organophosphate pesticides via the enzyme acylpeptide-hydrolase (ACPH), which has been recently identified as a direct target of action for some organophosphate compounds.
  
  
  METHODS
  Three population groups were recruited during three years (2011-2013): Group I having no exposure to pesticides, which included people living in Chilean coastal areas far from farms (external control); Group II included those individuals living within the rural and farming area (internal control) but not occupationally exposed to pesticides; and Group III living in rural areas, employed in agricultural labour and having had direct contact with pesticides for more than five years. Blood samples to assess biomarkers were taken and neuropsychological evaluations carried out seasonally; in three time frames for the occupationally exposed group (before, during and after fumigation period); in two time frames for internal control group (before and during fumigation), and only once for the external controls. Neuropsychological evaluations considered cognitive functions, affectivity and psychomotor activity. The biomarkers measured included ChE, AChE and ACPH. Statistical analysis and mathematical modelling used both laboratory results and neuropsychological testing outcomes in order to assess whether ACPH would be acceptable as biomarker for chronic exposure to OPP.
  
  
  CONCLUSIONS
  This study protocol has been implemented successfully during the time frames mentioned above for seasons 2011, 2012 and 2013-2014.
authors.affiliation: Department of Public Health, Faculty of Medicine, Universidad Católica del Norte, Calle Larrondo 1281, Postal Code 1780000, Coquimbo, Chile. mramirezs@ucn.cl.
authors.forename: Muriel
authors.initials: M
authors.lastname: Ramírez-Santana
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Calle Larrondo 1281, Postal Code 1780000, Coquimbo, Chile. lzuniga@ucn.cl.
authors.forename: Liliana
authors.initials: L
authors.lastname: Zúñiga
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Calle Larrondo 1281, Postal Code 1780000, Coquimbo, Chile. scorral@ucn.cl.|Psychology Department, FACSO, Universidad de Chile, Santiago, Chile. scorral@ucn.cl.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Corral
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Calle Larrondo 1281, Postal Code 1780000, Coquimbo, Chile. rsandoval@ucn.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Sandoval
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. paul.scheepers@radboudumc.nl.
authors.forename: Paul T J
authors.initials: PT
authors.lastname: Scheepers
authors.affiliation: Department of Primary and Community Care, Radboud Institute for Health Sciences, Radboud university medical center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. koos.vandervelden@radboudumc.nl.
authors.forename: Koos
authors.initials: K
authors.lastname: Van der Velden
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. nel.roeleveld@radboudumc.nl.|Department of Pedatrics, Radboudumc Amalia Children's Hospital, Radboud university medical center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. nel.roeleveld@radboudumc.nl.
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Calle Larrondo 1281, Postal Code 1780000, Coquimbo, Chile. pancetti@ucn.cl.
authors.forename: Floria
authors.initials: F
authors.lastname: Pancetti
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000383:Agriculture; D015415:Biomarkers; D002677:Chile / Q000453:epidemiology; D002802:Cholinesterases / Q000097:blood; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology; D004781:Environmental Exposure / Q000032:analysis*; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000097:blood / Q000209:etiology*; D016273:Occupational Exposure / Q000032:analysis; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000097:blood*; D010575:Pesticides / Q000506:poisoning*; D011596:Psychomotor Disorders / Q000097:blood / Q000209:etiology; D012107:Research Design; D012307:Risk Factors; D012424:Rural Population
chemical_list: D015415:Biomarkers; D009943:Organophosphorus Compounds; D010575:Pesticides; D000110:Acetylcholinesterase; D002802:Cholinesterases; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase