title: The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure.
abstract: BACKGROUND
  More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic.
  
  
  METHODS
  We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic.
  
  
  RESULTS
  Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure.
  
  
  CONCLUSIONS
  The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life.
authors.affiliation: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok, Thailand; Departments of Preventive Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: molly.tolins@mssm.edu.
authors.forename: Molly
authors.initials: M
authors.lastname: Tolins
authors.affiliation: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok, Thailand.
authors.forename: Mathuros
authors.initials: M
authors.lastname: Ruchirawat
authors.affiliation: Departments of Preventive Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Philip
authors.initials: P
authors.lastname: Landrigan
mesh_terms: D000293:Adolescent; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced / Q000453:epidemiology; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000139:chemically induced / Q000453:epidemiology*; D008569:Memory Disorders / Q000139:chemically induced / Q000453:epidemiology*; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018377:Neurotransmitter Agents; D001151:Arsenic
keywords: arsenic; behavioral effects; children’s environmental health; cognition; developmental neurotoxicity; developmental origins of adult disease