title: Discontinuity in the cancer slope factor as it passes from high to low exposure levels--arsenic in the BFD-endemic area.
abstract: BACKGROUND
  The ingestion of inorganic arsenic causes bladder and lung cancers demonstrably at >400-500ug/L but questionably below 100-200ug/L. Using the standard 42-village cancer mortality dataset from the Blackfoot-disease (BFD) endemic area of southwest Taiwan (Wu et al., 1989), we examined the risk from low exposures by excluding the high exposures.
  
  
  METHODS
  Poisson regression analyses with the sequential removal of the highest exposure village have been performed using the median, mean, or maximum village well water arsenic level and demonstrated graphically.
  
  
  RESULTS
  Risk estimates are positive when villages with exposures of 200-400ug/L are included and significantly so when villages with >400ug/L are included. Risk estimates for exposures below 100ug/L are negative but rarely significantly so. The inflection point where the slope is no longer positive occurs in the range of 100-200ug/L, depending upon whether the exposure metric used is the median, the mean or the maximum.
  
  
  CONCLUSIONS
  There is a discontinuity in the cancer slope factor or risk from arsenic exposure that occurs in the range of 100-200ug/L. Above these levels, there are significantly positive risks, while below these levels there are not. The analysis reveals within this dataset an intrinsic non-linearity in the cancer risk. The literature speaks to this discontinuity, but this is the first demonstration within a single dataset that shows the discontinuity across the full exposure range and where the low-dose data are not compromised with high-dose data.
authors.affiliation: Center for Epidemiology and Global Health, CEOH, LLC., Washington, D.C., USA; Johns Hopkins University-Bloomberg School of Public Health, Baltimore, MD, USA; Georgetown University School of Medicine, Washington, D.C., USA. Electronic address: Steve@ceoh.com.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Lamm
authors.affiliation: Center for Epidemiology and Global Health, CEOH, LLC., Washington, D.C., USA.
authors.forename: Shayhan
authors.initials: S
authors.lastname: Robbins
authors.affiliation: Georgetown University Graduate School, Washington, D.C., USA.
authors.forename: Rusan
authors.initials: R
authors.lastname: Chen
authors.affiliation: American University Department of Mathematics, Washington, D.C., USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Center for Epidemiology and Global Health, CEOH, LLC., Washington, D.C., USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Goodrich
authors.affiliation: Johns Hopkins University-Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Manning
authors.initials: M
authors.lastname: Feinleib
mesh_terms: D001151:Arsenic / Q000009:adverse effects*; D020261:Arsenic Poisoning / Q000453:epidemiology* / Q000401:mortality; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000401:mortality; D008297:Male; D018570:Risk Assessment; D012307:Risk Factors; D012423:Rural Health; D013624:Taiwan / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000401:mortality; D014874:Water Pollutants, Chemical / Q000009:adverse effects*; D014881:Water Supply / Q000032:analysis*
chemical_list: D002274:Carcinogens, Environmental; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: Arsenic; Bladder cancer; Dose-response; Low level exposure; Lung cancer; Southwest Taiwan