title: Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making.
abstract: BACKGROUND
  Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment.
  
  
  OBJECTIVE
  Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available.
  
  
  CONCLUSIONS
  Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects.
  
  
  CONCLUSIONS
  For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population.
authors.affiliation: Department of Obstetrics and Gynecology, University of California, San Francisco, California, USA. woodrufft@obgyno.uscf.edu
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Woodruff
authors.forename: Lauren
authors.initials: L
authors.lastname: Zeise
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Axelrad
authors.forename: Kathryn Z
authors.initials: KZ
authors.lastname: Guyton
authors.forename: Sarah
authors.initials: S
authors.lastname: Janssen
authors.forename: Mark
authors.initials: M
authors.lastname: Miller
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Miller
authors.forename: Jackie M
authors.initials: JM
authors.lastname: Schwartz
authors.forename: George
authors.initials: G
authors.lastname: Alexeeff
authors.forename: Henry
authors.initials: H
authors.lastname: Anderson
authors.forename: Linda
authors.initials: L
authors.lastname: Birnbaum
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Vincent James
authors.initials: VJ
authors.lastname: Cogliano
authors.forename: Kevin
authors.initials: K
authors.lastname: Crofton
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Euling
authors.forename: Paul M D
authors.initials: PM
authors.lastname: Foster
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.forename: Earl
authors.initials: E
authors.lastname: Gray
authors.forename: Dale B
authors.initials: DB
authors.lastname: Hattis
authors.forename: Amy D
authors.initials: AD
authors.lastname: Kyle
authors.forename: Robert W
authors.initials: RW
authors.lastname: Luebke
authors.forename: Michael I
authors.initials: MI
authors.lastname: Luster
authors.forename: Chris
authors.initials: C
authors.lastname: Portier
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Rice
authors.forename: Gina
authors.initials: G
authors.lastname: Solomon
authors.forename: John
authors.initials: J
authors.lastname: Vandenberg
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Zoeller
mesh_terms: D003657:Decision Making; D006801:Humans; D018570:Risk Assessment