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Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making.

Authors
Woodruff-TJ; Zeise-L; Axelrad-DA; Guyton-KZ; Janssen-S; Miller-M; Miller-GG; Schwartz-JM; Alexeeff-G; Anderson-H; Birnbaum-L; Bois-F; Cogliano-VJ; Crofton-K; Euling-SY; Foster-PMD; Germolec-DR; Gray-E; Hattis-DB; Kyle-AD; Luebke-RW; Luster-MI; Portier-C; Rice-DC; Solomon-G; Vandenberg-J; Zoeller-RT
Source
Environ Health Perspect 2008 Nov; 116(11):1568-1575
NIOSHTIC No.
20034727
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. OBJECTIVES: 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. DISCUSSION: 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 oil 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.
Keywords
Chemical-hypersensitivity; Biochemical-analysis; Biohazards; Biological-effects; Environmental-exposure; Environmental-health; Thyroid-gland-disorders; Toxic-effects; Toxicology; Toxicopathology; Quantitative-analysis
Contact
Tracey J. Woodruff, University of California-San Francisco, Suite 1100, 1330 Broadway St., Oakland, CA 94612
CODEN
EVHPAZ
Publication Date
20081101
Document Type
Journal Article
Email Address
woodrufft@obgyn.ucsf.edu
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
11
ISSN
0091-6765
NIOSH Division
HELD
Priority Area
Healthcare and Social Assistance; Services
Source Name
Environmental Health Perspectives
State
WV; GA; CA; NC; MA; WI; ME; DC
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