title: Assessment of health risks resulting from early-life exposures: Are current chemical toxicity testing protocols and risk assessment methods adequate?
abstract: Abstract Over the last couple of decades, the awareness of the potential health impacts associated with early-life exposures has increased. Global regulatory approaches to chemical risk assessment are intended to be protective for the diverse human population including all life stages. However, questions persist as to whether the current testing approaches and risk assessment methodologies are adequately protective for infants and children. Here, we review physiological and developmental differences that may result in differential sensitivity associated with early-life exposures. It is clear that sensitivity to chemical exposures during early-life can be similar, higher, or lower than that of adults, and can change quickly within a short developmental timeframe. Moreover, age-related exposure differences provide an important consideration for overall susceptibility. Differential sensitivity associated with a life stage can reflect the toxicokinetic handling of a xenobiotic exposure, the toxicodynamic response, or both. Each of these is illustrated with chemical-specific examples. The adequacy of current testing protocols, proposed new tools, and risk assessment methods for systemic noncancer endpoints are reviewed in light of the potential for differential risk to infants and young children.
authors: The Procter & Gamble Company , Cincinnati, OH , USA.
authors: Susan P
authors: SP
authors: Felter
authors: George P
authors: GP
authors: Daston
authors: Susan Y
authors: SY
authors: Euling
authors: Aldert H
authors: AH
authors: Piersma
authors: Melissa S
authors: MS
authors: Tassinari
mesh_terms: D002648:Child; D002701:Chloramphenicol / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007223:Infant; D007854:Lead / Q000633:toxicity; D020258:Neurotoxicity Syndromes / Q000209:etiology; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D015262:Xenobiotics; D007854:Lead; D002701:Chloramphenicol
keywords: children; development; infants; life stage; quantitative risk assessment; sensitivity; subpopulations; susceptibility; uncertainty factor; variability; vulnerability