Framework for human health risk assessment of non-cancer effects resulting from short-duration and intermittent exposures to chemicals.
Durations of exposure to chemicals, whether for single, repeated or intermittent periods, may vary from those upon which most guidance values are normally based. Because it is presently not feasible to conduct toxicity studies or develop toxicity reference values (TRVs) specific to each scenario of interest, methods are needed to address these various durations, drawing as much as possible on existing TRVs. A working framework was developed to address the potential for non-cancer effects resulting from continuous short-duration and intermittent exposures to chemicals. The framework presents an integrated, tiered approach that assists the user in identifying when existing TRVs can be applied directly, and the adaptations needed to assess the acceptability of short-duration or intermittent exposure scenarios. Descriptions of when and how toxicokinetic and toxicodynamic aspects need to be taken into consideration are also presented. The framework incorporates the use of TRVs based on exposure periods as similar as possible to the "actual" exposure periods and application of dose averaging under limited, specified conditions. This framework has been developed to aid in improving the scientific basis for the evaluation of short-duration and intermittent exposures in a variety of settings. Copyright © 2016 John Wiley & Sons, Ltd.
Toxicology Excellence for Risk Assessment (TERA), University of Cincinnati, Cincinnati, OH, USA.
Lynne T
LT
Haber
SafeDose Ltd., Toronto, ON, Canada.
Reena
R
Sandhu
Health Canada, Ottawa, ON, Canada.|University of Toronto, Toronto, ON, Canada.
Angela
A
Li-Muller
Health Canada, Calgary, AB, Canada.
Asish
A
Mohapatra
Health Canada, Ottawa, ON, Canada.
Sanya
S
Petrovic
University of Ottawa, Ottawa, ON, Canada.
M E Bette
ME
Meek
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis*; D006801:Humans; D018570:Risk Assessment; D013997:Time Factors; D018675:Toxicity Tests; D066007:Toxicokinetics; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*
D015262:Xenobiotics
framework; intermittent exposure; mode of action; short-duration exposure; tiered analysis; toxicodynamics; toxicokinetics