Biomedical Engineering Reference
In-Depth Information
6 Exploring Differences Between
PBPK Models of Methanol
Disposition in Mice and Humans:
Important Lessons Learned
THOMAS B. STARR
TBS Associates, Raleigh, NC, USA
6.1 BACKGROUND
While the United States Environmental Protection Agency (USEPA)
classifies methanol as a “threshold” pollutant, the Agency has yet to
establish an inhalation Reference Concentration (RfC) for this impor-
tant commodity chemical. A Reference Concentration is defined as “an
estimate (with uncertainty spanning perhaps an order of magnitude) of a
continuous inhalation exposure to the human population (including
sensitive subgroups) that is likely to be without an appreciable risk of
deleterious effects during a lifetime” (USEPA, 2012). USEPA has been
in the process of revising its Integrated Risk Information System (IRIS)
methanol listing for several years now, and this process will most likely
culminate in specification of a methanol RfC. The possibility that the
Agency will characterize methanol as a potential human carcinogen
cannot be ruled out at this time, so extrapolated human cancer risks may
be the determining factor in setting an inhalation RfC. However, the
weight of scientific evidence points strongly toward noncancer devel-
opmental toxicity as the primary health concern for human exposure.
Either way, knowledge of methanol uptake, distribution, and disposition
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