Calabrese:
From Muller to mechanism: How LNT became the default model for cancer risk assessment
Volume 241, October 2018, Pages 289–302
This article is free access for 50 days
a b s t r a c t
This
paper summarizes the historical and scientific foundations of the
Linear No-Threshold (LNT) cancer risk assessment model. The story of
cancer risk assessment is an extraordinary one as it was based on an
initial incorrect gene mutation interpretation of Muller, the
application of this incorrect assumption in the derivation of the LNT
single-hit model, and a series of actions by leading radiation
geneticists during the 1946e1956 period, including a National Academy of
Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics
Panel (Anonymous, 1956), to sustain the LNT belief via a series of
deliberate obfuscations, deceptions and misrepresentations that provided
the basis of modern cancer risk assessment policy and practices. The
reaffirming of the LNT model by a subsequent and highly influential NAS
Biological Effects of Ionizing Radiation (BEIR) I Committee (NAS/NRC,
1972) using mouse data has now been found to be inappropriate based on
the discovery of a significant documented error in the historical
control group that led to incorrect estimations of risk in the low dose
zone. Correction of this error by the original scientists and the
application of the adjusted/corrected data back to the BEIR I (NAS/NRC,
1972) report indicates that the data would have supported a threshold
rather than the LNT model. Thus, cancer risk assessment has a poorly
appreciated, complex and seriously flawed history that has undermined
policies and practices of regulatory agencies in the U.S. and worldwide
to the present time.
© 2018 Elsevier Ltd. All rights reserved.
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