Relative effect potencies of dioxin-like compounds
Environmental Health Perspectives
A second important issue is the mode
of action of the index chemical and of the
congeners studied. In REP studies, simi larity
of the mode of action justifies the inclu-
sion of a compound in the TEF concept for
DLCs. e inclusion criteria include a struc-
tural relation ship to TCDD, binding to the
AhR, an AhR-mediated biological or toxic
response, and persistence and accumu la tion
in the food chain (Van den Berg et al. 2006).
However, at present, there is no published evi-
dence that long-term morphological changes
of the thyroid gland and hormonal shifts—
chosen as end points in this study—are exclu-
sively AhR–mediated processes. We previously
described a biphasic association between
serum concentration of a mixture of PCBs
(i.e., negative association in the cate-
gory of PCB levels < 530 ng/g vs. a positive
association in the category of PCB levels of
531–25,000 ng/g) (Langer et al. 2007c); that
association make even more diﬃ cult assigning
a mode of action in humans exposed to com-
plex environmental mixtures of DLCs and
NDL-PCBs. In addition, there is no agree-
ment on the presence of possible effects of
DLCs on thyroid function at environmental
exposure levels (Johnson et al. 2001; Pavuk
et al. 2003).
In the present study, the REPs calculated
via two diﬀerent approaches—one based on
thyroid morphology and the other on thy-
roid hormonal end point—showed consis-
tent results. In spite of using a design diﬀerent
from those of published REP studies, as well
as the unique scenario of our study, most of
our REPs, especially those for dioxins and
thyroid volume, ﬁt well within the ranges of
published REPs (Haws et al. 2006) (Table 1).
In plots of log REPs for thyroid volume
(Figure 1A) or FT
(Figure 1B) versus log
TEFs, however, the best ﬁt is markedly shifted
in the direction of our REPs. is is more pro-
nounced for FT
, which may be interpreted
as a greater sensitivity of this end point com-
pared with thyroid volume or with end points
leading to the assigned TEF values.
One strength of our study is that it
is based on changes of two human thyroid
parameters with apparently completely dif-
ferent patho genesis, but whose results largely
agree. Another strength is that we used actual
serum concentrations of compounds that reli-
ably reﬂect systemic body burden, rather than
data on daily intake. A weakness of our study
is that we worked with exposure to a mix-
ture of chemicals with diﬀerent potencies and
likely different modes of action, compared
with an exposure scenario under laboratory
conditions that takes into account a single
chemical. Further, single time exposure data
does not necessarily reﬂect the whole exposure
history of each participant. Another weak-
ness of our study was that the prevalence of
concentrations < LOD was high for some
compounds, and this likely limited our sta-
tistical precision. In spite of the short comings
of this study, the REPs we determined should
be considered in updating the present TEFs
with regard to long-term, low-dose exposure
of humans instead of relatively short-term
In the manuscript originally published
online, several errors resulted from the
incorrect calculation of β coefficients.
a) PCB 105 data for FT
in Table 1 and
Figure 1B were based on β coefficients
calcu lated from concentrations given in
nanograms per gram and compared with
the β coefficient for TCDD, which was
calcu lated from concentrations in picograms
per gram. b) In Figure 2, the β coeﬃcients
for PCB 181, PCB 126, and PCB 169
were calculated from picograms per gram
units instead of nanograms per gram units;
the correct values were extremely low and
have thus been omitted. ese errors have
been corrected here and do not affect the
conclusions of the paper.
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