to examples of low-dose studies]
Krimsky's book, Hormonal
Chaos, describes endocrine disruption as a paradigm shift
in toxicology. At the core of this shift are scientific
results demonstrating that endocrine disruption has impacts
at contamination levels far beneath those of traditional concern
to toxicologists. Some of these levels are so low that industry
has asserted the results are not reliable.
old paradigm focused on acute toxicity. How do high levels of contamination
affect health? How do they cause cancer? How do they kill directly?
How do they overcome the body's defenses, like a massive invading
army overwhelming the defenders simply by brute force and large
new paradigm recognizes that there are other ways that contamination
can work. Think of how terrorists overwhelm larger forces. Instead
of using the brute force of large numbers, a small number of molecules
can hijack the hormonal control of development and cause intense,
life long damage, undermining the immune system, eroding intelligence,
diminishing reproductive capacity.
terrorist attack on fetal development works because some chemicals
act as imposters, insinuating themselves in the body's natural hormone
system that normally directs fetal development. These natural hormone
signals work at very low concentrations. And the imposters do also,
sometimes at levels tens of thousands of times lower than the brute
force approach considered by traditional toxicology.
implications of this new paradigm are profound. Every person living
today carries measurable levels of several hundred synthetic chemicals,
contaminants that did not exist prior to the 20th century. While
we are fundamentally ignorant about the health impacts of most of
these compounds--and profoundly so about their interactions--toxicologists
had come to believe that background levels, the levels experienced
by most people, the levels that are virtually unavoidable living
in the world today, that those background levels were safe. This
assumption of safety was allowed because scientists were considering
them under the old paradigm, and with significant exceptions, they
were not seeing dead bodies. The new paradigm indicates that
an entire generation of science used to examine chemicals for safety
was misguided, ignoring vital impacts at low levels of exposure,
and likely to have given false assurances of safety.
of this new paradigm is also the acknowledgment that old assumptions
about the nature of the relationship between dose and response may
sometimes be violated. Traditional toxicology assumes that dose-response
curves are always monotonic: that
is, that higher doses have a greater effect than lower doses. This
assumption underpins all regulatory testing: if no effect is found
at high levels, then it is assumed that the contaminant is safe.
It also usually assumes that there is a threshold
level of exposure below which no effect occurs.
turns out hormone systems aren't always that simple. Sometimes
high doses shut off effects that occur at lower levels. This can
lead to dose response curves that are non-monotonic: low and intermediate
doses produce effects that are larger than high levels. In mathematical
terms, the slope of the dose response curve changes sign. The presence
of non-monotonic dose response curves
in endocrine disruption means that many toxicological tests have
led to erroneous conclusions about safety.
important assumption of these regulatory approaches is that there
is a threshold beneath which no effect
occurs. Here, too, endocrine disrupting chemicals violate long-held,
but not tested, assumptions.
this means is that not only have we simply not tested the toxicological
impacts of most chemicals, even those that have been tested have
not been examined adequately. These tests were all done by beginning
at high levels and working back down the dose response curve until
the effect seen at high levels disappeared. Once that level of "no-effect"
is reached, testing stops, assuming a threshold
and ignoring the possibility that non-monotonic
effects occur at lower levels.