MONOTONIC VERSUS NON-MONOTONIC
lack of predictability is a serious flaw in the current government
method which assumes that the chemical being tested always expresses
itself the same way at every concentration. It assumes a greater effect
at high concentration, a lesser effect at lower doses. In scientific
terms, this predictability is called a monotonic dose response.
EDCs and many other compounds are not so predictable because they
affect different biological structures when present in varying
concentrations. This is especially true for natural hormones, endocrine
disrupters, many pharmaceuticals and even the ethanol in wine, beer and
The Vandenberg/Myers study explained that, “For all
monotonic responses, the observed effects may be linear or nonlinear,
but the slope [of the plotted line or curve] does not change sign. This
assumption justifies using high-dose testing as the standard for
assessing chemical safety. When it is violated, high-dose testing
regimes cannot be used to assess the safety of low doses.”
The study then pointed out that EDCs as a group violate the rule by being non-monotonic.
WHY DOES NON-MONOTONIC MATTER?
chemical compounds are simply toxic: they damage and kill cells. The
higher the concentration, the more toxic and the more cells die – the
dose makes the poison.
Regardless of the concentration, these
chemicals kill cells the same way. And, at the level of no observed
adverse effects, they stop killing, or are tolerated by cells. This is a
monotonic dose response.
But non-monotonic chemicals can affect different mechanisms in the body depending on the concentration.
well-known non-monotonic response is the “U” shaped curve of the
“French Paradox” or the activity of pharmaceuticals including aspirin
and many hormones.
With these compounds, there is no effect at low
concentrations. As concentration levels increase, scientific studies
show an increasing beneficial effect. Then, beyond that level, the
beneficial effect diminishes and later, high levels can be toxic and
This odd behavior is non-monotonic because the
substances act on different parts of the body at different
concentrations. At high levels they are toxic. At lower levels, they act
on a variety of microscopic cell receptors and structures that allow
them to have a different and beneficial effect.
has shown that at very low levels, EDCs can magnify or suppress the
effects of natural hormones in the body or cause their own unique
But nothing in nature says non-monotonic behavior
always goes from damaging to beneficial as the concentrations go from
high to low. Significantly, the effects of EDCs and other
low-concentration chemicals are generally unstudied and unknown.
However, in those few cases where they are better understood, EDCs have
been found to have damaging effects.
Clearly, EDCs are an example
of non-monotonic behavior that can go from deadly toxic (poisoning
cells) to invisibly deadly (tumors, genetic effects, metabolic disorders
and other diseases).
Indeed, as a future article in this series
will explore, an increasing number of studies indicate that EDCs may be
responsible for part of the current obesity and diabetes epidemics. They
may also contribute to the decline of endangered species including
salmon, frogs and other “cold-blooded” animals which seem to be more
susceptible than mammals to chemical compounds.