EPA's reassessment of the risks of dioxin was already under way
when Richard Peterson's Wisconsin study hit with the shock of an
unanticipated asteroid. Here was evidence that dioxin could have
dramatic effects at very low doses-at levels close to those routinely
found in humans. In a matter of months, the tide turned and the
dioxin debate shifted from dioxin's cancer-causing potential to
its developmental and reproductive toxicity. In short order, EPA
scientists repeated the studies giving dioxin to pregnant rats and
found similar effects in female offspring.
turnaround in scientific thinking was stunning. The studies suggested
that the worst fears about dioxin might, in fact, be justified.
Dioxin might after all be more dangerous than anyone had suspected,
but contrary to what many had thought, its greatest threat was not
cancer. The newly emerging hazard was its power to disrupt natural
bad reputation helped insure a steady flow of
funding to a host of researchers who were probing what this chemical
did to the body and how it did it, but the University of Wisconsin
lab headed by Peterson was one of the few places exploring its effects
on the endocrine system. Robert Moore, one of Peterson's colleagues
at the School of Pharmacy and the Environmental Toxicology Center,
had set off on this line of research because he believed it held
the greatest potential for explaining the toxic effects of the notorious
posed a fascinating challenge for toxicologists like Moore and Peterson
because it is not your ordinary poison. Animals given lethal doses
of dioxin don't keel over quickly; they lose their appetite and
undergo a mysterious wasting before they actually die weeks later.
Dioxin also produces a variety of other nonlethal responses that
occasionally seem contradictory. It somehow disrupts estrogen responses,
acting sometimes as if it were an estrogen impostor and sometimes
as if it were blocking estrogen, yet studies have shown that dioxin
is not a simple estrogen mimic like DES. It produces apparently
estrogenic or antiestrogenic effects without consorting with the
estrogen receptor. For all the years of research, exactly how dioxin
does its harm has remained elusive. Peterson and Moore thought the
endocrine system might hold the key to this mystery.
they had suspected, their experiments with adult male rats confirmed
that dioxin could interfere with hormone levels. When adult rats
were given dioxin, it caused their testosterone levels to drop and
their testicles and accessory sex organs to lose weight. But it
took a lot of dioxin to produce such responses-almost enough to
start killing some of the rats used in the experiments.
Moore and Peterson felt it was easier to explore the mechanism of
toxicity if one used high doses, this approach began to fall into
disfavor by the mid-1980s. Critics were attacking high dose experiments
saying that they did not have direct relevance to the real world
where humans and animals are exposed to much smaller amounts of
the end, Moore and Peterson had little choice. The National Institute
of Health, which was funding their work, pushed them toward working
with lower doses that the federal agency regarded as more immediately
relevant to human health risks. "We got the message that we
had to get out of high dose research if we wanted to stay funded,"
before their high-dose TCDD experiments had ended, Moore read a
1983 paper by Dorothea Sager, a researcher at the University of
Wisconsin's Green Bay campus, which found a variety of changes,
including reduced fertility, in male rats exposed to PCBs through
their mother's milk. Sager's work demonstrated the critical importance
of timing, not just in the severity of the impact but also in its
very nature. Her findings inspired Moore and Peterson to look for
similar patterns as a result of TCDD exposure. They brought in a
graduate student, Tom Mably, to conduct the actual experiments.
team looked beyond the simple question of whether or not rats exposed
to dioxin could later produce offspring. This all-or-nothing approach
was grossly inadequate. They wanted instead to look at more sensitive
aspects of reproductive health, such as sperm counts and mating
behaviors, that are not often measured in toxicity research. As
Moore puts it, "we were looking for answers in different ways.
We were turning over different rocks." In fact, Moore reflects,
if they had done no more than the usual fertility tests, the work
would have sunk into obscurity without a ripple.
results far exceeded their expectations.