17 January 2003
Pesticide Tests on Humans Ever Meet Standards for Ethics?
Sharon Begley, Science Journal
World Health Organization lists aldicarb, a pesticide, as "extremely
hazardous." It calls the pesticide dichlorvos "highly
hazardous"; the U.S. Environmental Protection Agency classifies
it as a "possible human carcinogen."
if you are healthy and up for an adventure, pesticide makers will
pay you $500, $800, even $1,500 to imbibe one or the other, either
once or daily for 18 days with your morning OJ.
controversy over the scientific value and ethics of testing pesticides
on people is approaching full boil, spurred by intense pressure
from the pesticide industry to loosen federal policies and by a
lawsuit that manufacturers filed against the EPA to make it accept
data from such experiments. At last count, 14 studies of 11 pesticides
have been submitted since 1996.
push for human testing was triggered by the 1996 Food Quality Protection
Act. In exchange for allowing traces of carcinogenic pesticides
to remain on food (previously illegal), the act requires the EPA
to use an additional "safety factor" in setting allowed
residue levels, to protect children and fetuses.
makers have that safety factor in their cross hairs, hoping to persuade
the EPA that if healthy adults suffer no adverse effects after consuming
a bit of pesticide, then restrictions should be relaxed.
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recent experiments dosing people with pesticides haven't exactly
covered themselves in glory, ethically speaking. In one testing
dichlorvos, in Scotland, many of the volunteers were cashapped
possibility of financial coercion always is an ethical no-no. And
in several places, the consent form referred to dichlorvos as a
"drug" and said it was used as a medicine, misleading
volunteers, as The Wall Street Journal reported in 1998.
leave aside ethics concerns for a moment and focus on the science,
for unless an experiment on humans yields valuable data it is by
definition unethical. The argument in favor is simple: "There
is no substitute for the knowledge gained from human volunteer studies,"
as Monty Eberhart of Bayer CropScience, a major pesticide maker,
-- but only in the abstract. The current round of studies have used
small numbers (10 to 50, typically) of healthy adults, raising doubts
about the studies' statistical power. "If you see an effect,
you can be reasonably confident in that finding even if you used
only 10 or 15 people," says toxicologist Michael Gallo of the
Environmental and Occupational Health Sciences Institute in Piscataway,
N.J. "But to be confident that you have no effect is much more
difficult. You may just happen to have studied 10 people who are
not sensitive to the compound. To prove a negative you need many
more people," probably hundreds.
existing studies border on junk science for another reason: You
can't volunteer for them unless you're a healthy adult. Given this
"voluntarism bias," as epidemiologist Lynn Goldman of
Johns Hopkins University, Baltimore, calls it, there are real doubts
that a level found to produce no adverse effects in such a group
also is safe for children, the ill and the elderly.
you run a toxicology study, you don't ask, "So, what does this
chemical do, anyway?" You define an endpoint, such as, "How
does this chemical affect acetyl cholinesterase activity?"
is the basic fallacy of relying on these studies," says Dr.
Goldman, a former EPA pesticide official. The critical effects are
things like developmental neurotoxicity in children and fetuses,
and those might reflect chemical pathways unrelated to whatever
is causing toxicity in adults. Organophosphate pesticides have been
found to alter gene expression in the brains of fetal rats, for
instance, yet are tested for how they inhibit enzyme activity in
adult red blood cells.
let's say the endpoints are chosen properly, and the tests have
enough subjects to offer statistical power. Let's say, too, that
the studies adhere to ethical standards. Are they OK now?
still have an inherent ethical problem. When people volunteer to
test the safety of drugs, "those Phase 1 trials are for things
intended to make people better," says bioethicist Jeffrey Kahn
of the University of Minnesota, Minneapolis. "If the purpose
is to allow industry to get higher levels of pesticides into the
environment, then it's very questionable."
an EPA Science Advisory Panel studied the acceptability of experimenting
with pesticides on people, it concluded in 2000 that if the study
is conducted with rigorous ethical controls, if there is no other
way to fill data gaps and if the goal is to protect public health,
then the EPA should consider it. "We felt that only under the
most extraordinary circumstances should human testing be done,"
says toxicologist Ronald Kendall of Texas Tech University in Lubbock,
who chaired the panel.
very few experiments would likely meet those guidelines. As Prof.
Gallo, who is viewed as sympathetic to industry, asks, "For
existing pesticides, where we have a great deal of human data from
epidemiology and 'biomonitoring' of farmworkers exposed to pesticides,
why do we need these studies?"
for scientific and political cover, the EPA has asked a panel of
the National Academy of Sciences to answer that. Its report is expected
late this year.