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with even minuscule amounts of drugs or chemicals. We are protecting
against the 0.032 ounce bricks. Unlike drug treatment in humans, when a vet-
erinarian treats an animal, the dose must be selected that cures the disease,
does not produce toxicity, and does not produce residues in the milk or meat.
We eat our patients and thus must eliminate any residual drug to prevent
human exposure. Your physician treating you does not worry that leftover
drug remains in your body!
Much of this regulatory zeal was driven by the Delaney Clause, which
amended the Food, Drug and Cosmetic Act of 1938. This clause forbids the
addition of any amount of animal carcinogen to the food supply. This was
originally based on our belief at the time that even one molecule of a carcino-
gen could cause cancer in humans. This concept was largely influenced by the-
ories of radiation-induced cancer. Thresholds were not allowed. As we dis-
cussed, this is no longer considered valid since the processes of absorption,
distribution, elimination, metabolism and cellular defense, and repair mech-
anisms make this possibility far less than remote. However, the United States
34 CHAPTER 2
Congress mandated that there be zero tolerance for any chemical identified in
any animal test as being a carcinogen at any dose. In the late 1950s analytical
chemistry was such that parts-per-million detection of chemicals was consid-
ered an extremely sensitive assay. We can now detect a million times less
chemical, and at levels that were never anticipated when these laws were
passed. Using our brick analogy, we are now detecting bricks weighing one
millionth of a gram (a nanogram). Our brick is now microscopic, and even the
fictional inhabitants of Lilliput, from Gulliver s Travels, would not fret!
Congress and the regulatory community realized that analytical chemistry
was getting ahead of the biology, and in a 1968 amendment to the Delaney
Clause the DES Proviso they linked the allowable limit to the analytical
method. Thus carcinogenic drugs could be used in animals if one could not
find residues in the tissues. Beginning in the early 1970s, the FDA began work-
ing on a sensitivity-of-method approach to regulating residues, which was
ultimately published in 1987. This approach, currently in use, defines a
threshold residue level (see Appendix A for how these are set), below which
food is deemed safe even if analytical methods can detect a residue. The
residue level is set to a risk of cancer of 1 in 1,000,000. The scientific debate,
which lasted over a decade, is over, and almost everyone accepts that detec-
tion below this tolerance adds an immeasurable level of risk to the food sup-
ply. Analytical detection was finally uncoupled from a potential to cause bio-
logical effect. Yet even today, it is detection at these Lilliputian levels that caus-
es the media hysteria and a tremendous amount of unfounded anxiety in the
public s psyche.
This no-tolerance philosophy has removed a great number of chemicals
from our food supply and has probably forced the development of even safer
and more effective therapeutics. All drugs approved for animals today must
undergo extensive residue trials, and safe tolerances, having up to 1000-fold
safety factors, are established. Information programs such as FARAD, coupled
with testing programs, ensure that food products have tissue residues below
these safe levels. When surveys are done which indicate that a drug has
been detected in our food, there should not be panic. Detection does not equal
toxicity.
A practical observation is that the drug levels detected in the edible tissues
and in the milk in food-producing animals produce no biological effects to the
animal itself! This even includes animals that are treated for long periods of
their life, such as dairy cows. However, some alarmists would have one believe
that if people ate meat from these same animals, some adverse effect might
occur to them. I can assure you that I do not lose sleep over this risk. I would
limit my consumption of meat and milk because of its fat and cholesterol con-
tent, not because of any drug or chemical residues. Bacterial contamination of
certain meat products is a much more substantial and real threat to our safe-
DOSE MAKES THE DIFFERENCE 35
ty. Public concern and research should be focused on this aspect of food safe-
ty and not on theoretical risks of minuscule levels of chemicals.
This research, and the practice of food-animal medicine, has generated a
database that clearly shows just how distinct the effects of drugs are at toxi-
cological levels, at lower therapeutic levels, and at extremely low but
detectable residue levels. Each amount of drug occupies different regions of
the dose-response hierarchy. There is very little overlap between the ranges.
This hierarchical behavior of chemicals at different concentrations is analo-
gous to some fundamental principles on the order of nature, promulgated by
the Nobel laureate physicist Dr. Phillip W. Anderson in 1972. He proposes
that reality has a hierarchical structure with each level independent, to some
degree, of the levels above and below. He writes, At each stage, entirely new
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