Threshold hypothesis is a theory that it has it's believers, believers in the threshold hypothesis believe that carcinogens, like other toxic compounds, have a no-effect level and a threshold dose.
1. Animal systems have a variety of defense mechanisms able to detoxify and dispose of xenobiotic chemicals.
Many factors determine whether a particular chemical is activated to become a carcinogen
or is rendered innocuous.
2. The high doses used in many experiments for carcinogenicity can
change normal processes of cellular activation and deactivation and
can overwhelm natural defense mechanisms.
Tumors may be due to secondary effects of toxicity and tissue damage
from excessive amounts of the fed compound.
3. Even in cases where the DNA is actually damaged, repair of the
damage has been documented. Only under conditions in which the
repair mechanisms are exhausted will the damage become irreversible.
4. Not all species show the same susceptibility.
5. Dose should accurately reflect what reaches the tissue, not simply what is administered.
For instance , some substances are quite toxic,
but as they are absorbed with difficulty, they never reach the target tissue.
6. Accurate epidemiological data should have precedence over animal studies.
7. It is possible to establish a no-effect level.
Those skeptical of the threshold hypothesis cite evidence that some agents can directly alter DNA and conceivably could damage DNA with one molecule.
Counterarguments show evidence that even tissues suffering extensive DNA alkylation
did not necessarily become cancerous. In fact , they show that a chronic low dose of a chemical may force the DNA repair mechanisms to function more efficiently.
While it is conceivable that a single molecule might irreversibly damage the DNA, many believe it is statistically importable.
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