Is there a safe dose of any mutagen or carcinogen?
We live surrounded by radiation and by chemicals that
Is there any safe dose for humans of these agents (which include oxygen!)
The question is exceedingly difficult to answer and, I believe, at low doses, unanswerable. Why?
This graph shows several theoretical dose-response relationships.
- cause mutations in test organisms (like bacteria and yeast)
- cause an increase in the rate of cancers in experimental animals (rats and mice)
There is considerable evidence that at moderate doses of a mutagen or carcinogen, the response is linear (A). However, at very low doses of some chemicals, there may be a threshold (B) below which the agent has no effect. For other chemicals, and probably for radiation, it is likely that even the tiniest doses will have an effect (C), but the population exposed must be large enough to observe it. Note that even at zero dose, the line does not intercept the origin. This is because even unexposed animals (including people) show a spontaneous level of response (e.g., tumors).
At very high doses, the rate of response may increase faster than the dose (E) as, for example, the probability of a single cell suffering two mutations increases. On the other hand, very high doses may kill off damaged cells before they can develop into tumors (F).
High doses of radiation cause cancer. Various studies, including excellent ones on the survivors of Hiroshima and Nagasaki, show that a population exposed to a dose of 12,500 mrem will have a measurable increase (about 1%) in the incidence of cancer. Note that the measurements are made on a population, not on individuals. We can never say that a particular individual exposed to a particular dose of radiation will develop cancer. The induction of cancer is a chance ("stochastic") event unlike the induction of radiation sickness which is completely predictable. The element of chance arises because cancer is an event that occurs in a single cell unlucky enough to suffer damage to two or more specific genes.
However, the energy needed to cause mutations is very low. So if you expose a sufficiently large number of cells to even tiny doses of radiation, some cell is going to be unlucky. How can we evaluate the risk?
- 12,500 mrem causes a 1% increase in cancer in a population; i.e.,
- it should cause an increase of 1 cancer in every 100 people in the exposed population.
- But if our reasoning is correct, a population of 100,000 people exposed to 12.5 mrem should also yield one case of radiation-induced cancer.
- In any population, where the product of radiation dose times population size equals 1.25 x 106, one case of cancer will be induced.
- The product of exposure multiplied by the size of the exposed population is known as the collective dose. Its units are (person)x(mrem).
- The population of the U.S. in 1990 was about 250 million.
- so anything that increases the annual exposure of the U.S. population by as little as 1 mrem per year would cause an additional 200 cases of cancer.
(250 x 106 persons)(1 mrem)
_____________________________ = 200 cancers
1.25 x 106 person mrem/cancer
- the current death rate in the U.S. is about 0.0088; that is,
- 2.2 million people die each year (250 x 106 x 0.0088)
- 23-24% of these deaths are caused by cancer, so
- the number of cancer deaths each year exceeds 500,000
- How can we possible detect an increase of 200 faced with these large numbers?
(As of September 2000, more than 800 children who drank milk contaminated by the radioactive iodine [131I] released in the accident have come down with thyroid cancer. In this case, the ability of the thyroid gland to concentrate iodine within its cells resulted in those cells receiving a relatively high, not a low, dose.)
At one time it was found that the chemical dioxin, which can be produced as a contaminant in the manufacture of paper and cardboard, was leaching from milk cartons into milk itself.
- It has been estimated (in this case, using a collective dose value of 5 x 106 person mrem/cancer) that the radioactive fallout from the nuclear accident at Chernobyl (now often spelled "Chornobyl") in 1986 will cause an increase of 17,000 cancers over the lifetime of people living in the Northern Hemisphere.
- Large those this estimate seems, it is dwarfed by the 513 million cancer deaths that will occur anyway in this population.
- This is why I say above that the answer to the question of the dangers of low doses of radiation is unknowable.
And, in fact, this was the estimate made.
The uncertainties in such assumptions helps explain the controversy that has so often swirled around the test data on such chemicals as
- the concentration in the milk averaged 0.1 part per trillion (ppt) or 0.0001 µg in a liter (109 µg) of milk. Assuming:
- 0.1 µg per day given to rats increases their rate of tumors by 1%
- the idea of collective dose applies to chemicals (that is, a single molecule in an unlucky cell can turn it cancerous)
- people are 100 times more sensitive to dioxin than rats (probably not true) and
- people are 100 times larger than rats
- we conclude that there is a risk of 10 additional cancers in every million people consuming a liter (about a quart) of milk a day from cardboard containers.
Some chemicals appear to have a safety threshold
Cells have a number of different methods for detoxifying certain types of chemicals. So long as these mechanisms are not overwhelmed, they should provide a threshold of safety.
An example: dioxin
- Dioxin binds to a cytoplasmic receptor protein (like the steroid hormone receptors)
- only when the concentration of dioxin reaches a level high enough to fill all the binding sites on the receptor does the receptor move into the nucleus and damage DNA
29 October 2000