# How does one tell (or conclude) if a substance is carcinogenic?

It's common to read statements like:

1. Tetrachloroethene ($$\ce{CCl2=CCl2}$$) was earlier used as a solvent for dry cleaning, but since it contaminated ground water and is a suspected carcinogen, it has been replaced by ... .

2. Various hydrocarbons harms plant tissues, shed leaves, flowers and twigs. Many of them are also carcinogenic.

How do we tell or suspect one compound to be carcinogenic? And are all carcinogens organic compounds?

• Look up "Ames test" – Andrew Dec 21 '19 at 13:29
• It can be told by extensive, expensive and time consuming studies, and even than, some conclusions may not be decisive. – Poutnik Dec 21 '19 at 13:29
• Please see the applied tags as somewhat of a better place-holder than everyday-chemistry. As far as I know there is no tag (yet) that deals with carcinogenicity. – Martin - マーチン Dec 22 '19 at 22:17

How do we tell or suspect one compound to be carcinogenic?

As written in the comments to the question, this the result of large studies on the human population, correlating blood or urine levels of some substance to instances of cancer. Alternatively or concurrently, studies on animal models, such as mice, rats or even in-vitro studies may be carried out. As a result, regulatory bodies may include a substance in lists, which may preclude them from use in consumer products, manufacturing procedures etc.

Are all carcinogens organic compounds?

No, this does not have to be the case: plain arsenic and basically all inorganic cadmium compounds have been classified as suspected or definitively carcinogenic.

Now arsenic has been mentioned and interestingly, inorganic arsenic compounds interfere with the basic mechanism of DNA repair, which apparently increases frequency of chromosomal aberrations. So this is chemically predictable.

Cadmium has also been mentioned, but what is little known is "even tumor formation [52] can be suppressed by the simultaneous Zn treatment" cited in this work. So chemically predictably treated.

For organic compounds, I suggest a simple process to determine the POTENTIAL carcinogenic ability of an organic compound (I believe this is what you are, in effect, asking in being able to 'tell').

In the lab or reported in the research literature, is it apparent that the compound readily undergoes decomposition creating (directly or otherwise) radicals or groups in an environment of aqueous saltwater containing transition metals, CO2, oxygen and naturally produced HOCl or other reactive oxygen species (ROS) at pH levels found in the human body?

Some generated radicals, like the hydroxyl radical and the carbonate radical, for example, can attack DNA as it would any large organic compound to extract a hydrogen atom.

Damaged DNA can lead to cancer cells.

While, for example, short-lived hydroxyl radicals are good in breaking down problematic pesticides in natural waters, they are not recommended in large amounts in the human body.

Note, I am not recommending the direct testing of the decomposition of DNA, but just the expected (and conveniently measured) side products created with the associated breakdown of the organic compound in question. This may be suggestive of potential DNA damage, and at best, a predictive tool. Varying dosing levels may also be quite informative. This is categorically distinct from expensive short-term animal studies (examining tumors) and also investigations of long term low dose exposure and reported incidents of cancer in human populations with inferences drawn from correlation analysis.

If a compound displays a chemical potential to be carcinogenic, per above, you may still want to await the opinion of say Germany, England, or other countries with socialized medicine,.., to verify. But, in my opinion, I would just avoid/limit exposure and consume over the counter anti-oxidants (Vitamin C,...), especially if chemically related suspect compounds are now publicly believed to be carcinogenic.

Thanks Andrew for the reference to the Ames test! It, however, apparently employs "several strains of bacteria (Salmonella, E.coli) that carry mutation" which could limit the accessibility of the test.

DISCLOSURE: I have no financial interest, or am I employed, in the health supplement industry or the health care industry.

• While stressing cells with radical species is a mechanism for generating cancers, it is not necessary (and possible also not sufficient). Consider DNA intercalation compounds like several polycyclic aromatic hydrocarbons, or other molecules with planar aromatic moieties - no chemical reactions are involved. Another mutagenic source is thymine photodimeriaztion by UV light, independent of UV formation of radicals. – Nicolau Saker Neto Dec 21 '19 at 19:13
• Alkylation is another common non-radical mmechanism – Andrew Dec 21 '19 at 19:46
• This answer assumes that cancer can be attributed to DNA damage, which is the standard explanation but by no means exhaustive, and that DNA is damaged by free radicals, which is just the explanation du jour for DNA damage but I know several others (ionizing radiation, any poison that inhibits DNA repair, anything that inhibits the apoptosis mechanisms). The answer is also alluding that cancer can be predicted, which isn't even remotely true. – toolforger Dec 22 '19 at 7:09
• @toolforger All of those examples you listed ultimately lead to DNA damage except things that "inhibit apoptosis mechanism" which doesn't necessarily mean cancer because a cell can be free of apoptosis but not proliferate due to lack of growth factors. And the reason why cancer can't be predicted is because most DNA damaging agents are random in nature via the bases they damage. The only class of agents that you probably can't predict as carcinogenic are chemicals that aren't reactive but get converted to reactive intermediates in the liver. Like why benzene is carcinogenic but not toluene. – Cell Dec 22 '19 at 15:02
• @toolforger That was kind of my point. Anything that leads to increased DNA damage in vivo is carcinogenic. But not everything directly reacts to cause DNA damage. Like benzene if I recall correctly is carcinogenic because a breakdown intermediate in the liver is reactive with DNA. So an in vitro experiment with benzene and pure DNA in solution wouldn't tell you anything or with asbestos etc. The studies are necessary to uncover indirect carcinogens or weakly reactively ones. – Cell Dec 22 '19 at 17:51