Search on specialist websites and picloram is described as follows: it is a systemic herbicide used against broad-leaved weeds, shrubs and woody species. A pesticide considered particularly effective on pastures, forestry sites, along roads and railways, as well as on industrial land. Its use is widespread, even though the name is far less familiar to the general public than other substances that have attracted far greater scrutiny in recent years, such as glyphosate.

The pesticide picloram has never been classified as a carcinogen

Picloram's relative obscurity is mainly due to one factor: until now, it has never been classified as a carcinogen. Until now, that is — because a study published in the scientific journal Nature Medicine has linked exposure to the substance to the dramatic rise in colorectal cancers recorded in people under the age of 50.

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An analysis of #exposome traits in patients with early onset #CRC (<50 yrs) compared with late-onset CRC (≥70 yrs) based on epigenetic markers shows that pesticide usage, in particular picloram, is associated with early onset #colon and #rectal #cancer.
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The research was led by Jose A. Seoane of the Vall d'Hebron Institute of Oncology in Barcelona, Spain, who together with his co-authors drew on large-scale epidemiological data and molecular biology analyses. Their goal was to shed light on a trend that medicine has so far struggled to explain: while colorectal cancer rates are declining among older people, cases are rising steadily in those under 50.

"We began by comparing tumours taken from patients below that age threshold and from patients over 70," Seoane explained to the French daily Le Monde. The aim was to identify what are known as "epigenetic signatures" — the molecular imprint left on tissues — and attempt to determine which exposures might have triggered the diseases.

The Spanish researchers' hunt for "epigenetic signatures"

To do so, an extensive data-gathering effort was required, drawing on previous studies each of which had focused on a different element as a possible cause of the diseases: from fine particulate matter to obesity, smoking, lifestyle habits, alcohol consumption, and a range of pesticides.

By cross-referencing statistical data with the epigenetic signatures, the researchers found that the markers of exposure to picloram were overrepresented in patients with early-onset tumours. But that was not all: to further strengthen the hypothesis, they analysed pesticide use across 94 US counties (between 1992 and 2012), cross-referencing those figures with local cancer incidence data. The result was the same: exposure to picloram appeared to be correlated with new cases — even more so than glyphosate or atrazine.

Why the study could upend the methods used by regulatory bodies

Another reason why picloram has been linked to colorectal cancer in people under 50 relates to the fact that the pesticide was approved in the 1960s. This means that patients now under 50 came into contact with it from childhood through their diet.

But the study's main innovation lies in the fact that the researchers were not satisfied with a purely statistical analysis of the data. Instead, they explored the mechanisms by which the substance in question is capable of increasing disease risk. To date, the regulatory bodies responsible for granting market authorisations for pesticides focus primarily on their ability to induce DNA modifications in cells.

The Spanish analysis, by contrast, shows that certain substances are capable of "activating" specific genes without altering the DNA itself, yet making individuals more predisposed to developing cancer. This finding could therefore call into question the very foundations of the method currently used to judge whether the substances contained in pesticides are harmful to human health.