tox-blog #2: Glyphosate and the problem of conflicting studies.

in science •  last year

A certain pesticide has dominated lunch table talks of toxicologists over the last weeks and I just have to add my grain of salt to that discussion. 

Intro

As many of you will know, glyphosate is a herbicide that the EU authorities (parliament vs commission) recently battled over. The question was whether to renew its licence or not after the International Agency for Research on Cancer (IARC) described it as “probably carcinogenic”, while the European Food Safety Authority (EFSA) did not see a reason to ban it. So there is a rift between legal authorities, responsible agencies and also between scientists in the field.   
But how is it possible that two respected scientific panels come to completely different opinions on one and the same chemical? 

The problem

I think that the main issue here is a problem that is in general allowing great misinterpretations by non-scientist and is thus – sadly - eroding the public trust in the whole field of toxicology: conflicting studies.
In other words, when you look up toxicological studies on one and the same compound, you often find very different – and sometimes contradictory - results. 

While the public opinion seems to be positive that this was caused by a powerful money-throwing and arguably evil corporation (Monsanto), I am quite convinced that the reason is just the way our scientific discipline works (or has to work). 

To understand this, it's important to remember that there are different types of toxicological studies, with different strenghts and weaknesses:   

in vitro

Studies on cultured cells – so-called in vitro studies - are the fastest and cheapest method. They are used for “screening” – a fast check whether a compound exerts a certain toxic effect, and also for exploring the mechanism of known toxins at the cellular level. Results of in vitro studies are often preliminary – just the kick-off for more detailed research. Because they cannot take into account the behaviour of chemicals inside an organism (with all the complex mechanisms of uptake, metabolism, stability, distribution, etc.), data from in vitro studies cannot act as a stand-alone risk assessment.
And toxicologists know this. But others don’t. So very often you will see newspaper headlines that this or that compound was found to promote cancer or to protect from cancer or whatever, just to find out later it’s only a useless in vitro study they cited.    

in vivo (animals)

Let’s take a look at the second main type of tox studies, those which rely on feeding toxins to animals, mainly rats or mice. These in vivo studies are usually the follow-ups on promising in vitro results (yes, for us toxicologists a toxic effect is “promising”). They give you a lot more information than in vitro experiments, as here the behaviour of your toxin inside the animal body is taken into account. If you find a toxic effect in such a study, chances are well that your chemical is toxic for humans as well - at least in the concentrations applied, for often toxin ammounts used in the lab are ridiculously high.  
This kind of studies is used for chemical licencing by the authorities. But of course, animal studies have limitations as well. First off, every species is different and might react differently to a chemical - e.g. a rat could hypothetically tolerate higher concentrations of glyphosate than humans. Second, long-time exposure (several years) to small concentrations is not measureable in rodents – simply because they don’t live long enough. 

Cutie might be eating glyphosate...In my defense: I'm doing in vitro!

epidemiologic

On contrary to pharmaceutic scientists, toxicologists – for obvious reasons – cannot feed toxins to humans. So we have to use an indirect approach to gain toxicological data on humans – the so-called “epidemiologic study”. After several years that a chemical – let’s say a herbicide like glyphosate – is on the market and thus humans are exposed, researchers compare people with high exposure to people with no or low exposure to find out differences of – for example – cancer rates.
But this is tricky as well, as it is sometimes very difficult to isolate the effect of a single compound here. For example, if you want to compare consumers of organic food to consumers of glyphosate-treated food, you have to consider that the glyphosate – treated food probably came into contact with other pesticides as well.

Conclusion and back to glyphosate

To sum it up: risk assessment is very tricky. And the different kinds of studies, the different concentrations of the toxin used, but also the improvement of scientific methods over time can lead to conflicting results, that are hardly interpretable for non-toxicologists.   

And this is exactly what happened with the glyphosate story. Early on in vitro studies and animal studies showed no toxic effects. Then, two in vitro studies using way to high concentrations found toxic effects in certain cell lines.  Several epidemiologic studies found no toxicity whatsoever, but a few of them did find a slightly elevated risk to develop a certain type of cancer for high-exposure groups – not food consumers, but farmworkers who got into contact with pure glyphosate.   

So based on the same data, the EFSA said that the use of glyphosate in agriculture would not lead to toxic concentrations in food, and the IARC classified glyphosate as “probably carcinogenic”.    

And both are right.    

Based on the publicised data, one has to conclude that glyphosate is most probably safe to use. BUT there is of course the legit argument that you want to limit every risk, and even if the risk of glyphosate causing any toxic effects in consumers is very low, you would want to eliminate the possibility by banning it. 

As scientists could not come up with a conclusive answer, the decision came down to science-oblivious politicians looking for votes and campaign money. The rest is history, and at least 3 more years of conflict are to follow, until politicians meet to decide again.   


Sources:   

pictures from pixabay & pexels
IARC: http://monographs.iarc.fr/ENG/Monographs/vol112/mono112.pdf
EFSA: https://www.efsa.europa.eu/de/topics/topic/glyphosate

Disclaimer: In my blog, I'm stating my honest opinion as a  researcher, not less and not more. Discuss and disagree with me - if you  are bringing the better arguments, I might even rethink. 



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Boah, ein Glück, dass du Deutsch sprichst, sonst müsste ich jetzt meine gesamte Antwort auf Englisch verfassen :D

Also, ich hab bereits schon unter einem anderen Post mal eine Diskussion angefangen (LINK), wo ich als Glyphosat-Gegner (natürlich :D) gegen einen Glyphosat-Anhänger debattiere. Empfehlenswert sich das anzuschauen, wenn dich das Thema interessiert. Aber nun zurück.

Ich finde es sehr schön, wie du diesen Aspekt mit den unterschiedlichen Studien herausarbeitest, schließlich widersprechen sie sich ja nicht, wie viele denken. Denn eine Studie ist nie zu 100% richtig, einfach weil man nicht alles wissen kann.
Und zwischen wahrscheinlich krebserregend und wahrscheinlich nicht krebserregend ist jetzt nicht der größte Unterschied.

Als so viel über Glyphosat diskutiert wurde, habe ich mir damals ganz viele Artikel zu dem Thema durchgelesen, eben diese Studien mir angeschaut, die Beweggründe der Leute, die bei der Europaweiten Bürgerinitiative mit einem Nein zu Glyphosat gestimmt haben angeschaut. Und ich sag ehrlich, ich hab da auch mit abgestimmt, und zwar dagegen.

Aber eben nicht, weil es wahrscheinlich krebserregend ist, sondern, was mir eben besonders am Herzen liegt, weil Pestizide der Umwelt schaden, Pflanzen abtöten, Artensterben verursachen, wie das Bienensterben, und eben auch Genmutationen hervorrufen, die einen an die Krankenhauskeime erinnern, gefährlich und schwer zu bekämpfen.

Und was man dieser Diskussion immer beachten muss, was würde nach Glyphosat kommen ?
Es bringt nichts, wenn danach direkt ein genauso oder schädlicheres Produkt auf dem Markt kommt. Es braucht strengere Richtlinien für die Zulassung aller Pestizide.

Gruß Naturicia

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Servus.^^ Und danke für die ausführliche Antwort.

a) Danke für den link, ich schau da sicher mal rein.

b) "Ich finde es sehr schön, wie du diesen Aspekt mit den unterschiedlichen Studien herausarbeitest, schließlich widersprechen sie sich ja nicht, wie viele denken. Denn eine Studie ist nie zu 100% richtig, einfach weil man nicht alles wissen kann."

Danke, genau das war mein Ziel. Die Widersprüchlichkeit ist oft nur scheinbar gegeben, weil Studien aufgrund der unterschiedlichen Methodik oft nicht vergleichbar sind. Alle zusammen ergeben als Mosaik ein Gesamtbild - das aber auch nie perfekt ist.

c) "Und zwischen wahrscheinlich krebserregend und wahrscheinlich nicht krebserregend ist jetzt nicht der größte Unterschied."

"Wahrscheinlich nicht krebserregend" existiert als offzielles label glaube ich gar nicht, genauso wie "nicht krebserregend". Das liegt einfach daran dass die Nicht-Existenz einer Begebenheit wissenschaftlich praktisch unmöglich zu beweisen ist, weil es ja immer sein kann, dass einfach nicht die genügend Daten vorhanden sind bzw. die richtige Methodik gewählt wurde. Die Abstufung geht glaube ich so: möglicherweise krebserregend < wahrscheinlich krebserregend < krebserregend
Glyphosat steht also sogar schon auf der mittleren Stufe, was schon heißt, dass die IARC die daten für durchaus ausagekräftig haltet. Und trotzdem hat die EFSA auch irgendwie recht, denn die für die krebserregende Wirkung notwendigen Konzentrationen werden für den Konsumenten fast sicher nie erreicht.

d) "Aber eben nicht, weil es wahrscheinlich krebserregend ist, sondern, was mir eben besonders am Herzen liegt, weil Pestizide der Umwelt schaden, Pflanzen abtöten, Artensterben verursachen, wie das Bienensterben, und eben auch Genmutationen hervorrufen, die einen an die Krankenhauskeime erinnern, gefährlich und schwer zu bekämpfen."

Da stimme ich dir voll zu, die ökologische Wirkung ist für mich persönlich auch viel eher ein Argument gegen den übermäßigen Pestizideinsatz als die gesundheitliche Wirkung, die ja eigentlich auch gar nicht gegeben ist.

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Hey, ich muss sagen ich hab mich auch mit dem Thema beschäftigt und im ORF (bin Österreicher) war eine sehr gute Doku(Werljournal)+)) darüber, ist leider nicht mehr in der TVThek, aber ich werde mal meinen Senf auf Englisch dazu abgeben. Ich geb dir Recht mit deinem Post, aber man muss sagen, dass das ganze Thema viel größer ist als man ahnt. Es kommen Aspekte wie Biodiesel/Autoindustrie dann die Verbrechen die an den Bauern zB in Argentien verübt werden und natürlich die EU/Politik die dahinter steht und ihre Wirtschaft beschützt. stay tuned :)

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Servus. Bin auch Österreicher btw. ;-)
Und ja, das stimmt voll, das Thema ist viel größer. Ich habe hier nur den gesundheitlichen Aspekt behandelt, weil das halt auch mein Fachgebiet ist, und ich darüber relativ qualifiziert schreiben kann. Wobei ich denke die Entscheidung über Glyphosat alleine sollte man schon an gesundheitichen und ökologischen Dingen festmachen.
Die Thematik, die du erwähnst, hat dann denke ich weniger mit dem Herbizid an sich, sondern mehr mit dem Konzern, der dahinter steht, zu tun. Dass Monsanto ein *#(%&%$-Verein ist, darüber brauchen wir uns nicht streiten.^^

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Hello :)
Woher bist du?
Wie wurde es zu deinem Fachgebiet?
Grüße

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in aller Kürze: bin ursprünglich aus Tirol, lebe seit mehr als 10 Jahren in Wien (im 22. aktuell, also je nach Definition Wien oder auch nicht).
Hab Chemie/Biochemie studiert und arbeite jetzt als Wissenschaftler im Bereich Lebensmitteltoxikologie.

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Servus aus Bayern ^^,

danke für die ausführliche Antwort

Immer wieder gerne :)

"Wahrscheinlich nicht krebserregend" existiert als offzielles label glaube ich gar nicht

Das meinte ich auch nicht. Was ich aussagen wollte, ist, dass die andere Studie sagt, dass Glyphosat nicht krebserregend ist, aber da keine Studie immer komplett richtig ist, habe ich selbst das wahrscheinlich hinzugefügt.

Ich drück mich immer so kompliziert aus :D

Gruß Naturicia

Thanks a lot for your insights. I would rather be asked if there are any studies which identify the no hazardous dosages?

Also, I strongly don't believe if a substance destroys some organisms, inside a body will not do any harm. The right question would be rather how harmless/serious damage I can create? As u said the metabolism of a toxin, but also the environment that they got into is affected e.g. stomach, guts will it affect flora etc.
The scientist usually doesn't know what happens exactly but verifies trends, statistical correlations etc.
If you can please enlight us on some of these aspects, I will read with pleasure! Good luck & thanks for the info!

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Thank you for your interest, and sorry I am replying so late^^

Any toxic effect is always a question of dosage. If you go high enough with the dosage, even the most common compounds will get toxic. If there is data on exposure available, researchers in the lab can either give realistic doses to cells/animals - that means estimated maximum concentrations you would expect to occur. Studies conducted in that way did not show any toxicity of glyphosate.
Or researchers go way higher in concentrations - studies doing this have found toxicity. Also these studies can be valuable, especially when they establish something we call the "no observed adverse effect level" (NOAEL), which is the highest concentration where you can't see a toxic effect.
Agencies like EFSA (europe) or FDA (US) take into account both types of studies, but also epidemiologic studies and exposition data and then try to conclude whether there is a toxicity, and if yes, if it's enough to establish legal tresholds or if there has to be a ban. The latter is mostly the case for carcinogenic compounds.

I will for sure include some more stuff in future posts.

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What the Seralili glyphosate study proved.... that if you give Roundup to rats that develop cancers 80% of the time by adulthood, 80% of the rats will develop cancer by adulthood.

What the neonicotinoid studies now prove.... that if you give huge doses of insecticide to insects, they die.

We need much MUCH better science reporting, because right now they will publish any shit you throw at them.

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Well, the Seralini study was a) paid for by greenpeace and b) widely critized in the scientific community. The publication had to be withdrawn due to errors in methodology and statistics.
But of course, the public read a lot about the study and much less about its skeptical reception in the scientific community or even the withdrawal.

So I agree that scientific reporting has to get better. The media should hire people that can read a study and interpret it in a professional way.

Freut mich, dass deine Posts etwas Beachtung finden :) Und freut mich auch, dass es deine bessere Hälfte ebenfalls hergeschafft hat! LG

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mich auch ;-)
Schlägt wesentlich besser ein als erwartet, steemstem/curie sei Dank.

From my understanding, in the studies the 'pro-ban' people refer to, it was not that easy (although maybe impossible) to disentangle the source of the risk: the glyphosate or the products it is mixed with. Am I right here?

This being said, glyphosate as being classified as increasing the risks for cancer in the same way red meat, and many other things, is...

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as I wrote above, disentagling one compound from all the other factors is never easy and is a main problem of epidemiologic studies.
De Roos et al., 2005, tried that by statistically adjusting their results for factors like "age, smoking, other pesticides, alcohol, family history of cancer". Doing this they found glyphosate to increase the risk for a special cancer type (non hopkins lymphoma) by a factor of 2.6. That means if you are a farmworker using glyphosate, your annual risk of getting that cancer is about 0.026% instead of 0.01%.

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Thanks for the precisions :)

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np, was in a super-boring lab meeting, time enough to look it up again ;-)

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Lol! I see ;)

☠️ Let's keep the (potentially) toxic chemicals out of our food!? #eatclean

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Most people will emotionally agree (me included). But of course that's easier said then done. As you can see, even determining which chemical is toxic can prove very tricky. And organic nutrition hasn't yet been proven to be healthier, as I wrote last week. Plus it isn't productive (at least for now) enough to feed 8 billion people. Scienifically sound solutions are urgently needed.

Banning of glyphosate though controversial and inconclusive would be a step towards the right direction... in as much as most substances are being termed carcinogenic, there is wide spread belief that most are not.. but hey! Who wants to risk a life for a scientific adventure.
Nice article @sco.. and i must say, honest opinion

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thanks!

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Sure! Sign me up! Why wouldn't I, considering the quality of the "research" that show it to be harmful. Research? Pure propaganda more like it. Those rats with the huge tumors, they are specifically bred so that 80% have those by the time they're adults. Sorry rats, our bad. The data in that "study" is presented in such a muddled way as to obscure what it really shows... that rats that drink Roundup contaminated water will actually live longer than ones with fresh water. Every study I've looked at is like that, just awful. So who's behind all this? There are scads of lawyers lining up to file massive class-action suits (and they have already hired the scientists behind that IARC report to be "expert testimony". Then there's the organic food lobby, and oh how the idiots laughed when I mentioned "Big Organic" which actually has sales figures larger than Monsanto's, and with a much higher profit margin. Monsanto, of course, doesn't own the patent on glyphosate anymore, so why are they the bogey-man here? Roundup is amazing stuff. You apply it before seeding and rarely have to re-apply. It's even led to the development of no-till agriculture, so instead of dead soil tilled by burning diesel you've got biodiversity, living soil, less carbon in the atmosphere, it goes on and on. But certain ideologically driven activist groups simply will not listen to the facts, but work to create their own. These are the same people who condemn half a Million children to blindness each year!!! Sickening, but to them it's better than having a solution in "Golden Rice", a GMO product.
Disclosure: I live in rural Manitoba, Canada, where we have been slopping the stuff around for forty years. No cancer, no flipper-babies, no problem.

shameless self-promoting ;-)
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