I've had a few people send along this article, on the possible toxicological effects of the herbicide glyphosate, wondering what I make of it as a medicinal chemist. It's getting a lot of play in some venues, particularly the news-from-Mother-Nature outlets. After spending some time reading this paper over, and looking through the literature, I've come to a conclusion: it is, unfortunately, a load of crap.
The authors believe that glyphosate is responsible for pretty much every chronic illness in humans, and a list of such is recited several times during the course of the long, rambling manuscript. Their thesis is that the compound is an inhibitor of the metabolizing CYP enzymes, of the biosynthesis of aromatic amino acids by gut bacteria, and of sulfate transport. But the evidence given for these assertions, and their connection with disease, while it might look alarming and convincing to someone who has never done research or read a scientific paper, is a spiderweb of "might", "could", "is possibly", "associated with", and so on. The minute you look at the actual evidence, things disappear.
Here's an example - let's go right to the central thesis that glyphosate inhibits CYP enzymes in the liver. Here's a quote from the paper itself:
A study conducted in 1998 demonstrated that glyphosate inhibits cytochrome P450 enzymes in plants . CYP71s are a class of CYP enzymes which play a role in detoxification of benzene compounds. An inhibitory effect on CYP71B1l extracted from the plant, Thlaspi arvensae, was demonstrated through an experiment involving a reconstituted system containing E. coli bacterial membranes expressing a fusion protein of CYP71B fused with a cytochrome P450 reductase. The fusion protein was assayed for activity level in hydrolyzing a benzo(a)pyrene, in the presence of various concentrations of glyphosate. At 15 microM concentration of glyphosate, enzyme activity was reduced by a factor of four, and by 35 microM concentration enzyme activity was completely eliminated. The mechanism of inhibition involved binding of the nitrogen group in glyphosate to the haem pocket in the enzyme.
A more compelling study demonstrating an effect in mammals as well as in plants involved giving rats glyphosate intragastrically for two weeks . A decrease in the hepatic level of cytochrome P450 activity was observed. As we will see later, CYP enzymes play many important roles in the liver. It is plausible that glyphosate could serve as a source for carcinogenic nitrosamine exposure in humans, leading to hepatic carcinoma. N-nitrosylation of glyphosate occurs in soils treated with sodium nitrite , and plant uptake of the nitrosylated product has been demonstrated . Preneoplastic and neoplastic lesions in the liver of female Wistar rats exposed to carcinogenic nitrosamines showed reduced levels of several CYP enzymes involved with detoxification of xenobiotics, including NADPH-cytochrome P450 reductase and various glutathione transferases . Hence this becomes a plausible mechanism by which glyphosate might reduce the bioavailability of CYP enzymes in the liver.
Glyphosate is an organophosphate. Inhibition of CYP enzyme activity in human hepatic cells is a well-established property of organophosphates commonly used as pesticides . In , it was demonstrated that organophosphates upregulate the nuclear receptor, constitutive androstane receptor (CAR), a key regulator of CYP activity. This resulted in increased synthesis of CYP2 mRNA, which they proposed may be a compensation for inhibition of CYP enzyme activity by the toxin. CYP2 plays an important role in detoxifying xenobiotics .
Now, that presumably sounds extremely detailed and impressive if you don't know any toxicology. What you wouldn't know from reading through all of it is that their reference 121 actually tested glyphosate against human CYP enzymes. In fact, you wouldn't know that anyone has ever actually done such an experiment, because all the evidence adduced in the paper is indirect - this species does that, so humans might do this, and this might be that, because this other thing over here has been shown that it could be something else. But the direct evidence is available, and is not cited - in fact, it's explicitly ignored. Reference 121 showed that glyphosate was inactive against all human CYP isoforms except 2C9, where it had in IC50 of 3.7 micromolar. You would also not know from this new paper that there is no way that ingested glyphosate could possibly reach levels in humans to inhibit CYP2C9 at that potency.
I'm not going to spend more time demolishing every point this way; this one is representative. This paper is a tissue of assertions and allegations, a tendentious brief for the prosecution that never should have been published in such a form in any scientific journal. Ah, but it's published in the online journal Entropy, from the MDPI people. And what on earth does this subject have to do with entropy, you may well ask? The authors managed to work that into the abstract, saying that glyphosate's alleged effects are an example of "exogenous semiotic entropy". And what the hell is that, you may well ask? Why, it's a made-up phrase making its first appearance, that's what it is.
But really, all you need to know is that MDPI is the same family of "journals" that published the (in)famous Andrulis "Gyres are the key to everything!" paper. And then made all kinds of implausible noises about layers of peer review afterwards. No, this is one of the real problems with sleazy "open-access" journals. They give the whole idea of open-access publishing a black eye, and they open the floodgates to whatever ridiculous crap comes in, which then gets "peer reviewed" and "published" in an "actual scientific journal", where it can fool the credulous and mislead the uninformed.