RoundUp and Cholinesterase Inhibition

Monsanto states that glyphosate is not a cholinesterase inhibitor. The MSDS on RoundUp also says that glyphosate is not a cholinesterase inhibitor.  Yet, glyphosate is a an organophosphorus, and the "toxic effects of organophosphorus (OP) compounds are predicated on their irreversible inhibition of acetylcholinesterase (AchE) and other serine hydrolases."

(Viragh C, Kovach IM, Pannell L, 1999. Small Molecular Products of Dealkylation in Soman-Inhibited Electric Eel Acetylcholinesterase.  American Chemical Society, June 11, 1999.)

Merely saying glyohosate is not a cholinesterase inhibitor, however, does not define whether RoundUp itself in full formulation is a cholinesterase inhibitor, and there are no published studies that purport to answer this question.

In 1988, Yusuke Sawada, et al. did a study in which they concluded that the surfactant in RoundUp (POEA) is more toxic than RoundUp's main ingredient, glyphosate.  A study by Servizi et al in 1987 found that POEA is two to three times more toxic than glyphosate, and that the synergy of the two ingredients may even be more acutely toxic than the two ingredients combined.

The answer to whether RoundUp in full formulation is a cholinesterase inhibitor can only be determined by looking at anecdotal evidence.  Many doctors, however, based on Monsanto's advertising that glyphosate is not a cholinesterase inhibitor, refuse to test RoundUp poisoning victims for cholinesterase inhibition, so even anecdotal evidence is not readily available.

(Sawada Y, Nagai Y, Ueyama M, Yamamoto I, 1988. Probable toxicity of surface-active agent in commercial herbicide containing glyphosate.  Lancet. 1988 Feb 6;1(8580):299.)

(Servizi JA, Gordon RW, Martens DW, 1987. Acute toxicity of Garlon 4 and Roundup herbicides to salmon, Daphnia, and trout.
Bull Environ Contam Toxicol. 1987 Jul;39(1):15-22. )

  1. An October 27, 1999 article by PANUPS (Pesticide Action Network Updates Service) offers the information that according to a European Community report on glyphosate (not released at that time), glyphosate poses a significant risk to certain beneficial insects.

(PANUPS, 1999. Glyphosate May Harm Beneficial Organisms, October 27, 1999)

In a 1993 article on organophosphate poisoning, British researcher, T. C. Marrs, indicated that "certain OPs are exploited for their anticholinesterase effects, including defoliants such as 'DEF', herbicides such as glyphosate."  The article goes on to say that the cholinergic syndrome is "caused by acetylcholinesterase inhibition."

(Marrs, TC, 1993.  Organophosphate poisoning.  Pharmacol Ther 1993; 58(1): 51-66.)

An area that has yet to be explored is the impact of the degradation process for glyphosate on the serine cycle. The serine cycle plays a strong part in cholinesterase inhibition in humans.  From available research, it is easy to conclude that, while glyphosate itself might not technically be anticholinergic, the degradants of glyphosate might very well be cholinesterase inhibitors.

Glyphosate's degradation pathway shows that, depending one which soil organisms are present, glyphosate degrades into sarcosine, formaldehyde, AMPA, and Methylamine.

Formaldehyde is not only carcinogenic, but impairs the serine cycle, an important part of the human metabolic process.  According to a document on the ESTHER database, "cholinesterases are readily phosphorylated at the active site serine by a variety of organophosphorus agents (OP) and carbamates."

(www.ensam.inra.fr/cholinesterase/chem/chemInhibition2.html.  The ESTHER "Chemical Mechanism of Acetylcholinesterase Inhibition" introduction.)

(Goldberg I, Mateles RI , 1975. Growth of Pseudomonas C on C1 compounds: enzyme activities in extracts of Pseudomonas C cells grown on methanol, formaldehyde, and formate as sole carbon sources.
J Bacteriol 1975 Apr;122(1):47-53)

There is reported evidence of a patient who, after exposures to RoundUp, showed a depressed pseudocholinesterase. SmithKline Beecham's Normal Values reference range is 3200 - 6600.  On 6/4/96, after three major exposures to RoundUp, this patient's pseudocholinesterase was 2887.  On 7/8/96, after an additional major exposure to RoundUp, this patient's pseudocholinesterase was 2700.  The last reading during the period of this patient's exposures to RoundUp was 2733 on 8/7/96.  Only with the assistance of successful drug therapy (large doses of dextromethorophan) was this reading reversed to 3586 on 10/22/96.

In a study reported in the Journal of Environmental Science Health in January 2001, El-Demerdash, Yousef, and Elagamy EI of the Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Egypt reported that glyphosate demonstrated toxicity on the following vital human enzymes: serum acetylcholinesterase (AChE), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AlP).

Compared with paraquat, glyphosate was found to be more toxic to Ache, LDH, and A1P, demonstrating that glyphosate is indeed a cholinesterase inhibitor despite claims by Monsanto.