"Oh, what a tangled web we weave, when first we practice to deceive"
from Sir Walter Scott's poem "Marmion."
Photo’s from an official U.K. Government document written by the Ministry of Pensions and National Insurance (now called the Department for Work and Pensions - (DWP) titled:
‘NATIONAL INSURANCE INDUSTRIAL INJURIES ACT 1946
REVIEW OF THE PRESCRIBED DISEASES SCHEDULE’, originally published in 1958 and reprinted in 1962 were found amongst numerous papers, newspaper clips and official documents on organophosphates (OP’s), the poisoning of farmers and Industrial Injuries Disablement Benefit (financial aid), in a file which had been archived by the U.K. Government’s DWP in 2002:
Catalogue description
Organophosphate poisoning to farmers caused by sheep dip
This record is closed
Opening date: 01 January 2079’
https://discovery.nationalarchives.gov.uk/details/r/C16553622
Access to this file was gained in 2023 with a link provided to the documents.
The file doesn’t only contain documents specific to poisoning from sheep dip formulations, but also documents on OP poisoning generally.
The link to the documents no longer works. To view them now, you have to go to the National Archives at Kew, near London.
(How many of the documents I have personally viewed and photographed still remain in the file is unknown.)
The photos of the pages on Industrial Injuries confirm that the U.K. Government knew of the dangers in 1958, not only regarding organophosphate formulations used in agriculture (pesticides and sheep dips), but the dangers of exposure to fumes containing organophosphates in formulations such as aircraft oil used in industry and that they ‘might give rise to a chronic form of poisoning’.
It starts with page 7:
‘Poisoning by phosphorus, tri-cresyl phosphate and tri-phenyl phosphate. (Disease Nos. 3, 11 and 12)
Organic phosphorus compounds which may have toxic effects are being used increasingly in agriculture as insecticides and it is important that it should be quite clear that poisoning by these substances is covered under the Act. At present doubts could reasonably be entertained as to why this was so. The harmful effects of these organic compounds of phosphorus are quite different from those of the simple element and present a quite distinct clinical picture; the present Schedule already exhibits two examples of the separate prescription of poisoning by compounds of phosphorus which have distinct modes of action; namely, poisoning by tri-cresyl phosphate (Disease No. 11) and poisoning by tri-phenyl phosphate (Disease No. 12). There might therefore be some grounds for inferring that poisoning by any other compound of phosphorus producing a clinical picture different from the first classic conception of phosphorus poisoning was not covered. We were assured both that in medical circles “phosphorus poisoning” does connote poisoning by the organic compounds we have in mind and also that there has never been any intention that such conditions should be excluded from the scope of the prescription. Nevertheless we think that the matter should be put beyond any possible doubt.
We do not recommend the comprehensive description “Poisoning by phosphorus and it’s compounds” because almost all living matter contains some phosphorus and there would be a very real danger that conditions might be included which could not reliably be related to the effects of any employment. On the other hand it would be difficult to limit the field by specifying in the Schedule each toxic compound of phosphorus since these are legion. We consider the best solution to the problem of finding a formula for phosphorus poisoning which will include such conditions as may properly be prescribed as industrial disease is to refer to the character of the toxic effects of the organic compounds which constitute an industrial risk. A review of the toxic qualities of the various phosphorus compounds likely to be encountered in industry and agriculture suggested that all but two of the poisonous organic compounds of phosphorus, against which insurance is needed, produce their effects by anti-cholinesterase action, i.e., by inhibiting the action of certain enzymes on the nerve endings which form part of the mechanism of muscular control. The two exceptions are tri-cresyl and tri-phenyl phosphate which as noted above are already prescribed. As for the inorganic compounds, as far as it is known only one which is used in industry might give rise to a chronic form of poisoning in circumstances which would not constitute injury by accident for benefit purposes, namely phosphine: it would therefore be quite practicable to mention this specifically in the definition of the disease. We accordingly recommend that the disease be defined as “Poisoning by phosphorus or phosphine or poisoning due to the anti-cholinesterase action of organic phosphorus compounds”.
Tri-cresyl phosphate and tri-phenyl phosphate, though organic compounds of phosphorus, are not generally accepted as true cholinesterase inhibitors and might not be covered by the formula we have just recommended. We consider that no useful purpose would be served by altering the present arrangement whereby poisoning by either of these two substances is prescribed seperately.’
The pages then carry on reviewing some of the other diseases being considered for amendment and begins to summarise on page number 18:
‘Ammendments considered
Poisoning by phosphorus or phosphine or poisoning due to the anti-cholinesterase action of organic compounds (Disease No. 3), poisoning by tri-cresyl phosphate (Disease No. 11) and poisoning by tri-phenyl phosphate (Disease No. 12).
Poisoning by two compounds of phosphorus, tri-cresyl phosphate and tri-phenyl phosphate, is listed as Disease Nos. 11 and 12, but we received evidence that there are other compounds of a similar nature, e.g. tri-methyl phosphate and tributyl phosphate, which have similar toxic effects and are not at present covered. Although poisoning with those substances often occurs as the result of a single exposure and could reasonably be dealt with under the industrial injuries accident provisions, we recommend covering all compounds of phosphorus and that in order to rationalise the schedule, they should be included in a reworded disease covering Disease 3, 11 and 12. We suggest that this should read:
Description of disease or injury:- Poisoning by phosphorus or an inorganic compound of phosphorus or by the anti-cholinesterase or the pseudo anti-cholinesterase action of organic phosphorus compounds.
Nature of occupation:- Any occupation involving the use of or handling of, or exposure to the fumes, dust or vapour of, phosphorus or a compound of phosphorus, or a substance* containing phosphorus.
The term “pseudo anti-cholinesterase” has been used to cover the mode of action of tri-cresyl phosphate and tri-phenyl phosphate as these two are not usually accepted as true cholinesterase inhibitors.’
*That wording is important because it confirms the Government were aware that Organophosphates are rarely used on their own, but in complex mixtures/formulations containing solvents and other volatile organic compounds; and as shown in the Health and Safety Executive’s (HSE) Medical Series 17 document of 1980, they knew the solvents within formulations containing organophosphates could cause additional effects and influence the toxicity:
‘Biological Effects
When poisoning with proprietary formulations of organo-phosphorus compounds occurs, the presence and influence of the solvents should not be forgotten. Local skin effects will almost certainly be due to the solvent; in exceptional and severe cases the progress of the intoxication can be seriously affected by the presence of an organic solvent.
http://www.oprus2001.co.uk/ms171980.pdf
I contacted numerous government departments requesting a hard copy of the Industrial Injuries document and also requested historical scientific documents which fully explained ‘the distinct mode of action’ stated for poisoning by tri-cresyl and tri-phenyl phosphate.
I was eventually informed by the UKHSA that many historical documents connected to organophosphate poisoning were placed in a storage facility which suffered a fire in 2007 and that it’s likely that those documents were amongst them.
Acetylcholinesterase (AChE) is known as true cholinesterase and butyrylcholinesterase (BChE) is known as pseudo cholinesterase or plasma cholinesterase.
‘What is Cholinesterase
Cholinesterase is the enzyme responsible for the hydrolysis of acetylcholine released by the central and peripheral nervous system. True cholinesterase and pseudocholinesterase are the two types of cholinesterase. Another name for the true cholinesterase is acetylcholinesterase (AChE). It occurs in neurons and red blood cells in large amounts. The primary location of acetylcholinesterase is postsynaptic neuromuscular junctions, especially in muscles and nerves. The primary function of acetylcholinesterase is to break down acetylcholine (ACh) immediately. Here, acetylcholine is a naturally-occurring neurotransmitter. Acetic acid and choline are the breakdown products of acetylcholine.
Furthermore, the role of acetylcholinesterase is to terminate neuronal transmission, which in turn removes the signaling between synapses. However, acetylcholine disperses and activates nearby neurons. Critically, Organophosphates inhibit acetylcholinesterase, an essential component of nerve agents and pesticides.’
‘What is Pseudocholinesterase
Pseudocholinesterase is a serine hydrolase primarily produced in the liver. It catalyzes the hydrolysis of choline esters, most prominently succinylcholine and mivacurium. Other names of pseudocholinesterase include plasma cholinesterase, serum cholinesterase, acetylcholine acetylhydrolase, and butyrylcholinesterase (BuChE). The ratio of butyrylcholinesterase to acetylcholinesterase is 1000 to 1. Therefore, the primary cholinesterase form in the human body is butyrylcholinesterase. Also, the primary function of butyrylcholinesterase is to affect the activity of neurons, specifically within the hippocampus, amygdala, thalamus, and different deep layers of the cerebral cortex.’
https://pediaa.com/what-is-the-difference-between-cholinesterase-and-pseudocholinesterase/
Another example of the knowledge they had in the 1950’s is written in a review by D. R. Davies, M.Sc., F.R.I.C. from The U.K. Government’s Chemical Defence Experimental Establishment at Porton Down.
(I only have this review article as a pdf which I can’t add on this platform.)
‘Separate cholinesterase determinations of red cells and plasma* when compared with pre-exposure values permit the recognition of cumulative effects of repeated exposures and the differentiation of chronic from severe acute exposures. Low plasma values indicate mild acute poisoning. Low red cell values, with normal plasma values indicate recovery from a previous acute or repeated intoxication. Low values for both indicate severe acute intoxication.
Cholinesterase estimations have also been of diagnostic value in individual cases in which the symptoms have been ambiguous and when there was need of a timely warning for accidentally exposed persons who have not yet developed symptoms.’
‘Fawley et al. stress the limitations of cholinesterase inhibition in evaluating the degree of exposure and severity for reasons which have already been indicated in the opening paragraph of this section. In chronic exposures they believe that cholinesterase measurements would be valuable in detecting slight multiple exposures. They say, however, that both plasma and erythrocyte levels have been of value as evidence of parasympathomimetic stimulation which may be a delayed phenomenon in subacute exposure. They observed plasma and erythrocyte cholinesterase levels in animals as low as 5 per cent. of normal, several weeks before the onset of convulsions and death.’
*Red Cell Cholinesterase = true/AChE and Plasma = Pseudo/BChE.
- Which again, corresponds with what was written in the U.K. Health and Safety Executive’s Medical Series 17 documents from the 1980’s:
U.K. HSE Guidance Note MS 17 (1980)
http://www.oprus2001.co.uk/ms171980.pdf
U.K. HSE Guidance Note MS 17 (1987)
http://www.oprus2001.co.uk/ms171987.pdf
This is a ‘Toxcard’ article (2023) in relation to chronic toxicity from repeated low level exposures:
‘The focus of this Tox Card are the chronic toxicity syndromes associated with organophosphate exposure. It is often the presentation of farm workers and others that come into contact with the agent, either through inhalation, ingestion, or dermal exposure, and exposure can be either intentional or unintentional. Exposures in small quantities over a long period of time leads to symptoms of chronic toxicity.’
https://www.emdocs.net/toxcard-chronic-organophosphate-toxicity/
Yet, according to the U.K. Government and their expert committees and councils, this does not and cannot happen.
And this is what Artificial Intelligence currently knows about TCP and TPP:
“Tricresyl phosphate (TCP) and triphenyl phosphate (TPP) are chemicals that can inhibit butyrylcholinesterase (BChE), also known as pseudocholinesterase. These compounds are classified as pseudo anticholinesterase agents because they interfere with the normal function of BChE, which is responsible for hydrolyzing certain neurotransmitters and other substrates.
Inhibition of BChE by these chemicals can lead to various toxicological effects, including prolonged neuromuscular blockade and potential neurotoxicity. TCP, in particular, has been associated with a condition known as "organophosphate-induced delayed neuropathy," which can result from exposure to certain organophosphate compounds.
While the term "pseudo anticholinesterase" may not be widely used in current toxicological literature, the concept of BChE inhibition and its implications for health and safety remains relevant, as inhibition of butyrylcholinesterase (BChE) can occur from repeated, cumulative low-level exposures to tricresyl phosphate (TCP) or triphenyl phosphate (TPP).
BChE plays a crucial role in the metabolism and detoxification of various compounds. When BChE is inhibited, it can result in an accumulation of substrates that the enzyme would normally break down, potentially leading to adverse health effects.
Cumulative exposure can be particularly concerning in occupational settings or environments where these chemicals are used, as individuals may not experience immediate symptoms but could still be at risk for long-term health effects due to the gradual inhibition of BChE.
Monitoring BChE activity can be an important aspect of assessing exposure and potential health health risks.
The primary mechanism of injury from Tricresyl phosphate (TCP) is related to its impact on the body's ability to metabolize and detoxify certain substances, including TCP itself. Here's a clearer breakdown of the process:
Butyrylcholinesterase (BChE) plays an important role in metabolizing and breaking down various ester-containing compounds, including some toxins and phosphorylated chemicals like TCP. It's often referred to as a detoxifying enzyme because it helps neutralize potentially harmful compounds in the body.
- When BChE is inhibited by TCP, the body’s ability to process and eliminate TCP and similar chemicals is reduced. This leads to toxic buildup in the body.
Toxic Accumulation of TCP:
- TCP is an organophosphate compound, and when BChE is inhibited, it can prevent the normal breakdown of TCP. As a result, TCP can accumulate in the body, particularly in tissues that have a high affinity for the chemical, such as the nervous system.
- The accumulation of TCP (and potentially its metabolites) can contribute to neurological and systemic toxicity, especially if there is chronic or repeated exposure.
Secondary Neurological Effects:
- The inhibition of BChE by TCP can result in neuropathy and muscle weakness, primarily because of the impaired clearance of neurotoxic metabolites.
Chronic exposure may lead to long-term nerve damage, as the body struggles to eliminate these harmful chemicals.
The Impact of BChE Inhibition:
- BChE inhibition can lead to a cascade of effects:
- Impaired detoxification: The body loses its ability to break down and clear TCP and other toxic substances.
- Potential neurotoxicity: Since BChE also plays a role in protecting the nervous system from certain toxins, its inhibition can leave the nervous system more vulnerable to damage.
- Cognitive and neurological dysfunction: Over time, the accumulation of toxins and the failure to metabolize them efficiently can result in brain fog, memory issues, and fatigue.
Cholinergic Toxicity (Indirect) – AChE vs BChE:
- Though BChE inhibition doesn't directly cause the accumulation of acetylcholine like AChE inhibition, it can still lead to secondary effects on cholinergic systems. For example, acetylcholinesterase (AChE) is still essential for breaking down acetylcholine in nerve synapses, and if TCP causes generalized toxicity in the nervous system, it can lead to muscle dysfunction, weakness, and other symptoms due to cholinergic dysregulation.
- TCP’s main impact is through BChE inhibition which leads to indirect neurological damage and accumulation of toxic metabolites that affect nerve function, but not via the cholinergic overstimulation seen with classic AChE inhibitors.
Key Mechanism Summary:
- TCP → Inhibition of BChE → Impaired detoxification → Accumulation of toxic metabolites (e.g., TCP) → Neurological and systemic damage.
- Effects: This can lead to muscle weakness, chronic fatigue, neuropathy, and potentially cognitive decline, especially in cases of chronic, low-level exposure.”
“With impaired detoxification, when the liver cannot metabolize and remove chemicals, these substances can accumulate in the bloodstream, potentially leading to toxicity and damage to other organs. They can also be stored in fat tissues - lipophilic (fat-soluble) chemicals, in particular, tend to accumulate in adipose (fat) tissue while others may deposit in organs such as the kidneys, heart, lungs, or even the brain. This accumulation can lead to various health issues, as the body may struggle to eliminate these toxins, potentially resulting in organ damage or dysfunction over time.”
(Which explains why so many pilots and cabin crew have evidence from fat biopsies of many of the toxic chemicals used in aviation being in their bodies.)
In addition:
“Tri-ortho-cresyl phosphate (TOCP), one of the esters used in TCP, can directly inhibit acetylcholinesterase (AChE), an enzyme crucial for breaking down the neurotransmitter acetylcholine in the body. When AChE is inhibited, acetylcholine accumulates, leading to uncontrolled muscle spasms, paralysis, and potentially fatal respiratory issues.
TOCP, even in trace amounts, can be metabolized in the liver into more toxic compounds. One of the primary metabolites is di-ortho-cresyl phosphate (DOCP), which is also an inhibitor of acetylcholinesterase (AChE).
The metabolism of TOCP can lead to increased toxicity, as these metabolites can further disrupt normal cholinergic signaling and contribute to neurotoxic effects. This metabolic conversion is part of the reason why TOCP is considered hazardous and can lead to serious health issues, including organophosphate-induced neurotoxicity.
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide, also known as cresyl saligenin phosphate (CBDP) is another metabolite of tri-ortho-cresyl phosphate (TOCP). Like TOCP and di-ortho-cresyl phosphate (DOCP), CBDP is also known to inhibit acetylcholinesterase (AChE) which can lead to similar toxic effects.
The presence of these metabolites underscores the potential dangers of exposure to organophosphate compounds like TOCP, as they can lead to significant health risks through their metabolic products.”
The U.K. Government’s DWP prescription for Industrial Injuries Disablement from poisoning by phosphorus was changed again in 1992 as shown in this document, where Tricresyl and Triphenyl phosphate (and others with a similar mode of action) were removed altogether:
http://www.oprus2001.co.uk/pdc3.htm
So I asked AI ChatGPT -
Which category from this document (shown in the link above) would you put Tricresyl phosphate and those organophosphates with similar action in - Causative Agent 1,2,3 or 4?
And this is it’s response:
‘Based on the information provided in the document, tricresyl phosphate and similar organophosphate compounds would fall under Causative Agent 4, which pertains to organo-phosphorus pesticides. This category describes the harmful effects of organophosphorus compounds, including their action as anti-cholinesterase agents, which is relevant to the mechanism of action of many organophosphates, including tricresyl phosphate.
While tricresyl phosphate is not a pesticide in the traditional sense, it is an organophosphate and can exhibit similar toxicological effects, particularly in terms of cholinesterase inhibition. Therefore, it aligns with the characteristics outlined in Causative Agent 4.’
So I went back with “But tricresyl phosphate primarily inhibits BChE .”
And this is the reply:
‘You are correct that tricresyl phosphate (TCP) primarily inhibits butyrylcholinesterase (BChE) rather than acetylcholinesterase (AChE), which is the primary target of many organophosphate pesticides. However, both BChE and AChE are part of the cholinergic system, and inhibition of either can lead to similar toxicological effects.
In the context of the document you provided, while TCP may not fit perfectly into the category of organophosphorus pesticides (Causative Agent 4), it still shares characteristics with organophosphates in terms of its chemical structure and potential for toxicity. Therefore, it could be considered under the broader category of organophosphorus compounds, which includes various agents that can have neurotoxic effects.
If you are looking for a more precise classification, it may be worth noting that TCP could also be discussed in relation to Causative Agent 3 (Inorganic compounds of phosphorus other than phosphine) due to its chemical nature, but it is primarily recognized for its action as an organophosphate. Ultimately, the classification may depend on the specific context of exposure and the regulatory framework being applied.’
What happened with the prescription in the U.K. for Industrial Injuries Disablement is both incredible and absolutely scandalous.
This account of events was written by Richard Bruce, a former farmer, on the website he created in order to record and log as much information as possible, but also to help others who had been poisoned.
Richard was chronically poisoned by pesticides which also contained benzene, xylene and trichloroethane in the 1980’s and 1990’s as well as by a mix of pesticides which was illegal.
He has worked tirelessly in his efforts to expose this scandal caused by scientific experts over the years who worked within the U.K. Government.
Unfortunately, problem continues, because as those so called ‘experts’ who initiated and controlled the the scandal retired, new people took over and picked up where they left off.
http://www.oprus2001.co.uk/pdc3update.htm
This is the link to his website where you will see a link to the Organophosphorus file further down on the home page:
http://www.oprus2001.co.uk/index.htm
Aside from cholinesterase inhibition, here are some of the other pathways and mechanisms of illness & disease (injury) which can be caused by chemical formulations such as aircraft engine oils, hydraulic fluids (and pesticides and sheep dips) which include organophosphates as a part of the formula.
It’s important to understand that changes in the body happen in a progressive and insidious manner, (similar to cholinesterase inhibition) from repeated chronic (low level) exposures and can even occur following a single acute (high level) exposure such as a fume event onboard an aircraft:
Endocrine disruption:
Endocrine disrupting toxicity of aryl organophosphate esters and mode of action (2022 Review)
‘Aryl OPEs (AOPEs), which are widely used in industrial and consumer products, are regarded as emerging endocrine disruptors. Taking triphenyl phosphate, 2-ethyl-hexyl diphenyl phosphate, tricresyl phosphate, and isomers of mono-, di-, and tri-isopropylated triaryl phosphates as representative AOPEs, this article reviewed their endocrine disrupting toxicity, metabolic disrupting toxicity, and their underlying molecular mechanisms via various signaling pathways.
In general, AOPEs showed endocrine-disrupting effects by disrupting the hormone level and by behaving estrogen receptor, androgen receptor, mineralo-corticoid receptor, glucocorticoid receptor, and thyroid hormone receptor agonistic/antagonistic activity. AOPEs also exerted metabolic disrupting effects in the cardiovascular system and liver by disrupting the lipids hemostasis and by binding with liver X receptor and peroxisome proliferator-activated receptor c.’
Study (2020) - breast cancer from hormonal (estrogenic) effects in relation to exposure to Tricresyl Phosphate - which could help to explain the high incidence of breast cancer amongst airline crew.
Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways
‘Conclusions
In the present study, three TCP isomers, ToCP, TmCP and TpCP, showed antagonistic activities on ERα, and we demonstrated for the first time that they exerted estrogenic effects through GPER. They promoted MCF7 and SKBR3 breast cancer cells migration via GPER. As a biological counterpart, ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP only triggered GPER-mediated calcium mobilization. In molecular docking, ToCP interacted differently with GPER....’
https://www.sciencedirect.com/science/article/abs/pii/S0269749119370150?via%3Dihub
Study - 2020 Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism
Organophosphate esters (OPEs) can exhibit various toxicities including endocrine disruption activity. Unfortunately, the low-dose endocrine-disrupting effects mediated by estrogen receptors (ERs) are commonly underestimated for OPEs and their metabolites. Here, structure-oriented research was performed to investigate the estrogenic/antiestrogenic effect of 13 OPEs (including three metabolites) and the potential mechanism. All of the OPEs exerted antiestrogenic activities in both E-screen and MVLN assays. OPEs with bulky substituents, such as phenyl rings (triphenyl phosphate (TPP), tricresyl phosphate (TCP), diphenylphosphoryl chloride, and diphenylphosphite) or relatively long alkyl chains (dibutylbutylphosphonate (DBBP)), exerted relatively strong ER antagonism potency at micromolar concentrations. The established quantitative structure–activity relationship indicated that the antiestrogenic activities of the OPEs mainly depended on the volume, leading eigenvalue, and hydrophobicity of the molecule. Molecular docking revealed that the three OPEs with the bulkiest substituents on the phosphate ester group (TPP, TCP, and DBBP) have a similar interaction mode to the classical ER antagonist 4-hydroxytamoxifen. The correlation between the antiestrogenic activity and the corresponding ER binding affinity was statistically significant, strongly suggesting that the OPEs possess the classical antagonism mechanism of interfering with the positioning of helix 12 in the ER.
https://pubs.acs.org/doi/pdf/10.1021/acs.est.0c04376
Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs) (2021)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8365328/
Cardiac complications in endocrine diseases (2009)
HORMONES AND ENDOCRINE DISRUPTING CHEMICALS
WHAT YOU NEED TO KNOW - pdf from the Endocrine Society
Abstract - Eurotox 2005 Document
Page S29 - Number 56 -
TOXICOLOGICAL CONCERNS OF PESTICIDES
J. Kniewald
Laboratory of Toxicology, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, Croatia
‘Toxic residues from pesticides are found everywhere: in water systems, in animals, in the vast majority of human beings, even in that most sacred nectar—mother’s milk. The acute reactions to many pesticides are well documented, affecting the liver, kidneys, lungs, skin, eyes and brain. Long-term chronic effects on humans include a whole series of cancers, liver and kidney disfunction, sterility, neurological disorders and birth defects. Many developmental and reproductive disorders are caused by the complex interactions of multiple pesticides with our hormone systems. Pesticides, that take a long time to biodegra-date in the environment, accumulate in organisms as they move up the food chain. Humans, as top predators, can accumulate relatively high concentrations of pesticides through the food supply. New evidence indicates that proper functioning of the human body’s endocrine/hormone system can be severely altered by low-level cumulative pesticide exposure. This indicates that it can cause chronic reproductive, immunological and neurological disorders. Low-level exposure of unborn children to pesticides can affect a wide range of developmental processes, from reproductive system formation to brain function. The most common types of hormone disruption are hormone mimicking, hormone blocking or disturbing the production process of the hormones. As pesticide synergy exists, exposure to multiple pesticides may be thousands of times more potent in mimicking estrogen than it was previously thought. Does this mean that current tolerance levels (NOAEL, ADI, MRL) set for individual pesticide residues allowed in our food are, when combined, actually far above dangerous limits? What are the implications for the unborn, children and adolescents? How should the pesticides be substituted by application of modern biotechnological procedures? What are the alternatives?’
ZLATKO KNIEWALD
University of Zagreb, Department of Biochemical Engineering, Emeritus
Biochemical Engineering
Address: Croatia
https://unizg.academia.edu/ZLATKOKNIEWALD
(Professor Emeritus, PhD, MSc, dipl eng biotechnology.)
Oxidative stress:
Redox signaling and inflammatory statuses of farmers exposed to agrochemicals (2021)
https://periodicos.ufsm.br/cienciaenatura/article/download/44026/pdf/314885
Oxidative stress, inflammation, and cancer: How are they linked (2010)
‘Under a sustained environmental stress, ROS are produced over a long time, and thus significant damage may occur to cell structure and functions and may induce somatic mutations and neoplastic transformation [9, 10]. Indeed, cancer initiation and progression has been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation [11].’
https://pmc.ncbi.nlm.nih.gov/articles/PMC2990475/
IOS - Increased Oxidative Stress
Interview with Dr Thomas Levy:
‘The consistent common denominator of all diseases is the presence of IOS. And the lessening or resolution of that IOS is the key to the effective treatment of all disease. IOS is literally the single parameter that determines whether a cell or tissue is diseased. When no IOS is present, no disease is present. It’s that simple.’
‘What causes IOS? The answer is simple: toxins. Toxins are always pro-oxidant in their impact. They always, directly or indirectly, take electrons from biomolecules, either through a direct oxidation or by initiating one or more biochemical reactions that result in oxidation. Any free radical, pro-oxidant, or other molecule that produces an increase in oxidative stress is, by virtue of its activity, a toxin. In fact, the “toxicity” of a toxin is nothing more than the degree to which it can cause biomolecules to become oxidized and to remain so.’
Mitochondrial dysfunction:
Mitochondrial dysfunction and organophosphorus compounds (2013)
https://core.ac.uk/download/pdf/162006305.pdf
Oxidative Stress and Mitochondrial Injury in Chronic Multi symptom Conditions: From Gulf War Illness to Autism Spectrum Disorder (2012)
https://www.nature.com/articles/npre.2012.6847.1.pdf
The effects of organophosphate pesticides on mitochondria (2022)
‘Organophosphates (OPs) are an important class of toxic agents that are applied for controlling pests. Toxic effects of OPs have been found at concentrations below inhibition of acetylcholinesterase(AChE). OPs are able to cause damage in various tissues, leading to acute and chronic diseases. A limited number of OPs are able to directly bind to cholinesterases in the parent form. Mitochondria is the main target for adverse effects of OPs. Mitochondria has a main role in the toxicity of OPs by inducing reactive oxygen species production that plays as signaling molecules that is considered as a non-cholinergic mechanism of OPs toxicity. Redox signaling regulates proliferation, differentiation, and function in the cells. Several experimental studies have indicated that exposure to OPs causes oxidative stress due to mitochondrial dysfunction.’
https://www.sciencedirect.com/science/article/abs/pii/B9780323884624000249
Editorial: Mitochondrial Dynamics in Endocrine Physiology and Disease (2022)
‘The effects of altered mitochondrial dynamics in the nervous system and during neurodegeneration and aging have also been widely recognized. Areas of the brain that sense changes to hormonal and nutritional status can present altered mitochondria fission and fusion events. In a comprehensive literature review, Haigh et al. highlight how changes in mitochondrial dynamics trigger modifications in neuronal signaling, and alteration in the ability of the brain to modulate metabolic functions such as feeding behavior and blood glucose levels. In the brain, the dysregulation of mitochondrial dynamics affecting energy production, such as mutations in the mitochondrial DNA that alter the assembly of the respiratory chain, have been associated with the development of neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease, as presented here by Novack et al.’
https://pmc.ncbi.nlm.nih.gov/articles/PMC8889580/
HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy (2021)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8438325/
Coenzyme Q10 in the Treatment
of Mitochondrial Disease (2017)
Immune System Effects:
This document was translated by the U.K. Government’s Health and Safety Executive (HSE) in 1981 -
‘The data obtained permit the assumption that in chronic intoxication sufferers it is not a general immunodepression that is observed, but a T-immuno-deficiency condition associated with prolonged quantitative and functional suppression of the T-system of immunity and progressive autoimmunisation of the organism. The existence of a certain deficit in the immune system in turn requires a correction to this link in the chain, as was suggested previously in the literature (O. C. Alekseyeva, 1979 ).
This demonstrates that assessment of the state of the T- and B-systems of immunity may be usefully employed in cases of occupational diseases, particularly pesticide intoxications, for diagnostic purposes, and also to assist in developing methods of pathogenic therapy aimed at correcting the disturbed link in the immune system.’
http://www.oprus2001.co.uk/hseimmune.htm
Written in the 1992 publication by Bryan Ballantyne and Timothy C. Marrs:
‘Clinical and Experimental Toxicity of Organophosphates and Carbamates’:
"Studies show that antiChEs* at non-toxic, non-cholinergic doses can moderate the generation of immune responses. Suppression of immune function can increase host susceptibility to viral, bacterial and parasitic infections and increase the incidence of tumours, and possibly lengthen the course of an infection”.
“Perturbation of normal homoeostasis of the immune system may lead to deleterious side-effects that may not be observed until the facet of the immune system that was affected is required to defend the host from a foreign antigen.”
Genetic Damage/Cytotoxicity:
U.K. Government (DEFRA) Study
‘Prediction of susceptibility to long-term genotoxic effects of organophosphate pesticide exposure - (2003-2007)
Project Number- VM02301
Description
The project aims to:- investigate the extent, and inter-individual variations in the manifestation, of DNA damage by OPs of diverse chemical structures elucidate the mechanism(s) involved in the manifestation of the DNA damage determine inter-individual variations in capacity to repair the damage indicate the influence of metabolic capacity in balance with the individual’s ability to repair the DNA damage inherent to each OP These data will provide information which could be used by DEFRA for risk assessment of genotoxicity following chronic exposures to OPs. This research is directly relevant to DEFRA’s mission of protecting public interest in relation to environmental impacts.’
‘Conclusions and significance
The significance of increased oxidative DNA damage is difficult to predict for individual subjects, but it is likely that chronic exposure to pesticide mixtures, including OPs, can lead to cumulative cytogenetic effects. This is of great concern for pesticide operatives but also for the health of the general public, particularly susceptible groups such as children. This research strongly suggests that increased oxidative stress was pivotal to the DNA damage seen in the farmers, but several other mechanisms may also play a role depending on the exposure profile to the various OP chemical structures.
Since the populations monitored for DNA damage were small it is imperative to carry out further studies of chronically exposed individuals to ascertain the importance of this research.’
https://randd.defra.gov.uk/ProjectDetails?ProjectId=12337
Did the U.K. Government’s DEFRA carry out more research?
If they did, there’s no evidence of it.
Cytoxicity - Introductory Chapter:
https://www.intechopen.com/chapters/61438
Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers (2023):
https://pmc.ncbi.nlm.nih.gov/articles/PMC10186727/
Repeated exposure to low levels of fumes, dust or vapour from chemical substances/formulations containing organophosphates can cause multi-system dysfunctions within the human body via various pathways and mechanisms most of which which are interconnected.
The U.K. government’s scientific advisors at the Industrial Injuries Advice Council (IIAC), despite being informed of these pathways and mechanisms in 2023, have stated:
“There are currently no plans for IIAC to review the PD C3* prescription as organophosphate poisoning is not on its current work-program.”
*-PD C3 = Prescribed Disease C3.
This is the current membership of the IIAC.
https://www.gov.uk/government/organisations/industrial-injuries-advisory-council/about/membership
With regards to cabin crew (and this includes pilots):
2021 - IIAC
‘103. A question submitted in advance of the meeting was discussed:
is IIAC currently reviewing - or does it propose to review - evidence for a link between alleged long-term (chronic) or acute (‘fume event’) tricresyl phosphate inhalation and Prescribed Disease C3b?
104. The Chair stated that organophosphates had been looked at by the Council but not in cabin crew. Toxic air is a topic which the Council regularly monitors and, so far, no substantial evidence has emerged for this topic or occupation. The Chair agreed to take this up with the person who posed this question but stated there is insufficient evidence for Council to take this further at the moment.’
So, until the IIAC decide to add Prescribed Disease C3 (Poisoning by Organophosphates) to its work programme and investigate both the current and historical science on the issue of chronic (low level) repeated exposures as well as acute (high level) exposures such as those which occur during fume events onboard aircraft, from substances/formulations containing organophosphates (aircraft oil and hydraulic fluid) and re-instate the known harms which can be caused by organophosphates including tri-cresyl and tri-phenyl phosphate (and others like them), and ultimately makes the appropriate recommendations to the DWP in order for them to officially make the necessary changes, the current position and all that remains of the prescription for Industrial Injury Disablement Benefit via the DWP for those who are injured is shown in the link to the DWP handbook below.
So many cases of chronic poisoning by OP’s have been hidden away over the years, as they are prescribed as accidental via the DWP’s accident provision.
There is nothing accidental about poisoning by chemical mixtures containing OP’s.
The original intent for the production of organophosphorus chemicals was to cause harm. These chemicals are extremely toxic and it’s highly likely that there is increased toxicity because of the influence of other chemicals, particularly the solvents used (as shown in the HSE MS17 from 1980), as well as the effects from heating due to the high temperatures in the aircraft engines.
Being onboard aircraft with no filtration or monitoring systems in place and with no possible way of avoiding the fumes, is it any wonder that many crew have died at young ages and so many more are currently living with chronic injuries and diseases?
This DWP Handbook provides advice and guidance to the doctors contracted to the DWP from Maximus U.K. who make decisions on claims of injury, who have no idea about this type of poisoning and no up to date information or references on the subject and who also do not know the history on OP’s/formulations containing OP’s as this information has never been provided to healthcare professionals in the U.K.
See Pages 101-102 and read the absolute lies the DWP had audacity to publish for the current (2016) edition:
In particular- see 5.8.3. On page 102:
“There is no evidence to suggest that these effects occur with small cumulative exposures.”
I think sufficient evidence has been provided in this petition update alone, and there’s plenty more.
It’s important to remember that the people who sit on these government advisory committees and councils don’t work for us or for the protection of our health.
They are employed by the government for the benefit of the government as well as for industry. In fact, they work against us.
One member of the Industrial Injuries Advice Council has even advised a defendant (airline) involved in the U.K. litigation on aircraft cabin air which is due to go to court next year.
And if that is not a conflict of interests from a member of a supposed ‘independent’ committee, I don’t know what is.
This whole sorry saga is a scandal of epic proportions which I have only touched on in this update; and sadly, the vast majority of other countries are involved in this cover-up too.
We have been betrayed, not only by our governments and those behind the scenes running them, but by many within the scientific and medical communities who remain silent on this issue or who work for and lie on behalf of the chemical or aviation industries because money is their priority.
As for those who conduct research on behalf of those industries which show results of no adverse effects, and those who defend these industries in legal cases
- I have no words; well, certainly not words that could be published here.
But, there are some very good, highly intelligent and honest people within the scientific community who have been steadfast in their commitment to human health as well as their convictions and integrity; some of whom have been dragged through the mud because of it like Gilles Éric Séralini - a hero of our time.
I salute all of them.
The truth on this issue is going to come out and there will be no hiding place for those involved and those responsible when it does.
What a tangled web of deceit they wove, in the belief that no one would ever know or work out what they had done.
More can be read in this article by Stephen E. Mawdsley -
Burden of Proof: The Debate Surrounding Aerotoxic Syndrome (2022)
‘A lack of information about fume events meant that physicians were unprepared to help patients. Most physicians attending to pilots or flight attendants complaining of AS were uncertain about the cause or what tests to perform.48 According to physician Dr Chris Winder, even short-term exposure to toxic chemicals from jet engine lubricants may lead to a wide range of symptoms.49 Furthermore, clinical judgements may have been influenced by the airline industry. Physician Dr Mark Donohoe, who treated patients who believed they had AS, reported being approached by industry physicians and asked to reconsider his clinical diagnoses.50 Some researchers expressed concern that a corporate affiliation bias inspired industry physicians to challenge those who raised concerns.51 The combination of complex symptoms, a lack of diagnostic criteria and the potential for industry pressure appear to have limited wider clinical discussions.’
https://journals.sagepub.com/doi/full/10.1177/00220094221074819
Meanwhile, the aviation industry is still permitted to expose crew and passengers to toxic fumes onboard aircraft. Here are some of the recent fume events published on the Aviation Herald which I received this morning from Bearnairdine Beaumont who runs the ‘Unfiltered VIP’ website.
Bearnairdine was a Purser and Cabin Crew Trainer for Lufthansa. She was poisoned by toxic fumes onboard aircraft and from exposure to Permethrin, used in insecticide sprays onboard aircraft.
Incident: Swiss B773 near Singapore on May 4th 2025, smell in cockpit
https://avherald.com/h?article=52749d47&opt=0
Incident: Kalitta B772 near Detroit on May 6th 2025, smoke in cockpit
https://avherald.com/h?article=52773b5d&opt=0
Incident: Jet2 B738 near Luxembourg on May 3rd 2025, smoke on board
https://avherald.com/h?article=5273d4ed&opt=0
Incident: Easyjet Europe A21N at Milan on May 3rd 2025, smoke in cabin
https://avherald.com/h?article=5273c86a&opt=0
Incident: Vueling A320 at Barcelona on Apr 29th 2025, smoke in cabin
https://avherald.com/h?article=5271dd14&opt=0
Incident: Aeromexico E190 near Tampico on Apr 29th 2025, smoke in cockpit
https://avherald.com/h?article=527163f3&opt=0
I’ll finish with a man who was a visionary, way ahead of his time. He knew what happening in the late 1950’s and early 1960’s and could foresee what was coming:
LORD DOUGLAS OF BARLOCH
On Dangers From Toxic Chemicals - debated on Wednesday 20 March 1963 in The House of Lords:
‘The question which I think requires the most careful consideration is the effect of small quantities taken in year after year. The human body undoubtedly is provided with a very effective detoxifying apparatus in the liver. No doubt in most cases this is able to protect us against many of the poisons which are found in nature and to which men have been obliged to adapt themselves throughout the long course of evolutionary development. It would be very rash and unreasonable to expect that this bodily mechanism could always protect us against novel and extremely powerful poisons to which human beings had never before been exposed. Even if our bodies can deal with these things to some extent, the day may arrive when the strain thrown upon the liver proves to be too much and the protection which we have hitherto enjoyed ceases. What happens then?
There is already ground for the conclusion that the pattern of human illness is changing. The infectious diseases have in many cases yielded to sanitation and better conditions of living, but other diseases, such as cancer, and diseases affecting the blood, the marrow and the cells have become more prevalent. Many of them are of slow onset and cannot clearly be identified with any specific cause. Therefore we must be extremely careful. It is very unwise to assume that anything is safe unless there is conclusive proof.
We have had an example recently in the case of the drug thalidomide which has brought this fact home to most people, and it is worth recalling that the manufacturers in the United States distributed large quantities of these pills to some 1,400 doctors upon an experimental basis. None of these doctors apparently made any adverse report. This is a case where the adverse effects manifested themselves fairly quickly. How much more difficult are the cases in which the ill-effects develop only after many years? Cancer, as we all know, is one of those diseases which may be caused by radiation or by many different chemicals in very small doses.
On these grounds, my Lords, I consider it established beyond doubt that the human environment should be protected against all chemicals unless they are proved to be non-toxic, and that a constant watch should be kept on the food supply to ensure that it does not contain residues of agricultural pesticides or other poisons.
You can read the full debate here:
For further information on Aerotoxic Syndrome, useful medical information, testimonies from victims, Aerotoxic legal cases and much more - please visit:
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