Most OPs are readily translocated in living organisms.
Many have the ability to travel to every cell in the body. Hence their usefulness in parasite control where application to an animal will result in both internal and external parasites being killed.
Some have greater residual properties than others, therefore bestowing the treated animal with weeks of protection.
Some are lipophilic and are thus attracted to and maybe temporarily stored in lipids which are found more in some cells than others, e.g. lipid-rich brain cells. Lipids are also found in the structure of membranes sometimes as phospholipids, which also happen to use the enzyme cholinesterase, which is known to be affected by OPs. [Back to Top]
ORGANO PHOSPHATE BREAKDOWN
OPs are considered to break down relatively quickly, providing insect-killing properties which do not leave long term residues.
OPs break down through a process of phosphorylation, oxidative phosphorylation, alkylation, and, for methylated OPs, methylation.
All these chemical breakdown processes are utilised at a molecular level to provide energy.
Phosphorylation is employed to fuel the signalling process on membrane surfaces.
Oxidative phosphorylation is the energy which drives the powerhouses of the cells, the mitochondria. [Or so the story goes-RW...] The enzyme cyclic AMP is almost ubiquitously used for its oxidative phosphorylating processes in transcription and reception for the hormone and immune system, both within the cell and on its outer surface.
Methylation is the fuel employed by the DNA in the cell nucleus in the transcription and reception of mRNA, which are sent as signals or instructions including those for hormones and the immune system.
There are further reactions of importance also fuelled by OPs such as alkylation.
Thus in their very process of breaking down OPs can provide an unnatural extra fuel to essential molecular reactions. [Back to Top]
THE EFFECTS OF ORGANO PHOSPHATES ARE CUMULATIVE
A short burst of the energy provided by OP exposure should be quickly and easily burnt up, as long as the exposure does not constitute an overdose or a lethal dose.
Compounds which break down quickly obviously would have different properties to those which are stored and broken-down more slowly. Although slower breakdown may avoid acute effects it may add to risks from re-exposure and have synergistic effects on other treatments.
Re-exposure and sustained low-level exposure effectively provide continuous low level added intracellular energy. Which must result in stress to the systems involved, distress if sustained, with eventual burn out if there is no respite.
Commercial preparations of OPs contain additives, such as dispersal solvents, adjuvants, and, when applied externally, wetters and surfactants to stick to the coat and penetrate the epidermis. All of these compounds have their own toxicological effect. [Back to Top]
Every animal is equipped with a complex system of fail-safes and barriers, which are designed to sift out and protect from toxins and unnatural compounds.
Toxins that are ingested will initially need to pass barriers in the gut. However OPs provide fuel, the raw constituents of which are provided from what we eat. The extent to which the gut is able to break down OPs, and the fact that they contain basic constituents for fuelling cellular activity which travel on to be used by bodily systems, should be considered and understood.
Toxins applied to the skin must pass the epidermis, yet we know from the commercial uses and applications of OPs these can very efficiently travel through the skin.
The liver can be an efficient filter as long as it is not damaged, or becomes damaged through intermittent assault and chronic overload.
Membranes are another barrier, not only around cells, in varying degrees of speciality but around organs, creating for example the blood brain barrier, or the myelin sheath. Yet a cell's thirst for the energy that OPs can provide may well override the membrane barriers. In fact at membrane level they my be used and broken down, incorporated and stored for later use or passed through to the internal cell for use.
Within the cell trace elements and minerals are utilised in further detoxification processes, but these resources may be deficient, or the cell's ability to utilise them damaged.
Finally, should OPs reach the nucleus membrane their fuel is still of use, and hence has a passport to enter the very heart of cellular knowledge and instruction. Hence the attribution of some OPs to be mutagenic and teratogenic. [Back to Top]
RESEARCH INTO ORGANO PHOSPHATES
Existing research into the toxicological effects of OPs is extensive and has been internationally accumulating for nearly a century. It reveals broad-ranging damage can occur to neurological, immunological, and endocrine systems. OPs can invoke gastric, cardiac, respiratory malfunctions and allergic response.
As scientific research techniques improve greater and more accurate knowledge of these effects have been recorded.
Although recorded extensively in research journals there is a lack of application to the actual situation. For example Chronic Fatigue Syndrome [CFS] is exactly the collection of symptoms one would expect from chronic exposure to OPs and mirrors much of what is listed in Health and Safety document MS17. Yet it has taken years to obtain any acceptance that this condition could be associated with OP poisoning, even when those exhibiting the syndrome have recorded excessive exposures.
When OP poisoning is not diagnosed and exposure continues, the whole system becomes stressed, and which functions and organs become affected, will be dependant on the compounds exposed to, and the other synergists present in the environment.
These include ALL treatment exposures. This is a statement published by WHO in the book Organophosphorus pesticides: A General Introduction Ref. 6.2.3 Effects on the immune system. In a review by Zackov (1983) it was stated that "most â€¦ organophosphorus pesticides elicit autoimmune reactions and suppress antibodies against vaccines"
Past illnesses or toxicological damage which may have previously weakened specific organs or functions will naturally exhibit heightened stress and malfunction. As will the complex genetic strengths and weaknesses we inherit which make us all individual and creates our species strength through its complex genetic diversity.
This is particularly pertinent when considering recent generations exposure to OPs when initially developing in the womb. Foetal exposure to OPs is recorded to cause sometimes gross mutagenic effect, and occasionally teratogenic effects. Yet subtle intracellular weakness created by OPs at initial development may create pathways to disease susceptibility in life particularly when the initiating toxins are present. [Back to Top]
A need for adequate surveillance.
A proper and adequate independent surveillance system for both humans and animals should exist. The same organisation as passes the products fit for use should not investigate adverse reactions and illness claimed to emanate from those products.
This is as essential for animals as it is for humans, we can learn a great deal from the animal experience. Animals are a living experiment in a real-life, not controlled laboratory situation, with a shorter life span. I recommend to you as I have to others a surveillance tool devised by Mrs Wolferstan FRCVS, to collate and interpret veterinary and farm husbandry and health on farms. It is my belief a tool such as this should be applied as part of post-licensing surveillance of products.
Inadequate surveillance of human adverse reactions was confirmed in the COT [Committee on Toxicology] report by the fact that it stated it could gain no meaningful data from the existing surveillance systems. I can only remind this workshop again of the recommendation of the 5th Agricultural Select Committee in 1995 that 'Human surveillance should be removed from the VMD. [Veterinary Medicines Directorate] This responsibility should be carried out instead by an independent research institute or university department.'
I wrote extensively to the COT working group with regard to the essential need of our modern day ever-increasingly toxic environment, for this as a fundamental medical right, and of the useful information and knowledge that could flow from such centres to the medical communities, which may lead to better treatments and awareness of dangers. [Back to Top]
Distribution and use of existing research knowledge
The book Clinical and Experimental Toxicology of Organophosphates and Carbamates by Ballantyne and Marrs should be reprinted and placed in all medical libraries, it is to my knowledge the finest collection of research into the effects of OPs. Its contents should be observed by specialists in the areas documented, and it should be discussed in the education of our aspiring doctors and vets.
I am most anxious that public money is not wasted on further research into areas which already abound with published evidence. COT has considered effects to the neurological system but a serious and comprehensive review of the available literature on OP effects on the hormone, immune, and enzyme systems should be undertaken, with the view that OPs may be causative and or exacerbating agents to identified illnesses.
With regard to the transmissible diseases such as spongiform encephalopathies particular note should be taken of the circumstances under which they initially emanate. There may be one of a number of toxicologically induced neurological diseases which become transmissible by passing certain tissues in certain pharmaceutical preparations. This area does require investigation, as does the situation quoted earlierâ€¦ Effects on the immune system. In a review by Zackov (1983) it was stated that "most â€¦ organophosphorus pesticides elicit autoimmune reactions and suppress antibodies against vaccines" Again I remind the workshop of the importance of the above statement with regard to the animal situation, particularly when animal tissues are sourced for pharmaceuticals. This area should be fully discussed with relationship to Transmissible Spongiform Encephalopathies and ongoing research. [Back to Top]