Comments on the COT Report on Organophosphates

Part 2. The next 6 comments on the COT Report and the replies.

30th November 1999, the reply of 24th January 2000 and the reponses of 25th January 2000

7. How can the Group deny knowledge of the dangers of OP exposure to mechanisms other than the cholinesterase system when they use levels of Creatine to measure exposure? Table 4.4
Creatine levels are used to determine exposure to solvents a but it is also known that creatine plays a major role in the energy transfer system and that OPs can corrupt that system. It was quite wrong of the group to ignore this risk, particularly as phosphocreatine acts as a store of energy in muscles and nerve cells by phosphorylating ADP back to ATP, producing creatine. In the 1980s it was found that a third of cancers b could be attributed to deformed human Ras genes and G-proteins are a similar protein group which link up with molecules called guanosine and are part of the cells internal signalling system.
Creatine is one of two guanidine proteins known in the 1950s c as "amino-acid derivatives of great physiological interest". Arginine was the other amino-acid named at the time and creatine is now known to be a "derivative of arginine, glycine and methionine, reversibly phosphorylated to phosphocreatine, which transfers its phosphate to ADP via the enzyme creatine kinase." d
Guanine and guanosine are linked to GTP which in turn is involved with adenylate cyclase and ATP / cAMP in hormones, RNA / DNA and protein synthesis. Cyclic GMP is guanosine monophosphate, a second messenger formed from GTP, which activates G-kinase and is involved in both visual and olfactory systems. Rhodopsin and the cascade mechanisms are involved with cGMP in colour vision, which is also altered by OPs, and cGMP is also involved with neurotransmission which includes the admitted damage to the acetylcholinesterase system. Phosphates act as on/off switches b in command chains which involve Ras proteins which in turn are also involved in handling stress. The Working Group should have been aware of these links which were known long before their investigation into OPs was begun.
Reply
Table 4.4 refers to creatinine not creatine. The creatinine is used to standardise the urine measurements with regard to urine concentration, and not to measure exposure which is based on the urinary metabolite levels.
Furthermore the Group did recognise that there were a number of other potential mechanisms in addition to cholinesterase inhibition.
Response
Point 7. If you intend attempts at confusion you should first ensure that the victim is ignorant of the facts.
Creatinine as you very well know is the urinary excretion of the breakdown product of creatine.
Whilst the Working Group made brief reference to potential mechanisms of toxicity other than that of anticholinesterase action it failed in its duty to the citizens of this country by ignoring them completely as a cause for concern despite the obvious links with currently increasing human health problems.
The COT should be reminded that it is those increasing problems which are currently crippling the NHS.

8. Why did the Group dismiss the action of the co-formulants so lightly when many of them are neurotoxic in their own right? 4.10 Their true actions on the human body when used in commercial OP formulations is not known. Benzene derivatives in combinatin with OPs are likely to present the most risk to human health due to the fact that benzene forms cholesterol which in turn forms all the major hormones. In addition benzene, xylene and toluene, the common co-formulants, are all known to be direct CNS toxins, respiratory depressants and sensitisers. Benzene and its derivatives have long been known to be carcinogenic, are linked to leukaemia, and are stored in the bone marrow for long periods of time. Furthermore, as I explained to one of the Group in a telephone conversation, this is acknowledged, as is OP long-term damage, in Government papers. To avoid this issue is to avoid what MS17 has long admitted to be the major cause of the symptoms experienced by OP victims. It also conveniently avoided the need to explain the observed persistence of chemicals claimed to have a short active life 4.3 despite evidence to the contrary held by Government departments p128 19/08/99 - including 10 Downing Street.
This is clearly an area which has not been adequately researched and requires urgent attention both for individual formulations and for commonly experienced combination exposures.
Reply
The Group gave detailed consideration to the co-formulants used in veterinary medicines and pesticide products and felt that interactions would not be likely to cause significant neurotoxic effects through known mechanisms of toxicity.
Xylene and toluene only produce CNS effects at relatively high exposure levels and are not sensitisers. There is no reason to believe that they will interact with effects of OPs due to cholinesterase inhibition. The benzene content in the aliphatic or aromatic hydrocarbon solvent will be minimal.
Response
Point 8. See point 6. MS17 states that the solvents considerably encourage symptom development.
The DoH publication pesticide poisoning 1996 states that doctors should pay careful attention to all the pesticides (and their solvents) and Industrial Injury papers list the risks from Benzene and its homologues toluene and xylene for which creatinine is also the exposure indicator. On their own they are dangerous but I suggest that their actions are enhanced when formulated with OP compounds which is why they are used.
The recognised dangers have been intimated to me in correspondence with the PSD but I suggest that you read the information provided by Government and review your comments. Reports such as narcotic, irritant , anaesthetic action, bone disease, alcohol intolerance, respiratory depression, loss of memory, irritability, ringing in the ears, CNS poison, allergic effects and cyanosis, with liquids and vapours being more readily absorbed than solids, particularly from splashed clothing, hardly support your view that there are no effects other than cholinesterase inhibition. Alkyl benzenes are often the only other ingredients with toxic potential declared on the labels by the manufacturers and I suspect the content is greater than you indicate.

9. The Group must explain what the implications of their work will be in the field. They suggest that "The evidence relating to chronic low-level exposure to OPs, insufficient to cause acute toxicity, is less convincing"8.10 Are they suggesting that past governments which issued documents warning of the dangers were wrong or misinformed?
Are they suggesting that there is no real need for limits on exposure such as ADI, MRL and OEL legal limits which were introduced to limit just such exposures?
Are they suggesting that the COSHH Regulations should be withdrawn because there is no risk? Those Regulations may not be enforced by the HSE but in theory at least the law recognises the danger from OPs as a particular concern.
Now that we once again have a Government financed paper claiming that the risks are small will employers take even more risks with the health of their workers and the general public? This is a dangerous signal and I suspect that there will be more cases similar to our local Boswell Case e as a result.
Reply
The Working Group clearly recognised that exposure to OPs can produce acute toxicity (this is not an issue on which they were asked to comment) and furthermore that long term neurotoxic effects may occur following episodes of acute exposure. The report does not alter the current position with regard to regulatory controls and ADIs, MRLs, OELs etc for specific OPs. These are set following an assessment of specific OPs on a case by case basis. They did find the scientific evidence for chronic effects following low dose exposure (insufficient to cause overt acute toxicity) less convincing, but they recommended that further research be carried out to address some outstanding issues.
Response
Point 9. It is clear that the safety levels set for some of the more commonly used OPs are based on false information regarding half-life and toxic action, the latter a direct result of ignoring all other toxic mechanisms aside from the anticholinesterase action. For example the potential to mutate bacteria, damage reproduction capability, inhibit essential enzyme and DNA production and therefore the carcinogenic risks.
The human health effects indicate that the research is currently under way using the population as the test animals. If you doubt this read the DoH Pesticide Poisoning handbook sent to GPs and in the section on glyphosate you will see that, apart from the false claim that this OP does not have anticholinesterase properties, the change in surfactants has "inadequate human experience to verify" safety.

10. Did those who wrote this report take on board any of the information they were sent by those who had suffered from OP poisoning?
They obviously ignored my own submissions despite the time taken and the detail offered. They ignored Government documents. They ignored the views of those I know who gave evidence both in person and in writing. Perhaps it was their decision to limit their investigation to the nervous system effects which allowed them to avoid these issues but that was not their brief. They were asked if "prolonged or repeated low-level exposure to OPs could lead to chronic ill-health effects" 1.1
Clearly the evidence is plain that such exposures to a cumulative and irreversible poison do just that and the recognition of PDC3 a is proof enough, especially when we realise that NTE has never been isolated f, its action not fully understood and that OPs which fail to inhibit its action in hens have actually been found to induce OPIDN in man.
Similar end results may follow from the other recogised reactions.
They answer the question in the text. "5.21 In summary, there are various putative mechanisms whereby long-term toxic effects could follow acute cholinergic episodes. These mechanisms may explain why adverse effects may be seen a long time after acetylcholinesterase levels have returned to normal.
Mechanisms that could lead to irreversible damage to nerves and muscle fibres include organophosphorylation of proteases and other esterases, muscle fasciculation, necrosis and anoxia."
and on page 91, 8.2 "In the course of the work it became apparent that the large majority of the relevant scientific evidence concerned neurological, psychological or psychiatric health effects.
In addition, these were the types of illness most frequently attributed to OP exposure by those who made written or oral submissions to the Working Group. Although the evidence on other possible class effects of OPs was sparse, to address it satisfactory would have required additional expertise that was not represented in the Working Group and additional time which would have delayed significantly the completion of this report. A decision was made, therefore, to concentrate upon health effects in the nervous system."

As is so often found when health effects might harm the profitability of industry the "Nelsonís Eye" approach is hard at work. They know where to look for the evidence but if they see it they must act and so they refuse to see the obvious.
Nelson was a wise man. He knew that to follow his orders would have resulted in disaster. His was just a small local skirmish and his actions proved to be justified.
The Working Group has turned a blind eye to the cause of a growing health problem across the country.
Failing to address the issues in the past has brought us to this terrible impasse while the well-being of current and future generations is put at risk. We must act now before it is too late.
Reply
The Group gave consideration to all the evidence provided, both in submissions and in the scientific literature (see also answers to point 3 regarding data from individual sufferers and point 1 regarding concentrating on neurotoxicity).
,b>Response
Point 10. Considering the evidence is not the same as including the evidence in the published opinion. It is clear that the evidence provided by victims was dismissed by the Working Group as unsupportable in the full knowledge that the DoH and other Government departments have conspired together to ensure that the evidence which will support submissions from victims has become "unavailable". Clearly even the scientific literature supporting the views of those victims was also considered and rejected.

11. Why did Ministers allow the chairman of COT to chair the Working Party when it is clear to us all that COT are part of the problem? I now see why they refused to list their chemical company links.g
Reply
Members of the COT Working Group were covered by the same code of conduct with regard to declaration of interests as the COT itself. None of the Working Group members had personal interest, but one of the COT (named) did and he was excluded from the discussion of this when the COT endorsed the report. Three members of the Working Group declared non-personal non-specific interests.
Details are given in Appendix 9 and 10.
Response
Point 11. Since many of the Working Group were COT members I find it difficult to see how they would not have had a personal interest in hiding the terrible truth that they had allowed such chemicals into our food.
Simply because a member leaves a debate does not mean that his influence leaves with him and it is clear from information given to me that members also have links with several OP manufacturers.

12. Why did Ministers permit members of the COT committee to work with him when they have obviously had to review some of their own work as indicated in the list of members and the papers listed for reference. 47,230,235,237,239,240 Clearly it is difficult to find qualified scientists who are not connected in some way to the chemical companies, and I suspect that this may be the reason, but it is becoming increasingly obvious that the relationship between members of many vital committees to these companies may be of considerable importance when we attempt to discover why the current situation has arisen. Similar problems present in GM technology and with the OP chemicals to which crops are resistant.
The Group have even failed to properly address the chosen toxic action on the nervous system by refusing to include those made seriously ill by the chemicals.
This is another fatal blow to the credibility of the document for which we have waited so long.
Reply
The suggestions that experts should have been excluded from the Working Group if they had published work in this area, which was cited in the Report, is unreasonable. The criteria for selection was that the individuals were recognised experts in appropriate fields and were not members of the Medical and Scientific Panel of the VPC at that time. The Group thus provided a fresh look by independent scientists at the area. It is pertinent that none had been involved in the 28 epidemiology studies that were considered most informative to the remit of the group.
Response
Point 12. You cannot claim that individuals who reviewed their own work were taking a "fresh look" at the information. Nor can you claim independence when there are commercial links either through research or other means.Again you dismiss the concerns by referring only to the information you consider to be important.

Further comment follows the references.

References.

p Page number in the COT Report
1.1 Numbers represent numbered paragraphs as published in the COT Report.

a Notes on the Diagnosis of Prescribed Diseases Dept of Social Security 1992
b New Scientist 27/5/1995 "Just obeying orders" Stephen Day.
c Encyclopaedia Britannica 1959 edition.
d Penguin Dictionary of Biology. Thain and Hickman1996
e HSE prosecution of former Government advisor for illegal pesticide use resulting in food contamination with illegal types and levels of pesticides. Injuries to human health, with evidence, were ignored.
f Mechanisms of Joint Neurotoxicity of n-Hexane, Methyl Isobutyl Keytoneand O-Ethyl O-4-Nitrophenyl Phenylphosphonothiate in Hens. Abou-Donia et al 1991
g Letter to PSD 11th May 1999.

The weak have one weapon : The errors of those who think they are strong.
Georges Bidault (1899-1983)

Reply
Finally, I am sorry that you were so clearly disappointed with the content of the Report. I hope that my comments have gone some way to reassuring you that the Working Group did approach its task thoroughly and considered all the available scientific data. The Group realised that the information available was incomplete and made recommendations for research in a number of areas. These are now being considered by Government.
Response
I consider the report to be simply another step in the face-saving exercise currently under way in the various ministries involved. Contrary to your view I was not disappointed by it as it fulfilled my predictions to the letter and gave us the opportunity to see into the reasons why such reports are produced by Government.
Had the COT accepted the information given freely to them by those of us attempting to protect our children then there would be no need for costly further research.
Research for which I am sure the financial backers demand their preferred results.

Dated 16/9/2000

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