The hunt for Tricresylphosphate (TCP)

Preliminary Remarks

Advances in medicine and toxicology are constantly progressing. All the same, there are chemical combinations for which nothing is known for certain. For example regarding the so-called "hit and run" substances. These are chemical and/or biological substances which, once they have entered the human body, cause damage and then dissolve: often without a trace. Especially when some time has passed.

In 2020, such a situation was once again on everyone's lips worldwide when well-known Russian opposition politician Alexei NAVALNY was poisoned on a tour to Siberia. He was taken to a hospital in Omsk, where the doctors, according to their official statements could not find anything except a "metabolic disorder"; with international support he was then flown to the Berlin Charité, where he is lying in a coma. On day 3 after the incident Berlin could no longer say what happened, because also (nerve) poisons such as Sarin or Novichok cover their tracks: "hit and run".

This is what we will be discussing in the following. Because the chemical and biochemical processes are complicated and involve many technical terms, everything will be explained in a simplified but nevertheless correct way. The same applies to the resulting problems for those who are affected by them.

How TCP can attack the vital survival mechanism and cause considerable damage is first explained by means of a graphic illustration:

TCP and acetylcholinesterase:
How the vital muscle-nerve mechanism works and can be inhibited

This entire presentation is part of the Fume-Event-Files and can be accessed directly at www.ansTageslicht.de/Tricresylphosphate.

Severe, even dramatic fume events in airplanes happen regularly. We know this from many reports. Even if they only reflect a small part of the actual "incidents" because of so-called "underreporting" - as with many other problems: you only see the tip of the iceberg (see ADRIAENSEN 2019).

We do not know exactly which pollutants or in what quantities they enter the cockpit and/or cabin, at least not from measurements. We only know from experiments (e.g. the EASA-AVOIL study) which substances can be produced by pyrolysis, i.e. at elevated temperatures through decomposition processes of chemical and biological substances: 127 substances, most of whose effects are still unknown, and which, when a fume event occurs, mainly enter the human organism via the lungs.

Because no such event (fume event) has ever been measured, we do not know anything precise - not about the number of chemical substances and their composition, nor anything about the strength of the individual substances (dose). There is little interest in real knowledge on the part of the aviation industry. Or even: zero interest. Because nothing happens (more at An uncovering of tricks, methods and strategies, how to downplay fume events).

All measurements that have been used by industry (manufacturers, airlines, trade associations) as arguments on the legal battlefield are measurements taken on flights on which such incidents have not occurred. Between 60 and 120 flights are/were recorded with measurements taken within the framework of research projects. With a frequency of 1 incident per 2,000 flights - a frequency which is conceded by the airlines themselves - such field research has got to be negative according to the probability calculation. According to the average statistical frequency distribution, 2,000 flights would have to be measured. If you are 'lucky', a little less, if you are unlucky, correspondingly more.

This is exactly what has not yet happened. Although there would be a comparatively straightforward procedure to use to get by with far fewer flights. But this would have to be sufficiently discussed from an ethical point of view, which will not happen in this context.

Since there is no usable data that could reflect such a fume event in a measurable form, measurements can only be taken afterwards, i.e. after landing and the corresponding time periods on the way to a hospital. This is where the human biomonitoring (HBM) comes into play. It is designed for such cases: you look retrospectively at what has been accumulated via inhaled substances in the human body, or what has been "metabolised" in the meantime.

Metabolism: certain chemical substances ("substrates") are converted into metabolites in the organism. By means of such processes innumerable functions are controlled, e.g. in the human body (see the diagram above).

Metabolism can also be a useful defence mechanism, for example when the body is confronted with substances that are harmful to it. It then tries to process these foreign substances by means of metabolism, i.e. to break them down into other substances that are less dangerous or better: harmless. This process is usually associated with an increase in the water solubility of the pollutants so that they can be excreted via the kidneys (urine).

This does not always work. With alcohol, it works quite well, but only for limited periods of time, as long as the quantity to be processed is not excessive and the processing organ (in this case the liver) is still in tact. In the case of alcohol poisoning, the defence mechanism fails. The same applies in the case of poisoning (e.g. snake bite or synthetic toxins, such as nerve poisons), if the substances are too toxic (too toxic in effect) or simply too large in quantity; the body can become overwhelmed. Because every person - psychologically, mentally and genetically speaking - is built and functions differently (polymorphisms), it works better/faster for one person, but different for another. 

Summary: If one knows the metabolisation process and can identify and also quantitatively measure the newly created substance(s), such an indicator ("marker") can be used to draw conclusions about the initial substance. But only then.

Such subsequent measurements can be made in this "biological material":

• Blood and/or
• Urine

According to the German "Occupational Medicine Rules" (AMR 6.2, point 3.4, no. 5, first sentence), such analyses are officially considered to be a substitute for measurements in the air. The problem here is that the pollutants or their metabolites gradually degrade: on the one hand, the rate of degradation varies from substance to substance, on the other hand, this happens individually in one person somewhat faster (as with alcohol), in another somewhat longer. If you wait too long, you cannot detect anything: Because either everything has been broken down and/or excreted.

This is what is meant by "scienticic discussion":

For the German Statutory Accident Insurance (DGUV), which is the umbrella organisation for all „Berufsgenossenschaften“ (BG = employer’s liability insurer associations), scientists working in the institutes are financed and organised by the DGUV (e.g. IPA-Institute) on the one hand, and on the other hand, the vast majority of occupational physicians at German universities are also in their service by being awarded research contracts and/or by appearances as experts in court. This concerns the vast majority of German occupational physicians. We have dealt with this shadowy realm, a nationwide scientific cartel, which is unknown to the public (more at www.ansTageslicht.de/DGUV - only in German language available).

One can therefore speak of directly or indirectly industry-funded science and research, just as it has become commonplace in the decades of scientific debate on tobacco or asbestos. Only very few scientists or occupational physicians escape this lucrative mainstream and do not work for or on behalf of the aviation industry - it concerns the representatives of independent science and research.

There are several reasons why the focus was primarily on TCP. For one, toxicity indicators were placed on all oil cans (turbine oil) throughout the years. Since the TCP has come into the media public eye, manufacturers have banned such indications in their "Safety Data Sheets". On the other hand, some media have mainly reported on this chemical additive, which is added to synthetic turbine oils (1-5%) to prevent the oils from evaporating immediately at high temperatures (up to 500 degrees Celsius) and the turbine shafts from overheating.

It has been known for a long time that this chemical is highly toxic. In the 1930s, widespread cases of poisoning ocurred (e.g. the "ginger palsy" case, in which around 20,000 people suffered lasting damage). In 1958, the first comprehensive toxicological standard work on TCP was published  (abridged version by HENSCHLER - in German language).

Gradually, the knowledge was expanded in some areas. For example, there are no metabolites of the toxic TCP or ToCP in the human organism. In other words, one can not detect TCP (more precisely: ToCP, see above graph) to which one was exposed (CASIDA 1961).

TCP metabolites have so far only been detectable in animals. For example, in rats that had been given TCP orally (by drinking) (KUREBAYASHI 1985). However, this concerned a) only the (non-toxic) starting substance tri-p-cresyl phosphate (in the TCP triangle above, bottom right) and b) its metabolite p-hydroxybenzoic acid, DCP and p-cresyl-p-carboxyphenyl phosphate. So completely different substances.

These detection methods cannot be transferred to humans without further ado; on the one hand, the human organism functions somewhat differently than that of a rat, and on the other hand the toxin is not usually consumed. When it appears in an airplane, it is absorbed through the lungs, and this metabolic process might work differently than if the toxin were to pass through the digestive tract. The effect of the toxin when absorbed through the lungs is much stronger than if it were absorbed through the gastrointestinal tract.

For a long time after that, there was little new evidence - TCP was considered toxic and everyone knew that, so there was not really any reason to continue research on it.

One person experimented and did research nevertheless: a professor of pharmacology and cancer biology and neurobiology - at the same time an expert in the field of toxicology at the University Medical Institute in Durham, North Carolina. Since the beginning of the 1980s, Prof. ABOU-DONIA has been investigating chemical and poisoning induced neurological damage in animals and humans. In particular damage caused by organic phosphates.

In this context he also made a name for himself in connection with the so-called Gulf War Syndrome: combined effects of drugs and pesticides used simultaneously to protect soldiers (e.g. permethrin or chlorpyrifos) have a synergistic neurotoxic effect; findings which were later confirmed by other scientists. Also in his view: toxins based on organophosphates. Then the road to tricresyl phosphate was not far away.

ABOU-DONIA examined rats, fed them TCP and analysed a) how long it took, b) via which excretion routes, c) which substances or metabolites had left the animal body again and what could be measured from them. His results, published in 1990:

1. ToCP could not be detected in urine or faeces.
2. The metabolites that were found were completely different substances that had little to do with TCP. In other words: TCP cannot be reconstructed in this way.

In 2003, his major study on the health effects on humans: organophosphate-based substances (which include pesticides) trigger 3 actions.

• First, they irreversibly inhibit the vital enzyme acetylcholinesterase (AChE). As a result, the neurotransmitter ACh is no longer broken down and acts excessively in all organs.
• Secondly, multiple exposure to TCP can lead to neurotoxic damage known as "Organophosphorus ester-induced delayed neurotoxicity (OPIDN)" - damage to health that (can) occur with a delay.
• And thirdly, acute exposure to high doses of TCP as well as long-term, low-level exposure can cause chronic neurotoxic symptoms: "Organophosphorus ester-induced chronic neurotoxicity (OPICN)".

At the turn of the millennium, the media in countries with lively air traffic (USA, Australia, UK worldwide) reported more and more frequently on incidents for which the term "fume event" had become established.

In Germany, a Lufthansa pilot, who had been involved in 50 such fume events by 2008, tried to address this problem internally, but failed - the airline had no interest in addressing the whistleblower ("internal whistleblowing"). In 2007, contractual arrangements between the Australian airline Ansett and the British manufacturer BAE in 1993 became known in Australia, according to which BAE had agreed to pay damages if Australian aircrew had successfully sued in court for damage to health. In the USA, Boeing took action: It developed a different fresh air system in connection with its new Boeing 787 ("Dreamliner"), where air is no longer tapped via the turbines ("bleed air") but on the fuselage ("ram air"). The new aircraft was commissioned in 2011.

In Germany, the subject of "Poison in Aircraft?" became a matter of broad public interest from the beginning of 2009 through several television reports, including those of WDR. The professional associations spoke internally of a "media campaign". The focus of the reporting was on the health damage to those affected and the wipe and air samples taken by the editors containing the poison TCP as journalistic evidence (the chronology of all this can be found at Contaminated Cabin Air: a health problem becomes certainty).

2009 was also the year in which Birgit K. SCHINDLER, a chemistry student at the University of Erlangen, worked on her dissertation: not in the field of chemistry, but in occupational medicine at "IPASUM", the "Institute and Polyclinic for Occupational, Social and Environmental Medicine", whose director still is, Prof. Hans DREXLER. The IPASUM is considered the number 1 in the social ranking of all chairs of occupational medicine, because at the end of the 1960s, occupational medicine was founded there in Germany: the so-called Erlangen VALENTIN School (more on this at www.ansTageslicht.de/Valentin). SCHINDLER's topic: flame retardants or the determination of analytical methods for their determination "in human body fluids".

It concerned 3 substances: TCP (tri-cresyl phosphate), TBP (tri-butyl phosphate), TPP (tri-phenyl phosphate) and other chemical compounds belonging to the group of organophosphates used, among other things, as plasticisers and flame retardants. The work was supervised by a university lecturer at IPASUM, who prepared two scientific publications in parallel with the completion of the thesis by the doctoral candidate, which were published immediately afterwards: in the interest or on behalf of the „Berufsgenossenschaft Verkehr“. Result: For TBP and TPP, methods for detecting and measuring metabolites can be found, but not for TCP.  This is only possible if a measurement sample is spiked with TCP in the laboratory.

Both SCHINDLER publications do not discuss the negative result of not having found any evidence for TCP. The author does not address the questions that a scientist would normaly ask. For example:

1.     whether the correct metabolite produced in the metabolisation process has been found at all

2.     or whether the initial quantities to be measured were sufficient to provide measurable evidence

3.     or whether the so-called "minimum level of detection" or the detection limit was set too high, and

4.     whether genetic differences between the objects in the metabolic processes could possibly explain the negative measurement result.

None of this can be read in the two publications (SCHINDLER 2009a, SCHINDLER 2009b).

A scientist who believes s/he has found a new method to explain a relationship and wants to present it to the expert public must prove for their new finding a) validity (method works) and b) reliability (the result found can be repeated regularly with the method). If s/he cannot do this or if such a search (e.g. tests) turns out negative, there are 2 options for explanation:

• Option 1: The connection does not exist in this way. It can therefore not be proven.
• Option 2: The connection exists, but it could not be proven with the method used so far. So you have to try other methods.

This does not happen in SCHINDLER’s work in 2009.

Despite this, the state of scientific knowledge in 2009 looks like this: There is no method for detecting and measuring TCP in human urine.

Publications by other scientists in the USA in 2011 (LYASOVA et al, FURLONG et al) will not advance any further either: TCP or ToCP gets into the human body during a drastic fume event, but it cannot be detected in the urine of humans either in its original state or by means of an adequate metabolite.

In 2013, SCHINDLER, who has since become an employed scientist at the DGUV and BG's own IPA Institute in Bochum (until 2012), which commissioned the publications published in 2009, will publish a further paper: Occupational exposure of air crews to tricresyl phosphate isomers and organaphosphate flame retardants after fume events.

This time the focus was directly on TCP and ToCP and 332 urine samples were evaluated, which were voluntarily handed in by aircrews who thought they were exposed to a fume event. There was no fixed definition for such an event and so it is not known whether this sample included one or more dramatic fume-event incidents, which were registered as "serious incidents" with the AAIB, for example.

Regardless of the statements in terms of content and considerable methodological weaknesses of this study, which we have summarised at www.ansTageslicht.de/Schindler-Study, metabolites have now been defined for the first time, for which, however, no evidence above a self-defined "level of detection (LOD)" could be found.

Original conclusion of the author (SCHINDLER et al 2013):

• "The lack of data on TCP in cabin air during fume events makes it currently difficult to assess the exposure of air crews to TCP" (p. 646)
• "The reported health effects in air crews can hardly be attributed to an o-TCP exposure" (p. 647).

In brief: No TCP could be detected. Ergo there was none, according to the logic of Birgit K. SCHINDLER.

This is in complete contrast to what other scientists, e.g. in the USA, think. But that does not matter for the German statutory accident insurance in Germany. Its argumentation is therefore successful in German social courts all over the country. It was no different with the hazardous substance asbestos: the employers' liability insurance associations have sufficient financial power and political influence to prevent what is unpopular (more on this here Why asbestos is still being fought over: the showdown to date, Asbestos Chronology Part III - only in German available).

There is no method for detecting and measuring TCP in human urine.

Nor in human blood, in which only a reduced enzyme activity of cholinesterase can be detected or antibodies can be observed as a reaction to neurological degradation processes. There is no direct conclusion to the substance that triggers these reactions. More about this in another context, which deals with the indirect detection of TCP in blood plasma (NOT YET ONLINE).

Only neurological damage can be measured in real terms (ABOU-DONIA 2003 and others). But someone who has been harmed by a fume event is under the obligation to provide evidence and must provide "full proof" of the causal connection.

Similar to the way the Russian authorities (wanted to) see no connection in the case of the Russian opposition politician Alexei NAVALNY, who was poisoned in Augsut 2020, this is happening in industry-funded science, especially in (mainstream) occupational medicine, which expresses these doubts in its expert opinions before the German social courts.

Different conclusions can be drawn from this:

• Disinterest in the health and safety of aircrew
• Ignorance of the safety thinking actually practised in the aviation industry (advertising slogan "Your safety comes first for us")

From a legal point of view, one could even speak of thwarting evidence in the face of deliberate inaction.

In spite of these findings documented here: BG Verkehr regularly and undauntedly asserts to all flight personnel who have been involved in a fume event, as well as to the social courts, that the health damage that has occurred and can be diagnosed since the fume event, cannot have anything to do with the substance TCP: Because no di-o-cresylphosphate, no di-m-cresylphosphate and no di-p-cresylphosphate could be detected as metabolites in the urine samples.

The same argumentation is put forward by mainstream occupational health practitioners who are commissioned by the German social courts as experts or "experts". They are usually - directly or indirectly - in close contact with the system of the German Social Accident Insurance (DGUV) and the professional associations supporting it (as we have reconstructed decidedly elsewhere: www.ansTageslicht.de/DGUV as well as in the graphic at www.ansTageslicht.de/Schattenreich - both sites only in German).

The social welfare judges have - actually - a so-called "official duty of investigation". However, this duty is rarely fulfilled. And so it is no wonder that lawsuits brought by those affected before these courts in order to obtain justice end negatively for them: in 90% of all cases. The Federal Ministry of Labour and Social Affairs has given us this figure (www.ansTageslicht.de/BMAS).

As long as this structural imbalance between the over-powerful system of statutory accident insurance, occupational medicine and the German social courts on the one hand, and those affected by illness at work on the other, is not permanently shaken, nothing will change. 

We have summarised elsewhere what can be done at the individual level: What can be done, which can be found under the link www.ansTageslicht.de/WhatCanYouDo . For those who are looking for concrete tips and help, contact the German Contaminated Cabin Air Patient Initiative: www.p-coc.com, which is based in Nuremberg. There you can get help. Or contact the Aerotoxic Team

This documentation refers to only 1 single of all substances that can be released during fume events, which according to a suggestion by the aircraft expert Prof. Dr.-Ing. Dieter SCHOLZ should better be called "Cabin Air Contamination Event", and which can enter the aircraft via the air supply from the turbine ("bleed air"). It is also planned to subject the other potential hazardous substances to a closer analysis within the framework of this Fume-Event-Files. This will only be possible gradually. Next, the (indirect) detection problems of TCP in the blood will be addressed (keywords acetylcholinesterase and butyrylcholinesterase).

The fact that we have focused on TCP first is related to the tricks and strategies of the „Berufsgenossenschaft Verkehr“. In the context of social court disputes, it writes extensive "statements" with a bloated literature appendixes (which it only makes rudimentary use of in its descriptions). If one looks at such "statements" in terms of content analysis, as communication scientists do, it quickly becomes clear that the structure, argumentation and the reference to demonstrably incorrect contexts can only serve one purpose: to confuse and deceive the readers, who are primarily social court & welfare judges. The fact that such methods were a regular part of the strategies of all the „Berufsgenossenschaften“ in Germany has also been documented in detail elsewhere: in a chapter entitled An Uncovering of Tricks, Methods and Strategies, how to downplay Fume Events

This text on TCP can be accessed directly and linked at www.ansTageslicht.de/Tricresylphosphate. The German version is accessable at www.ansTageslicht.de/TCP.

ABOU-DONIA MB, NOMEIR AA, BOWER JH, MAKKAWY HA (1990): Absorption, distribution, excretion and metabolism of a single oral dose of [14C]tri-o-cresyl phosphate (TOCP) in the male rat. Toxicol 65: 61-74 - www.sciencedirect.com/science/article/abs/pii/0300483X9090079V

ABOU-DONIA MB: Organophosphorus ester-induced chronic neurotoxicity. In Arch Environ Health 58: 484-497- pubmed.ncbi.nlm.nih.gov/15259428/

ADRIAENSEN A (2019): ‚Fragmentation of Information‘ in International Data Gathering from Aircraft Fume Events. In: J Health Pollution 24: 4-11

CASIDA JE, ERO M, BARON RL (1961): Biological Activity of a Tri-o-Cresyl Phosphate Metabolite. In: Nature 191: 1396-1397 - https://link.springer.com/content/pdf/10.1038/1911396a0.pdf

DokZentrum ansTageslicht.de (2020): Critisism of the SCHINDLER et al Study 2013, www.ansTageslicht.de/Schindler-Study

FURLONG CE (2011): Exposure to triaryl phosphates: metabolism and biomarkers of exposure. In: J Biol Phys Chem, 11: 165-171 - www.itcoba.net/28FU11A.pdf

HENSCHLER, D (1958): Die Trikresylphosphatvergiftung. Experimentelle Klärung von Problemen der Ätiologie und Pathogenese. In: Die klinische Wochenschrift. 36: 663-674

KUREBAYASHI H, TANAKA A, YAMAHA T (1985): Metabolism and Disposition of the Flame Retardant Plasticizer, Tri-para-cresyl Phosphate, in the Rat. In: Toxicol App. Pharmacol 77: 395-404 - https://doi.org/10.1016/0041-008X(85)90179-6https://doi.org/10.1016/0041-008X(85)90179-6

LYASOVA M, LI B, SCHOPFER M et al (2011): Exposure to tri-o-cresyl phosphate detected in jet airplane passengers. In: Toxicol Appl Pharmacol 256:337-347 - https://doi.org/10.1016/j.taap.2011.06.016
https://doi.org/10.1016/j.taap.2011.06.016

SCHINDLER, B., FORSTER K, ANGERER J (2009a): Determination of human urinary organophosphate flame retardant metabolites by solid-phase extraction and gas chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci, 877(4): 375-381 - https://www.sciencedirect.com/science/article/abs/pii/S1570023208009306

SCHINDLER B, FÖRSTER K, ANGERER J (2009b): Quantification of two urinary metabolites of organo-phosphorus flame retardants by solid-phase extraction and gas chromatography–tandem mass spectrometry. In: Anal Bioanal Chem 395: 1167-1171  - https://link.springer.com/article/10.1007/s00216-009-3064-6

SCHINDLER BK, WEISS T, SCHÜTZE A, KOSLITZ St, BRODING HC, BÜNGER J, BRÜNING Th (2013): Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame retardants after fume events, Arch Toxicol  87: 645-648 - https://link.springer.com/content/pdf/10.1007/s00204-012-0978-0.pdf

(JL)