Mycotoxins and Disease: A key, but scientifically flawed new paper for proving plaintiff cases

By Dr. Ronald E. Gots, MD, PhD

A recent study by Croft et al ("Clinical Confirmation of Trichothecene Mycotoxicosis in Patient Urine," Journal of Environmental Biology. Vol. 23 (3), 2002, pp 301-320) appears, on its surface, to provide compelling scientific evidence of inhalational mycotoxin disease in individuals residing in contaminated residences. It also strongly argues that urine tests for trichothecene mycotoxins are the new gold standard for assessing causation and linking symptoms or diseases to indoor environments. This extensive study, replete with citations, experimental elements and, ultimately, far-reaching interpretations is both dramatic and highly useful for plaintiff claims. The problem is that this study is so replete with fundamental scientific and methodological errors that its conclusions range from speculations, to sheer nonsense. A brief overview of this very important study will be provided here. A more complete review of its fatal scientific flaws will be discussed in subsequent reports. This is a study which must be throughly understood by attorneysplaintiff and defensewho deal with mold-related personal injury claims.

Dr. Croft, a veterinarian, is the lead author. He describes four cases of individuals in detail and hundreds of others from an apartment complex, allegedly living in mold-contaminated environments, who purportedly fit the diagnosis of trichothecene mycotoxicosis. Using a variety of tests (including an unusual skin patch test) and urine extraction of alleged trichothecenes, he confirms exposure. Injecting rats with the urine extract produces similar disorders further supporting his claims. A described autopsy of a deceased subject adds to the impact of his claims.

This paper appears to the non-scientist to be a careful, thorough study. Its conclusions seem strong and well-founded. Every disease and symptom from aneurysms to pancreatic and prostate cancer through every one of at least fifty symptoms, are claimed to arise from trichothecene intoxication. Notwithstanding its peer-reviewed status and seeming validity, its flaws are so manifest that they will require careful dissection in reports to follow. A few key errors include:

No controls;

A claim, but no valid confirmation, of mycotoxin presence in the urine or the bloodstream;

The use of novel, ill-supported tests

Attribution of every imaginable symptom and disease to the alleged exposure, with no consideration of other far more likely, alternate causes;

Failure to consider normal dietary sources of trichothecenes;

There are many more.

Further analysis will follow in subsequent reports.

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Further Review of "Clinical Confirmation of Trichothecene Mycotoxicosis in Patient Urine,"

By Dr. Ronald E. Gots, MD, PhD

This is a further discussion of the paper by Croft, et al, ("Clinical Confirmation of Trichothecene Mycotoxicosis in Patient Urine," Journal of Environmtl. Biology, 23(3) 301-320 (2002)). In this paper, Croft and his group (hereinafter, "Croft") claim to establish through various scientific tests mycotoxicosis that is caused in humans through exposure to mold-contaminated housing.

I have chosen a few key areas to focus upon in this analysis, which is, by no means, an exhaustive review of the paper.  Croft's paper is replete with overstatements, mischaracterizations, experimental design flaws and misuse of citations allegedly supporting the authors' methodologies. These points are sufficient to call into doubt all of the claims in this paper. Having now reviewed all of the articles cited by the authors, I shall summarize a few critical findings.

The authors cite Ueno (1977, 1980, 1983) for their historical discussion of the manifestations of trichothecene mycotoxicosis. In none of Ueno's papers were the descriptions of illnesses comparable to those described by Croft.  For example, in Ueno (1977), specific illnesses associated with specific mycotoxins were described. The toxicological features of mycotoxis-induced illnesses are dependent upon the specific mycotoxin and the species of animal affected. Ueno characterized some of these distinctive disorders by their source, others by their clinical characteristics, e.g., B Alimentary toxic aleukia (ATA), moldy corn toxicosis, bean hull toxicosis, stachybotrytoxicosis and others.

Contrary to Croft's assertion, T-2 toxin is primarily eliminated via the GI tract and found in the feces. A smaller amount is found in the urine. The metabolic pathways by which mycotoxins are handled in the body vary among animal species. Since human metabolism is less well described than is animal, we are not currently in a position to make blanket statements about the metabolic processes that relate to T-2 toxin.

Croft asserts in his paper that certain urine extraction methods precipitate trichothecenes.  This note is unreferenced and cannot be checked.  Further, Croft claims that tests conducted on human urine indicate substantial corollaries to the same tests already observed using animal urine. This suggests that urinalysis confirms diagnoses in humans. These claims are not referenced, therefore, the methodology, which is certainly not a generally established practice, cannot be assessed or verified.  Any conclusions based on this methodology are neither valid nor reliable, notwithstanding the claims made in this paper.

Croft attempts to use Koch's postulate, the generally-accepted scientific standard for determining the presence of a pathogen and its cause of an illness, to establish that mycotoxicosis is caused by mold exposure. Croft's characterization of Koch's postulates, however, is entirely erroneous.  Moreover, he does not adhere to any of them in his scientific investigations. These investigators have presented no objective, confirmatory data, only conclusory statements, that they have extracted trichothecenes from these patients' urines. They then say that "reproducing" the disease in animals proved that the trichothecenes were causal. First, we have no confirmation of trichothecene extraction. Second, considering the generalized symptoms and "diseases" described in these patients, one wonders what is meant by "the disease."

In the patient discussions, exposures are never established, merely assumed. Temporal relationships between exposures and diseases varied from several months to twelve years. The medical descriptions of these patients are discussed in a fashion so sophomoric that they sound more like Reader's Digest than a clinical paper description. Notably, there is no mention of the diagnoses provided by treating physicians. This is particularly notable in Case 4, in which the pathologic features of a devastating encephalomyelopathy were identified. There are dozens of diseases known: mycotoxicosis is not one of them.

Croft erroneously cited a test and misused a skin patch test upon which the investigators relied heavily. The patch test for "alcohol dehydrogenase" (Higuchi et al) supposedly measured an enzyme affected by mycotoxins. First, there is no established basis for the assumption that "mycotoxins" affect alcohol dehydrogenase. Second, the Hibachi letter (it is a Letter-to-an-Editor, not a peer-reviewed study) was designed to test Asians, a significant proportion of whom have an inherited deficiency in aldehyde (not alcohol, as Croft stated) dehydrogenase which makes them intolerant to alcohol. Croft somehow assumed that a positive test in their subjects reflected mycotoxin effect, an effect which is medically unknown. Even assuming that this skin test was positive (Croft got the enzyme wrong), it could well have suggested an inherited defect as noted by the authors they cited. Finally, Croft went far beyond the test protocol of the cited author. They used a different method and a different scoring system, protocols which have not been validated. Nevertheless, they use this test extensively, suggesting that it quantified the extent of toxicity: a misleading, unwarranted suggestion.

Another important component of Croft's "study" involved the alleged extraction of trichothecenes from urine. They give no references for their method and there is little reason to believe that trichothecenes were extracted. Their conclusory statement that this was tested by thin layer chromatography is neither properly discussed nor convincing. This is particularly so when they say that TLC was consistent with those reported for trichothecenes, but which of the trichothecenes? Each comes out at a different place on TLC.

SPECT scans were used to demonstrate "neurotoxicity" by these authors, yet such scans have little value for that purpose. A consensus document and review articles by the Neuroimaging Council have addressed this issue. In fact, SPECT scans presented by the consultant used in this Croft paper have been excluded in court proceedings as being misleading.

The authors invoke other bizarre tests for mycotoxin presence in urine. They say that urine samples left at room temperature for five months showed no "putrefaction" and excessive protein at the bottom of the container. How and why these constitute measures of the presence of mycotoxins is merely stated with no support and no logical basis. Even assuming that the authors were finding mycotoxins, the "study" is fatally flawed by lack of controls. Croft states that one of the authors was the control, but since he entered the subject homes and felt ill, how could he have been a control? He was exposed to the environment and had a response similar to that of the other study subjects.

Finally, the sheer range of symptoms, as well as the presence of actual serious and even fatal, diseases described in this article are a veritable compendium of all human ailments. It would have been quite helpful if the authors had provided more information about standard diagnostic testing and diagnoses made by various treating physicians. I strongly suspect, however, that they would have, had that been possible.

Reference
Croft, W.A., Jastromski, B.M., Croft, A.L., and Peters, H.A."Clinical Confirmation of Tricothecene Mycotoxicosis in Patient Urine,"  Journal  of Environmtl. Biology, 23(3) 301-320, (2002).

About ICTM:

Since 1975, the principals of ICTM have assisted attorneys, corporate counsel, insurers, and facilities managers in the review and management of thousands of environmental claims-mold, chemicals and others. The company has extensive experience in helping attorneys develop strategies and tactics to support counsel from discovery through motions to exclude experts, to jury presentations. In addition, ICTM has managed indoor air quality testing, remediation costs and risk communication for public and private organizations in hundreds of matters concerning commercial and municipal buildings, schools, homes, apartments, and condos. ICTM has developed a methodology that describes the steps needed to evaluate and manage the medical and toxicological aspects of claims of illnesses allegedly arising from environmental exposures.

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