Health effects of mycotoxins in indoor air: a critical review.

Industrial hygienists (IHs) are called upon to investigate exposures to mold in indoor environments, both residential and commercial. Because exposure standards for molds or mycotoxins do not exist, it is important for the industrial hygienist to have a broad knowledge of the potential for exposure and health effects associated with mold in the indoor environment. This review focuses on the toxic effects of molds associated with the production of mycotoxins, and the putative association between health effects due to mycotoxin exposure in the indoor environment. This article contains background information on molds and mycotoxins, and a brief summary and review of animal exposure studies, case reports, and epidemiological studies from the primary literature concerning inhalation of mycotoxins or potentially toxin-producing molds. The relevance of the findings in the reviewed articles to exposures to mold in indoor, non-agricultural environments is discussed. Although evidence was found of a relationship between high levels of inhalation exposure or direct contact to mycotoxin-containing molds or mycotoxins, and demonstrable effects in animals and health effects in humans, the current literature does not provide compelling evidence that exposure at levels expected in most mold-contaminated indoor environments is likely to result in measurable health effects. Even though there is general agreement that active mold growth in indoor environments is unsanitary and must be corrected, the point at which mold contamination becomes a threat to health is unknown. Research and systematic field investigation are needed to provide an understanding of the health implications of mycotoxin exposures in indoor environments.

Multiple chemical sensitivities: distinguishing between psychogenic and toxicodynamic.

The fundamental issue in the multiple chemical sensitivity (MCS) debate is whether this phenomenon is primarily a psychogenic or toxicodynamic disorder, that is, whether symptoms are due to an emotional response to perceived chemical toxicity or to a pathological interaction between chemical agents and organ systems. The distinction between psychogenic or toxicodynamic is essential to the medical management of an MCS patient. A behavioral origin leads to a behavioral therapy, whereas a toxicodynamic etiology may necessitate avoidance and exposure control methodologies. Regulatory, legislative, judicial, and occupational control responses are also dependent upon the critical distinction between psychogenic and organic etiologies. If people are being poisoned by low levels of chemicals, one set of responses follows. If, on the other hand, MCS sufferers are symptomatic for emotional reasons, the response is different. Everything that is known about MCS to date strongly suggests behavioral and psychogenic explanations for symptoms. The premature use of the term multiple chemical sensitivities has hampered effective exploration of and response to this phenomenon, because it suggests, to the lay person, a physiological explanation. It is time that this disorder be properly characterized so that sufferers receive the care they need and so that new "victims" are not recruited.

Multiple chemical sensitivities--public policy.

The phenomenon of multiple chemical sensitivities is a peculiar manifestation of our technophobic and chemophobic society. It has been rejected as an established organic disease by the American Academy of Allergy and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition. Despite this, it has achieved credibility in workmen's compensation claims, tort liability, and regulatory actions, all of which are briefly reviewed.

Medical hypothesis and medical practice: autointoxication and multiple chemical sensitivities.

Searching for simple explanations for ill health is as normal as human nature itself. In every era people have suffered varieties of symptoms not readily explained by "known" diseases of the day. To provide explanations and treatment approaches, individuals with symptom complexes were frequently provided a unifying disease label. At the turn of the 20th century, that label was autointoxication. Today, it is multiple chemical sensitivities (MCS). Autointoxication, a popular turn-of-the-century phenomenon illustrates that absent common, reproducible, definable, and measurable findings and consistent, objective endpoints, newly named fad disorders have not survived long term. Autointoxication was a disorder very similar in manifestations to MCS. It was, we now know, a pseudodisease, the treatment of which was based upon an unproven hypothesis. If MCS cannot withstand the probing of scientific investigation, it too will disappear as a diagnosis.

Multiple chemical sensitivities: a symposium on the state of the science.

Multiple chemical sensitivities (MCS) defies diagnostic categorization because of its pansystemic manifestations, its lack of consistent symptomatology, and its absence of specific, measurable endpoints, either physical stigmata or laboratory findings. Controlled studies have been few and difficult to perform. Moreover, the phenomenon resists systematic investigation for two reasons. First, it has coalesced into a movement championed by zealous proponents and organized adherents. Second, it has gained support in the courts, the legislatures, and the regulatory agencies which have provided special protection and monetary awards to this phenomenon before science and medicine have defined it as a medical disorder. One hotly contested issue in the MCS debate is the relative role of organic versus psychological contribution to the symptoms of MCS patients. This is a critical issue most importantly because it determines approaches to treatment, secondarily because it affects regulatory action, disability determination, and compensability. The interest of the ISRTP in this phenomenon derives from the significant regulatory impact of this diagnosis on OSHA standards, EPA regulations, and FDA standards. The symposium was convened to explore the quality of the science underlying MCS with respect to diagnosis, and, particularly, to cause. The general objective of the symposium was to discuss the state of the science regarding MCS and its implications in regulatory toxicology and public health. The panel of speakers represented a variety of disciplines including toxicology, immunology, occupational medicine, psychiatry, psychology, epidemiology, and public health. The symposium was attended by a diverse audience representing the medical, scientific, business, legal, and regulatory communities. The majority of speakers critically questioned the characterization of MCS as a clinical entity, in light of historical comparisons to earlier false diagnoses, toxicological implausibility, and clinical inconsistencies.

Activation of intestinal mucosal adenylate cyclase by Shigella dysenteriae I enterotoxin.

Because the mechanism whereby Shigella dysenteriae I enterotoxin induces intestinal secretion is unclear, the effect of this toxin on adenylate cyclase activity in rabbit ileal mucosa was studied under various in vitro and in vivo conditions. Activation of adenylate cyclase by Shigella enterotoxin was observed only when substrate (ATP) concentrations above the Km of adenylate cyclase were employed. These concentrations of ATP are greater than those required to demonstrate activation of adenylate cyclase by cholera toxin. Under optimal assay conditions, doses of Shigella toxin between 5.4 and 900 mug of toxin protein and in vivo incubation times between 6 and 18 hr all increased adenylate cyclase activity by about 100%. Shigella toxin produced significant but highly variable increases in mucosal cyclic AMP concentrations, which were less that the rises seen with a comparable dose of cholera toxin. This variability in cyclic AMP response to Shigella toxin and the disparity between Shigella and cholera toxins' effects on mucosal cyclic AMP are probably the result of the different kinetics of adenylate cyclase activated by these enterotoxins. Mucosal Na-K-ATPase activity was unaffected by Shigella toxin. These observations suggest that alterations in fluid and electrolyte transport induced by Shigella enterotoxin may, in part, be mediated by the adenylate cyclase-cyclic AMP system.

Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin.

Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.

Na+-K+-activated adenosine triphosphatase and intestinal electrolyte transport. Effect of adrenal steroids.

Sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) is associated with electrolyte transport in many tissues. To help delineate its role in intestinal transport, changes in rat intestinal electrolyte and water transport induced by injecting methylprednisolone acetate 3 mg/100 g or deoxycorticosterone acetate (DOCA) 0.5 mg/100 g per day for 3 days were correlated with changes in Na-K-ATPase activity. Methylprednisolone increased sodium and water absorption, potassium secretion, transmural potential difference, and Na-K-ATPase activity in the jejunum, ileum, and colon. Examination of isolated epithelial cells demonstrated that the jejunal and ileal increase in Na-K-ATPase occurred in both the villus tip and crypermeability, Mg-ATPase, and adenylate cyclase activities were unchanged by methylprednisolone. DOCA increased sodium and water absorption, potassium secretion, transmural potential difference, and Na-K-ATPase activity in the colon alone. Colonic Mg-ATPase and adenylate cyclase activities were unaffected. Jejunal and ileal enzyme activity, electrolyte transport, and permeability were unchanged by DOCA. Methylprednisolone and DOCA were not additive in their effect on colonic Na-K-ATPase activity. Methylprednisolone and DOCA increased electrolyte and water transport and Na-K-ATPase activity concomitantly in specific segments of small intestine and colon. These data are consistent with an important role for Na-K-ATPase in intestinal electrolyte and water transport.