Toxicology and Industrial Health current issue

Mold and mycotoxin symposium: Towards healthy homes

Kilburn, K. H — Fri, 23 Oct 2009 04:11:59 PDT

Epidemics of mold poisoning past and present

Meggs, W. J — Fri, 23 Oct 2009 04:11:59 PDT

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure

Empting, L. — Fri, 23 Oct 2009 04:11:59 PDT

Human exposure to molds, mycotoxins, and water-damaged buildings can cause neurologic and neuropsychiatric signs and symptoms. Many of these clinical features can partly mimic or be similar to classic neurologic disorders including pain syndromes, movement disorders, delirium, dementia, and disorders of balance and coordination. In this article, the author delineates the signs and symptoms of a syndrome precipitated by mold and mycotoxin exposure and contrasts and separates these findings neurodiagnostically from known neurologic diseases. This clinical process is designed to further the scientific exploration of the underlying neuropathophysiologic processes and to promote better understanding of effects of mold/mycotoxin/water-damaged buildings on the human nervous system and diseases of the nervous system. It is clear that mycotoxins can affect sensitive individuals, and possibly accelerate underlying neurologic/pathologic processes, but it is crucial to separate known neurologic and neuropsychiatric disorders from mycotoxin effects in order to study it properly.

The biocontaminants and complexity of damp indoor spaces: more than what meets the eyes

Thrasher, J. D, Crawley, S. — Fri, 23 Oct 2009 04:12:00 PDT

Nine types of biocontaminants in damp indoor environments from microbial growth are discussed: (1) indicator molds; (2) Gram negative and positive bacteria; (3) microbial particulates; (4) mycotoxins; (5) volatile organic compounds, both microbial (MVOCs) and non-microbial (VOCs); (6) proteins; (7) galactomannans; (8) 1-3-β-D-glucans (glucans) and (9) lipopolysaccharides (LPS — endotoxins). When mold species exceed those outdoors contamination is deduced. Gram negative bacterial endotoxins, LPS in indoor environments, synergize with mycotoxins. The gram positive Bacillus species, Actinomycetes (Streptomyces, Nocardia and Mycobacterium), produce exotoxins. The Actinomycetes are associated with hypersensitivity pneumonitis, lung and invasive infections. Mycobacterial mycobacterium infections not from M. tuberculosis are increasing in immunocompetent individuals. In animal models, LPS enhance the toxicity of roridin A, satratoxins G and aflatoxin B1 to damage the olfactory epithelium, tract and bulbs (roridin A, satratoxin G) and liver (aflatoxin B1). Aflatoxin B1 and probably trichothecenes are transported along the olfactory tract to the temporal lobe. Co-cultured Streptomyces californicus and Stachybotrys chartarum produce a cytotoxin similar to doxorubicin and actinomycin D (chemotherapeutic agents). Trichothecenes, aflatoxins, gliotoxin and other mycotoxins are found in dust, bulk samples, air and ventilation systems of infested buildings. Macrocyclic trichothecenes are present in airborne particles <2 µm. Trichothecenes and stachylysin are present in the sera of individuals exposed to S. chartarum in contaminated indoor environments. Haemolysins are produced by S. chartarum, Memnoniella echinata and several species of Aspergillus and Penicillium. Galactomannans, glucans and LPS are upper and lower respiratory tract irritants. Gliotoxin, an immunosuppressive mycotoxin, was identified in the lung secretions and sera of cancer patients with aspergillosis produced by A. fumigatus, A. terreus, A. niger and A. flavus.

Molds, mycotoxins, and sick building syndrome

Straus, D. C — Fri, 23 Oct 2009 04:12:00 PDT

The following is a review of some of the work we have done since 2004 regarding the importance of molds and their mycotoxins in the phenomenon of sick building syndrome (SBS). In these studies we showed that the macrocyclic trichothecene mycotoxins (MTM) of Stachybotrys chartarum (SC) are easily dissociated from the surface of the organism as it grows and could therefore be consequently spread in buildings as the fungus experiences additional water events. We then showed that SC and Penicillium chrysogenum (PC) colonies remain viable long after a water source has been removed, and the MTM produced by SC remain toxic over extended periods of time. We next showed that PC when inhaled, can release in vivo, a protease allergen that can cause a significant allergic inflammatory reaction in the lungs of mice. We then showed, in a laboratory study, that the MTM of SC can become airborne attached to spores or SC particulates smaller than spores. Following that study, we next showed that the same phenomenon actually occurred in SC infested buildings where people were complaining of health problems potentially associated with SBS. Finally, we were able to demonstrate the presence of MTM in the sera of individuals who had been exposed to SC in indoor environments. This last study was done with enough mold exposed individuals to allow for the statistical significance of SC exposure to be evaluated.

Mycotoxins in animal and human patients

Coppock, R. W, Jacobsen, B. J — Fri, 23 Oct 2009 04:12:00 PDT

The majority of human food and animal feed production occurs in a highly managed agroecosystem. Management decisions include variety grown, tillage and irrigation methods and practices, fertilization, pest and disease control, harvesting methods, and storage and transportation practices. This system is generally managed for optimum returns to labor and capital investments. The spores of toxigenic fungi have ubiquitous distribution and toxigenic fungi exploit food sources when conditions of moisture and temperature are above minimums for growth. The safety margins in the agroecosystem are close and are influenced by extrinsic factors such as climatic events. Control of fungal growth is important in management of raw feedstuffs, foodstuffs, condiments-spices, botanicals, and other consumable substances as they are grown, harvested, stored, and transported. The risk factors for mycotoxin production are weather conditions during crop growth and when the crop is mature, damage to seeds before, during, and after harvest, how commodities are physically handled, the presence of weed seeds and other foreign material in grain, and how commodity moisture and temperature are managed during storage and transportation. Diversion of commodities and by-products from human consumption to animal feedstuffs can increase the risk of mycotoxicoses in animals. The toxicology of selected toxigenic fungi and the mycotoxins they produce are reviewed.

Health effects of Aspergillus in food and air

Klich, M. A — Fri, 23 Oct 2009 04:12:00 PDT

This review summarizes the health aspects of the medically important fungal genus Aspergillus. The morphology and systematics of the genus are explained as well as its biogeography. Major mycotoxins, the aspergilli that produce them, affected crops, and symptoms of the toxicoses are summarized, as are the major mycoses caused by aspergilli. The current status of the relationship between Aspergillus in the indoor environment and health issues are discussed.

Fungal exposure endocrinopathy in sinusitis with growth hormone deficiency: Dennis-Robertson syndrome

Dennis, D., Robertson, D., Curtis, L., Black, J. — Fri, 23 Oct 2009 04:12:00 PDT

A retrospective study was carried out on 79 patients with a history of mold exposure, fatigue, and chronic rhinosinusitis (CRS) to determine whether there is a causal relationship between fungal exposure and chronic sinusitis, fatigue, and anterior hypopituitarism, especially growth hormone deficiency (GHD). Of the patients, 94% had a history of CRS, endoscopically and/or computed tomography (CT) confirmed; 100% had chronic fatigue and 100% had either significant history of indoor mold exposure and/or positive mold plate testing as measured by settle plates, with an average colony count of 21 (0-4 normal). A total of 62 had positive mold plate testing and 17 had positive history of mold exposure. Of 75, 73 (97.3%) had positive serum immunoglobulin G (IgG)-specific antibodies to fungal antigens. Out of 8, 7 were positive for urinary trichothecenes. Resting levels of insulin-like growth factor 1 (IGF-1) averaged 123 ng/mL (range 43-285, normal 88-249 ng/mL). Despite normal resting levels of IGF-1, significant deficiency of serum human growth hormone (GH) was confirmed by insulin tolerance test (ITT) in 40 of 50 tested. In all, 51% (40/79) were GH deficient. Primary or secondary hypothyroidism in T3 and/or T4 was seen in 81% (64/79) patients; 75% (59/79) had adrenocorticotrophic hormone (ACTH) deficiency. Fungal exposure endocrinopathy likely represents the major cause of GHD, affecting approximately 4.8 million people compared to approximately known 60,000 cases from all other causes. A literature review indicates a possible mechanism of GHD in fungal exposure is that the fungal glucan receptors in the lenticulostellate cells of the anterior pituitary bind to fungal cells wall glucans and activate the innate immune system, which activates macrophages that destroy the fungus and lenticulostellate tissue. Treatment of patients included normal saline nasal irrigations, antifungal and antibiotic nasal sprays, appropriate use of oral antibiotics and antifungals, facial steamer with CitriDrops. Thymate and/or Intramax vitamin supplements, hormone replacement, and reduction of indoor mold levels. Resolution of rhinosinusitis was seen in 93% (41 of 45) of the patients who achieved a mold count by settling plates of 0-4 colonies. Thirty patients were unable to lower their mold counts below four colonies and had various degrees of mucosal disease and fatigue remaining. Fatigue was improved in all 37 patients who received GH and cortisol and/or thyroid hormone, which were deficient. Fatigue was partially relieved in 7 of the 37 who did not achieve mold counts of fewer than four colonies.

Neurobehavioral and pulmonary impairment in 105 adults with indoor exposure to molds compared to 100 exposed to chemicals

Kilburn, K. H — Fri, 23 Oct 2009 04:12:00 PDT

Patients exposed at home to molds and mycotoxins and those exposed to chemicals (CE) have many similar symptoms of eye, nose, and throat irritation and poor memory, concentration, and other neurobehavioral dysfunctions. To compare the neurobehavioral and pulmonary impairments associated with indoor exposures to mold and to chemicals. 105 consecutive adults exposed to molds (ME) indoors at home and 100 patients exposed to other chemicals were compared to 202 community referents without mold or chemical exposure. To assess brain functions, we measured 26 neurobehavioral functions. Medical and exposure histories, mood states score, and symptoms frequencies were obtained. Vital capacity and flows were measured by spirometry. Groups were compared by analysis of variance (ANOVA) after adjusting for age, educational attainment, and sex, by calculating predicted values (observed/predicted x 100 = % predicted). And p < .05 indicated statistical significance for total abnormalities, and test scores that were outside the confidence limits of the mean of the percentage predicted. People exposed to mold had a total of 6.1 abnormalities and those exposed to chemicals had 7.1 compared to 1.2 abnormalities in referents. Compared to referents, the exposed groups had balance decreased, longer reaction times, and blink reflex latentcies lengthened. Also, color discrimination errors were increased and visual field performances and grip strengths were reduced. The cognitive and memory performance measures were abnormal in both exposed groups. Culture Fair scores, digit symbol substitution, immediate and delayed verbal recall, picture completion, and information were reduced. Times for peg-placement and trail making A and B were increased. One difference was that chemically exposed patients had excess fingertip number writing errors, but the mold-exposed did not. Mood State scores and symptom frequencies were greater in both exposed groups than in referents. Vital capacities were reduced in both groups. Neurobehavioral and pulmonary impairments associated with exposures to indoor molds and mycotoxins were not different from those with various chemical exposures.

Detection of macrocyclic trichothecene mycotoxin in a caprine (goat) tracheal instillation model

Layton, R. C, Purdy, C. W, Jumper, C. A, Straus, D. C — Fri, 23 Oct 2009 04:12:00 PDT

This study demonstrates the detection and dynamics of macrocyclic trichothecene mycotoxin (MTM) tissue loading using a commercially available assay in a goat model. The detection of MTMs has been difficult and complex due to the uncertainty of what tissues to examine and when to sample. Twelve goats (two groups of each) were instilled with Stachybotrys chartarum conidial suspension via the trachea. The first group was challenged repeatedly with fungal conidia containing 1 mg/kg of MTM per instillation whereas the second group was exposed once, to spores with a calculated concentration of 5 µg/kg of mycotoxin. These toxin estimates were generated by the QuantiTox^TM Kit assay; a conidium of S. chartarum possessed 8.5 pg of MTM. After repeated exposure of 3 days, MTM was detected in one of six animals. This animal and two others from the same group had mycotoxin detected in their serum 24 hours after challenge at a comparable level (1.69 ng/mL) to the six animals challenged with a single dose (2.02 ng/mL) at the same time post-instillation. Results showed that MTMs are detectable in experimental animals soon after challenge and contribute to the understanding of the role of these mycotoxins in the disease process following mold exposure.

Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?

Kilburn, K. H, Thrasher, J. D, Immers, N. B — Fri, 23 Oct 2009 04:12:00 PDT

Increased prevalence of the autism spectrum disorders (ASD) and the failure to find genetic explanations has pushed the hunt for environmental causes. These disorders are defined clinically but lack objective characterization. To meet this need, we measured neurobehavioral and pulmonary functions in eight ASD boys aged 8 to 19 years diagnosed clinically and compared them to 145 unaffected children from a community with no known chemical exposures. As 6 of 35 consecutive mold/mycotoxin (mold)-exposed children aged 5 to 13 years had ASD, we compared them to the 29 non-ASD mold-exposed children, and to the eight ASD boys. Comparisons were adjusted for age, height, weight, and grade attained in school. The eight ASD boys averaged 6.8 abnormalities compared to 1.0 in community control boys. The six mold-exposed ASD children averaged 12.2 abnormalities. The most frequent abnormality in both groups was balance, followed by visual field quadrants, and then prolonged blink reflex latency. Neuropsychological abnormalities were more frequent in mold-exposed than in terbutaline-exposed children and included digit symbol substitution, peg placement, fingertip number writing errors, and picture completion. Profile of mood status scores averaged 26.8 in terbutaline-exposed, 52 in mold exposed, and 26 in unexposed. The mean frequencies of 35 symptoms were 4.7 in terbutaline, 5.4 in mold/mycotoxins exposed and 1.7 in community controls.

The treatment of patients with mycotoxin-induced disease

Rea, W. J, Pan, Y., Griffiths, B. — Fri, 23 Oct 2009 04:12:00 PDT

Twenty-eight incapacitated individuals (average 43 years old, 7 males, 21 females, range 12-70) exposed to molds and mycotoxins were studied and treated with a protocol of cleaning up or changing their environment to be mold free. Injections of the optimum dose of antigens were given as part of the treatment protocol as was oral and intravenous (i.v.) antioxidants; heat depuration (sauna); physical therapy with massage and exercise under environmentally controlled conditions; oxygen therapy at 4-8 L/min for 2 hours with a special wood-grade cellophane reservoir and a glass oxygen container. Many patients were sensitive to plastics; therefore, exposures to these were kept to a minimum. Autogenous lymphocytic factor was given as an immune modulator. Of 28 patients, 27 did well and returned to work. One patient improved but did not return to work during the period of study.

Molds, mycotoxins, and nutrition

Overberg, R. — Fri, 23 Oct 2009 04:12:00 PDT

Many of the patients with mold and chemical exposure that come to Environmental Health Center — Dallas (EHC-D) show signs of impaired digestion. Improving their digestion improves their nutritional status and also improves their detoxification abilities. Mold and chemical exposure also affect the patient’s short-term memory and executive function. This presents a challenge when it comes to teaching the patient how to improve their nutritional status and detoxification. At the EHC-D, we use several instructions methods that have resulted in the patient’s grasping the concepts and then being able to implement the required changes.

Mold remediation in a hospital

Lee, T. G — Fri, 23 Oct 2009 04:12:00 PDT

As occupants in a hospital, patients are susceptible to air contaminants that can include biological agents dispersed throughout the premise. An exposed patient can become ill and require medical intervention. A consideration for patients is that they may have become environmentally sensitive and require placement in an environment that does not compromise their health. Unfortunately, the hospital environment often contains more biological substances than can be expected in an office or home environment. When a hospital also experiences water intrusion such as flooding or water leaks, resulting mold growth can seriously compromise the health of patients and others such as nursing staff and physicians (Burge, Indoor Air and Infectious Disease. Occupational Medicine: State of the Art Reviews, 1980; Lutz et al., Clinical Infectious Diseases 37: 786—793, 2003). Micro-organism growth can propagate if the water is not addressed quickly and effectively. Immunocompromised patients are particularly at risk when subjected to fungal infection such that the US Center for Disease Control issued guideline for building mold in health care facilities (Centers for Disease and Control [CDC], Centers for Disease and Control: Questions and Answers on Stachybotrys chartarum and Other Molds, 2000). This paper is based on mold remediation of one portion of a hospital unit due to water from construction activity and inadequate maintenance, resulting in mold growth. A large proportion of the hospital staff, primarily nurses in the dialysis unit, exhibited health symptoms consistent with mold exposure. Unfortunately, the hospital administrators did not consider the mold risk to be serious and refused an independent consultant retained by the nurse’s union to examine the premise (Canadian Broadcasting Corporation [CBC], Nurses file complaints over mold at Foothills. Canadian Broadcasting Corporation, 2003). The nurse’s union managed to have the premise examined by submitting a court order of detention and inspection and for an interlocutory injunction to allow their consultants to undertake air quality testing. Mold remediation procedures are readily available and are not to be discussed here (Silicato, http://www.nibs.org/BETEC/M6/ 13-Silicato_Mold-Remediation.pdf, 2004). However, the difficulty of determining the qualifications of consultants, contactors and project managers are discussed. It also describes the need and importance of a buffer zone between the occupied areas and the mold abatement containment area.

Creating healthier buildings

Small, B. M — Fri, 23 Oct 2009 04:12:00 PDT

Some conventional building design, construction and maintenance practices create conditions that are capable of causing illness in healthy individuals or exacerbating illness in already sensitized individuals. Staying in faulty building environments may unnecessarily prolong environmental-related illness. Physician and patient awareness of such common building failures may help to diagnose environmental triggers of current illness. Architects would benefit from collaboration with environmental physicians to understand the importance of healthier building design to building occupants. Architectural education and practice is slowly incorporating better methods, often in the context of greening and sustainability. Architects are presently being advised that the needs of approximately 15% of the general population who are significantly sensitive cannot be ignored in building design. The author reviews a number of building failures and itemizes a set of relatively simple principles and design concepts that would help create new and renovated buildings that are healthier than current buildings.

Towards healthy homes

Kilburn, K. H. — Fri, 23 Oct 2009 04:12:00 PDT