HEALTH                    

Lacking hard data from tests of the strains of Fusarium oxysporum and Pleospora papaveracea proposed for use as mycoherbicides, we can only make reasonable speculation until such tests under several controlled conditions are completed.  Such reasonable speculation could be based upon work that has already been performed on other strains of Fusarium  and Pleospora.  

Toxicity of Fusaria

After scientists studied the outbreak of Fusarium intoxication of animals in the 1980's, an association between Fusarium and its yet unknown toxins was established (Sheldon, 1904).

Below, we will look at what is known about the toxicty of Fusarium, starting first with the book by Marasas et al, Toxigenic Fusarium Species: "The genus Fusarium contains important mycotoxin-producing species that have been implicated in human diseases, such as alimentary toxic aleukia, Urov or Kashin-Beck disease, Akakabi-byo or scabby grain intoxication, and esophageal cancer. Many of these mycotoxin-producing species have also been implicated in several animal diseases, including hemorrhagic, estrogenic, emetic, and feed refusal syndromes, fescue foot, degnala disease, moldy sweet potato toxicosis, bean hulls poisoning, and equine leukoencephalomalacia. The interest in toxigenic Fusarium species is increasing world-wide due to the discovery of a growing number of naturally occurring Fusarium mycotoxins that have practical importance as threats to human and animal health."  Quoted from Toxigenic Fusarium Species by Marasas et alia, Penn State U, 1984

EFFECT ON MAMMALS: First Report of Production of Fumonisins B₁, B₂, and B₃ from Fusarium oxysporum var redoleaans [http://www.nal.usda.gov/ttic/cgi-bin/tektran-abs-printV3.pl/ttic/tektran/data/
oooo5/98/0000059895.html?mycoherbicide#first-hit }

This ARS (Agricultural Research Service) report (#0000059895) Interpretive summary points out that :

"FB1 is an important phytotoxin and mammalian toxin. This is the first report of fumonisins produced by Fusarium oxysporum which is a well-known pathogen of economically important crops. It is possible that the fumonisins are involved in the pathogenesis of F. oxysporum." (Bold within entries is our emphasis thoughout.)

Significance: Since in the keywords "mycoherbicide" is listed, one assumes that the study looks at Fusarium oxysporum as a mycoherbicide and therefore has serious implications for the use of Fusarium oxysporum as a mycoherbicide. This shows that Fusarium oxysporum does, indeed, produce recognized toxins.

On Humans

EFFECTS ON SKIN: Guidelines of Care for Superficial Mycotic Infections of the Skin Onychomycosis

[http://www.aad.org/Guidelines/onychomycosis.html]

This American Academy of Dermatology report J AM ACAD DERMATOL 1996;34:116-21 says in part:

"Onychomycosis is a common disorder that can result in significant morbidity. Clean, healthy nails are important in our society and dystrophic nails can be a social impediment and cause significant embarrassment, thereby affecting a patient's self-esteem. In addition, thickened nails can be painful, interfere with the function of the nail unit, affect the ability to use the hands and fingers, and cause pain on walking. Onychomycosis occurs in association with trauma, systemic disease, and immunocompromised states including HIV infection."

Superficial white onychomycosis.

This can be caused by T. mentagrophytes and several nondermatophyte molds including Aspergillus terreus, Fusarium oxysporum, and Acremonium species. Because this is an infection of the superficial nail plate surface, topical antifungals combined with surgical curettage or scraping of the infected portions of the nail plate may be effective.

Significance: This shows that effects of Fusarium oxysporum are not only in immunocompromised persons but also those with trauma, or systemic disease.

EFFECT ON HUMANS INDOORS: Significance of Molds in Indoor Proliferation

http://members.aol.com/summerbelr/Richard9.htm 

[Ed. We quote this webpage in length because it reflects the conventional wisdom about Fusarium oxysporum's ability to infect humans. However do note our "Significance" note after the entry!]

Of the regularly occurring indoor mold proliferation species, only a few have significant potential as opportunistic pathogens, and even these usually require a relatively strongly immunocompromised patient before they can be regarded as dangerous. Warm, moist environments, such as dirty heating ducts affected by condensation, or vanes and other apparati near heating system humidifiers, may grow Aspergillus fumigatus, the best known opportunistic mold fungus. This species also tends to occur in potted plant soils, particularly where these have not been exchanged for fresh soils (e.g., by repotting) for several years. Usually, a patient needs to have a relatively high degree of neutropenia (deficit in neutrophil type white blood cells, an essential component of the immune system) before he or she is seriously threatened with invasive disease by this organism. Most such patients are persons taking leukemia chemotherapy or drugs designed to prevent rejection of transplanted organs. Occasionally other predisposing factors are found, such as heavy, prolonged corticosteroid use. AIDS patients are at little risk for such diseases unless they develop lymphomas or are taking potentially neutropenia-inducing drugs such as ganciclovir. In recent years, because of the emergence of antibiotic-resistant bacteria in hospitals, some hospitals have begun to send severely neutropenic patients home. These patients are at high risk of infection by indoor infestations of A. fumigatus, A. niger, A. nidulans, A. flavus, A. terreus, Pseudallescheria boydii, Fusarium solani, F. oxysporum, F. moniliforme, F. proliferatum, and some other species. People who do not have these specific immunocompromising conditions, however, are not at significant risk of invasive disease from any of these fungi (with the possible exception of P. boydii punctured into the dermis or the eye).

Significance: This description of the indoor effects of Fusarium spp. mold concludes that only certain immunocompromising conditions would make one vulnerable and reflects the statements in the O.N.D.C.P. handout, apparently written by Dr. David Sands called: "Biological Control of Coca - An Assessment of Environmental Aspects 09/01/98." However... this conclusion cannot be assumed for a "massive" inundation of Fusarium oxysporum, that is contemplated for its use as a mycoherbicide against drug plants. Although the handout claims that field tests show it is effective, they do NOT mention any testings at the spore/mycelia levels--as yet unspecified--needed to effectively kill the drug crops in highly varying environmental conditions.

A significant question is why hasn't the US government done the tests on the pathogen it is pushing. In an article by C. P. Kurtzman, Microbial Properties Research, Title: Exploitation of the ARS Microbial Germplasm Collection for Agricultural and Industrial Uses, the author cites the evident ease with which toxicity tests are done and points out that Microbial Properties Researsch has as one of its objectives to: "Provide molecular sequence comparisons and nucleotide databases of agriculturally important species for the purposes of rapid detection and identification of plant pathogens, mycotoxigenic fungi, food spoilage yeasts and biocontrol microorganisms. Specific examples include the following: Many genetically distinct species were identified within the Gibberella fujikuroi complex and are being tested for mycotoxin production."

EFFECT ON DIABETES PATIENT: Fusarium Oxysporum - A Rare Fungus Infection In A Diabetic Patient

http://www.bhj.org/journal/1996/3804-oct/abstract-03.htm 

Presented by: Lina Deodhar, Sudhir Singh, AK Gupta, Bhavna Vyas(Abstracts of papers presented at the 36th Monthly Research Meeting of the Medical Research Centre, Bombay Hospital on Monday, 8th April ‘96)

Fusarium species are not part of the normal human flora. They are ubiquitous soil saprophytes and plant pathogens. In human, Fusarium species have been reported to cause localized infections such as keratitis onychomycosis, skin infections and less commonly, deep infections like brain abscess, septic arthritis, osteomyelitis, endophthalmitis and peritonitis. The most common species involved in human infections are F. solani. F. oxysporum and F. moniliforme. Herewith, we are presenting a case of Fusarium oxysporum infection in a diabetic patient. A 73 year old male from Kenya was admitted in the hospital for ulcer and gangrenous lesions on both feet. Patient was known diabetic for 20 years, and also had ischaemic heart disease. Debridement of gangrenous area was done and the material was sent for culture and sensitivity, on three occasions. Patient had severe anaemia but the leucocyte count was on the higher side. From all the three samples, fungus - morphologically resembling Fusarium species was grown along with gram negative bacteria. The culture was sent to mycology division, P.G.I. Chandigarh and the species was confirmed as Fusarium oxysporum.

Significance: Fusarium oxysporum seems to appear in areas in which it would never be suspected. In this case in gangrenous feet. This would indicate that assuming that Fusarium oxysporum will affect only severely immunocompromised patients is not a valid assumption. Here the patient was certainly debilitated but did not suffer from HIV, but diseases which are relatively common, diabetes and heart disease.

EFFECT ON CORNEA OF EYE: FUNGAL KERATITIS (excerpts)

http://www.emedicine.com/oph/topic99.htm

By George Alexandrakis, MD, Bascom Palmer Eye Institute, University of Miami School of Medicine

...Fungi gain access into the corneal stroma through a defect in the epithelium, then multiply and cause tissue necrosis and an inflammatory reaction. The epithelial defect is usually due to trauma, for example from contact lens wear, foreign material or prior corneal surgery. The organisms can penetrate an intact Descemet’s membrane and gain access into the anterior chamber or posterior segment. Mycotoxins and proteolytic enzymes augment the tissue damage.

Where?

"In the US:

The incidence of fungal keratitis varies according to geographical location and ranges from 2% of keratitis cases in New York to 35% in Florida. Fusarium species is the most common cause of fungal corneal infection in the southern U.S. (45-76% of fungal keratitis), while Candida and Aspergillus are more common in northern states. In a recent large series of fungal keratitis from south Florida, Fusarium oxysporum was the most common isolate (37%), followed by Fusarium solani (24%), Candida, Curvularia, and Aspergillus in order of decreasing frequency.

Internationally:

Aspergillus species is the most common isolate in fungal keratitis worldwide. Large series of fungal keratitis from India report that Aspergillus is the most common isolate (27-64%), followed by Fusarium (6-32%), and Penicillium (2-29%)."

. . .

"Mortality/Morbidity:

Fungal organisms can extend from the cornea into the sclera and intraocular structures. Fungi can cause severe infections, such as scleritis, endophthalmitis, or panophthalmitis. These infections are usually very difficult to treat and may result in severe visual loss or even loss of the eye."

Significance: The risks of Fusarium oxysporum in mycoherbicidal form, needs to be evaluated considering as well the poverty of coca farmers in rural areas of Latin America and the lack of available, skilled, sophisticated medical facilities and personnel who would be able to trace the source of such diseases if caused by fungal inundations.

EFFECT ON EYES: Mycotic keratitis: Medical Mycology Research Center, Department of Pathology, University of Texas Medical Branch, Galveston, Texas

http://fungusweb.utmb.edu/mycology/hairskinnail-infections.html 

Definition:

Following trauma to the cornea by plant material, soil, or surgery, mycotic ulcers can

develop with an associated severe inflammatory reaction, vascularization, ciliary flush, flare of the anterior chamber, and folding of Descemet's membrane. ... Following the resolution of the infection, surgery may be necessary, depending upon the degree of damage to the eye.

. . .

Laboratory Direct examination:

The diagnosis of mycotic keratitis must include the demonstration of the fungus in corneal scrapings and the recovery of a compatible fungus. Clinical material can be mounted in 10% KOH or stained by the Gram, PAS, GMS, Giemsa or calcofluor techniques. Fungi are usually deep within the corneal structure, not on the surface.

Extensive debridement may be necessary to obtain satisfactory clinical material.

Swabs are unsatisfactory.

. . .

Mycology (principal fungi)

Acremonium spp.
Aspergillus flavus
Aspergillus fumigatus
Aspergillus niger
Bipolaris spp.
Candida albicans
Curvularia spp
Exserohilum spp.
Fusarium oxysporum
Fusarium solani
Lasiodiplodia theobromae

Significance: This kind of trauma to the eye by plant material or soil, would be more than likely relatively common in rural areas, and note the specialty training needed to do the extensive debridement needed for clinical material.

On Animals

EFFECT ON RATS: Metabolism, Mass Spectral Analysis and Mode of Action of Trichothecene Mycotoxins

[http://www.dtic.mil:80/cgi-bin/stinet-waisgate?port+2001&ip-address+dtics
6&database-name+/wais/indexes/DTIC-U2-TR-Database&headline+ADA1
79011%20Metabolism%2c%20Mass%Spectral%20analysis
%20and%20Mode]

A report (ADA 179011) from DTIC (Defence Technical Information Center) shows that in a study of 98 isolates of Fusarium in 1984 that:

"The isolates [from cereal grains and soils in Norway] were grown on a solid rice medium in culture and tested for toxicity by feeding to white, female 20-day old weanling rats. The isolates of F. oxysporum showing the toxic signs described above [ed.: does not describe them above) do not produce any trichothecenes; moreover, the toxin/s is very nonpolar and behaves chromatographically much different than any others I have ever seen. Its chemical structure as far as I can determine at this time is not known or else has not been published. The significance of our findings may have implication in the toxic signs and symptoms described by victims of chemical-biological warfare in Southeast Asia for the following reason. The rapid onset of hemorrhaging described by these victims could not be explained for the most part by either T-2 or DAS [recognized toxins]; however, the unknown toxin described above has potential in explaining the toxicity observed. [Our emphasis]

Significance: A non-trichothecene fraction of a Fusarium oxysporum shows toxic effect on the rats, indicating that other toxins present in Fusarium oxysporum.

EFFECT ON RATS: Isoverrucarol production by Fusarium oxysporum CJS-12 isolated from corn.

[http://www.scabusa.org/newpage5.htm]

Kempf, H. J. and G. Wolf (1990). Appl Environ Microbiol. Washington, D.C. : American Society for Microbiology. Jan 56(1): 260-263.

Isoverrucarol (3,15-dihydroxy-12,13-epoxy-trichothec-9-ene) was isolated and purified from wheat cultures of a toxic strain of Fusarium oxysporum CJS-12. The toxin was characterized by thin-layer chromatography, gas chromatography-mass spectrometry, mass spectrometry, and 1H and 13C nuclear magnetic resonance spectrometry. Isoverrucarol caused toxic effects in rats, including loss of appetite, bodily weakness, severe mucosae of the stomach, and death, when administered orally at 10 and 20 mg/kg of body weight. The toxin also caused a definite dermatitic reaction of epidermis and an edematic-necrotic response of the dermis.

Significance: Lists another toxin produced by a Fusarium oxysporum in corn which causes severe damage and death to rats.

EFFECT ON RATS AND CHICKEN EMBRYOS: Sambutoxin, a new mycotoxin produced by toxic fusarium isolates obtained from rotted potato tubers. Kim, J. C. and Y. W. Lee (1994). Applied and environmental microbiology 60(12): 4380-4386.

http://www.scabusa.org/newpage5.htm 

Ninety-nine isolates of Fusarium species were obtained from rotted potato tubers from various parts of Korea. Of these isolates, 80 were identified as Fusarium oxysporum, F. solani, or F. sambucinum. The isolates of these species were grown on autoclaved wheat grains and examined for toxicity in a rat-feeding test. A total of 8 of 57 F. oxysporum isolates, 3 of 14 F. solani isolates, and 5 of 9 F. sambucinum isolates caused the death of the rats. Of the 16 toxic isolates, 1 isolate of F. oxysporum produced a substantial amount of moniliformin, which could account for its toxicity. None of the other 15 isolates produced trichothecenes, moniliformin, fusarochromanone, fumonisin B₁, or wortmannin. F. sambucinum PZF-4 produced an unknown toxin in wheat culture. This new toxin, given the trivial name sambutoxin, caused toxic effects in rats, including body weight loss, feed refusal, hemorrhage in the stomach and intestines, and, finally, death when rats were fed diets supplemented with 0.05 and 0.1% sambutoxin. The toxin was also toxic to chicken embryos, and the 50% lethal concentration was 29.6 micrograms per egg.

Significance: A new toxin, labeled "Sambutoxin" found in 8 of 57 or 14% of Fusarium oxysporum isolates taken from potato tubers in Korea caused death to rats. One of the Fusarium oxysporum isolates also produced "a substantial amount of moniliformin, considered a biowarfare agent.??

Formulations for application of bioherbicides

Biodac--"A revolutionary carriera cellulose complex, for the application of pesticides, biopesticides [Ed. i.e. bioherbicides] and other agricultural treatments. **[JB - refer to **after this entry on Biodac]

Excerpted from: A replication of the Material Safety Data Sheet (MSDS) for Biodac (R)

http://www.grantekinc.com/bio-msds.html 

ARS listed Biodac as "A formulation of Fusarium oxysporum pathogenic to coca was developed (Biodac)

. . .The formulation produces extensive secondary spores and remains viable for at least 10 months."

In ARS CRIS listings: •1275-22000-147-00D - Agency ARS 1275 --1993-98

-DISCOVERY DEVELOPMENT AND MECHANISM OF ACTION OF BIOCONTROL AGENTS FOR PERENNIAL AND ANNUAL WEEDS - Lumsden, Bailey, Lewis; 93/10/01 - 98/9/30

[Eds.We are unclear as to whether Biodac is the base for the BPDL formulation, or Biodac resulted from their research.]

While Grantek's information indicates Biodac is non-hazardous, the same page warns:

SECTION V.

HEALTH HAZARD INFORMATION

FIRST AID

Eye Contact: Flush with water or eye drops to remove particles.

Skin Contact: Wash with soap and water.

Inhalation: Remove by expiration. [Ed. How's this?]

Ingestion: Induce vomiting.

SECTION VII.

SPILL, LEAK, AND DISPOSAL PROCEDURES

Spills, Leaks: Sweep up and contain for disposal

Waste Disposal Method: Incinerate or bury in an approved landfill in compliance with all federal, state, and local laws.

SECTION VIII.

SPECIAL PROTECTION INFORMATION

Respiratory Protection (Specify Type): None Required

Ventilation: Use local exhaust to control possible air-borne material.

Other: None

Protective Gloves: Gloves recommended for prolonged exposure.

Eye Protection: Eyeglasses with side shields recommended.

Significance: The media or formulation material used to store and deliver the Fusarium oxysporum if sprayed or applied indiscriminately on top of people or children or around their homes, could also be harmful since the delivery would be in a hostile atmosphere in which the people involved would not know the precautions to take.

**And lest anyone think that fungi for biocontrol are not biopesticides, the website of the International Biopesticide Consortium for Development [http://www.biopesticide.org/biopesticides.htm] "Benefits of biopesticides include effective control of insects, plant diseases and weeds..." and list fungi and viruses under "Weed control".

Yet ironically, Fusarium oxysporum itself IS certainly considered a pest according to USDA/Aphis

4. Pest List: Pests Associated with Zingiber in Japan

Table 2 shows our pest list for Japanese Zingiber. As few pest were reported for Z. mioga, we developed the pest list for the generic level We generated the list after review of the information sources listed in USDA (1995). The pest list includes limited information on the distribution of each pest, pest-commodity association, and regulatory history.

. . .

Fungi

Cercospora zingiberi Togashi & Katsuki (Fungi

Imperfecti: Hyphomycetes)

Fusarium oxysporum Schlechtend.:Fr. f.s. zingiberi

Trujillo (Fungi Imperfecti: Hyphomycetes)

[http://www.aphis.usda.gov/ppq/ss/cobra/japnmiog.html]

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