The upcoming standard; mycotoxin testing.

Environmental, biological, veterinary, commodity testing.

By ELISA method, sensitive to less than one billionth of a gram.

Considered probably the best biomarker of exposure.

Listed by the AMA for Medical Toxicology,

Forensic Medicine, Emergency Medicine.

AMA listing for Medical Toxicology

Information about practice.

Map and directions for clinic.

Additonal Information including verdicts.

This is one of the best up to date summaries on the field of trichothecenes.

A must buy!!!!

	A Review of the Scientific Literature as it Pertains to Gulf War Illnesses Volume 5: Chemical and Biological Warfare Agents William S. Augerson

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Excellent Resource on Mycotoxins and Cancer!!! A must buy!!!

Volume 56
Some Naturally Occurring Substances:
Food Items and Constituents,
Heterocyclic Aromatic Amines and Mycotoxins

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Excellent resource on CANCER; must buy!!!!!!!!

IARC Monographs
on the Evaluation of Carcinogenic Risks
to Humans and their Supplements:
A complete list

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Moldy Buildings: Portand Maine; "Education Weekly"

Quotes from: Dr. Dorr G. Dearborn - Case Western University Pediatrics.

"Molds grow on any surface when moisture and oxygen are present"

"Mold is ubiquitous"

"When budgets get tight, the last priority is maintenance, and virtually all of these cases are related to water damage."

"Acute allergies, headaches, memory loss, muscle cramps, fatigue..."

"We made a huge error...which she believes delayed cleaning up the school. "We learned our lesson the hard way." "In the end it took $5 million in state and district money to clean up the school." "The teachers filed their $6 million dollar lawsuit..."

EXCELLENT REVIEW OF TRICHOTHECENES (T-2 TOXIN) AND CANCER

FROM THE WORLD HEALTH ORGANIZATION AND

THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER.

A MUST!!!!

For definition of Groups, see Preamble Evaluation.

VOL.: 56 (1993) (p. 467)
CAS No.: 21259-20-1
Chem. Abstr. Name: Trichothec-9-ene-3,4,8,15-tetrol, 12,13-epoxy, 4,15-diacetate 8-(3-methylbutanoate), (3a,4b,8a)-

5.1 Exposure data

T-2 Toxin is produced primarily by Fusarium sporotrichioides, which occurs rarely on cereals such as wheat and maize. The toxin is considered to have played a role in largescale human poisonings in Siberia during this century.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

T-2 Toxin was tested for carcinogenicity in mice and in trout by oral administration in the diet and in rats by intragastric administration. In mice, it increased the incidences of pulmonary and hepatic adenomas in males. The studies in trout and rats were inadequate for evaluation.

5.4 Other relevant data

T-2 Toxin causes outbreaks of haemorrhagic disease in animals and has been associated with alimentary toxic aleukia in humans.

No data were available on the genetic and related effects of T-2 toxin in humans.

Experimental data were drawn mainly from single studies. T-2 Toxin induced DNA damage and chromosomal aberrations in rodents in vivo, in cultured human cells and in cultured rodent cells. It inhibited protein synthesis in various mammalian and human cell types in vitro. Chromosomal aberrations were also induced in insects. It induced gene mutation in cultured rodent cells but not in bacteria. It did not induce DNA damage in bacteria.

5.5 Evaluation

No data were available on the carcinogenicity to humans of toxins derived from Fusarium sporotrichioides.

There is limited evidence in experimental animals for the carcinogenicity of T-2 toxin.

Overall evaluation

Toxins derived from Fusarium sporotrichioides are not classifiable as to their carcinogenicity to humans
(Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Suppl. 7 (1987) (p. 73)

Synonyms

• Fusariotoxin T2
  
• Insariotoxin
  
• 8a(3-Methylbutyryloxy)4b,15-diacetoxyscirp-9-en-3a-ol
  
• Mycotoxin T2
  
• NSC 138780
  
• T-2 Mycotoxin
  
• Toxin T2
  
• T₂-Toxin
  
• T₂-trichothecene
  
• 3a-Hydroxy-4b,15-diacetoxy-8a-(3-methylbutyryloxy)-12,13-epoxy-d9-tricothecene

Last updated 08/21/1997

A MUST!!!

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(T-2 toxin is the main toxin produced by Stachybotrys and some Fusarium species, also Trichoderma, etc. T= Trichothecene. Also main consistuent of "allegedly Yellow Rain")

Article on Multiple Chemical Sensitivity on children:

Harvard Medical School:

A 4-Year-Old Girl with Manifestations of Multiple Chemical Sensitivities

Alan Woolf1,2 1Pediatric Environmental Health Subspecialty Unit and Clinical Toxicology Program, Children's Hospital Boston, Boston, Massachusetts, USA; 2Harvard Medical School, Boston, Massachusetts, USA

Abstract Children's Hospital Boston Harvard Medical School Multiple chemical sensitivities (MCS) syndrome, also known as idiopathic environmental intolerance, is a controversial diagnosis that encompasses a wide range of waxing and waning, subjective symptoms referable to more than one body system and provoked by exposure to low levels of chemicals, foods, or other agents in the environment. Although MCS has been studied extensively, a unifying mechanism explaining the illness remains obscure, and clinicians are divided as to whether such a medical entity exists separately from psychosomatic syndromes. MCS is an adult diagnosis; there is little reference to pediatric cases in the scientific literature. In this case from the Pediatric Environmental Health Subspecialty Unit at Boston's Children's Hospital, I present the case of a preschool child who had suffered from milk allergy and poor weight gain as an infant, and then later developed asthma, allergic symptoms, sinusitis, headaches, fatigue, and rashes precipitated by an expanding variety of chemicals, foods, and allergens. I review definitions, mechanisms, diagnostic strategies, and management, and discuss some uniquely pediatric features of MCS as illustrated by this case. Key words: idiopathic environmental intolerance, multiple chemical sensitivities. Environ Health Perspect 108:1219-1223 (2000). [Online 20 November 2000]

.

In Harm's Way: Toxic Threats to Child Development

Learning, behavioral and developmental disabilities including Attention Deficit Hyperactivity Disorder (ADHD) and autism prevent our children from reaching their full human potential. Seventeen percent of children in the United States have been diagnosed with one or more developmental disabilities. These disorders have widespread societal implications, from health and education costs to the repercussions of criminal behavior. Though trends are difficult to establish with certainty, there is a growing consensus that learning and behavioral disorders are increasing in frequency.

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California State Department: Mold resources:

Website: lots of useful informations on numerous referral websites.

Portable classrooms and mold.

Regarding: MOLD AND THE INDOOR AIR ENVIRONMENT: 

  "I am grateful and pleased that the college has taken a proactive measure in correcting these air quality issues," said Del Mar Regent Dorothy Spann. "This is a serious problem that needs to be looked at very carefully."
   "But I don't believed that they analyzed the problem completely," Spann said. "I think there are more problems, particularly in the auditorium." 
  

Monday, March 22, 1999 L O C A L   N E W S Local News Index | Local News Archives C-J Extra | The Courier-Journal Home Page

Hospital still faces fungus-death suits

This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization or the World Health Organization.

"Expensive"

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WHO: INTERNATIONAL AGENCY FOR RESEARCH ON CANCER.

EXCELLENT REVIEW ON AFLATOXIN CAUSING CANCER.

For definition of Groups, see Preamble Evaluation.

VOL.: 56 (1993) (p. 245)

Aflatoxin B₁
CAS No.: 1162-65-8

Aflatoxin B₂
CAS No.: 7220-81-7

Aflatoxin G₁
CAS No.: 1165-39-5

Aflatoxin G₂
CAS No.: 7241-98-7

Aflatoxin M₁
CAS No.: 6795-23-9

5.1 Exposure data

Aflatoxins are a group of relatively stable toxins produced mainly by two Aspergillus species that are ubiquitous in areas of the world with hot, humid climates. Whether exposure is predominantly to aflatoxin B₁ or to mixed B₁ and G₁ depends on the geographical distribution of the Aspergillus strains. Aspergillus flavus, which produces aflatoxins B₁ and B₂, occurs worldwide; A. parasiticus, which produces aflatoxins B₁, B₂, G₁ and G₂, occurs principally in the Americas and in Africa. Exposure occurs primarily through dietary intake of maize and groundnuts. Exposure to aflatoxin M₁ occurs mainly through consumption of milk, including mother's milk. Life-time exposure to aflatoxins in some parts of the world, commencing in utero, has been confirmed by biomonitoring.

5.2 Human carcinogenicity data

One cohort study of a small number of Dutch oilpress workers exposed to aflatoxin-containing dusts indicated increased mortality from cancer, but no death from hepatocellular carcinoma was observed. A cohort study in China found significant excess mortality from liver cancer among individuals in villages where foods were heavily contaminated with aflatoxins. A cohort study of Danish workers exposed to aflatoxin from imported feed found an excess of hepatocellular carcinoma among those who had had major exposure to aflatoxin-contaminated feed in the period 10 or more years before diagnosis. In a cohort study in China, a significant elevation in risk for hepatocellular carcinoma was found among people with aflatoxin metabolites in the urine, after adjustment for hepatitis B surface antigen positivity. The elevation in risk was particularly high among those excreting aflatoxin B₁-guanine adducts; however, there was no association between dietary and urinary aflatoxin levels among subjects in whom both were detected.

Of three hospital-based case-control studies in which an attempt was made to evaluate exposure to aflatoxin B₁, one (in the Philippines) found a significantly greater risk for hepatocellular carcinoma among people whose intake of aflatoxin was estimated to be heavy than in those with light aflatoxin intake. The other two studies, one in Hong Kong and one in Thailand, gave negative results. In Thailand, one study on hepatocellular carcinoma and another on cholangiocarcinoma also found no association with the presence of aflatoxin B₁-albumin adducts in sera.

The two cohort studies in China addressed combined exposure to hepatitis B virus and aflatoxins and suggested that each has an independent effect.

Several correlation studies have been performed, the majority showing a strong association between estimated aflatoxin intake and incidence of hepatocellular carcinoma. In only a few was it possible to evaluate simultaneously any correlation with the prevalence of hepatitis infection. Of those that did so, two - one in Swaziland and one in China - showed a stronger correlation with exposure to aflatoxin B₁ than with hepatitis B viral infection. The largest such study, in China, did not show an association with the presence of aflatoxin B₁ metabolites in urine. The study from Swaziland was the only one in which it was shown that subjects had concomitant exposure to aflatoxin B₁ and G₁.

5.3 Carcinogenicity in experimental animals

Mixtures of aflatoxins and aflatoxin B₁ have been tested extensively for carcinogenicity by various routes of administration in several strains of mice and rats, in hamsters, several strains of fish, ducks, tree shrews and monkeys. Following their oral administration, mixtures of aflatoxins and aflatoxin B₁ caused hepatocellular and/or cholangiocellular liver tumours, including carcinomas, in all species tested except mice. In rats, renal-cell tumours and a low incidence of tumours at other sites, including the colon, were also found. In monkeys, liver angiosarcomas, osteogenic sarcomas and adenocarcinomas of the gall-bladder and pancreas developed, in addition to hepatocellular and cholangiocellular carcinomas. In adult mice, aflatoxin B₁ administered intraperitoneally increased the incidence of lung adenomas. Intraperitoneal administration of aflatoxin B₁ to infant mice, adult rats and toads produced high incidences of liver-cell tumours in all of these species. Subcutaneous injection of aflatoxin B₁ resulted in local sarcomas in rats. Exposure of fish embryos to aflatoxin B₁ induced a high incidence of hepatocellular adenomas and carcinomas. Intraperitoneal administration of aflatoxin B₁ to rats during pregnancy and lactation induced benign and malignant tumours in mothers and their progeny in the liver and in various other organs, including those of the digestive tract, the urogenital system and the central and peripheral nervous systems. In several species, aflatoxin B₁ administered by different routes induced foci of altered hepatocytes, the number and size of which was correlated with later development of hepatocellular adenomas and carcinomas.

Aflatoxin B₂ induced foci of altered hepatocytes and hepatocellular adenomas following its oral administration to rats. A low incidence of hepatocellular carcinomas was observed after intraperitoneal administration of aflatoxin B₂ to rats.

Oral administration of aflatoxin G₁ induced foci of altered hepatocytes, hepatocellular adenomas and carcinomas and renal-cell tumours in rats and liver-cell tumours in fish. The hepatocarcinogenic effect of aflatoxin G₁ was weaker than that of aflatoxin B₁. Subcutaneous injection of aflatoxin G₁ in rats resulted in local sarcomas, which developed at a lower incidence and at later times than those induced by aflatoxin B₁ at the same dose level and by the same route. Oral administration of aflatoxin G₂ to trout had no hepatocarcinogenic effect in one experiment.

Aflatoxin M₁, a hydroxy metabolite of aflatoxin B₁, produced fewer hepatocellular carcinomas following its oral administration to rats and fish than aflatoxin B₁ given at the same dose level and by the same route. Aflatoxin Q₁, another metabolite of aflatoxin B₁, produced a high incidence of hepatocellular carcinomas following its oral administration to fish. Administration to rats and fish of aflatoxicol, yet another metabolite of aflatoxin B₁, induced hepatocellular carcinomas in both species; the tumour incidence was lower than that in animals treated with aflatoxin B₁ at the same dose level.

A large number of experiments have been carried out in which aflatoxins were administered in combination (prior to, during and following) with diets, viruses, parasites, known carcinogens and a number of different chemicals in order to study the modulating effects, including chemoprevention, of the agents on aflatoxin-induced carcinogenesis. Enhancing and inhibitory effects on the carcinogenicity of aflatoxins have been observed.

5.4 Other relevant data

Aflatoxin B₁ is consistently genotoxic, producing adducts in humans and animals in vivo and chromosomal anomalies in rodents and, in a single study, in rhesus monkeys in vivo. In human and animal cells in culture, it produces DNA damage, gene mutation and chromosomal anomalies; in animal cells in vitro, it also induces cell transformation. In insects and lower eukaryotes, it induces gene mutation and recombination. In bacteria, it produces DNA damage and gene mutation.

Aflatoxin B₁ is hepatoxic in humans and animals and is nephrotoxic and immunosuppressive in animals.

Aflatoxin B₂ has not been studied extensively, and most data are derived from single reports. Aflatoxin B₂ becomes bound to DNA of rats treated in vivo, after metabolic conversion to aflatoxin B₁. In rodent cells, it induces DNA damage, sister chromatid exchange and cell transformation, but not gene mutation. In fungi, it produces neither gene mutation nor recombination, whereas it produced gene mutation in bacteria.

Aflatoxin G₁ binds to DNA and produces chromosomal aberrations in rodents treated in vivo. In cultured human and animal cells, it induces DNA damage, and, in single studies, it induced chromosomal anomalies. It induces mutation in fungi and DNA damage and gene mutation in bacteria.

There are few published genetic studies on aflatoxin G₂ and aflatoxin M₁. Aflatoxin G₁ produced DNA damage and sister chromatid exchange in animal cells in culture. Aflatoxin M₁ produced DNA damage in cultured rodent cells and gene mutation in bacteria.

Humans metabolize aflatoxin B₁ to an 8,9-epoxide, forming DNA and albumin adducts by the same activation pathways as susceptible animal species. Humans metabolize aflatoxin B₁ to the major aflatoxin B₁-N7-guanine and -serum albumin adduct at levels comparable to those in susceptible animal species (rat).

Glutathione S-transferase-mediated conjugation of glutathione to the 8,9-epoxide reduces DNA damage, and this mechanism is important in reducing the tumour burden in experimental animals. Animal species, such as the mouse, that are resistant to aflatoxin carcinogenesis have three to five times more glutathione S-transferase activity than susceptible species, such as the rat. Humans have less glutathione S-transferase activity for 8,9-epoxide conjugation than rats or mice, suggesting that humans are less capable of detoxifying this important metabolite.

Studies of human microsomal activation of aflatoxin B₁ show that at non-saturating concentrations of aflatoxin B₁ the rate of formation of the 8,9-epoxide is similar to that found in sensitive species (rat and monkey).

The value of aflatoxin B₁-N7-guanine as an indicator of risk for developing tumours is demonstrated by experiments with chemoprotective agents that show concordance between reduction of levels of DNA adduct formation and reduced incidence of liver tumours in rats and trout.

The presence of DNA- and protein-aflatoxin adducts in humans, the urinary excretion of aflatoxin B₁-N7-guanine adducts by humans, and the ability of human tissues to activate aflatoxin B₁ to form DNA adducts in vitro provide evidence that humans have the biochemical pathways required for aflatoxin-induced carcinogenesis. The following evidence is consistent with those biochemical mechanisms.

Studies with bacteria show that activated aflatoxin B₁ specifically induces G to T transversions. On the basis of experiments conducted in vitro, aflatoxin B₁ specifically targets the third and not the second nucleotide of codon 249 (AGG) of the human p53 gene, an effect not seen with benzo[a]pyrene-7,8-diol-9,10-epoxide when tested at the same level of binding.

A high frequency of mutations at a mutational `hotspot' (the third nucleotide of codon 249 in exon 7) has been found in p53 tumour suppressor genes in hepatocellular carcinomas from patients resident in areas considered to offer a high risk of exposure to aflatoxins and where there is a high incidence of hepatocellular carcinoma. In contrast, this mutation is rare in hepatocellular carcinomas from regions of low exposure to aflatoxins (including Australia, Japan, southern Africa, Germany, Spain, Italy, Turkey, Israel, Saudi Arabia, the United Kingdom and the USA).

5.5 Evaluation

There is sufficient evidence in humans for the carcinogenicity of naturally occurring mixtures of aflatoxins.

There is sufficient evidence in humans for the carcinogenicity of aflatoxin B₁.

There is inadequate evidence in humans for the carcinogenicity of aflatoxin M₁.

There is sufficient evidence in experimental animals for the carcinogenicity of naturally occurring mixtures of aflatoxins and aflatoxins B₁, G₁ and M₁.

There is limited evidence in experimental animals for the carcinogenicity of aflatoxin B₂.

There is inadequate evidence in experimental animals for the carcinogenicity of aflatoxin G₂.

Overall evaluations

Naturally occurring aflatoxins are carcinogenic to humans (Group 1).

Aflatoxin M₁ is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Suppl. 7 (1987) (p. 83)

Subsequent evaluation: Vol. 82 (2002)

Synonyms for Aflatoxin B₁

• 6-Methoxydifurocoumarone
  
• 2,3,6aa,9aa-Tetrahydro-4-methoxycyclopenta[c]furo[3´,2´:4,5]furo[2,3-h][l]benzopyran-
  1,11-dione

Synonyms for Aflatoxin B₂

• Dihydroaflatoxin B₁
  
• 2,3,6aa,8,9,9aa-Hexahydro-4-methoxycyclopenta[c]furo[3´,2´:4,5]furo[2,3-h][l]benzopyran-
  1,11-dione

Synonym for Aflatoxin G₁

• 3,4,7aa,10aa-Tetrahydro-5-methoxy-1H,12H-furo[3´,2´:4,5]furo[2,3-h]pyrano[3,4-c][l]-
  benzopyran-1,12-dione

Synonyms for Aflatoxin G₂

• Dihydroaflatoxin G₁
  
• 3,4,7aa,9,10,10aa-Hexahydro-5-methoxy-1H,12H-furo[3´,2´:4,5]furo[2,3-h]pyrano[3,4-c][l]-
  benzopyran-1,12-dione

Synonym for Aflatoxin M₁

• 4-Hydroxyaflatoxin B₁

Last updated 08/21/1997

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Interesting review and information.

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