T-2 mycotoxin: Difference between revisions

{{|date=October 2008}}

| Verifiedfields = changed

| verifiedrevid = 438853897

| Reference = <ref>http://www.cbwinfo.com/Biological/Toxins/T2.html T-2 Toxin: essential data</ref>

| OtherNames = T-2 Toxin<br>Fusariotoxin T 2<br>Insariotoxin<br>Mycotoxin T 2

| ChEBI = 9381

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 152423

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = I3FL5NM3MO

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| MainHazards =

| FlashPt =

| = }}

'''T-2''' is a [[trichothecene]] [[mycotoxin]]. It is a naturally occurring [[mold]] byproduct of ''[[Fusarium]]'' [[fungus]] which is toxic to humans and animals. The clinical condition it causes is ''alimentary toxic aleukia]]'' and a host of symptoms related to organs as diverse as the skin, airway, and stomach may come from consumption of moldy whole .

Alimentary toxic aleukia (ATA), a disease which is caused by trichothecenes like T-2 mycotoxin, killed many thousands of USSR citizens in the [[Orenburg Oblast|Orenburg District]] in the 1940s. It was reported that the mortality rate was 10% of the entire population in that area. During the 1970s it was proposed that the consumption of [[food contamination|contaminated]] food was the cause of this mass poisoning. Because of World War II, harvesting of grains was delayed and food was scarce in Russia. This resulted in the consumption of grain that was contaminated with ''Fusarium'' molds, which produce T-2 mycotoxin.<ref>{{cite conference | vauthors = Pitt JI | title = An introduction to mycotoxins. | veditors = Semple RL, Frio AS, Hicks PA, Lozare JW | conference = Mycotoxin Prevention and kontrol in Food Grains. Proceedimgs of Assistance for The Training Course. | location = Bangkok | date = July 1989 }}</ref>

In 1981, the [[United States Secretary of State]] [[Alexander Haig]] and his successor [[George P. Shultz]] accused the Soviet Union of using T-2 mycotoxin as a chemical weapon known as "[[yellow rain]]" in Laos (1975–81), Kampuchea (1979–81), and [[Soviet–Afghan War|Afghanistan]] (1979–81), where it allegedly caused thousands of casualties.<ref>{{cite report | vauthors = Shultz GP | title = Chemical warfare in Southeast Asia and Afghanistan: an update. | publisher = US Department of State, Bureau of Public Affairs, Office of Public Communication, Editorial Division | date= 1982 }}</ref> Although several US chemical weapons experts claim to have identified "yellow rain" samples from Laos as trichothecenes, other experts believe that this exposure was due to naturally occurring T-2 mycotoxin in contaminated foods.<ref>{{cite journal | vauthors = Caldwell RD |title='Yellow rain' or natural toxins? |journal=Nature |volume=301 |issue=5902 |year=1983 |pages=651 |bibcode=1983Natur.301Q.651C |doi=10.1038/301651a0|s2cid=4263047 |doi-access=free }}</ref> Another alternative theory was developed by Harvard biologist [[Matthew Meselson]], who proposed that the "yellow rain" found in Southeast Asia originated from the excrement of jungle bees.<ref name = "NYT_1987" /> The first indication for this theory came from finding high levels of [[pollen]] in the collected samples, giving the substance its yellow color. It was also found that jungle bees in this area fly collectively in great numbers, at altitudes too high to be easily seen, producing showers of feces that could have been mistaken for sprays from aircraft.<ref>{{cite book | vauthors = Meselson MS, Robinson JP |chapter=The Yellow Rain Affair: Lessons from a Discredited Allegation |chapter-url=http://belfercenter.hks.harvard.edu/publication/18277/yellow_rain_affair.html |pages=72–96 |date=June 2008 | veditors = Clunan AL, Lavoy PR, Martin SB |title=Terrorism, War, or Disease? Unraveling the Use of Biological Weapons |location=Stanford |publisher=Stanford University Press |access-date=2015-09-03 |archive-date=2014-07-27 |archive-url=https://web.archive.org/web/20140727042947/http://belfercenter.hks.harvard.edu/publication/18277/yellow_rain_affair.html |url-status=dead }}</ref> Further testing later determined that the oily liquid was, in fact, the pollen-filled feces of jungle bees.<ref name = "NYT_1987">{{Cite news|date=September 3, 1987|title=Yellow Rain Falls|work=New York Times |url= https://query.nytimes.com/gst/fullpage.html?res=9B0DE7DA173AF930A3575AC0A961948260 |access-date=January 20, 2022|archive-url=https://web.archive.org/web/20121109120608/http://www.nytimes.com/1987/09/03/opinion/yellow-rain-falls.html|archive-date=November 9, 2012|quote=Yellow rain is the excrement of jungle bees. It's yellow from digested pollen grains, and it rains down from swarms of bees too high to be seen. His theory turns out to be exactly right. The Government's own studies, still unpublished, prove that the source is bees, not bombs.}}</ref> A similar case in China was brought to light, and in this instance the cause of the phenomenon had also been bee excrement.<ref>{{Cite journal| vauthors = Zhang Z |date=1977|title=A Study of the Origin and the Pollen Analysis of "Yellow Rain" in Northern Jiangsu|journal=Kexue Tongbao|volume=22|pages=409–12}}</ref> Despite this conclusive analysis, the United States has not withdrawn its allegations and declares that the issue has not been fully resolved.

T-2 mycotoxin is also thought to be a cause of [[Gulf War syndrome]]. US troops suffered from mycotoxicosis-like symptoms after an Iraqi missile detonated in a US military camp in Saudi Arabia during [[Operation Desert Storm]] in the Persian Gulf War, in 1991. It has been shown that Iraq researched trichothecene mycotoxins, among other substances, and thus was capable of its possession and employment in [[chemical warfare]]. Nevertheless, much of the key information from these incidents remains classified, leaving these matters still unresolved.<ref>{{cite journal | vauthors = Zilinskas RA | title = Iraq's biological weapons. The past as future? | journal = JAMA | volume = 278 | issue = 5 | pages = 418–424 | date = August 1997 | pmid = 9244334 | doi = 10.1001/jama.1997.03550050080037 }}</ref>

== Chemical properties ==

This compound has a tetracyclic [[sesquiterpenoid]] 12,13-epoxytrichothene ring system, which relates it to the trichothecenes.<ref>{{EMedicine|article|830892|CBRNE - T-2 Mycotoxins}}</ref> These compounds are generally very stable and are not degraded during storage/milling and cooking/processing of food. They do not degrade at high temperatures either. This compound has an epoxide ring, and several acetyl and hydroxyl groups on its side chains. These features are mainly responsible for the biological activity of the compound and make it highly toxic. T-2 mycotoxin is able to inhibit [[DNA synthesis|DNA]] and [[RNA synthesis]] [[in vivo]] and [[in vitro]]<ref>{{cite journal | vauthors = Marin S, Ramos AJ, Cano-Sancho G, Sanchis V | title = Mycotoxins: occurrence, toxicology, and exposure assessment | journal = Food and Chemical Toxicology | volume = 60 | pages = 218–237 | date = October 2013 | pmid = 23907020 | doi = 10.1016/j.fct.2013.07.047 }}</ref> and can induce [[apoptosis]].<ref>{{cite journal | vauthors = Torp M, Langseth W | title = Production of T-2 toxin by a Fusarium resembling Fusarium poae | journal = Mycopathologia | volume = 147 | issue = 2 | pages = 89–96 | date = 1999 | pmid = 10967967 | doi = 10.1023/A:1007060108935 | s2cid = 13540977 }}</ref> However, in vivo the compound rapidly metabolizes to HT-2 mycotoxin (a major [[metabolite]]).<ref>{{cite journal | vauthors = Wu QH, Wang X, Yang W, Nüssler AK, Xiong LY, Kuča K, Dohnal V, Zhang XJ, Yuan ZH | display-authors = 6 | title = Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update | journal = Archives of Toxicology | volume = 88 | issue = 7 | pages = 1309–1326 | date = July 2014 | pmid = 24894432 | doi = 10.1007/s00204-014-1280-0 | s2cid = 14146122 }}</ref>

==Mechanism of action==

The [[toxicity]] of T-2 toxin is due to its 12,13-epoxy ring.<ref name="T-2 Mycotoxin Review">{{cite journal | vauthors = Li Y, Wang Z, Beier RC, Shen J, De Smet D, De Saeger S, Zhang S | title = T-2 toxin, a trichothecene mycotoxin: review of toxicity, metabolism, and analytical methods | journal = Journal of Agricultural and Food Chemistry | volume = 59 | issue = 8 | pages = 3441–3453 | date = April 2011 | pmid = 21417259 | doi = 10.1021/jf200767q }}</ref> [[Epoxide]]s are in general toxic compounds; these react with [[nucleophile]]s and then undergo further [[enzymatic reaction]]s. The [[reactivity (chemistry)|reactivity]] of epoxides can lead to reactions with endogenous compounds and cellular constituents like DNA bases and proteins.<ref>{{Cite book | vauthors = Timbrell JA |url= https://www.taylorfrancis.com/books/mono/10.3109/9781420007084/principles-biochemical-toxicology-john-timbrell |title=Principles of Biochemical Toxicology |date=2013-01-28 |publisher=CRC Press |isbn=978-0-429-12493-8 |edition=4th |location=Boca Raton |doi=10.3109/9781420007084}}</ref>

These reactions could be the reason for the noticed actions and effects of T-2 mycotoxin. The toxic compound influences the [[metabolism]] of [[cell membrane|membrane]] [[phospholipid]]s, leads to an increase of liver lipid [[peroxidase]]s and has an inhibiting effect on DNA and RNA synthesis. In addition it can bind to an integral part of the 60s ribosomal subunit, [[peptidyltransferase]], thereby inhibiting [[protein synthesis]].

These effects are thought to be the explanation for T-2 toxin inducing apoptosis (cell death) in different tissues as the [[immune system]], the gastrointestinal tissue and also fetal tissue. With regard to apoptosis there has been noticed that the level of the pro-apoptotic factor Bas (Bcl-2-associated X protein) was increased and the level of Bcl-xl, an anti-apoptotic factor, was decreased in human chrondocytes ([[cartilage]] cells). When exposed to T-2 mycotoxin. Furthermore, the level of Fas, an apoptosis-related cell-surface antigen and p53, a protein regulating the cell cycle, were increased.

[[File:T-2 Mycotoxin Biosynthesis.png|thumb|Simplified biosynthesis of the T-2 Mycotoxin in F. sporotrichioides]]

==Synthesis==

T-2 mycotoxin is produced naturally by Fusarium fungi of which the most important species are: ''F. sporotrichioides'', ''F. langsethiae'', ''F. acuminatum'' and ''F. poae''. These fungi are found in grains such as [[barley]], [[wheat]] and [[oats]]. The production of this compound for research and commercial purposes is generally accomplished by cultivating some strain of T-2 mycotoxin producing fungi on [[agar plate]]s. On these agar plates the fungi appear powdery and can yield substantial amounts of T-2 mycotoxin. For the isolation of the compound [[high pressure liquid chromatography]] is commonly used (HPLC).<ref>{{cite web | title = T-2 toxin from fusarium sp., powder, ≥98% (HPLC) | url = http://www.sigmaaldrich.com/catalog/product/sigma/t4887?lang=en&region=NL | work = Sigma-Aldridge }}

</ref>

In the ''Fusarium'' species, [[biosynthesis]] of the T-2 mycotoxin often starts with trichodiene, and many of the species share a common route of [[Redox|oxidizations]] and [[Cyclic compound|cyclizations]]. As an example, from the ''F. sporotrichioides'' species, the important oxidation steps that occur start from trichodiene and goes to isotrichodiol. From there, the eleventh carbon atom is oxidized to form isotrichotriol. The ninth carbon is then oxidized, and trichotriol is formed, which then cyclizes to make isotrichodermol. After that, the fifteenth carbon is oxidized to form didecalonectrin, which leads to the fourth carbon being oxidized, and diacetoxyscirpenol is formed. The second to last step is the oxidation of the eighth carbon to make neosolaniol, which then undergoes slight modification to create the T-2 toxin.<ref>{{cite journal | vauthors = Desjardins AE, Hohn TM, McCormick SP | title = Trichothecene biosynthesis in Fusarium species: chemistry, genetics, and significance | journal = Microbiological Reviews | volume = 57 | issue = 3 | pages = 595–604 | date = September 1993 | pmid = 8246841 | pmc = 372927 | doi = 10.1128/MMBR.57.3.595-604.1993 }}</ref>

==Toxicity==

=== ADME properties ===

{{See also|ADME}}

==== Absorption and exposure ====

Humans and animals are generally exposed to T-2 mycotoxins through food. Certain grains can contain the toxin which makes it a threat to human health and an economic burden.<ref>{{cite journal | vauthors = Wan Q, Wu G, He Q, Tang H, Wang Y | title = The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique | journal = Molecular BioSystems | volume = 11 | issue = 3 | pages = 882–891 | date = March 2015 | pmid = 25588579 | doi = 10.1039/C4MB00622D }}</ref> Unlike most biological toxins T-2 mycotoxin can be absorbed through intact skin. The compound can be delivered via food, water, droplets, [[aerosol]]s and smoke from various dispersal systems. This makes it a potential [[biological weapon]], however large amounts of the compound are required for a [[lethal dose]]. T-2 mycotoxin has an {{LD50}} of approximately 1 milligram per kilogram of body weight.

The [[EFSA]] estimates that the mean exposure of T-2 in the EU lies between 12 and 43&nbsp;ng/kg bw/day.<ref>{{cite journal | vauthors = Escrivá L, Font G, Manyes L | title = In vivo toxicity studies of fusarium mycotoxins in the last decade: a review | journal = Food and Chemical Toxicology | volume = 78 | pages = 185–206 | date = April 2015 | pmid = 25680507 | doi = 10.1016/j.fct.2015.02.005 }}</ref> This range is below the TDI of 100&nbsp;ng/ kg body weight for the sum of HT-2 and T-2 toxins which is used by the EFSA.

==== Distribution ====

T-2 mycotoxin is distributed uniformly throughout the body without preference to a specific organ or site. In rodents, [[Blood plasma|plasma]] concentration levels peak around roughly thirty minutes after exposure, and in one study, the [[Biological half-life|half-life]] of the T-2 toxin was seen to be less than twenty minutes. In a different study involving pigs, the distribution after four hours of IV injection was seen to be 15–24% in the GI tract and 4.7–5.2% in various other tissues.<ref name = "Toxicological Effects">{{cite journal | vauthors = Adhikari M, Negi B, Kaushik N, Adhikari A, Al-Khedhairy AA, Kaushik NK, Choi EH | title = T-2 mycotoxin: toxicological effects and decontamination strategies | journal = Oncotarget | volume = 8 | issue = 20 | pages = 33933–33952 | date = May 2017 | pmid = 28430618 | pmc = 5464924 | doi = 10.18632/oncotarget.15422 }}</ref>

==== Metabolism ====

Once absorbed and distributed to various tissues, the T-2 mycotoxin goes through various metabolic reactions before it gets excreted. In vivo studies showed that the most occurring reactions are [[ester]] [[hydrolysis]] and [[hydroxylation]] of the isovaleryl group. Deepoxidation and [[glucuronide]] conjugation do also occur. Ht-2 is the main metabolite. For the hydroxylation, the cytochrome p450 enzyme complex is suggested to be involved. T-2 triol and T-2 tetraol are most likely to be formed via [[acetylcholine esterase]]s. Some of the metabolic reactions of the mycotoxin are performed by the [[microflora]] in the gut. The formed metabolites in these reactions are species- and pH-dependent. The ester cleavages are however performed by the mammal itself and not by the microflora. In [[red blood cell]]s T-2 mycotoxin is metabolized to neosolaniol, and, in [[white blood cell]]s, to HT-2 via hydrolysis catalyzed by carboxylesterases.

==== Excretion ====

Following absorption, distribution, and metabolism, T-2 mycotoxin is excreted fairly quickly, where 80–90% of it is excreted within 48 hours.<ref name = "Toxicological Effects" /> The main methods of excretion seem to be from the urine and feces,<ref name = "Ch 34 Trichothecene Mycotoxins">{{cite book | vauthors = Wannemacher RW, Weiner SL |title=Medical aspects of chemical and biological warfare | chapter = Chapter 34: Trichothecene Mycotoxins |date=1997 |publisher = U.S. Government Printing Office |isbn=9789997320919 |pages=655–676}}</ref> where excretion through [[bile]] contributes heavily to the feces route of excretion.<ref name="T-2 Mycotoxin Review" /> There is also very little of the parent T-2 mycotoxin in the excretions, meaning most of the initial compound is metabolized beforehand.<ref name = "Ch 34 Trichothecene Mycotoxins" />

=== Toxic effects ===

T-2 is highly toxic when inhaled. Acute toxic symptoms include vomiting, diarrhea, skin irritation, itching, rash, blisters, bleeding and [[dyspnea]].{{cn|date=June 2024}} If the individual is exposed to T-2 over a longer period alimentary toxic aleukia (ATA) develops.

At first the patient experiences a burning sensation in the mouth, throat and stomach. After a few days the person will suffer from an acute [[gastroenteritis]] that will last for 3 to 9 days. Within 9 weeks the [[bone marrow]] will slowly degenerate. Also the skin starts bleeding and the total number of [[leukocyte]]s decreases. Problems with the nervous system can occur.

In the end the following symptoms might occur: a high fever, [[petechial haemorrhage]], [[necrosis]] of muscles and skin, bacterial infections of the necrotic tissue, [[enlarged lymph nodes]]. There is the possibility of [[asphyxiation]] because of [[larynx|laryngeal]] [[oedema]] and [[stenosis]] of the [[glottis]]. The lack of oxygen is then the cause of death. Otherwise the patient will die of [[bronchial pneumonia]] and lung bleeding.<ref>{{cite report | vauthors = Semple RL, Frio AS, Hicks PA, Lozare JV | title = Mycotoxin prevention and control in foodgrains. | work = UNDP/FAO Regional Network Inter-Country Cooperation on Preharvest Technology and Quality Control of Foodgrains (REGNET) and the ASEAN Grain Postharvest Programme | location = Thailand | date = 1989 }}</ref>

=== Effects on animals ===

T-2 mycotoxin is also toxic to animals. The compound is known for having lethal and sub-lethal effects on farm animals. It is often found in contaminated cereal grains that are fed to these animals.<ref>{{cite journal | vauthors = Cortinovis C, Pizzo F, Spicer LJ, Caloni F | title = Fusarium mycotoxins: effects on reproductive function in domestic animals--a review | journal = Theriogenology | volume = 80 | issue = 6 | pages = 557–564 | date = October 2013 | pmid = 23916251 | doi = 10.1016/j.theriogenology.2013.06.018 }}</ref> Most of the toxic effects are shared between humans and animals. After exposing [[zebra fish]] embryos to a concentration of 20&nbsp;μmol/L or higher [[malformation]] and [[mortality rate]]s increased. The malformations included tail deformities, [[cardiovascular]] defects and changes in behavior in early stages of life. This is the result of an increase in the amount of epoxides, which causes cell apoptosis.<ref>{{cite journal | vauthors = Yuan G, Wang Y, Yuan X, Zhang T, Zhao J, Huang L, Peng S | title = T-2 toxin induces developmental toxicity and apoptosis in zebrafish embryos | journal = Journal of Environmental Sciences | volume = 26 | issue = 4 | pages = 917–925 | date = April 2014 | pmid = 25079423 | doi = 10.1016/S1001-0742(13)60510-0 }}</ref> Other studies have shown that T-2-toxin causes lipid peroxidation in rats after feeding it to them. As the effect of T-2 toxin, elevated reactive oxygen species (ROS) levels were observed in several mammalian species. However, in spite of the general harmful effects caused by the toxin, in a study carried out in different chicken derived hepatic cell culture models, no alterations were found in the redox status of the cells.<ref>{{cite journal | vauthors = Mackei M, Orbán K, Molnár A, Pál L, Dublecz K, Husvéth F, Neogrády Z, Mátis G | display-authors = 6 | title = Cellular Effects of T-2 Toxin on Primary Hepatic Cell Culture Models of Chickens | journal = Toxins | volume = 12 | issue = 1 | pages = 46 | date = January 2020 | pmid = 31941063 | pmc = 7020465 | doi = 10.3390/toxins12010046 | doi-access = free }}</ref>

The compound also seems to reduce the fertility of ewes and heifers. Research has shown that a high dose of T-2 delays the [[ovulation]] due to a delayed [[ovarian follicle|follicle]] maturation. This possibly retards the following [[luteinisation]], which makes it impossible for female animals to conceive.

T-2 also has an effect on the fertility of bulls. In 1998 it was discovered that moldy hay influenced the quality of semen of bulls. Analysis of the moldy hay showed that T-2 was present. The compound decreased [[sperm motility]] and testosterone levels and increased the frequency of morphological abnormalities in the sperm cells.

The liver is another target for the mycotoxin. It is one of the first organs where the compound passes through after ingestion. Here it causes a reduced expression of [[CYP1A]] proteins in rabbits, pigs and rats. [[CYP3A]] activity decreases in pigs too. These enzymes help metabolize drugs that pass through the liver. Decrease in the activity could lead to an increase of unmetabolized drugs in the plasma. This can have a dangerous effect on an animal's health.<ref>{{cite journal | vauthors = Goossens J, De Bock L, Osselaere A, Verbrugghe E, Devreese M, Boussery K, Van Bocxlaer J, De Backer P, Croubels S | display-authors = 6 | title = The mycotoxin T-2 inhibits hepatic cytochrome P4503A activity in pigs | journal = Food and Chemical Toxicology | volume = 57 | pages = 54–56 | date = July 2013 | pmid = 23524315 | doi = 10.1016/j.fct.2013.03.009 }}</ref>

All of the mentioned effects happen when T-2 is ingested in high doses. Animals are able to metabolize the compound with enzymes from the CYP3A family, just like humans.

== Treatments ==

At the moment, there is no specific therapy for T-2 mycotoxin poisonings.<ref name = "Ch 34 Trichothecene Mycotoxins" /> Exposure of the mycotoxin is typically followed by standardized treatment for toxic compounds in order to reduce the effect of the toxin. This includes using [[Activated charcoal (medication)|activated charcoal]], which has a high binding capacity of 0.48&nbsp;mg of T-2 mycotoxin to 1&nbsp;mg of charcoal.<ref name = "Ch 34 Trichothecene Mycotoxins" /> For dermal contact, soap and water is used to reduce the dermal effects.<ref name = "Ch 34 Trichothecene Mycotoxins" /> As a kind of [[Preventive care|prophylaxis]], [[antioxidants]] are believed to have properties that may provide benefits.<ref name = "Toxicological Effects" />

== Application ==

There are currently no applications, aside from war, for T-2 mycotoxins; however, there are some plausible therapeutic uses. Due to their abilities, research shows possible uses for the mycotoxin as growth promoters, [[antibiotic]]s, [[Antiviral drug|antivirals]], as an [[Antileukemic drug|antileukemic]], and as an [[Antimalarial medication|antimalarial]].<ref name = "Toxicological Effects" />

== See also ==

* [[Yellow rain]]

{{reflist}}

== Further reading ==

{{refbegin}}

* {{cite book | chapter = Mycotoxin (T-2) | pages = 107–111 | title = Medical Management of Biological Casualties: Handbook. | publisher = US Army Medical Research Institute of Infectious Diseases (USAMRIID) | date = 1998 | chapter-url = https://books.google.com/books?id=dnqaKkEsHpcC&q=T-2%20mycotoxin&pg=PA107 }}

* {{cite journal | vauthors = Bamburg JR, Riggs NV, Strong FM | title = The structure of toxins from two stains of Fusarium tricinctum. | journal = Tetrahedron | volume = 24 | pages = 3329–3336 | date = 1968 | issue = 8 | doi = 10.1016/S0040-4020(01)92631-6 | pmid = 5648271 }}

* {{cite book | vauthors = Bamburg JR, Strong FM | chapter = 12,13-Epoxytrichothecenes. | title = Microbial Toxins | volume = VII | veditors = Kadis S, Ciegler A, Ajl SJ | publisher = Academic Press | location = New York, NY | pages = 207–292 | date = 1971 }}

{{refend}}

== External links ==

* [https://web.archive.org/web/20041216003845/http://www.gulflink.osd.mil/bw_ii/bw_tabe.htm US Military Gulf War Syndrome site]

* [http://mold-help.org/content/view/505/ T-2 mycotoxin exports to Iraq] {{Webarchive|url=https://web.archive.org/web/20050204072125/http://mold-help.org/content/view/505/ |date=2005-02-04 }}

* [http://cns.miis.edu/npr/pdfs/81tucker.pdf The 'Yellow rain' controversy]

* [https://web.archive.org/web/20050218155113/http://www.ascb.org/publicpolicy/psa02.html Meselson report summary]

{{Chemical agents}}

{{Toxins}}

[[Category:Trichothecenes]]

[[Category:Epoxides]]

[[Category:Acetate esters]]

[[Category:Food safety]]

[[Category:Secondary alcohols]]

[[Category:Alkene derivatives]]

[[Category:Blister agents]]

[[Category:Protein synthesis inhibitors]]

[[Category:Dermatoxins]]