Microcystin
Microcystins—or cyanoginosins—are a class of toxins produced by certain freshwater cyanobacteria, commonly known as blue-green algae. Over 50 different microcystins have been discovered so far, of which microcystin-LR is the most common. Chemically they are cyclic heptapeptides produced through nonribosomal peptide synthases. Cyanobacteria can produce microcystins in large quantities during algal blooms which then pose a major threat to drinking and irrigation water supplies, and the environment at large. Characteristics. Microcystins—or cyanoginosins—are a class of toxins produced by certain freshwater cyanobacteria; primarily "Microcystis aeruginosa" but also other "Microcystis", as well as members of  the "Planktothrix", "Anabaena", "Oscillatoria" and "Nostoc" genera. Over 50 different microcystins have been discovered so far, of which microcystin-LR is the most common. Chemically they are cyclic heptapeptides produced through nonribosomal peptide synthases. Microcystin-LR is the most toxic form of over 80 known toxic variants, and is also the most studied by chemists, pharmacologists, biologists, and ecologists. Microcystin-containing 'blooms' are a problem worldwide, including China, Brazil, Australia, South Africa, the United States and much of Europe. Hartebeespoort Dam in South Africa is one of the most contaminated sites in Africa, and possibly in the world. Microcystins contain  several uncommon non-proteinogenic amino acids such as dehydroalanine derivatives and the uncommon β-amino acid ADDA. Microcystins covalently bond to and inhibit protein phosphatases PP1 and PP2A and can thus cause pansteatitis. Formation. The microcystin-producing "Microcystis" is a genus of freshwater cyanobacteria and thrives in warm water conditions, especially in stagnant waters. The EPA predicted in 2013 that climate change and changing environmental conditions may lead to harmful algae growth and may negatively impact human health. Algal growth is also encouraged through the process of eutrophication (oversupply of nutrients). In particular, dissolved reactive phosphorus promotes algal growth. Exposure  pathways. There are several ways of exposure to these hepatotoxins that humans can encounter one of which is through recreational activities like swimming, surfing, fishing, and other activities involving direct contact with contaminated water. Another rare, yet extremely toxic, route of exposure that has been identified by scientists is through hemodialysis surgeries. One of the fatal cases for microcystic intoxication through hemodialysis was studied in Brazil where 48% of patients that received the surgery in a specific period of time died because the water used in the procedure was found to be contaminated. Microcystins are chemically stable over a wide  range of temperature and pH, possibly as a result of their cyclic structure. Microcystin-LR water contamination is resistant to boiling and microwave treatments. Microcystin-producing bacteria algal blooms can overwhelm the filter capacities of water treatment plants. Some evidence shows the toxin can be transported by irrigation into the food chain. Lake Erie blooms. In 2011, a record outbreak of blooming microcystis occurred in Lake Erie, in part related to the wettest spring on record, and expanded lake bottom dead zones, reduced fish populations, fouled beaches, and damaged the local tourism industry, which generates more than $10 billion  in revenue annually. In August 2014, the City of Toledo, Ohio detected unsafe levels of microcystin in its water supply due to harmful algal blooms in Lake Erie, the shallowest of the Great Lakes. The city issued an advisory to approximately 500,000 people that the water was not safe for drinking or cooking. An Ohio state task force found that Lake Erie received more phosphorus than any other Great Lake, both from crop land, due to the farming practices, and from urban water-treatment centres. San Francisco Bay Area. In 2016, microcystin had been found in San Francisco Bay Area  shellfish in seawater, apparently from freshwater runoff, exacerbated by drought. Iowa. In 2018, the Iowa Department of Natural Resources found microcystins at levels of .3 µg/L, or micrograms per liter, which is equivalent to .3 parts per billion in the raw water supplies of 15 out of 26 public water systems tested. Human health effects upon exposure. Microcystins cannot be broken down by standard proteases like pepsin, trypsin, collagenase, and chymotrypsin due to their cyclic chemical nature. They are hepatotoxic, i.e., able to cause serious damage to the liver. Once ingested, microcystin travels to the liver via the  bile acid transport system, where most is stored, though some remains in the blood stream and may contaminate tissue. Acute health effects of Microcystin-LR are abdominal pain, vomiting and nausea, diarrhea, headache, blistering around the mouth, and after inhalation sore throat, dry cough, and pneumonia. Studies suggest that the absorption of microcystins occurs in the gastrointestinal tract. Furthermore, it was found that these hepatotoxins inhibit the activity of protein enzymes phosphatase PP1 and PP2A causing hemorrhagic shock and were found to kill within 45 minutes in mice studies. There appears to be inadequate information to assess the carcinogenic potential  of microcystins by applying EPA Guidelines for Carcinogen Risk Assessment. A few studies suggest a relationship may exist between liver and colorectral cancers and the occurrence of cyanobacteria in drinking water in China. Evidence is, however, limited due to limited ability to accurately assess and measure exposure. Regulation. In the US, the EPA issued a health advisory in 2015. A ten day Health Advisory was calculated for different ages which is considered protective of non-carcinogenic adverse health effects over a ten-day exposure to microcystins in drinking water: 0.3 μg/L for bottle-fed infants and young children of  pre-school age and 1.6 μg/L for children of school age through adults.