シクロ[D-Ala-L-Leu-[(3S)-3-メチル-D-βAsp-]-L-Arg-[(2S,3S)-2-メチル-3-[(1E,3E,5S,6S)-3,5-ジメチル-6-メトキシ-7-フェニル-1,3-ヘプタジエン-1-イル]-βAla-]-D-γGlu-N-メチル-Dha-]

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a POTW is acceptable only after review by the governing authority. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must meet Hazardous Material Criteria for disposal.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

Previous studies have demonstrated that chlorine and potassium permanganate are feasible oxidants for the removal of microcystins (MCs) present in drinking water resources, although the oxidation might lead to toxic oxidation products.

... Nanofiltration membranes are an effective barrier against anatoxin-a and microcystins in drinking water. Anatoxin-a and especially microcystins were almost completely removed, regardless of the variations in feed water quality (natural organic matter and competitive toxin), the water recovery rate and the pH values. Anatoxin-a removal was governed by electrostatic interactions and steric hindrance, whereas for microcystins the latter was the main mechanism. In turn, fluxes were significantly impacted by background organics and, especially, inorganics (pH, calcium).

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Microcystin-LR (6 total), please visit the HSDB record page.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Because adequate surveillance is difficult and few immediate management options are available (other than precluding or discouraging use or cancelling water sports activities such as competitions), provision of adequate public information is a key short-term measure. Medium- to long-term measures are identification of the sources of nutrient (in many ecosystems phosphorus, sometimes nitrogen) pollution and significant reduction of nutrient input in order to effectively reduce proliferation not only of cyanobacteria, but of potentially harmful algae as well. /Cyanotoxins/

Within areas subject to the occurrence of marine toxic algae or cyanobacteria, it is important to carry out adequate monitoring activities and surveillance programs. In affected areas, it is appropriate to provide health information to general practitioners and the general public, in particular recreational water users. Precautionary measures include avoiding areas with visible algal concentrations and/or algal scums in the sea as well as on the shore, avoiding sitting downwind of any algal material drying on the shore and showering to remove any algal material. /Cyanobacteria and toxic algae/

PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for Microcystin-LR (14 total), please visit the HSDB record page.

0.0013 [mg/m3]

0.014 [mg/m3]

0.083 [mg/m3]

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

WHO Provisional Guideline: 0.001 mg/L (for total microcystin-LR, free plus cell-bound)

The maximum acceptable concentration (MAC) for the cyanobacterial toxin microcystin-LR in drinking water is 0.0015 mg/L (1.5 ug/L). This guideline is believed to be protective of human health against exposure to other microcystins (total microcystins) that may also be present.

Guidelines or standards for cyanobacterial toxins in drinking water. [Table#7417]

... Mice injected ip with microcystin (Mcyst) (LD50 50-100 ug/kg) accumulate Mcyst in the liver and die within 2-4 hr with massive intrahepatic hemorrhage. Pretreatment of mice with cyclosporin A (CP), rifamycin (Rif), trypan blue (TB), and trypan red (TR) protected the animals from a lethal dose of the toxin. The studies reported here using the freshly isolated rat hepatocyte model were undertaken in order (1) to evaluate the contribution of Mcyst transport in hepatocytes to the mechanism of chemoprotection for Mcyst in vivo toxicity by CP, Rif, TB, and TR and (2) to better characterize the hepatic Mcyst transporter in this model and determine its relationship to other bile acid/organic anion transporters that have already been fully described. Incubations with 125I-Mcyst were used to measure Mcyst uptake and accumulation in hepatocytes. It has been shown that at the cellular level Mcyst binds to and inhibits protein phosphatases 1 and 2A (PP) at nanomolar concentrations. Lethal doses of Mcyst in mice resulted in rapid profound inhibition of hepatic PP activity. PP activity was also inhibited in hepatocytes incubated with 100-500 nM Mcyst. PP inhibition in these studies was used as a marker of metabolic effects of the toxin. The chemoprotectants CP (5 uM), Rif (50 uM), TR (20 uM), and TB (20 uM) decreased accumulation of Mcyst (320 nM, a toxic concentration) after 30 min incubation to 37, 26, 30, and 66%, respectively, of that of cells treated with Mcyst only. Inhibition of PP activity in these cells was decreased. Inhibition of PP activity in hepatocytes was also decreased by known inhibitors of Mcyst transport: 50 uM of the bile acids cholate and taurocholate (TC) and 50 uM sulfobromophthalein. For all compounds tested the amount of Mcyst accumulated in the hepatocytes correlated qualitatively with the extent of PP inhibition. From these results it can be concluded that inhibition of Mcyst uptake by hepatocytes is the most likely mechanism of chemoprotection for Mcyst in vivo toxicity for TR, TB, CP, and Rif. Uptake of Mcyst was unaffected by changes in the ionic composition of the uptake buffer but was significantly decreased when PP activity of hepatocytes was inhibited by preincubation with Mcyst. /Microcystin/

Microcystin-LR (MCLR) is a potent hepatotoxin that rapidly produces death in experimental animals. ... Cyclosporin A (CsA) can prevent the toxic and lethal effects of MCLR in mice. The LD50 of MCLR in mice is approximately 61 ug/kg, and 100 ug/kg produces death in 100% of treated mice. The minimum dose of CsA which prevented lethality in mice given 100 ug MCLR/kg ip was 10 mg/kg. This dose of CsA did not protect mice against higher doses of MCLR. Survival of all mice given 100 ug MCLR/kg was achieved if 10 mg CsA/kg was given 0.5-3 hr prior to the MCLR but not if the CsA was co-administered or given after the MCLR... chemoprotective effects.

The potential benefits of dietary supplementation of selenium, an antioxidant, to protect against the mouse liver injury induced by the toxin, microcystin-LR, has been investigated. BALB/c mice were pretreated for two weeks with sodium selenite (1.5 ug/mouse/day) before an intraperitoneal injection of microcystin-LR. Selenium-supplementation was found to provide some protection to the action of the toxin. In addition selenium pretreatment reduced the liver damage caused by lethal and sub-lethal toxin doses as reflected in liver pathology, decreased serum ALT and lipid peroxidation levels as well as prevention of glycogen loss compared to non-selenium supplemented toxin treated mice. The increased level of liver glutathione peroxidase activity following selenium-supplementation may indicate the possible route of selenium protection in the mice.

Microcystins (MCs) are potent hepatotoxins produced by cyanobacteria in water systems that induce oxidative stress in fish. The present study investigated the effect of vitamin E (vit E) pretreatment on MCs-induced oxidative damage in liver, kidney, and gills of tilapia fish (Oreochromis niloticus). Groups of fish were fed vitamin E supplements (200 or 700 mg/kg diet) for seven days, or received only commercial fish food, and then were exposed to a single oral dose of cyanobacterial cells (120 ug/fish microcystin-LR (MC-LR)), and were sacrificed in 24 hr. The potential benefits of vit E were evaluated based on lipid peroxidation (LPO), protein oxidation, catalase (CAT, Enzyme Commision (EC) number 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1), glutathione peroxidase (GPx, EC 1.11.1.9), glutathione reductase (GR, EC 1.8.1.7), and the ratio reduced glutathione/oxidized glutathione (GSH/GSSG). Microcystins induced a 1.6-fold increase in LPO values in liver, whereas vitamin E pre-treated fish did not show any alteration on this biomarker. Enzyme activities levels were also ameliorated by the chemoprotectant whereas protein oxidation and GSH/GSSG did not show any significant change. The higher vitamin E dose used showed to have the greater protective effects, particularly on the biomarkers LPO and CAT activity. The results show that vit E could have a potential utility as preventive or therapeutic measure in MC-exposed fish.

For more Interactions (Complete) data for Microcystin-LR (16 total), please visit the HSDB record page.

LD50; Species: Artemia salina (Brine shrimp) larvae, 1 day old; Conditions: saltwater, static, 30 °C, salinity 15 ppt; Concentration: 3750 ug/L (2930-5680 ug/L) for 24 hr

LC50; Species: Spodoptera littoralis (Egyptian cotton leafworm) larvae, 60-100 mg; intrasegmentally 4.72 mg/kg (3.70-6.18 mg/kg)

LD50; Species: Plutella xylostella (Diamondback moth) 3rd instar; chemical incorporated into the food (treated leaf surface) 1.02 ug/sq cm (0.78-1.21 ug/sq cm) for 24 hr

LD50; Species: Plutella xylostella (Diamondback moth) 3rd instar; chemical incorporated into the food (treated leaf surface) 0.89 ug/sq cm (0.73-1.11 ug/sq cm) for 48 hr

For more Ecotoxicity Values (Complete) data for Microcystin-LR (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based upon its tendency to absorb to sediment or generally remain in solution(1,2), microcystin-LR is expected to be immobile in soil(SRC). Microcystin-LR can exist as neutral or weakly anionic(1,2). Anions generally do not adsorb to soils containing organic carbon and clay as compared to their neutral counterparts(3). Volatilization of microcystin-LR from moist soil surfaces is not expected to be an important fate process because the compound can exist as a weak anion, and anions do not volatilize. Biodegradation half-lives ranging from 0.2 to 3.6 days have been reported for microcystin-LR in sewage, lakes, and lake sediments, suggesting that biodegradation may be an important environmental fate process in soil(1).

AQUATIC FATE: Microcystins as a neutral species are expected to absorb to suspended solids and precipitate out of solution into sediment; however, as reported, microcystins that exist as a weak anion do not tend to absorb to sediments or suspended particulates, and instead tend to remain in solution(1,2). Microcystin-LR will exist partially in the anion form at pH values of 5 to 9(2), and therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Biodegradation half-lives ranging from 0.2 to 3.6 days have been reported for microcystin-LR in sewage, lakes, and lake sediments, suggesting that biodegradation may be an important environmental fate process in water(1). Microcystin-LR in reservoir water is reported to have a half-life of less than 1 week, and in ambient waters, biodegradation occurs with a half-life of about 1 week(3). Samples of fish were assessed for the presence of microcystins, resulting in bioaccumulation factors ranging from 14 to 2,409(4), According to a classification scheme(5), BCF values of zero to 30 are low and from 100 to 1,000 are high(SRC).

ATMOSPHERIC FATE: Microcystin-LR is very water soluble and non-volatile(1), indicating microcystin-LR will exist solely in the particulate phase in the atmosphere. Particulate-phase microcystin-LR may be removed from the air by wet and dry deposition(SRC). Microcystin-LR contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Microcystin-LR was reported over 1 ppm in 50 out of 67 samples of dietary supplements collected from blue-green algae harvesters, wholesalers, and retailers, as reported by the Oregon Health Division. Microcystin-LR was reported in 9 random samples of dietary supplements above safe limits for daily consumption, as reported by Health Canada(1). Microcystins were not detected in 6 water chestnut samples collected from markets located in Wuxi, China in October 2007(2).

IDENTIFICATION AND USE: Microcystin-LR (MCLR) is the most investigated cyanobacterial peptide toxin because it is frequently present in cyanobacterial blooms in rivers and lakes. Cyanobacterial toxins are classified by how they affect the human body: Hepatotoxins affect the liver and are produced by some strains of Microcystis, Anabaena, and Oscillatoria. They consist of cyclic hetapepides, termed microcystins and nodularins, which are cyclic pentapeptides. HUMAN STUDIES: Through the recreational use of contaminated water, cyanobacterial blooms of Microcystis, Anabaena, and others have been linked to incidence of human illness in many countries. In Canada, human illnesses have been reported in Saskatchewan, with symptoms including stomach cramps, vomiting, diarrhea, fever, headache, pains in muscles and joints, and weakness. Similar symptoms as well as skin, eye, and throat irritation and allergic responses to cyanobacterial toxins in water have also been reported in other countries. An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting after routine hemodialysis treatment on 13-20 February 1996. Subsequently, 100 patients developed acute liver failure, and many of them died. From liver concentrations and exposure volumes, it was estimated that 19.5 ug/L microcystin was in the water used for dialysis treatments. MCLR had a clastogenic effect in human lymphoblastoid cell line. The analysis of the micronucleus content in HepG2 cells suggested that MCLR induces both chromosome breaks and loss. MCLR induced cell death in primary human hepatocytes in vitro. ANIMAL STUDIES: The microcystins are primarily hepatotoxins. After acute exposure by iv or ip injection of microcystin, severe liver damage is characterized by a disruption of liver cell structure (due to damage to the cytoskeleton), a loss of sinusoidal structure, increases in liver weight due to intrahepatic hemorrhage, hemodynamic shock, heart failure and death. Other organs affected are the kidneys and lungs and the intestines. MCLR-induced hepatotoxicity occurs through specific inhibition of serine/threonine protein phosphatases 1 and 2A, which leads to hyperphosphorylation of many cellular proteins. This eventually results in cytoskeletal damage, loss of cell morphology, and the consequent cell death. Inhibition of protein phosphatases is the main mechanism associated with the potential tumor-promoting activities of MCLR. It can induce excessive formation of reactive oxygen and nitrogen species, which results in DNA damage. Although MCLR is not a bacterial mutagen, in mammalian cells it can induce mutations, as predominantly large deletions, and it has clastogenic actions. MCLR also disrupts the mitotic spindle, and interferes with DNA damage repair processes, which contribute to genetic instability. Furthermore, MCLR increases expression of early response genes, including proto-oncogenes, and genes involved in responses to DNA damage and repair, cell-cycle arrest, and apoptosis. In rats oral exposure to MCLR had adverse affects on neurobehaviors, and induced inflammation in memory-related brain regions. MCLR induced developmental neurotoxicity in zebrafish. In mice, perinatal MCLR exposure interfered with the development of the prostate in the offspring, evidenced by prostatic necrosis, hyperplasia, inflammation, and fibrosis. Exposure to MCLR in zebrafish results in the disturbance of thyroid hormone homeostasis. MCLR significantly impaired the spermatogenesis in mice possibly through the effect on Hypothalamic-Pituitary-Gonadal Axis. MCLR crosses the blood-testis barrier and interferes with DNA damage repair pathway and also increases expression of the proto-oncogenes in testis. MCLR treated mice exhibit oxidative stress in testis through the alteration of antioxidant enzyme activity. ECOTOXICITY STUDIES: Cyanobacterial water blooms can significantly alter the normal development of amphibian embryos. Low concentrations of dissolved microcystin had no harmful effect on Daphnia. On the contrary, stimulatory effects were detected. With microcystin given at a higher dosage or for a longer exposure, the effect on Daphnia magna was fatal. Acute MCLR exposure has the potential to disturb the homeostasis of thyroid hormone metabolism, leading to a hypothyroidism state in the juvenile Chinese rare minnow. MCLR at environmentally relevant concentrations is able to induce impairments on fish gonadal development in zebrafish. In C. elegans, MCLR induced adverse effects on spermiogenesis. MCLR could affect terrestrial plants seedling germination and growth.

/AQUATIC SPECIES/ Toxic cyanobacterial blooms are potential global threats to aquatic ecosystems and human health. The World Health Organization has set a provisional guideline limit of 1 ug/L microcystin-LR (MCLR) in freshwater. However, MCLR concentrations in several water bodies have exceeded this level. Despite this recommended human safety standard, MCLR-induced endocrine-disrupting effects and reproductive toxicity on male frog (Rana nigromaculata) were demonstrated in this study. Results showed that sperm motility and sperm count were significantly and negatively correlated with exposure time and concentration. By contrast, abnormal sperm rate was positively correlated with both parameters. Ultrastructural observation results revealed abnormal sperm morphologies, vacuoles in spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. These results indicated that MCLR could induce toxic effects on the reproductive system of frogs, significantly decrease testosterone content, and rapidly increase estradiol content. Prolonged exposure and increased concentration enhanced the relative expression levels of P450 aromatase and steroidogenic factor 1; thus, endocrine function in frogs was disrupted. This study is the first to demonstrate in vivo MCLR toxicity in the reproductive system of male R. nigromaculata. This study provided a scientific basis of the global decline in amphibian populations.

/AQUATIC SPECIES/ Microcystins (MCs) are a group of cyclic heptapeptide hepatotoxic peptides produced by cyanobacteria. Microcystins-LR (MC-LR) can inhibit the activities of protein phosphatase type 1 and type 2A (PP1 and PP2A) and induce excessive production of reactive oxygen species (ROS). However, the detailed toxicological mechanism involving oxidative stress in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the effects of sublethal intraperitoneal doses of MC-LR on the oxidative stress and pathological changes in carp liver were investigated. No significant changes of xanthine oxidase were observed, suggesting it might not contribute to over-production of ROS in the liver of fish during 48 hr exposure to sublethal intraperitoneal doses of MC-LR. Superoxide dismutase activity in the 50 ug/kg group was significantly induced at 1-24 hr. The strongest inhibition of the catalase activity was shown at 48 hr after 120 ug/kg MC-LR exposure, with an inhibition rate of 33.7% compared to the control group. In general, a significant depletion of intracellular reduced glutathione was found at 5-12 hr after 50 and 120 ug/kg MC-LR exposure, which was mainly due to the conjugation reaction to MC-LR catalyzed by glutathione-S-transferase and its subsequent excretion. Oxidative damages induced by MC-LR were evidenced by the significant elevation in malondialdehyde levels. In addition, a series of histopathological alterations in fish livers were observed, and the most severe hepatic injuries were found at 5-12 hr, which could contribute to the efflux of intracellular GSH. Our study further supports the important role of oxidative stress involved in MC-LR induced liver injury in aquatic organisms.

Microcystins were detected in 6 out of 18 water chestnut samples collected from Lake Tai, China in October 2007, with the maximum concentration reported at 7.02 ng/g. Microcystin-LR was reported at a maximum concentration of 1.02 ng/g, and was detected in 5 of the samples(1).

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for microcystin-LR is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Monitoring requirements for unregulated contaminants. (a) General applicability. This section specifies the monitoring and quality control requirements that must be followed if you own or operate a public water system (PWS) that is subject to the Unregulated Contaminant Monitoring Regulation (UCMR), as specified in paragraphs (a)(1) and (2) of this section. In addition, this section specifies the UCMR requirements for State and Tribal participation. For the purposes of this section, PWS "population served," "State," " PWS Official," "PWS Technical Contact," and "finished water" apply as defined in section 141.35(a). The determination of whether a PWS is required to monitor under this rule is based on the type of system (e.g., community water system, non-transient non-community water system, etc.), and its retail population, as indicated by SDWIS/Fed on December 31, 2015.[Table#7415]

EPA has issued 10-Day Drinking Water Health Advisories (HAs) for the cyanobacterial toxins microcystins and cylindrospermopsin. EPA recommends HA levels at or below 0.3 micrograms per liter for microcystins and 0.7 micrograms per liter for cylindrospermopsin in drinking water for children pre-school age and younger (less than six years old). For school-age children through adults, the recommended HA levels for drinking water are at or below 1.6 micrograms per liter for microcystins and 3.0 micrograms per liter for cylindrospermopsin.

The hepatotoxins are produced by various species within the genera Microcystis, Anabaena, Oscillatoria, Nodularia, Nostoc, Cylindrospermopsis, and Umezakia, although not all strains do so. Most hepatotoxins (all cyclic heptapeptides) are microcystins. At least 50 congeners of microcystins are known, and several of these may be produced during a bloom. The chemical structure of microcystins includes two variable amino acids and an unusual aromatic amino acid, ADDA (3-amino-9- methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid), containing a substituted phenyldecadienoic acid. Different microcystins have different lipophilicities and polarities, which could affect their toxicity. ... Microcystis and Anabaena blooms occur widely in the temperate regions of the world. In general, 50-75% of bloom isolates can produce toxins, often with more than one toxin being present. Toxic and non-toxic blooms of the same species can be found together.

It is important to measure total microcystins, which includes microcystins occurring free in water and microcystins bound to or inside cyanobacterial cells and which includes all microcystins, not just microcystin-LR. Thus, sample preparation may need to include sonification (to break up cells) and a variety of extraction procedures in order to isolate the different (ie, more lipophilic or polar) microcystins. Most of the existing studies on the levels of microcystins in water supplies have not clearly indicated whether total or free microcystins were measured

Drinking water disinfection by chlorine is known to reduce concentration of microcystin, but compounds formed (dihydroxy-microcystin, monochloro-hydroxy-microcystin, monochloro-microcystin, monochloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin and trichloro-hydroxy-microcystin) are rarely considered. In this work the chlorination of microcystin-LR has been studied by monitoring reactants consumption and reaction products using the linear trap quad-Orbitrap (LTQ-Orbitrap) technology. Microcystin-LR was totally transformed within 2 min, meanwhile chlorine was consumed until 30 min with a rate of 12 M/M of toxin. Four new by-products of microcystin-LR were identified as well as their isomers: monochloro-microcystin, monochloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin and trichloro-hydroxy-microcystin. In addition, four new isomers were also observed, corresponding to the dihydroxy-microcystin already known. Besides, another compound previously observed was identified as monochloro-hydroxy-microcystin.

Microcystin-LR (lysine-arginine) is the most investigated cyanobacterial peptide toxin because it is frequently present in cyanobacterial blooms in rivers and lakes ... The peptide toxins are contained primarily within the cyanobacterial cells and are rarely released before the cells die or are destroyed (for instance, following water treatment or in the stomach, after ingestion). Due to widespread eutrophication in many settings, these toxins may occur more frequently and at unnaturally high concentration. In natural water bodies and in water storage reservoirs, the concentrations of toxin vary widely from undetectable to several milligrams per liter in cyanobacterial scums.