User:Littleblackraincloud/Anatoxin-a

Occurrence
Anatoxin-a is a neurotoxin produced by multiple genera of freshwater cyanobacteria that have been found in water bodies on every continent except Antarctica. Because of this, rivers, lakes, streams, and other recreational waters are at risk of anatoxin-a contamination. Additionally, some anatoxin-a producing cyanobacteria like Aphanizomenon favaloroi are known to be salt tolerant thus it is possible for anatoxin-a to be found in estuarine or other brackish environments.

Blooms of cyanobacteria that produce anatoxin-a (among other cyanotoxins) are increasing in frequency due to climate change; increasing temperatures, earlier and more persistent stratification of water columns, and eutrophication facilitate conditions conducive to bloom formation. Cyanobacteria experience maximum growth rates at relatively high temperatures (~31°C/88°F) when compared to other phytoplankton like dinoflagellates (~22 °C/72°F), diatoms (~15°C/59°F), and chlorophytes (~26°C/79°F). This allows cyanobacteria to outcompete eukaryotic phytoplankton in warming climates. These expansive cyanobacterial harmful algal blooms, known as cyanoHABs, increase the concentration of cyanotoxins in the surrounding water, threatening the health of both aquatic and terrestrial organisms. The persistent and recurrent nature of cyanoHABs can partially be attributed to the presence of cyanobacteria containing specialized cells called akinetes which act as survival mechanisms when the cyanobacteria are subjected to inhospitable conditions. One example is Cylindrospermum raciborskii, an anatoxin-a producing cyanobacteria able to survive relatively cold temperatures and low light conditions because it can utilize akinetes.

Some species of cyanobacteria that produce anatoxin-a don't produce surface water blooms but instead form benthic mats. Genera of this type include Anabaena (Dolichospermum), Phormidium, and Oscillatoria. Low water flow and presence of herbicides has been found to increase proliferation of benthic mats. Cases of anatoxin-a related animal deaths have occurred due to ingestion of detached benthic cyanobacterial mats that have washed ashore.

Anatoxin-a producing cyanobacteria have also been found in soils and aquatic plants. Anatoxin-a sorbs well to negatively charged sites in clayey, organic-rich soils and weakly to sandy soils. One study found both bound and free anatoxin-a in 38% of aquatic plants sampled across 12 Nebraskan reservoirs, with much higher incidence of bound anatoxin-a than free. Aquatic plants that take up anatoxin-a can be passed along to bottom-feeders.

Effects
Laboratory studies using mice showed that characteristic effects of acute anatoxin-a poisoning via intraperitoneal injection include muscle fasciculations, tremors, staggering, gasping, respiratory paralysis, and death within minutes. Zebrafish exposed to anatoxin-a in water had altered heart rates.

There have been cases of non-lethal poisoning in humans who have ingested water from streams and lakes that contain various genera of cyanobacteria that are capable of producing anatoxin-a. The effects of non-lethal poisoning were primarily gastrointestinal: nausea, vomiting, diarrhea, and abdominal pain.

Oral
Ingestion of drinking water or recreational water that is contaminated with anatoxin-a can pose fatal consequences since anatoxin-a was found to be quickly absorbed through the gastrointestinal tract in animal studies. Dozens of cases of animal deaths due to ingestion of anatoxin-a contaminated water from lakes or rivers have been recorded, and it is suspected to have also been the cause of death of one human (citation on main page). One study found that anatoxin-a is capable of binding to acetylcholine receptors and inducing toxic effects with concentrations in the nano-molar (nM; 1x10-9 M) range if ingested.

Dermal
Dermal exposure is the most likely form of contact with cyanotoxins in the environment. Recreational exposure to river, stream, and lake waters contaminated with algal blooms has been known to cause skin irritation and rashes. The first study that looked at in vitro cytotoxic effects of anatoxin-a on human skin cell proliferation and migration found that anatoxin-a exerted no effect at 0.1 µg/mL or 1 µg/mL, and a weak toxic effect at 10 µg/mL only after an extended period of contact (48 hours).

Inhalation
No data on inhalation toxicity of anatoxin-a is currently available, though severe respiratory distress occurred in a water skier after they inhaled water spray containing a fellow cyanobacterial neurotoxin, saxitoxin. It is possible that inhalation of water spray containing anatoxin-a could pose similar consequences.

Water regulations
The World Health Organization in 1999 and EPA in 2006 both came to the conclusion that there was not enough toxicity data for anatoxin-a to establish a formal tolerable daily intake (TDI) level, though some places have implemented levels of their own.

United States
Anatoxin-a is not regulated under the Safe Drinking Water Act, but states are allowed to create their own standards for contaminants that are unregulated. Currently there are four states that have set drinking water advisory levels for anatoxin-a as seen in the table below. On October 8, 2009 the EPA published the third Drinking Water Contaminant Candidate List (CCL) which included anatoxin-a (among other cyanotoxins), indicating that anatoxin-a may be present in public water systems but is not regulated by the EPA. Anatoxin-a's presence on the CCL means that it may need to be regulated by the EPA in the future, pending further information on human health effects. In 2008 the state of Washington implemented a recreational advisory level for anatoxin-a of 1 µg/L in order to better manage algal blooms in lakes and protect users from exposure to the blooms. In 2016 proposed changes were made to California's voluntary guidance on cyanoHABs in recreational waters; any detection of anatoxin-a in recreational waters (with a method capable of detecting anatoxin-a in concentrations lower than 1 µg/L) triggers placement of a caution sign and increased water monitoring to safeguard pets and livestock from poisoning. Detection of ≥20 µg/L anatoxin-a (Tier 1) prompts a warning sign discouraging swimming for humans and animals, and detection of ≥90 µg/L anatoxin-a (Tier 2) prompts a danger sign recommending people and pets keep clear of the water at all times.

Canada
The Canadian province of Québec has a drinking water Maximum Accepted Value for anatoxin-a of 3.7 µg/L.

New Zealand
New Zealand has a drinking water Maximum Accepted Value for anatoxin-a of 6 µg/L.

Water treatment
** Copied from article and edited** Directly removing the cyanobacteria in the water treatment process through physical treatment (e.g., membrane filtration) is another option because most of the anatoxin-a is contained within the cells when the bloom is growing. However, anatoxin-a is released from cyanobacteria into water when they lyse, so physical treatment may not remove all of the anatoxin-a present. Additional research needs to be done to find more reliable and efficient methods of both detection and treatment.

Dietary supplements
Multiple studies have detected anatoxin-a in various blue-green algae dietary supplements labeled "Spirulina" and "A. flos-aquae" that were marketed for human and animal consumption. The cyanobacteria genera Spirulina is not known to be a producer of anatoxin-a, but contamination of Spirulina supplements with anatoxin-a producing cyanobacteria is possible because Spirulina is often cultivated in natural waterbodies. Additionally, Spirulina has very similar morphology to Arthrospira which is considered a potential anatoxin-a producer. Presence in supplements of anatoxin-a's metabolites, epoxyanatoxin-a and dihydroanatoxin-a, in the absence of anatoxin-a itself indicates that anatoxin-a used to be present. This means that there's a potential health hazard in consuming cyanobacterial supplements, especially since they are not regulated like pharmaceuticals.