Domoic Acid

Published in the June 2024 issue of Clinical & Forensic Toxicology News

History

“Seabird Invasion Hits Coastal Homes; Thousands of birds floundering in streets,” read a headline from the Santa Cruz Sentinel on August 18, 1961. A huge flock of sooty shearwaters, the seabird mentioned in the article, in Capitola, California, crashed into homes in the middle of the night and were found dead or stunned by the impact by residents. Alfred Hitchcock was in the area for pre-production of his newest film The Birds, based on the short story by Daphne Du Maurier, and contacted the paper for more information. He used the (terrifying) incident as inspiration in the film. The strange behavior of these birds was later attributed to domoic acid toxicity from ingesting anchovies. Domoic acid is a naturally occurring marine biotoxin. It is produced by organisms causing red tide blooms, most commonly the diatoms Pseudonitzschia australias and Nitzchia pungens and the red algae Chondria armata. Domoic acid bioaccumulates in small fish, like anchovies, and in shellfish when diatoms and algae are taken up by ingestion or respiration. The risk for elevated toxin levels increases during algal blooms, which occur during warmer months around the world’s oceans. Birds and mammals—including humans—can experience domoic acid toxicity after ingesting the contaminated marine life. While there are few recorded large outbreaks in animals and humans, the impact is severe enough for fish and wildlife centers to test and track domoic acid levels in the local fish and shellfish populations as well as in water levels. A multitude of pelicans died in 1991, in Canada, due to consumption of infected anchovies. In 1998, 400 sea lions died from domoic acid poisoning off the coast of California. The largest human exposure to domoic acid occurred in 1987 when 100 residents of Prince Edward Island experienced gastrointestinal and neurological illness after eating locally farmed mussels.

Pharmacology and toxicology

Domoic acid is related in structure to kainic acid, glutamic acid, and aspartic acid. Domoic acid acts as a direct glutamate receptor agonist, binding to kainate receptors at neuronal endings. Glutamate is the main excitatory neurotransmitter in the central nervous system and is needed for attention, learning, memory, perception, and movement. Kainate, AMPA, and NMDA receptors are ionotropic glutamate receptors that typically function as ion channels for sodium or calcium. NMDA and AMPA receptors are responsible for the quick glutamate activity required for memory and learning. Activating these receptors leads to calcium and sodium influx, which depolarizes and excites the membrane. If there is excessive excitation from glutamate, or glutamate analogs such as domoic acid, seizures, neuronal damage, neurodegeneration, and apoptosis can occur. Toxicity has been reported at levels of domoic acid ranging from 60 to 1200 mg/kg. State health officials determined domoic acid levels must remain below 20 ppm, or the shellfish and fish are not safe for consumption. The toxin is heat-stable, so cooking shellfish and fish will not prevent toxicity.

Health impacts

Domoic acid causes amnesic shellfish poisoning, a condition characterized by nausea, vomiting, diarrhea, and abdominal cramps within 24 hours of ingestion. Neurological effects, such as headache, confusion, short-term memory loss (hence its name), confusion, and occasional seizure or coma may occur within 48 hours of ingestion. Symptoms of ingestion usually begin about 5 hours post-ingestion but can range up to 30 hours. Neurologic impacts are more prevalent in older patients. Recovery can take days for gastrointestinal symptoms to years for neurological symptoms. Supportive care is the only treatment, as there is no antidote to the toxin. Amnesic shellfish poisoning has a 2% mortality rate, and 10% of patients have long-term antegrade memory deficits or motor and sensory neuropathy. Post-mortem brain examinations showed neuronal damage to the hippocampus and amygdala.

Testing

While clinical patient samples from the 1987 outbreak were analyzed by SPE sulfonic acid cation exchange columns followed by HPLC, no domoic acid was identified in these samples, though the detection level was not specified. Domoic acid was found in mussels leftover from the patients’ households, restaurants, or shellfish retailers and was tested via bioassay and HPLC. Testing is usually performed by public health and fish and wildlife agencies to monitor levels of fish and shellfish and determine if the waters are safe for harvesting and fishing. Testing began in California in 1991 by the California Department of Public Health after domoic acid was detected in Monterey Bay. Multiple public health labs in the United States and the U.S. Food and Drug Administration also perform routine shellfish testing for domoic acid, which has greatly decreased the incidence of widespread outbreaks. ELISA kits, bioassays, and LCMS are the most common techniques to identify the toxins in shellfish, fish, and seawater.

References

Aguilera MA. The story behind Hitchcock’s crazed ‘Birds’. Scripps Institution of Oceanography. 2012. https://scripps.ucsd.edu/news/story-behind-hitchcocks-crazed-birds (Accessed April 8, 2024).
Baselt RC. Disposition of toxic drugs and chemicals in man, 12th ed. 2020. Biomedical Publications, Seal Beach, CA.
Domoic acid. Washington Department of Fish and Wildlife. 2024. https://wdfw.wa.gov/fishing/basics/domoic-acid (Accessed April 8, 2024).
Domoic acid frequently asked questions. California Department of Public Health. 2017. https://www.cdph.ca.gov/Programs/CEH/DRSEM/Pages/EMB/Shellfish/Domoic-Acid.aspx#:_:text¼In%201991%2C%20the%20California%20Department,first%20detected%20in%20Monterey%20Bay (Accessed May 21, 2024).
Nelson LS, Howland MA, Lewin NA, et al. Goldfrank’s toxicologic emergencies, 11th ed. 2019. McGraw-Hill Education.
Perl TM, Bédard L, Kosatsky T, et al. An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Eng J Med 1990;322:1775–80.
Pulido OM. Domoic acid toxicologic pathology: A review. Mar Drugs 2008;6:180–219.
Trabing W. Seabird invasion hits coastal homes. Santa Cruz Sentinel. 1961. https://the.hitchcock.zone/wiki/Santa_Cruz_Sentinel_(18/Aug/1961)_-_Seabird_Invasion_ Hits_Coastal_Homes (Accessed April 8, 2024).

Alexandria Reinhart, PhD, NRCC, is an assistant laboratory director at NMS Labs.

The author has nothing to disclose.

What does this compound have in common with Alfred Hitchcock?

Domoic acid is thought to be the toxin that caused strange behavior in birds in Capitola, California in 1961. Alfred Hitchcock directed the film "The Birds" in 1963 after visiting the area and reading newspaper accounts of the events. He also based the film on a short story by Daphne du Maurier in which the birds attack people in Britain.

Domoic acid is a structural analogue of glutamic acid produced by a series of related diatoms including Pseudonitzschia australias, and N. pungens. The clinical poisoning is referred to as amnesic shellfish poisoning (ASP). The toxin is produced in large quantities during an algae bloom and is consumed by fish and shellfish. Domoic acid seems to have no effect on the shellfish but if eaten by birds, man and other mammals produces systemic poisoning. The blooms occur virtually all over the world and in the U.S. occur on both coasts. The blooms and the associated toxin are monitored closely by state and federal wildlife and agricultural departments.

Many poisonings have been reported in public press over the past 40 years with the latest reports being this year.

The only human cases that I found occurred in Canada. At the end of November 1987, 153 cases of acute intoxication after ingestion of toxic mussels were reported associated with blooms of the marine diatom Pseudonitschia pungens. The International Bird Rescue Research Center (IBRRC) tracks domoic acid outbreaks mostly in southern California and videos and stories about poisonings can be found online. These outbreaks threaten in addition to the birds other animals that feed on the algae such as dolphins, sea lions, and particularly important to humans, shellfish. An area where domoic acid is important is in Washington State where razor clams are a popular delicacy. The Washington State Department of Health monitors the domoic acid concentration in the clam and closes clam collections when levels are high. See their website for graphs of historical and current levels of domoic acid in various locations.