Unit 9 Toxic Factors in Fish Products PDF

NUTR*4510 Toxicology, Nutrition & Food Unit 9: Toxic Factors in Fish Products - Shows early documentation of fish poisoning → symptoms of neurotoxity Seafood Toxins 1. Ciguatoxin - Toxin made by phytoplankton (G. toxicus) around reefs, then bioaccumulates up the food chain - Acc...

NUTR*4510 Toxicology, Nutrition & Food Unit 9: Toxic Factors in Fish Products - Shows early documentation of fish poisoning → symptoms of neurotoxity Seafood Toxins 1. Ciguatoxin - Toxin made by phytoplankton (G. toxicus) around reefs, then bioaccumulates up the food chain - Accumulates in the skin, head, viscera, and roe (eggs) of big reef fish like barracuda, grouper, snapper, etc. - Lipid soluble - Heat stable – i.e., does not degrade with cooking - Causes “ciguatera”: most common fish-borne illness world-wide Phase I metabolism via CYP3A4 … AND During the first 24 hours post-exposure metabolism through CYP2 family members (2B9, 2B10, 2J9, 2J11 and 2J13) After >24 hours after ciguatoxin exposure other CYP4 family members (4A1, 4A10, 4A14) are upregulated and functional to help metabolize the ciguatoxin Phase II metabolism through glutathione conjugation (various GST enzymes catalyze this reaction) 2. Saxitoxin - Toxin made by phytoplankton (G. dinoflagella) - Bioconcentrated by filter feeding bivalve mollusks (mussels, clams, oysters, scallops) - Water soluble - Heat stable - Causes “paralytic shellfish poisoning” - Not metabolized in mammals (to our knowledge) as the intact saxitoxin structure has been detected in the liver, spleen and brain of exposed mammals Seafood Toxins 3. Tetrodotoxin - Origin of toxin is unknown – likely produced by a bacteria, then bioconcentrated by host - Found in several species of puffer fish, blue ringed octopus, some newts and frogs, etc. - Water soluble - Heat stable - Causes “puffer fish poisoning” - Lethal @ 1-4 mg of toxin exposure → within ~17 minutes after eating tetrodotoxin can experience cardiovascular and respiratory failure Tetrodotoxin → Metabolism pathway in humans has not been determined and the structures of any Phase I or Phase II metabolites of tetrodotoxin are unknown. Metabolism in humans is believed to differ from metabolism of tetrodotoxin in in marine species. Different analogues and oxidized tetrodotoxin metabolites are found in different marine organisms so it’s hypothesized that tetrodotoxin can also bioaccumulate through the aquatic food chain  Seafood Toxins Neurological effects Toxicity: - Seafood toxins exert similar adverse health effects but differ in their time course of action (e.g., tetrodotoxin exerts effects very fast): - Hyperesthesia… increased sensitivity to stimulation, including pain, touch, and thermal sensation. It can affect one or all of the senses - Paresthesia…the feeling of tingling, numbness or “pins and needles.” - Sensation of floating - Headache - Ataxia…poor muscle control that causes clumsy movements - Vertigo - Respiratory failure (due to diaphragm paralysis)… death ALSO… Cardiovascular effects = hypotension, pulmonary edema Gastrointestinal effects = abdominal pain, diarrhea, vomiting saxitoxin tetrodotoxin ciguatoxin  Review of Action Potentials www.studyblue.com Seafood Toxins: Mechanism of Action - Transmission of a nerve signal along a neuron from one end to the other occurs as a result of electrical changes across the membrane of the neuron (i.e., an action potential) 1. After the threshold is reached, voltage-gated sodium ion (Na+) channels open and Na+ moves into the neuron. The now positive membrane potential depolarizes 1 2 nearby regions of the neuron, thus propagating the signal 2. (Na+ channels close) Voltage-gated potassium (K+) channels open and K+ moves out of the neuron. The now negative membrane potential is ready for another signal. - Ciguatoxin enhances depolarization (step 1), preventing further nerve signal propagation (takes longer to reach the resting state) - Saxitoxin and Tetrodotoxin prevent depolarization, preventing nerve signal propagation  Metabolism of Fish Toxins Ciguatoxin → Phase I metabolism via CYP3A4 … AND During the first 24 hours post-exposure metabolism through CYP2 family members (2B9, 2B10, 2J9, 2J11 and 2J13) Other CYP4 family members (4A1, 4A10, 4A14) are upregulated for a longer amount of time (i.e., >24hrs after ciguatoxin exposure Phase II metabolism through glutathione conjugation (various GST enzymes catalyze this reaction) Saxitoxin → Not metabolized in mammals as the intact saxitoxin structure has been identified in the liver, spleen and brain of exposed mammals Tetrodotoxin → Metabolism pathway in humans has not been determined and the structures of any Phase I or Phase II metabolites of tetrodotoxin are unknown. Metabolism in humans is believed to differ from metabolism of tetrodotoxin in in marine species. Different analogues and oxidized tetrodotoxin metabolites are found in different marine organisms so it’s hypothesized that tetrodotoxin can also bioaccumulate through the aquatic food chain Sport Fish Toxins/Xenobiotics (Local Freshwater Fish) Characteristics of Toxins: - Lipophilic (to varying degrees) - Chemically stable – i.e., resistant to degradation - Metabolically stable – i.e., resistant to metabolism (phase I and phase II) - Good bioavailability – i.e., easily absorbed from water/diet (in both fish and humans) - Low toxicity to intermediate levels of the food chain (e.g., fish) Conditions that Favour Xenobiotic Bioaccumulation in Fish: 1. Proximity to sites of contamination 2. Increasing age (older fish, larger SIZE) - More time for bioaccumulation - Diet favours larger prey with greater bioaccumulation of toxins - Increased body fat 3. Lipid content - Higher body fat encourages storage of lipophilic toxins 4. Diet - Higher positions in the food chain bioaccumulate more toxin Common sport fish toxins in the Great Lakes Many others  Reflects long lives (i.e., long half lives) and resistance to degradation of these xenobiotics: - PCBs - Mercury (or methyl-mercury) - Dioxins and Furans Common Contaminants Monitored in Ontario Fresh Water Fish Mercury - Mercury, is converted to methylmercury and absorbed by a fish either from water passing over its gills or it is ingested with its diet. Since fish eliminate mercury at a very slow rate, concentrations of this substance gradually increase. Fish at the top of the food web such as Walleye and Pike usually have the highest mercury levels. Polychlorinated biphenyls (PCBs) - PCBs are a group of chlorinated organic compounds first commercially developed in the late 1920s and banned in the 1970s. They persist for decades in the natural environment and readily accumulate in the aquatic ecosystem. Dioxin-like PCBs - These are a select group of PCBs with harmful properties similar to dioxins. Dioxins/Furans - Dioxins and furans are unintentional by-products of several industrial processes and, in some cases, incomplete combustion. Of 210 different dioxins and furans, 17 are toxic enough to be of concern. Toxaphene - Toxaphene is an extremely persistent insecticide in the aquatic environment. It was removed from general use in Canada in 1974 and restricted in the United States in 1982. PerFluoroAlkyl and PolyFluoroAlkyl Substances (PFAS) - PFAS are a family of chemicals that make materials water, stain and oil repellent and have been in a wide array of consumer products since the 1950s. PFAS do not break down easily. Selenium - Selenium is a metal found in fish tissue but only occasionally at levels requiring consumption restrictions. Arsenic - Arsenic is a metal found in fish tissue but only occasionally at levels requiring consumption restrictions. PolyBrominated Diphenyl Ethers (PBDEs) - PBDEs are used as flame retardants in building materials, electronics and many household products. Some of these chemicals have been banned or phased out in recent years. PolyChlorinated Naphthalenes (PCNs) - PCNs are industrial chemicals. While no longer used in Canada, they may be produced unintentionally in different chemical processes. Chromium - Chromium is a metal found in fish tissue but only occasionally at levels requiring consumption restrictions. Photomirex - See mirex below. Mirex - Mirex is a chlorinated carbon compound used as a pesticide in the southern United States but never registered for such use in Canada. Some mirex is transformed into photomirex. Lead - Metals such as lead are found in fish tissue but only occasionally at levels requiring consumption restrictions. Cadmium - Cadmium is a metal found in fish tissue but only occasionally at levels requiring consumption restrictions. Bioaccumulation up the Food Chain  Toxins in Sport Fish/Great Lake Fish Species 1. Polychlorinated biphenyls (PCBs) - 209 variations - Developed in late 1920s and used in electrical and hydraulic equipment - Now banned, but still leaking from transformers and dumps due to their longevity - Very lipophilic – i.e. strong bioaccumulation in high-fat fish - Average content in Lake Ontario fish is 30-fold above safety limit! - Half-life in humans: 5 - 15 years Health Effects: - Suspected carcinogen: induces CYP1A family mRNA and protein expression via AhR but are resistant to metabolism (i.e., phase I reactions) - Large exposure causes chloracne, anemia, and immune suppression in adults - Lower exposure levels can cause impaired cognitive development in the developing fetus 2. Dioxins - 75 variations; most toxic: 2,3,7,8-terachlorodibenzo-p-dioxin (TCDD) - No common uses; exist as byproduct of many industrial process, e.g. pulp and paper, pesticide and chemical industries - Contamination leaking from chemical dumps in the Niagara River region - Lipophilic – significant bioaccumulation in high-fat fish - Half-life in humans: >5 years Health Effects: - Suspected carcinogen: induces CYP1A family mRNA and protein expression via AhR but are resistant to metabolism (i.e., phase I reactions) - Large exposure causes chloracne in adults - Lower exposure levels can cause various developmental problems in the fetus  Toxins in Sport Fish/Great Lake Fish Species 3. Methyl-mercury (CH3-Hg) - Mercury naturally occurs in many watersheds - Mercury was widely used in industry, but decreased from 1960s onwards - Mercury (Hg) is converted to methyl-mercury (CH3-Hg) by bacteria - CH3-Hg is taken up by diet or across gills in fish - Lipophilic – significant bioaccumulation in high-fat fish species, but also observe significant bioaccumulation in fish with lesser body fat compositions - Half-life in humans: 30 – 120 days Health Effects - Binds protein sulfhydryl or thiol (SH) groups (e.g. cysteine residues) → impact on protein function - Visual, hearing and other sensory problems observed in adult poisoning - Severe deficiency in cognitive development in the developing fetus* - Effects observed in the fetus are at 1/5 of the exposure level required for adult toxicity * Developmental neurotoxicity - Extremely stable (i.e. resistant to chemical degradation and metabolism) lipophilic compounds bioaccumulate in maternal fat - During pregnancy, maternal fat is mobilized for energy, especially if morning sickness is significant - X are released and are transferred through the placenta to the developing fetus - Lipophilic compounds localize to the lipid-rich environment of the developing brain…  Restrictions in SIZE of fish consumed and the number of fish servings consumed per month Restrictions for children and pregnant females versus healthy adults https://www.ontario.ca/data/guide-eating-ontario-fish-advisory- database  Interpreting the Guidelines….what is a “meal of fish”? Number of fish fillets in one fish meal: Consumption advice is based on an average fish meal of 227 grams (8 ounces (=half a pound) or approximately a fillet of dinner plate length for an adult weighing 70 kilograms (154 pounds). half of your palm is approximately 2 ounces of fish your whole palm is approximately 4 ounces of fish the palm of your hand including your fingers is approximately 8 ounces of fish This amount (8 ounces) is the basis for the consumption advice in the advisory tables