Glossary and Supplementary Information



5-HT In vivo synaptic serotonin

AA Arachidonic acid

ADHD Attention Deficit Hyperactivity Disorder

AEDS Atopic eczema/dermatitis syndrome

AHA American Heart Association

AHR Airway hyperresponsiveness

AHRQ Agency for Healthcare Research and Quality

AI Adequate Intake

ALA Alpha-linolenic acid

ALSPAC Avon Longitudinal Study of Parents and Children

AMI Acute myocardial infarction

ANOVA Analysis of variance

AOCS American Oil Chemists Society

APC Aerobic bacterial counts

APGAR Activity, Pulse, Grimace, Appearance, and Respiration

APO Apolipoprotein

APTT Activated partial thromboplastin time

ARS Agricultural Research Society

AUC Area under the curve

BDI Beck Depression Inventory

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Seafood Choices: Balancing Benefits and Risks A Glossary and Supplementary Information GLOSSARY Abbreviations/Acronyms 5-HT In vivo synaptic serotonin AA Arachidonic acid ADHD Attention Deficit Hyperactivity Disorder AEDS Atopic eczema/dermatitis syndrome AHA American Heart Association AHR Airway hyperresponsiveness AHRQ Agency for Healthcare Research and Quality AI Adequate Intake ALA Alpha-linolenic acid ALSPAC Avon Longitudinal Study of Parents and Children AMI Acute myocardial infarction ANOVA Analysis of variance AOCS American Oil Chemists Society APC Aerobic bacterial counts APGAR Activity, Pulse, Grimace, Appearance, and Respiration APO Apolipoprotein APTT Activated partial thromboplastin time ARS Agricultural Research Society AUC Area under the curve BDI Beck Depression Inventory

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Seafood Choices: Balancing Benefits and Risks BMD Benchmark dose BMDLs Benchmark dose lower bound BMI Body Mass Index CAD Coronary artery disease CAPS Childhood Asthma Prevention Study CAT Clinical Adaptive Test CD Cluster of differentiation (molecule) CDC Centers for Disease Control and Prevention CDDs Chlorinated dibenzo-p-dioxins CDFs Chlorinated dibenzofurans CFR Code of Federal Regulations CGOST Combined Cow and Gate Premium and Osterfeed formulae CHD Coronary heart disease CI Confidence interval CLAMS DQ Clinical Linguistic and Auditory Milestone Scale—Development Quotient CNPase 2′,3′-cyclic nucleotide 3′-phosphodiesterase CNS Central nervous system COPD Chronic obstructive pulmonary disease COT Committee on Toxicity CRP C-reactive protein CSFII Continuing Survey of Food Intake by Individuals CSPI Center for Science in the Public Interest CVD Cardiovascular disease DART Diet and Reinfarction Trial; Diet and Angina Randomized Trial DALY Disability adjusted life years DBD Disruptive Behavior Disorders DBP Diastolic blood pressure DDE Dichlorodiphenyldichloroethane DDST Denver Developmental Screening Test DDT Dichlorodiphenyltrichloroethane DGA Dietary Guidelines for Americans DGAC Dietary Guidelines Advisory Committee DGLA Dihomo-gamma-linolenic acid DHA Docosahexaenoic acid DHHS Department of Health and Human Services DNA Deoxyribonucleic acid DPA Docosapentaenoic acid DQ Developmental quotient DRI Dietary Reference Intake

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Seafood Choices: Balancing Benefits and Risks DSM Diagnostic and Statistical Manual of Mental Disorders DTA Docosatetraenoic acid ECG Electrocardiogram EFA Essential fatty acids EFSA European Food Safety Authority EPA Eicosapentaenoic acid EPDS Edinburgh Postpartum Depression Scale EPIC European Prospective Investigation into Cancer and Nutrition ETA Eicosatrienoic acid FAO Food and Agriculture Organization of the United Nations FDA Food and Drug Administration FDCA Federal Food, Drug, and Cosmetic Act FFQ Food Frequency Questionnaire FSA Food Standards Agency (UK) FVEP Flash-visual evoked potential GLA Gamma-linolenic acid GRAS Generally recognized as safe GSH-Px Glutathione peroxidase HACCP Hazard Analysis and Critical Control Point Hb Hemoglobin HDL-C High-density lipoprotein cholesterol HHS Health and Human Services HIV Human immunodeficiency virus HR Hazard ratio HRA Health risk appraisal HRT Hormone replacement therapy HSCL Hopkins Symptom Checklist HUFA Highly unsaturated fatty acid HVA Homovanillic acid IFN-γ Interferon-gamma IgG Immunoglobin G IgM Immunoglobin M IHC Interactive Health Communication IHD Ischemic heart disease IL Interleukin IMT Intima-media thickness IOM Institute of Medicine

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Seafood Choices: Balancing Benefits and Risks IQ Intelligence quotient IRR Incidence rate ratio ISAAC International Study of Asthma and Allergy in Childhood ISSC Interstate Shellfish Sanitation Conference JECFA Joint FAO/WHO Expert Committee on Food Additives and Contaminants K-ABC Kaufman Assessment Battery for Children KPS Knobloch, Passamanik, and Sherrad’s Developmental Screening Inventory LA Linoleic acid LCPUFA Long-chain polyunsaturated fatty acids LDL-C Low-density lipoprotein cholesterol LNA Linolenic acid LOAEL Lowest observed adverse effect level MCDI MacArthur Communicative Development Inventory MDI Bayley Scales of Infant Development Mental Index MEC Multiethnic Cohort Study MFFT Matching Familiar Figures Test MI Myocardial infarction MPCOMP Mental Processing Composite MPN Most probable number NCP Northern Contaminants Program NHANES National Health and Nutrition Examination Survey NIH National Institutes of Health NLV Norwalk-like viruses NMFS National Marine Fisheries Service NOAA National Oceanic and Atmospheric Administration NOAEL No observed adverse effect level NONVERB Nonverbal abilities NRC National Research Council NYHA New York Heart Association OA Oleic acid OR Odds ratio OVA Ovalbumin PC Phosphatidylcholine PCB Polychlorinated biphenyls

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Seafood Choices: Balancing Benefits and Risks PCDD Polychlorinated di-benzo-p-dioxin PCDF Polychlorinated di-benzo-p-furan PCR Polymerase chain reaction PDI Psychomotor Developmental Index PE Phosphatidylethanolamine PGF2α Prostaglandin F2α PHP Post-harvest processing PL Phospholipid Ppm Parts per million PT Prothrombin time PUFA Polyunsaturated fatty acids QALYs Quality Adjusted Life Years RBC Red blood cell RCT Randomized clinical trial or randomized controlled trial RDA Recommended Dietary Allowance RR Relative risk RRR Relative risk reduction RTE Ready-to-eat SACN Scientific Advisory Committee on Nutrition (UK) SBP Systolic blood pressure SCDS Seychelles Child Development Study SCID-CV Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders—Clinical Version SE Standard error SEQPROC Sequential processing SIMPROC Simultaneous processing TCDD Tetrachlorodibenzo-p-dioxin TDE Tetrachlorodiphenylethane TDI Tolerable Daily Intake TEF Toxicity Equivalency Factor TEQ Toxicity Equivalency TF Total fatty acids TG Triglycerides TNF-α Tumor necrosis factor alpha TOVA Test of Variables of Attention UNEP United Nations Environmental Programme USDA US Department of Agriculture US EPA US Environmental Protection Agency

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Seafood Choices: Balancing Benefits and Risks VEP Visual evoked potential VLDL Very low-density lipoprotein VRM Visual recognition memory WHO World Health Organization WIC Special Supplemental Nutrition Program for Women, Infants, and Children Definitions 24-hour recall A method of collecting food consumption data; an interviewer solicits detailed information regarding what a study participant ate and drank in the previous 24 hours or on the previous day Adipose tissue Fat tissue Aflatoxin Any of a group of toxic compounds produced by certain molds that contaminate stored food supplies such as animal feed and peanuts Analysis of variance (ANOVA) To identify sources of variability; to describe the relationship between a continuous dependent variable and one or more nominal independent variables Anglers Those who crab and/or fish Anthropogenic Of human origin Aquaculture Rearing or cultivating marine or freshwater fish or shellfish under controlled conditions for food Arrhythmia An irregular heartbeat Assay The evaluation of a substance for impurities, toxicity, etc. Atherosclerosis A condition in which plaques containing cholesterol and lipids are deposited on the innermost layer of the walls of large and medium-sized arteries Atopic Of, relating to, or caused by a hereditary predisposition toward developing certain hypersensitivity reactions, such as hay fever, asthma, or chronic urticaria, upon exposure to specific antigens Axonal The usually long process of a nerve fiber that generally conducts impulses away from the body of the nerve cell Bayesian hierarchical model A statistical method to make inferences about an unknown parameter in a multi-level model Benchmark dose modeling A technique for quantitative assessment of noncancer health effects; based on the level at which the prevalence of a defined health abnormality exceeds the background prevalence of the abnormality by a specified amount Benefit-risk analysis Comparison of the benefits of a situation to its related risks Best practices A technique or methodology that, through experience and research, has reliably proven to lead to a desired result

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Seafood Choices: Balancing Benefits and Risks Bioaccumulative pollutants Substances that increase in concentration in living organisms as they take in contaminated air, water, or food because they are very slowly metabolized or excreted Biomagnification The process by which the concentration of toxic substances increases in each successive link in the food chain Body burden The total amount of a chemical in the human body or in human tissue from exposure to contaminants in the environment Boston naming test A type of picture-naming vocabulary test used in the examination of children with learning disabilities and the evaluation of brain-injured adults Calcarine fissure A narrow groove in the mesial surface of the occipital lobe of the cerebrum Case-control study An epidemiological and observational study in which persons are selected because they have a specific disease or other outcome (cases) and are compared to a control (referent comparison) group without the disease to evaluate whether there is a difference in the frequency of exposure to possible disease risk factors; also termed a retrospective study or case referent study Cerebellum A region of the brain that plays an important role in the integration of sensory perception and motor output Chloracne A severe skin condition with acne-like lesions that occur mainly on the face and upper body after exposure to high doses of dioxin and dioxin-like compounds Cholesterol The chief sterol in all animal tissues, especially brain, nerve, adrenal cortex, and liver; it functions as a constituent of bile and as a precursor of vitamin D; cholesterol circulates in the blood as lipoprotein, in combination with protein and other blood lipids Ciguatera A natural toxin occurring sporadically in certain fish harvested from specific tropical to subtropical regions (i.e., South Florida, the Caribbean, and Hawaii) Clostridium botulinum (C. botulinum) A specific microorganism that, under anaerobic conditions and thermal abuse, can produce an extremely potent toxin (destroyed by sufficient heating); produces spores that can be hazardous to babies, individuals on antibiotic therapy, or immunocompromised individuals Cochrane review Systematic literature reviews based on the best available information about health care interventions. They explore the evidence for and against the effectiveness and appropriateness of treatments (medications, surgery, education, etc.) in specific circumstances Complex mixture A mixture that is a combination of many chemicals, has a commonly known generic name, and is naturally occurring; a fraction of a naturally occurring mixture that results from a separation process; or a modification of a naturally occurring mixture or a modification of

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Seafood Choices: Balancing Benefits and Risks a fraction of a naturally occurring mixture that results from a chemical modification process Confounder A factor that is associated with both the exposure and outcome of interest and can distort the apparent magnitude or direction of the studied effect Congener One of two or more compounds of the same kind with respect to classification Correlation coefficient A measure of the extent to which two variables are related Cortical Relating to the outer portion of an organ Crustaceans Aquatic arthropods characteristically having a segmented body, a chitinous exoskeleton, and paired, jointed limbs; includes lobsters, crabs, shrimps, and barnacles Cytokines Hormone-like proteins which regulate the intensity and duration of immune responses and are involved in cell-to-cell communication De novo Anew; often applied to particular biochemical pathways in which metabolites are newly biosynthesized Dioxins and dioxin-like compounds Unintentional contaminants that are released into the environment from combustion processes and accumulate, through the food chain, in the lipid component of animal foods Disappearance model The total supply of imported and landed food converted to edible weight, subtracting exports, nonfood uses, and other decreases in supply, adding imports, and then dividing by the total population to estimate per capita consumption Dose-response relationship A relationship between the amount of an agent (either administered, absorbed, or believed to be effective) and changes in certain aspects of the biological system, apparently in response to the agent Dysarthria A disturbance of speech and language Effect modifier Variation(s) in the association between an exposure and outcome occurring across different strata of a third variable (e.g., the association between oral contraceptive use and myocardial infarction differs between smokers and nonsmokers) Efficacy measurement endpoint Measure of an intervention’s influence on a disease or health condition Epidemiology The study of the distribution and determinants of health-related states and events in populations and the control of health problems Erythrocyte A mature red blood cell Essential fatty acids Fatty acids that cannot be synthesized by the body and therefore must be included in the diet (e.g., ALA) Etiology Cause and origin of a disease

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Seafood Choices: Balancing Benefits and Risks Experimental trials A type of study in which human or animal exposure to a substance occurs in a controlled environment for the purpose of studying its effects; in humans, experimental trials are only ethical when there is equipoise between the two arms of the trial Fate and transport Models used by risk assessors to estimate the movement and chemical alteration of contaminants as they move through the environment (e.g., air, soil, water, groundwater) Fibrinogen A protein in blood plasma that is essential for the coagulation of blood Filter-feeding animal An aquatic animal, such as a clam, barnacle, or sponge, that feeds by filtering particulate organic material from water First Nation An organized aboriginal group or community, especially any of the bands officially recognized by the Canadian government Flora The microorganisms that normally inhabit a bodily organ or part Food frequency questionnaire (FFQ) A method of collecting food consumption data; a self-administered questionnaire that asks a study participant how often he/she consumed, on average, a list of specific foods in the past weeks, months, or years to determine a usual long-term diet Functional foods Foods or dietary components that may provide a health benefit beyond basic nutrition Genotoxin A toxin (poisonous substance) that harms the body by damaging DNA molecules Geometric mean A measure of central tendency by which all N terms are multiplied together and the Nth root extracted; useful for summarizing highly skewed data and ratios Global (in the sense of study) Involving the whole population Grating stimuli A geometric pattern used as a substitute for letters or symbols in tests of visual acuity in infants Half-life The time required for the elimination of half a total dose from the body Hazard ratio (HR) Broadly equivalent to relative risk (RR); applying information collected at different times, it is useful when the risk is not constant with respect to time; the term is typically used in the context of survival over time; if the HR is 0.5, then the relative risk of death for one group is half the risk of death in the other group Health Professionals Follow-up Study A study initiated in 1986 and conducted by researchers at the Harvard School of Public Health; enrolled 51,529 male health professionals (dentists, pharmacists, optometrists, osteopath physicians, podiatrists, and veterinarians), aged 40–75, to evaluate the relationship between nutritional factors and the incidence of serious illnesses such as cancer, heart disease, and other vascular diseases in men; follow-up questionnaires were mailed out every two years to

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Seafood Choices: Balancing Benefits and Risks update exposure information and identify cases; designed to complement the all-female Nurses’ Health Study (see below) Health risk appraisal (HRA) An instrument commonly used in worksite preventive health care to identify the likelihood that an individual will develop a preventable or chronic disease, based on personal, medical, and lifestyle indications; comprises a questionnaire, risk estimation, and educational information Histamine A hormone/chemical transmitter involved in local immune responses, regulating stomach acid production, and in allergic reactions as a mediator of immediate hypersensitivity; has been implicated in seafood toxicants from certain species of fish exposed to thermal abuse Homeostasis The state of equilibrium in the body with respect to various functions and to the chemical compositions of the fluids and tissues Hot spots Localized areas with high pollutant concentrations Immunoglobulin A (IgA) The class of antibodies produced predominantly against ingested antigens, found in body secretions such as saliva, sweat, or tears, and functioning to prevent attachment of viruses and bacteria to epithelial surfaces In vitro In an artificial environment outside the living organism Intima-media thickness A unique diagnostic and monitoring service to determine the presence of coronary atherosclerosis in its early stages; refers to a measurement of the first two layers of the artery (intima and media) Intrauterine growth retardation A condition resulting in a fetal weight less than the 10th percentile of predicted weight for gestational age Inuit A general term for a group of culturally similar indigenous peoples inhabiting the Arctic coasts of Siberia, Alaska, the Northwest Territories, Nunavut, Québec, Labrador, and Greenland Lean meat equivalent Amounts of meat alternatives that count as equivalent to 1 ounce of cooked lean meat, e.g., 1/2 cup of cooked dry beans or peas, 1/2 cup tofu, 2 tablespoons of peanut butter, 1/3 cup of nuts, or 1/4 cup of seeds Leukocyte White blood cell; blood cells that engulf and digest bacteria and fungi; an important part of the body’s defense system Linear model Fitting a straight line to the data to help describe a pattern in the data; the term “linear” refers to the fitted straight line, and the term “model” refers to the equation that summarizes the fitted line Lipids Members of a large group of organic compounds insoluble in water and soluble in fat solvents; lipids of nutritional importance include essential fatty acids, triglycerides, and sterols Lipophilic compounds Substances capable of dissolving, of being dissolved in, or of absorbing lipids; lipid soluble

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Seafood Choices: Balancing Benefits and Risks Lipoprotein A compound protein consisting of protein and lipid; has the solubility characteristics of protein and hence is involved in lipid transport High-density lipoprotein (HDL) A complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood; high levels are associated with a decreased risk of atherosclerosis and coronary heart disease Low-density lipoprotein (LDL) A lipoprotein that transports cholesterol in the blood; composed of a moderate amount of protein and a large amount of lipid; high levels are thought to be associated with increased risk of atherosclerosis and coronary heart disease Listeria monocytogenes A principal pathogenic bacterium that has been associated with safety risk from a large variety of foods, including seafoods Lipoprotein (a) [Lp(a)] An LDL-like particle that is produced in the liver; numerous studies have found that concentrations of plasma Lp(a) above 0.3 g/L (note reference ranges may vary between laboratories) are associated with an increased risk of coronary heart disease Maximum likelihood A popular statistical method used to make inferences about parameters of the underlying probability distribution of a given dataset Mechanistic Of or relating to the philosophy of mechanism, especially tending to explain phenomena only by reference to physical or biological causes Meta-analysis Combined results of several studies that address a set of related research hypotheses Metaphase A stage of mitosis; condensed chromosomes, carrying genetic information, align in the middle of the cell before being separated into each of the two daughter cells Methylmercury The form of mercury of greatest concern with regard to seafood consumption; results when mercury from other forms is deposited in bodies of water and biotransformed through the process of methylation by microorganisms; it bioaccumulates through the food chain, and thus its highest concentrations are in large long-lived predatory species Minimal risk level An estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure Mitotic Of or relating to mitosis, the process by which a cell separates its duplicated genome into two identical halves Molar A unit of concentration for solutions Molluscan Of or relating to numerous chiefly marine invertebrates, typically having a soft unsegmented body, a mantle, and a protective calcareous shell; includes edible shellfish and snails

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Seafood Choices: Balancing Benefits and Risks Monte Carlo analysis Randomly generates values for uncertain variables over and over to simulate a model Muktuk The skin and underlying fat (blubber) layer of a whale Multicenter A single study conducted in more than one location Multipliers Quantifies the additional effects of an exposure/intervention beyond those that are immediately attributable to the intervention alone Multivariate analysis A method in which several dependent variables can be considered simultaneously; not to be confused with multivariable analysis that involves several variables, even if only one dependent variable is considered at a time Myocardial infarction Sudden insufficiency of arterial or venous blood supply involving the middle layer of the heart usually as a result of a closed, or closing, coronary artery Myometrium The muscular wall of the uterus MyPyramid Released in 2005 by the US Department of Agriculture (USDA) to help consumers make choices from every food group, find their balance between food intake and physical activity, and get the most nutrition out of their calories; replaced the Food Guide Pyramid; can be found at http://www.mypyramid.gov Norovirus A group of related, single-stranded RNA, nonenveloped viruses that cause acute gastroenteritis in humans; transmitted primarily through the fecal-oral route, either by consumption of fecally contaminated food or water, or by direct person-to-person spread Northern dwellers Native people living in the far north Nunavik The arctic region of Québec, Canada; an Inuit homeland Nurses’ Health Study A study initiated in 1976 and conducted by researchers at the Channing Lab, Harvard Medical School and the Departments of Epidemiology and Nutrition, Harvard School of Public Health; enrolled 121,700 female registered nurses aged 30–55 living in 11 states to assess risk factors for cardiovascular disease and cancer; follow-up questionnaires were mailed out every two years to update exposure information and identify cases and, as of 1980, included a diet assessment Observational studies Study types that follow a population (either prospectively or retrospectively) to examine how exposure to risk factors influences one’s probability of developing a disease in the absence of intervention; includes cross-sectional studies, cohort studies, and case-control studies Occipital cortex The part of the brain used to process visual information Odds ratio (OR) In a case-control study (see above), the exposure odds among cases compared to the exposure odds among controls, where the exposure odds are the number of individuals with the exposure relative to the number of individuals without the exposure (e.g., if 3 out of 10 people are exposed, then the exposure odds are 3:7)

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Seafood Choices: Balancing Benefits and Risks Omega-3 fatty acids (n-3 fatty acids) Polyunsaturated fatty acids found in oil from fatty fish as well as plant sources; characterized by the presence of a double bond 3 carbons from the methyl end in the carbon chain; includes alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) Omega-6 fatty acids (n-6 fatty acids) Polyunsaturated fatty acids found in animal and vegetable sources of fat; characterized by the presence of a double bond 6 carbons from the methyl end in the carbon chain; includes linoleic acid (LA) and arachidonic acid (AA) One component pharmacokinetic model Assumes that the drug in question is evenly distributed throughout the body into a single compartment and that the rate of elimination is proportional to the amount of drug in the body; only appropriate for drugs which rapidly and readily distribute between the plasma and other body tissues P-value As in hypothesis testing; the probability of getting a value of the test statistics as extreme as, or more extreme than, the value observed, if the null hypothesis (i.e., no association, no effect of treatment) were true; the alternative hypothesis determines the direction of “extreme”; usually p<0.05 means that the null hypothesis is rejected and the association between the exposure and outcome is statistically significant Parenteral The introduction of substances into an organism by intravenous, subcutaneous, intramuscular, or intramedullary injection Paresthesia A skin sensation, such as burning, prickling, itching, or tingling, with no apparent physical cause Pathogenic bacteria Bacteria that cause disease or abnormality Pelagic fish Fish living in open oceans or seas rather than waters adjacent to land or inland waters Persistent organic pollutants (POPs) Organic chemicals that remain intact in the environment for long periods, become widely distributed geographically, bioaccumulate up the food chain by accumulating in fatty tissues of animals, and pose a risk of causing adverse effects to human health and to the environment Plasma lipids Lipids in the fluid portion of anticoagulated blood Platelet A type of blood cell that helps prevent bleeding by causing blood clots Population attributable risk The proportion of disease in a population that would be prevented if the risk factor were removed from the entire population Post hoc Formulated after the fact; for example, a post hoc analysis is designed and applied to data already collected for another study Precentral gyrus The convolution of the frontal lobe of the brain that is bounded in back by the central sulcus and that contains the motor area

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Seafood Choices: Balancing Benefits and Risks Preeclampsia A toxic condition developing in late pregnancy characterized by a sudden rise in blood pressure Prophylactic Preventing disease Prospective cohort study An epidemiological and observational study in which a defined group of persons known to be exposed to a potential disease risk factor is followed over time and compared to a group of persons who were not known to be exposed to the potential risk factor, to evaluate the differences in rates of the outcome; also termed a prospective observational study, follow-up study, incidence study Prostaglandins Lipid-based membrane-associated chemical messengers synthesized by most tissue cells; act locally as a hormone-like substance; may be synthesized from both omega-3 and omega-6 fatty acids Provisional tolerable weekly intake Exposure limit presented in micrograms of contaminant per week and per 1 kg body mass Public Health Service Act Defines the federal agencies and their personnel who are are part of the federal Public Health Service Reference Dose (RfD) An estimate (with uncertainty spanning perhaps an order of magnitude) of daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime Regression coefficient The slope of the straight line that most closely relates two correlated variables; the number of units that a dependent variable changes for each one unit increase in an independent variable Relative risk (RR) Rate of the outcome of interest in a population compared with the rate in the reference population Risk assessment An organized process used to describe and estimate the likelihood of adverse health outcomes from environmental exposures to chemicals; the four steps are hazard identification, dose-response assessment, exposure assessment, and risk characterization Salmonella spp. A genus of bacteria including several pathogenic species that have been associated with risk from contaminated foods, including seafoods Saturated fat Fatty acids with no double bonds; fats that are solid enough to hold their shape at room temperature (about 70°F) Science-based knowledge Conclusions (findings and recommendations) based on clear and consistent evidence from both observational and experimental study designs Scombroid poisoning Intoxication by foods that contain high levels of histamine caused by bacterial contamination Serum lipids Lipids in the fluid portion of coagulated blood Shellfish Common terminology used to identify crustacean and/or molluscan seafoods

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Seafood Choices: Balancing Benefits and Risks Standard deviation A statistic that shows how tightly all the various data points are clustered around the mean in a set of data Tertile A contiguous grouping (low, middle, high) of one-third of a sample or population Thermal abuse Improper refrigeration or heat exposure during preparation, storage, or transfer Toxicant Any substance or material that can injure living organisms through physicochemical interactions Toxicity equivalency factor A numerical index that is used to compare the toxicity of different congeners and substances Toxicokinetic The processes of absorption, distribution, metabolism, and excretion that occur between the time a toxic chemical enters the body and when it leaves Toxin A poisonous substance (of animal, mineral, vegetable, or microbial origin) that can cause damage to living tissues Trophic Of or relating to nutrition Triglycerides (TG) A naturally occurring ester of three fatty acids and glycerol that is the chief constituent of fats and oils Uncertainty factor (UF) One of several (generally 10-fold factors) used in operationally deriving the Reference Dose (RfD) from experimental data. UFs are intended to account for (1) the variation in sensitivity among members of the human population; (2) the uncertainty in extrapolating animal data to the case of humans; (3) the uncertainty in extrapolating from data obtained in a study that is of less-than-lifetime exposure; and (4) the uncertainty in using Lowest Observed Adverse Effect Level data rather than No Observed Adverse Effect Level data Value trade-off The willingness to pay a higher price for something with a higher value rating attached Vibrio vulnificus A bacterium usually associated with raw molluscan shellfish Voluntary Seafood Inspection Program A program for inspection and certification of seafood processing plants, designed to ensure quality more than product safety; conducted by the National Marine Fisheries Service SUPPLEMENTARY INFORMATION ON NUTRIENTS OF SPECIAL INTEREST IN SEAFOOD Omega-3 Fatty Acids Omega-3 fatty acids occur widely throughout the plant and animal kingdoms. Algae, fungi, bacteria, insects, and some vertebrates possess the array of enzymes needed for de novo synthesis of these fatty acids (Gill and Valivety, 1997a). Genetically complex plants, though they may be good

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Seafood Choices: Balancing Benefits and Risks sources of alpha-linolenic acid (ALA), rarely produce polyunsaturated fatty acids longer than 18 carbons and thus are not sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Though more genetically complex animals can synthesize EPA and DHA from ALA (Qiu, 2003), the rate of synthesis in most species is low. Fish are good sources of EPA and DHA primarily because their natural diets contain these fatty acids, not because they are able to synthesize them de novo. Organisms low on the food chain consume the algal and microbial sources of EPA and DHA, which become concentrated in the lipid stores of those species higher up in the food chain. Derivation of the Omega-3 Fatty Acids Omega-3 fatty acids are long-chain polyunsaturated fatty acids that are characterized by the presence of a double bond at the omega position (3 carbon atoms from the methyl end) in the carbon chain. This position is what identifies them as omega-3 fatty acids. EPA and DHA are not endogenously synthesized from saturated, monounsaturated, or omega-6 fatty acids; they can only be made from the precursor omega-3 fatty acid, ALA. Figure A-1 shows the synthesis pathways for omega-3 fatty acids. The omega-3 fatty acids include: Alpha-linolenic acid, 18:3 n-3, a plant-derived source of fatty acid. ALA can be converted to the omega-3 fatty acids EPA and DHA through a series of desaturation and chain elongation events, but the conversion in humans is inefficient and varies with the content of other fatty acids in the diet (see discussion below for more information about conversion efficiency); Eicosapentaenoic acid, 20:5 n-3, a fatty acid synthesized from ALA and found primarily in fatty fish. EPA is a precursor molecule in the human synthesis of one family of eicosanoids, including prostaglandins, thromboxane, leukotrienes, hydroxy fatty acids, and lipoxins. These compounds serve as modulators of cardiovascular, pulmonary, immune, reproductive, and secretory functions at the cellular level; Docosahexaenoic acid, 22:6 n-3, a fatty acid synthesized from ALA and found primarily in fatty fish. It is a component of all membrane structural lipids in neural and retinal tissues and spermatozoa. The developing brain accumulates large amounts of DHA late in fetal life. This accumulation continues through at least the first 2 postnatal years. Selenium Selenium is an element classified within Group VIA in the periodic table following oxygen and sulfur but preceding tellurium and polonium.

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Seafood Choices: Balancing Benefits and Risks FIGURE A-1 Biosynthesis of long-chain fatty acids. NOTES: LA = Linoleic acid; AA = Arachidonic acid; ALA = Alpha-linolenic acid; EPA = Eicosapentaenoic acid; DPA = Docosapentaenoic acid; DHA = Docosahexaenoic acid. SOURCE: Derived from IOM, 2002/2005. This position in the periodic table leads to the classification of selenium as a metalloid element with unique chemistry and biochemistry, i.e., exhibiting both metallic and nonmetallic properties. Selenium can form bonds with other selenium atoms, a characteristic referred to as catenation and shared with other elements like carbon, silicon, and sulfur. Elemental selenium is found in three forms: the gray-black form or metallic hexagonal selenium, an amorphous white form, and a monoclinic red form. Selenium has six electrons in the 4s and 4p, orbital and the empty dπpπ bonds of selenium, like sulfur, can be filled by pπ electrons of oxygen. Selenium and sulfur have

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Seafood Choices: Balancing Benefits and Risks similar radii Δ, 1.03 and 1.07 (covalent radii), and similar electronegativities of 2.44 and 2.48, respectively. Thus, the chemical reactivity of selenium and sulfur are similar. However, the reduction potential of selenous and selenic acids are much greater than those of the analogous sulfur acids so that when both are in the same mixture, selenite will be reduced to elemental selenium but sulfite will be oxidized to sulfate. Selenium Essentiality Selenium occurs in all the cells and tissues of mammalian species and reflects the level of dietary selenium over a wide range of intakes. Selenium was recognized as an essential nutrient when Schwarz and Foltz (1957) showed that a form of liver necrosis developed in rats if either vitamin E or selenium was excluded from their diet. It is now recognized that both selenium and vitamin E have important roles in the detoxification of hydroperoxides and free radical byproducts (Sunde, 2001). Selenium deficiency has been demonstrated in premature infants and patients utilizing long-term selenium-free enteral or parenteral solutions. Deficiency symptoms include red blood cell hemolysis, cardiomyopathy, growth retardation, cataract formation, abnormal placenta retention, lack of spermatogenesis, and skeletal muscle degeneration. There is a decline of selenoproteins, particularly glutathione peroxidase activity. Selenium deficiency has been found to be endemic in regions of China, where it is called Keshan disease. Children are particularly susceptible, and the disease is characterized by cardiomyopathy. Selenite-enriched salt has been shown to assist in the reversal of this deficiency, but it is likely that selenium is only one factor. Coxsackie virus has been isolated from persons with Keshan disease, and recent animal research has provided evidence that viral infections may be influenced by selenium status. The Institute of Medicine has recommended an intake of no less than 55 and no more than 400 µg of selenium per day as sufficient to meet the needs of the average adult (IOM, 2000). Selenium is an essential element in a group of proteins, i.e., selenoproteins. Sulfur amino acids and selenium are involved in the synthesis of these selenoproteins via selenophosphate to form selenocysteine, catalyzed by the enzyme selenophosphate synthetase. Approximately 25 selenoproteins have been identified, with half characterized with respect to their function (Kryukov et al., 2003). Of those characterized for function, over half perform free radical detoxification. The list of established selenoproteins and their respective biological functions are listed in Table A-1 (Sunde, 2000). The selenium is incorporated into the peptide backbone of selenium-containing proteins as selenocysteine. Novel metabolic pathways are necessary to convert various dietary forms of selenium into the selenocysteine entity. Dietary selenate and selenite are reductively converted to selenide,

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Seafood Choices: Balancing Benefits and Risks TABLE A-1 Selenoproteins and Biological Functions Selenoproteins Function Cytosolic glutathione peroxidase, GPX1 Major form of selenium, protects against hydroperoxides Phospholipid hydroperoxide glutathione peroxidase, GPX4 Lipophilic, works within membranes to destroy peroxides Gastrointestinal glutathione peroxidase, GPX2 Protect intestine against external peroxides Extracellular glutathione peroxidase, plasma GPX, GPX3 Secreted GPX, major form of selenium in milk Selenoprotein W, SELW Small 9.8 kDa selenoprotein found in muscle, postulated to have antioxidant function Selenoprotein P, SELP Major plasma selenoprotein, postulated to protect the cardiovascular system against oxidant damage Thioredoxin reductase, TRRs Reduce small intracellular molecules, regulate intracellular redox state, and may have important roles in antioxidant defense Iodothyronine deiodinase Activation and metabolism of thyroid hormone Sperm capsule selenoprotein   SOURCE: Derived from Sunde, 2001. usually in the intestinal or erythrocyte cells. Selenium released from selenomethionine breakdown will also enter this pool as selenide. Subsequently, synthesis of selenocysteine involves several unique intermediates but it is the selenide that serves as the precursor to selenocysteine. Selenium Food Sources Plant and animal levels of selenium vary widely, reflecting the wide range of selenium content of soils (Sunde, 2001). Corn, rice, and soybeans grown in a selenium-poor region of China contain 0.0005, 0.007, and 0.010 µg/g, respectively, while those grown in seleniferous areas of China can have a selenium content as high as 8.1, 4.0, and 11.9 µg/g, respectively. Organ meats and seafood are usually good sources for this element (USDA, 2005), with levels ranging from 0.4 to 1.5 µg/g, whereas levels in muscle meats

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Seafood Choices: Balancing Benefits and Risks range from 0.1 to 0.4 µg/g, and in dairy products, less than 0.1 to 0.3 µg/g. Drinking water usually has a negligible selenium content, unless it comes from well waters in seleniferous areas (Sunde, 2001). Selenium Toxicity Berzelius first reported the existence of selenium as a metal in 1817. In nature, selenium is often found in combination with lead, copper, mercury, and silver as selenides, similar to sulfur counterparts. Localized seleniferous areas can be found in various parts of the Great Plains in North America. Seleniferous areas also have been identified in Ireland, Israel, Australia, Russia, and South Africa. In grazing livestock of North America, the disease associated with excess selenium intake is known as alkali disease or blind staggers. Selenium accumulator plants ingested by livestock are often the source of selenosis or selenium poisoning. Selenium poisoning can be a mild chronic condition, or severely acute, resulting in death. Acute selenium poisoning resulting in death is often preceded by blindness, abdominal pain, salivation, grinding of the teeth, and paralysis. Death is usually due to respiratory failure, which is often complicated by starvation resulting from loss of appetite, marked restriction of food intake, anemia, and severe pathological changes in the liver (Hogberg and Alexander, 1986). Dullness and lack of vitality, emaciation and roughness of coat, loss of hair, erosion of the joints, atrophy of the heart and cirrhosis of the liver, and anemia characterize chronic selenium poisoning. Chronic selenium poisoning can occur in rats and dogs given diets containing 5–10 ppm selenium. It is likely that the minimum toxic level is 4–5 ppm selenium. Acute toxicity in humans occurs when selenium intake is in excess of 750 µg/day. Usually toxicity occurs when individuals are exposed to high dietary intake and industrial conditions (smelters) that increase the body burden of selenium. The precise ways in which selenium at toxic intakes exerts toxicity are not completely understood. Inhibition of oxygen consumption by tissues appears to be mediated through a poisoning of succinic dehydrogenase. When selenium intake is high, it can be methylated through S-adenosylmethione by either microsomal or cytosolic methyltransferases, forming the products methyl, dimethyl, trimethyl derivatives. Dimethyl selenide is the volatile seleno derivative giving the garlic-like odor (Sunde, 2001). References Gill I, Valivety R. 1997. Polyunsaturated fatty acids, part 1: Occurrence, biological activities and applications. Trends in Biotechnology 15:401–409. Hogberg J, Alexander J. 1986. Selenium. In: Friberg, L, Norberg, G, Vouk VB, eds. Handbook on the Toxicology of Metals. Vol 2. Amsterdam, Netherlands: Elsevier. Pp. 482–512.

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Seafood Choices: Balancing Benefits and Risks IOM (Institute of Medicine). 2000. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press. Pp. 284–324. IOM. 2002/2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN. 2003. Characterization of mammalian selenoproteins. Science 300:1439–1443. Qui X. 2003. Biosynthesis of docosahexaenoic acid (DHA, 22:6–4, 7, 10, 13, 16, 19): Two distinct pathways. Prostaglandins, Leukotrienes and Essential Fatty Acids 68:181–186. Schwartz K, Foltz CM. 1957. Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. Journal of the American Chemical Society 79(12):3292–3293. Sunde RA. 2001. Selenium. In: Bowman BA, Russel RM, eds. Present Knowledge in Nutrition. Washington, DC: International Life Sciences Institute Press. Pp. 352–365. USDA (US Department of Agriculture). 2005. National Database for Standard Release 18. [Online]. Available: http://www.nal.usda.gov/fnic/foodcomp/Data/SR18/sr18.html) [accessed December 4, 2006].

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