Food Toxicology final exam

What is goiter? What are the causes?

Goitrogens inhibit synthesis of thyroid hormone or iodine uptake, therefore goiter (enlarged thyroid gland) may occur due to goitrogen exposure. Goirtogens found in brassica plants

How does solanine interfere neurotransmission?

Solanine inhibits the activity of acetylcholinesterase (blocks the enzyme) • 1. Acetylcholine neurotransmitter is released from nerve ending • 2. Acetylcholine attaches to its receptors, causing the muscle to contract • 3. Acetylcholinesterase enzyme breaks apart acetylcholine, thereby removing it from its receptors and allowing the muscle to relax o Solanine inhibits the activity of acetylcholinesterase.

Which fish and shellfish poisoning(s) is associated with red tide?

(PSP) Saxitoxin and Amnesic Shellfish poisoning (Domoic Acid)

Acute toxicity test

- Adverse effect occurring by a short time. Administration of a single dose or multiple doses given in 24 hours and extensive tissue damage -Ex: Hydrogen cyanide inhaled by dogs led to immediate coma or death

Acceptable Daily Intake

-Acceptable Daily Intake (ADI) = ED99 -ADI is the amount of a chemical a person can be exposed to on a daily basis over an extended period of time (usually a lifetime) without suffering deleterious effects.

Common limitations in animal and human research studies

...

Exposure to a teratogenic influence at around how many months of gestation is most likely to produce anatomical defects in the developing fetus?

0 to 2 months

Observational Study

A study just observing certain phenomenon, you are not changing their lifestyle Ex: Observing people who only eat organically to see if they are really healthier than those who don't

Risk Assessment

A systematic scientific characterization of potential adverse health effects following exposure to hazardous agents

fat soluble vitamins

ADEK

What is the cause of favism?

Acute hemolytic anemia due to consumption of raw or cooked fava beans. It is a sex-linked, inherited disease.

Chronic Toxicity test

Adverse effects resulting from long-term, low-level exposure which would not be evident in subchronic testing; Mostly rodents are selected; Dosed daily; Cover major portion of lifespan

Assuming two students have the same dose of exposure to a toxicant, but one student has faster rate to detoxify a toxicant in the liver than the other student. Could you get two possible reasons?

Age -The activities of many enzymes are lower in babies than adult Gender -The activity of UDP-glucuronosyltransferase is 47% higher in male rats than in female rats

Ames Test

Ames test (bacterial reverse mutation assay): a test for determining if a chemical is a mutagen/carcinogen devised by Dr. Ames in 1973 (assuming a substance that is mutagenic for the bacteria may also turn out to be a carcinogen). It is a short-term in vitro test.

in vivo

Animal trial. Healthy animals; animals with same strain/species, similar age and weight range, and genetically stable Control group is required Detailed records are maintained for each animal Pathological examination is required after completion of toxicity test

What do antioxidants do? Examples?

Antioxidants can neutralize free radicals, and prevent oxidation of other chemicals. Examples:•Ascorbic acid (vitamin C), α-Tocopherol (vitamin E), BHA&BHT

water soluble vitamins

BC

What toxic substance is associated with inappropriately processed cassava root

Cyanide

Exposure assessment

Determine the amount, frequency, duration and route of exposure (chemicals enter your body through skin, respiratory system, ingestion)

Endocytosis

Energy (ATP) is needed to move molecules across membrane (cell membrane is extended to engulf molecules) Ex: white blood cells

The products (metabolites) from Phase 1 reactions of biotransformation are always less toxic than their parent substances

FALSE

Which plant toxin had been used as a contraceptive?

Gossypol for men in China

grapefruit juice should not be taken together with some medicines. Could you explain the reason?

Grapefruit juice has the chemicals to inhibit Phase 1 reaction -In this case medicine could not be broken down so an overdose could happen

Subchronic Toxicity test

Harmful/ adverse effects occurring by daily or frequent exposure to a toxic substance over a period of time; Two species (rodents and nonrodents) to be tested

What is FAS (fetal alcohol syndrome)?

Infants born to mothers who drink, even in modest amounts, may be born with fetal alcohol syndrome, which often consists of growth retardation, unusual facial features, and mental retardation.

What is the primary site for biotransformation?

LIVER

Where is bile made, stored and secreted?

Made in the liver, stored in the gallbladder, secreted in the small intestine

Why are food additives used in foods?

Maintain the quality of foods -Antioxidants, preservatives Provide essential agent in processing -Emulsifiers, thickeners, etc Provide more nutrients -Vitamin-fortified foods Make foods appealing -Coloring agents, flavor enhancer, etc Substitutes of sugar and fat -Artificial sweeteners and artificial fat

Risk Communication

Make risk assessment and risk management comprehensible to the public

Margin of Safety for food additive

NOEL/ED99=100

Spinach may impair mineral absorption in the digestive tract because of the presence of the anti nutrient, _____________, in spinach

Oxalic acid/ oxalate

The basic difference between Phase 1 and Phase 2 reactions are

Phase 1 reactions oxidize or reduce the substance wheras Phase 2 reactions conjugate a substrate

Risk

Probability that the hazard will occur under specific exposure condition

Delaney Clause

Prohibits the use of food additives shown to cause cancer in humans and animals ("zero tolerance" concept)

What alkaloid is used to flavor tonic water

Quinine

Which shellfish/fish poisoning is not caused by the presence of neurotoxins?

Scombroid

What seafood poisoning causes the symptoms similar to allergy?

Scombroid poisoning -histamine is produced

In vitro

Test tube studies.To determine mutagenic/carcinogenic potential or physiological changes with the exposure to a substance in cell cultures or bacteria.

Is the toxicant metabolized into a less toxic compound after phase 1 reaction?

The outcome can either be more toxic (bioactivation) or less toxic (detoxification)

Interventional study

The researcher intervenes in the study Ex: Say I want to see the effects that eating Chipotle for a week has on someone's health so I change their eating habits to be only chipotle for a week

Which alkaloid in chocolate is toxic to dogs?

Theobromine -Dogs should avoid chocolate because of slow metabolism of theobromine ●The half life of theobromine: ~2-3 hrs in humans; ~18 hrs in dogs

Genetic Toxicity Test

To determine the tendency of a substance to induce mutations in a test organism.

How are toxic substances metabolized in the body?

Toxic substances are metabolized in the body by transforming the substance into new chemicals called metabolites

How come some foods cannot be eaten together with medicines act as MAO inhibitors?

Vasoactive amines can be metabolized by MAO. The toxicity of vasoactive amines show up when there is no MAO. We have an enzyme (MAO) in our body to degrade vasoactive amines

What vitamin is added to nitrite cured meat to lessen nitrosamine formation?

Vitamin C (ascorbate)

Anecdotal evidence

What are the flaws you may find in many claims related to food and nutrition? Give one example.

From the slope of the curve we can learn the rate at which a toxic effect (or beneficial effect) builds up A steeper slope tells us the response rate increases very quickly, the chemical is more toxic & not very tolerable

What can you learn from comparing slopes of cumulative response curves of different toxins?

Safety is freedom from danger, injury, or damage. Absolute safety of a substance cannot be proven

What is the definition of safety?

If A has a bigger value of MOS it means that it is safer than drug B MOS >3= okay medicine, safe for general public MOS= 10 means the curves are really far apart

When you compare two medicines, A and B, what does it mean if A has bigger value of MOS than B?

the dose

Whether a chemical is harmful or beneficial depends largely on

Facilitated diffusion

a carrier-mediated transport of water soluble substances that mimic the structures of endogenous substances that normally exist in the body. NO NEED OF ATP Ex: glucose transporter

Risk Characterization

a process of estimating the probable incidence of an adverse effect to human who is under the circumstances of exposure. (Combination of hazard identification, dose-response assessment, exposure assessment)

Active Transport

active transport requires ATP for energy, works against substrate concentration gradients (low->high), and is saturable. ATP is needed to move molecules across membrane

Food allergy

an altered immunological reactivity to a foreign material (allergen).

Chromatography

an elegant method of chemical separation. Using only a few simple principles, this method can separate and purify practically all chemicals. -The mobile phase (containing the substance of interest) moves through the stationary phase, and the chemicals in mobile phase will migrate at different rates through the stationary phase. The separation of chemicals is on the basis of small differences in sizes, charges, affinity to compounds in the stationary phase, etc.

Lecithin

an emulsifier in food processing, they attract both water and fatty substances o Lecithin makes a good emulsifier because the hydrophobic end dissolves in oil droplets and the hydrophilic end dissolves in water (stops oil and water from splitting) -located in the cell membrane

Red tide

an overabundance of nutrients in the water leads to an over production of algae (dinoflagellates). Algae releases neurotoxins and use up oxygen in the water. This results in the death of fish population (but shellfish can survive).

Recommended Dietary Allowance (RDA)

average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy people.

Retrospective study

collecting information from the past Ex: Does eating a lot of meat cause stomach cancer? Collect information from someone's eating habits This would NOT make sense as a prospective study because you're not gonna start feeding someone BBQ meat to see if they get cancer

Cross sectional study

data are collected on the whole study population at a single point in time to examine the relationship between disease (or other health related state) and other variables of interest. Ex: find bone density for people at the age of 20 Ex: An example of a cross-sectional study would be a medical study looking at the prevalence of breast cancer in a population. The researcher can look at a wide range of ages, ethnicities and social backgrounds. If a significant number of women from a certain social background are found to have the disease, then the researcher can investigate further

Risk Management

decision making, development of regulatory options, evaluation of public health, economic, social and political context for options, involvement of more related communities in decision making

Dose-response assessment

determine relationship between dose and response (What dose causes a response?)

Dominant Lethal Test

determines genetic changes in mammals.

Sucrose

disaccharide sugar. made of glucose and fructose

Simple diffusion

fat soluble molecules move across lipid membranes, small water-soluble molecules move across water pores, NO NEED OF ENERGY (ATP) moving direction: follow concentration gradient (high -> low), can penetrate cell membranes w/out energy

GRAS list

generally recognized as safe -Common use in foods prior to January 1, 1958 without known detrimental effects or health hazards

food intolerance

has nothing to do with the immune system. its just an attack of enzymes or lack of enzymes needed to digest a specific food. Ex: lactose intolerance

Tolerable upper intake level (UL)

highest intake level with no risk of adverse effect increase to almost all individuals

coloring agent "lake"

insoluble form (mix dyes with aluminum hydroxide) used in items containing fat/oil or lacking sufficient moisture, e.g., coated tablets, chewing gum, cake mix, hard candies, etc.

What organ is at risk if we ingest pyrrolizidine alkaloid?

liver

What are the major routes of exposure?

o Digestive system: Important for environmental exposure to food and water contaminants; major route for medicine/drug o Respiratory Tract: Important for environmental and occupational to air contaminants; some medicine/drugs utilize this route o Skin: An important environmental and occupational exposure route; many consumer and pharmaceutical products are applied directly to skin

Enterohepatic cycle

o Liver (via bile) --> small intestine--> portal vein--> liver o Prolongs the life of a xenobiotic in the body

What are the primary storage sites for toxic substances in the body?

o Liver and kidneys: storage of azo dye, cadmium o Lipid cells: sink for lipid-soluble substance (DDT, PCB) o Bone: ions (similar to Calcium) o Thyroid gland: iodine; Goiter (iodine deficiency)Hair, nail, skin: arsenic oAdipose tissue: for lipid soluble toxicants

P-value

o The probability range (or p value), which is commonly used, generally is accepted to be less than 0.05. This value indicates that the same LD or TD value would be obtained in 95 out of a hypothetical 100 repetitions of the experiment. o If P <.05 you reject the hypothesis

What does phase 1 reaction do?

o Transform non-polar compounds into more polar compounds(can get along with water) by oxidation (see below), reduction and hydrolysis o Toxins may become more toxic (bioactivation) or less toxic (bioinactivation or detoxification) o The most important enzyme system: cytochrome P-450

Routes of Excretion

o Urinary excretion by urinary system: most chemicals o Fecal excretion by GI system: unabsorbed substances and bile o Exhaled air by respiratory system. o Others: sweat, milk, tears, saliva

How does alcohol affect neurotransmission?

o When alcohol enters the brain it delivers a double sedative punch. First, it interacts with GABA receptors to make them even more inhibitory (slowing down or preventing a process, reaction, or function.) o Second, it binds to glutamate receptors, preventing the glutamate from exciting the cell. o Alcohol particularly affects the areas of the brain involved in memory formation, decision making and impulse control.

What does the Phase 2 reaction do?

oConjugate a component (mostly polar components) to make previously oxidized/reduced compounds hydrophilic and ready for excretion• oThe most important phase II reaction is glucuronidation (conjugate glucuronic acid). Other reactions include: sulfation ( conjugate sulfonate, "-SO3-"), and acetylation (conjugate "-CH2COOH"), etc.

Nitrosamines

oNitrate combined with amines during cooking or in the stomach --> Nitrosamines - Nitrosamines can cause mutation of DNA--> changes of DNA sequence may lead to cancer. Nitrosamines can also be found in cigarette smoke.

Sodium nitrite's role in the curing of meat

oPreventing botulism (inhibit the growth of C. botulinum) oGiving meat a distinctive pink/red color) oGiving desirable "cured" flavors

Which fish produces tetrodotoxin?

pufferfish

Margin of Safety (MOS ) medicine

ratio of lethal dose to 1% of the population to the Effective Dose to 99% of the population LD1/ED99

nonspecific (systemic) toxic effect

sometimes may occur at multiple sites EX:Strong acids and bases cause protein denaturation Protein denaturation=change of protein shape

Hazard Identification

the act of determining what the hazard is and its ability to cause harm

The fundamental concept of food toxicology

the dose determines the toxicity

dose-response relationship

the dose determines the toxicity, there are toxic and non toxic doses in any substance

NOEL

the highest dose of a substance that does not result in the appearance of a defined physiological or biochemical response

Longitudinal Study

the main variable is time, following an individual or a group for many years Ex: pregnancy outcomes with high protein diets, follow women during their pregnancy journey

selective toxic effect

toxic effect at a specific site (e.g., toxic effect to damage the liver, toxic effect to damage/interfere the nerve cells)

Absolute safety of a food additive cannot be proven

true

Prospective study

watches for outcomes

Coloring agent "dye"

water-soluble form used in beverages

Objectives of Risk Assessment

• Balance risk and benefits • Set target levels of risk • Set priorities for program organizations • Estimate residual risks and extent of risk reduction after steps are taken to reduce risks