Toxicology: Food Toxicology

Front 1

• What is food toxicology?

Back 1

o It is the study of the nature, properties, effects, and detection of toxic substances in food, and their disease manifestations in humans.

Front 2

• How is food toxicology unique?

Back 2

o The nature of food makes it unique. Food is subjected to unpredictable forces of nature and therefore unreliable.
o We need to assess the safety of the substances added to food and the natural substances in food.
o Safe is a term which is used mostly for food toxicology.

Front 3

• What is the unanimous principle of safety in food toxicology?

Back 3

o safety concerns should focus on both nature of the substance and its intended conditions of use.

Front 4

• Where do food tox studies mostly focus on and why?

Back 4

o Focus on digestion and metab. In GI tract because in most cases, it’s not the ingested substance that causes the problem, it’s the products of the digestion that are absorbed.

Front 5

• When did food laws evolve from the ancient times and why?

Back 5

o They mostly coincided with the industrial revolution because there was a loss of control of the food supply.
o Many people were moving from agricultural environments to urban ones which led to the need of transport/storage/preservation/processing/packaging of food. This often involved usage of toxic chemicals so more regulation was needed.

Front 6

• What were the two major problems that stressed the need for regulation?

Back 6

o Toxic colors and preservatives were added to foods, some being carcinogens.
o A bunch of patents on quack medicines, some that were worthless and others that contained unregulated amounts of drugs like cocaine, opium, etc.

Front 7

• What was the first US State food law? Where was it enacted?

Back 7

o It was enacted in MA in 1874.
o It stated that any food sold not wholesome without the buyers knowledge was punishable by fine, imprisonment or standing in pillory depending on severity

Front 8

• What were the problems with the early state laws that were enacted during the 1800s?

Back 8

o Not all states had laws, some had conflicting laws, they weren’t being properly enforced all the time, numerous variations were present in labeling, and there was no national law yet.

Front 9

• Who was Harvey Wiley and what is he known for?

Back 9

o He is considered as a founding father of the FDA. He conducted a clinical study with people called the Poison Squad in 1902-1904. He gave the people in the study food to eat that contained preservatives (many of which could be toxic) and had their body fluids tested.

Front 10

• What did Upton Sinclair do?

Back 10

o In 1906, he wrote a novel called The Jungle which talked about the disgusting conditions of the meat processing industry which caused an uproar in the communities.

Front 11

• What did the Federal Meat Inspection Act of 1906-1907 do?

Back 11

o It called for mandatory inspection of livestock before slaughter
o Mandatory postmortem inspection of the carcasses
o Established sanitary standards for the slaughterhouses and the processing plants
o Authorized the US Dept. of Agriculture to continuously monitor and inspect these facilities.

Front 12

• What was the Pure Food and Drug Act of 1906?

Back 12

o It was the first comprehensive federal food law. It was met with a lot of opposition from industry.

Front 13

• What were the problems with the Pure Food and Drug Act of 1906?

Back 13

o The follow through wasn’t great. Food adulteration was still common.
o There were few purity food standards
o There were limited analytical techniques
o It was weak on food and drug safety
o It put the burden of proof on the FDA (it was one agency that had to go out and enforce all of it, which was tough).

Front 14

• What was the 1937 Raspberry flavored death incident?

Back 14

o The drug, an elixir of sulfanilamide, was adulterated with ethylene glycol which is toxic to the kidneys. People took the drug for a minor condition and died.
o It resulted in revisions of the Pure Food and Drug Act.

Front 15

• What is the Food, Drug and Cosmetic Act of 1938?

Back 15

o It was the revision of the Pure Food and Drug Act.
o It also included cosmetics and therapeutic devices.
o It forbid toxic substances unless it was unavoidable
o It authorized safe tolerances for pesticide residues
o It tightened up on false claims.
o It created standards for many foods.

Front 16

• What were the problems of enforcement with the Food, Drug and Cosmetic Act of 1938?

Back 16

o The burden of proof was still on the FDA and WWII created a lot more work.
o There was a chemical revolution so more drugs, new chemicals, and new processing

Front 17

• What 3 amendments did the 1949 committee chaired by James T Delaney come up with? What was the main goal of these amendments?

Back 17

o The Miller Pesticide Amendment in 1954
o The Food Additive Amendment in 1958
o Color Additive Amendment in 1960
o The main goal was to shift the burden of proof of safety from FDA to the industry

Front 18

• What was the Delaney Clause? What problems did it cause?

Back 18

o It was a clause put in by the committee stating that no chemical shown to be a carcinogen can be added to food or animal feeds. There was a zero tolerance/zero risk policy.
o It caused a problem for the pesticide industry and other industries as the technology increased. It wasn’t applied to just food additives but for everything so a lot of things potentially had to be taken off the shelf even if the levels of carcinogens were negligible

Front 19

• What did the Food Quality Protection Act of 1996 do?

Back 19

o It abolished the Delaney clause for pesticides that showed negligible risks of the carcinogens they’ve contained. It also established a 10 fold safety factor for children.

Front 20

• What is GRAS? How is a substance determined as GRAS? How is GRAS different from Food Additives?

Back 20

o GRAS is Generally Regarded as Safe
o Scientific experts determine whether the substance added to a food is GRAS and publish it for public use. (things like salt, vitamins, etc.)
o The legal distinction between the two is that for Food Additives, scientists have to conduct studies and submit them to the FDA. The FDA has to review the studies and give them a pre-market approval before putting that substance into the food. For GRAS, you don’t have to go through the pre-market approval so the process is expedited.

Front 21

• How can a food be declared unfit?

Back 21

o If it contains unavoidable contaminants that might render the food injurious. However, there are certain levels of the unavoidable contaminants that are allowed (but in parts per billion) in the product which if exceeded can cause it to be taken off the shelf.

Front 22

• What is a food additive?

Back 22

o A substance which may, by its intended use, become a component of food, either directly or indirectly, or which may otherwise affect the characteristics of food
o It can include substances used in producing, manufacturing, processing, preparing, treating, packaging, transporting, holding, or any source of radiation.

Front 23

• What are the different types of food additives?

Back 23

o Direct food additives
o Indirect food additives
o Certified color additives
o Exempt color additives
o Unintentional additives

Front 24

• What are examples of exempt chemicals?

Back 24

o GRAS substances. These don’t have to be pre-approved and therefore is a quicker process; however, the FDA can come back and force it to be removed from the market
o Prior sanctioned substances approved by FDA/USDA before 1958 (like sodium nitrate)

Front 25

• What are regulated food additives?

Back 25

o They are food additives that are not color, GRAS, or prior sanctioned.
o They all require FDA approval and their functions must be justified out of 32 functions.
o They regulatory guidelines are all found in the Redbook.

Front 26

• What are the regulations of color additives? How many types are there?

Back 26

o They require the same testing as food additives.
o They are not eligible to be GRAS and have to be tested at all the FDA concern levels.
o 2 types: certified (by FDA chemists for purity) and Exempt (mostly naturally occurring)

Front 27

• Describe certified color additives. What must be required of them?

Back 27

o They are usually synthetic chemical compounds like aromatic amines and azos.
o They generally have prefixes of FD&C which means it’s safe for food, drugs, and cosmetics.
o Every batch has to be FDA certified.

Front 28

• Describe exempt color additives.

Back 28

o They are naturally occurring like caramel, dried algae, carmine, etc.
o They fade readily, lack intensity and uniformity as well as a precise chemical identity

Front 29

• What kinds of safety tests are run for Food additives?

Back 29

o They must be concurrent with the FDA Redbook guidance.
o There are tests like acute/short term exposure, subchronic and chronic exposure, carcinogenic/mutagenic, developmental tox., immunotox, neuro tox, metabolic, and more

Front 30

• What is the reference dose (RfD)?

Back 30

o It is an estimate of a daily oral exposure to the human population that is likely to be without a huge risk of deleterious effects during a life time
o It can be derived from NOAEL, LOAEL or benchmark dose

Front 31

• What is an acceptable daily intake (ADI)?

Back 31

o It is the amount of a chemical that a person can be exposed to on a daily basis over an extended period of time (usually their lifetime) without suffering deleterious effects

Front 32

• What is an estimated daily intake (EDI)? What must be required of the EDI?

Back 32

o It is a value that is used to determine how much of the substance an individual will be using on a daily basis.
o It is the amount of food consumed daily (intake) x concentration of additive in food (concentration). You have to use the sum of all the sources of the additive in both food and non-food.
o The sum of the EDIs for an additive from all sources cannot exceed the ADI

Front 33

• What are the food safety concern levels (CLs)? What do they determine?

Back 33

o There are three levels CLI, CLII, and CLIII.
o It takes in the consideration the toxicity and the exposure level.
o The CL determines the that toxicity tests are required.There’s category A B and C where C is the highest.

Front 34

• What are the three toxicity categories?

Back 34

o Category A: Low toxic potential
o Category B: intermediate or unknown toxicity
o Category C: High degree of toxic concern

Front 35

• What are the toxicity categories and CLs table values?

Back 35

Front 36

• What does the Concern Level 1 toxicity testing consist of?

Back 36

o Short-term repeated dose studies (not less than 28 days)
o Short term carcinogen tests like gene toxicity
o Doesn’t require much testing

Front 37

• What does the Concern Level 2 toxicity testing consist of?

Back 37

o Sub chronic (90 days with 2 species)
o Multi generation reproduction studies with teratology phases
o Short term carcinogen tests like genetic toxicity

Front 38

• What does the Concern Level 3 toxicity testing consist of ?

Back 38

o Carcinogen studies (rats and mice)
o Chronic feeding study (about 1 year which might be combined with a carcinogen study)
o Chronic study in non-rodent for 1 year
o Multi-generation reproduction with teratology phase
o Short-term carcinogen studies

Front 39

• What are indirect food additives?

Back 39

o These are additives that are not added directly to food. It could enter food through migration of packaging materials, holding containers or processing surfaces. (like cans glass, cardboard etc.)

Front 40

• What kinds of testing must be done for these indirect food additives?

Back 40

o We have to determine how much of the additive is migrating into the food. We do migration studies using solvents to simulate it. Things like 8% or 50% EtOH or corn oil

Front 41

• What kind of studies are done on indirect food additives that have negligible migration? What value is negligible?

Back 41

o Acute toxicity studies only.
o Negligible value is less than .05 ppm

Front 42

• What kind of studies are done on indirect food additives that have a value of .05-1.0ppm?

Back 42

o Subchronic studies with 2 species

Front 43

• What kind of studies are done on indirect food additives that have a value greater than 1.0ppm?

Back 43

o Chronic studies using 2 species, carcinogenicity studies, multigenerational reproduction and teratology studies

Front 44

• What are dietary supplements?

Back 44

o It is a food (not a drug or food additive) that is taken by mouth and is intended to supplement the diet.
o It contains 1 or more of the following: vitamins, minerals, herbs, AA, enz., organ tissue, metabolites, extracts, or concentrates.
o They can be in the form of pills, tablets, capsules, liquids or powders.
o Its label must clearly state that it is a dietary supplement.

Front 45

• What regulations were involved with dietary supplements? When was it established? What did it state?

Back 45

o The Dietary Supplements Health and Education Act (DSHEA) was established in 1994 to provide the legal framework specifically for dietary supplements.
o No claim can be made for a dietary supplement to treat, cure, or mitigate a disease (or else it is considered a drug). It can however make claims that it affects or maintains the structure or function of the body (structure/function claims)

Front 46

• What effect does the Delaney clause have on food additives?

Back 46

o The Delaney clause is applied to food additives. If a food additive is carcinogenic, it can’t be used (0 tolerance policy with strict regulations)
o The FDA requires clear, unequivocal reproducible evidence for cancer (no Risk assessments can be used)
o Only primary carcinogens. Secondary carcinogens are not considered as evidence.

Front 47

• What is the difference between primary and secondary carcinogens?

Back 47

o Primary- are carcinogens that cause cancer through a genotoxic MoA. So it has an effect on your DNA.
o Secondary- carcinogens that will lead to cancer through a non genotoxic MoA. i.e. nutritional, hormonal, physiological imbalances resulting in cancer.

Front 48

• What does the Delaney clause NOW apply to?

Back 48

o Regulated food additives, color additives, and drugs.
o It doesn’t apply to unavoidable contaminants, GRAS substances, priori sanctioned ingredients, or non-functional trace contaminants.

Front 49

• What substances are banned by the Delaney clause?

Back 49

o Packaging materials like Flectol H and mercaptimidazoline
o Food additives like safrole, cinnamyl, anthranilate, thiourea, diethylpyrocarbonate

Front 50

• What is an adverse reaction to food?

Back 50

o General term that can be applied to a clinically abnormal response attributed to an ingested food or food additive

Front 51

• What is food hypersensitivity?

Back 51

o It is an immunologic/allergy type reaction, either cellular or hormonal, resulting from ingestion of a food/additive. It can occur after even a small ingestion and it only happens to a small part of the population.
o It requires PRIOR EXPOSURE to the antigen. FIRST EXPOSURE COULD BE ASYMPTOMATIC

Front 52

• What is food anaphylaxis?

Back 52

o A classic allergic hypersensitivity reaction to food or additive that most often involves IgE antibody and release of chemical mediators. It could lead to death

Front 53

• What are symptoms for food allergies?

Back 53

o Respiratory sx include asthma, wheezing, bronchiospasms, dyspnea,
o Cutaneous sx include urticarial, eczema, rash, pruritis
o GI sx include NVD and abdmonial pain
o There could also be inflammation, vasoconstriction, hypotension, chest pain ,and anaphylaxis.

Front 54

• What is food intolerance? What’s an example?

Back 54

o It is a general term describing an abnormal physiologic response to an ingested food/additive
o The reaction could be immunologic, idiosyncratic, metabolic, pharmacologic, or toxic response
o Example is celiac disease

Front 55

• Define Food toxicity

Back 55

o It is an adverse effect caused by direct action of food/additive on the host recipient without involvement of immune mechanisms. It could involve non immune release of chemical mediators. Toxins may be contained within the food or released by microorganisms/parasites containing food products.
o Ex is fungal toxins, bacterial toxins, tetrodotoxin from pufferfish, domoic acid from mollusks.

Front 56

• What is food idiosyncrasy?

Back 56

o It is a quantitatively abnormal response to food substance/additive
o It differs from physiological or pharm. Effects and resembles hypersensitivity but doesn’t involve immune mechanisms. Usually for those who may be genetically predisposed.
o Favism, fish odor syndrome, lactose intolerance, asparagus urine, etc.

Front 57

• What is an anaphylactoid reaction to food?

Back 57

o It is an anaphylaxis like reaction to a food or additive as a result of non-immune release of chemical mediators. The reaction mimics the symptoms of hypersensitivity.
o Example would be sulfite positing or red wine insensitivity.

Front 58

• What is a pharmacological food reaction?

Back 58

o It is an adverse reaction to a food or additive as a result of a naturally derived or added chemical that produces a drug like or pharm. Effect in hose. Ex would be tyramine in patients with MAO inhibitor drugs.

Front 59

• What is a metabolic food reaction?

Back 59

o It is the toxic effects of a food when eaten in excess or improperly prepared. Like vit. A toxicity

Front 60

• What are the 8 major allergens that were required by FALCPA to be put on labels if the products contained them?

Back 60

o Dairy, eggs, peanuts, tree nuts, crustacean shellfish, wheat, soybean, and fish.

Front 61

• What substances can tolerances be set for?

Back 61

o Pesticide residue in food
o Heavy metals like Pb, As, and CD
o Chlorinated organics

Front 62

• What substances cannot have tolerances set for them? why?

Back 62

o Toxins in fish, shell fish, turtles
o Microbiologic agents (e.coli)
o Bovine spongiform encephalopathy
o Substances produced by cooking
o They can’t be established because they are regarded as avoidable of such hazard that a safe level can’t be set. (FDA either bans these or it can’t be regulated)