Toxicity test:

Acute (in vivo test): adverse effects occurring by a short-time administration of a single
dose or multiple doses given within 24 hrs
Genetic: to determine the tendency of a substance to induce mutations in a test organism
(mutation = DNA base change; mutagen = the substance to induce mutations)
o Ames test (short-term in vitro test; bacterial reverse mutation assay): evaluate a
chemicals genotoxicity/carcinogenicity by measuring its ability to induce reverse
mutation in bacteria; example: hydrogen cyanide HCN
o Dominant lethal test: determines genetic changes in mammals (in the next
generation); example: acrylamide in mice
Metabolic/pharmacokinetics: the use of modeling and mathematic description to
understand absorption, distribution, biotransformation, and elimination of a toxicant over
time
Sub-chronic/sub-acute: adverse effects occurring by daily or frequent exposure to a toxic
substance over a period of time (sub-acute: 14, 21, 28 days; sub-chronic: 90 days);
example: paprika in mice
Chronic: adverse effects resulting from long-term, low-level exposure which would not
be evident in sub-chronic testing; MOS = 100 = NOEL/ED99; example: cadmium and
bone density loss
Reproductive: reproductive and developmental (teratogenesis) testing is an important
aspect of sub-chronic testing; determines adverse effects on the male/female reproductive
systems and on developing organisms from the exposure to a chemical
o General fertility and reproductive performance test (may induce fertility?)
o Check the potential of chemicals to disrupt embryo/fetal development (may
interfere with fetal development?)
o Check toxicity effects on offspring (may have impact on offspring?)

Mechanism of Toxins
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Nonspecific toxic effects (systemic): may occur at multiple sites, example: acids/bases to
denature protein
Special toxic effects:
o Mutagenesis:
Mutation = DNA base change
Mutagenesis/mytagenicity = the process of forming mutation
Mutagen = the substance causing mutation
Mutant = the organism exposed to mutagen
Different types of mutation: point; addition or deletion of DNA bases;
chromosome rearrangement; silent mutation
o Carcinogenesis:
Tumor = abnormal cell growth of somatic cells

o Teratogenesis: malformation in an unborn organism or human due to exposure of

a toxic substance (thalidomide)
Efficiency of liver metabolism, excretion, tissue storage, and protein
binding of the maternal system
The rate of passage of a teratogen across the placenta
***Timing: human fetus is most susceptible to anatomical defects at
around 30 days of gestation (first trimester)
***Deficiency of folate/folic acid during early stage of pregnancy leads to
neural tube defect of fetus
Selective effects:
o Neurotoxicity:
Neural tissues may be damaged by:
Lack of oxygen
Diminished cellular respiration by metabolic inhibitor
Direct damage to the structures and enzymes within neurons by
nutrient deficiency or accumulation of heavy metals
Interference of neural transmission: inhibition of neural
transmission (sedative drugs); stimulation of neural transmission
(caffeine, cocaine); block neural transmission (curare to block
transmission between neuron and muscle)
Fetal alcohol syndrome: affects growth retardation, unusual facial
features, mental retardation
A neural tube defect of fetus due to folate deficiency in pregnant
mothers
Hepatotoxicity (liver toxicity): water-soluble substances go through liver
Fatty liver, liver hepatitis, cirrhosis (3 stages of liver damage due
to chronic alcohol consumption)
Acetaminophen (Tylenol) and liver damage
Hematotoxicity (blood toxicity): damages on blood cells function or
structure
Anemia = deficiency of some nutrients causes anemia (too few
RBC or too little hemoglobin)
Iron-deficiency anemia/hypochromic anemia/low hemoglobin
production
Folate deficiency: hampers cell division
Vitamin-B deficiency anemia:
DNA mutation
Skeletal toxicity:

Vitamin D: deficiency causes rickets in children (softening and

weakening of bones) and osteomalacia in adults; toxicity of
vitamin D causes calcification of soft tissue (heart, kidney)
Vitamin C: develops collagen structure of the bones
Vitamin A: bone growth, maintaining tissue integrity and night
vision

Natural Toxins in Animal Foodstuffs

o Bile is made in liver, stored in gallbladder, and secreted into small intestine;
functions: breaks up globs of fat
o Vitamin A: symptoms deficiency: night blindness, dry and hardening of
protective lining of organs, slow bone growth; excess of intake: joint/bone pain
and soreness, headache, hair loss, nausea
o Beta-carotene is precursor found in plants. Vitamin A can only be found in
animals and stored in liver
o Scombroid poisoning (fish poisoning): improper stored fish (mahi-mahi, tuna,
mackerel); elevated histamine produced by bacterial degradation of substances in
the muscle protein.
o RED TIDE:
PSP (saxitoxin): consumption of shellfish; neural toxin blocking sodium
ion pores of nerve and muscle membranes; symptoms: numbness,
drowsiness, respiratory paralysis
NSP (brevetoxin): consumption of shellfish; symptoms: numbness,
drowsiness, no respiratory paralysis
Ciguatera poisoning (Ciguatoxin; fish poisoning): consumption of subtropical/tropical fish (barracuda, amberjacks, sea bass, red snapper);
symptoms: affects GI tract and nervous system, blurred vision, ***altered
cold sensation
o NOT related to red tide:
Puffer fish (fugu) poisoning (Tetrodotoxin): puffer fish, sun fish, and some
amphibians; symptoms: numbness, muscular paralysis, respiratory arrest;
no antidote
o Allergy: altered immunological reactivity to a foreign material (allergens are
proteins)
Natural Toxins in Plant Foodstuffs
-

Solanine in potatoes: inhibits cholinesterase activity

Caffeine and theobromine in coffee, tea, and chocolate: alkaloid called methylxanthine;
theobromine is bad for dogs
Pyrrolizidine alkaloid: liver toxin; ingestion through herbal remedy or contaminated food

Quinie: drug to treat malaria; added to tonic water (bitter taste)

Non-alkaloid:
Goitrogen (anti-thyroid-hormone substance): found in Brassica plants (cabbage, broccoli,
turnip, cassava; mechanism: either inhibit thyroid hormone synthesis, or inhibit iodine
uptake by thyroid gland
Cyanogens (cyanogenic glycosides): found in bitter almond, lima beans, cassava; produce
HCN through enzymatic reactions/biotransformation; mechanism: block cellular
respiration process
Favism: genetic disease (people carrying defect gene coding for G6PD cant process
certain metabolic processes leading to rupture of RBC membrane; hemolytic anemia;
consumption of raw and cooked fava beans (broad bean)
Gossypol: found in cottonseed and unrefined cotton oil; causes infertility; destruction of
cardiac muscle.
Absorption of calcium and zinc is reduced in GI tract in the presence of oxalates and
phytates in the food, leading to mineral deficiency
Lectins: a family of proteins that can bind carbs in cell walls or membrane, leading to
agglutination of cells and other biochemical changes; damage of the lining of GI tract
leading to impaired absorption of nutrients; found in legume seeds; ricin found in castor
beans
Oxalates: found in spinach; decreases absorption of calcium
Vasoactive amines: derived from amino acids can effect vascular system; constrict blood
vessel, leading to increase/reduce blood pressure; monoamine oxidase system (MAO)
cam metabolize vasoactive amines; toxicity shows up when theres no MAO.
Sassafras: safrole: flavoring root beer; liver cancer

Bacterial and Viral Toxins

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Foodborne infection: involve the pathogen itself; intoxication: involve the pathogens
toxic product
Staphylococcus: gram-positive; found on skin, in nasal passages; transmitted to food by
direct handling, sneeze or cough
MRSA: methicillin-resistant Staphylococcus super bug
Gram-staining: 2 dyes are used; the PG layer of gram-positive bacteria can trap crystal
violet (purple) during the first staining PG layer of gram-negative bacteria traps safranin
(pink) after the outer membrane of cell wall permeated during 2nd staining
Home-canned veggies and processed meats are associated with botulism. Honey is the
major source of spores of C. botulism; gram-positive; anaerobic;
Adding sodium nitrite to prevent growth of botulism toxins
E. coli is associated with HUS (hemolytic uremic syndrome); kidney failure;
hamburger/ground meat

Microbes grow rapidly between 40F to 140F (4C-60C)

To prevent foodborne illnesses:
o Keep a clean environment
o Avoid cross contamination
o Proper food handling (wash hands)
o Store food at right temps
o Cook food thoroughly
o Use disinfection and irradiation
HACCP: systemized food safety procedure used in many food industries
Prion is the infectious agent of mad cow disease
Norwalk virus/Norovirus