Notes Food Hazards – Toxicology
Week 1 – Introduction Food Hazards
Food safety – assurance that food will not cause harm to the consumer when it’s prepared and/or eaten
according to its intended use
Hazard – a biological, chemical or physical agent in food (or condition of food) with the potential to cause an
adverse health effect
Potential hazards and risks in food:
! When a GMO ingredient is > 0.9% of the total product, it should be specifically mentioned on the label
Week 1 – Food Hazards Introduction, History and Principles
Toxicology – study of the adverse toxic effects of chemicals on living organisms
Historical perspective:
1. Hunting, fishing, gathering:
- Knowledge on acute toxic properties of plants, mushrooms and some minerals (e.g. Monkshood)
- Probably less knowledge of chronic effects
- Ancient Europa and Asia used to poison hunting spears and enemy water supplies during war (Cardiac
arrythmias (slowing heat rate) and hypotension (lowering blood pressure))
2. Agricultural development:
- Cooking allowed cultivation of new plants containing natural toxins as crop
- Storage and transport introduced new toxic compounds such as moulds (mycotoxins)
Dose response relationship – establishes causality that the chemical has in fact induced the observed effects.
Determines the rate at which injury builds up: slope of dose-response curve (discovered by Paracelsus in the
middle ages)
3. Industrial development:
- Distance between food sources and consumer increases
- New preservation methods such as canning
- Addition of chemical additives for preservation or colouring
- Legal steps to guarantee good quality of food in the 19th century
- Alarm phase – phase during the industrial revolution in the 20th century and WWII. Many pesticides
(e.g. DDT), war gasses, munition drugs, industrial chemicals and synthetic fibres were used.
DDT (dichlorodiphenyltrichloroethane) – and other organohalides such as dieldrin and aldrin were used as
insecticide, causing problems such as vomiting, tremors, seizures, effects on liver, reproduction problems and
,possibly cancer (book written by Rachel Carson who said you cannot use chemicals endlessly without looking
at the consequences)
Dioxins (TCDD) – persistent organic pollutant, linked to problems with reproductive health, the immune
system, hormone levels and tooth enamel.
Softenon (thalidomide) – introduced as sleeping aid, but recognized as cause of malformations as thalidomide
inhibits angiogenesis, the formation of blood vessels
Week 1 – Food Hazards Mechanisms
Toxins can be divided into two groups:
1. Directly toxic chemicals – have certain physiochemical properties (some metals, strong acids and bases,
nicotine and CO)
2. Reactive metabolites – formed during biotransformation processes, called bioactivation (insertion of
electrons, very reactive groups)
Reaction of ultimate toxicant with target:
1. Non-covalent binding:
- structural similarity with natural ligand: competition for physiological receptor (agonist stimulates signal
transduction and transcription, antagonist blocks signal transduction)
- no structural similarity natural ligand (blocker reduces permeability activity, modulator increases
permeability activity)
2. Covalent binding: reactions with macromolecules (DNA, RNA and protein alkylation by electrophiles cause
gene-mutation, resulting in loss of function)
3. Reactive oxygen species: hydrogen abstraction (by reactive oxygen species (ROS) and other radicals, such
as hydroxyl radicals OH, superoxide anion radicals O2- and hydrogen peroxide H2O2, causing damage to
proteins by inactivation, DNA by mutation and lipids by lipid peroxidation)
Formation of reactive oxygen species – radicals formed during biotransformation:
Catalysed Haber-Weiss reaction – increases the impact of superoxide anions O2- and H2O2 by the formation of
reactive hydroxyl radicals OH:
Lipid peroxidation – disturbs membrane structure:
4. Electron transfer
,Methemoglobinemia – condition in which the haemoglobin is in the form of metalloprotein, in which the iron
in the heme group is in the Fe3+ (ferric) state instead of the Fe2+ (ferrous) state. Methemoglobin cannot bind
oxygen, which means it cannot carry oxygen to tissues.
Examples of toxins:
- CO – binds 220x stronger to the heme Fe2+ groups of haemoglobin than O2, resulting in anemia
- Tetrodotoxin – from puffer fish, blocks Na+ channels neurons, resulting in paralysis
- Saxitoxin – paralytic shellfish poison (PSP), blocks Na+ channel
- Aflatoxin B1 – produced by aspergillus flavus, found in nuts, beer and wheat, causing mutations in the
P53 tumor suppressor gene and genes coding for capillary density of tumors, resulting in liver cancer
- Acetylcholinesterase (AChE) inhibitors, such as insecticides like parathion and warfare gasses like sarin,
soman and tabun – form covalent bonds with serine OH groups in the active site of AChE enzymes, so
the hydrolysis of neurotransmitter is inhibited, increasing both the level and duration of action of the
neurotransmitter acetylcholine.
- Mustard gas – highly reactive compound that acts by means of covalent addition to cellular target
molecules, causing blistering of the skin because of its corrosiveness.
! The effect of the reaction of the toxicant depends on the function of the target:
Molecular repair:
- Reverse the oxidation of proteins or methylation of DNA
- Replace peroxidised lipids or DNA nucleotides
Cellular repair:
1. Apoptosis – programmed cell death (without causing subsequent effects in the tissue):
- Membrane stays intact
- Shrinking cytoplasm/nucleus
- Cell fragmentation
- ATP dependent
- No inflammatory response
- Physiological stimuli
2. Necrosis – cell death which only happens if cells are exposed to high concentrations of chemicals and
apoptosis cannot occur (causing adverse effects in the tissue)
- Loss of membrane integrity
- Swelling cytoplasm/mitochondria
- Cell lysis
- No energy required
, - Inflammatory response
- Non physiological stimuli
3. Proliferation – producing new tissue to replace damaged tissue removed by apoptosis or necrosis. Failure of
repair causes uncontrolled proliferation (disrepair), causing scars, cancer or fibrosis (excessive accumulation of
extracellular matrix (collagen))
Variation in toxic response:
- Intra (within) species or between individuals of one species (genetic polymorphisms)
- Age
- Nutrition and life style
- Gender
- Combined exposures
Importance dose response curve:
- Data establishes NOAEL: threshold level at which safe levels of exposure can be derived
- To be sure the adverse effects are coming from the chemical studied
! Threshold values can only be derived for non-genotoxic chemicals. For genotoxic chemicals, chemicals that
damage the DNA and may induce cancer, no NOAEL can be derived, because every molecule will increase the
chances of developing cancer.
Week 2 – Absorption, Distribution and Excretion
Absorption – passing cell membranes:
1. passive diffusion through the membrane phospholipids
2. passive filtration through aqueous pores
3. active transport
4. facilitated diffusion
5. phagocytosis and pinocytosis
Passive diffusion and filtration – molecules are moved down a concentration gradient:
- Small molecules up to Mw 100-200 (ethanol, ureum)
- Influenced by lipophilicity (ability to dissolve in lipids = non-polarity), ionisation and blood flow
Role of ionisation of chemicals:
Effect of pH on ionisation: pH in the stomach is low (±2), pH in the intestines is high (±7). Charge is hindering
the uptake through a membrane. Ionized molecules can therefore not be absorbed easily. Acids are mostly
taken up in the stomach and amines are mostly taken up in the intestines.
Role of blood flow: maintain a concentration gradient across the membrane. Diffused chemicals are taken
away, to maintain a gradient across the cell membrane and continue diffusion.
Active transport – molecules are moved up a concentration gradient:
- Selective transport system and the potential for competitive inhibition
- Requires energy (ATP), sensitive to inhibition by metabolic inhibitors
- Transport system is saturated at high substrate concentrations (Tmax)
