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What are hazards in food system? • Physical – Fish bones, nail, hair, etc… • Chemical – Environmental pollutants • Heavy metal • Polymers – Pesticides – Antibiotic residues – Food additives (legal or illegal) • Biological – Bacteria – Fungi – viruses – Parasites – Prion • Natural toxins – Bacterial toxins – Mycotoxins – Animal toxins • Puffer fish, cigatoxins, PSP, – Plant toxins • Toxicity is determined by the dosage • Anything and everything is toxic Risk assessment • Define risk, danger, and hazard • Types of hazards • Toxicity of the hazards – Toxic dosage – Concentrations of the hazards – Contact and absorption pathway • Food, water, air, and skin. – Balance of absorption and detoxication • Age, gender, body size, health status • Decide which hazard • Toxicological studies of the hazard • Concentrations of the hazard in food or environment • Maximally possible absorption concentration – The worst case scenario • Evaluation of toxicity of substances • Epidemiological studies of human or other populations exposed to the toxic compound • Animal test (in vivo) • Test lower organisms (in vivo) • Test cell cultures (in vitro) • Computer calculations (in silico) Epidemiological studies • Incidental via environment, occupation, or diet – Accidentally uptaken from environment, occupation, or diet • Intentional, for example, with a drug or food additive – Intentionally added into food system – Human volunteers – Phase I and Phase II • Cohort studies – Drug vs. placebo • Case control • Cross-sectional • Ecological studies – Compare different geographic areas • Absolute excess risk – A=the number of the cases of an illness in an exposed population – B=the number of nonaffected individuals in the control population – C=the number of the exposed nonaffected individuals – D=the number of the individuals who have fallen ill without any exposure to the toxicant Animal tests • Quantitative-structure activity relationship QSAR • Nonobserved adverse effect level (NOAEL) • Lowest adverse effect level (LAEL) • Safety factor – Inter-species – Intra-species • Body area and dosage • Animals from wild populations or open colonies • Animals from closed colonies (pure line) Organism-independent factors influencing compound toxicity • • • • • • Species Genetic Genertic Age Dietary conditions Health conditions • Cell culture • Computer • Acute • Sub-chronic • Chronic – Acceptable daily intake (ADI) – Tolerable daily intake (TDI) – Reference daily intake (RDI) Toxicological safety and risk analysis • Toxicological safety – There is not a single chemical compound in the world has been conclusively proved to be absolutely harmless. – Therapeutic index (TI) – TI=TDx/EDx – TD: toxic dosage; ED effective dosage – Higher TI has a higher therapeutic effect and lower toxic effect (high toxic dosage and low effective dosage) • GRAS: generally regarded as safe • The substance has been used for a long period of time without obvious toxic effect, such as salt (NaCl), sugar, vinegar (acetic acid), lactic acid, ect…. • Risk assessment • Risk management • Risk communication Risk assessment • Risk = hazard x exposure 1. Hazard identification 2. Dose-response 1. TI 3. Exposure assessment 1. The worst case scenario 2. Air, food, water, contact, 4. Risk characterization Hazard identification • Human epidemiology – Real cases • Animal toxicity tests – Dose-response – Replacement, reduction and refinement – If any intro test exist, the animal test should be replaced – The number of animal should be reduced – The method should be refined • In vivo, in vitro and other studies – Toxicokinetics – Absorption – Distribution (including inside the human body and environment) – metabolism Dose-response • Extrapolation from high doses in animal tests to much lower doses of a potential human exposure • • • • On-hit model Linearized multistage model Multihit model Probability unit model • Physiologically based pharmacokinetic model – Absorption – Distribution – Metabolism – Accumulation – Elimination • Assessment of exposure – The worst case scenario – Food, water, air, contact – Average intake amount • Risk characterization – NOAEL and LOAEL – 70 year • individual difference (the same species) • Interspecies difference • Lower than chronic doses are being used in the animal studies • Use LOAEL instead of NOAEL • ADI=NOAEL/safety factor Evaluation of toxicity of substances • • • • • Epidemiological studies Animal tests with higher organisms (in vivo) Tests with lower organisms Tests with cell culture Computer calculations Epidemiological studies • Well documented accidents with chemicals • Occupational exposure of workers • Volunteers – New drug – Phase I, II, and III • • • • Cohort studies Case-control studies of an incident Cross-sectional ecological Animal test • For safety reason, human is considered as 10 times more sensitive than animials. • Body area • M2=k x w/100 • Animal number – Small number of animals with high dose • The difference between human and the tested rats • Animal source – Wild population – Closed colonies – Stemming from colonies by C-section • Intraspecies and intrapopulaitionvariabilities of the character and strength of toxic response • Dependence on species • Genetic variabilities • Generic variabilities (sex or gender difference) • Dependence on age • Dietary condition – Stimulation of a limited number of colonic bacteria strains is an alternative mechanism, which natural compounds may use to facilitate the defense of an organism against food-borne toxicants. E. g. inulins • Health condition – Pathological conditions of the liver – Simultaneous contact with several xenobiotics • • • • • Cell culture test Computer calculations Acute toxicity tests Subacute/subchronic tests Chronic tests