Transcript 投影片 1

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
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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
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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
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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
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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
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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
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Cell culture test
Computer calculations
Acute toxicity tests
Subacute/subchronic tests
Chronic tests