Lesson 1 Flashcards
Definition of clinical toxicology
Study of interaction between substances and biological system.
The goal is to gain knowledge about the toxic effect of agents in order to evaluate qualitatively and quantitatively the risks of the contanct with an organism
Definition of occupation toxicology: which parameter needs to be calculated?
it evaluates risk for health due to the exposure to chemical, biological or physical agents in the work environment.
You have to calculate the TVL (threshold limit values) of exposure to promote safe condition
Definition of nutritional toxicology
Study of the potential risks deriving from food
Which parameters may be useful for nutritional toxicology in order to estimate the safe dose
o ARfD (acute reference dose): estimation of the quantity (expressed over body weight) of a certain chemical substance present in a dietary product that can be ingested in a temporal window of maximum 24h
o NOAEL: maximum dose that doesn’t provoke organic toxic modification
o FS: arbitrary safety factor used to extrapolate values for humans
o ADI (admissible daily intake): daily assumption of a quantity of substance (during the whole life) that don’t cause significant risks for human health.
It’s the ratio between no observed adverse level (NOAEL) and the safety factor (FS)
How can we define a toxin ? (according to damage)
We can define a toxin according to their:
- Capacity to provoke damage (qualitative)
- Damage derived from the assumption or exposure (quantitative)
Which are the two possible effects of an intoxication? (localization)
- Local: toxic effect related to the first site of contact (skin or gastroenteric apparatus if oral administration, respiratory tract if air)
- Systemic: after exposure the substance is distributed in the organism with damage to cells and tissues of organs or systems far away from the contact site
Some toxic agents can provoke both effects.
Definition of acute toxicity
syndrome that appear after oral or parenteral administration of a single dose of a liquid or solid substance. It can be defined with the DL50 (median lethal dose).
Definition of genotoxicity
Property of chemical agents that damages the genetic information within a cell causing mutations.
Define Toxicity (T) with a formule
Toxicity (T) is function of concentration of the active compound (C) and/or its target metabolites (R).
It’s also influenced by the affinity between the receptor and the toxic compound (ARC)
T=C⋅R⋅ARC
Definition of oxidative stress
imbalance between the physiological production of free radicals and reactive oxygen species (ROS) and the presence of endogenous antioxidant agents in the cell.
Which are the consequences of ROS accumulation in the cell?
- point mutation in the DNA
- alteration of calcium homeostasis and consequent alteration in mitochondria functionality
Definition of antidote
A substance that is used in therapy to counteract the toxic action of xenobiotic
Which are the phases of risk characterization?
1- Hazard identification
2- Characterization of danger
3- Evaluation of human exposition
What is the hazard identification?
It’s an evaluation of the intrinsic toxicity of the substance, you have to check:
- Toxicokinetics and toxicodynamics
- Acute toxicity
- Genotoxicity
- Subchronic and chronic toxicity
- Carcinogenicity
What is the characterization of danger?
It’s an evaluation of the relevance of toxic effects in the human species.
For non-pharmaceutical substances (ex: dietary additives) we can check the ADI and evaluate the daily assumption of a quantity of substance that don’t cause significant risk for human health.
For pharmaceutical substances we have to harvest clinical data in different groups of people (clinical trial).
