TOXICOLOGY, AND HUMAN HEALTH

Toxicity measures how harmful a substance is.

It mainly depends on dose – the amount of absorbed matter.

Three types of toxic entities:• Chemical• Biological• Physical

Chemicals include inorganic substances such as lead, hydrofluoric acid, and chlorine gas, organic compounds such as methyl alcohol, most medications, and poisons from living things.

Biological toxic entities include bacteria and viruses that are able to induce disease in living organisms. Biological toxicity can be complicated to measure because the "threshold dose" may be a single organism. Theoretically one virus, bacterium or worm can reproduce to cause a serious infection.

Physically toxic entities include things not usually thought of under the heading of "toxic" by many people: direct blows, concussion, sound and vibration, heat and cold, non-ionizing electromagnetic radiation such as infrared and visible light, and ionizing radiation such as X-rays and alpha, beta, and gamma radiation.

Factors influencing toxicity:

Pathway of administration (whether the toxin is applied to the skin, ingested, inhaled, injected)

The time of exposure (a brief encounter or long term)

The number of exposures (a single dose or multiple doses over time)

The physical form of the toxin (solid, liquid, gas)

The genetic makeup of an individual

An individual's overall health, and many others.

Toxicity can be measured by the effects on the target (organism, organ, tissue or cell). Individuals typically have different levels of response to the same dose of a toxin

The type and the amount of health damage that resultsfrom exposure to agent are called the response.

An accute effect is an immediate harmful reaction to an exposure ranging from dizzines or a rash to death.

A chronic effect is a permanent consequence (kidneyor liver damage) of exposure to a harmful substance

A population-level measure of toxicity is the median lethal dose LD50. It is the amount of a toxic matter received in one dose that kills exactly 50% of the animals (usually rats and mice) in a test population within a 14-day period

Legally, a poisson is a chemical that has a median lethal dose of 50 mg or less per kg of body weight.

As Paracelsus proposed centuries ago, dose differentiates whether a substance will be a remedy or a poison.

Some examples that illustrate this concept are:

The relation between the dose and the effect

Toxic matters vary in their toxicity

The primary routes of exposure by which toxicmatters can gain entry into the body are:

The route of toxic matters

Fat soluble matters must be transformedinto water soluble matters to be excreted

Skin route

Transport through blood

Behavior of toxic matters in organism

Toxic matter that penetrate into cells can be attached to:

DNAenzimesproteins.

The new complex (matter-receptor) change the space arrangement of molecule’s receptors and can cause a damage of the cells (necrosis, transformation to a cancerous tumors, etc.)

Specific aspects of disposition of greatest importance are:

• duration and concentration of substance at the portal of entry• rate and amount that can be absorbed• distribution in the body and concentration at specific body sites• efficiency of biotransformation and nature of the metabolites• the ability of the substance or it's metabolites to pass through cell

membranes and come into contact with specific cell components (e.g., DNA).

• the amount and duration of storage of the substance (or it's metabolites) in body tissues

• the rate and sites of excretion

Examples of how toxicokinetics of a substance can influence its toxicity:

Absorption:A highly-toxic substance, which is poorly absorbed, may be no more of a hazard than a substance of low toxicity that is highlyabsorbed.

Biotransformation:Two substances with equal toxicity and absorption may differ in hazard depending on the nature of their biotransformation. A substance biotransformed into a more toxic metabolite (bioactivated) is a greater hazard than a substance that is biotransformed into a less toxic metabolite (detoxified).

Kinetics of the toxic mattersAbsorption, distribution, biotransformation, and elimination are inter-related processes as illustrated in the following figure.

Toxicokinetics is essentially the study of "how a substance gets into the body and what happens to it in the body". Four processes are involved in toxicokinetics.

Limit levels of the toxic matters – can be estimated only for those toxic matters for which the level doses exist

NOEL - No Observed Effect Level. The highest dose in a toxicity study at which there were no toxic or adverse effects observed.

Acceptable Daily Intake (ADI) - The amount of a chemical to which a person can be exposed each day over a long period of time (usually lifetime) without suffering harmful effects.

MIC - Maximum (allowable) imission concentration. A recommendation for the highest level for long-term exposure to a chemical in the air outdoor and indoor which will not produce adverse effect (eg. for gases, aerosols, dust). (TLV –threshold limit value, USA)

Limit levels of the toxic matters in working place

MAC-P Maximum permissible concentration at working place. It does not cause any harm or toxic impact to staffs, it should not be reached.

BATBiologically acceptable concentration of matter and its products created through metabolism, which does not cause any harm or toxic impact to staffs.

TRKTechnical target (ruling) concentration of gas, fume, aerosols, which is not allowed to rich at working place.