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Responses of living organisms when exposed to toxins

1. covalent bonding- modifications of normal biological effects mediated by the cell receptor

When most small-molecule drugs meet a protein target, they nestle close to their intended. But the
flirtatious relationship between drug and target is often fleeting, with the drug repeatedly drifting away
and coming back. Like a teenager with no interest in settling down, the drug forms no permanent bond
with its target.

Some small molecules, however, do forge lasting ties. Their irreversible covalent bonds with proteins
link compound and protein for good.

2. Genotoxic interaction

Chemical interaction with DNA possibly leading to heritage change

 Clastogenic (chromosal ) effects


 Mutagenic (base pair) effects
 Development and reproductive toxicity – adverse effects on conception and structure and
function of the conception
 In genetics, genotoxicity describes the property of chemical agents that damages the genetic
information within a cell causing mutations, which may lead to cancer. While genotoxicity is
often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic
substances are mutagenic. The alteration can have direct or indirect effects on the DNA: the
induction of mutations, mistimed event activation, and direct DNA damage leading to
mutations. The permanent, heritable changes can affect either somatic cells of the organism or
germ cells to be passed on to future generations. Cells prevent expression of the genotoxic
mutation by either DNA repair or apoptosis; however, the damage may not always be fixed
leading to mutagenesis.

3. Receptor interaction

Toxicant at low concentrations modify or inhibit some biological process by binding at a specific site or
molecule have a specific acting mode of toxic action. However, at high enough concentrations, toxicants
with specific acting modes of toxic actions can produce narcosis that may or may not be reversible.
Nevertheless, the specific action of the toxicant is always shown first because it requires lower
concentrations. Uncouplers of oxidative phosphorylation. Involves toxicants that uncouple the two
processes that occur in oxidative phosphorylation: electron transfer and adenosine triphosphate (ATP)
production.

Acetylcholinesterase (AChE) inhibitors. AChE is an enzyme associated with nerve synapses that it’s
designed to regulate nerve impulses by breaking down the neurotransmitter Acetylcholine (ACh). When
toxicants bind to AChE, they inhibit the breakdown of ACh. This results in continued nerve impulses
across the synapses, which eventually cause nerve system damage. Examples of AChE inhibitors are
organophosphates and carbamates, which are components found in pesticides (see Acetylcholinesterase
inhibitors).

Irritants. These are chemicals that cause an inflammatory effect on living tissue by chemical action at the
site of contact. The resulting effect of irritants is an increase in the volume of cells due to a change in
size (hypertrophy) or an increase in the number of cells (hyperplasia). Examples of irritants are
benzaldehyde, acrolein, zinc sulphate and chlorine.

Central nervous system (CNS) seizure agents. CNS seizure agents inhibit cellular signaling by acting as
receptor antagonists. They result in the inhibition of biological responses. Examples of CNS seizure
agents are organochlorine pesticides.

Respiratory blockers. These are toxicants that affect respiration by interfering with the electron
transport chain in the mitochondria. Examples of respiratory blockers are rotenone and cyanide.

4. Immune mediated hypersensitive reactions –antigenic chemicals resulting to allergic reaction.

Cell-mediated immunity is an immune response that does not involve antibodies, but rather involves the
activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines
in response to an antigen.

5. Immune suppression- increased susceptibility to infectious agents and tumorigenesis.

Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of
the immune system itself have immunosuppressive effects on other parts of the immune system, and
immunosuppression may occur as an adverse reaction to treatment of other conditions

6. Necrosis – cell or tissue death

Necrosis (from the Greek "death, the stage of dying, the act of killing" from dead") is a form of cell injury
which results in the premature death of cells in living tissue by autolysis.

Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma which
result in the unregulated digestion of cell components.

In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death.

While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental
and can be fatal.Cellular death due to necrosis does not follow the apoptotic signal transduction
pathway, but rather various receptors are activated, and result in the loss of cell membrane integrity
and an uncontrolled release of products of cell death into the extracellular space.

7. Enzyme inhibition – biochemical pathway interruption e.g interference with phosphate molecule
synthesis

An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an
enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme
inhibitors. They are also used in pesticides.

8. Lethal synthesis- toxicant incorporation into biochemical pathway

lethal synthesis. The metabolic conversion of a substance that has been taken up by a cell into another
substance that results in the cell's death. It is colloquially called suicide metabolism
9. Neoplasmic -

Neoplasia is a type of abnormal and excessive growth of tissue. The growth of a neoplasia is
uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if
the original trigger is removed. This abnormal growth usually (but not always) forms a mass. When it
forms a mass, it may be called a tumor.

10. Lipid peroxidation- free radical oxidation of fatty acids leading to death

Lipid peroxidation is the oxidative degradation of lipids. It is the process in which free radicals "steal"
electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free
radical chain reaction mechanism. It most often affects polyunsaturated fatty acids, because they
contain multiple double bonds in between which lie methylene bridges (-CH2-) that possess especially
reactive hydrogen atoms. As with any radical reaction, the reaction consists of three major steps:
initiation, propagation, and termination. The chemical products of this oxidation are known as lipid
peroxides or lipid oxidation products (LOPs).

11. Inflammation -Local and systematic response Local effects

Some substances have only a localized effect on one part of the body - where the hazardous agent
comes into contact with or enters the body. For example, the local effect can be on the skin, such as an
acid burn, or in the digestive tract when a hazardous agent is ingested. Some substances like ammonia,
chlorine, welding fumes and exhaust fumes can cause local irritation to the lungs when they are inhaled.

B. Systemic effects

Systemic effects are problems caused inside the body once a hazardous agent has entered. Systemic
effects can occur in the blood when the substance is absorbed into the bloodstream, and in the organs
that either store the toxic material (such as the bones and the brain), neutralize it (such as the liver), or
remove it from the body (such as the kidney and bladder).

A typical systemic effect in the blood is anaemia (a shortage of red blood cells) which can be caused by a
number of chemicals, including: lead, beryllium, cadmium, mercury compounds and benzene. Benzene
can damage the cells that form blood, leading to leukaemia.

The liver can be damaged by toxic substances because it tries to break down many of them once they
have entered the body. Some chemicals known to damage the liver are: benzene, DDT, dioxane, phenol
and trichloroethylene. Vinyl chloride monomer, used in the plastics industry, is known to cause a rare
form of liver cancer.The kidneys and bladder also can be affected by many toxic substances because
they are major routes of exit out of the body.

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