DEFINITION
* Toxicology is the study of the
harmful effects of chemicals on biologic systems.
* An interdisciplinary science with
input from biochemistry, physiology, pathology, pharmacology, chemistry and
public health.
* Environmental toxicology focuses on
exposure to toxic substances in the general environment- air, food and water
and also the occupational environment.
CLASSIFICATION
* Physical state
*
Airborne
toxics – dusts, fumes, mists, vapour
*
Liquids
*
solid
* Chemical groups
*
Metals
*
Solvents
eg toluene, xylene, benzene etc
*
Acids
*
Alkalis
>
Organophosphorous
compounds
* According to target organs
*
Liver Lungs
*
Kidney Skin
*
Blood Nervous system
ABSORBTION
* Respiratory – dusts, fumes, vapours
etc
water soluble toxins exert
immediate effects in the respiratory system.
*
Less
soluble substances dissolve more slowly producing acute pneumonitis and
pulmonary oedema.
*
Asphyxiants
– interrupt the supply of oxygen. Simple asphyxiants eg N2 displaces O2 in the
air. Chemical asphyxiants – CO combines with Hb to form carboxyhaemoglobin.
DISTRIBUTION
- Destination of toxins determined by
n
Ability
to cross membrane barrier
n
Concentration
in the blood
n
Affinity
for particular body compartments
- Some substances are transported by binding.
*
Haem
– CO
*
RBC
– Pb
*
Albumin
– Hg
*
Globulins
– Fe, Zn
STORAGE
* At site of action eg CO
* Affinity eg where naturally
occurring element with similar properties exist _ Pb and Ca.
* Fat soluble substance may be stored
in adipose tissue eg DDT, dieldrin.
Toxin can
be mobilized from the stores.
BIOLOGICAL
EFFECTS
* TYPES OF EFFECTS
*
Acute/
chronic toxicity
*
Allergy
*
Carcinogenicity
*
Reproductive
and developmental effects
Effects are
usually dose respondent
Dose response
curve
LD50 – a measure
of potency
METABOLISM
n Breakdown of toxins to simpler
molecules
n
Oxidation
n
Reduction
n
Conjugation
n
Hydrolysis
EXCRETION
* Routes
*
Kidney
*
Biliary
tract
*
Lungs
*
Breast
milk
*
Sweat
*
Hair
*
Saliva
EXAMPLES OF
TARGET ORGANIC RESPONSES
* Liver
*
Hepatocellular
damage eg ethyl alcohol, cyclophosphamide
* Carcinogenic effects
- Aflatoxin
- Vinyl chloride monomers
* Kidney
-
Tubular
damage – heavy metals Pb, Cd and Hg. paraquat
* Blood
-
Pb
inhibits production of haemoglobin
1. inhibits the formation of globin moiety
2. red
cell membrane fragility
-
Benzene
and radiation a- plastic anaemia
1.
leukaemia
* Lungs
*
Acute
responses. Irritants, allergies
*
Chronic
responses. Fibrogenic dusts
*
Carcinogenic
– asbestos, nickel
* CNS
*
Acute
response – solvents eg acetone, toluene,
headache, dizziness, confusion, narcosis
*
Chronic
*
Pb
– foot or wrist develop- motor neuron damage
*
Mn
– damage to cerebellum- parkinsonism
*
Organophosphates
– inhibits acetyl cholinesterase and
carbonates .
ACH accumulates at parasympathetic nerve
ending.
increased red cell cholinesterase.