INHALATION TOXICOLOGY

Effects of chemicals that enter the

body by inhalation
 DEFINITION

Assesses effects of chemicals that are inhaled

accidentally e.g. industrial chemicals
pesticides or chemicals ihaled deliberately e.g.
pharmaceutical products
 IMPORTANCE OF INHALATION ROUTE
Accidental exposure greater than other routes
Presents large volume of solvent e.g. 36m3 of air
inhaled daily.
N/B if there is 5mg/m3 of dust in air, then 180mg of
dust inhaled per day.
Large surface area of delicate membrane (respiratory
tract)
Main exposure route in industries and disasters
Association of dusty occupations to inhalation --- coal
mining and lung disease, asbestos and mesothelioma,
cigarette smoking and lung disease.
 IMPORTANCE OF INHALATION ROUTE

Association of dusty occupations to inhalation

route.
(a) Coal mining and lung disease
(b) Asbestos and mesothelioma
(c) Cigarette smoking and lung disease
(d) Toxic gases in warfare
 DETERMINANTS OF DOSE IN
INHALATION
Concentration in air
Particle size
Duration of exposure
Solubility
Rate of clearance from lungs
Breathing patterns
Electrostatic charge
 DETERMINANTS OF DOSE IN
INHALATION

Concentration in air
- higher concentration leads to higher dose.
N/B if substance is irritant.
Particle size of chemical
- particle size determines pattern of
distribution along respiratory tract.
 DETERMINATS OF DOSE IN
INHALATION

Particle size Area of deposition

> 10m nose
0.5 - 1m down the respiratory tract
< 0.5m upper respiratory tract and
tracheobronchial little in
deep lung (due to diffusion
effect).
 DETERMINANTS OF DOSE IN
INHALATION
This determinates the location of different
lessions due to different chemicals.
e.g. lung cancer due cigarette smoke due to
particle size of 0.2 to o.5m.
N/B during inhalation cigarette smoke is faintly
blue but a whitish cloud when exhaled. This is
due to water absorption during inhalation and
particles size reaches 2 to 5m by time of
exhalation.
 DETERMINATION OF DOSE IN
INFLAMATION

Duration of exposure:
- important in determining total dose inhaled.
Breathing pattern
- important in that it influences both the total
amount of substance deposited in the lungs
and the area in which it is deposited.
 DETERMINANTS OF DOSE IN
INHALATION

Electrostatic charge.
- Aerosols become charged during production.
Total deposition of chrged aerosols in the
respiratory tract is 20% higher than neutral
aerosols
 TOXICOLOGY OF GASES, VAPOURS
AND AEROSOLS
Habers Law: The product of concentration
and time is constant in terms
of the toxicity produced. i.e.
you should get the same
toxicity from a long exposure
to a low concentration as you
would from a short exposure
to a high concentration.
Physicochemical properties of gases of importance to
site and retention of toxin
 TOXICOLOGY OF GASES, VAPOURS
AND AEROSOLS
Vapour pressure - the higher the SVP at a
given temperature the greater the volatility of
the gas, the more likely to cause lesions
deeper in the respiratory tract.
Water solubility - highly water soluble gases
e.g. ammonia, formaldehyde are absorbed
rapidly in the URT. Poorly soluble gases e.g.
phosgene pass down deep into lungs and
cause damage there.
REACTION OF THE RESPIRATORYTRACT
TO GASES
Irritation of the airways leading to
bronchoconstriction and oedema
Necrosis of the cells lining the airways,
resulting in increased permeability and
oedema
Production of fibrosis
Bronchoconstriction as a result of an allergic
response
oncogenesis