Download description of contaminants

EFFECTS ON THE
RESPIRATORY TRACT
Yves Alarie, Ph.D
Professor Emeritus
University of
Pittsburgh,USA
A. BRIEF LOOK AT ANATOMY
AND PHYSIOLOGY
B.
ACUTE EFFECTS
A convenient and practical way to classify airborne
chemicals is by taking the first level of the respiratory
tract (from nose to alveoli) at which they act as the
exposure concentration increases from zero.(1)
a) Sensory Irritants
i)
Definition
Chemical which when inhaled via the nose will stimulate
trigeminal nerve endings, evoke a burning sensation of the
nasal passage and inhibit respiration. Also will induce
coughing from laryngeal stimulation and lachrymation from
corneal stimulation.
ii)
Other Characteristics
At high concentration, particularly on moist facial
skin, they will induce a burning sensation. Some
have odor and taste (SO2). Many will induce
airways constriction, usually at higher
concentration.
iii) Other Terms Used to Describe
Their Action
Upper respiratory tract irritant, nasal or corneal
stimulant, common chemical sense stimulant,
chemogenic pain stimulant, suffocant, lachrymator,
tear gas, sternutator, "eye, nose and throat"
irritant.
iv)
Typical Examples
Chloracetophenone, o-chlorobenzylidene malononitride, βnitrostyrene, diphenylaminoarsine, sulfur dioxide, ammonia,
acrolein, formaldehyde.
v)
Mechanisms
All reactive (i.e., toward nucleophilic groups such as SH or
cleaving S-S bonds in proteins) chemicals will be potent sensory
irritants except oxidants such as ozone, nitrogen dioxide. Also
phosgene and sulfur mustard are not sensory irritants. These are
all pulmonary irritants, see below. Chemicals of low reactivity
(solvents) are in general weak sensory irritants. Several
mechanisms have been proposed by which both reactive and
nonreactive chemicals stimulate the sensory irritant receptor. 36
vi) Potency
Their potency can be obtained by measuring the
concentration needed to decrease the
respiratory rate by 50% (RD50) in exposed male
Swiss Webster mice using a body
plethysmograph technique.37 This bioassay
became a standard method in 1984.38
vii) Extrapolation to Humans
The RD50 values obtained for 41 industrial chemicals
are very well correlated with Threshold Limit Values
(TLVs) established for the protection of industrial
workers. The RD50 value multiplied by 0.03 will yield a
value close to the TLV.39 Therefore 0.03  RD50 yields
the likely highest level to be permitted in industry to
prevent sensory irritation, and by extension to prevent
any other toxic effect to occur. This has been recently
confirmed for 89 industrial chemicals.40
viii) Estimation of Potency
The RD50 can be estimated for nonreactive chemicals
(solvents) from their physical properties, particularly
vapor pressure, their gas/hexadecane partition
coefficient or gas/olive oil partition coefficient but
not gas/water partition coefficient41,42. Furthermore,
the potency of their mixtures can be estimated
easily43.
ix) Typical Results and Extrapolation to Humans
The following pages present different aspects of this
approach and extrapolation of the results to
humans.
b)
Bronchoconstrictors
(Airways Constrictors).
i) Definition
They act primarily on the conducting airways and should
probably be called "airways constrictors". They may act on
the larger or smaller airways causing their constriction and
as a result will increase resistance to airflow in and out of
the lung (increase in airway resistance). If acting on the
smaller airways some regions of the lungs may be closed
to ventilation resulting in air trapping in the lungs, and a
decrease in dynamic lung compliance will result.
ii)
Mechanisms
Their action may be via a direct effect on airways smooth
muscles, by axonal reflex, vago-vagal reflexes following
stimulation of vagal nerve endings, by liberation of
histamine or other mediators.
iii)
Other Effects
Increase mucus secretions, induce inflammatory reaction.
iv)
Typical Examples
Histamine and cholinergic agonists, sulfur dioxide,
following sensitization by allergens such as foreign
proteins or chemicals acting as haptens (toluene
diisocyanates, trimellitic anhydride, etc., see below).
v) Potency
Their potency can be evaluated by measuring airway
resistance and lung compliance or by measuring specific
airway conductance44,45. Or, from flow-volume loops
measurements46. However, the fastest and easiest
method to detect such effects is the use of a whole body
plethysmograph with CO2 challenge47. Many airborne
chemicals have been evaluated this way48. Some49
have recently suggested using minute volume (VT  f).
This is nonsense.
The animal of choice is the guinea pig for any of the
mentioned methods.
vi) Extrapolation to Humans
Unfortunately the results obtained in animals have
not been systematically collected so that qualitative
or quantitative extrapolation to humans can be
made. At best, what we can say is that if a chemical
is found to induce airways constriction in guinea pigs
it will do so in humans.
vii) Systems and Results
The following pages introduce you to various systems
used and typical results.