Intratracheal instillation is the introduction of a substance directly into the
trachea. It is widely used to test the
respiratory toxicity of a substance as an alternative to
inhalation
Inhalation (or Inspiration) happens when air or other gases enter the lungs.
Inhalation of air
Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...
in
animal testing.
Intratracheal instillation was reported as early as 1923 in studies of the
carcinogenicity of
coal tar. Modern methodology was developed by several research groups in the 1970s.
By contrast, tracheal administration of pharmaceutical drugs in humans is called
endotracheal administration.
Background
As compared to inhalation, intratracheal instillation allows greater control over the dose and location of the substance, is cheaper and less technically demanding, allows lower amounts of scarce or expensive substances to be used, allows substances to be tested that can be inhaled by humans but not small mammals, and minimizes exposure to laboratory workers and to the skin of laboratory animals. Disadvantages include its nonphysiological and invasive nature, the
confounding
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
effects of the delivery vehicle and anesthesia, and the fact that it bypasses the
upper respiratory tract. Instillation results in a less uniform distribution of the substance than inhalation, and the substance is cleared from the respiratory tract more slowly.
Their results provide a quick screen of potential toxicity and can be used to test its mechanism, but may not be directly applicable to
occupational exposure
An occupational exposure limit is an upper limit on the acceptable concentration of a hazardous substance in workplace air for a particular material or class of materials. It is typically set by competent national authorities and enforced by legi ...
that occurs over an extended period.
Some of these difficulties are overcome by another method,
pharyngeal aspiration, which is less technically difficult and causes less trauma to the animal,
and has a pulmonary deposition pattern more similar to inhalation.
Methodology
Intratracheal instillation is often performed with
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
,
rats, or
hamsters, with hamsters often preferred because their mouth can be opened widely to aid viewing the procedure, and because they are more resistant to lung diseases than rats.
Instillation is performed either through inserting a needle or
catheter down the mouth and throat, or through surgically exposing the trachea and penetrating it with a needle. Generally, short-acting inhaled
anesthetic drugs such as
halothane,
metaphane, or
enflurane are used during the instillation procedure.
Saline solution is usually used as a delivery vehicle in a typical volume of 1–2 mL/kg body weight.
A wide range of substances can be tested, including both soluble materials and insoluble particles or fibers, including
nanomaterials.
See also
*
Tracheal intubation
References
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Occupational safety and health
Toxicology
Trachea