Intratracheal instillation is the introduction of a substance directly into the

trachea The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air- breathing animals with lungs. The trachea extends from the ...

. It is widely used to test the respiratory toxicity of a substance as an alternative to inhalation in

animal testing Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...

. Intratracheal instillation was reported as early as 1923 in studies of the

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...

icity of

coal tar Coal tar is a thick dark liquid which is a by-product of the production of coke and coal gas from coal. It is a type of creosote. It has both medical and industrial uses. Medicinally it is a topical medication applied to skin to treat psorias ...

. 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 effects of the delivery vehicle and anesthesia, and the fact that it bypasses the

upper respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to t ...

. 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 that occurs over an extended period. Some of these difficulties are overcome by another method,

pharyngeal aspiration Pharyngeal aspiration is the introduction of a substance into the pharynx and its subsequent aspiration into the lungs. It is used to test the respiratory toxicity of a substance in animal testing. It began to be used in the late 1990s. Pharyn ...

, 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,

rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...

, or

hamsters Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The ...

, 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 In medicine, a catheter (/ˈkæθətər/) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgi ...

down the mouth and throat, or through surgically exposing the trachea and penetrating it with a needle. Generally, short-acting inhaled

anesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

drugs such as

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

, metaphane, or

enflurane Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but ...

are used during the instillation procedure.

Saline solution Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein i ...

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 * Nanomaterials describe, in principle, materials of which a single unit is sized (in at least one dimension) between 1 and 100 nm (the usual definition of nanoscale). Nanomaterials research takes a materials science-based approach to na ...

References

{{Reflist, 30em Occupational safety and health Toxicology Trachea

Background

Methodology

See also

References