Review of the U.S. Navy’s Exposure Standard for Manufactured Vitreous Fibers by National Research Council

Author:National Research Council
Language: eng
Format: epub
Tags: Environment and Environmental Studies : Environmental Health and Safety
Publisher: NATIONAL ACADEMY PRESS
Published: 2000-08-06T16:00:00+00:00

INTRATRACHEAL INSTILLATION

Studies that use intratracheal instillation as a route of rodent exposure to fibers are generally regarded as easier and less expensive than inhalation studies. Bolus administration often leads to uneven distribution of fiber-shaped particles throughout the lung and localized overloading (ECETOC 1996). Nevertheless, these types of studies might have value for the initial screening of fibrous compounds. A European Commission (EC) directive for classification and labeling of synthetic mineral fibers (Commission Directive 97/96/EC of December 5, 1997) allows for the use of either the short-term inhalation biopersistence assay or the intratracheal-instillation biopersistence assay in exonerating fibers from classification as a carcinogen. The protocols for performing those tests have been defined by the European Chemical Bureau (EC 1999). The biopersistence protocols are accepted by the EC for interim use and are being validated in a multicenter ring test. The subcommittee believes that instillation tests are useful for ranking the biopersistence of MVF fibers, but their validation will require data on more fiber types than are presently available. Validation should include the deposition of instilled fibrous material into the alveolar regions of the lung, and correlation of biopersistence of the instilled material (as defined by the investigators) with the development of pathological pulmonary effects.

In spite of the limited data available from these studies, intratracheal instillation of materials remains a popular alternative to inhalation exposure for several practical reasons: small quantities of the test compound can be used, thus reducing waste and increasing safety when hazardous materials are being tested; the technique is inexpensive because it does not require expensive exposure chambers and elaborate vapor or aerosol generation apparatus; complex technical support is not necessary for producing and monitoring vapor or aerosol exposures; and high concentrations of particles or fibers can be administered to the respiratory tract at numerous doses with precise control and measurement.

There are also disadvantages to instillation that stem from the differential distribution in the lung of instilled particles compared with inhaled particles. Instilled particles move to the gravity-dependent portions of the lung because the injected material settles, whereas inhaled airborne particles tend to be well distributed throughout the respiratory system, particularly in the small airways. The high local concentration of instillates or their carrier liquids can cause local tissue damage, particularly at high particle or fiber doses. That can lead to local hemorrhage and even death by mechanisms not directly relevant to the study. The acute inflammatory response that develops in response to the high particle burden and liquid suspension of the carrier could actually contribute to the formation of lesions observed in instillation studies. In contrast, the inhalation technique avoids these local and regional overload effects because the lungs of the exposed animals do not receive the full bolus of particles in one dose. Inhalation models best simulate human exposure because only respirable particles reach the lung parenchyma. Instillation techniques, in contrast, can result in the delivery of nonrespirable (large) particles to the alveolar regions, where they normally would not deposit.

Instillation is an acceptable form of dosing

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