Issues of dosimetry in inhalation toxicity.

Abstract:

:A major issue of inhalation toxicity is that of dose. An inhaled dose is more difficult to determine than the dose from other routes of administration. Via oral or parenteral routes, a discrete amount of test substance is given in a bolus. In inhalation toxicology, the delivered dose depends on the exposure concentration and duration, particle size, and associated changes in breathing patterns. Over the past few decades, the concept of dose as applied to toxicological studies has changed considerably. Initially, 'dose' simply meant the concentration in the atmosphere in inhalation studies (or the amount ingested or instilled into the gastrointestinal tract in oral dosing studies) times the duration of study. The extrapolation from one route to another is subject to tremendous errors, and caution is advised when doing so. Default values are, therefore, not recommended and conversion factors must be calculated for each individual situation, making appropriate assumptions about body weight, minute volume, percentage deposition, retention and absorption, also taking into account pulmonary and extrapulmonary pathomechanisms as well as the exposure regimen used in the bioassay and that of actual interest. Also with systemically acting agents caution is advised to perform simple route-to-route extrapolations in the absence of a detailed pharmacokinetic understanding and knowledge of the critical toxophoric moieties.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Pauluhn J

doi

10.1016/s0378-4274(03)00077-8

keywords:

subject

Has Abstract

pub_date

2003-04-11 00:00:00

pages

229-38

eissn

0378-4274

issn

1879-3169

pii

S0378427403000778

journal_volume

140-141

pub_type

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