Development of a Mouse Whole-Body Exposure System from a Directed-Flow, Rat Nose-Only System

Abstract

In many inhalation exposure experiments, such as pharmacokinetic studies in unrestrained pregnant animals, i t is desirable to expose unrestrained animals and to remove animals from the exposure system at intermediate time points. A two-tiered, 32-port, directed-flow, noseonly exposure system was modified with extended 0.635-mm stainless steel inlet tubes to create a whole-body, modified nose-only (WB-MNO) exposure system. lndividual pregnant CD-1 mice held within a rat nose-only tube were exposed to a well-mixed methanol (MeOH) atmosphere. The volume of an individual mouse (-30 ml) constituted approximately 1 5 % of the 600-ml tube volume. Maternal M e O H pharmacokinetics were obtained on gestational day 8 following 6-11 WB-MNO MeOH exposures at either 10,000 or 15,000 ppm. Results from these WB-MNO exposures were compared with a 6-h, 15,000 ppm M e O H exposure using a Hinners-type 1-m' whole-body inhalation chamber (WB-HI. The WB-MNO exposure atmosphere was produced using a wick generator heated to 29-35°C and a fluid-metering pump. The vapor was mixed with the total air supply (12-15 Llmin). Atmospheric M e O H concentrations (mean + SEM) achieved were 10,224 ? 35 and 15,210 2 39 ppm for the WB-MNO and 14,980 2 70 ppm for the WB-H exposures. End-of-exposure maternal plasma MeOH concentrations were 65 + 25 (10,000 ppm, WB-MNO), 223 2 23 (15,000 ppm, WB-MNO), and 194 f 13 m M (15,000 ppm, WB-H). These findings suggest that the WB-MNO system results in maternal M e O H pharmacokinetics that are similar to those observed using more conventional WB-H exposure systems. The WB-MNO should lend itself to numerous additional applications for pharmacokinetic and toxicity studies. ~In many inhalation experiments, it is desirable to expose unrestrained animals and to remove certain animals from the exposure system at intermediate time points. Whole-body exposure systems are ideal for the unrestrained exposure of animals, but most do not lend themselves t o the easy removal of animals during the exposure. O n e application in which an unre-

Comparative Evaluation of the Impact of Subacute Exposure of Smokeless Tobacco and Tobacco Smoke on Rat Testis

“…The prepubertal and adult rats were each divided into 7 groups containing 6 rats per group and exposed to cigarette smoke, smokeless tobacco, and nicotine. A pilot experiment was done to determine the tolerability of rats to different amounts of cigarette smoke equivalent to 0.25, 0.5, and 1 mg of nicotine using the whole body exposure method as described by Dorman et al [ 30 ] and Wong [ 31 ]. Using cigarette containing 1 mg nicotine per stick, the equivalent tobacco smoke doses were 1/4, 1/2, and 1 stick, respectively.…”

“…The doses of nicotine used are standard doses in most toxicological investigations [ 30 – 32 ]. Nicotine was serially diluted with normal saline to obtain suitable working concentrations and animals were injected subcutaneously.…”

Chloroform Inhalation Exposure Conditions Necessary to Initiate Liver Toxicity in Female B6C3F1 Mice

“…Exposures were conducted in glass, single-animal, whole-body exposure tubes similar to those described by Dorman et al (1996). The total airflow through each exposure system was maintained at approximately 32 l/min, providing a flow of approximately 2.0 l/min through each of the 16 exposure tubes per system.…”

Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene

“…The mice were exposed in nose-only inhalation towers that were Hoechst 33342 (HO) and thiazole orange (TO) were purchased from adapted for whole-body exposure [Dorman et al, 1996]. A separate Aldrich Chemical Co. Phosphate-buffered saline (PBS), pH 7.4, was tower was used for each of the five treatments.…”

“…Exposure concentra- 27711. tions in the atmosphere of styrene-butadiene rubber industries in the United States range from 0.1 to 12.3 ppm G.M. Farris' current address is Los Alamos National Laboratory, Los Alamos, NM 87545. styrene and 0.1 to 174 ppm BD [Meinhardt et al, 1978[Meinhardt et al, , 1982Fajen et al, 1993].…”