Superfund Research Program

Inhalation Toxicology Core

Project Leader: Peter S. Thorne
Grant Number: P42ES013661
Funding Period: 2006 - 2015

Project-Specific Links

Final Progress Reports

Year:   2014  2009 

Four specific aims were established for the Inhalation Toxicology Core:

Aim 1) Generate controlled PCB atmospheres in exposure chambers and collect airborne PCBs resulting from vaporization of common industrial PCB mixtures to facilitate the creation of a model exposure mixture.

Aim 2) Perform acute, subacute and subchronic inhalation exposures to laboratory animals to defined mixtures of low molecular weight PCBs.

Aim 3) Provide a rodent vivarium for experimental animals used for the ISRP and execute a quality assurance program to monitor their health and welfare.

Aim 4) Perform necropsies on exposed, control and sentinel rodents and distribute tissues to project investigators in the ISRP.

The Inhalation Toxicology Core supports the Analytical Core and Synthesis Core by providing state-of-the-art animal facilities and meticulously controlled inhalation exposures to a realistic mixture of airborne PCB congeners. The Inhalation Toxicology Core links laboratory based studies to field studies by creating PCB exposure atmospheres that represent those measured in the field. This year, the core conducted 2 inhalation exposure experiments: 1) time course elimination study of Aroclor 1242 and 2) sub-chronic exposure inhalation exposures to Chicago Air Mixture (CAM). In both studies the core used Sprague-Dawley rats and an inhalation exposure system capable of generating controlled atmospheres of vapor-phase PCB mixture. This system was developed in the Inhalation Toxicology Core.

In the first elimination study, animals were exposed to Aroclor 1242 for 2 hours and necropsied at 5 different time points (immediately, 1, 3, 6, and 12 hours) post exposure. Livers, lungs, blood, brains, and adipose tissue were collected. The research team found that inhaled atmospheres of PCBs were rapidly distributed to other organs, and the elimination was in the nature of first-order kinetics. They accumulated in adipose tissue but decayed within hours in the lung, liver and blood, with half lives increasing in the order of liver (5.6 hr) < lung (8.2 hr) < brain (8.5 hr) < blood (9.7 hr). PCB concentrations were in the same range in lungs, liver and adipose tissue, lower in brain and the lowest in blood. The congeners detected in tissues included mostly PCBs with mono- or di-para-substitution (PCB 8, 20*28, 21*33, 31, 49*69 etc). Congeners with pairs of adjacent hydrogen atoms, especially in the meta and para position, tended to be eliminated more readily. The excretion/accumulation rates indicated that the elimination depended on the chlorine substitution pattern as well as the target tissue. This study demonstrated that inhalation is a route of exposure to mono- to pentachlorobiphenyls and, in addition to other routes of exposure, can contribute to the body burden of lower chlorinated congeners.

In the second, sub-chronic study, rats were exposed to CAM (65:35, Aroclor 1242 vs. Aroclor 1254, respectively) for 1.5 hours/day for 4 weeks. Sham animals were exposed to laboratory filtered air. Evaluation of lung inflammatory responses in bronchoalveolar lavage fluid (cellularity, activity of LDH, total protein), CYP activity in lungs and livers, GSH/GSSG in lungs and histopathology of respiratory system did not reveal significant differences between CAM-exposed animals and shams. Similarly, no difference between groups was found in 10 cytokines measured except IL-2, which was slightly elevated in CAM-exposed animals. Researchers observed significant differences between groups in GSH/GSSG levels in blood. Determination of PCB congeners in lung, liver, blood, brain, uterus, kidney, thymus, and adipose tissue is in progress. The Inhalation Toxicology Core has continued to maintain the ISRP rodent vivarium and has supplied experimental animals for use in three of the projects. The core has provided instruction on rodent handling, care and use to investigators, post-doctoral fellows and graduate students and has assisted with dosing, necropsy and tissue processing.