Subchronic inhalation exposure study of an airborne polychlorinated biphenyl mixture resembling the Chicago ambient air congener profile

Abstract

Although inhalation of atmospheric polychlorinated biphenyls (PCBs) is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago air mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 h/day via nose-only inhalation for 4 weeks, 520 ± 10 μg/m(3). Congener-specific quantification in tissue and air samples was performed by gas chromatography-tandem mass spectrometry (GC/MS/MS). In contrast to the lower-chlorinated congener-enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of end points to catalogue the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity, and histopathologic abnormalities. Glutathione oxidized/reduced ratio (GSSG/GSH) was increased in the blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose, estimated at 134 μg/rat.

Figure 1

Average congener distribution profiles in the CAM vapor during 4 wk exposure (A) and in Chicago air (B), adapted from Hu et al. 2010 (6) (with permission), with inset plot showing congeners from PCB 75 to PCB 209.

Figure 2

Average distribution profiles of all congeners in lung, blood, liver, brain and adipose tissue after subchronic inhalation exposure to the CAM vapor. Values are expressed as mean mass percent ± standard error (n=4 for adipose tissue, n=6 for the remaining tissues).

Figure 3

The concentrations of major congeners (congeners that accounted for over 5% of ∑PCB in any tissue) found in each tissue type after subchronic inhalation exposure to the CAM vapor. The right-hand plot shows the congeners that had concentrations below 30 ng/g lipid weight. Neurotoxic congeners are sorted by NEF values in the top half of the plot. Non-neurotoxic congeners are sorted by their degree of chlorination in the bottom.

Figure 4

The concentrations of TEQ for major dioxin-like congeners (A) and NEQ for the six largest contributors (B) in the CAM vapor and in each tissue after subchronic inhalation exposure. NEQ was distributed between up to 38 congeners in tissue although only the six largest contributors are listed. Values are expressed in the units of ng/g lipid weight for the tissue and in μg/m³ for the air. Y-axes are plotted on logarithmic scale.

Figure 5

Total glutathione (A), glutathione disulfide (GSSG) (B) and percentage of GSSG in total glutathione (C) in liver, lung and blood exposed to the CAM vapor. Values are expressed as mean ± standard error. Asterisks indicate a significant increase from control group, * = p < 0.05; ** = p < 0.01.