Irritancy and allergic responses induced by exposure to the indoor air chemical 4-oxopentanal

Abstract

Over the last two decades, there has been an increasing awareness regarding the potential impact of indoor air pollution on human health. People working in an indoor environment often experience symptoms such as eye, nose, and throat irritation. Investigations into these complaints have ascribed the effects, in part, to compounds emitted from building materials, cleaning/consumer products, and indoor chemistry. One suspect indoor air contaminant that has been identified is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the ozonolysis of squalene and several high-volume production compounds that are commonly found indoors. Following preliminary workplace sampling that identified the presence of 4-OPA, these studies examined the inflammatory and allergic responses to 4-OPA following both dermal and pulmonary exposure using a murine model. 4-OPA was tested in a combined local lymph node assay and identified to be an irritant and sensitizer. A Th1-mediated hypersensitivity response was supported by a positive response in the mouse ear swelling test. Pulmonary exposure to 4-OPA caused a significant elevation in nonspecific airway hyperreactivity, increased numbers of lung-associated lymphocytes and neutrophils, and increased interferon-γ production by lung-associated lymph nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may elicit irritant and allergic responses and may help to explain some of the adverse health effects associated with poor indoor air quality.

FIG. 1.

Ear swelling and allergic sensitization potential as a result of dermal exposure. Analysis of irritation (A) and sensitization potential (B) after exposure to 4-OPA. Bars represent means ± SE of 5 mice per group. Numbers above the bars represent SIs. Levels of statistical significance are denoted as **p ≤ 0.01 as compared with vehicle control.

FIG. 2.

MEST. Analysis of ear swelling at 24, 48, and 72 h post-4-OPA challenge (10%). Sensitization concentration is indicated on the graph. Measurements were taken on the right ear, whereas the left ear was included as a negative control. Bars represent means ± SE of 5 mice per group. Levels of statistical significance are denoted as *p ≤ 0.05 and ** p ≤ 0.01 as compared with background (BG) control.

FIG. 3.

Increased AHR after long-term 4-OPA exposure. Analysis of AHR after nonspecific challenge in BALB/c mice following dermal and pulmonary exposure to 4-OPA. Mice received 4 days of dermal exposure (concentration indicated on graph) followed by four pulmonary challenges of 4-OPA (1%). Data presented represent nonspecific challenge with MCh. Bars represent means ± SE of 7 mice per group. Levels of statistical significance are denoted as *p ≤ 0.05 and **p ≤ 0.01 as compared with vehicle control (no dermal or pulmonary exposure to 4-OPA).

FIG. 4.

BAL infiltrates after short-term exposure to 4-OPA. Analysis of percent neutrophils (A), eosinophils (B), and alveolar macrophages (C) after exposure to 4-OPA. Mice received 4 days of dermal exposure (concentration indicated on graph) followed by a pulmonary challenges of 4-OPA (1%). Aspiration controls (no dermal exposure) were also included on the graphs. Bars represent means ± SE of 7 mice per group. Levels of statistical significance are denoted as *p ≤ 0.05 and **p ≤ 0.01 as compared with vehicle control (no dermal or pulmonary exposure to 4-OPA).

FIG. 5.

Lung mRNA expression after 4-OPA exposure measured by quantitative real-time PCR. Quantitative real-time PCR analysis of CCL2 (A) CCL19 (B) or IFN-γ (C) mRNA expression. Mice received 4 days of dermal exposure (concentration indicated on graph) followed by a pulmonary challenge of 4-OPA (1%). Bars represent means ± SE of 7 mice per group. Levels of statistical significance are denoted as *p ≤ 0.05 and **p ≤ 0.01 as compared with vehicle control (no dermal or pulmonary exposure to 4-OPA).

FIG. 6.

4-OPA sensitization results in increased cytokine production in the DLN. Analysis of INF-γ (Α), IL-5 (B), and IL-4 (C) protein expression generated by stimulated LALN after long-term exposure to 4-OPA. Mice received 4 days of dermal exposure (concentration indicated on graph) followed by four pulmonary challenges of 4-OPA (1%). Aspiration controls (no dermal exposure) and dermal control (no aspiration exposure) were also included on the graphs. Bars represent mean fold change ± SE of 7 mice per group. Levels of statistical significance are denoted as *p < 0.05 as compared with vehicle control (no dermal or pulmonary exposure to 4-OPA).