Journal of Toxicology & Environmental Health Part A: Current Issues

Bassett, David; Hirata, Fusao; Gao, Xiufeng; Kannan, Rangaramanujam; Kerr, Janet; Doyon-Reale, Nicole; Wilson, Susan; Lieh-Lai, Mary

doi: 10.1080/15287391003614018pmid: 20391114

A high percentage of asthma is associated with aeroallergen exposures. Glucocorticoids such as methylprednisolone represent a major method for managing chronic asthma. However, studies suggested that corticosteroid therapy might have the potential to stimulate rather than inhibit adaptive immune inflammatory reactions, raising concerns about possible adverse reactions due to excessive repeated methylprednisolone treatment. Therefore, a murine model of allergen-induced inflammation was characterized and used to investigate the effects of repeated intraperitoneal (ip) and transnasal treatments with methylprednisolone (0–20 mg/kg body weight) and cyclosporin A (20 mg/kg body weight). Sensitized BALB/c female mice were exposed daily to ovalbumin (OVA) aerosols for up to 5 d with 24-h postexposure analyses for airway responses to methacholine aerosols and inflammatory cell recoveries by bronchoalveolar lavage (BAL) and tissue collagenase dispersion. Although increased tissue neutrophils, lymphocytes, monocytes, and macrophages reached maximal levels after 2 daily OVA exposures, recoverable eosinophil numbers continued to rise over the 5-d period. Daily ip treatments with a 5-mg/kg body weight dose of methylprednisolone diminished both OVA-induced airway responses to methacholine and inflammatory-cell accumulations to levels comparable to those observed with cyclosporin A. However, treatments with higher doses of methylprednisolone reversed this anti-inflammatory effect, indicated by a return to untreated levels of OVA-induced eosinophil recovery. A similar biphasic response in eosinophil recoveries was observed using daily transnasal methylprednisolone treatments that correlated with a concomitant fall and rise in BAL interleukin-13. These results supported the hypothesis that repeated high-steroid treatments might activate rather than suppress allergen-induced immune responses.

Riviere, Jim E.; Brooks, James D.; Yeatts, James L.; Koivisto, Elisha L.

doi: 10.1080/15287391003614026pmid: 20391115

Occupational and environmental exposures to chemicals are major potential routes of exposure for direct skin toxicity and for systemic absorption. The majority of these exposures are to complex mixtures, yet most experimental studies to assess topical chemical absorption are conducted neat or in simple aqueous vehicles. A component of many industrial mixtures is surfactants that solubilize ingredients and stabilize mixtures of oily components when present in aqueous vehicles. The purpose of this series of experiments was to use two well-developed experimental techniques to assess how solution interactions present in a pure nonbiological in vitro system (membrane coated fibers, MCF) compare to those seen in a viable ex vivo biological preparation (isolated perfused porcine skin flap, IPPSF). Two widely encountered anionic surfactants, sodium lauryl sulfate (SLS) and linear alkylbenzene sulfonate (LAS), were studied in 10% solutions. The rank orders of absorption were: water: pentachlorophenol (PCP) > 4-nitrophenol (PNP) > parathion > fenthion > simazine > propazine; SLS: PNP > PCP > parathion > simazine > fenthion > propazine; and LAS: PNP > PCP > simazine > parathion > fenthion > propazine. For all penetrants, absorption was greater in SLS compared to LAS mixtures, a finding consistent with smaller micelle sizes seen with SLS. For these low-water-solubility compounds, absorption was greater from aqueous solutions in nearly every case. The inert three-fiber MCF array predicted absorptive fluxes seen in the ex vivo IPPSF, suggesting lack of any biological effects of the surfactants on skin.

Larsen, Søren T.; Matsubara, Shigeki; McConville, Glen; Poulsen, Steen S.; Gelfand, Erwin W.

doi: 10.1080/15287391003614034pmid: 20391116

Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed to develop a mouse model to gain insight into the development of airway hyperresponsiveness (AHR) to methacholine (MCh) in mice after exposure to both allergen and ozone. Mice were exposed for 20 min per day for 10 consecutive days to an aerosol of 1% ovalbumin (OVA) or saline followed by a single 3-h exposure to clean air or 100, 250, or 500 ppb ozone. Ozone induced AHR in mice previously exposed to OVA when compared to non-exposed (saline) control mice. After a 10-d exposure to OVA, a single exposure to a low (100 ppb) ozone concentration was sufficient to induce AHR. The AHR response was associated with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice.

Shi, Yongli; Yadav, Santosh; Wang, Feng; Wang, He

doi: 10.1080/15287391003614042pmid: 20391117

Amorphous silica engineered nanoparticles (ENP) are used for drug delivery and food additive under current regulations. Although the adverse effects of amorphous silica ENP may be negligible, contamination by bacterium products may enhance the toxic potential of these so-called safe products. Lipopolysaccharide (LPS), an endotoxin component generated by gram-negative bacteria, is a potential contaminant of amorphous silica ENP due to its ubiquitous presence in the environment. The combined effects of amorphous silica ENP and LPS are therefore of particular concern. In this study, A549 cells were exposed to amorphous silica ENP in combination with LPS for comparison with the cells treated with ENP. Measurements of MTT assay and lactate dehydrogenase (LDH) activity indicated that the toxicity of amorphous silica ENP was low but co-treatment of the cells with LPS significantly enhanced this toxicity. Decreased cell viability and increased LDH activity release occurred earlier and at lower concentration levels in co-treated cells. Co-treatment of LPS with amorphous silica ENP might also enhance the increase in oxidative stress produced by amorphous silica ENP. However, there were no detectable changes in nitric oxide generation and 8-hydroxy-2-deoxy guanosine formation in the cells treated with either ENP or ENP plus LPS, indicating low effect on oxidative DNA damage. These results showed that LPS may enhance the oxidative stress induced by amorphous silica ENP to initiate cytotoxicity of these engineered nanoparticles.

Hsieh, Ya-Lun; Yang, Ya-Hui; Wu, Trong-Neng; Yang, Chun-Yuh

doi: 10.1080/15287391003684789pmid: 20391118

This study was undertaken to determine whether there was a correlation between air pollutant levels and hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period 1996–2006. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (>23°C) statistically significant positive associations were found for all pollutants except sulfur dioxide (SO2). On cool days (<23°C), all pollutants were significantly associated with increased MI admissions except SO2. For the two-pollutant model, ozone (O3) and nitrogen dioxide (NO2) were significant in combination with each of the other four pollutants both on warm and cool days for higher admissions for MI. This study provides evidence that higher levels of ambient air pollutants increase the risk of hospital admissions for MI.

Carlson, Gary P.

doi: 10.1080/15287391003689143pmid: 20391119

Styrene is a widely used chemical, but it is known to produce lung and liver damage in mice. This may be related to oxidative stress associated with the decrease in the levels of reduced glutathione (GSH) in the target tissues. The purpose of this study was to investigate the effect of styrene and its primary metabolites R-styrene oxide (R-SO) and S-styrene oxide (S-SO) on GSH levels in the lung lumen, as determined by amounts of GSH in bronchioalveolar lavage fluid (BALF) and in plasma. When non-Swiss albino (NSA) mice were administered styrene (600 mg/kg, ip), there was a significant fall in GSH levels in both BALF and plasma within 3 h. These returned to control levels by 12 h. The active metabolite R-SO (300 mg/kg, ip) also produced significant decreases in GSH in both BALF and plasma, but S-SO was without marked effect. Since GSH is a principal antioxidant in the lung epithelial lining fluid, this fall due to styrene may exert a significant influence on the ability of the lung to buffer oxidative damage.