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Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induced p53 activation and involvement of reactive oxygen species (ROS) in p53 activation as well as the role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6 cells to vanadate led to transactivation of p53 activity in a time-and dose-dependent manner. It also caused mitochondrial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H 2 O 2 by N-acetyl-L-cysteine (a general antioxidant) or catalase (a specific H

Up to 60 million people working indoors experience symptoms such as eye, nose and throat irritation, headache, and fatigue. Investigations into these complaints have ascribed the effects to volatile organic compounds (VOCs) emitted from building materials, cleaning formulations, or other consumer products. New compounds can result when the VOCs react with hydroxyl or nitrate radicals or ozone present in indoor environments. Several oxygenated organic compounds, such as glyoxal, methylglyoxal, glycolaldehyde, and diacetyl, have been identified as possible reaction products of indoor environment chemistry. Although research has previously identified diacetyl and glyoxal as sensitizers, additional experiments were conducted in these studies to further classify their sensitization potential. Sensitization potential of these four compounds was assessed using quantitative structure-activity relationship (QSAR) programs. Derek for Windows and National Institute for Occupational Safety and Health logistic regression predicted all compounds to be sensitizers, while TOPKAT 6.2 predicted all compounds except for methylglyoxal. All compounds were tested in a combined irritancy and local lymph node assay (LLNA). All compounds except for glyoxal were found to be irritants and all tested positive in the LLNA with EC3 values ranging from 0.42 to 1.9%. Methylglyoxal significantly increased both the B220(+) and IgE(+)B220(+) cell populations in the draining lymph nodes and total serum IgE levels. The four compounds generated by indoor air chemistry were predicted by QSAR and animal modeling to be sensitizers, with the potential for methylglyoxal to induce IgE. The identification of these compounds as sensitizers may help to explain some of the health effects associated with indoor air complaints.

Perfluorinated alkyl acids (PFAAs) are used in a multitude of applications and are categorized as high-production volume chemicals produced in quantities exceeding 10,000 lbs/year. As a result, widespread exposure has been documented in adults, children, and infants. It is generally accepted that children are more sensitive to the effects of xenobiotic exposures during fetal and postnatal periods of development; therefore, considerable efforts are required to investigate the potential impact of a model PFAA, perfluorooctane sulfonate (PFOS) on children's immunological health. Using the pairing of female C57BL/6N mice with male C3H/HeJ, developmental immunotoxicity was evaluated in B6C3F1 pups following oral maternal exposure to PFOS on gestations days 1-17. Exposure levels included 0.1, 1, and 5 mg/kg/day PFOS. Natural killer (NK) cell activity, SRBC IgM plaque assay, CD4/8 lymphocytic subpopulations, nitrite production in peritoneal macrophages, and body/organ weights were evaluated at 4 and 8 weeks of age in F1 pups. No significant dose-responsive changes in maternal or pup body weights, flow cytometry, or macrophage function were observed, yet hepatomegaly was indicated in F1 male pups at 4 weeks of age. Functional deficits were not evident until 8 weeks of age when NK cell function and IgM production were significantly decreased. When compared with females, male pups were more sensitive to the effects of PFOS thereby establishing a no observed adverse effect level and low observed adverse effect level of 0.1 and 1.0 mg/kg/day (males only) following maternal PFOS exposure level, respectively. This study establishes that the developing immune system is sensitive to the effects of PFOS and results in functional deficits in innate and humoral immunity detectable at adulthood.

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