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Aliso Viejo, California, United States

Kerger B.D.,Cardno ChemRisk LLC | James R.C.,ToxStrategies | Galbraith D.A.,Cardno ChemRisk LLC
Frontiers in Genetics | Year: 2014

The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asbestos exposure. When the diagnosis of mesothelioma is based on histologic features alone, primary mesotheliomas may resemble various primary or metastatic cancers that have directly invaded the serosal membranes. Some of these metastatic malignancies, particularly carcinomas and sarcomas of the pleura, pericardium and peritoneum, may undergo desmoplastic reaction in the pleura, thereby mimicking mesothelioma, rather than the primary tumor. Encasement of the lung by direct spread or metastasis, termed pseudomesotheliomatous spread, occurs with several other primary cancer types, including certain late-stage tumors from genetic cancer syndromes exhibiting chromosomal instability. Although immunohistochemical staining patterns differentiate most carcinomas, lymphomas, and mestastatic sarcomas from mesotheliomas, specific genetic markers in tumor or somatic tissues have been recently identified that may also distinguish these tumor types from asbestos-related mesothelioma. A registry for genetic screening of mesothelioma cases would help lead to improvements in diagnostic criteria, prognostic accuracy and treatment efficacy, as well as improved estimates of primary mesothelioma incidence and of background rates of cancers unrelated to asbestos that might be otherwise mistaken for mesothelioma. This information would also help better define the dose-response relationships for mesothelioma and asbestos exposure, as well as other risk factors for mesothelioma and other mesenchymal or advanced metastatic tumors that may be indistinguishable by histology and staining characteristics. © 2014 Kerger, James and Galbraith.

Monnot A.D.,Cardno ChemRisk LLC | Christian W.V.,Cardno ChemRisk LLC | Abramson M.M.,Cardno ChemRisk LLC | Follansbee M.H.,Syracuse Research Corporation
Food and Chemical Toxicology | Year: 2015

Lead (Pb) content in lipstick and other consumer products has become an increasing concern. In 2010, the United States Food and Drug Administration tested 400 lipstick samples and found a maximum Pb concentration of 7.19 ppm. To assess the safety of lipstick in adults that chronically apply lipstick as well as instances where children might incidentally ingest lipstick products, the United States Environmental Protection Agency's (US EPA) Adult Lead Model and Integrated Exposure Uptake Biokinetic Model for Lead in Children were used to determine the blood Pb concentrations of adults and children ingesting varying amounts of lipstick of different Pb concentrations. Modeled blood Pb concentrations were compared with oral ingestion guidelines and to the Centers for Disease Control and the US EPA's actionable blood Pb levels of 5 and 10 μg/dL. Background Pb exposure was the primary contributor to estimated blood Pb levels (BLLs) in children and adults, and Pb exposure from lipstick did not significantly increase estimated BLLs. These results suggest that the safety of consumer products and cosmetics should be assessed not only by the presence and amounts of hazardous contents, but also in conjunction with an assessment of estimated background exposures and comparison to health-based standards. © 2015 Elsevier Ltd.

Sahmel J.,Cardno ChemRisk LLC | Gaffney S.,Cardno ChemRisk LLC | Knutsen J.,University of Colorado | Epstien B.,Epstien Environmental Resources LLC | Paustenbach D.,Cardno ChemRisk LLC
International Journal of Vehicle Safety | Year: 2014

Carbon monoxide (CO) is a well-known asphyxiant. As part of an incident investigation involving two fatalities, a study was conducted to determine key factors that influence CO concentrations inside motor homes/recreational vehicles. Test parameters examined included the condition of the on-board generator exhaust pipe (attached/detached), generator load (<1-20 amps), position of ventilation hatches (open/closed), parking location (adjacent/perpendicular to a masonry wall), and weather conditions (breezy/calm). A tracer gas test was also performed of the motor home undercarriage because of concerns for possible damage (no visible damage was observed). Results showed that all five parameters affected the CO concentrations detected within the motor home, but the generator exhaust tailpipe was found to have the greatest impact. Further, a specific combination of conditions, along with documented invisible undercarriage leaks, was necessary for CO concentrations to become high enough to produce acutely toxic and fatal conditions inside the motor home. Copyright © 2014 Inderscience Enterprises Ltd.

Monnot A.D.,Cardno ChemRisk LLC | Christian W.V.,Cardno ChemRisk LLC | Paustenbach D.J.,Cardno ChemRisk LLC | Finley B.L.,Cardno ChemRisk LLC
Critical Reviews in Toxicology | Year: 2014

Chromium (Cr) (III) is a trace metal essential to human health and exposure typically occurs via the diet on a daily basis. Some groups of individuals, such as those consuming Cr(III) supplements or patients with Cr-containing implants, may have elevated blood Cr(III) concentrations. Although blood Cr(III) levels are thought to be an accurate metric of exposure, little is known about the relationship between these concentrations and possible adverse health risks. This study evaluated the various effects reported in animal and human epidemiological studies of Cr(III) exposure in an attempt to correlate them with blood Cr(III) concentrations. The target endpoints identified in this analysis included the hematological, hepatic, and renal systems. Animal and human physiological-based pharmacokinetic (PBPK) models were used to estimate steady state blood Cr(III) concentrations from a variety of dosing regimens. Based on the animal studies, our results suggest that blood Cr(III) concentrations as high as 480-580 μg/L are not associated with any responses. For each of the three health endpoints considered in this analysis (hematological, hepatic, and renal) no adverse effects were observed below 3,700 μg/L. Some hematological responses were observed at 3,700 μg/L, and adverse effects clearly occurred at 7,500 μg/L. These findings can be used to assess potential health risks to individuals with elevated blood Cr(III) concentrations. © 2014 Informa Healthcare USA, Inc.

Christian W.V.,Cardno ChemRisk LLC | Oliver L.D.,Cardno ChemRisk LLC | Paustenbach D.J.,Cardno ChemRisk LLC | Kreider M.L.,Cardno ChemRisk LLC | Finley B.L.,Cardno ChemRisk LLC
Journal of Applied Toxicology | Year: 2014

In this paper, quantitative methods were used to evaluate the weight of evidence regarding a causative relationship between cobalt-chromium (CoCr)-containing hip implants and increased cancer risk. We reviewed approximately 80 published papers and identified no-observed-adverse-effect level (NOAEL) and/or lowest-observed-adverse-effect level (LOAEL) values for specific endpoints of interest: genotoxic effects from in vitro studies with human cell lines as well as genotoxicity and tumor formation in animal bioassays. Test articles included Co particles and ions, Cr particles and ions, and CoCr alloy particles as well as CoCr alloy implants. The NOAEL/LOAEL values were compared with body burdens of Co/Cr particles and ions we calculated to exist in systemic tissues of hip implant patients under normal and excessive wear conditions. We found that approximately 40 tumor bioassays have been conducted with CoCr alloy implants or Co/Cr particles and ions at levels hundreds to thousands of times higher than those present in hip implant patients, and none reported a statistically significant increased incidence of systemic tumors. Results from in vitro and in vivo genotoxicity assays, which are relatively less informative owing to false positives and other factors, also indicated that DNA effects would be highly unlikely to occur as a result of wear debris from a CoCr implant. Hence, the toxicological weight of evidence suggests that CoCr-containing hip implants are unlikely to be associated with an increased risk of systemic cancers, which is consistent with published and ongoing cancer epidemiology studies involving patients with CoCr hip implants. © 2014 John Wiley & Sons, Ltd.

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