Aliso Viejo, California, United States
Aliso Viejo, California, United States

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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.

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.

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.

Tvermoes B.E.,Cardno ChemRisk LLC | Unice K.M.,Cardno ChemRisk LLC | Paustenbach D.J.,Cardno ChemRisk LLC | Finley B.L.,Cardno ChemRisk LLC | And 2 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Over-the-counter cobalt supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution with long-term use. Objective: We assessed blood kinetics, biochemical responses, and clinical effects in 5 adult men and 5 adult women who voluntarily ingested ∼1.0 mg Co/d (0.080-0.19 mg Co · kg-1 · d-1) of a commercially available cobalt supplement over a 3-mo period. Design: Volunteers were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical variables before, during, and after dosing. Hearing, vision, cardiac, and neurologic functions were also assessed in volunteers before, during, and after dosing. Results : After ∼90 d of dosing, mean cobalt blood concentrations were lower in men than in women. Mean cobalt whole blood and serum concentrations in men were 20 μg/L (range: 12-33 μg/L) and 25 μg/L (range: 15-46 μg/L), respectively. In women, mean cobalt whole blood and serum concentrations were 53 μg/L (range: 6-117 μg/L) and 71 μg/L (range: 9-149 μg/L), respectively. Estimated red blood cell (RBC) cobalt concentrations suggested that cobalt was sequestered in RBCs during their 120-d life span, which resulted in a slower whole blood clearance compared with serum. The renal clearance of cobalt increased with the serum concentration and was, on average, lower in women (3.5 ± 1.3 mL/min) than in men (5.5 ± 1.9 mL/min). Sex-specific differences were observed in cobalt absorption and excretion. There were no clinically significant changes in biochemical, hematologic, and clinical variables assessed in this study. Conclusion: Peak cobalt whole blood concentrations ranging between 9.4 and 117 μg/L were not associated with clinically significant changes in basic hematologic and clinical variables. This study was registered at as NCT01990794. © 2014 American Society for Nutrition.

Perez A.L.,Cardno ChemRisk LLC | De Sylor M.A.,Cardno ChemRisk LLC | Slocombe A.J.,Cardno ChemRisk LLC | Lew M.G.,Cardno ChemRisk LLC | And 2 more authors.
Environmental Toxicology and Chemistry | Year: 2013

Recently, concern has grown regarding the presence of triclosan (TCS) in waters because of its potential for causing ecological and human health effects. The authors present a statistical analysis of TCS concentrations reported between 1999 and 2012 in freshwater environments in the United States and provide a comparison with available health-based and aquatic guidance values. Data from 46 peer-reviewed and unpublished investigations from 45 states and 1 US territory were included in the meta-analysis, encompassing the following coded water types: untreated (raw wastewater), effluent (wastewater treatment plant effluent), effluent-impacted environmental, environmental, and finished drinking water (total n=2305). Triclosan was most frequently detected in untreated waters (92% detection frequency; mean±standard error, 11270±2925ng/L; n=237), but concentrations were significantly reduced in effluent waters (83% detection frequency 775±311ng/L; n=192, α=0.05). Triclosan concentration in effluent-impacted environmental waters (62% detection frequency; 130±17ng/L; n=228) was not significantly reduced from effluent waters but was significantly greater than TCS in environmental waters not classified as effluent impacted (11% detection frequency; 13±3ng/L; n=1195). In finished drinking water, TCS was largely undetected (1% detection frequency; 4±2ng/L n=453), suggesting that for the United States, drinking water is not an appreciable source of TCS exposure. In posttreatment waters, average TCS concentrations were below part-per-billion levels. Although no US regulatory standard exists for TCS in aquatic systems, comparison of averages reported in the present study with a predicted-no-effect concentration (PNEC) of 500ng/L showed that 5.3% of effluent-impacted environmental waters were above the PNEC for changes in algal biomass, while only 0.25% of environmental waters surpassed this value. © 2013 SETAC.

PubMed | Cardno ChemRisk LLC
Type: Journal Article | Journal: Environmental monitoring and assessment | Year: 2016

A 3-month air monitoring study was conducted in Washington County, Pennsylvania, at the request of local community members regarding the potential risks resulting from air emissions of pollutants related to hydraulic fracturing operations. Continuous air monitoring for total volatile organic compounds was performed at two sampling sites, including a school and a residence, located within 900m of a hydraulic fracturing well pad that had been drilled prior to the study. Intermittent 24-hour air samples for 62 individual volatile organic compounds were also collected. The ambient air at both sites was monitored during four distinct periods of unconventional natural gas extraction activity: an inactive period prior to fracturing operations, during fracturing operations, during flaring operations, and during another inactive period after operations. The results of the continuous monitoring during fracturing and flaring sampling periods for total volatile organic compounds were similar to the results obtained during inactive periods. Total volatile organic compound 24-hour average concentrations ranged between 0.16 and 80ppb during all sampling periods. Several individual volatile compounds were detected in the 24-hour samples, but they were consistent with background atmospheric levels measured previously at nearby sampling sites and in other areas in Washington County. Furthermore, a basic yet conservative screening level evaluation demonstrated that the detected volatile organic compounds were well below health-protective levels. The primary finding of this study was that the operation of a hydraulic fracturing well pad in Washington County did not substantially affect local air concentrations of total and individual volatile organic compounds.

PubMed | University of Michigan, Cardno ChemRisk LLC and Brooks Applied Labs
Type: | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2016

Costume cosmetics (lipstick, body paints, eyeshadow) were analyzed for metals using inductively coupled plasma mass spectrometry (ICP-MS). Sb was detected in all samples (range: 0.12-6.3mg/kg; d.f. 100%), followed by Pb (<0.15-9.3mg/kg), Ni (<0.20-6.3mg/kg), Co (<0.5-2.0mg/kg); with d.f. 80% each, Hg (<0.00015-0.0020mg/kg; d.f. 50%) and As (0.53mg/kg, d.f. 10%). Ingestion and dermal exposures were estimated for child- and adult-intermittent and adult-occupational users. Adult-occupational users exceeded the U.S. EPA Reference Dose (RfD) for Sb and the CA Proposition 65 maximum allowable dose level (MADL) for Pb was exceeded for all user scenarios. The Pb dose from body paint was sufficient to raise blood lead levels (BLL) in all user scenarios above baseline BLLs from 0.2g/dL to 1.9g/dL per the Adult Lead Model (ALM) and child Integrated Exposure Uptake Biokinetic (IEUBK) blood Pb models. Change in BLL was less than 1g/dL amongst the child and adult-intermittent users, the benchmark change in BLL developed for health risk assessments for children. Adult-occupational users exceeded the CA Proposition 65 NSRL intake value of 15g/day, which corresponds to an increase of 1.2g/dL above baseline levels using ALM. Exposure of occupational users of costume cosmetics should be evaluated further to prevent unnecessary metal exposure.

PubMed | Cardno ChemRisk LLC and TKingsbury LLC
Type: Journal Article | Journal: Integrated environmental assessment and management | Year: 2016

Manufacturers lack a reliable means for determining whether a chemical will be targeted for deselection from their supply chain. In this analysis, 3 methods for determining whether a specific chemical (triclosan) would meet the criteria necessary for being targeted for deselection are presented. The methods included a list-based approach, use of a commercially available chemical assessment software tool run in 2 modes, and a public interest evaluation. Our results indicated that triclosan was included on only 6 of the lists reviewed, none of which were particularly influential in chemical selection decisions. The results from the chemical assessment tool evaluations indicated that human and ecological toxicity for triclosan is low and received scores indicating that the chemical would be considered of low concern. However, triclosans peak public interest tracked several years in advance of increased regulatory scrutiny of this chemical suggesting that public pressure may have been influential in deselection decisions. Key data gaps and toxicity endpoints not yet regulated such as endocrine disruption potential or phototoxicity, but that are important to estimate the trajectory for deselection of a chemical, are discussed. Integr Environ Assess Manag 2017;13:198-207. 2016 SETAC.

Alcohol concentrations in biological matrices offer information regarding an individuals intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties.

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