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Summit Toxicology LLP

Pepper Pike, OH, United States
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Aylward L.L.,Summit Toxicology LLP | Hays S.M.,Summit Toxicology LLP
Toxicology Letters | Year: 2014

Since 2007, the Canadian Health Measures Survey (CHMS) has been collecting biomonitoring data from the general Canadian population and has provided, to date, nationally representative concentrations for hundreds of environmental biomarkers in blood or urine. Biomonitoring Equivalents (BEs) have been developed as tools to help interpret biomonitoring data in a health risk context at a population level. In this paper, BEs are used to relate biomonitoring data from the CHMS (2007-2011) to existing exposure guidance values developed by Health Canada and other government agencies. Chemical-specific hazard quotients (HQs) and/or cancer risk estimates are calculated using existing BEs corresponding to environmental chemicals analyzed in the CHMS.For the majority of environmental chemicals, calculated HQ values are less than 1 indicating exposure is below published exposure guidance values. Individual biomonitoring data for two biomarkers of metal exposure (inorganic arsenic and cadmium) resulted in HQ values exceeding 1 suggesting that exposure may be above existing guidance values for a portion of the population, at least intermittently. This type of analysis may be used by researchers, risk assessors, and risk managers in prioritization efforts. © 2014.

Kirman C.R.,Summit Toxicology LLP | Grant R.L.,Texas Commission on Environmental Quality
Regulatory Toxicology and Pharmacology | Year: 2012

A case study was prepared for noncancer risk assessment of 1,3-butadiene (BD) based upon the ovarian atrophy effects in rodents with specific consideration of the guidelines described by NAS (2009). Ovarian toxicity has been identified in the past as a sensitive endpoint for BD, and serves as the basis for noncancer risk assessment by regulatory agencies. A meta-analysis was conducted in which the available dose-response data from rats and mice were normalized using an internal dose estimate (DEB in blood) that is causally related to ovarian toxicity. A time-to-response (multistage-Weibull) model was used to simultaneously fit the pooled rodent data sets with exposure durations ranging from 13 to 105. weeks. Human variation in ovarian follicle count was assumed to reflect variation in sensitivity to the adverse effects associated with follicle depletion (i.e., premature menopause). Information on follicle count in women was used in two ways: (1) the window of susceptibility (from birth to menopause) was defined as 49.6. years for women born with an average follicle count, 38.7. years for women born with a low follicle count, and 60.0. years for women born with a high follicle count; and (2) follicle count was assumed to reflect human susceptibility due to toxicodynamic factors. The multistage-Weibull model was used to predict dose-response curves for three scenarios (average, low, and high follicle counts at birth to generate reference concentration values ranging from 0.2 to 20. ppm). This case study illustrates how information on mode of action can be used to guide key decisions in the dose-response assessment with respect to identifying a dose measure, low-dose extrapolation method, background exposure, and sensitive subpopulations. © 2011 Elsevier Inc..

Becker R.A.,American Chemistry Council | Hays S.M.,Summit Toxicology LLP | Robison S.,Procter and Gamble | Aylward L.L.,Summit Toxicology LLP
Journal of Toxicology | Year: 2012

Evaluation of a larger number of chemicals in commerce from the perspective of potential human health risk has become a focus of attention in North America and Europe. Screening-level chemical risk assessment evaluations consider both exposure and hazard. Exposures are increasingly being evaluated through biomonitoring studies in humans. Interpreting human biomonitoring results requires comparison to toxicity guidance values. However, conventional chemical-specific risk assessments result in identification of toxicity-based exposure guidance values such as tolerable daily intakes (TDIs) as applied doses that cannot directly be used to evaluate exposure information provided by biomonitoring data in a health risk context. This paper describes a variety of approaches for development of screening-level exposure guidance values with translation from an external dose to a biomarker concentration framework for interpreting biomonitoring data in a risk context. Applications of tools and concepts including biomonitoring equivalents (BEs), the threshold of toxicologic concern (TTC), and generic toxicokinetic and physiologically based toxicokinetic models are described. These approaches employ varying levels of existing chemical-specific data, chemical class-specific assessments, and generic modeling tools in response to varying levels of available data in order to allow assessment and prioritization of chemical exposures for refined assessment in a risk management context. Copyright © 2012 Richard A. Becker et al.

Aylward L.L.,Summit Toxicology LLP | Becker R.A.,American Chemistry Council | Kirman C.R.,Summit Toxicology | Hays S.M.,Summit Toxicology
Regulatory Toxicology and Pharmacology | Year: 2011

In chemical risk assessment, exposures in humans are often compared to no-observed-adverse-effect levels or benchmark doses for sensitive adverse responses (" points of departure") in laboratory species to assess whether a sufficient "margin of exposure" (MOE) is attained to ensure safety. Conventionally, the default target MOE based on external dose is drawn from uncertainty factors of 10 each for inter- and intra-species extrapolation. The increasing availability of blood-based biomonitoring data in humans as well as measured and modeled blood concentrations in laboratory animals in key studies underlying chemical risk assessments may allow assessments of MOE to be made by comparing blood concentrations of parent compound in humans compared to those in the laboratory species at the point of departure for the risk assessment. This exploratory analysis provides an initial evaluation of whether the default MOE of 100 typically applied on an external dose basis is protective when applied on the basis of comparison of blood concentrations between laboratory animals and humans. The evaluation is conducted using a generic physiologically-based pharmacokinetic model of the structure typically applied to volatile organic compounds. Additional considerations relative to other classes of compounds are also addressed. Based on this evaluation, for chemicals with characteristics consistent with the modeling conducted here under certain conditions, the default MOE of 100 is more protective when applied to comparative blood concentrations than when applied on an external dose basis. Depending upon the chemical characteristics, the toxicokinetic components of the inter- and/or intra-species uncertainty factor could be reduced or eliminated when inter- and intra-species comparisons and extrapolations are made based on blood concentrations of parent compound of interest. © 2011 Elsevier Inc.

LaKind J.S.,LaKind Associates LLC | LaKind J.S.,University of Maryland, Baltimore | Naiman D.Q.,Johns Hopkins University | Hays S.M.,Summit Toxicology | And 2 more authors.
Journal of Exposure Science and Environmental Epidemiology | Year: 2010

Trihalomethanes (THMs) can form as byproducts during drinking water disinfection, which is crucial for limiting human exposure to disease-causing pathogens. The US Environmental Protection Agency (USEPA), recognizing both the importance of water disinfection for public health protection and potential risks associated with THM exposure, developed disinfection byproduct rules with the parallel goals of ensuring safe drinking water and limiting the levels of THMs in public water systems. The National Health and Nutrition Examination Survey (NHANES) THM blood data can be used as a means for assessing US population exposures to THMs; biomonitoring equivalents (BEs) can provide human health risk-based context to those data. In this paper, we examine the blood THM levels in the 1999-2004 NHANES data to (i) determine weighted population percentiles of blood THMs, (ii) explore whether gender and/or age are associated with blood THM levels, (iii) determine whether temporal trends can be discerned over the 6-year timeframe, and (iv) draw comparisons between population THM blood levels and BEs. A statistically significant decrease in blood chloroform levels was observed across the 1999-2004 time period. Age-related differences in blood chloroform levels were not consistent and no gender-related differences in blood chloroform levels were observed. The concentrations of all four THMs in the blood of US residents from the 2003 to 2004 NHANES dataset are below BEs consistent with the current US EPA reference doses. For bromodichloromethane and dibromochloromethane, the measured median blood concentrations in the United States are within the BEs for the 10 -6 and 10 -4 cancer risk range, whereas measured values for bromoform generally fall below the 10 -6 cancer risk range. These assessments indicate that general population blood concentrations of THMs are in a range considered to be a low to medium priority for risk assessment follow-up, according to the guidelines for interpretation of biomonitoring data using BEs. © 2010 Nature Publishing Group All rights reserved.

Aylward L.L.,Summit Toxicology LLP | Kirman C.R.,Summit Toxicology LLP | Schoeny R.,U.S. Environmental Protection Agency | Portier C.J.,Agency for Toxic Substances and Disease Registry | Hays S.M.,Summit Toxicology LLP
Environmental Health Perspectives | Year: 2013

Background: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment-based values now allow interpretation of these biomonitoring data in a public health risk context. Objectives: We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER. Methods: We identified available risk assessment-based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates. Conclusions: Most analytes in the NER show HQ values of < 1; however, some (including acrylamide, dioxin-like chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10-4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.

PubMed | Toxicology Excellence For Risk Assessment, RG York and Associates LLC, University of Cincinnati, Summit Toxicology and 2 more.
Type: Journal Article | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2015

Ethanol-based topical antiseptic hand rubs, commonly referred to as alcohol-based hand sanitizers (ABHS), are routinely used as the standard of care to reduce the presence of viable bacteria on the skin and are an important element of infection control procedures in the healthcare industry. There are no reported indications of safety concerns associated with the use of these products in the workplace. However, the prevalence of such alcohol-based products in healthcare facilities and safety questions raised by the U.S. FDA led us to assess the potential for developmental toxicity under relevant product-use scenarios. Estimates from a physiologically based pharmacokinetic modeling approach suggest that occupational use of alcohol-based topical antiseptics in the healthcare industry can generate low, detectable concentrations of ethanol in blood. This unintended systemic dose probably reflects contributions from both dermal absorption and inhalation of volatilized product. The resulting internal dose is low, even under hypothetical, worst case intensive use assumptions. A significant margin of exposure (MOE) exists compared to demonstrated effect levels for developmental toxicity under worst case use scenarios, and the MOE is even more significant for typical anticipated occupational use patterns. The estimated internal doses of ethanol from topical application of alcohol-based hand sanitizers are also in the range of those associated with consumption of non-alcoholic beverages (i.e., non-alcoholic beer, flavored water, and orange juice), which are considered safe for consumers. Additionally, the estimated internal doses associated with expected exposure scenarios are below or in the range of the expected internal doses associated with the current occupational exposure limit for ethanol set by the Occupational Safety and Health Administration. These results support the conclusion that there is no significant risk of developmental or reproductive toxicity from repeated occupational exposures and high frequency use of ABHSs or surgical scrubs. Overall, the data support the conclusion that alcohol-based hand sanitizer products are safe for their intended use in hand hygiene as a critical infection prevention strategy in healthcare settings.

Hays S.M.,Summit Toxicology L.L.P. | Aylward L.L.,Summit Toxicology L.L.P.
International Journal of Hygiene and Environmental Health | Year: 2012

Human biomonitoring (HBM) has proven an extremely valuable tool for determining which chemicals are getting into people, detecting trends in population exposures over time, and identifying populations with exposures above background. The potential significance of the HBM data in the context of existing toxicology data and risk assessments can be assessed if chemical-specific quantitative screening criteria are available. Such screening criteria would ideally be based on robust datasets relating potential adverse effects to biomarker concentrations in human populations. However, such assessments are data intensive and exist for only a few chemicals. As an interim approach, the concept of Biomonitoring Equivalents (BEs) has been developed. A Biomonitoring Equivalent (BE) is defined as the concentration or range of concentrations of a chemical or its metabolites in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guidance value such as a Reference Dose (RfD) or Tolerable or Acceptable Daily Intake (TDI or ADI). This paper provides an overview of the derivation of BEs and how BEs can be used to interpret human biomonitoring data in a public health risk context. © 2011 Elsevier GmbH.

Heffernan A.L.,University of Queensland | Aylward L.L.,Summit Toxicology LLP | Toms L.-M.L.,Queensland University of Technology | Sly P.D.,University of Queensland | And 2 more authors.
Journal of Exposure Science and Environmental Epidemiology | Year: 2014

Biomonitoring has become the "gold standard" in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens - combining multiple individual specimens into a single sample - can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure-outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, the use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results.© 2014 Nature America, Inc.

PubMed | ExxonMobil, University of Maryland Baltimore County, Colorado State University, American Chemistry Council and 7 more.
Type: | Journal: Environment international | Year: 2016

Single point estimates of human health hazard/toxicity values such as a reference dose (RfD) are generally used in chemical hazard and risk assessment programs for assessing potential risks associated with site- or use-specific exposures. The resulting point estimates are often used by risk managers for regulatory decision-making, including standard setting, determination of emission controls, and mitigation of exposures to chemical substances. Risk managers, as well as stakeholders (interested and affected parties), often have limited information regarding assumptions and uncertainty factors in numerical estimates of both hazards and risks. Further, the use of different approaches for addressing uncertainty, which vary in transparency, can lead to a lack of confidence in the scientific underpinning of regulatory decision-making. The overarching goal of this paper, which was developed from an invited participant workshop, is to offer five approaches for presenting toxicity values in a transparent manner in order to improve the understanding, consideration, and informed use of uncertainty by risk assessors, risk managers, and stakeholders. The five approaches for improving the presentation and communication of uncertainty are described using U.S. Environmental Protection Agencys (EPAs) Integrated Risk Information System (IRIS) as a case study. These approaches will ensure transparency in the documentation, development, and use of toxicity values at EPA, the Agency for Toxic Substances and Disease Registry (ATSDR), and other similar assessment programs in the public and private sector. Further empirical testing will help to inform the approaches that will work best for specific audiences and situations.

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