Author Archives: ToxStrategies

New Book Publication by Dr. Rob James

ToxStrategies is pleased to announce the recent publication of Principles of Toxicology:  Environmental and Industrial Applications (3rd Edition), co-edited and co-authored by our Senior Science Advisor, Dr. Rob James. Dr. James co-authored three chapters, covering topics such as the general principles of toxicology, hepatotoxicity, and human health risk assessment. Dr. Janice Britt, a Senior Managing Scientist with ToxStrategies, also contributed to this publication by authoring a chapter on the properties and effects of pesticides xenical 120.

A copy of this publication is available for purchase here.

ToxStategies at Battelle 2015

ToxStrategies’ experts prepared 2 presentations for the 2015 Battelle Eighth International Conference on Remediation and Management of Contaminated Sediments in New Orleans, Louisiana, January 12–15.

Senior Scientist Dr. Jon Urban was in attendance, presenting a poster entitled Lower Passaic River RMO-8: An Alternative Human Health Risk Assessment during the Tuesday evening session, “Ecological and Human-Health Risk Assessment.”

Principal Dr. Mark Harris was also in attendance, presenting ToxStrategies’ work entitled Lower Passaic River RMO-8: An Alternative Preliminary Remediation Goal during the Wednesday evening poster session, “Establishing Remediation Goals.”

Battelle 2015 is a forum for sharing research results, practical experiences and opportunities toward the goal of remediating, restoring and maintaining the environmental and economic vitality of waterways.

For more information on the conference, click here.

NRC Review of NTP’s Listing of Formaldehyde as a Known Human Carcinogen Released on August 8, 2014

Washington, D.C.

A National Research Council (NRC) report released on August 14, 2014 largely endorsed an earlier National Toxicology Program (NTP) review that had concluded formaldehyde is a human carcinogen.  Noting the NTP program provides no criteria for determining when there is sufficient human evidence, it developed its own procedure using the expert judgment of the committee; still, the NRC panel essentially agreed with study selections and conclusions made earlier by the NTP.  Importantly, nothing in the NRC committee review of the literature addressed the notable limitations, concerns or controversies of the National Cancer Institute (NCI) studies that have been previously raised by other scientists (e.g., Marsh et al, 2010). NRC’s failure to address these issues does little to resolve the controversy that already existed regarding the hazard potential of this compound. In addition, this failure would also seem to raise questions as to how the NCI studies provide strong support for either hypothesis, or allows for the elimination of concern for chance, bias, or confounding as the NRC panel stated they do.  The failure to discuss the identified limitations of the observations initially reported for the NCI cohort also raises concerns for the completeness of the literature evaluation the NRC panel performed.

Regarding the current mechanistic data, the NRC acknowledged the absence of a coherent and plausible mechanism for how formaldehyde (which does not reach the bone marrow) might cause myeloid leukemia. Importantly, in its analysis of mechanistic and animal studies the NRC did not distinguish between studies that used formaldehyde and those that used formalin. The  U.S. EPA has recently questioned the utility of formalin studies for assessing the effects of inhaled formaldehyde. The NRC also did not consider whether effects observed in laboratory mice were secondary to a well-documented respiratory effect that occurs when mice are exposed to irritant gases such as formaldehyde. Notably, the NRC cited one recent study using formalin (see above) and mice (see above) that appeared to mistake a blood vessel for a serious bone marrow lesion. In an interesting twist, the NTP has recently completed a formaldehyde study in mice genetically predisposed to develop leukemia and reported no signs of adverse effects—yet these findings do not appear to be referenced anywhere in the NRC report. Most strikingly, the NRC concludes that systemic delivery of formaldehyde is unlikely, but states that experimental studies provide evidence for “systemic mechanistic events”, which they suggest could be associated with irritation, inflammation, and stress at the site of contact. For nasopharyngeal cancer (NPC), the available animal and mechanistic data favor a high-dose, thresholded dose-response.

To summarize, concern for the potential cancer risk associated with high-dose formaldehyde exposure has been a debatable issue for sometime now.  The epidemiology studies performed by NCI scientists represent the main studies suggesting high occupational formaldehyde exposures carries some risk of NPC and acute myeloid leukemia (AML), but these studies have been criticized for methodological shortcomings and studies in other countries have also failed to confirm the NCI findings.  The NRC panel did not evaluate and discuss this issue and provides no new analysis that might help resolve the controversy surrounding formaldehyde’s potential cancer hazard.  Thus, it appears this controversy may continue unabated, as may concerns for any risk assessments using slope factors derived from these controversial studies.

Drs. <a href="https://www.toxstrategies.com/people/janice-britt article source.htm” target=”new”>Britt, James and Thompson of ToxStrategies, Inc. are very familiar with all aspects of formaldehyde toxicology and risk assessment having published numerous articles on these topics in the peer reviewed scientific literature.

Risk assessment of cumulative environmental exposure to perchlorate, nitrate and thiocyanate based on NHANES biomonitoring data

We are pleased to announce a recently published study by scientists from ToxStrategies that evaluated the National Health and Nutrition Examination Survey (NHANES) data from multiple survey cycles to assess potential effects to thyroid hormones from cumulative exposures to perchlorate, nitrate, and thiocyanate. This study, titled “The effect of perchlorate, nitrate, and thiocyanate on free thyroxine for potentially sensitive subpopulations of the 2001-2002 and 2007-2008 National Health and Nutrition Examination Survey,” was published in the Journal of Exposure Science and Environmental Epidemiology. Using the NHANES data, we conducted multiple regression models of free thyroxine (T4) in serum and urinary chemical concentrations, which also included covariates known to impact thyroid hormone status. In addition, meta–analyses of the NHANES females in the two survey cycles were conducted. We observed that perchlorate, nitrate, and thiocyanate can affect free T4 levels in non-pregnant females. The effects were not observed in males and pregnant females. Our study indicates that the potential for cumulative risk of co-exposures exist, and risk assessment of perchlorate exposures should be conducted in consideration of effects from nitrate and thiocyanate exposures.

Evaluation of Impact of Shale Gas Operations in the Barnett Shale Region on Volatile Organic Compounds in Air and Potential Human Health Risks

We are pleased to announce the publication of a recent study by ToxStrategies’ scientists that was designed to evaluate potential community-wide exposures to volatile organic compounds (VOCs) in air in the Barnett Shale region as a means of assessing the potential impact of shale gas production activities on human health. The publication, titled Evaluation of Impact of Shale Gas Operations in the Barnett Shale Region on Volatile Organic Compounds in Air and Potential Human Health Risks, was published in Science of the Total Environment, and is available online via Open Access at: http://www.sciencedirect.com/science/article/pii/S0048969713010073 This study represents the first-ever, large scale evaluation of potential health impacts from shale gas operations based on an analysis of measured chemical concentrations of VOCs in ambient air. As a part of this study, we reviewed more than 4.6 million data points generated by the Texas Commission on Environmental Quality (TCEQ) via their extensive air monitoring network in the Barnett Shale region. This region of Texas contains one of the largest, most active gas fields in North America, stretching across 5000 square miles and with an estimated 15,870 producing wells as of 2011. Based on our comprehensive assessment we concluded that shale gas production activities have not resulted in community-wide exposures to VOCs at levels that would pose a health concern. Given the high density of active wells in this region, our findings may be useful for understanding potential health risks in other shale play regions.

ToxStrategies Welcomes Dr. Susan Borghoff

We are pleased to announce that Dr. Susan Borghoff has joined ToxStrategies, Inc. as a Senior Managing Scientist and she will be based in Research Triangle Park, NC. She is a board-certified toxicologist with over twenty-five years of experience designing and managing diverse research programs and regulatory-driven toxicology studies. Dr. Borghoff is a recognized expert in evaluating modes-of-action by which specific chemicals cause toxicity and cancer in rodents and understanding the metabolism and pharmacokinetics using PBPK models for extrapolation of risk to humans. Dr. Borghoff is also a recognized expert in endocrine disruption having provided scientific oversight of more than 40 GLP regulatory studies for the USEPA-mandated Endocrine Disruption Screening Program.

Dr. Borghoff has served as a reviewer on a number of panels/working groups for international organizations including USEPA, NCI, NIEHS, IPCS, ECETOX, and IARC. She is an active member of the Society of Toxicology and has served on Council, as a member of the Program, Awards, and Education Committees and currently is a member of the TSCA Reform Task Force. She has also served as an Associate Editor for Toxicological Sciences and on the editorial board for Chemical Biological Interactions and Toxicology Letters. Dr. Borghoff received her Ph.D. and MSPH in Environmental Sciences and Engineering from the University of North Carolina, and a B.S. in Chemistry from East Stroudsburg University in Pennsylvania. Dr. Borghoff became a Diplomat of the American Board of Toxicology in 1994

To read more about Dr. Susan Borghoff and get her contact information, please visit her company web page.

ToxStrategies Welcomes Mr. Don Schmitt

We are pleased to announce that Mr. Donald F. Schmitt has joined ToxStrategies, Inc. as a Senior Managing Scientist and will be based in the Chicago area. Mr. Schmitt has 30 years of corporate and consulting experience in toxicology, risk assessment, and regulatory affairs. He has significant experience in evaluating the safety of foods and food ingredients, additives and contaminants, feed additives, cosmetics, and environmental and occupational exposures. He has developed regulatory strategies for FDA-regulated products in support of regulatory compliance, product defense, product development and claims, and pre-market approval. Mr. Schmitt has conducted pre-clinical toxicity evaluations of drugs, medical devices, and biologics for both the government and private sectors. He has designed, contracted, and monitored pre-clinical safety studies required for regulatory clearance of new food additives, cosmetic ingredients, and human and veterinary drugs for clients. Additionally, he has provided technical support and assisted in the preparation of a variety of reports and submissions to regulatory authorities including Generally Recognized as Safe (GRAS) affirmation petitions/notifications, food contact notifications (FCNs), new dietary ingredient notification (NDIs), direct and indirect food additive petitions, health claims petitions, clinical study Investigator Brochures, and Investigational New Drug and New Drug Applications (INDs/ NDAs).

To read more about Mr. Don Schmitt and get his contact information, please visit his company web page.

ToxStrategies Welcomes Dr. Rayetta G. Henderson and Ann Holbrow Verwiel

ToxStrategies is pleased to announce the addition of two health scientists, Dr. Rayetta G. Henderson and Ann Holbrow Verwiel.

Dr. Henderson – Research Triangle Park, North Carolina
Dr. Rayetta Henderson joined our team as a senior health scientist and is located in the Research Triangle Park, North Carolina area. She has managed scientific programs for the EU’s Registration, Evaluation & Authorisation of Chemicals (REACH) and Classification, Labeling, and Packaging (CLP) Regulations and has experience supporting trade associations in the development of strategies for addressing metal-specific issues related to REACH and CLP. In this role, she served as a scientific representative on a number of technical working groups, including legal and financial subgroups. She is knowledgeable of the UN’s Globally Harmonized System (GHS) including hazard assessment and classification for jurisdictions worldwide. Dr. Henderson has substantial experience designing, monitoring, and interpreting scientific data from toxicity studies and alternative method studies in support hazard evaluations.

Dr. Henderson has studied and performed health effects assessments on various chemicals including perfluorinated compounds (PFCs), dioxin-like compounds, and metals, particularly nickel and nickel-containing substances. Dr. Henderson earned her Ph.D. in Toxicology from the University of North Carolina at Chapel Hill, where her research focused on understanding the mechanism of action leading to the developmental toxicity of perflurooctane sulfonate (PFOS).

To read more about Dr. Rayetta Henderson and get her contact information, please visit her company web page.

Ann Holbrow Verwiel – San Francisco Bay Area, California
Ann Holbrow Verwiel joined our team as a managing health scientist and is located in our new San Francisco Bay Area office. She has more than 20 years of experience in environmental consulting in the areas of human health risk assessment, site assessment, and environmental regulation. Over her career, she has focused on integrating risk assessment into an overall risk management approach to problem definition, investigation, and mitigation. She has successfully applied this approach in negotiations with regulatory agencies and public groups to significantly reduce the cost/extent of investigation, assessment, and mitigation. She has published and presented papers on a wide variety of topics, including Monte Carlo analysis of the conservatism in risk assessment, environmental fate and transport of contaminants, and environmental auditing.

Ms. Verwiel has managed and conducted numerous human health risk assessments that addressed a wide variety of chemicals in soil, soil vapor, air, and groundwater. She has evaluated the chemical signatures, fate and transport mechanisms, and likely current and future human exposures as key first steps in the health risk evaluation. In the area of air toxics, she has worked to develop investigation strategies and perform assessments of exposure to indoor and ambient air that included emission source evaluation; modeling; and soil vapor, indoor air, and ambient air measurements. She also has assisted several entities with air toxic analysis to meet the requirements of Proposition 65, AB2588 Toxic “Hot Spots” Act, and the California Environmental Quality Act (CEQA). She has worked with regulatory public participation specialists, public affairs officers, and others to develop written summaries and presentation materials that convey complex technical issues to the public. She has provided litigation support for several projects, involving disputes between property owners and facility operators, alleged air emissions exposures, and Proposition 65 litigation.

To read more about Ms. Ann Verwiel and get her contact information, please visit her company web page.