Author Archives: ToxStrategies

ToxStrategies is pleased to announce the additions of Dr. LeeAnn Racz as a Senior Engineer and Ms. Jennifer Bare as a Scientist III.  

Dr. Racz comes to the Exposure Sciences Practice with a diverse background in environmental assessment, human health risk assessment, and industrial hygiene, gained in large part from her 23-year career in the U.S. Air Force. She is a Board-Certified Environmental Engineer and Certified Industrial Hygienist, with expertise in environmental health and workplace exposure assessment and environmental engineering and has led teams involved in compliance education, emergency response readiness, and response and recovery at aircraft crash and other accident sites. She has also directed radiation safety programs and managed radiation surveys. As a consultant, Dr. Racz recently worked with a global manufacturing company to develop and implement pandemic protective measures. 

 Ms. Bare is an environmental engineer specializing in quantitative exposure modeling and reconstruction, human health risk assessment, chemical transport analysis, and data management. She designs and applies chemical exposure models for volatile and semi-volatile organic compounds, particulates, and metals, and also reconstructs and predicts community exposures to industrial emissions. Her experience also includes assessing products and chemicals that are regulated under California’s Proposition 65 and USEPA’s Toxic Substances Control Act (TSCA). 

The Biden Administration has directed the Environmental Protection Agency (EPA) to evaluate policies under the Toxic Substances Control Act (TSCA) New Chemicals Program to ensure their compliance with statutory requirements.  This evaluation has resulted in significant changes, announced by EPA on March 29, 2021 as to how EPA will assess and manage the risks associated with new chemicals, including changes to:

• The introduction of significant new use rules (SNURs),
• Assumptions about protections afforded by OSHA’s standards as part of New Chemical risk evaluations

SNURs: EPA announced that the agency will no longer exclude conditions of use of a new chemical from their review based on the existence of proposed SNURs. Instead, EPA will review all reasonably foreseen conditions of use. Where a use may present an unreasonable risk, or where there is insufficient information to make a safety determination, EPA will issue an order to address those potential risks, whether or not it is the applicant’s intended or planned use. This new practice will require more information and extend the level of effort and time for EPA New Chemical reviews.

Worker Protection Through Existing OSHA Standards: EPA will no longer assume that workers are adequately protected under OSHA’s worker protection standards and Safety Data Sheets (SDSs) when evaluating the risks of a new chemical. Instead, EPA will identify the absence of worker safeguards as a reasonably foreseeable conditions of use. Under this approach, if potentially unreasonable risks are identified, then necessary worker protections will be mandated through a TSCA order. Thus, reliance on OSHA standards, personal protective equipment, and knowledge provided by hazard communication programs will no longer be incorporated into New Chemical risk evaluations or the resulting risk management actions. EPA has not clarified whether this policy might result in replacement of OSHA occupational exposure limits (OELs) that could be deemed to not meet EPA risk acceptance criteria. It seems likely that this approach will be also be adopted in EPA high-priority existing chemical risk evaluations. A previous article on the ToxStrategies website discussed the significant differences between EPA TSCA worker risk assessments and OSHA assessments used to establish OELs.

Ms. Mina Suh, along with colleagues within EpidStrategies (a Division of ToxStrategies), and external collaborators, has been conducting research on respiratory syncytial virus (RSV), especially as it relates to infants and children in the United States. In a prospective viral surveillance study, which was recently accepted for publication by the Journal of Pediatrics (preview here), Ms. Suh and researchers from the medical research community described common respiratory infections, including influenza, RSV, and rhinovirus/enterovirus, in infants from December 2019 through April 2020, across outpatient, emergency department, and inpatient settings in Davidson County, Tennessee. Testing for SARS-Cov-2 was added with the onset of Covid-19.  Results show that RSV is detected across various clinical settings (outpatient, emergency department, inpatient) and has the highest disease severity compared to other viral pathogens. The authors conclude that continued surveillance of infants, in different clinical settings, is needed to fully assess the burden exerted by RSV, and importantly, to inform vaccine development. 

The team of epidemiologists at EpidStrategies (a Division of ToxStrategies), along with colleagues in industry and academia, have been deeply involved in ongoing research on respiratory syncytial virus (RSV) in children. This work is reflected in a trio of abstracts being accepted for presentation at pediatrics-related conferences. Among the studies presented are one noting lower occurrence levels of RSV during the current pandemic, and one evaluating congenital heart disease among RSV-affected children 2 years and younger. The third study compared RSV-related hospitalizations before and after the American Academy of Pediatrics changed their guidance to recommend against the use of palivizumad, an immunoprophylaxis that was being used for at-risk infants. 

The recently accepted RSV-related abstracts are: 

William Malcolm, Kimberley Fisher, Charles T. Wood, Naimisha Movva, Mina Suh, Zachary Wolf, Suresh Balu, Mark Sendak, Bradley Hintze, Meghan White,  Jon Fryzek, Christopher B. Nelson. Infant lower respiratory tract infections, including those caused by RSV, are significantly below historical levels during the COVID-19 pandemic. Pediatrics Academic Societies 2021, April 30 – May 4, 2021.

Jaime Fergie, Tara Gonzales, Mina Suh, Xiaohui Jiang, Jon P. Fryzek, Naushin Hooda, Ashley Howard, Adam Bloomfield. Higher–risk congenital heart disease (CHD) among children aged ≤24 months with respiratory syncytial virus hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH). 37th Annual Children’s National Symposium: ECMO and the Advanced Therapies for Cardiovascular and Respiratory Failure, Feb 21–23, 2021. 

Jaime Fergie, Tara Gonzales, Mina Suh, Xiaohui Jiang, Jon P. Fryzek, Naushin Hooda, Ashley Howard, Adam Bloomfield. Higher-risk congenital heart disease (CHD) among children aged ≤24 months with respiratory syncytial virus hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH) at RSV season before and after the 2014 American Academy of Pediatrics (AAP) guidance. California Association of Neonatologists’ 27th Annual Cool Topics in Neonatology Conference, March 5–7, 2021. 

ToxStrategies is pleased to announce new quantitative structure activity relationship [(Q)SAR] service offerings, including ICH M7 pharmaceutical impurity assessments. We offer expertise in the use and interpretation of Derek Nexus and Leadscope Model Applier (LSMA) to meet guidance specifications that are essential to the pharmaceutical industry. We are well versed in the use of these (Q)SAR platforms to provide predictions for a variety of endpoints, such as bacterial and mammalian genotoxicity, carcinogenicity, acute toxicity, skin sensitization, target organ toxicities, reproductive and developmental toxicity endpoints, and others. These commercially available (Q)SAR programs are used to support mutagenicity assessment on projects ranging from single drug impurities to complementing analyses of compound synthesis pathways, including starting materials, intermediates, metabolites, and impurities. Derek and LSMA are used during lead optimization to identify ideal candidates, and to assess extractable and leachable compounds associated with packaging components or medical devices. With the increased regulatory acceptance and interest in using (Q)SAR predictions to complement standard safety assessments, these analyses are needed at numerous program development stages across pharmaceutical, food, and other industrial sectors.   

In addition to expertise in the use of Derek and LSMA, ToxStrategies’ scientists are experienced in implementing open-source (Q)SAR models, including OECD QSAR Toolbox, VEGA, USEPA EpiSuite, and others, to meet R&D and regulatory needs in assessing ingredients, contaminants, or other chemicals, such as those used in cosmetics or found in food or drinking water. With our diverse practice areas and broad project experience, (Q)SAR analyses can be integrated seamlessly into program design and project workflow to meet 21st Century toxicology needs. 

 Please contact Amy Mihalchik at amihalchik@toxstrategies.com for more information.

We look forward to collaborating with you!  

March 27, 2021, is fast approaching and a date to note on your calendar. This day marks the implementation of the European Commission’s new regulation and update to the General Food Law Regulation, aimed at increasing the transparency of risk assessments for foods. This new regulation directly affects how the European Food Safety Authority (EFSA) performs their risk assessments and how stakeholders interact with EFSA, notify studies, and submit dossiers. While the goal of the initiative is to increase the transparency of the risk assessment by strengthening the reliability, objectivity, and independence of the scientific studies performed, it’s yet to be seen how smooth and effective the transition will be—this regulation is a complete re-design of the European Union’s previous review and submission process and is to be implemented in a short time.   

 ToxStrategies has been an active participant in the Transparency Regulation Implementation Training Program that EFSA launched in January of 2021 to help stakeholders better understand and prepare for the new requirements under this regulation. In parallel with the Training Program, EFSA has also published detailed Practical Arrangements to outline how the new rules will be put into practice. It is evident from reviewing these materials that the Transparency Regulation may pose additional challenges to applicants, particularly during the first year of implementation.  

 For example, when the new submission framework goes into effect on March 27, 2021, all scientific studies supporting an application must be notified through EFSA before they are commissioned or carried out (according to Article 32b or 32c1 of the Regulation). This process is complicated further by being different for new applicants than for applicants for re-authorization. Stakeholders already in the process of preparing applications (before March 27, 2021) may run into logistical issues with implementing the Transparency Regulation, especially if they need to complete studies in time to meet submission deadlines for application renewals. In addition to this example, ToxStrategies has identified multiple issues that an applicant might encounter during this transition period. 

If you are interested in learning more, please contact Dr. Allison Franzen at afranzen@toxstrategies.com

Among President Biden’s many Executive Orders in the first days of his administration was one titled, “Protecting Public Health and the Environment and Restoring Science to Tackle the Climate Crisis.” In response to this and other orders and directives, the U.S. Environmental Protection Agency (USEPA) is planning to review on five final rules the Agency issued under the prior administration (on January 6, 2021) under the Toxic Substances Control Act (TSCA) that address five persistent, bioaccumulative, and toxic (PBT) chemicals (listed below).

The USEPA determined that these chemicals require expedited action under TSCA, given the Agency’s charge to protect human health and the environment. The USEPA review will reevaluate information that was available during the promulgation of the final PBT rules as well as new information. As a part of the review process, USEPA issued an invitation for the public to comment on the final PBT rules, stating that such input could include “whether further exposure reductions… could be achieved, including… for potentially exposed or susceptible subpopulations and the environment; implementation issues…; and whether to consider additional or alternative measures or approaches.” Comments in response to this invitation must be submitted to USEPA by May 17, 2021 (docket identification number EPA–HQ–OPPT–2021–0202); contact information is available in the Federal Register.

The five PBT chemicals at issue are:

• 2,4,6- tris(tert-butyl)phenol (2,4,6-TTBP) (CASRN 732–26–3);
• decabromodiphenyl ether (decaBDE) (CASRN 1163–19–5);
• phenol, isopropylated phosphate (3:1) (PIP (3:1)) (CASRN 68937–41–7);
• pentachlorothiophenol (PCTP) (CASRN 133–49–3); and
• hexachlorobutadiene (HCBD) (CASRN 87–68–3).

Dr. Candace Doepker will present a webinar titled, “Myths and Facts about Caffeine: An Expert Evaluation of the Current Science.” Sponsored by the International Food Information Council (IFIC), the webinar will go live at 1 p.m. ET on March 30, 2021 (registration available here). The information presented will include IFIC’s latest research on consumer behavior regarding caffeine, and Dr. Doepker will address topics such as caffeine toxicity and safety, its metabolism in the body, and current controversies in caffeine research.

Dr. Doepker is a toxicologist and is a Principal Scientist and the Practice Director of ToxStrategies’ Foods & Consumer Products Practice. She has chaired the IFIC’s Caffeine and Food Ingredients Committee and served on the Scientific Advisory Board of the National Coffee Association.