ToxStrategies scientists Drs. Allison Franzen and Susan Borghoff are among the authors of a new paper in the journal Critical Reviews in Toxicology. The work identifies an adverse outcome pathway (AOP), for kidney tumors that occur specifically in male rats through a mode of action (MoA) that is not relevant to humans—inducing α2u-globulin nephropathy (α2u-N). The authors define both the molecular initiating event (MIE) and key events (KEs) that lead to the occurrence of kidney tumors in male rats following chronic exposure to chemicals that have been shown to operate through this a2u-N MoA. Based on the confidence in the data identified to support this AOP, it can be used for hazard identification with the development of assays for the MIE and selected KEs, thereby decreasing the use of animal testing for regulatory applications.
ToxStrategies scientists Dr. Rayetta Henderson, Kara Franke, Lauren Payne, and Dr. Allison Franzen have published an article titled, “Cannabidiol Safety Data: A Systematic Mapping Study” in Cannabis and Cannabinoid Research. This study is the first systematic map of the safety-related information available for CBD in the peer-reviewed literature and is part of an ongoing effort to establish a foundation for future research initiatives to support the determination of a safe CBD intake level for consumer use. The objective was to systematically map the publicly available safety-related literature for CBD, to provide a comprehensive overview of the current state of knowledge, assist in identifying data gaps and trends, and inform future hazard-based decision making. Available evidence was gathered and collated to demonstrate the current landscape of studies that report health outcomes to inform safety evaluation, as well as to identify outcomes or other subtopics that may warrant further research.
A publication titled, “Benefit-Risk of Coffee Consumption and All-Cause Mortality: A Systematic Review and Disability Adjusted Life Year Analysis,” by ToxStrategies authors Candace Doepker, Naimisha Movva, Sarah Cohen, and Daniele Wikoff, has been accepted by Food and Chemical Toxicology. The paper is unique, in that a quantitative analysis was used within the benefit-risk assessment for foods (BRAFO) paradigm to assess potential harm and/or benefits of drinking coffee. In the paper, the BRAFO framework is applied to guide risk managers in decision making; in that context, the authors conclude that any policy that directs consumers to avoid drinking coffee may be a detriment to the overall health of the population, given the substantial potential benefits of coffee consumption on all-cause mortality for adults.
The journal pre-print is available online, and the published manuscript will be available soon.
The Reproductive and Developmental Toxicology Specialty Section of the Society of Toxicology recently awarded its Scientific Achievement Award to ToxStrategies Senior Consultant Dr. John Rogers. The Section presents this award annually to recognize a member’s lifetime contribution to the field of reproductive and developmental toxicology, including such factors as leadership, impact on the field, and mentorship. In presenting the award during the Section’s annual meeting, held virtually on May 3, Dr. Atlee Watson recognized Dr. Rogers’ career longevity, beginning with service in the EPA in the 1980s, as well as his active leadership in SOT and the RDTSS, and his role in numerous scientific panels, seminars, and continuing education initiatives.
A team of 21CT and EpidStrategies scientists are authors on a manuscript being published in Regulatory Toxicology and Pharmacology. The study examines current practices for assessing risk associated with environmental exposure to hexavalent chromium, comparing approaches based on margin of exposure to those using linear extrapolation. The authors assert that regulatory lung cancer potency estimates for Cr(VI) are based on outdated research, whereas more current mechanistic data support an epigenetic role for Cr(VI) and a non-mutagenic mode of action. The article cites a need for new epidemiology data to inform risk assessment of low-intensity exposures, concluding, however, that Cr(VI) in ambient air poses little concern for human health.
ToxStrategies scientists Dr. Chad Thompson, Dr. Allison Franzen, and Ms. Seneca Fitch and their colleagues have published a pair of papers in a special issue of Critical Reviews in Toxicology that celebrates the journal’s 50th anniversary. The two articles focus on the modes of action (MOAs) by which exposure to formaldehyde is related to leukemia and nasal cancer. The topics are timely, in light of USEPA’s designation of formaldehyde as a high-priority substance under the Toxic Substances Control Act. With regard to leukemia, the research consisted of a systematic literature review dealing with such MOAs, concluding that postulated causation of leukemia by formaldehyde intake is not biologically plausible based on current evidence. The other study looked at formaldehyde-induced nasal tumors in rats and their relevance to humans, emphasizing numerous studies published since 2006 and highlighting the evidence for non-genotoxic mechanisms of cytotoxicity and regenerative cell proliferation in the MOA for tumor formation.
A recently published article by ToxStrategies scientists presents the systematic identification, appraisal, and integration of mechanistic data in an assessment of the potential carcinogenicity of the non-nutritive sweetener acesulfame K (Ace K). Based on the evaluation of more than 800 measurements/assay endpoints related to one or more key characteristics of carcinogens (KCC) reported in the literature, and via high-throughput screening data, the authors found a lack of evidence for activity across the mechanistic database. These results align with the overall lack of tumor response to Ace K in mammalian carcinogenicity studies, corroborating previous reports of a lack of carcinogenicity related to Ace K exposure. This open-access publication is the third in a series of assessments for non-nutritive sweeteners, following aspartame and sucralose, all published in Food and Chemical Toxicology.
A recently published article by ToxStrategies scientists, with Dr. Daniele Wikoff as lead author, presents the systematic identification, appraisal, and integration of mechanistic data in an assessment of potential carcinogenicity of the non-nutritive sweetener aspartame. Based on the evaluation of over 1300 measurements/assay endpoints related to one or more key characteristics of carcinogens (KCC) reported in the literature and via high-throughput screening data, the authors found a lack of evidence for activity across the mechanistic database. These results align with the overall lack of tumor response to aspartame in rodent cancer bioassays, corroborating previous reports of a lack of carcinogenicity related to aspartame exposure. The open access article can be found here: https://www.sciencedirect.com/science/article/pii/S0278691519306568
A new article from authors in the Center of Excellence for 21st Century Toxicology describes a framework to systematically and quantitatively integrate mechanistic data in assessments of potential carcinogenicity. The framework builds on the key characteristics organizational approach that is being implemented by authoritative bodies globally, by accounting for the quality and relevance of individual studies when developing weight-of-evidence conclusions regarding the activity of key characteristics. The proposed framework provides a flexible solution to quantitively integrate all available data in a systematic and transparent manner that accords greater weight to data that are best suited to the assessment of potential human carcinogenicity. The paper by Dr. Daniele Wikoff and colleagues has been accepted for publication in Toxicological Sciences and is on the 21CT website.