A team of ToxStrategies 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 The authors assert that regulatory lung cancer potency estimates for Cr(VI) are based on outdated research, whereas more current mechanistic data support an epigenetic role for Cr(VI) and a non-mutagenic mode of action.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 have developed a range of plausible toxicity values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on application of systematic review methods and quantitative integration of dose response using meta-regression. This research is being published in the journal Toxicological Sciences and will advance risk assessments involving this class of compounds, providing important information to guide risk-based decision-making.
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 Dr. Grace Chappell, Dr. Susan Borghoff, and Dr. Janice Britt presents the evaluation of mechanistic data in an assessment of potential neurobehavioral effects for the seven synthetic colors that are approved for use in food by the US FDA. The assessment was specific to in vitro and other new approach methods (NAMs). A systematic identification of molecular events potentially related to neuro-relevant processes and outcomes was conducted to enable mapping of high-throughput screening (HTS) assays from the ToxCast/Tox21 database to such molecular events and/or related genes. Based on the mapping, neuro-relevant HTS data for seven FDA-approved synthetic food colors were evaluated, as well as neuro-relevant NAMs data for the colors identified in published literature. The findings support an overall lack of neuro-related activity associated with the seven food colors, with the exception of neurotransmitter signaling by erythrosine. The open-access article was published in Food and Chemical Toxicology.
EpidStrategies epidemiologists Dr. Jon Fryzek and Ms. Lauren Bylsma will present a poster at the “Rare Diseases and Orphan Products Breakthrough Summit,” to be convened October 21st and 22nd in Washington, D.C., by the National Organization for Rare Disorders (NORD). Their poster is titled, “Cohort Study of High Frequency Basal Cell Carcinoma (BCC) Patients in Denmark.”
The rare-disease summit is an opportunity for EpidStrategies to offer its broad expertise in rare-disease epidemiology, including calculation of incidence and prevalence and assembly of rare-disease cohorts for natural history studies, treatment characterization, and evaluation of health-care resource use. As NORD states, “…The Time is Now to prioritize action in making positive changes for the millions of Americans living with rare diseases.”
ToxStrategies was excited to exhibit, for the first time, at Supply Side West (SSW) on October 17 and 18, in Las Vegas. According to the trade association Food ingredients North America, more than 17,000 ingredient buyers and suppliers from the dietary supplement, food, beverage, personal care, and sports nutrition industries attended SSW to learn about new trends and science from over 1,300 exhibitors and 140 hours of educational and conference programming.
ToxStrategies has a reputation for applying sound science and innovative solutions, and we work in the areas of hazard identification, risk assessment, GRAS evaluations, dietary supplements, FSMA , and label compliance for both human food and animal feed. Our highly experienced, multidisciplinary team helps clients ensure the use of safe and regulation-compliant ingredients.
ToxStrategies scientists have published an article proposing an oral reference dose (RfD) for the per‐ and polyfluoroalkyl substance (PFAS) commonly known to as GenX. The new proposed value differs from those put forth by many regulatory agencies. The assessment relies on mechanistic data to show that many of the effects observed in rodents involve PPARa, which is well recognized to exhibit differential responses in rodents and humans. Using updated histopathological nomenclature, liver effects in mice that were previously scored as necrosis were more accurately scored as apoptosis (i.e., programmed cell death)—which is consistent with involvement of PPARa. With this new insight, the ToxStrategies assessment evaluates and synthesizes the available toxicity data for GenX and uses frequentists and Bayesian benchmark dose (BMD) modeling methods to derive both deterministic and probabilistic RfD values that are protective of noncancer effects. The open-access article appears in the Journal of Applied Toxicology. A video abstract of this article (produced by Research Square) can be found here.
Scientists from EpidStrategies, a Division of ToxStrategies, will attend and present at the 35th International Conference on Pharmacoepidemiology & Therapeutic Risk Management (ICPE). The meeting will be held on August 24–28, 2019, in Philadelphia, with a theme of “Using Real World Data and Designs to Optimize Decisions.” EpidStrategies scientists have collaborated to create five posters that will showcase recent work on Klebsiella pneumoniae, algorithms to identify specific heart-failure patients, meta-analyses related to metastatic colorectal cancer, and rare-disease epidemiology using the Danish databases.
The authors and poster titles are listed below, and copies of posters will be available on request after the conference.
Naimisha Movva and Dr. Jon Fryzek
Hospitalizations due to Klebsiella pneumoniae Pneumonia in the United States
Lauren Bylsma and Dr. Jon Fryzek
The Incidence of Infusion Reactions Associated with Monoclonal Antibody Drugs Targeting the Epidermal Growth Factor Receptor in Metastatic Colorectal Cancer Patients: A Systematic Literature Review and MetaSp-analysis
Lauren Bylsma and Dr. Jon Fryzek
Prevalence of Kras, Nras, and Braf Gene Mutations in Metastatic Colorectal Cancer (mCRC) Patients: A Systematic Literature Review
This poster has the honor of being selected for a Spotlight Session for the Special Interest Group (SIG) Molecular Epi, Biomarkers, and Pharmocogenetics