Poster for ACT discusses direct-to-brain pharmaceutical administration

ToxStrategies/21CT scientists are among the authors of a poster for the Annual Meeting of the American College of Toxicology, to be held virtually on November 10 through 19, 2021. The poster (by Amy Kimzey, Brian Welsh, and Marcie Wood) discusses the process of deriving exposure-based limits for impurities that might be encountered in pharmaceuticals for direct-to-brain administration and presents relevant case studies. The poster reviews three case studies—a salt, an alcohol, and an endogenous molecule—that exemplify the challenges of determining a limit for direct-to-brain administration routes.  Dr. Kimzey will be available live on Monday, November 15 from 3:30 to 5:30 EST for a Q&A regarding their findings.

 

New publication allays manufacturers’ concerns over ochratoxin A in coffee

 

A new article by ToxStrategies authors (available from the Journal of Food Science online ahead of print) looks at the potential for the naturally occurring mycotoxin ochratoxin A (OTA) in coffee to produce adverse effects in consumers through the lens of a food safety plan. The Food Safety Modernization Act (FSMA) names OTA among the listed chemical hazards that should be considered as part of a food safety plan, and animal studies have shown kidney toxicity, in particular, to rodents given high doses of it. The study by Melissa Heintz, Candace Doepker, Daniele Wikoff, and Scott Hawks is intended to assist food manufacturers by documenting best current practices to mitigate OTA in the context of its potential presence in coffee products, as well as the possible associated risk. Studying the peer-reviewed literature, food recall databases, and authoritative reviews, the researchers concluded that good agricultural practices and historical precedent indicate that no additional preventive controls are warranted for U.S. coffee manufacturers, based on low severity and likelihood of risk.

Dr. McMillan to present at Science Symposium

Dr. McMillan to present at science symposium

ToxStrategies Senior Consultant Dr. Donna McMillan will be among a distinguished panel of speakers in a Virtual Science Symposium sponsored by the Personal Care Products Council. The symposium will focus on “Current Issues in Safety Assessment,” and Dr. McMillan will draw on her 30 years of industry experience with safety evaluations of consumer products. Her work in safety assessment of botanical and natural substances (BNS) will inform her segment on BNS safety in consumer products.

The symposium takes place on October 26–27, 2021, and information and registration are available on the Council’s website.

 

Federal court upholds legality of GRAS self-determinations

The U.S. FDA and the food industry shared a victory as a federal judge dismissed a suit seeking to find unlawful the process by which companies have been allowed to determine, without notification to FDA, that a food or supplement ingredient is Generally Recognized as Safe (GRAS). Such self-determinations, in use for more than six decades, can exempt substances from pre-market review by FDA and had drawn the ire of (and a lawsuit from) the Center for Science in the Public Interest and the Environmental Working Group. Among other complaints, the lawsuit claimed that self-GRAS evaluations unlawfully subdelegate FDA’s duty to ensure food safety, exceed the FDA’s statutory authority, and violate the Federal Food, Drug, and Cosmetics Act. The decision by Judge Vernon Broderick, of the Southern District Court of New York, effectively ends the litigation (although further appeal is possible), leaving the self-GRAS regulatory framework in place.

ToxStrategies to Chair and Present at SETAC Session on Environmental Justice

The Society of Environmental Toxicology and Chemistry (SETAC) will have its SETAC North America 42nd Annual Meeting (also known as SciCon4) this year on November 14–18. Dr. Bill Rish of ToxStrategies will chair a session titled “Environmental Justice: Methodologies to Incorporate Environmental Justice into Human Health Risk Assessment.” The conference will be virtual, and the session presentations will be available on demand. In addition to chairing the session, two of the nine presentations will be given by ToxStrategies scientists, including:

Dr. LeeAnn Racz  

Exposure Monitoring Toward Environmental Justice

Dr. Bill Rish and Ms. Ann Verwiel

Quantitative Methods for Environmental Justice in Human Risk Assessment: An Overview

Other topics include:

  • EPA’s new guidelines for cumulative risk assessment (CRA), presented by Lawrence Martin, EPA’s leader of CRA guideline development
  • Epidemiology data and methods for vulnerable groups
  • Vulnerable group-specific exposure factors
  • Minnesota’s cumulative air pollution risk model to investigate Environmental Justice
  • Contribution to vulnerability from climate change, extreme events, and water access
  • Incorporating Environmental Justice issues into environmental research needs

Dr. Rish and Ms. Verwiel will also moderate two 50-minute live sessions Tuesday, November 16th starting at 9:30 am PST, wherein session speakers will discuss four key questions:

  1. How can non-chemical stressors, subpopulation susceptibilities and vulnerabilities, and chemical exposures be combined in a quantitative risk assessment? Or can they?
  2. Can quantitative metrics and measures be developed to help decision makers determine whether risks are equitable and acceptable?
  3. Given past environmental justice shortcomings, what is the appropriate role for quantitative risk assessment in making environmental decisions such as siting, discharge limits, air and water quality standards, or regional planning/prioritization?
  4. What are the priority data and research needed to improve the use of risk assessment and epidemiology to support equitable environmental decision making?

 

Workshop suggests journal editors can influence the quality of published systematic reviews

With the increasing prevalence of systematic reviews in toxicology and environmental research, a team of prominent scientists in the field convened a workshop to address the issue of ensuring scientific quality and integrity in this body of study. Dr. Daniele Wikoff, of ToxStrategies, was a member of this team, helping to apply the principles and methods of systematic review to the review process itself. The team proposed 58 editorial interventions, of which 26 were assessed as “potentially effective.” Of that group, five actions were highlighted as relatively easy for editors to implement in the effort to improve the quality of systematic reviews. The study was published in ALTEX, a journal focusing on alternatives to animal experimentation.

Radiation Risks in Space, the Final Frontier

           

Plans for a return to the Moon in 2024 and manned exploration of Mars, as well as a burgeoning commercial space tourism movement, have renewed concern about human exposure to radiation in space. There are several sources of space radiation[1]:

  • Radiation belts caused by Earth’s magnetic field (i.e., the inner “Van Allen” radiation belt and the outer radiation belt
  • Galactic cosmic radiation
  • Sporadic solar particle events, when particles emitted by the sun become accelerated and shoot into space
  • “Trapped radiation” resulting from interactions between space radiation and planetary or lunar soil.

On Earth, we are protected from space radiation by the Earth’s magnetic fields and atmosphere. Routine space tourism flights will be into low earth orbit, which, while higher in radiation exposures than on the Earth, will receive protection from the Earth’s magnetosphere.

However, space radiation is different from the kinds of radiation we experience here on Earth. Radiation exposure is one of the major concerns for astronaut health. According to the National Aeronautics and Space Administration (NASA), “Space radiation is comprised of atoms in which electrons have been stripped away as the atom accelerated in interstellar space to speeds approaching the speed of light – eventually, only the nucleus of the atom remains. Beyond Low Earth Orbit, space radiation may place astronauts at significant risk for radiation sickness, and increased lifetime risk for cancer, central nervous system effects, and degenerative diseases.”[2]

When the next astronaut to reach the moon walks on the lunar surface in 2024, they will experience a radiation dose of approximately 140 millirem/day from galactic cosmic radiation and neutrons emanating from irradiated lunar soil. This is 100 to 200 times higher than the natural background radiation dose they would receive on Earth (about 300 millirem/year). According to NASA, astronauts can be exposed to radiation doses in the range of 5,000 to 200,000 millirem at times—for example, during a solar particle event. That is the equivalent of 150 to 6,000 chest x-rays.[3]

There are large uncertainties and data gaps in attempting to predict potential health impacts from potential space radiation exposures incurred by space travelers. Few to no epidemiological data on cancer incidence or mortality exist for the space radiation environment. Data from the manned lunar landings to date, from which space radiation exposure was short-term given the flight plans, do not provide a sufficient basis for predicting human health effects of radiation exposures that occur beyond low earth orbit. Neither do any human circumstances exist that are analogous to galactic cosmic radiation exposure. Recommendations from the National Council on Radiation Protection & Measurements (NCRP) for an acceptable level of space radiation exposure are extrapolated from observations of Hiroshima atomic bomb survivors, those who have undergone radiation therapy for cancer or for medical diagnosis, and nuclear facility workers who had intake of radionuclides that exposed brain tissue. These populations received radiation exposures that differ from the chronic, low-level cosmic radiation exposure (interspersed with random acute solar particle event exposures) that will occur in space.

Attempts have been made to predict health impacts from galactic cosmic radiation at various dose levels, using extrapolation from low-linear-energy-transfer epidemiology studies.[4] Epidemiologic studies have been conducted in astronauts and pilots who spend prolonged times at high altitudes, but these studies are insufficient to assess space radiation exposures beyond low earth orbit.[5]

As we move forward with space travel, data specific to the space-flight environment will be compiled to support health risk predictions and develop protection strategies. EpidStrategies and ToxStrategies scientists will continue to be involved in this important new frontier of health risk assessment. More information about ToxStrategies’ and EpidStrategies’ range of capabilities in all types of radiation risk assessment here.

 

 

[1] FAQ (nasa.gov)
[2] Why Space Radiation Matters | NASA
[3] ibid
[4] Cucinotta et al., 2001
[5] Peterson LE, Pepper LJ, Hamm PB, Gilbert SL. Longitudinal study of astronaut health: mortality in the years 1959-1991. Radiat Res. 1993;133:257-264.; Hamm PB, et al. Risk of cancer mortality among the Longitudinal Study of Astronaut Health (LSAH) participants. Aviat, Space Environ Med. 1998;69:142-144.; Gundestrup M, Storm HH. Radiation-induced acute myeloid leukemia and other cancers in commercial jet cockpit crew: a population-based cohort study. Lancet. 1999;354:2029-2031.; Mason TJ, Miller RW. Cosmic radiation at high altitudes and U.S. cancer mortality, 1950-1969. Radiat Res. 1974;60:302-306.

EPA announces important policy changes surrounding risk evaluations completed for the first 10 chemicals

On June 30, 2021, the U.S. Environmental Protection Agency (EPA) announced important policy changes surrounding risk evaluations issued under the Toxic Substances Control Act (TSCA) by the previous administration and the path forward for the first 10 chemicals that have already undergone risk evaluations.  These changes include:  1) expanding consideration of exposure pathways and fenceline community exposure screening level approach; 2) revisiting the assumption that PPE is always used in occupational settings when making risk determinations for a chemical; and 3) revisiting the assessments to make the determination of unreasonable risk just once for the whole chemical when it is clear the majority of the conditions of use warrant one determination.

The first 10 risk evaluations did not assess air, water or disposal exposures to the general population because these exposure pathways were already regulated, or could be regulated, under other EPA-administered statutes such as the Clean Air Act, Safe Drinking Water Act, or Clean Water Act. They also did not evaluate certain subpopulations, such as disadvantaged and fenceline communities,  that could see higher exposures or be more susceptible. Based on these considerations, reconsidering PPE assumptions, and the whole chemical approach, EPA will revisit and possibly revise some of these 10 risk evaluations.

The EPA announcement can be reviewed in its entirety at: EPA Announces Path Forward for TSCA Chemical Risk Evaluations

More information on TSCA risk evaluations can be found here.