Author Archives: ricknelson

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.

Thompson CM, Fitch SE, Ring C, Rish W, Cullen JM, Haws LC. 2019. Development of an oral reference dose for the perfluorinated compound GenX. J Appl Toxicol 39:1267–1282.

Oral reference dose for GenX from Research Square on Vimeo.

On August 1, 2019, the U.S. EPA announced a new website where visitors can view and search monthly updates for any active Premanufacture Notices (PMNs), Significant New Use Notices (SNUNs), and Microbial Commercial Activity Notice (MCANs) that may be of interest (searchable by case number). The site is named, “Statistics for the New Chemicals Review Program under TSCA.” Users can download a spreadsheet with a list of all active cases and the current status of each. Any information on a substance that a submitter designates as Confidential Business Information (CBI) remains confidential.

ToxStrategies has announced an opening for a Scientist III or Senior Scientist. Specifically, the firm seeks a toxicologist (or similar discipline) with experience conducting systematic reviews to join our expanding Health Science consulting practice. The position involves application of these approaches to hazard- and risk-based evaluations of foods, chemicals, and consumer products. The successful candidate will have a working knowledge of systematic review concepts, as well as expertise in systematic review tools such as DistillerSR. This includes experience developing protocols, conducting literature searches, screening evidence, and appraising studies using risk-of-bias techniques. Mastery of narrative synthesis and data visualization is preferred. Please check here for additional details and needed qualifications.

Ms. Seneca Fitch, ToxStrategies scientist, has been invited by the Evidence-Based Toxicology Collaboration (EBTC) Board of Trustees at Johns Hopkins Bloomberg School of Public Health to join the Scientific Advisory Council. In this role, she will serve a 3-year term in addition to her ongoing involvement within the organization’s Tox21 working group. The EBTC SAC is an international group of scientists from a variety of organizations, including government agencies, NGOs, industry, and academia. Members provide expertise in evidence-based methods, participating in EBTC projects and advising the EBTC Board and Director on new areas of research and other issues relevant to the toxicology community.

On March 20, 2019, the EPA released lists of the next 20 high-priority and 20 low-priority existing chemicals that are candidates for TSCA risk evaluations. The Agency released this list to provide the public an opportunity to submit relevant information over the next 90 days, such as the uses, hazards, and exposure for these chemicals. Publication also activates a statutory requirement for EPA to complete the prioritization process in the next 9 to 12 months, allowing EPA to designate 20 chemicals as high priority and 20 chemicals as low priority by December 2019. According to EPA and TSCA, when prioritization is complete, chemicals designated as high priority will begin a 3-year risk evaluation process to determine whether each chemical, under the conditions of use, presents an unreasonable risk to human health and the environment. The designation of a chemical as a low priority means that further risk evaluation is not warranted at this time.

Based on our review, it appears that all 20 high-priority chemicals are from the 2014 Update of the TSCA Work Plan. TSCA requires that at least 50 percent of all high-priority chemicals be from the Work Plan. For this round, EPA has used 100 percent from the Work Plan list. The low-priority chemicals all are from EPA’s Safer Chemicals Ingredients List (SCIL).

TSCA also requires that EPA give preference to Work Plan chemicals with the following characteristics:

• Persistence and bioaccumulation scores of three
• Known human carcinogens
• High acute or chronic toxicity

ToxStrategies has examined the TSCA Work Plan and has the following observations:

• None of the selected high-priority chemicals have persistence and bioaccumulation scores of three. In fact, eight of the 20 candidates have persistence and bioaccumulation scores of one, particularly the phthalates, which are selected based on aquatic toxicity but have low persistence and low bioaccumulation potential.
• None of the selected high-priority chemicals are from the seven substances that scored 3 on all three criteria (hazard, exposure, persistence/bioaccumulation) and remain in the TSCA Work Plan after eliminating the first 10 already being evaluated. This includes four metals; no metals have been selected to date.
• TSCA Work Plan scores for the 20 high-priority candidates are summarized below.

ToxStrategies’ scientists continue to develop innovative solutions to address some of the most challenging scientific issues that face our clients.  Several recent examples of such projects were presented at the Society of Toxicology 58th Annual Meeting. The SOT 2019 conference was held in Baltimore, MD (March 10–14, 2019). To see a list of our presentations, click here,  and if you would like to receive a copy of one, please contact us.

On February 14, EPA released its first-ever comprehensive nationwide Per- and Polyfluoralkyl Substances (PFAS) Action Plan. The plan is the result of a cross-agency effort and is focused predominantly on protecting the nation’s drinking water. The PFAS Action Plan includes numerous aspects that may have both immediate and long-term effects on regulated parties:

• EPA will work toward establishment of Maximum Contaminant Levels (MCLs) under the Safe Drinking Water Act, potentially complicating the regulatory landscape with additional standards.
• EPA could list two of the most studied PFAS (PFOA and PFOS) as hazardous substances under CERCLA, giving the Agency the ability to impose remediation requirements.
• Additional substances will need to be monitored and controlled through new Effluent Limitation Guidelines (ELGs) under the Clean Water Act.
• EPA plans to develop new analytical methods to detect additional PFAS among the thousands of possible compounds. New toxicity factors and analytical requirements may lead to regulation of PFAS by groups or using toxicity equivalency factors.
• Public awareness of the global presence of PFAS in the environment, people, and animals will require creative approaches to risk communication and could invite public action and litigation.

Priority implications of the Action Plan are discussed in greater detail here. Our scientists and engineers stand ready to help clients as the PFAS regulatory landscape unfolds.