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Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.

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Public Health Significance

Hazardous agents often are replaced by new or existing substances due to factors such as public pressure, economic consequences, and regulatory bans. However, information about a given replacement’s potential to lead to similar or greater harm to human health than the original substance — a scenario called a regrettable substitution — is often limited or not available.

In the United States and worldwide, there have been many instances of regrettable substitutions. For example, DDT (dichlorodiphenyltrichloroethane), a pesticide banned by the Stockholm Convention due to its biological persistence, bioaccumulation, and toxicity, was replaced by organophosphate pesticides, which are associated with acute and chronic health effects.

Currently, limited emphasis is placed on developing strategies and methods that proactively evaluate potential human health effects of alternative substances.

Program Objectives

The Safe and Sustainable Alternatives (SSA) program is structured around the following three objectives:

  • Explore and establish stakeholder relationships and collaborations that identify critical gaps, opportunities, and strategies for proactive toxicological assessments of substances of public health concern.
  • Identify and qualify effective tools and approaches through case studies that establish translational utility and refine proactive strategies for evaluation of alternative substances.
  • Evaluate the relative potential for human health effects resulting from exposure to select alternative substances.

This program aims to provide quantitative, actionable information to industry, regulators, and the public in an efficient and timely manner.


Building on the NIEHS Division of Translational Toxicology’s strong reputation for advancing trusted science that informs public health decision-making, the SSA program will promote research approaches that aid the identification of safer alternatives. That will be accomplished through partnerships with scientists from industry; local, state, federal, and international governments; nongovernmental organizations; and academia.

Through computational and predictive research tools, bioactivity screening, in vitro models, and in vivo studies, the program will advance strategies to improve understanding of the potential for adverse human health effects posed by replacement substances. Communication with stakeholders will identify gaps in existing safety evaluation strategies, which will guide future efforts.

SSA program objectives intersect with those of multiple external partners, such as the U.S. Environmental Protection Agency, the European Chemicals Agency, Association for the Advancement of Alternatives Assessment, and GreenScreen. There also are many local, state, federal, and international agencies that are interested in addressing the problem of regrettable substitutions but lack the requisite expertise and resources.

In addition, the private sector, including individual corporations, industry advocacy groups, trade associations, and professional societies, seeks enhanced information on suitable alternatives. Various external groups are working in the areas of product safety and sustainability, environmental impacts, and environmental justice. The SSA program will expand collaborative efforts with these organizations and further evolve emerging methodologies.

Select Studies

Study Description Findings / Supporting Files
PFAS Multiple research studies addressing the ADME (absorption, distribution, metabolism, and excretion) and toxicity of per- and polyfluoroalkyl substances (PFAS)
  • Long- and short-chain PFAS affected the same organ systems — liver, thyroid
  • Higher doses of short-chain PFAS were needed to have similar effects on liver and thyroid hormone when compared to long-chain PFAS
  • TOX Report 96
  • TOX Report 97
AFFF PFAS Bioaccumulation Bioaccumulation of PFAS and biological responses with aqueous film-forming foams (AFFFs) using in vivo and in vitro model systems.
  • C6 fluorotelomer 6,2-FTSA extensively accumulated in rat liver and blood plasma with oral AFFF exposures
  • Some PFAS constituents within AFFFs did not appreciably accumulate in rat liver or plasma
  • Summary Report to the Department of Defense in preparation
  • Multiple manuscripts in preparation
Bisphenols Multiple research studies addressing the ADME and toxicity of bisphenol analogues
  • Literature reviews of 24 analogues
  • Tox21/ToxCast bioactivity data reveal BPA analogues to be more similar to one another than estradiol
  • ADME-toxicokinetics were similar between BPA, BPS, and BPAF
  • Maternal transfer was demonstrated with BPAF
  • Reproductive toxicity with BPAF in progress