How Should the 3 R's Be Revised and Why?

The Principles of Humane Experimental Technique established what many know today as the "3 R's"-refinement, reduction, and replacement-when it was published in 1959. Since their formulation, these principles have guided decision-making for many about nonhuman animal subjects' uses in laboratory-based research. Discussion about how to amend or replace the 3 R's is ongoing, driven mainly by philosophical ethics approaches to nonhuman animal rights and by scientific advancement. This article explores merits and drawbacks of possible updates to and interpretations of the 3 R's.

Engagement of scientists with the public and policymakers to promote alternative methods.

Scientists are usually good at teaching, sometimes even to lay audiences. But communicating with journalists, activists, or policymakers can be a different story - hesitancy to make mistakes as well as the temptation to disproportionally promote one's own case come into play. The multitude of social media and other web-based outlets has diversified and accelerated the communication of science. Real-time reactions, sharing of data, tools and results, increasing invitation of personal opinion, demand for transparency, political correctness, and loss of trust in experts are challenges to researchers in general. The field of alternatives to animal testing is more political and important to lay audiences than many others, so its scientists must be especially aware of these challenges. Public engagement offers the opportunity to form community and create wide support for non-animal research and its implementation. This requires scientists to step out of the ivory tower of higher education and engage with diverse interest groups by outreach activities, interviews, and press releases, etc. by employing tailored communication.

Establishing a communication and engagement strategy to facilitate the adoption of the adverse outcome pathways in radiation research and regulation.

BACKGROUND: Studies on human health and ecological effects of ionizing radiation are rapidly evolving as innovative technologies arise and the body of scientific knowledge grows. Structuring this information could effectively support the development of decision making tools and health risk models to complement current system of radiation protection. To this end, the adverse outcome pathway (AOP) approach is being explored as a means to consolidate the most relevant research to identify causation between exposure to a chemical or non-chemical stressor and disease or adverse effect progression. This tool is particularly important for low dose and low dose rate radiation exposures because of the latency and uncertainties in the biological responses at these exposure levels. To progress this aspect, it is essential to build a community of developers, facilitators, risk assessors (in the private sector and in government), policy-makers, and regulators who understand the strengths and weaknesses of, and how to appropriately utilize AOPs for consolidating our knowledge on the impact of low dose ionizing radiation. Through co-ordination with the Organisation of Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) High-Level Group on Low-Dose Research (HLG-LDR) and OECD's AOP Programme, initiatives are under way to demonstrate this approach in radiation research and regulation. Among these, a robust communications strategy and stakeholder engagement will be essential. It will help establish best practices for AOPs in institutional project development and aid in dissemination for more efficient and timely uptake and use of AOPs. In this regard, on June 1, 2021, the Radiation and Chemical (Rad/Chem) AOP Joint Topical Group was formed as part of the initiative from the NEA's HLG-LDR. The topical group will work to develop a communication and engagement strategy to define the target audiences, establish the clear messages and identify the delivery and engagement platforms. CONCLUSION: The incorporation of the best science and better decision making should motive the radiation protection community to develop, refine and use AOPs, recognizing that their incorporation into radiation health risk assessments is critical for public health and environmental protection in the 21st century.

An examination of radon awareness, risk communication, and radon risk reduction in a Hispanic community.

Purpose: Radiation risk communication is a critical component of radiation protection and the public's understanding of radiation risks and benefits. Risk communication becomes even more complicated when considering cultural and language differences. In the US, many diverse communities face risk communication challenges. We obtained radon testing data to evaluate patterns of radon testing in Allentown, the third largest city in Pennsylvania. Radon exposure is the second leading cause of lung cancer after smoking and is associated with over 21,000 lung cancer deaths in the US annually. It is estimated that 1 in every 15 homes in the US has elevated radon levels above the recommended action level set by the US Environmental Protection Agency. Allentown has some of the highest reported levels of indoor radon in the country, yet only a small portion of the population has tested their homes. This is true particularly among self-identified Hispanics, who make up nearly half of the city's population. This study seeks to (1) characterize the difference in testing rates between self-identified Hispanics and non-Hispanics in Allentown, (2) quantify the level of radon awareness and knowledge, (3) identify potential obstacles to radon testing among the Allentown population that self-identifies as Hispanic, and (4) determine whether more effective risk communication is needed.Method: Radon test results in Allentown were analyzed to better understand the nature of radon testing. To evaluate radon awareness and knowledge, a cross-sectional study was conducted using a face-to-face survey. This data was informative in assessing testing and mitigation practices, ethnicity, income level, age, education level, homeowner status, zip code and primary language.Results: Ethnicity was an independent predictor of radon awareness and knowledge. Statistically significant differences were found between the number of self-identified Hispanics (39%) and non-Hispanics (84%) who indicated that they had ever heard of radon; 13% of Hispanics and 49% of non-Hispanics knew that they lived in an area with typically high radon levels. There was a statistically significant association between self-reported ethnicity and radon testing with non-Hispanics (43%) more likely to test their homes for radon than Hispanics (32%).Conclusion: Individual and community understanding of the risks of exposure to radiation sources such as radon is dependent upon communication that informs and spurs appropriate action. This study demonstrates the need for culturally appropriate radon risk communication strategies targeted to a Hispanic population. Successful communication will raise awareness and knowledge that can lead to better public health protection.

Personalized Cancer Risk Assessments for Space Radiation Exposures.

Individuals differ in their susceptibility to radiogenic cancers, and there is evidence that this inter-individual susceptibility extends to HZE ion-induced carcinogenesis. Three components of individual risk: sex, age at exposure, and prior tobacco use, are already incorporated into the NASA cancer risk model used to determine safe days in space for US astronauts. Here, we examine other risk factors that could potentially be included in risk calculations. These include personal and family medical history, the presence of pre-malignant cells that could undergo malignant transformation as a consequence of radiation exposure, the results from phenotypic assays of radiosensitivity, heritable genetic polymorphisms associated with radiosensitivity, and postflight monitoring. Inclusion of these additional risk or risk reduction factors has the potential to personalize risk estimates for individual astronauts and could influence the determination of safe days in space. We consider how this type of assessment could be used and explore how the provisions of the federal Genetic Information Non-discrimination Act could impact the collection, dissemination and use of this information by NASA.

Ten Fundamental Legal Terms and Concepts That Are Useful in Understanding Laboratory Animal Law Across Nations.

Almost all researchers, veterinarians, technicians, and students who work with laboratory animals are familiar with the laws, regulations, and policies governing the use of animals in their jurisdictions. This knowledge can be learned in an academic setting, but is often gained by "on the job" training conducted by facilities and institutions where these professionals work. In addition, these laws and regulations exist along a continuum; some countries have detailed and expansive animal law regimes, while others have few, if any laws. Accordingly, those who carry out research involving animals know local laws and regulations, but might not be aware of the laws, regulations, and policies of other jurisdictions.As scientific research becomes increasingly globalized, there is a growing need to gain an understanding of the laws and regulations of other countries. This article seeks to help bridge this gap in knowledge by defining 10 fundamental legal terms and concepts that are important in understanding the similarities and differences among the legal traditions of different nations and international agreements that impact laboratory animal research. The article focuses on Western law terms and concepts, because many laboratory animal statutes that have been enacted in these countries and international treaties and protocols can be viewed through a Western legal lens.

Comparison of the Canadian and US Laws, Regulations, Policies, and Systems of Oversight for Animals in Research.

The Canadian and United States' approaches to oversight of animals in research are both based on the "3Rs" principles outlined in Russell and Burch's classic text, The Principles of Humane Experimental Technique. Each country seeks to protect the welfare of animals, while permitting the legitimate goals of scientific research to be attained according to the legal principles, cultures, and strengths and constraints of their jurisprudential and societal traditions. Canada is one of the most decentralized federations in the world, and regulation of activities is based to a great extent on custom and practice. The United States is more hierarchical and, at least with respect to laws governing animal research, more centralized. Accordingly, the Canadian approach is rooted in the concepts of social contracts, with a greater emphasis on guidance and policy and less reliance on legislation. No federal (national) direct legislation of laboratory animal welfare exists, although the federal government uses its criminal and spending authorities to shape behavior. The central feature of the Canadian system is the Canadian Council on Animal Care, which was formed to support universities and government departments involved in animal-based science. Animal care committees play a central role in implementing the guidelines and policies in facilities that carry out animal research. The United States has enacted two federal (national) laws applicable to animals in research. The Animal Welfare Act is a more traditional, command-and-control law that gives authority to the US Department of Agriculture to promulgate regulations, inspect facilities, and enforce violations. The Health Research Extension Act, which amended the US Public Health Services (PHS) Act, applies to any activity conducted or supported by the PHS, including research efforts supported by the US National Institutes of Health. It is largely nonregulatory and establishes a system of assurances and policies that covered research facilities must follow. States play only a minor role in animal research protection. As in Canada, institutional animal care and use committees are tasked with self-regulation of activities that use animals for research.

Introduction: Global Laws, Regulations, and Standards for Animals in Research.

This issue contains a collection of papers describing the state of animal laws, regulations, and standards in counties worldwide, grouped by geographic regions (i.e., North America, South America, Pacific Rim, Africa, and the Middle East). An overview of the US and Canadian legal requirements for animal welfare is provided, along with consideration of potential gaps in the US Animal Welfare Act. The EU Directive on the protection of animals used for scientific purposes and its transposition is discussed, and challenges facing laboratory animal protection regimes in Latin America and the Pacific Rim are examined. Legislation for laboratory animal use has been enacted in India and Australia, while animal protection regimes have not yet been enacted in the Middle East and Africa. International harmonization is a particularly important challenge for the global scientific community and private accreditation by organizations such as AAALAC International, plays a key role in promoting high standards for animal care and use programs globally. This article highlights three future trends. First, international efforts at harmonization will continue, and seek to keep pace with the globalization of science. Second, nations that have not yet developed robust legal systems applicable to laboratory animal welfare will seek out the expertise of those nations that have well established regimes. Third, for countries with mature animal protection systems, animal use in research will continue to be of societal concern, and efforts to change existing laws will not abate. The opportunity to use animals in laboratory research is not an entitlement. It is a privilege accorded by society to certain members of the scientific community and along with it comes the responsibility to adhere to, and seek improvement in, applicable laws, regulations, policies and standards.

Predictors of Indoor Radon Concentrations in Pennsylvania, 1989-2013.

BACKGROUND: Radon is the second-leading cause of lung cancer worldwide. Most indoor exposure occurs by diffusion of soil gas. Radon is also found in well water, natural gas, and ambient air. Pennsylvania has high indoor radon concentrations; buildings are often tested during real estate transactions, with results reported to the Department of Environmental Protection (PADEP). OBJECTIVES: We evaluated predictors of indoor radon concentrations. METHODS: Using first-floor and basement indoor radon results reported to the PADEP between 1987 and 2013, we evaluated associations of radon concentrations (natural log transformed) with geology, water source, building characteristics, season, weather, community socioeconomic status, community type, and unconventional natural gas development measures based on drilled and producing wells. RESULTS: Primary analysis included 866,735 first measurements by building, with the large majority from homes. The geologic rock layer on which the building sat was strongly associated with radon concentration (e.g., Axemann Formation, median = 365 Bq/m3, IQR = 167-679 vs. Stockton Formation, median = 93 Bq/m3, IQR = 52-178). In adjusted analysis, buildings using well water had 21% higher concentrations (ß = 0.191, 95% CI: 0.184, 0.198). Buildings in cities (vs. townships) had lower concentrations (ß = -0.323, 95% CI: -0.333, -0.314). When we included multiple tests per building, concentrations declined with repeated measurements over time. Between 2005 and 2013, 7,469 unconventional wells were drilled in Pennsylvania. Basement radon concentrations fluctuated between 1987 and 2003, but began an upward trend from 2004 to 2012 in all county categories (p < 0.001), with higher levels in counties having ≥ 100 drilled wells versus counties with none, and with highest levels in the Reading Prong. CONCLUSIONS: Geologic unit, well water, community, weather, and unconventional natural gas development were associated with indoor radon concentrations. Future studies should include direct environmental measurement of radon, as well as building features unavailable for this analysis. CITATION: Casey JA, Ogburn EL, Rasmussen SG, Irving JK, Pollak J, Locke PA, Schwartz BS. 2015. Predictors of indoor radon concentrations in Pennsylvania, 1989-2013. Environ Health Perspect 123:1130-1137; http://dx.doi.org/10.1289/ehp.1409014.

Historical trends in radiation protection, policy and communications: 1964 to the present.

The past 50 y have seen substantial developments in radiation epidemiology, technology, dosimetry, regulations, and protection efforts. During the last five decades, radiation communication has also evolved, growing more sophisticated as communication science and practice have advanced and matured. This talk covers the trends in radiation protection over the past 50 y, illustrated by progress in science and practice of risk communication and changes in societal expectations, and examines challenges that will confront radiation risk communication in the future.

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing.

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

A replacement-first approach to toxicity testing is necessary to successfully reauthorize TSCA.

The Toxic Substances Control Act is the principal US law governing industrial chemicals. Over the past three and one half decades, it has become clear that a considerable toxicological information gap exists about chemicals in commerce. The current provisions of the US TSCA law have failed to fill, and perhaps even exacerbated, that gap. For at least the past 5 years, bills have been introduced before the US Congress to reauthorize TSCA.Filling the toxicological information gap has been one of the driving forces for this call for substantial change. This article describes efforts to modernize TSCA, with an emphasis on the new provisions that would be put into place if the legislation became law. The article shows that only by implementing a "replacement-first" strategy - a strategy that is not currently incorporated into TSCA reauthorization efforts - can TSCA modernization efforts potentially fill the toxic data voids.

Communication of radiation benefits and risks in decision making: some lessons learned.

This paper is focused on summarizing the "lessons learned" from discussions at the 2010 NCRP Annual Meeting on effective communications on the subject of radiation benefits and risks in public exposures. Five main lessons learned are discussed in regard to effective methods of public communication: the use of new social media communication tools such as Facebook and Twitter, emergency situations that require rapid societal and personal messaging, medical radiological procedures where benefits must be described in comparison to long-term health risks of radiation exposures, and information that should be provided to stakeholders in situations such as environmental radionuclide contamination to which members of the public may be exposed. It is concluded that effective communications in which radiation benefits are contrasted with health risks of exposure are an important aspect of making and implementing decisions on employing radiation health protection procedures.

Diagnostic radiation exposure in pediatric trauma patients.

BACKGROUND: The amount of imaging studies performed for disease diagnosis has been rapidly increasing. We examined the amount of radiation exposure that pediatric trauma patients receive because they are an at-risk population. Our hypothesis was that pediatric trauma patients are exposed to high levels of radiation during a single hospital visit. METHODS: Retrospective review of children who presented to Johns Hopkins Pediatric Trauma Center from July 1, 2004, to June 30, 2005. Radiographic studies were recorded for each patient and doses were calculated to give a total effective dose of radiation. All radiographic studies that each child received during evaluation, including any associated hospital admission, were included. RESULTS: A total of 945 children were evaluated during the study year. A total of 719 children were included in the analysis. Mean age was 7.8 (±4.6) years. Four thousand six hundred three radiographic studies were performed; 1,457 were computed tomography (CT) studies (31.7%). Average radiation dose was 12.8 (±12) mSv. We found that while CT accounted for only 31.7% of the radiologic studies performed, it accounted for 91% of the total radiation dose. Mean dose for admitted children was 17.9 (±13.8) mSv. Mean dose for discharged children was 8.4 (±7.8) mSv (p<0.0001). Burn injuries had the lowest radiation dose [1.2 (±2.6) mSv], whereas motor vehicle collision victims had the highest dose [18.8 (±14.7) mSv]. CONCLUSION: When the use of radiologic imaging is considered essential, cumulative radiation exposure can be high. In young children with relatively long life spans, the benefit of each imaging study and the cumulative radiation dose should be weighed against the long-term risks of increased exposure.