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Abstract: This paper presents newly discovered evidence from the personal correspondence of four US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) Genetics Panelists that their 1956 report to the public was written by a third party and was neither reviewed nor approved by the Panel prior to its publication and release to the public. The letters revealed that the 1956 Report contained serious errors and did not represent the views of the Panel. The failure of the US NAS to notify the public that the Report had not been reviewed and approved by the Panel represents a serious breach of ethics. Further ethical issues relate to the failure of the NAS to (1) correct the errors in the Report within an appropriately timely manner and (2) reveal the lack of approval by the Panel even after the Report's release. In light of these discoveries and the profound historical-and continuing-significance of the 1956 Report to all conventional cancer-related risk assessment processes, we opine that this ethical improbity must be acknowledged and that this document must be retracted by the NAS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Health Physics Society.)

Ethylene oxide is a highly reactive chemical primarily used as an intermediate in chemical production and as a sterilant of medical equipment and food products; it also is produced endogenously as a result of physiological processes. We conducted a systematic review of the potential carcinogenicity of inhaled ethylene oxide in humans using methods that adhere to PRIMSA guidelines and that incorporate aspects from the Institute of Medicine (IOM) (now the National Academy of Medicine) as well as several US Environmental Protection Agency (EPA) frameworks for systematic reviews. After a comprehensive literature search and selection process, study quality was evaluated following a method adapted from the EPA Toxic Substances Control Act (TSCA) framework. The literature screening and selection process identified 24 primary studies in animals or humans and more than 50 mechanistic studies. Integrating epidemiological, animal, and mechanistic literature on ethylene oxide and cancer according to the IOM framework yielded classifications of suggestive evidence of no association between ethylene oxide and stomach cancer, breast cancer and lymphohematopoietic malignancies at human relevant exposures. However, we acknowledge that there is additional uncertainty in the classification for lymphohematopoietic malignancies owing to a paucity of evidence for specific types of these tumors, each of which is a distinct disease entity of possibly unique etiology., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

With a rule published on 6 January 2021, the US Environmental Protection Agency (EPA) considers for the first time sub-threshold responses, abandoning the use of default dose-response models. This may affect worldwide scientific research, in terms of research design and methodology, and regulatory actions in China and other countries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This paper evaluates the scientific basis for the adoption of the linear non-threshold (LNT) dose response model for radiation-induced leukemia. This LNT risk assessment application for leukemia is significant because it: (1) was generalized for all tumor types induced by ionizing radiation and chemical carcinogens at relatively high doses and; (2) it was based on the mechanistic assumption of low dose linearity for somatic cell mutations as determined from responses in mature spermatozoa of fruit flies. A serious problem with the latter assumption is that those spermatozoa lack DNA repair. The acceptance of the LNT dose response model for cancer risk assessment was based on the convergence of recommendations of the BEAR I Genetics Panel (1956a) for reproductive cell gene mutations and those of Lewis (1957a) for somatic cell mutation and its capacity to explain apparent and/or predicted linear dose responses of ionizing radiation-induced leukemia in multiple and diverse epidemiological investigations. Use of that model and related dose response beliefs achieved rapid, widespread and enduring acceptance in the scientific and regulatory communities. They provide the key historical foundation for the sustained LNT-based policy for cancer risk assessment to the present. While previous papers in this series have challenged key scientific assessments and ethical foundations of the BEAR I Genetics Panel, the present paper provides evidence that Lewis: 1) incorrectly interpreted the fundamental scientific studies used to support the LNT conclusion even though such studies show consistent hormetic-J-shaped dose response relationships for leukemia in Hiroshima and Nagasaki survivors; and, 2) demonstrated widespread bias in support of an LNT conclusion and related policies, which kept him from making an objective and fair assessment. The LNT recommendation appears to have been uncritically accepted and integrated into scientific and regulatory practice in large part because it inappropriately appealed to existing authority and it garnered the support of those who were willing to risk greatly exaggerating the public's fears of environmentally-induced disease, such as enhanced risk of leukemia, with the goal of stopping the atmospheric testing of atomic bombs. Adoption of the LNT recommendation demonstrated extensive penetration of ideological influence affecting governmental, scientific and regulatory evaluation at the highest levels in the United States. This paper demonstrates that the scientific foundations for cancer risk assessment were inappropriately and inaccurately assessed, unethically adopted and require significant historical, scientific and regulatory remediation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This paper demonstrates that unethical conduct by the US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel led to their recommendation of the Linear Non-Threshold (LNT) Model for radiation risk assessment and its subsequent adoption by the US and the world community. The analysis, which is based largely on preserved communications of the US NAS Genetics Panel members, reveals that Panel members and their administrative leadership at the NAS displayed an integrated series of unethical actions designed to ensure, (1) the acceptance of the LNT and (2) funding to radiation geneticist panel members and professional colleagues. These findings are significant because major public policies in open democracies, such as cancer risk assessment and other issues impacted by public fears of radiation or chemical exposures, require ethical foundations. Recognition of these ethical failures of the BEAR I Genetics Panel should require a high level administrative, legislative and scientific reassessment of the scientific foundations of cancer risk assessment, with the likely result necessitating revision of current policies and practices. The BEAR I Genetics Panel, 1956 Science journal publication should immediately be retracted because it contains deliberate misrepresentations of the scientific record that were designed to manipulate scientific and public opinion on radiation risk assessment in a dishonest manner., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The National Academy of Sciences (NAS) Atomic Bomb Casualty Commission (ABCC) human genetic study (i.e., The Neel and Schull, 1956a report) showed an absence of genetic damage in offspring of atomic bomb survivors in support of a threshold model, but was not considered for evaluation by the NAS Biological Effects of Atomic Radiation (BEAR) I Genetics Panel. The study therefore could not impact the Panel's decision to recommend the linear non-threshold (LNT) dose-response model for risk assessment. Summaries and transcripts of the Panel meetings failed to reveal an evaluation of this study, despite its human relevance and ready availability, relying instead on data from Drosophila and mice. This paper explores correspondence among and between BEAR Genetics Panel members, including James Néel, the study director, and other contemporaries to assess why the Panel failed to use these data and how the decision to recommend the LNT model affected future cancer risk assessment policies and practices. This failure of the Genetics Panel was due to: (1) a strongly unified belief in the LNT model among panel members and their refusal to acknowledge that a low dose of radiation could exhibit a threshold, a conclusion that the Néel/Schull atomicbomb study could support, and (2) an excessive degree of self-interest among panel members who experimented with animal models, such as Hermann J. Muller, and feared that human genetic studies would expose the limitations of extrapolating from animal (especially Drosophila) to human responses and would strongly shift research investments/academic grants from animal to human studies. Thus, the failure to consider the Néel/Schull atomic bomb study served both the purposes of preserving the LNT policy goal and ensuring the continued dominance of Muller and his similarly research-oriented colleagues., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The linear non-threshold (LNT) dose response model for cancer risk assessment has been a controversial concept since its initial proposal during the 1930s. It was long advocated by the radiation genetics community in the 1950s, some two decades prior to being generally adopted within the chemical toxicology community. This paper explores possible reasons for such major differences in the acceptance of LNT for cancer risk assessment by these two key groups of scientists., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This paper provides an historical assessment of how the linear non-threshold (LNT) model became adopted as policy by the United States Environmental Protection Agency (US EPA) in 1975 [1] and how prior United States National Academy of Sciences (US NAS) radiation advisory panels may have affected this EPA decision. The paper highlights a generally unrecognized set of recommendations of the 1960 Biological Effect of Atomic Radiation [2] Genetics and Medical/Pathology Panels that did not support LNT for cancer risk assessment due to their judgements of its scientific limitations and unacceptable uncertainties. These convergent, independent and high profile recommendations were not promoted by the sponsors (i.e., Rockefeller Foundation and the NAS), and were ignored by the media, Congress and the scientific community in contrast to the vast attention directed to the linearity recommendation for germ cell mutation by the BEAR Genetics Panel in 1956 [3,4]. The subsequent Biological Effects of Ionizing Radiation (BEIR) I Committee (1972) [5] report ignored these BEAR Panel (1960) [2] recommendations, only commenting on the BEAR 1956 linearity supporting recommendation [3,4]. These actions are documented and assessed for how they influenced why and how EPA adopted linearity for cancer risk assessment based on the BEIR I report., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The United States Environmental Protection Agency (US EPA) has recently proposed changes to strengthen the transparency of its pivotal regulatory science policy and procedures. In this context, the US EPA aims to enhance the transparency of dose-response data and models, proposing to consider for the first time non-linear biphasic dose-response models. While the proposed changes have the potential to lead to markedly improved ecological risk assessment compared to past and current approaches, we believe there remain open issues for improving the quality of ecological risk assessment, such as the consideration of adaptive, dynamic and interactive effects. Improved risk assessment including adaptive and dynamic non-linear models (beyond classic threshold models) can enhance the quality of regulatory decisions and the protection of ecological health. We suggest that other countries consider adopting a similar scientific-regulatory posture with respect to dose-response modeling via the inclusion of non-linear biphasic models, that incorporate the dynamic potential of biological systems to adapt (i.e., enhancing positive biological endpoints) or maladapt to low levels of stressor agents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The assumption that chemical and radiation induced cancers act in a manner that is additive to background was proposed in the mid-1970s. It was adopted by the U.S. Environmental Protection Agency (EPA) in 1986 and then subsequently by other regulatory agencies worldwide for cancer risk assessment. It ensured that cancer risks at low doses act in a linear fashion. The additive to background process assumes that the mechanism(s) resulting in induced (i.e., treatment related) and spontaneous (i.e., control group) cancers are identical. This assumption could not be properly evaluated due to inadequate mechanistic data when it was proposed in the 1970s. Using the findings of modern molecular toxicology, including oncogene activation/mutation, gene regulation, and molecular pathway analyses, the additive to background assumption was evaluated in the present paper. Based on published studies with 45 carcinogens over 13 diverse mammalian models and for a broad range of tumor types compelling evidence indicates that carcinogen-induced tumors are mediated in general via mechanisms that are not identical to those affecting the occurrence of the same type of spontaneous tumors in appropriate control groups. These findings, which challenge a fundamental assumption of the additive to background concept, have significant implications for cancer risk assessment policy, regulatory agency practices, as well as fundamental concepts of cancer biology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This paper summarizes the historical and scientific foundations of the Linear No-Threshold (LNT) cancer risk assessment model. The story of cancer risk assessment is an extraordinary one as it was based on an initial incorrect gene mutation interpretation of Muller, the application of this incorrect assumption in the derivation of the LNT single-hit model, and a series of actions by leading radiation geneticists during the 1946-1956 period, including a National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel (Anonymous, 1956), to sustain the LNT belief via a series of deliberate obfuscations, deceptions and misrepresentations that provided the basis of modern cancer risk assessment policy and practices. The reaffirming of the LNT model by a subsequent and highly influential NAS Biological Effects of Ionizing Radiation (BEIR) I Committee (NAS/NRC, 1972) using mouse data has now been found to be inappropriate based on the discovery of a significant documented error in the historical control group that led to incorrect estimations of risk in the low dose zone. Correction of this error by the original scientists and the application of the adjusted/corrected data back to the BEIR I (NAS/NRC, 1972) report indicates that the data would have supported a threshold rather than the LNT model. Thus, cancer risk assessment has a poorly appreciated, complex and seriously flawed history that has undermined policies and practices of regulatory agencies in the U.S. and worldwide to the present time., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This paper is an historical assessment of how prominent radiation geneticists in the United States during the 1940s and 1950s successfully worked to build acceptance for the linear no-threshold (LNT) dose-response model in risk assessment, significantly impacting environmental, occupational and medical exposure standards and practices to the present time. Detailed documentation indicates that actions taken in support of this policy revolution were ideologically driven and deliberately and deceptively misleading; that scientific records were artfully misrepresented; and that people and organizations in positions of public trust failed to perform the duties expected of them. Key activities are described and the roles of specific individuals are documented. These actions culminated in a 1956 report by a Genetics Panel of the U.S. National Academy of Sciences (NAS) on Biological Effects of Atomic Radiation (BEAR). In this report the Genetics Panel recommended that a linear dose response model be adopted for the purpose of risk assessment, a recommendation that was rapidly and widely promulgated. The paper argues that current international cancer risk assessment policies are based on fraudulent actions of the U.S. NAS BEAR I Committee, Genetics Panel and on the uncritical, unquestioning and blind-faith acceptance by regulatory agencies and the scientific community., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The NAS Genetics Panel (1956) recommended a switch from a threshold to a linear dose response for radiation risk assessment. To support this recommendation, geneticists on the panel provided individual estimates of the number of children in subsequent generations (one to ten) that would be adversely affected due to transgenerational reproductive cell mutations. It was hoped that there would be close agreement among the individual risk estimates. However, extremely large ranges of variability and uncertainty characterized the wildly divergent expert estimates. The panel members believed that sharing these estimates with the scientific community and general public would strongly undercut their linearity recommendation, as it would have only highlighted their own substantial uncertainties. Essentially, their technical report in the journal Science omitted and misrepresented key adverse reproductive findings in an effort to ensure support for their linearity recommendation. These omissions and misrepresentations not only belie the notion of an impartial and independent appraisal by the NAS Panel, but also amount to falsification and fabrication of the research record at the highest possible level, leading ultimately to the adoption of LNT by governments worldwide. Based on previously unexamined correspondence among panel members and Genetics Panel meeting transcripts, this paper provides the first documentation of these historical developments.

The Genetics Panel of the National Academy of Sciences' Committee on Biological Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose-response model in 1956, abandoning the threshold dose-response for genetic risk assessments. This recommendation was quickly generalized to include somatic cells for cancer risk assessment and later was instrumental in the adoption of linearity for carcinogen risk assessment by the Environmental Protection Agency. The Genetics Panel failed to provide any scientific assessment to support this recommendation and refused to do so when later challenged by other leading scientists. Thus, the linearity model used in cancer risk assessment was based on ideology rather than science and originated with the recommendation of the NAS BEAR Committee Genetics Panel. Historical documentation in support of these conclusions is provided in the transcripts of the Panel meetings and in previously unexamined correspondence among Panel members.

This paper extends a series of historical papers which demonstrated that the linear-no-threshold (LNT) model for cancer risk assessment was founded on ideological-based scientific deceptions by key radiation genetics leaders. Based on an assessment of recently uncovered personal correspondence, it is shown that some members of the United States (US) National Academy of Sciences (NAS) Biological Effects of Atomic Radiation I (BEAR I) Genetics Panel were motivated by self-interest to exaggerate risks to promote their science and personal/professional agenda. Such activities have profound implications for public policy and may have had a significant impact on the adoption of the LNT model for cancer risk assessment.

This paper extends several recent publications indicating that Hermann J. Muller: (1) Made deceptive statements during his Noble Prize Lecture on December 12, 1946, that were intended to promote the acceptance of the linear dose-response model for risk assessment for ionizing radiation and (2) that such actions of Muller were masked by a series of decisions by Muller's long-time colleague and esteemed radiation geneticist Curt Stern, affecting key publications in the mutation literature. Such actions further enhanced acceptance of the linearity dose-response model while preventing Muller's deceptions from being discovered. This paper provides documentation that Muller reinforced such practices within the scientific literature in the early 1950s, by supporting scientifically questionable actions of Stern. Detailed documentation is provided that demonstrates how these actions affected national and international risk assessment policy for ionizing radiation and chemical carcinogens via the recommendations of the National Academy of Sciences Biological Effects of Atomic Radiation committee in 1956, to adopt the linear dose-response model.

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673-674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201-213, 1929; Oliver in Science 71:44-46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose-response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide.

The EPA risk assessment practice denies the inclusion of beneficial responses in the evaluation process. This practice represents a marked deviation from the original guidelines set forth within NEPA, which required the integrated goal of environmental protection as including both a reduction in risk as well as an enhancement of health benefit. It is time for regulatory agencies such as EPA to incorporate both harm and benefit within its risk assessment process., (Copyright © 2012. Published by Elsevier Inc.)

Which dose-response model best explains low-dose responses is a critical issue in toxicology, pharmacology, and risk assessment. The present paper utilized the U.S. National Cancer Institute yeast screening database that contains 56,914 dose-response studies representing the replicated effects of 2189 chemically diverse possible antitumor drugs on cell proliferation in 13 different yeast strains. Multiple evaluation methods indicated that the observed data are inconsistent with the threshold model while supporting the hormetic model. Hormetic response patterns were observed approximately four times more often than would be expected by chance alone. The data call for the rejection of the threshold model for low-dose prediction, and they support the hormetic model as the default model for scientific interpretation of low-dose toxicological responses.

Increasing evidence that low-level exposure to toxic agents induces beneficial effects indicates the need to examine if and how the current EPA Reference Dose (RfD) derivation process could take this phenomenon into account. This paper examines conditions that affect how the RfD process could incorporate chemically induced beneficial effects while preventing toxic responses. Incorporation of beneficial responses in the RfD process will be affected by: (1) Size of the dosage range over which the beneficial effects are observed; (2) Proximity of the optimal beneficial response dosage to the NOAEL; (3) Size of the intraspecies UF. Based on data estimating the distance of the median dosage of the optimal beneficial response from the NOAEL and the recently described lack of independence of the inter- and intraspecies uncertainty factors (UFs), noncarcinogenic toxic substances whose RfDs are based on animal model data are predicted to have their toxic effects prevented and possible beneficial effects optimized in the general population by use of an intraspecies UF of 5. In contrast, current EPA practices of employing a 10-fold UF for intraspecies variation in animal-model-based RfD derivation while protecting against harmful effects also lead to the general population missing estimated beneficial effects. Such a conclusion has important policy implications since no debate has been directed toward the distribution of population-based pollution-related benefits, but only toward the prevention of their harmful effects.

Increasing evidence that low-level exposure to toxic agents induces beneficial effects indicates the need to examine if and how the current EPA reference dose (RfD) derivation process could take this phenomenon into account. This paper examines conditions that affect how the RfD process could incorporate chemically induced beneficial effects while preventing toxic responses. Incorporation of beneficial responses in the RfD process will be affected by: (i) Size of the dosage range over which the beneficial effects are observed; (ii) proximity of the optimal beneficial response dosage to the NOAEL; and (iii) size of the intraspecies UF. Based on data estimating the distance of the median dosage of the optimal beneficial response from the NOAEL and the recently described lack of independence of the inter- and intraspecies uncertainty factors (UFs), noncarcinogenic toxic substances whose RfDs are based on animal model data are predicted to have their toxic effects prevented and possible beneficial effects optimized in the general population by use of an intraspecies UF of 5. In contrast, current EPA practices of employing a 10-fold UF for intraspecies variation in animal model-based RfD derivation, while also protecting against harmful effects, leads to the general population missing estimated beneficial effects. Such a conclusion has important policy implications since no debate has been directed toward the distribution of population-based pollution-related benefits but only toward the prevention of their harmful effects.

This paper assesses the fundamental assumption that multiple uncertainty factors (UFs) are independent of each other and therefore may be combined through a multiplicative scheme. It is argued that a lack of independence is seen in several cases such as that between the interindividual and less-than-lifetime UFs with respect to an age component and results in an error in double counting of UFs. The paper proposes revised UF values based on the concept of the relationship of independent and interdependent UFs. This uncertainty factor revision is then applied to a large number of contaminants for which EPA either has or has proposed MCLs or DWELs.

The Council for Health and Environmental Safety of Soils (CHESS) was organized in 1987 to develop a consensus soil risk assessment methodology to be used as a framework for establishing standards for soil contamination to protect the environment and public health. The wide range of contaminating substances of possible health concern in soil is affecting land use and development, causing excessive economic expenditures, and the regulatory approaches for control are disperse. The International Society of Regulatory Toxicology and Pharmacology agreed to sponsor the Council and through a Governing Board composed of experienced scientists from the federal government, state departments of public health and environmental protection, academia, and the private sector including industry and environmental organizations. The Board was created to support the goals of CHESS, its mode of operation, and to establish funding policies and directions. A technical council agreed to develop a peer-reviewed consensus methodology to assess public health risks from contaminated soil by technical committees composed of recognized experts in the area of soil contamination and other relevant disciplines. This methodology would then be made available to federal and state agencies, the private sector, and the scientific community at large. After extensive study, a final decision was made to develop a decision-tree framework to be used at the state and local levels for application to all types of soil contamination. Following extensive studies it was agreed the ubiquitous nature of petroleum contamination in soil has direct and immediate public health implications and CHESS therefore directed its first efforts to this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Four cases are presented which suggest that the present U.S.E.P.A. drinking water standard for selenium of 10 micrograms/L in inappropriate. The rationale upon which this standard is based is that selenium is carcinogenic, induces dental caries formation, and is highly toxic to animals. However, a critical assessment of this literature can not support these claims. Case no. 1 demonstrates that there is insufficient evidence to classify selenium as a carcinogen. Data derived from the three respective groups of researchers claiming a carcinogenic effect induced by selenium are obscure due to 1) the inability to accurately identify malignancies, 2) the apparent opposite effects of different selenium compounds, and 3) the lack of proper controls. Case no. 2 reviews recent evidence that selenium reduces the incidence of cancer in laboratory animals and in man, an effect which can probably be attributed to the antioxidant properties of selenium compounds. Case no. 3 provides evidence which does not permit the classification of selenium as a cariogenic element. Epidemiological studies supporting such a claim are inadequate since they lack properly matched control groups. Animal data do not support this link as well. Case no. 4 is a review of studies which clearly demonstrate the essentiality of selenium, an aspect of selenium metabolism that was not considered when the 10 micrograms/L standard was promulgated. In light of the four cases presented and an assessment of selenium toxicity in man, it is concluded that the 10 micrograms/L standard can not be justified. Instead, it is suggested that 50 micrograms/L selenium should provide sufficient protection from the toxic effects of this element. This is consistent with the current state of knowledge with respect to the potential adverse health effects associated with selenium.

The U.S. Environmental Protection Agency's (EPA) proposed drinking water standard for radium-226 (226Ra) of 5 pCi/l is evaluated according to its health basis and carcinogenic implications. Proposed health risks of 226Ra in drinking water by other leading theoreticians (Evans, Gofman-Tamplin and Peterson) are also considered in light of the EPA proposal. It is concluded that the EPA proposal to raise the standard for 226Ra in drinking water is not justified on the basis of present knowledge of 226Ra carcinogenic effects.

How the United States and Canada approach the process and implementation of drinking water standards is critically examined. Despite many similarities in their approaches to regulating drinking water contaminants, there are a number of important differences, including approaches to dealing with genotoxic versus presumed epigenetic carcinogens and selection of biostatistical quantitative risk assessment models. Such international comparisons provide a valuable means to discern how others have attempted to solve similar problems and thereby provide an excellent opportunity to test the validity of one's own methodologies.

High school sophomores residing in a community with elevated levels of sodium in the drinking water (107 mg/1) exhibited a marked upward shift in blood pressure distribution patterns for systolic and diastolic blood pressures in both males and females as compared with a similar group in the control community (8 mg/1). The students group from the high sodium community appears to exhibit a blood pressure distribution characteristic of persons several years older.

The validity of deriving ambient air quality standards or levels via threshold level values (TLVs) is assessed via two methodologies: (1) using current U.S. standards for ambient air standards and occupational standards where the data base is very robust and (2) using Soviet occupational and community air standards where the standards are based on experimentally derived toxicological endpoints. The analysis indicates that the TLV-derived approach using TLV/420 and the appropriate averaging time is in wide disagreement with both validating methodologies.