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  1. Article: EPA transparency proposal: testimony of Edward J. Calabrese, Ph.D, October 3, 2018.

    Calabrese, Edward J

    Journal of cell communication and signaling

    2018  Volume 13, Issue 1, Page(s) 145–147

    Abstract: ... 1970s were based on the discovery of X-ray-induced gene mutations by Hermann J. Muller ...

    Abstract The historical foundations of cancer risk assessment and its adoption by the US EPA in the mid 1970s were based on the discovery of X-ray-induced gene mutations by Hermann J. Muller, its transformation into the linear nonthreshold (LNT) single-hit theory and the recommendations of the model by the US National Academy of Sciences, Biological Effects of Atomic/Ionizing Radiation, Genetics Panels in 1956 and 1972. This testimony summarizes substantial recent revelations which profoundly challenge the use of LNT as a default in cancer risk assessment, showing multiple significant scientific errors and incorrect interpretations, mixed with deliberate misrepresentation of the scientific record by leading ideologically motivated radiation geneticists. These novel historical and scientific findings demonstrate that the scientific foundations of the LNT single-hit model were seriously flawed and should not have been adopted for cancer risk assessment. The testimony supports the recommendation by the EPA to move away from the use of the LNT as a default in cancer risk assessment and to the formal consideration of alternative dose response models such as the threshold, hormetic and other non-linear modeling approaches.
    Language English
    Publishing date 2018-12-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2299380-0
    ISSN 1873-961X ; 1873-9601
    ISSN (online) 1873-961X
    ISSN 1873-9601
    DOI 10.1007/s12079-018-0497-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cancer risk assessment, its wretched history and what it means for public health.

    Calabrese, Edward J

    Journal of occupational and environmental hygiene

    2024  Volume 21, Issue 4, Page(s) 220–238

    MeSH term(s) Humans ; Public Health ; Neoplasms ; Risk Assessment
    Language English
    Publishing date 2024-03-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2131820-7
    ISSN 1545-9632 ; 1545-9624
    ISSN (online) 1545-9632
    ISSN 1545-9624
    DOI 10.1080/15459624.2024.2311300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5821: Show issues Location:
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  3. Article ; Online: Confirmation that Hermann Muller was dishonest in his Nobel Prize Lecture.

    Calabrese, Edward J

    Archives of toxicology

    2023  Volume 97, Issue 11, Page(s) 2999–3003

    Abstract: In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response ...

    Abstract In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for ionizing radiation-induced germ cell mutations was linear and that there was ''no escape from the conclusion that there is no threshold''. However, a newly discovered commentary by the Robert L. Brent (2015) indicated that Curt Stern, after reading a draft of part of Muller's Nobel Prize Lecture, called Muller, strongly advising him to remove reference to the flawed linear non-threshold (LNT)-supportive Ray-Chaudhuri findings and strongly encouraged him to be guided by the threshold supportive data of Ernst Caspari. Brent indicated that Stern recounted this experience during a genetics class at the University of Rochester. Brent wrote that Muller refused to follow Stern's advice, thereby proclaiming support for the LNT dose-response while withholding evidence that was contrary during his Nobel Prize Lecture. This finding is of historical importance since Muller's Nobel Prize Lecture gained considerable international attention and was a turning point in the acceptance of the linearity model for radiation and chemical hereditary and carcinogen risk assessment.
    MeSH term(s) Male ; Humans ; Nobel Prize ; Carcinogens ; Germ Cells ; Linear Models ; Radiation, Ionizing
    Chemical Substances Carcinogens
    Language English
    Publishing date 2023-09-04
    Publishing country Germany
    Document type Letter
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-023-03566-5
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  4. Article ; Online: Thresholds for radiation induced mutation? The Muller-Evans debate: A turning point for cancer risk assessment.

    Calabrese, Edward J

    Chemico-biological interactions

    2023  Volume 382, Page(s) 110614

    Abstract: In 1949 Robley Evans [1] published a paper in Science supporting a threshold dose response for ionizing radiation-induced mutation, contradicting comments of Hermann Muller during his 1946 Nobel Prize Lecture [2] and subsequent presentations. Evans sent ... ...

    Abstract In 1949 Robley Evans [1] published a paper in Science supporting a threshold dose response for ionizing radiation-induced mutation, contradicting comments of Hermann Muller during his 1946 Nobel Prize Lecture [2] and subsequent presentations. Evans sent a final draft [3] prior to publication to over 50 leading geneticists/radiologists, including Muller, with this correspondence being generally extremely supportive, including letters from the radiation geneticists Curt Stern, James Neel and Donald Charles. Of interest is that Muller engaged in a dispute with Evans, with Evans dismissing Muller's comments as containing "a few points of scientific interest, and many matters pertaining to personalities and prejudices." A foundation of the Evans threshold position was the study by Ernst Caspari, which was done under the direction of Curt Stern, at the University of Rochester/Manhattan Project, and for which Muller was a paid consultant, thereby having insider knowledge of the research team, results and internal debates. Muller published a series of articles after the Evans Science publication that marginalized the Caspari findings, claiming that his control group was aberrantly high, which caused his threshold conclusion to be incorrect. Internal correspondence in 1947 between Muller and Stern reveals that Muller supported the use of the Caspari control group based on consistency with his own laboratory data. This correspondence shows that Muller reversed his position three years later, soon after the Evans publication. In that same 1947 correspondence with Stern, Muller also claimed that the mutational findings of Delta Uphoff, who was replicating the Caspari study, could not be supported because of aberrantly low control group values only to reverse himself to support the LNT model. The present paper links Muller's threshold rejection/LNT supporting actions to the timing of the debate with Evans concerning Evans' use of the Caspari data to support the threshold model. It is of historical significance that the duplicitous actions of Muller were rewarded, with his newly expressed reversed views becoming generally accepted (while his previously documented contrary views were hidden/remained private). At the same time, the marginalizing of the Caspari findings greatly impacted recommendations to support LNT by major advisory committees.
    MeSH term(s) Humans ; Dose-Response Relationship, Radiation ; Risk Assessment/methods ; Radiation, Ionizing ; Mutation ; Neoplasms/genetics
    Language English
    Publishing date 2023-06-23
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 218799-1
    ISSN 1872-7786 ; 0009-2797
    ISSN (online) 1872-7786
    ISSN 0009-2797
    DOI 10.1016/j.cbi.2023.110614
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  5. Article ; Online: How Hermann J. Muller Viewed the Ernest Sternglass Contributions to Hereditary and Cancer Risk Assessment.

    Calabrese, Edward J / Giordano, James

    Health physics

    2024  Volume 126, Issue 3, Page(s) 151–155

    Abstract: Abstract: As one of the most influential radiation geneticists of the 20th century, Hermann J ...

    Abstract Abstract: As one of the most influential radiation geneticists of the 20th century, Hermann J. Muller had a major role in the development and widespread acceptance of the linear no-threshold (LNT) dose response for hereditary and cancer risk assessments worldwide. However, a spate of historical reassessments have challenged the fundamental scientific foundations of the LNT model, drawing considerable attention to issues of ethical probity and the scientific leadership of Muller. This review paper raises further questions about the objectivity of Muller with respect to the LNT model. It is shown that Muller supported Ernest Sternglass's findings and interpretations concerning radiation-induced childhood leukemia, which have been widely and consistently discredited. These findings provide further evidence that Muller's actions with respect to radiation cancer risk assessment were far more ideologically than scientifically based.
    MeSH term(s) Humans ; Child ; Linear Models ; Risk Assessment ; Neoplasms
    Language English
    Publishing date 2024-01-22
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2406-5
    ISSN 1538-5159 ; 0017-9078
    ISSN (online) 1538-5159
    ISSN 0017-9078
    DOI 10.1097/HP.0000000000001774
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Muller misled the Pugwash Conference on radiation risks.

    Calabrese, Edward J / Selby, Paul B

    Journal of occupational and environmental hygiene

    2024  Volume 21, Issue 2, Page(s) 136–143

    Abstract: ... at this first Pugwash Conference by the Nobel Prize-winning radiation geneticist, Hermann J. Muller ...

    Abstract The Pugwash Conferences have been a highly visible attempt to create profoundly important discussions on matters related to global safety and security at the highest levels, starting in 1957 at the height of the Cold War. This paper assesses, for the first time, the formal comments offered at this first Pugwash Conference by the Nobel Prize-winning radiation geneticist, Hermann J. Muller, on the effects of ionizing radiation on the human genome. This analysis shows that the presentation by Muller was highly biased and contained scientific errors and misrepresentations of the scientific record that resulted in seriously misleading the attendees. The presentation of Muller at Pugwash served to promote, on a very visible global scale, continued misrepresentations of the state of the science and had a significant impact on policies and practices internationally and both scientific and personal belief systems concerning the effects of low dose radiation on human health. These misrepresentations would come to affect the adoption and use of nuclear technologies and the science of radiological and chemical carcinogen health risk assessment, ultimately having a profound effect on global environmental health.
    MeSH term(s) Humans ; Dose-Response Relationship, Radiation ; Radiation, Ionizing ; Risk Assessment/methods ; Nobel Prize
    Language English
    Publishing date 2024-01-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2131820-7
    ISSN 1545-9632 ; 1545-9624
    ISSN (online) 1545-9632
    ISSN 1545-9624
    DOI 10.1080/15459624.2023.2268664
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  7. Article: Induced Pluripotent Stem Cells and Hormesis.

    Calabrese, Edward J

    Dose-response : a publication of International Hormesis Society

    2022  Volume 20, Issue 1, Page(s) 15593258221075504

    Abstract: This paper represents the first assessment of agent-induced hormetic dose responses in induced pluripotent stem cells and their derived cells. The hormetic dose responses were induced by a broad range of chemicals, including pharmaceuticals (eg, ... ...

    Abstract This paper represents the first assessment of agent-induced hormetic dose responses in induced pluripotent stem cells and their derived cells. The hormetic dose responses were induced by a broad range of chemicals, including pharmaceuticals (eg, metformin), dietary supplements/extracts from medicinal plants (eg, curcumin), and endogenous agents (eg, melatonin). The paper assesses the mechanistic foundations of these induced hormetic dose responses, their therapeutic implications and comparison with hormetic responses in multiple adult and embryonic stem cells.
    Language English
    Publishing date 2022-03-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2440820-7
    ISSN 1559-3258
    ISSN 1559-3258
    DOI 10.1177/15593258221075504
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  8. Article: Hormesis and Endothelial Progenitor Cells.

    Calabrese, Edward J

    Dose-response : a publication of International Hormesis Society

    2022  Volume 20, Issue 1, Page(s) 15593258211068625

    Abstract: Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone. In general, these studies demonstrate the ... ...

    Abstract Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone. In general, these studies demonstrate the capacity of these agents to enhance EPC proliferation and angiogenesis functional applications, having a focus on repairing endothelial tissue damage due to acute injury (e.g., stroke), as well as damage from chronic conditions (e.g., atherosclerosis) and normal aging processes.
    Language English
    Publishing date 2022-02-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2440820-7
    ISSN 1559-3258
    ISSN 1559-3258
    DOI 10.1177/15593258211068625
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  9. Article ; Online: Linear non-threshold (LNT) fails numerous toxicological stress tests: Implications for continued policy use.

    Calabrese, Edward J

    Chemico-biological interactions

    2022  Volume 365, Page(s) 110064

    Abstract: The linear non-threshold (LNT) dose-response model has long been employed by regulatory agencies to assess cancer risks from exposures to chemical carcinogens and ionizing radiation. Herein a series of fundamental historical, physical, chemical, and ... ...

    Abstract The linear non-threshold (LNT) dose-response model has long been employed by regulatory agencies to assess cancer risks from exposures to chemical carcinogens and ionizing radiation. Herein a series of fundamental historical, physical, chemical, and biologically based toxicological "stress tests" were "administered" to the LNT model, showing important limitations for its use in low dose extrapolation for all endpoints but with particular focus on cancer risk assessment where it is commonly applied. These limitations reveal that its capacity to make low-dose cancer-risk predictions is seriously flawed, precluding its use as a reliable model to estimate low dose cancer risks.
    MeSH term(s) Dose-Response Relationship, Radiation ; Humans ; Linear Models ; Neoplasms ; Policy ; Radiation, Ionizing ; Risk Assessment
    Language English
    Publishing date 2022-08-05
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 218799-1
    ISSN 1872-7786 ; 0009-2797
    ISSN (online) 1872-7786
    ISSN 0009-2797
    DOI 10.1016/j.cbi.2022.110064
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  10. Article ; Online: Evolution frames the dose response for all endpoints including application to cancer risk assessment: Time for a mid-course correction.

    Calabrese, Edward J

    The Science of the total environment

    2022  Volume 852, Page(s) 158466

    Abstract: An underappreciated perspective is that the quantitative features of the dose-response in the low dose zone are a genetically based biological characteristic with a highly conserved evolutionary basis. Failure to recognize and take this into account has ... ...

    Abstract An underappreciated perspective is that the quantitative features of the dose-response in the low dose zone are a genetically based biological characteristic with a highly conserved evolutionary basis. Failure to recognize and take this into account has been a major failing of toxicology and radiation biology, affecting regulatory agencies worldwide. The present perspective clarifies the historical foundations of this misstep and calls for a mid- course correction that replaces the public health based Precautionary Principle for risk assessment with one based on the principles of evolutionary biology.
    MeSH term(s) Humans ; Risk Assessment ; Neoplasms ; Dose-Response Relationship, Radiation
    Language English
    Publishing date 2022-08-31
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2022.158466
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