Archives of Toxicology

, Volume 83, Issue 3, pp 203–225 | Cite as

The road to linearity: why linearity at low doses became the basis for carcinogen risk assessment

  • Edward J. CalabreseEmail author
Review Article


This article assesses the historical foundations of how linearity at low dose became accepted by the scientific/regulatory communities. While the threshold model was used in the 1920s/1930s in establishing radiation health standards, its foundations were challenged by the genetics community who argued that radiation induced mutations in reproductive cells followed a linear response, were cumulative and deleterious. Scientific foundations of linearity for gonadal mutations were based on non-conclusive evidence as well as not being conducted at low doses. Following years of debate, leaders in the genetics community participated in the U.S. National Academy of Sciences (NAS) (1956) Biological Effects of Atomic Radiation (BEAR) BEAR I Committee, getting their perspectives accepted, incorporating linearity for radiation-induced mutational effects in risk assessment. Overtime the concept of linearity was generalized to include somatic effects induced by radiation based on a protectionist philosophy. This affected the course of radiation-induced and later chemically-induced carcinogen risk assessment. Acceptance of linearity at low dose from chemical carcinogens was strongly influenced by the NAS Safe Drinking Water Committee report of 1977 which provided the critical guidance to the U.S. EPA to adopt linear at low dose modeling for risk assessment for chemical carcinogens with little supportive data, much of which has been either discredited or seriously weakened over the past 3 decades. Nonetheless, there has been little practical change of regulatory policy concerning carcinogen risk assessment. These observations suggest that while scientific disciplines are self correcting, that regulatory ‘science’ fails to display the same self-correcting mechanism despite contradictory data.


Threshold Dose response Risk assessment Carcinogen Mutagen Mutation Linearity Somatic mutation hypothesis 



Effort sponsored by the Air Force Office of Scientific Research, Air Force Material Command, USAF, under grant number FA9550-07-1-0248. The U.S. Government is authorized to reproduce and distribute for governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsement, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government. Even though their work is copiously cited in this paper, I wanted to highlight the important contributions of Whittemore (1986) and Jolly (2003) in their dissertations on critical assessment of the history of the dose response as seen through the eyes of historians of science.


  1. Ames BN (1973) Carcinogens are mutagens: their detection and classification. Environ Health Perspect 6:115–118. doi: 10.2307/3428066 PubMedCrossRefGoogle Scholar
  2. Ames BN, Lee FD, Durston WE (1973a) An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci USA 70:782–786. doi: 10.1073/pnas.70.3.782 PubMedCrossRefGoogle Scholar
  3. Ames BN, Durston WE, Yamasaki E, Lee FD (1973b) Carcinogens are mutagens—simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 70:2281–2285. doi: 10.1073/pnas.70.8.2281 PubMedCrossRefGoogle Scholar
  4. Ames BN, Durston WE, Yamasaki E, Lee FD (1973c) Carcinogens are mutagens—simple test system. Mutat Res 21:209–210Google Scholar
  5. Atomic Energy Commission (1950) Thirteenth Semiannual Report, July 1930, Control of Radiation Hazards in the Atomic Energy Program. Government Printing Office, WashingtonGoogle Scholar
  6. Auerbach C (1939–1940) Tests of carcinogenic substances in relation to the production of mutations in Drosophila melanogaster. Proc Roy Soc Edin 60:164–173Google Scholar
  7. Auerbach C, Robson JM (1946) Chemical production of mutations. Nature 157:302. doi: 10.1038/157302a0 CrossRefGoogle Scholar
  8. Avery OT, MacLeod CM, McCarty M (1944) Studies on chemical natures of substance inducing transformation by desoxyribonucleic acid fraction isolated from pneumococcus type III. J Exp Med 79:137–158. doi: 10.1084/jem.79.2.137 CrossRefPubMedGoogle Scholar
  9. Barclay AE, Cox S (1928) Radiation risks of the roentgenologist. Am J Roentgenol Rad Ther 19:551–561Google Scholar
  10. Barendsen GW (1975) The effectiveness of small doses of ionizing radiations for the induction of cell reproductive death, chromosomal change and malignant transformation. In: Presented at 5th symposium on microdosimetry, Verbania Pallanza, Italy, September 22Google Scholar
  11. Beadle G (1957) Biology division, C., Biology 1957 at the California Institute of Technology: a report for the year 1956–1957 on the research and other activities of the Division of Biology, pp 126Google Scholar
  12. Berenblum I, Shubik P (1949) An experimental study of the initiating stage of carcinogenesis, and a re-examination of the somatic cell mutation theory of cancer. Br J Cancer 3:109–117PubMedGoogle Scholar
  13. Bhattacharya S (1949) A study of the inability of methylcholanthrene to produce mutations in Drosophila melanogaster. Proc Zool Sox Bengal 2:187–193Google Scholar
  14. Blum HF (1953) Regarding the somatic mutation hypothesis of cancer. Science 118:197–198. doi: 10.1126/science.118.3059.197 PubMedCrossRefGoogle Scholar
  15. Brooks P, Lawley PD (1964) Evidence for the binding of polynuclear aromatic hydrocarbons to the nucleic acids of mouse skin. Relation between carcinogenic power of hydrocarbons and their binding to deoxyribonucleic acid. Nature 202:781–784. doi: 10.1038/202781a0 CrossRefGoogle Scholar
  16. Brown JM (1976) Linearity versus nonlinearity of dose-response for radiation carcinogenesis. Health Phys 31:231–245PubMedGoogle Scholar
  17. Bruce RD, Carlton WW, Ferber KH, Hughes DH, Quast JF, Salsburg DS, Smith JM, (Members of the Society of Toxicology ED01 Task Force), Brown WR, Cranmer MF, Sielken JR, Van Ryzin J, Barnard RC (1981) Re-examination of the ED01 study why the society of toxicology became involved. Fundam Appl Toxicol 1:26–128Google Scholar
  18. Brues AM (1958) Critique of linear theory of carcinogenesis. Science 128:693–699. doi: 10.1126/science.128.3326.693 PubMedCrossRefGoogle Scholar
  19. Burdette WJ (1950) Lethal mutation rate in Drosophila treated with methylcholanthrene. Science 112:303–306. doi: 10.1126/science.112.2907.303 PubMedCrossRefGoogle Scholar
  20. Burdette WJ (1951a) Administration of diethylstilbestrol to the tu-36a strain of Drosophila melanogaster. Rec Genet Soc Am 20:93–94Google Scholar
  21. Burdette WJ (1951b) Tumor incidence and lethal mutation rate in a tumor strain of Drosophila treated with formaldehyde. Cancer Res 11:555–558PubMedGoogle Scholar
  22. Burdette WJ (1952a) Tumor incidence and lethal mutation rate in Drosophila treated with 20-methylcholanthrene. Cancer Res 12:201–205PubMedGoogle Scholar
  23. Burdette WJ (1952b) Effect of nitrogen mustard on tumor incidence and lethal mutation rate in Drosophila. Cancer Res 12:366–368PubMedGoogle Scholar
  24. Burdette WJ (1953) The somatic mutation hypothesis of cancer genesis. Science 118:196–197. doi: 10.1126/science.118.3059.196 PubMedCrossRefGoogle Scholar
  25. Burdette WJ (1955) The significance of mutation in relation to the origin of tumors: a review. Cancer Res 15:201–226PubMedGoogle Scholar
  26. Calabrese EJ (2004) Hormesis: from marginalization to mainstream. A case for hormesis as the default dose-response model in risk assessment. Toxicol Appl Pharmacol 197:125–136. doi: 10.1016/j.taap.2004.02.007 PubMedCrossRefGoogle Scholar
  27. Calabrese EJ (2005a) Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology. Toxicol Appl Pharmacol 204:1–8. doi: 10.1016/j.taap.2004.11.015 PubMedCrossRefGoogle Scholar
  28. Calabrese EJ (2005b) Historical blunders: how toxicology got the dose-response relationship half right. Cell Mol Biol 51:643–654PubMedGoogle Scholar
  29. Calabrese EJ (2008) Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 27:1451–1474. doi: 10.1897/07-541.1 PubMedCrossRefGoogle Scholar
  30. Calabrese EJ, Baldwin LA (2000a) Chemical hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol 19:2–31. doi: 10.1191/096032700678815585 PubMedCrossRefGoogle Scholar
  31. Calabrese EJ, Baldwin LA (2000b) The marginalization of hormesis. Hum Exp Toxicol 19:32–40. doi: 10.1191/096032700678815594 PubMedCrossRefGoogle Scholar
  32. Calabrese EJ, Baldwin LA (2000c) Radiation hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol 19:41–75. doi: 10.1191/096032700678815602 PubMedCrossRefGoogle Scholar
  33. Calabrese EJ, Baldwin LA (2000d) Radiation hormesis: the demise of a legitimate hypothesis. Hum Exp Toxicol 19:76–84. doi: 10.1191/096032700678815611 PubMedCrossRefGoogle Scholar
  34. Calabrese EJ, Baldwin LA (2000e) Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis. Hum Exp Toxicol 19:85–97. doi: 10.1191/096032700678815620 PubMedCrossRefGoogle Scholar
  35. Carlson EA (1981) Genes, radiation and society: the life and work of H.J. Muller. Cornell University Press, IthacaGoogle Scholar
  36. Caron J (2003) Edward Lewis and radioactive fallout—the impact of Caltech biologists on the debate over nuclear weapons testing in the 1950s and 1960s. Thesis, Bachelor of Science. California Institute of Technology, PasadenaGoogle Scholar
  37. Catcheside DG (1946) Genetic effects of radiations. Br Med Bull 4:18–24Google Scholar
  38. Catcheside DG (1948) Genetic effects of radiations. Adv Genet Incorp Mol Genet Med 2:271–358Google Scholar
  39. Court-Brown WM (1958a) Nuclear and allied radiations and the incidence of leukaemia in man. Br Med Bull 14:168–173PubMedGoogle Scholar
  40. Court-Brown WM (1958b) Radiation-inducted leukemia in man, with particular references to the dose-response relationship. J Chronic Dis 8:113–122PubMedCrossRefGoogle Scholar
  41. Cowie DB, Scheele LA (1941) A survey of radiation protection in hospitals. J Natl Cancer Inst 1:767Google Scholar
  42. Demerec M (1948) Induction of mutations in Drosophila by dibenzanthracene. Genetics 33:337–348Google Scholar
  43. Drake JW (1978) Some guidelines for determining maximum permissible levels of chemical mutagens. In: Flamm WG, Mehlman MA (eds) Advances in modern toxicology, Volume 5-Mutagenesis. Hemisphere Publishing Corporation, New York, p 926Google Scholar
  44. Drake JW, Abrahamson S, Crow JF, Hollaender A, Lederberg S, Legator MS, Neel JV, Shaw MW, Sutton EE, von Borstel RC, Zimmering S, de Serres FJ (1975) Environmental mutagenic hazards. Science 187:503–514. doi: 10.1126/science.163482 CrossRefGoogle Scholar
  45. Driver HE, White INH, Butler WH (1987) Dose-response relationships in chemical carcinogenesis: Renal mesenchymal tumors induced in the rat by single dose dimethylnitrosamine. Br J Exp Pathol 68:133–143PubMedGoogle Scholar
  46. DuShane G (1957) Loaded dice. Science 125:964Google Scholar
  47. Environmental Protection Agency (EPA) (1976) Health risk and economic impact assessments of suspected carcinogens. Fed Regist 41:21402–21405Google Scholar
  48. Environmental Protection Agency (EPA) (1979) Water quality criteria. Fed Regist 44:15926–15931Google Scholar
  49. Environmental Protection Agency (EPA) (1980) Water quality criteria documents; availability. Fed Regist 45:79318–79356Google Scholar
  50. Evans RD (1949) Quantitative inferences concerning the genetic effects of radiation on human beings. Science 109:299–304. doi: 10.1126/science.109.2830.299 PubMedCrossRefGoogle Scholar
  51. Federal Radiation Council (FRC) (1960) Background material for the development of radiation protection standards. Report No. 1. Federal Radiation Council, Washington, DCGoogle Scholar
  52. Finkel MP (1958) Mice, men, and fallout. Science 128:637–641. doi: 10.1126/science.128.3325.637 PubMedCrossRefGoogle Scholar
  53. Foulds L (1969) Neoplastic development, vol I. Academic Press, New YorkGoogle Scholar
  54. Freese E (1973) Thresholds in toxic, teratogenic, mutagenic, and carcinogenic effects. Environ Health Perspect. doi: 10.2307/3428074
  55. Furth J (1957) Hearings on the nature of radioactive fallout and its effects on man, in joint committee on atomic energy. United States Government Printing Office, Washington, DC, p 2000Google Scholar
  56. Glucksmann A, Lamerton LF, Maynford WV (1957) Cancer, Chapter 12. In: Raven RW (ed), Butterworths, LondonGoogle Scholar
  57. Hanson FB (1928) The effect of X-rays in producing return gene mutations. Science LXVII:562–563. doi: 10.1126/science.67.1744.562 CrossRefGoogle Scholar
  58. Hanson FB, Heys F (1929) An analysis of the effect of the different rays of radium in producing lethal mutations in Drosophila. Am Nat 63:201–213. doi: 10.1086/280254 CrossRefGoogle Scholar
  59. Hanson FB, Heys F (1932) Radium and lethal mutations in Drosophila further evidence of the proportionality rule from a study of the effects of equivalent doses differently applied. Am Nat 66:335–345. doi: 10.1086/280441 CrossRefGoogle Scholar
  60. Hanson FB, Heys F, Stanton E (1931) The effect of increasing X-ray voltages on the production of lethal mutations in Drosphila melanogaster. Am Nat 65:134–143. doi: 10.1086/280355 CrossRefGoogle Scholar
  61. Henschen F (1968) Yamagiwas tar cancer and its historical significance—from Percival Pott to Katsusaburo Yamagiwa. Gann 59:447–451PubMedGoogle Scholar
  62. Henshaw PS (1941) The biological significance of the tolerance dose in X-ray and radium protection. J Natl Cancer Inst 1:789–805Google Scholar
  63. Houle CD, Ton TT, Clayton C, Huff J, Hong HL, Sills RC (2006) Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice. Toxicol Pathol 34:752–762. doi: 10.1080/01926230600935912 PubMedCrossRefGoogle Scholar
  64. International Commission on Radiological Protection (ICRP) (1966) The evaluation of risks from radiation, ICRP Publication 8. Pergamon Press, OxfordGoogle Scholar
  65. Joint Committee on Atomic Energy (JCAE) of the Congress of the United States (1957) Hearings on the nature of radioactive fallout and its effects on man. 2 vols. plus summary. Government Printing Office, WashingtonGoogle Scholar
  66. Joint Committee on Atomic Energy (JCAE) of the Congress of the United States (1959) Hearings on fallout from nuclear weapons tests. 3 vols. plus summary. Government Printing Office, WashingtonGoogle Scholar
  67. Joint Committee on Atomic Energy (JCAE) of the Congress of the United States (1960a) Selected materials on radiation protection criteria and standards: Their basis and use. Government Printing Office, WashingtonGoogle Scholar
  68. Joint Committee on Atomic Energy (JCAE) of the Congress of the United States (1960b) Statement of Dr. E.B. Lewis, Division of Biology, California Institute of Technology. Radiation protection and somatic effects. In: Selected materials on radiation protection criteria and standards: their basis and use. Government Printing Office, Washington, pp 404–407Google Scholar
  69. Joint Committee on Atomic Energy (JCAE) of the Congress of the United States (1960c) Statement of Dr. Austin M. Brues, Director, Division of Biological and Medical Research, Argonne National Laboratory, Argonne, IL. Radiation protection and somatic effects. In: Selected materials on radiation protection criteria and standards: their basis and use. Government Printing Office, Washington, pp 408–437Google Scholar
  70. Jolly JC (2003) Thresholds of uncertainty: radiation and responsibility in the fallout controversy. Dissertation, Oregon State University, p 591Google Scholar
  71. Kathren RL (1996) Pathway to a paradigm: the linear nonthreshold dose-response model in historical context: the American Academy of Health Physics 1995 radiology centennial Hartman oration. Health Phys 70:621–635. doi: 10.1097/00004032-199605000-00002 PubMedCrossRefGoogle Scholar
  72. Kennaway EL (1955) The identification of a carcinogenic compound in coal-tar. BMJ 2:749–752PubMedGoogle Scholar
  73. Kimball AW (1958) Evaluation of data relating human leukemia and ionizing radiation. J Natl Cancer Inst 21:383–391PubMedGoogle Scholar
  74. Lamerton LF (1958) An examination of the clinical and experimental data relating to the possible hazard to the individual of small doses of radiation. Br J Radiol 31:229–239PubMedCrossRefGoogle Scholar
  75. Lamerton LF (1964) Radiation carcinogenesis. Br Med Bull 20:134PubMedGoogle Scholar
  76. Larson CD (1989) Historical development of the national primary drinking water regulations. In: safe drinking water act: amendments, regulations and standards. Lewis Publishers, Chelsa, pp 3–15Google Scholar
  77. Latarject R (1948) Production dune mutation bacterienne par des substances cancerigenes ou non. Comp Ren Des Seances Soc Biol Filiales 142:453–455Google Scholar
  78. Lawley PD (1994) Historical origins of current concepts of carcinogenesis. Adv Cancer Res 65:18–111Google Scholar
  79. Lewis EB (1957) Leukemia and ionizing radiation. Science 125:965–972. doi: 10.1126/science.125.3255.965 PubMedCrossRefGoogle Scholar
  80. Lipshitz HD (2005) From fruit flies to fallout: Ed Lewis and his science. Dev Dyn 232:529–546. doi: 10.1002/dvdy.20332 PubMedCrossRefGoogle Scholar
  81. Loechler EL (1996) The role of adduct site-specific mutagenesis in understanding how carcinogen-DNA adducts cause mutations: perspective, prospects and problems. Carcinogenesis 17:895–902. doi: 10.1093/carcin/17.5.895 PubMedCrossRefGoogle Scholar
  82. Loveless A, Hampton CL (1969) Inactivation and mutation of coliphage T2 by N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea. Mutat Res 7:1–12. doi: 10.1016/0027-5107(69)90043-8 PubMedGoogle Scholar
  83. Malling HV (2004a) Incorporation of mammalian metabolism into mutagenicity testing. Mutat Res 566:183–189. doi: 10.1016/j.mrrev.2003.11.003 PubMedCrossRefGoogle Scholar
  84. Malling HV (2004b) History of the science of mutagenesis from a personal perspective. Environ Health Perspect 44:372–386Google Scholar
  85. Mole RH (1958) The dose-response relationship in radiation carcinogenesis. Br Med Bull 14:184–189PubMedGoogle Scholar
  86. Muller HJ (1927) Artificial transmutation of the gene. Science 66:84–87. doi: 10.1126/science.66.1699.84 PubMedCrossRefGoogle Scholar
  87. Muller HJ (1928) The problem of genic modification. Verhandlungen des V. Internationalen Kongresses fur Vererbungswissenschaft (Berlin, 1927) in Zeitschrift fur inductive abstammungs- und Vererbungslehre. Suppl Band 1:234–260Google Scholar
  88. Muller HJ (1930) Radiation and Genetics. Am Nat 64:220–257. doi: 10.1086/280313 CrossRefGoogle Scholar
  89. Muller HJ (1951) In: Baitsell GA (ed) Science in progress, 7th series. Yale University Press, New Haven, pp 95–165Google Scholar
  90. Mustacchi PO, Shimkin MB (1956) Radiation cancer and Clunet. J Cancer 9:1073–1074. doi: 10.1002/1097-0142(195611/12)9:6<1073::AID-CNCR2820090602>3.0.CO;2-9 CrossRefGoogle Scholar
  91. Mutscheller A (1925) Physical standards of protection against roentgen ray dangers. Am J Roentgenol Rad Ther 13:65–70Google Scholar
  92. Mutscheller A (1928) Safety standards of protection against X-ray dangers. Radiology 10:468–476Google Scholar
  93. National Academy of Sciences (NAS)/National Research Council (NRC) (1956) The biological effects of atomic radiation: a report to the public. NAS/NRC, WashingtonGoogle Scholar
  94. National Academy of Sciences (NAS)/National Research Council (NRC) (1959) A commentary on the report of the United Nations scientific committee on the effect of atomic radiation. NAS Publication 647. NAS/NRC, WashingtonGoogle Scholar
  95. National Academy of Sciences (NAS)/National Research Council (NRC) (1972) The effects on populations of exposure to low levels of ionizing radiation. National Academy, WashingtonGoogle Scholar
  96. National Committee on Radiation Protection, Measurements (NCRPM) (1960) Somatic radiation dose for the general population. Science 131:482–486. doi: 10.1126/science.131.3399.482 CrossRefGoogle Scholar
  97. Nordling CO (1952) Theories and statistics of cancer. Nord Med 47:817–820PubMedGoogle Scholar
  98. Nordling CO (1953) A new theory of the cancer-inducing mechanism. Br J Cancer 7:68–72PubMedGoogle Scholar
  99. Oliver CP (1930) The effect of varying the duration of X-ray treatment upon the frequency of mutation. Science 71:44–46. doi: 10.1126/science.71.1828.44 PubMedCrossRefGoogle Scholar
  100. Oliver CP (1931) An analysis of the effect of varying the duration of x-ray treatment upon the frequency of mutations. Doctor of Philosophy Thesis, University of Texas, AustinGoogle Scholar
  101. Olivieri G, Bodycote J, Wolff S (1984) Adaptive response of human-lymphocytes to low concentrations of radioactive thymidine. Science 223:594–597. doi: 10.1126/science.6695170 PubMedCrossRefGoogle Scholar
  102. Pochin EE (1958) Radiation and leukaemia. Lancet 1:51–52CrossRefGoogle Scholar
  103. Richter A, Singleton WR (1955) The effects of chronic gamma radiation on the production of somatic mutations in carnations. Genetics 41:295–300Google Scholar
  104. Rous P (1910) A transmissible avian neoplasm (Sarcoma of the common fowl). J Exp Med 12:696–705. doi: 10.1084/jem.12.5.696 CrossRefPubMedGoogle Scholar
  105. Rous P (1959) Surmise and fact on the nature of cancer. Nature 183:1357–1361. doi: 10.1038/1831357a0 PubMedCrossRefGoogle Scholar
  106. Safe Drinking Water Committee (1977) Drinking water and health. National Academy of Sciences, WashingtonGoogle Scholar
  107. Samson L, Cairns J (1977) New pathway for DNA-repair in Escherichia coli. Nature 267:281–283. doi: 10.1038/267281a0 PubMedCrossRefGoogle Scholar
  108. Serebrovsky AS, Dubinin NP (1930) X-ray experiments with Drosophila. J Hered 21:259–265Google Scholar
  109. Setlow JK (1964) Effects of UV on DNA-correlations among biological changes, physical changes and repair mechanisms. Photochem Photobiol 3:405–413. doi: 10.1111/j.1751-1097.1964.tb08163.x CrossRefGoogle Scholar
  110. Sievert R (1925) Einige untersuchungen uber vorricht ungen zum schutz gegen roentgenstrahlen. Acta Radiol 4:61. doi: 10.3109/00016922509133488 CrossRefGoogle Scholar
  111. Singleton WR (1954a) The effect of chronic gamma radiation on endosperm mutations in maize. Genetics 39:587–603PubMedGoogle Scholar
  112. Singleton WR (1954b) Radiation effects on living systems. J Heredity 45:58–64Google Scholar
  113. Solomon MS, Morgenthaler P-ML, Turesky RJ, Essigmann JM (1996) Mutational and DNA binding specificity of the carcinogen 2-amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline. J Biol Chem 271:18368–18374. doi: 10.1074/jbc.271.41.25240 PubMedCrossRefGoogle Scholar
  114. Stadler LJ (1930) Some genetic effects of X-rays in plants. J Hered 21:3–19Google Scholar
  115. Sturtevant AH (1954) Social implications of the genetics of man. Science 120:405–407. doi: 10.1126/science.120.3115.405 PubMedCrossRefGoogle Scholar
  116. Sturtevant AH (1965) A history of genetics. Harper and Row Publishers, New York, pp 71–72Google Scholar
  117. Taylor LS (1971) Radiation protection standards. CRC monotopics series. Chemical Rubber Company Press, ClevelandGoogle Scholar
  118. Timofeeff-Ressovsky NW, Zimmer KG, Delbruck M (1935) Nachrichten von der gesellschaft der wissenschaften zu Gottingen. Uber die nature der genmutation und der genstruktur Biologie Band 1, Nr. 13Google Scholar
  119. Trosko JE, Upham BL (2005) The emperor wears no clothes in the field of carcinogen risk assessment: ignored concepts in cancer risk assessment. Mutagenesis 20:81–92. doi: 10.1093/mutage/gei017 PubMedCrossRefGoogle Scholar
  120. United Nations Scientific Committee on the effects of atomic radiation (1958) Report of the United Nations Scientific Committee on the effects of atomic radiation. New York, United Nations. General Assembly Official Records, Thirteenth Session, Supplement No. 17 (A/3838)Google Scholar
  121. United Nations Scientific Committee on the effects of atomic radiation (1962) Report of the United Nations Scientific Committee on the effects of atomic radiation. New York, United Nations. General Assembly Official Records, Seventeenth Session, Supplement No. 16 (A/5216)Google Scholar
  122. United Nations Scientific Committee on the effects of atomic radiation (1964) Report of the United Nations Scientific Committee on the effects of atomic radiation. New York, United Nations. General Assembly Official Records, Nineteenth Session, Supplement No. 14 (A/5814)Google Scholar
  123. Uphoff DE, Stern C (1949) The genetic effects of low intensity irradiation. Science 109:609–610. doi: 10.1126/science.109.2842.609 PubMedCrossRefGoogle Scholar
  124. Valadez JG, Guengerich FP (2004) S-(2-Chloroethyl)glutathione-generated p53 mutation spectra are influenced by differential repair rates more than sites of initial DNA damage. J Biol Chem 279:13435–13446. doi: 10.1074/jbc.M312358200 PubMedCrossRefGoogle Scholar
  125. Watson JD, Crick FHC (1953) Molecular structure of nucleic acids—a structure for deoxyribose nucleic acid. Nature 171:737–738. doi: 10.1038/171737a0 PubMedCrossRefGoogle Scholar
  126. Weil CS (1972) Statistics vs. safety factors and scientific judgment in the evaluation of safety for man. Toxicol Appl Pharmacol 21:454-463PubMedCrossRefGoogle Scholar
  127. Weinstein A (1928) The production of mutations and rearrangements of genes by X-rays. Science LXVII:376–377. doi: 10.1126/science.67.1736.376 CrossRefGoogle Scholar
  128. Whittemore GF Jr (1986) The National Committee on Radiation Protection, 1928–1960: from professional guidelines to government regulation. Thesis. Department of History of Science. Harvard University, CambridgeGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Environmental Health Sciences Division, Department of Public HealthUniversity of MassachusettsAmherstUSA

Personalised recommendations