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

Abstract

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.

Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

“…Studies have shown, however, the existence of adaptive doseresponse relationships with low doses being protective and high doses causing detrimental effects, contradicting the LNT model. 4,5 This adaptive response is in fact part of a general cellular response to stress that is evolutionally conserved. 6 Hence, many have argued that the use of the LNT model has led to unfounded levels of public fear regarding low levels of radiation exposure, and misunderstandings about the safety of diagnostic imaging for medical use.…”

Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects

“…Similar research was also initiated by a number of other investigators in the immediate aftermath of Muller's seminal findings. However, the results that emerged did not experimentally resolve the issue of the shape of the mutagenicity doseresponse [48]. In fact, the lowest dose tested was still strikingly high, being 275 rads, a truly massive dose to the fruit fly's gonads.…”

“…Priestley [33]. Although the research of Aitken [33], Cushny [39], and others was in the pharmacological domain, support was also offered in the toxicological [43][44][45], radiation/occupational health [46][47][48], and immunological [49] areas for the generalizing of the threshold dose-response concept. Thresholds were also widely observed in numerous other scientific domains, ranging from the behavioral to the physical sciences, supporting a broad and integrative general scientific concept [50].…”

Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases

“…The concept of this protection was the "tolerance dose" (rate). The standard issued by the ICRP in 1934 specified no more than 0.2 roentgen per day, which is about 700 mGy per year (Calabrese, 2009). A study of British radiologists suggests that radiologists who entered the profession prior to 1921 had higher cancer mortality than their peers, while those who entered after 1920 had a lower mortality (from cancer and all other causes) than their peers (Smith and Doll, 1981).…”