Derivation of low-dose extrapolation factors from analysis of curvature in the cancer incidence dose response in Japanese atomic bomb survivors

2000 ◽  
Vol 76 (7) ◽  
pp. 939-953 ◽  
Author(s):  
M. P. Little, C. R. Muirhead
2018 ◽  
Vol 47 (3-4) ◽  
pp. 97-112 ◽  
Author(s):  
M.P. Little

For stochastic effects such as cancer, linear-quadratic models of dose are often used to extrapolate from the experience of the Japanese atomic bomb survivors to estimate risks from low doses and low dose rates. The low dose extrapolation factor (LDEF), which consists of the ratio of the low dose slope (as derived via fitting a linear-quadratic model) to the slope of the straight line fitted to a specific dose range, is used to derive the degree of overestimation (if LDEF > 1) or underestimation (if LDEF < 1) of low dose risk by linear extrapolation from effects at higher doses. Likewise, a dose rate extrapolation factor (DREF) can be defined, consisting of the ratio of the low dose slopes at high and low dose rates. This paper reviews a variety of human and animal data for cancer and non-cancer endpoints to assess evidence for curvature in the dose response (i.e. LDEF) and modifications of the dose response by dose rate (i.e. DREF). The JANUS mouse data imply that LDEF is approximately 0.2–0.8 and DREF is approximately 1.2–2.3 for many tumours following gamma exposure, with corresponding figures of approximately 0.1–0.9 and 0.0–0.2 following neutron exposure. This paper also cursorily reviews human data which allow direct estimates of low dose and low dose rate risk.


2021 ◽  
Vol 60 (1) ◽  
pp. 23-39
Author(s):  
Klervi Leuraud ◽  
David B. Richardson ◽  
Elisabeth Cardis ◽  
Robert D. Daniels ◽  
Michael Gillies ◽  
...  

AbstractThe Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (P = 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures.


1992 ◽  
Vol 33 (4) ◽  
pp. 342-361 ◽  
Author(s):  
HIROFUMI NAKATSUKA ◽  
YUKIKO SHIMIZU ◽  
TSUTOMU YAMAMOTO ◽  
ICHIRO SEKINE ◽  
HARUO EZAKI ◽  
...  

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