Cancer Risk from Exposure to Plutonium and Uranium

General comment (Major)

Please consider indicating explicitly in executive summary that due to technical limitations (mostly driven by available Mayak data), lifetime excess mortality risk for lung cancer needed to be calculated as lifetime attributable risk only in the ICRP Publication 103 reference Euro-American male population whose intake takes place in their 20s, while acknowledging that lung cancer risk may differ with various factors. Adding detail calculation process with values for the lifetime lung cancer mortality is preferable for traceability.

In general, RBE is determined as ratio of is effective doses for radiation of interest vis-à-vis reference radiation. Also, RBE generally increases with decreasing dose, dose rate, dose per fraction etc, and therefore RBE maximum is used for radiation protection purposes. Here, RBE was determined as ratio of LAR given a linear function of dose for plutonium, DDREF of 2 for high-energy photons, and limited exposure scenarios. RBE may also differ greatly depending on exposure scenarios, given that lung cancer risk in the LSS is higher in females than males and increases with age at exposure. These may be discussed in section 2.4 or 2.5.

General comment (minor)

Throughout the draft. Confidence intervals may be added for those only point estimates of which are described (e.g., Line 1575). SRR may have been used to stand not only for “standardised rate ratio” (see Lines 1770, 1780, 1785, 1786 and 2487) but also for “standardised registration ratio” (see Line 2466).

Abstract and main points.

Assessment of circulatory disease may be briefly discussed.

Discussion

Discussion on the lag year will be helpful for understanding.

L54

who were exposed at a high dose rate, mainly to “external” gamma rays.

L575-621

More information about “Bayesian techniques” should be provided. How the posterior distributions on doses derived has been changed by the Bayesian updating with the urinary data? Illustrative explanation of prior and posterior distributions, and summary of the main difference of lung dose between MWDS-2008 and 2013 would be helpful.

L623-634

Schematic diagram of lung showing the location of basal, secretory, epithelial, Clara cells, and so on, will help to explain the distribution of the alpha emitters and their biological effects in lung.

L961

Please consider briefly explaining types of errors: shared (common to all individuals within a group) vs unshared (unique to an individual within a group), and classical (random individual) vs Berkson (grouped).

L1219–1220

“Only 9% of these workers had plutonium doses exceeding 0.2 Gy and only about 2% had doses exceeding 1 Gy” may be “Only 9% of these workers had plutonium doses exceeding 0.1 Gy and only about 2% had doses exceeding 0.5 Gy”.

1226

“excess relative risks” not “relative risks”.

1358

“clearly” may be removed given relative risk of 1.16.

1655

“no significant excess” not “no excess”.

L1673 and 2456

“1.27 mGy” or “1.25 mGy”: the mean lung absorbed dose seems slightly different.

L1801

“estimation of risk” should be “inference or transfer of risk”

L1808

“given intake history” should be “hypothetical intake condition for calculation”

L1814

Please cite ICRP Publication 103 and ICRP Task Group 102 report.

L1822-24

Add an explanation as below: We used here a similar approach, using updated dosimetric models and risk coefficients, based on unitary scenarios of plutonium exposure “and Euro-American baseline mortality data as a reference.”

Figs 2.5 and 2.6

Although annual lung absorbed doses are displayed in Figs 2.5 and 2.6, it is better to indicate cumulative doses for each age which are used to calculate the ERR with considering the lag year.

L1934-1939

This information is very important and should be appeared in the Main Points.

Tables 2.8 and 2.11.

“Excess risk of lung cancer death” may be expressed “per mGy”, not “per Gy”, given the level of plutonium dose considered (despite that LAR is a linear function of dose).

L2016 and 2103

Should “2.5.2” be “2.4” or “2.4.2”?

L2171–2172 and 2186–2188

w_R has been used for tissue reactions (non-cancer skin changes and vision-impairing cataracts) in addition to cancer.

L2260-2261

While DDREF is used to calculate the radiation detriment (i.e. radiation risk inference), w_R is used to consider the type of radiation when an absorbed dose is estimated for equivalent dose and effective dose calculation. In addition, w_R is usually compared with the quality factor for operational quantity. Discussing the DDREF and w_R in the same level will be speculative and confusing.

L2311 and L2646

Please add an explanation for “F, M, and S”.

L2371–2372 and 2387–2388

The Ligett et al 2012 suggesting ≤1 µg/g of kidney seems contradictory to the 2001/2002 UK reports indicating adverse effects detectable at 0.1–0.5 µg per g of kidney, and this may need to be discussed for clarity.

L2400

Add a reference for “but there could be kidney failure in later life.”

Tables 3.2, 3.3 and 3.4

Some studies such as Yiin et al. (2017), Bouet et al. (2019) and Silver et al. (2013) report very low negative or very high positive risk estimate. Brief discussion may be added, even these estimates are not statistically significant.

L2555–2557

This sentence may be removed, or rephrased the LSS results being taken into account ( https://pubmed.ncbi.nlm.nih.gov/20518663/ ).

L2620–2624

The two sentences seem contradictory to each other.

L3464–3466

Definition of DDREF may be predicated on paragraph 74 of ICRP Publication 60 (i.e., applicable at any dose rate at <0.2 Gy and at <0.1 Gy/h at ≥0.2 Gy).

Glossary

“HR”, “LAR”, “OR” and “SIR/SMR/SRR” may be added under “Risk” or elsewhere.