Early and late effects of radiation in normal tissues and organs: threshold doses for tissue reactions and other non-cancer effects of radiation in a radiation protection context

Draft document: Early and late effects of radiation in normal tissues and organs: threshold doses for tissue reactions and other non-cancer effects of radiation in a radiation protection context
Submitted by Mikhail Balonov, Institute of Radiation Hygiene; ICRP C2
Commenting as an individual

This is long-awaited report that should clarify recent findings in human radiobiology and epidemiology and their relevance to radiation protection. The comments will be limited with the issue of radiation-induced cataract. Reviewer sees three significant inconsistencies in interpretation of the recent experimental findings of radiation-induced cataract and their implementation for radiation protection purposes.

1. The opacities detected by modern microscopical ophtalmological techniques (e.g. slit lamp) and the clinically significant cataracts that result in visual impairment are of different radiological importance for human health and are caused by different radiation doses – see schematic Fig 2.8 on p. 103. That is the latter that seem to be directly relevant to radiation protection as there is no evidence so far that an opacity per se develops to a clinically significant cataract.

However, Fig. 4.1 presents biostatistical parameters (OR/RR) derived from various studies regardless of opacity/cataract grade that complicates data interpretation. It would be more informative to present separately the data relevant to radiation-induced opacities and to clinically significant cataracts. Other factors that should be accounted for are the endpoint and age at exposure and at examination, see below.

Furthermore, Table 4.2 presents threshold doses estimated formally in the three recent epidemiological papers of very high quality. However, it should be understood that in two of them (Nakashima et al and Worgul et al.) the presented threshold doses are actually relevant to subclinical effects. Thus, among the CC cases only 26% (162/618) are ascribed to clinically significant cataracts and among the PS cases only 4% (9/214) (Nakashima et al). In the very comprehensive and informative paper of Worgul et al, the threshold doses are also determined mostly for subclinical cataract Stage 1 that represent 96% cases for prevalence and 98% for incidence. That means that only 2 to 4% of those cases are of clinical significance.

Thus, estimates of threshold dose for subclinical cataracts of 0.3 to 0.7 Gy or Sv may not contradict well known much higher values relevant to clinically significant cataracts.

2. On the other hand, it would be useful to clarify in Section 2.6 the interaction between radiation-induced cataracts (PSC and possibly CC) and senile nucleus cataracts with regard of eventual visual impairment that is relevant, e.g., to interpretation of very important paper of Nerishi et al. In this paper, only the lens operated cases in senior persons (average age of about 73 y at the time of operation) were considered. In those persons, the senile cataract may dominate in or substantially contribute to the visual impairment, and the role/contribution of radiation-induced cataract could be minor. This partially explains the low threshold radiation dose for senior persons that resulted in the need for lens replacement.

More generally, if this explanation is correct, this raises the issue of inverse age-depended sensitivity of the eye lens to radiation exposure. The older is the person and the larger is contribution of senile cataract to the lens opacity, the smaller dose may be sufficient to result in the eventual visual impairment. This point might explain why the method used by Nerishi et al proved to be so sensitive at low doses and why more radiation-induced cataract cases have been clinically detected in LSS subjects in recent years.

That point does not contradict to well known direct age dependence of radiation-induced cataract (PSC or other) on age at exposure. Both kinds of age dependence should be accounted for in the interpretation of such multiple-factor data as presented by Nerishi et al.

Another important point that comes from that paper is that there is no substantial fading effect for radiation-induced cataracts as they could be revealed even in more than half a century after the exposure.

3. Thus, in case of radiation-induced cataracts we first time are dealing with the radiation effect when senior persons are more sensitive to a clinically significant tissue reaction. More precisely, when radiation doses are comparable, the clinically significant health effect may appear earlier in senior people because of summation of the radiation-induced effect with the senile one. As there is little fading, the exposure of young persons will result in a similar effect but later on, in some years or even decades.

This special effect of summation of radiation-induced cataract with senile cataract, which results in unusual age-dependant sensitivity, should be somehow accounted for in the establishing of the dose limit for the eye lens.  If this consideration is correct, then the most sensitive occupational group are the workers at the end of their professional carrier, i.e. senior workers at the age of 60+ y.

As Nerishi et al. have shown, the threshold radiation dose for this age group is rather low, less than 1 Gy. On the other hand, it is hardly possible to implement radiation protection of the lens of the eye with the dose limit that is lower than the limit for the effective dose. It brings to the recommendation that the annual limit for equivalent dose of the lens of the eye in planned occupational exposure during the 50-y working time period might be established at the same level as the limit for effective dose, i.e. 20 to 50 mSv per year.