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 Cari Borrás, Federal University of Pernambuco, Recife, Brazil
Commenting as an individual

This is an outstanding document with extensive literature reviews, which will become a good database for future consulting. However, for radiation protection specialists with limited knowledge on radiation biology, the text is very dense and repetitious. Often it appears to present contradictory statements especially regarding basic issues such as single-hit events, stochastic effects and zero dose thresholds. The cell survival curve is described three times, every time from a slightly different angle. A careful reading shows there are no inconsistencies, but…

 

It is recommended that the whole text be checked by a technical reviewer to make sure not only that there are no inconsistencies, but also that the different approaches taken in the various sections are complimentary and not repetitious. In fact, it is questionable why the same facts (such as the use and effect of modifiers), have to be presented in each one of the last three chapters; can there be no cross-references?

 

An example of apparent “inconsistency” is in Lines 9177-9179 vs Lines 9249-9252 and Line 9270 and Line 12543. In lines 9177-9179, it says that “drugs such as G-CSF” “are not approved (I guess by the FDA?) to treat lethally irradiated personnel”. In Lines 9249-9252 it says they are “the only regulatory approved (no mention of who is the regulatory agency here) drugs available for the treatment of radiation-induced myelosuppression and potential lethal exposures within the haematopoietic ARS”. The latter paragraph is under a heading (Line 9218) of “Treatment … in the clinic”. Where other than in a clinic will “lethally irradiated personnel” be treated? Line 9272 again talks about that they are approved to treat myelosuppression. And in Line 12543 it says, “Growth factor administration can increase survival rates in radiation accident victims”. So, should they be used whether approved or not?

 

It would also help the reader if the first time an acronym is used, the full spelling be given. This is particularly important in Chapters 2 and 3, especially when dealing with chemical compounds and biochemical processes. Examples of acronyms that have to be spelled the first they appear are as follows:

Line 5070 and Line 5412    “LI”

Line 5241                              “EC”

Line 6015                              “TSH”

Line 6071                              “ACTH”

Line 6127 (twice)                 “LH”

Line 6175                              “PNC”

Line 9292                              “AR”

Line 9310                              “HSC”

Line 9321                              “ATM”. Again, this is an editorial issue.

 

Obsolete terms such as “exposure dose” should not be used. For example in

Line 1246-1247        “exposure dose rate” should be changed to “dose rate”.

Line 5118                  “exposure dose” should be changed to “dose”

Lines 5460, 5795,     “therapeutic exposure doses” should be changed to either “Doses from therapeutic exposure” or simply to “Therapeutic exposure”?

  

Other editorial matters involve the use of words that seem inappropriate. For example, it is recommended that the following changes be made:

Line 203 and Line 12531    “recommended” by “estimated”

Line 1757                              “predict” by “estimate”

Line 1874                              “Preclinical data” by “Animal studies”

Line 5136                              “Reduced lung volume and compliance” by ??? (what does “compliance” here mean?

Line 10991                            “growth velocity” by “growth rate”

 

Another matter that would help the reader to follow the document is to change the sequence of certain paragraphs, especially in Lines 1831-1955,  Section 1.2.3. , where it would be better to start with Animal studies (now called Preclinical data), follow it with Clinical data and end with Chronic radiation syndrome as it is now.

 

Other paragraphs whose sequence could be changed to help the reader are in:

Lines 4484 -4515, where paragraph (267) should come after (265) and before (266). The reason is that Paragraph (267) deals with a study that contradicts the paper by Okladnikova et al., discussed in (265).

 

In regards to self-consistency, it is questionable why Lines 2886-2986, “Section 2.3.5, Risks to the offspring” exist. The document makes clear in the introduction that it will not dwell on stochastic effects, yet hereditary effects are clearly stochastic. Consequently, the whole section should be removed from this document.  (It is very well written, though; it should be incorporated into another ICRP publication).

 

Lines 3522-3526, Paragraph (188), contain another paragraph that should be deleted. The statement made is a truism – uses of radiological techniques have increased worldwide – but why should this appear in Section 2.5 on Cardiovascular and Cerebrovascular Systems? Perhaps such a caveat on the risk from medical exposures should be made in the introduction, as it is pertinent but not just limited to cardiovascular and cerebrovascular risks. (The section deals with doses <5 Gy; yet in some fluoroscopically-guided interventional procedures, doses may be higher.  The problem is particularly serious when neonates are exposed to assess the extent of congenital abnormalities, which may require repetitive interventions as the children grow.)

 

Another issue deals with the use of mSv rather than mGy throughout the document. When referring to a publication, it seems OK to give the unit used by the original authors, but in the expression of threshold doses within this report shouldn’t mGy be used? mSv is a unit for equivalent and effective doses that cause stochastic effects. The draft leaves open the issue whether cataract formation is a stochastic or a deterministic phenomenon, it only states that the estimated threshold is 0.5 Gy. Yet in Line 12888 it says 500 mSv.  For consistency, this should be changed to 0.5 Gy.  In fact, Lines 13485-13497 (at the end of the document in Appendix B) address this issue very well. Rather than being at the end, this “Footnote” should appear at the beginning of the document, especially since it implies that it may be OK to use mSv since the “threshold model” “remains uncertain”. The question at hand is more than the usage of units but the concept of stochastic vs deterministic effects!

 

Finally, there are certain omissions, the reason of which could be clarified.  In the description of acute radiation syndromes, the haematopoietic and GI syndromes are well discussed. Why are there no references to the neurovascular one? Criticality accidents that resulted in death within hours did show neurovascular signs… This is the case, for example, of the 1958 Los Alamos accident, where the irradiated person died within 35 hours after the exposure. (In the web, a summary of the event can be found at: www.fas.org/sgp/othergov/doe/lanl/pubs/00326644.pdf). Have the clinical observations been reinterpreted? If so, a statement why neurovascular effects from high doses of radiation are no longer considered should be made.

 

Another publication which can be added to the review of gastrointestinal injuries is: Cari Borrás, D.Sc., Juan Pablo Barés, M.D., Damian Rudder, M.Sc., Ali Amer, M.Sc., Fernando Millán, M.D. and Oscar Abuchaibe, M.D.  Clinical effects in a cohort of cancer patients overexposed during external-beam pelvic radiation therapy.  International Journal for Radiation Oncology, Biology, Physics.  Vol 59, No.2, pp. 538-550, 2004.

 

The text also needs to be edited for language; there are orthographic errors.


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