ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES

1. ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES Biokinetic Models

2. Biokinetic Models - Unit Outline • Ingestion • Entry through Wounds and Skin • Systemic Activity • Excretion

3. Ingestion

4. Ingestion - Gastrointestinal tract model • ICRP 30 model has 4 compartments, • Stomach, • Small intestine, • Upper large intestine and • Lower large intestine • Uptake to blood in the small intestine - specified by fractional uptake (f1) values

5. Gastrointestinal tract model ICRP 30 Ingestion Stomach (ST) ST B Small intestine (SI) Body fluids SI Upper large intestine (ULI) ULI Lower large intestine (LLI) LLI Faecal Excretion Transfer constant,  = 1/residence time All tabulated values for ingestion are based on this model

6. New Human Alimentary Tract (HAT) model - ICRP 100 • ICRP 60 introduced specific risk estimates and wT for radiation-induced cancer of the oesophagus, stomach and colon • Dose estimates needed for each region • ICRP 30 model: • Did not include the oral cavity or the oesophagus • Treated the colon as two regions - upper and lower large intestine.

7. New HAT model ICRP 100 /2 • Considerable data is now available on material transit times through the different regions of the gut using non-invasive techniques • Information has become available on the location of the sensitive cells and retention of radionuclides in different regions • New data includes • Differences between solid and liquid phases • Age and sex related differences • Effect of disease conditions

8. New HAT model ICRP 100 /3 • Data are being used: • to determine default transit rates for the defined regions of the alimentary tract • for the 6 age groups given in ICRP 56 • New information: • For morphometrical and physiological parameters, • On the location of sensitive cells and in different regions of the alimentary tract

9. Anatomy and physiology of HAT • Primary functions • To move the food • Digestive function • Absorptive function • Excretion function via liver and biliary tract. • Additional functions • Defensive functions to protect the body from colonization by bacteria • Contains microbial population that produces vitamins

10. Anatomy and physiology of HAT • Overall structure • Detailed structure of different epitelia • Oral cavity, pharynx, oesophagus • Stomach, small and large intestines • Villi and crypts structure in small intestine

11. Structure of the HAT Model – ICRP 100 • Deposition and retention on teeth. • Entry per ingestion, from Respiratory Tract • Deposition in oral mucosa or wall of the Stomach and intestine • Transfer back from the oral mucosa or walls of ST and intestine back in the lumen • Transfer from various secretory organs or blood into the contents of certain segments of HAT.

12. Main differences with previous model /1 • Oral cavity not present in the ICRP30 model • In ICRP30 model the division of large intestine is in only 2 regions : ULI and LLI. (in HATM there are 3 regions for the colonic transit) • The ICRP30 model takes into account only decays of the radionuclide occurring during transit. In HATM it has been taken into account also transformations of the radionuclide due to retention in tissues.

13. Main differences with previous model /2 • In ICRP30 model absorption of a radionuclide is supposed to occur only in Small intestine. HATM includes pathways to account for absorption from : • Oral mucosa • Stomach, • Specific segment of colon • HATM provides age- and gender-specific transit times for all segments of the tract and for the upper segments (oral cavity, oesophagus and stomach) it provides also material specific transit times.

14. Transit times • Extremely large deviation from the norm can be found from constipation or diarrhoea, unusual diet or pharmaceuticals which can affect the actual transit times. • So the default transit times may not be appropriate for individual specific applications. • Uncertainties and variability in transit times are reported in ICRP 100. • Within a first-order kinetics a transit time of T days corresponds to a transfer coefficients of 1/T per day (d-1) • The review of data has been done for the transit times of all segments of HAT.

15. Transit times and tranfer coefficients for Adult Males

16. Absorption from content of HAT • Even if the absorption predominantly took place in the small intestine, provision is made for the inclusions of components of absorption from • oral cavity, • stomach or • any segment of the colon. • Absorption from any other segment of the alimentary tract is depicted as transfer from the contents to the wall of that segment, followed by transfer to blood in the portal vein to entry into the general circulation.

17. Absorption from content of HAT / 2 • In the planned ICRP reports that will recommend the use of the HATM for a range of elements, information for each element will be given in terms of fractional absorption, replacing the f1 values of Publication 30 (ICRP, 1979) with fA values. • Thus, fA denotes total absorption to blood in the HATM and represents the fraction of the material entering the alimentary tract. • It is given by the sum of the fractions of the material entering the alimentary tract, fi, absorbed in all of the regions of the alimentary tract:

18. Absorption from content of HAT / 3 • In the majority of cases, information will only be available on the total absorption of the element and its radioisotopes to blood with no information on regional absorption. As in the Publication 30 model the standard assumption will be that this absorption takes place entirely from the small intestine so fSI=fA. • On the contrary if an element is known to be absorbed from the stomach as well as from the small intestine, values of fST and fSI would be specified, where:

19. Absorption from content of HAT / 4 • For the implementation of the HATM in the absence of absorption from retention in the walls, teeth and oral mucosa, the following transfer coefficient li,B applies for the uptake to blood from compartment i of the HATM. • Where fi is the fraction of then intake assumed to be absorbed from compartment i and li,i+1 is the transfer compartment to the next compartment i+1.

20. Absorption from content of HAT / 5 • In the most common case with the absorption only from the small intestine to the blood the transfer coefficient is given by lSI,B is given by • Where lSI,RC is the coefficient for transfer from the small intestine to the right colon (6 d-1).

21. Absorption from content of HAT / 6 • In the case of an absorption also from the stomach fST, the transfer coefficient for uptake from the stomach is given by lST,B is given by • Where lST,SI is the coefficient for transfer from the stomach to the small intestine (20.57 d-1 for adults and total diet). In this case case the transfer coefficient for uptake from the small intestine ( lSI,B ) is given by:

22. Dosimetry of HAT • Geometric model for the calculation of SEE values for the tubulus part of the HATM

23. Dosimetry of HAT / 2 • Geometric model for the calculation of SEE values for the epitelial lining of the small intestine

24. Dosimetry of HAT / 3 • Depth of target cells in the different sub-regions of the HATM, in adult male. • The target cells are always the epithelial stem cells. • For some alpha and beta emitters this change in respect to ICRP30 model and substantially reduced dose estimates as the alpha or beta emissions originating in the content of the HAT do not penetrate the depth at which the sensitive cells are thought to reside.

25. Dosimetry of HAT / 4 • Comparison in SAF values (g-1) from ICRP 30 and HATM for the lumen of stomach in adult male. (in function of electron energy ).

26. Dosimetry of HAT / 5 • Comparison of committed equivalent doses and E(50) for Ru-106 and Pu-239 after ingestion, using HATM and ICRP 30 models.

27. Dosimetry of HAT / 6 • For the dose to the organ “colon” the mass weighted mean of the dose coefficients of the 3 sections of the colon i.e. (this implies that the relative risk of radiation effects is not significantly different in these 3 regions) • For the time being no calculation has already been performed with the HATM as the values of fA have not been indicated by ICRP for the different elements.

28. Entry through Wounds and Skin

29. Entry through wounds • Much of the material may be retained at the wound site, however • Soluble material can be transferred to other parts of the body via blood • Insoluble material translocated slowly to regional lymphatic tissue • Gradually dissolves and eventually enters the blood • Some insoluble material can be retained at the wound site or in lymphatic tissue for life • May need to excise contaminated tissues.

30. Entry through wounds. Soluble materials • Soluble materials may translocate from the wound site to the blood • Translocation rate depends on solubility • Distribution of the soluble component similar to material entering blood from lungs or GI, however • Some exceptions for radionuclide chemical forms entering blood directly

31. Wound model History • In the past ICRP and NCRP both developed a respiratory tract model in parallel • - About 10 years ago they agreed to share tasks to develop biokinetic models • - ICRP: Human Alimentary Tract Model (ICRP 100) • - NCRP: Wound Model • - Both committees had representation from both organisations

32. Announced Biokinetic NCRP Wound Model

33. The SOLUBLE Model • 4 types of “Soluble” compounds have been indicated by NCRP : • Avid • Strong • Moderate • Weak • related to the persistent retention in the wound site (chemical behavior)

34. Retention at the wound site for soluble materials

35. The COLLOID Model As difference from soluble materials the grouping of insoluble materials in wound are based on the physical properties of the deposited material. The three categories indicated by NCRP are Colloid, Particle and Fragment.

36. The PARTICLE Model In this model particles with diameter less than 20 micrometers are considered

37. Characteristics of the Wound Model - Input material-specific due to its physical and chemical state: soluble, colloids, particles (≤ 20 µm), fragments (> 20 µm) - Soluble material may become insoluble due to hydrolysis and vice versa - Release from the wound site to blood (soluble materials) and lymph nodes (particles) - 4 retention classes for soluble material: weak, moderate, strong and avid due to retention after 1, 16, and 64 d.

38. Values of parameters in NCRP wound model

39. Status of NCRP wound model - A set of final transfer rates is given for all 7 default categories - It will be published soon as NCRP report. - No dosimetric parameters for wound sources. - ICRP will adopt this model; the revision of ICRP Publication 30/54/68/78 will contain wound information.

40. Entry through intact skin • Several materials can penetrate intact skin • Tritium labeled compounds, • Organic carbon compounds and • Compounds of iodine, • A fraction of these activities enter the blood • Specific models need to be developed to assess doses from such intakes, e.g. behavior of tritiated organic compounds (OBT) after direct absorption is quite different from that after inhalation or ingestion

41. Entry through intact skin • Both the equivalent dose to the contaminated area and the effective dose need to be considered after skin contamination. • ICRP biokinetic models can only be used for the calculation of the effective dose arising from the soluble component, once the systemic uptake has been determined.

42. Systemic Activity

43. Uptake • The fraction of an intake entering the systemic circulation is referred to as the uptake • ICRP models for radionuclides in systemic circulation are used to calculate dose coefficients • Following review of data behavior of radionuclides in the body, a number of elemental models have been revised • Revised models were also used to calculate dose coefficients for workers

44. Revision of systemic models • Models for several elements have been revised, particularly to account for recycling of radionuclides between compartments (so they are more complicated!) • The model are more physiologically oriented, can be applied to calculate bioassay quantities, and evaluate dose to the general population not only to workers. • Previously, a number of radionuclides (e.g. 239Pu) were assumed to be retained on bone surfaces - a conservative assumption • Evidence indicates a fraction of plutonium is buried as a result of bone growth and turnover

45. Revision of systemic models/2 • Another fraction is desorbed and re-enters the blood • Some may be re-deposited in the skeleton and liver or be excreted • In contrast, ‘bone volume seeking’ nuclides, such as 90Sr and 226Ra, have been assumed to instantaneously distribute in bone volume

46. Revision of systemic models/3 • The process is actually progressive • Generic models for plutonium, other actinides, and for the alkaline earth metals have been developed to: • Allow for the known radionuclide behavior • Account for knowledge of bone physiology • The model for alkaline earth metals has also been applied, with some modifications, to lead and to uranium.

47. Revision of systemic models: generic model

48. Non-recycling generic model

49. Iodine • Description (from ICRP 67) • Of iodine that reaches the blood : • a fraction equal to 30% is accumulated into the thyroid gland, • a fraction of 70% is excreted directly in urine. • The biological half life in blood is taken as 0.25 d. • Iodide incorporated into thyroid hormones leaves the gland with an half time of 80 d and enters other tissues where it is retained with a half-time of 12 d. • Most iodide (80%) is subsequently released and is available in the circulation for uptake in the gland and urinary excretion. • The remainder (20%) is excreted in faeces in organic form.

50. Iodine • Model : ULI LLI