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
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
ORGAN TRANSIT TIMES TRANSFER COEFFICIENTS 1/T (d-1)
Mouth Total diet 12 s Total diet 7200
Oesophagus Total diet Fast Slow 90 10 7 s 40 s Total diet Fast Slow 90 10 12343 2160
Stomach Total diet 70 min Total diet 20.57
Small Intestine 4 h 6
Right Colon 12 h 2
Left Colon 12 h 2
Recto sigmoid 12 h 2
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 fSIfA.
• 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,i1 is
  the transfer compartment to the next compartment
  i1.

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 (gt 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
51
Iodine

• Age-dependent parameters

52
Caesium

• Description (from ICRP 67)
• Systemic caesium is taken to be distributed
  uniformly throughout all body tissues
• 10 of activity is assumed to be retained with a
  biological half life of 2 days (A)
• 90 of activity is assumed to be retained with a
  biological half life of 110 days (A)
• For female the half time of compartment B is
  significantly less than for males.
• In some countries there is also evidence of mean
  biological half time for adult males shorter than
  110 d.
• Urinary to faecal excretion ratio of 41 is
  recommended.

53
Caesium

• Model

54
Caesium

• Age-dependent parameters

55
Partitioning between urine and faeces
56
Skeleton

• Bone formation is made by bone-forming cells
  (osteoblasts). They synthesise the organic matrix
  and perform mineralisation. This results in a
  hard, durable structure (not permanent).
• Throughout life there is a continual modification
  (remodelling) of bone by bone-resorbing cells
  (osteoclasts).
• Two types of bone structures
• CORTICAL BONE (Compact)
• TRABECULAR BONE (Spongy, Cancellous)

57
Skeleton

• Cortical Bone
• Hard, dense bone
• Forms the outer walls of bones
• The bulk of compact bone is found in shafts of
  long bones (e.g. femur)
• Trabecular Bone
• Soft, spongy bone
• Forms the interior parts of flat bones and of end
  long bones
• It has much higher porosity than compact bone and
  soft tissue content (bone marrow).

58
Skeleton

• Figure related to the head of human femur (ICRP
  70)

59
Skeleton

• Figure of bones in humans (ICRP 70)
• Skull is about 14-15 (around 1/7) of the mass of
  all bones.

60
Skeleton

• Percentages of cortical and trabecular tissues in
  bones (ICRP 70)

61
Model for Sr, Ra and U
62
Model for Sr, Ra and U/2

• Skeletal activity first deposits on bone surfaces
• Return to plasma or migrates to exchangeable bone
  volume within a few days
• Some activity leaves exchangeable bone volume is
  assumed to return to bone surfaces
• Remainder is assigned to non-exchangeable bone
  volume
• Gradually moves to plasma by bone resorption

63
Model for Sr, Ra and U/3

• Soft tissue is represented by 3 compartments,
  ST0, ST1, and ST2
• For radium and uranium, the liver is kinetically
  distinct from other soft tissues
• Excretion of U through the kidney and exchange of
  activity between plasma and kidney tissues is
  also considered

64
Model for Th, Np, Pu, Am and Cm
65
Model for Th, Np, Pu, Am and Cm/2

• Th and Pu retention and
• excretion data are most
• easily reproduced using
• a 2 compartment model
• Liver 2 represents
• retention with t½ gt 1 year
• Liver 1 loses a portion of its activity to the GI
  tract over a relatively short period (1 year)
• Liver 2 shows greater retention of Pu

66
Model for Th, Np, Pu, Am and Cm/3

• Am and Cm ? Liver can
• be treated as a uniformly
• mixed pool, losing activity
• to blood and the GI tract
• with a Tb of 1 year
• Radioactive material enters Liver 1
• Part of the material is removed to the GI tract
  via biliary secretion
• The rest goes to blood.

Liver 1
Blood
GI tract contents
Faeces
67
Model for Th, Np, Pu, Am and Cm/4

• Kidneys are assigned two compartments,
• One loses activity to urine
• Another that returns activity to blood
• Urinary bladder contents is treated as a
  separate pool that receives all material destined
  for urinary excretion

68
Radioactive progeny

• A number of radionuclides decay to nuclides that
  are themselves radioactive
• It has been assumed that the decay products would
  follow the biokinetics of their parents
• A few exceptions made for decay products which
  are isotopes of noble gases or iodine
• The revised biokinetic models apply separate
  systemic biokinetics to the parent and its decay
  products for intakes of radioisotopes of lead,
  radium, thorium and uranium.

69
Excretion
70
Excretion

• Urinary bladder and colon are given wT values
• Specific information is given on excretion
  pathways in the urine and faeces in revised
  biokinetic models for workers.
• GI tract model is used to assess doses from
  systemic activity lost into the faeces.
• Secretion of radionuclides from the blood into
  the upper large intestine is assumed (e.g. for
  bone-seekers radionuclides)
• A urinary bladder model has been adapted for
  calculating doses to the bladder wall
• l 12 d-1 6 voids / d

71
References

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72
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73
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74
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