Internal alpha-particle emitters: their dose to bone marrow and the foetus

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1 Internal alpha-particle emitters: their dose to bone marrow and the foetus Denis L Henshaw, Janet E Allen, Julie J Close, Paul A Keitch and A Peter Fews H H Wills Physics Laboratory University of Bristol Tyndall Avenue, Bristol BS8 1TL, UK

2 238 U 226 Ra α 222 Rn 218 Po 214 Po α α β 214 Bi 214 Po β α 210 Pb β 210 Bi 210 Po β α 206 Pb Radon ( 222 Rn) and its short-lived decay products 210 Pb-supported 210 Po in bone The radionuclides of interest in the natural 238 U decay chain with respect to natural dose to haemopoietic tissue in the foetus and in childhood. Principal half-lives: 238 U years, 226 Ra 1600 years, 222 Rn 3.8 days, 210 Pb 22.3 years, 210 Po 138 days.

3 Principal topics Radon dose to bone marrow and the foetus Dose to bone marrow from long-lived α- emitters, principally 210 Po Risk assessment for childhood leukaemia Detectability in a case-control study

4 Radon dose to bone marrow When inhaled, radon distributes in the body according to its solubility, which is 0.41 in blood and 6.3 in fat i.e. radon is 16 times more soluble in fat than in blood Radon decays in the body giving rise to α-particle emission from both itself and the principal decay products 218 Po and 214 Po In addition, radon decay products in air may be inhaled and distribute round the body

5 Sinus Red blood corpuscle Fat cell 214 Po Stem cell 218 Po 222 Rn 214 Po Fat cell Trabecular bone Schematic diagram representing the α-particle decay of radon and its short-lived decay products inside a marrow fat cell

6 WHITE (FATTY) MARROW RED (BLOOD FORMING) MARROW Custer RP and Ahlfeldt FE, Studies on the structure and function of bone marrow. II. Variations in cellularity in various bones with advancing years of life and their relative response to stimuli. The Journal of Laboratory and Clinical Medicine, Vol XVII, No.10,

7 B = bone FC = fat cell BM = bone marrow Bone marrow within the lumbar vertebra of an 81 year-old female. Note the presence of fat cells (Allen et al. Int. J. Radiat. Biol., 68, , 1995).

8 B = bone CC = calcified cartilage M = marrow Foetal bone and marrow at 35 weeks gestation. Note the absence of fat cells

9 Mean values of annual equivalent dose rate to haemopoietic marrow derived from radon ( 222 Rn and decay products) and thoron ( 220 Rn and decay products) at the average UK indoor exposure of 20 Bq m -3, estimated from birth to age 70 years (from Richardson et al British Journal of Radiology, 64, ).

10 Radon and thoron derived equivalent dose to the human foetus at three representative indoor levels: 20 Bq m -3 (UK average); 42 Bq m -3 (world average) and 1,000 Bq m -3. Radionuclide Dose, µsv at 20 Bq m Bq m Bq m -3 Comment Pure 222 Rn Fat free marrow 222 Rn decay products 220 Rn decay products Assumes no transfer of bismuth Transfer of 212 Pb

11 Long-lived emitters

12 Most long-lived α-radionuclides concentrate in the skeleton, with the exception of 210 Po which is associated with bone only via its 210 Pb pre-cursor B = bone FC = fat cell BM = bone marrow

13 Average concentrations of long-lived α-radionuclides in the human skeleton α-radionuclide Typical levels (Bq kg -1 ) Key references 210 Po/ 210 Pb Czeglédi (1987), Hill (1965), Parfenov (1974), Henshaw et al. (1988) 226 Ra Fisenne & Keller (1981), Walton et al. (1959) 238 U ~0.05 Welford & Baird (1967), Hamilton (1972), Singh et al. (1985), Nozaki et al. (1970) 232 Th ~0.005 Singh et al. (1985) 239 Pu < Burkinshaw et al. (1987), Popplewell et al. (1985, 1988)

14 Bristol measurements of α-activity in human tissues by α-autoradiographic methods Layout of biological sample on TASTRAK autoradiograph

15 Autoradiograph of adult lumbar vertebra

16 Quantitative analysis features Total α-activity is detected Average background 5 α s per cm for several years storage Detection limit of 0.1 Bq kg -1 in unconcentrated tissue samples as small as 5 g Separate activity concentrations for 210 Po and 226 Ra plus some further spectral and cluster analysis

17 Area - dose conversion The detector has a net sampling thickness, so recorded α-particle tracks per cm can be converted to activity concentration in Bq kg -1 For 5.3 MeV 210 Po: 1 Bq kg -1 = 535 µsv y -1 (equivalent dose)

18 A cluster of ~160 α-particle tracks recorded on an autoradiograph of the bronchial epithelium of a 79 yr-old female. The views a, b, c and d were taken at the surface and at depths of 13, 23 and 28 µm respectively. Analysis indicates the presence of a natural uranium mineral grain together with its daughter nuclei.

19 Identifying α-particle track clusters Various α-track clusters 226 Ra and diffused 222 Rn with 218 Po and 214 Po

20 From: Biology II, Anatomy and Physiology, Chapter 46, Section 2.

21 Estimates of dose to red bone marrow Age group Dose rate µsv y -1 References Adult ~132 NRPB R274 table 5.6 Henshaw et al. 1988* 10 yr-old child ~180 Fetus 70 [range 0 160] (accrued dose µsv) Bristol, unpublished data *Radiation Protection Dosimetry 22(4), , 1988

22 Estimated foetal dose also 70 µsv (range µsv) B = bone CC = calcified cartilage M = marrow Foetal bone and marrow at 35 weeks gestation. Note the absence of fat cells

23 CD34+ cell (arrow), B = bone, G = granulocyte, RBC = red blood corpuscle Foetal bone marrow showing CD34+ cell (arrow)

24 Radon and thoron derived equivalent dose to the human foetus at three representative indoor levels: 20 Bq m -3 (UK average); 42 Bq m - 3 (world average) and 1,000 Bq m -3. Radionuclide Dose, µsv at 20 Bq m Bq m Bq m -3 Comment Pure 222 Rn Fat free marrow 222 Rn decay products 220 Rn decay products Assumes no transfer of bismuth Transfer of 212 Pb 210 Po in foetal skeleton (range 0 160) Measured at 20 Bq m -3, scaled for higher exposures Total

25 Geographical variations in levels of 210 Po in children across the UK

26 Using α-activity in children s teeth as a marker for levels on bone The spatial distribution of α-activity on the inner section surface of the upper right 4 tooth taken from a 13-year-old boy. The activity associated with the outer enamel surface arises from 210 Pbsupported 210 Po, whereas the activity associated with the circumpulpal region arises mainly from 226 Ra.

27 Activity concentrations in teeth The outer enamel surface best harbours integrated exposure to 210 Pb/ 210 Po (James et al. 2004a Int. J. Radiat. Biol., 80(3), ). Typical levels 8 12 Bq kg -1 but can reach over 40 Bq kg -1 Activity concentrations of 210 Pb in foetal teeth can be 40% of those in deciduous teeth from a 10 yr-old (however, little ingrowth of 210 Po in the foetus) Activity concentrations in teeth correlate well with those in bone So, we use teeth as a maker for levels in bone and dose to bone marrow

28 Correlation between 210 Po in teeth (expressed as ln [210Po α-activity concentration]) and distance from residence to the M5/M6 motorway crossing urban areas of the UK. The data refer specifically to children living east of the motorways. This corresponds to the side downwind of the prevailing southwesterly wind (from James et al. 2004b, Int. J. Radiat. Biol. 80(3), ). Distance from motorway (km) Pearson correlation coefficient, r (number of children) p-value < (87) 0.53 < (50) 0.01

29 5 ln [Activity conc n ] (Bq kg -1 ) p = n = Radon concentration (Bq m -3 ) 210 Po α-activity concentration in teeth versus mean indoor radon concentration by postcode in the UK.

30 Risk assessment COMARE 4th Report page 62:

31 Risk assessment contd. For high-let the 14% link divides: ~9% 210 Po RR = 1.09 at normal 210 Po levels compared with zero 210 Po ~5% Radon RR = 1.05 at 20 Bq m -3 compared with zero radon These estimates are extremely difficult to test in a case-control study design because of problems of ubiquitous exposure and of resolving small increases in risk

32 Radon leukaemia correlations There have been a number of reports of geographical associations between radon and leukaemia: Lucie 1989, Henshaw et al 1990, Alexander et al 1990, Butland et al 1990, Lucie 1990, Muirhead et al 1991 & 1992, Cohen 1993, Richardson et al 1995, Lyman et al 1986, Collman et al 1991, Viel 1993, Forastiere et al 1992, Hoffman et al 1993, Thorne et al 1996, Kohli et al 2000 And at this conference an association between radon and childhood leukaemia in France: P2-4 Anne-Sophie Evrard et al. Institut National de la Santé et de la Recherche Médicale, INSERM, Villejuif

33 Conclusion High-LET radiation dose to children s bone marrow is dominated by natural sources, principally radon and its short-lived decay products and from 210 Po Risk analysis suggests that 14% of the incidence of childhood leukaemia is linked to natural high-let radiation, with ~9% from 210 Po and ~5% from radon These risks would be higher in children living in high radon areas and areas of high traffic density The risk assessments could be challenged by the findings of genomic instability and the bystander effect In any case the magnitude of the purported links are essentially undetectable in a case-control study design owing to the problems of ubiquitous exposure and resolving power for small excess risks. However, geographical associations with radon continue to be reported.

34 Acknowledgements The work described here has been supported by: CHILDREN with LEUKAEMIA Department of Health (UK) Medical Research Council and UKCCCR.

35 Welcome to the International Scientific Conference for Childhood Leukaemia incidence causal mechanisms prevention