Biological consequences of ionizing radiation BNEN 2012-2013 Intro William D’haeseleer.

Biological consequences of ionizing radiation

BNEN 2012-2013 Intro

William D’haeseleer

Prologue (1)

• From Chemical context (Cfr P. Pôlet)

To illustrate this, I wish to tell the following anecdote.A British scientist had written a study about risks. His study had the correct inclination: he said that it is not the product, but the dose that makes the poison. The thesis of the British scientist was that you could blame every product if you only use the “appropriate” arguments. He wanted to test this and towards that purpose, he interviewed 123 at random in the London underground stations. His question was:

Prologue (2)

Prologue (3)

You certainly have understood this: indeed, he was talking about … . Well, about 5% said no, 19% said that they did not know, but 76% (>3/4) agreed to ban ! Unbelievable, but true. It shows the serious challenge the chemical industry is up to to improve its image and to overcome this sort of phobia.

Prologue (3)

You certainly have understood this: indeed, he was talking about … . Well, about 5% said no, 19% said that they did not know, but 76% (>3/4) agreed to ban water ! Unbelievable, but true. It shows the serious challenge the chemical industry is up to to improve its image and to overcome this sort of phobia.

Back to

Radioactivity Radioactivity

Ionizing RadiationIonizing Radiation

Ionizing particles Recall

• Directly ionizing particlesalpha (He-4++) & beta (e-/e+)

• Indirectly ionizing particlesGamma or X rays/photons & neutrons

Impact ionizing particles

• How dangerous is radiation? Cfr. B.L. Cohen:

Health impact ionized radiation …eh?

«When one of these particles or rays goes crashing through some material, it collides violently with atoms or molecules along the way…. In the delicately balanced economy of the cell, this sudden disruption can be disastrous. The individual cell may die; it may recover. But if it does recover… after the passage of weeks, months or years, it may begin to proliferate wildly in the uncontrolled growth we call cancer.»

Ref: S. Novic, “The careless atom”, Dell, NY, 1969

• B.L. Cohen continued:

• B.L. Cohen still continued:

Indeed, due to natural radiation:

number of e/i pairs in person 70 kg~ 109 = 1 billion per second

x 60 years (taking into account weight evolution 020y)

~ 1 à 2 1018 ionizations over one’s whole life = one billion times one billion !

How come we don’t all die like flies???

External radiation / Contamination

Fundamental difference between

External (ir)radiation

Contamination

Radioactive source Radioactive source outsideoutside body body

Radioactive source Radioactive source insideinside body body

• External (ir)radiation

- depends on type of radiation α β γ n

- shielding* natural: air / water / soil

* engineered: concrete, Pb

- distance

- irradiation time

• ContaminationEspecially for α & β sources !When inside the body, not possible to shield

α can cause considerable damageβ relatively dangerous

Contamination of the skin: “whipe” / “scrub” clean

• ContaminationNow also biological T1/2

time to remove half of radioisotope from body urine, stools, sweating, exhaling,…, vomiting,…

Effective T1/2 λeff = λph + λbio 1/Teff = 1/Tph + 1/Tbio

Smallest T1/2 dominates Teff

Special Characteristics

• Note the passive nature of radio-isotopes– Do not have “legs” do not migrate actively– Can only migrate passively must be

transported away by carrier (e.g., dissolved,…)

• Because of ionizations– Ionizing radiation (as a rule) well measurable

(compared to e.g., chemical / toxic substances)

Dose Concepts

Units & Radiation Concepts

• Recall Activity [=] Bq

Source characteristic

# disintegrations/sec

• Flux or Intensity or “exposure”[=] #/(sm2)

Field characteristic

# particles/(sm2)

• Absorbed Dose [=] J/kg or Gy

Receiver characteristic

Energy/mass

Joule/kg

Old unit rad; 1 Gy = 100 rad

• Dose Equivalent [=] Sv

Receiver characteristic in man

Energy/mass

Weighted for distribution deposited energy & biological damage

Old unit rem; 1 Sv = 100 rem

• Dose Equivalent [=] SvReceiver characteristic in man (for LL radiation)

Dose eq Abs Dose Quality Factor

(Sometimes correction factor for dose rate or fractionation N)

Q = 1 for X, gamma and Beta

Q = 20 for alphas

Q = 5 – 20 for neutrons (dependent upon energy)

• Collective Dose Equivalent [=] man-SvReceiver characteristic in men/women for populations (LL radiation)

1 Man-Sv = 1000 people at 1 mSv

= 100 people at 10 mSv

Only makes sense in linear relationship Dose & Effect

Careful for very small Doses & very large populations 0 x ∞ = unstable

Biological effects

• Physiology of man

Biological effects

• Cell Biology

Biological effects

• Possible biological consequences

Ionizations … free radicals … upset chemical bonds … potential damage cell… perhaps biological damage

Biological effects

• Interactions of radiation with cells: 4 stages

Initial physical stadium

Energy deposition & ionization

E.g., H2O → H2O+ + e-

Biological effects

Physico-chemical stadium

Interaction ions with H2O new products

E.g., H2O+ → H+ + OH

H2O + e- → H2O-

H2O- → H + OH-

Ions H2O- H2O+ H+ OH-

Free radicals OH H

Nuclear Energy 2011-2012William D’haeseleer

Biological effects

Chemical stadium

(some seconds)

Reaction products interact with organic molecules in the cell

Biological effects

Chemical stadium

(some seconds)

Reaction products interact with organic molecules in the cell

-Death of cell

-Impairing cell division

-Change (in nucleus of cell) transferred to daughter cells

Biological stadiumminutes - years

Biological effects

• Reference for more detail:

Biologic effects of radiation

1) Somatic effects (own-body related)a) Early effects due to acute high doses

= “deterministic effects”

b) Stochastic effects due to low doses

~ cancer development

2) Genetic effects (offspring-related)Stochastic in nature

Deterministic effects

• Due to acute & high dose radiation• Basically accidental situation• Appears after some hours to some weeks• Because depletion of cells in important

organs (death cell / impairing cell division)• Organs such as

– bone marrow– digestive track– brains

• Major characteristics of deterministic effects:

1. There is a threshold of dose below which the effects will not be observed.

2. Above this threshold, the magnitude of the effect (= “severity”) increases with dose.

3. The effect is clearly associated with the radiation exposure.

Ref: Stabin, 2008

• Dose ~ 1 Gy radiation sickness• Dose < 1.5 Gy probab no early death• Dose ~ 2 Gy could lead to death after 2 wks• 30LD50 ~ 3-4 Gy (or …5 with med care) for man

deadly dose for 50% of exposed people within 30 days

• Dose 3 - 10 Gy infection death• Above 10 Gy death after 3 à 5 days• Still higher doses: CNS death

Stochastic Somatic effects

• After certain weighting period can lead to cancer (solid cancers / leukemia)

• Based on observation of– Atom bomb survivors– Radiologists– Radiation therapy patients– Uranium mine workers etc

• Based on radiobiological research

• Actually extrapolation from ~ medium & high level doses

• Effects below ~ 100 à 200 mSv limited statistical significance

• Difficulty to estimate risk:– Long & variable waiting period (5…30y or more)

– Radiation-driven cancers indistinguishable from other cancers

– Human tests/experiments not justified– Animal tests/experiments not directly transferable to

humans

Curves for individual

Probability to get malignant/lethal cancer = f (dose equivalent)

LNT hypothesis

• Existence “adaptive response” & hormesis recognized, but insufficient exact justification to form basis for norms & standards

• For low doses, also dose rate is important: correction factor

DDREF: Dose & Dose Rate Effect Factor

Slope of LNT line:

~ 5 % per Sv

~ 5 x 10-5 per mSv

105 people with 1 mSv 5 radiation induced cancers

BEIR VII

BEIR VII 2007

Number of cases or deaths per 100,000 exposed persons

5 - 7 x 10-5 per mSv fatal cancers (solid & leukemia) DDREF= 1.5

deaths

• LNT disputed…by some authoritative scientists…

• Considered to be

an overestimate

Viewpoint French Academy of Sciences and Academy of Medicine…

American Scientists defending BEIR VII, US academy of Sciences…

A D Wrixon, “New ICRP recommendations”, Journal of Radiological Protection 28, 2008, 161–168 doi:10.1088/0952-4746/28/2/R02Available at: http://iopscience.iop.org/0952-4746/28/2/R02/pdf/0952-4746_28_2_R02.pdf

Formal ICRP Recommendation 2007Formal ICRP Recommendation 2007

Hence ~ 5 % / Sv or 50 ppm / mSv

Stochastic Genetic effects• Causes of mutations:

– Heat – Chemicals– Spontaneous mutations– Radiation

• NOT possible to distinguish between the causes!

• Effects: probability genetic disease (also LNT) - first-generation progeny (1990 numbers) ~ 0.3-0.5% / Sv or 3-5 x 10-6 / mSv - all later generations ~ 1% / Sv (1990 numbers)

Stochastic Genetic effects• Note:

Order of magnitude of about 1% per Sv (1990 numbers))

– In the US:

Natural radiation of individual to gonads ~ 0.85 mSv/a

About 300 million inhabitants

Hence 255,000 man Sv/a * 0.01 ≈ 2500 genetic diseases per

Is about 2% of all cases in the US

Stochastic Genetic effects• Note:

Order of magnitude of somebody’s risk to have a genetically “affected” child from exposure to 1 mrem=0.01 mSv (1990 numbers)

with ~ 3-5 x 10-6 / mSv ~ 3-5 x 10-8 / mrem before conception

= equivalent with waiting with conception by ~ 3 hrs

cafeine & alcohol: 1 cup of coffee ~ equivalent with 0.02 mSv

Stochastic Genetic effects

• But recent research has shown that earlier estimates (~1990) have been overestimated

“Radiation-induced hereditary effects have been clearly demonstrable in animal experiments involving mice and fruit flies, but never in any human populations, including the Japanese bomb survivors, medical populations, and populations affected by the Chernobyl disaster. As with cancer, there is a spontaneous rate of mutations that is ongoing in the human population, with no excess exposure to chemicals, radiation, or other mutagenic agents. About 1 in 200 pregnancies involve a baby with a chromosomal abnormality, and about 3-4% of all pregnancies result in some abnormality being expressed in the child. Increases above this baseline, for radiation-induced genetic effects, are expressed in a unique term called the Doubling Dose. This Doubling Dose is the radiation dose to the gonads that will eventually lead to a doubling of the expression of hereditary effects, over the “spontaneous” rate in the given population.” [...]

Ref: Michael G. Stabin, “Radiation Protection and Dosimetry – An Introductuin to Health Physics”, Springer, Berlin, 2008, p 98

[...] “In the most recent recommendations of the ICRP, however, the risk weighting factor has been decreased substantially [compared to earlier estimates], perhaps reflecting the fact that more time has gone by and no significant effects have been demonstrated in human populations.”

Ref: Michael G. Stabin, “Radiation Protection and Dosimetry – An Introductuin to Health Physics”, Springer, Berlin, 2008, p 98

A D Wrixon, “New ICRP recommendations”, Journal of Radiological Protection 28, 2008, 161–168 doi:10.1088/0952-4746/28/2/R02Available at: http://iopscience.iop.org/0952-4746/28/2/R02/pdf/0952-4746_28_2_R02.pdf

Formal ICRP Recommendation 2007Formal ICRP Recommendation 2007

Hence ~ 0.1 – 0.2 % / Sv or 1 - 2 ppm / mSv

Stochastic effects

Note: 1 rem = 0.01 Sv = 10 mSv

< 50 – 100 mSv

Stochastic effects

Background radiation

Background radiation• Due to natural, medical & industrial

exposure• In Belgium, total annual equivalent dose:

3.6 à 5 mSv3.6 à 5 mSv• Until ~ 2000, used value was 3.6 mSv/a

– Natural: 2.6 mSv/a• Body + Cosmic + Soil/Buildings = 1.0 mSv/a• Radon = 1.6 mSv/a (average for B)

– Man made: 1.0 mSv/a• Medical = 0.95 mSv/a• Industrial (all) = 0.05 mSv/a

Background radiation• In Belgium, total annual equivalent dose:

3.6 à 5 mSv3.6 à 5 mSv

• Currently, value is 5 mSv/a !!– Natural: 2.6 mSv/a

• Body + Cosmic + Soil/Buildings = 1.0 mSv/a• Radon = 1.6 mSv/a (average for B)

– Man made: 2.4 mSv/a• Medical = 2.35 mSv/a• Industrial (all) = 0.05 mSv/a

Overconsumption with CT scans etc…

only for diagnostics; no therapy

Ref. H. Vanmarcke (SCK)

3.6 à 5 mSv3.6 à 5 mSv

• Radon = 1.6 mSv/a (average for B)– But for Vl ~ 0.5 – 1 mSv/a– And for Wall ~ 2 – 4 mSv/a– Difference of Vl & Wall ~ same order as

average natural background!

Radon:

Daughter product of Ra-226

3.6 à 55 mSv mSv

• According to LNT estimate:• ~ 5 x 10-5 per mSv• 107 Belgians ~ 2500 fatal cancers per year• Due to natural & medical causes!

• In a lifetime (take 60 years):5 mSv/a x 60 = 300 mSv

• 300 mSv at 5%/Sv LNTH 0.015

Current safety standards

• General population:

Max extra artificial dose eq (excl med)

= 1 mSv/a1 mSv/a

• Employees in nuclear sector (Belgian law)

Max extra artificial dose eq (excl med)

= 20 mSv/a20 mSv/aIn normal / routine circumstances

EU directive specifies 100 mSv/5a

Current safety standards

• Employees in nuclear sector Max intervention dose recommended

= 250 mSv/a250 mSv/a

Max dose for “life saving” intervention= 500 mSv/a500 mSv/a

In exceptional / accidental circumstances (in Belgium)

Permissible Doses for Astronouts

References

• Some basic examples (a.o.)

Biological consequences of ionizing radiation BNEN 2012-2013 Intro William D’haeseleer.

plet slide

body slide

impact ionizing particles

irradiation time slide

ionizing particles gamma

natural radiation

chemical context cfr

intro william dhaeseleer

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