Absorption and Retentiono of Radionuclides

ANNEX D: ABSORPTION AND RETENTION OF RADIONUCLIDES
F. Paquet, J.D. Harrison
D.1. Introduction
(D1) The biokinetics of radionuclides are determined by many physiological, bio-

chemical, and physicochemical parameters. After ingestion, radionuclide behaviour
uticati, delovati
is influenced by its initial chemical form [i.e. the oxidation state, concentration, and
the exact chemical species present (chemical speciation)], its reaction with the chem-
sastojak
ical constituents of the contents of the alimentary tract, and the age, gender, health
status, and nutritional habits of the person.
(D2) Particular attention is given to the effects of speciation since chemical
changes taking place in the mouth, stomach, and small intestine have the potential
bitno
to markedly influence absorption of elements and their radioisotopes. However,
ipak, i pored toga
the mechanisms are unclear and the chemical species are often unknown. Neverthe-
razmisljanje, razmatranje
less, such changes require consideration and are relevant to the use of animal data to
proveriti, predvideti, predskazati
predict absorption in humans consuming mixed diets containing a variety of poten-
tial complexing agents (Cooper, 1985). When a radionuclide is ingested as a chelate
that is stable over a wide pH range, chemical changes in the alimentary tract are less
izloziti
likely to occur. Chelates such as that between plutonium and DTPA exhibit rela-
tively high intestinal absorption but the complex is so stable that it is not metabolised
and is rapidly excreted (Baxter and Sullivan, 1972; Sullivan et al., 1983a). However,
plutonium–DTPA is an extreme example; other complexes that are likely to be
formed in foods, such as plutonium citrate, are more readily absorbed than inorganic
plutonium but are metabolised and the plutonium is retained in tissues.
(D3) Early work on the nutritional requirements of animals established that the
bioavailability of elements depends on dietary composition. It has been shown, for
example, that the absorption of calcium by puppies was influenced by the type
zrno, zitarica
and amount of grain in the diet (Halloran and Delucas, 1980). It has also been
known for many years that there are considerable differences between levels of
absorption of different chemical forms of copper from rat intestine (Cooper,
1985). Studies on different elements have led to the conclusion that the chemical form
of an ingested element may affect its absorption, with the general observation that
incorporation into food may lead to greater absorption than ingestion of the inor-
ganic form of an element.
(D4) Transfer measurements from gastrointestinal segments have been useful in
characterising the absorption of different chemical compounds. Such experimental
procedures have shown that different gastrointestinal compartments are involved
in the absorption of different metals (Fritsch et al., 1986). However, in most cases,
neither the chemical transformations in the alimentary tract nor the exact site of
absorption have been defined.
(D5) Many experimental studies have been reported in which actinide absorption
has been measured in animals, and a few human volunteer studies have also been
performed. Human data are particularly valuable, but animal experiments provide
important information on the effect of variables such as chemical form, diet, and
233
ICRP Publication 100
age at intake. The available data appear to provide a good basis for recommending
the gut transfer factors for the ingestion of many radionuclides by adults, including,
for example, the most important actinide elements, neptunium, plutonium, and
pouzdan,siguran kao ni prostor, opseg, granica ni, niti
americium. The values for infants are less reliable as neither the extent nor the dura-
tion of the period of increased absorption in humans can be predicted with certainty
(Harrison, 1991).
(D6) There is good evidence from animal experiments, with supporting human data
for some elements, that the absorption of a large number of elements is greater in new-
born mammals than in adults (Harrison, 1995). A number of factors, including the milk
diet, may contribute to this increased availability of elements for absorption, but the
pinocytic activity associated with the uptake of intact gamma globulins from milk is
thought to play an important role (Sullivan, 1980a,b; Sullivan and Gorham, 1982).
(D7) Retention of elements and their radioisotopes in the mucosal lining tissues of
the alimentary tract and on teeth has been demonstrated in a number of studies (see
Chapter 3 and later in this annex). In particular, high levels of retention of radionuc-
lides in the small intestine has been shown to be associated with high levels of
absorption in neonatal mammals.
(D8) The alimentary tract is both a route of entry of radionuclides into the body
and an excretion route. Thus, radionuclides are secreted into the alimentary tract, in
zuc
many cases mainly in bile but also in other secretions and directly through the walls
of the various regions, leading to additional doses to alimentary tract regions.
(D9) The objective of this annex is to give an overview of the main biokinetic pro-
cesses occurring in the alimentary tract after ingestion of radioactive elements. Spe-
ciation, retention, and absorption of elements are treated separately for each defined
compartment from the mouth to the large intestine. Wherever possible, specific
examples are given for radionuclides of interest and/or for stable isotopes. The data
discussed do not repeat all information given in Chapter 3 on radionuclide absorp-
tion, retention, and secretion; the intention is to give additional information for
those with a specific interest in radionuclide biokinetics. The reviews are also not
exhaustive, although they give extensive information for specific radionuclides, par-
ticularly actinide isotopes. An appendix gives values of fractional absorption (f1)
used in previous ICRP publications to calculate doses following the ingestion or
inhalation of radionuclides.
D.2. Oral cavity
D.2.1. Speciation
(D10) Speciation in the oral cavity may result in the transformation of one chem-
ical form of a radionuclide to another. The net result depends on the stability of the
complex entering the mouth, the contact time, and the nature of oxidising, reducing,
or complexing agents present in the oral cavity. The real influence of the oral cavity
on radionuclide speciation is not well understood. Although it has been shown that
changes occur in the chemical form of a radionuclide after ingestion, the role of the
mouth in these processes relative to the stomach and small intestine is not clear.
234
(D11) This section provides a review of current knowledge on the chemical char-
acteristics of the oral cavity, as well as possible effects on radionuclide speciation.
Redox and chemical properties of the oral cavity
Composition of human saliva

(D12) In humans, saliva is produced as a mixture of secretions from three pairs of
large glands (parotid, submaxillary, sublingual) and from smaller glands in the oral
mucosa. Saliva varies enormously in amount and composition between individuals
and in the same individual from time to time. The secretions of the various salivary
glands are affected, both in amount and composition, by physical and nervous stim-
uli. One of the most marked influences is the presence of food in the mouth, which
greatly increases the production of saliva.
(D13) Water accounts for 994 g of every litre of human saliva, suspended solids
account for approximately 1 g, and dissolved substances account for approximately
5g (2 g inorganic and 3 g organic material). The suspended solids mainly consist of
cells from the buccal epithelium, disintegrating leucocytes, and oral bacteria, yeasts,
and protozoa.
(D14) Sodium and chloride ions are the most abundant inorganic constituents of
human saliva (Table D.1). The concentrations of both sodium and chloride ions in
saliva increase with the rate of salivary flow, with the rate of increase being constant.
Calcium and phosphate ions are important constituents. Inorganic phosphate ac-
counts for 90% of the total phosphorus, with the remainder occurring as hexose
phosphates, phospholipids, nucleoproteins, and nucleic acid. Undissolved calcium
phosphate is probably a normal salivary constituent, with the solid phase being sta-
bilised by the presence of proteins. Other inorganic ions occurring in substantial
amounts are potassium, magnesium, sulphate, and thiocyanate (Table D.1). Copper,
fluoride, iodide, and nitrite ions are present in lower concentrations. Saliva also con-
tains dissolved O2, N2, and CO2.
(D15) The total nitrogen content is 0.90 g/l (range 0.36–1.25) and the total protein
content is approximately 3 g/l. Mucin is the most abundant protein in stimulated sal-
iva (0.8–6.0 g/l). It is a mucoprotein, with approximately one-third of the molecule
being carbohydrate. Other proteins are beta globulin (43.3%), gamma globulin
(18.5%), lysozyme (18.1%), alpha globulin (11.1%), and albumin (7.6%).
(D16) Amylase is the only enzyme in saliva believed to play a significant part in
digestion. In the presence of NaCl, it hydrolyses starch and glycogen to dextrins
and maltose, given sufficient time.
(D17) Citrate ions are present at a concentration ranging from 2 to 20 mg/l.
pH and oxidation potentials

(D18) The electrochemical nature of the oral cavity has been investigated in order
to develop model systems for studying and understanding corrosion phenomena.
Ewers and Greener (1985) measured the pH and oxidation potential Eh (SCE) in
nine patients utilising micro-electrode techniques. In five sites common to all sub-
jects, the oxidation potential ranged from 58 to +212 mV and the pH ranged from
235
Table D.1. Constituents of human saliva (from Long et al., 1971)

Resting salivaa Stimulated salivab
Inorganic constituents
Sodium (mEq) 6.5–21.7 43.0–46.1
Potassium (mEq) 19.0–23.3 17.9–18.7
Calcium (mEq) 2.3–5.5 1.8–4.6
Magnesium (mEq) 0.16–1.06 –
Copper (lg) 100–470
Cobalt (lg) 0–125
Chloride (mEq) 10 43
Phosphorus total 193 –
Phosphorus inorganic 74–211
Phosphorus, lipid 0.5–2.0
Sulphur 76
Fluoride 0.1–0.2
Bromide 1–7
Iodide 0–3.5 0.2–3.5
Thiocyanate 26–270
Oxygen (ml) 10
Nitrogen (ml) 25
Carbon dioxide (ml) 82–253 190–500
Organic constituents
Reducing substances (as glucose) 110–300 140–300
Citrate 20–300
Lactate 10–50
Cholesterol 25–500
Ammonia 10–120
Creatinine 6–11
Urea 200 0–140
Uric acid 5–29 10–210
Amino acids
Alanine 5–29
Arginine 33–100
Aspartic acid 1.3–3.3
Cystine 1.6–4.5
Glutamic acid 5–13
Glycine 5–36
Histidine 3.5–20
Isoleucine 2–9
Leucine 0.2–3
Lysine 1.5–15
Methionine 0.05–0.1
Phenylalanine 6–25
Proline 3.5–15
Serine 3.3–12
Threonine 4–56
Tyrosine 2–10
Tryptophan 0–2.1
Valine 7–22
Vitamins
Ascorbic acid 0.3.7
Biotin (lg) 0.8
236
Table D.1 (continued)

Resting salivaa Stimulated salivab
Choline 6–36
Cobalamin (lg) 1.5–5
Folic acid (lg) 0.1 3–75
Vitamin K (lg) 15
Nicotinic acid (lg) 30 23–409
Pantothenic acid (lg) 80 12–190
Pyridoxine (lg) 600 1–17
Riboflavin (lg) 50
Thiamine (lg) 7 2–14
Values are expressed as mg (unless otherwise stated) of the constituents per litre of saliva.
a
Saliva collected in the absence of stimuli.
b
Saliva collected after artificial stimulation by means of paraffin wax.
6.1 to 7.9. Differences in pH and oxidation potential were related to site of measure-
ment, the periodontal health of the patient, and the nature and quantity of restor-
ative treatment (Ewers and Greener, 1985).
(D19) Resting saliva varies from pH 5.6 to 7.6 with a mean of approximately pH 6.7.
In children, the mean is approximately 0.1 of a unit higher. No sex difference has been
reported. Stimulated saliva ranges from pH 7.2 to 7.6. Saliva has a pronounced buf-
fering power due to its content of phosphate and bicarbonate ions (Long et al., 1971).
(D20) Nagler et al. (1997b) investigated the redox properties of rat parotid saliva.
They compared the redox activity of protein-rich saliva with protein-poor saliva. Sal-
iva samples were analysed for their redox activity by measuring the ascorbate-driven
and saliva (diluted 1:2)-mediated conversion of salicylate to its 2,3- and 2,5-
dihydroxybenzoate and catechol metabolites. They demonstrated that saliva has a
profound capacity for reducing redox activity caused by the transition metal ions,
iron, copper, and manganese, with protein-rich saliva being most effective (Nagler
et al., 1997a).
Oxidising and reducing agents in saliva
(D21) Duncan et al. (1995) showed that high concentrations of nitrite present in
saliva (derived from dietary nitrate) might, upon acidification, generate nitrogen oxi-
des in the stomach in sufficient amounts to provide protection from swallowed
pathogens. They showed that, in the rat, reduction of nitrate to nitrite is confined
to a specialised area on the posterior surface of the tongue, which is heavily colonised
by bacteria, and that nitrate reduction is absent in germ-free rats. In humans, in-
creased salivary nitrite production resulting from nitrate intake enhances oral nitric
oxide production (Duncan et al., 1995).
(D22) Pruitt et al. (1983) showed that human whole saliva contains hypothiocya-
nite ions (OSCN); the principal antimicrobial product of the salivary peroxidase
system. The peroxidase system requires a source of peroxide in order to produce
OSCN. In the human mouth, this source has been assumed to be primarily the per-
oxidogenic oral bacteria. The pH dependence of OSCN generation is in the range
of 6.5–7.0. Pruitt et al. (1983) also showed that there is a significant source of H2O2
within the parotid gland and that the OSCN generating potential of parotid saliva
237
is similar to that of whole saliva. The enhancement of OSCN levels in saliva by

addition of SCN and H2O2 is critically dependent upon pH and upon the relative
and absolute concentrations of H2O2 and SCN.
(D23) Jalil (1994) measured thiocyanate (SCN) and OSCN concentrations in
resting and stimulated whole saliva and stimulated parotid saliva from 20 healthy
young adults aged 21–29 years. In resting saliva, whole saliva, and parotid saliva,
the mean SCN concentrations (in mM) were 1.5 ± 0.6, 0.9 ± 0.6, and 1.2 ± 0.65,
respectively, whilst the mean OSCN concentrations (in lM) were 31 ± 14,
25 ± 13, and 30 ± 23, respectively.
(D24) Manson-Rahemtulla et al. (1988) purified a salivary peroxidase from
human saliva, with apparent molecular weights for the three subunits of 78,000,
80,000, and 280,000 Daltons. This peroxidase was similar to bovine lactoperoxidase
in amino acid composition, in ultraviolet and visible spectra, in reaction with cya-
nide, in susceptibility to 2-mercaptoethanol inactivation, and in thermal stability.
(D25) Horn et al. (1988) measured the ability of the oral mucosa of patients with oro-
pharyngeal tumours to reduce cytochrome c. All patients were heavy smokers and
drinkers. It was found that patient mucosa had substantially more reducing power
than control mucosa. Within the control group, the mucosa of smokers was most ac-
tive. The cytochrome c reduction was not inhibited by superoxide dismutase or cop-
per(II) 3,5-diisopropylsalicylate. The authors hypothesised that reduction of
cytochrome c by the oral mucosa of smokers and patients with mouth cancer was pri-
marily due to residues of cigarette tar containing conjugated quinones of mixed oxida-
tive states, which are strong reductants as well as producers of oxygen-centred radicals.
Effects on speciation
Example of iodine
(D26) Experiments with monkeys and rodents indicated that the biological activity
of an ingested sterilising agent is expressed via its chemical interaction with the
mucosal epithelia, secretory products, and dietary contents of the alimentary tract.
Evidence exists that a principal component of this redox interaction is iodide of die-
tary origin that is ubiquitous in the gastrointestinal tract. Thus, the observation that
subchronic exposure to chlorine dioxide (ClO2) in drinking water decreases serum
thyroxine levels in mammalian species can be best explained by changes produced
in the chemical form of the bioavailable iodide. Mechanistic studies indicate that oxi-
dising agents such as chlorine-based disinfectants oxidise the basal iodide content of
the gastrointestinal tract (Bercz et al., 1986). The resulting reactive iodine species
readily attach to organic matter by covalent bonding. It appears that the extent to
which such iodinated organics are formed is proportional to the magnitude of the
electromotive force and stoichiometry of the redox couple between iodide and the
disinfectant (Bercz et al., 1986).
Example of plutonium
(D27) Taylor et al. (1985a) developed an in-vitro model to study the speciation of
plutonium in the upper alimentary tract. The model consisted of three parts: a
238
‘mouth’ system in which reactions with fresh human saliva were studied; a simulated
‘stomach’ system in which the mouth content reacted with synthetic gastric juice; and
a ‘duodenal’ system in which the gastric contents were neutralised.
(D28) They showed that when 2 ng 239Pu, as plutonium nitrate, was added to
fresh human saliva, 60% rapidly formed an insoluble and sedimentable complex
(in 15–30 min) while 24% and 16%, respectively, bound to low-molecular-weight
compounds or became hydrolysed (Table D.2). In gastric and duodenal juice, pluto-
nium seemed to be mainly associated with low-molecular-weight compounds (36%
and 84%, respectively), while the hydrolysed fraction remained very low. No signifi-
cant binding with proteins was reported. When plutonium was administered as a cit-
rate (citrate concentration of 25 mM, ie, one-tenth of that in natural citrus fruit juice),
the results showed some differences. Fifteen to 30 min after administration into saliva,
plutonium was mainly bound to low-molecular-weight species (54%) and, to a lesser
extent, to proteins (13%). In gastric juice, plutonium was mainly present as an insol-
uble and sedimentable form (87%), while in duodenal juice, it was again associated
with low-molecular-weight compounds (81%). These forms have not been identified
but chromatographic procedures showed that the low-molecular-weight complexes
found in saliva and duodenal juice were different (Taylor, 2004; Taylor et al., 1985a).
(D29) Other similar studies were aimed at determining the effect of foodstuffs such
as tea or orange juice on the speciation of plutonium after administration into saliva.
The results suggested that in the presence of tea, over 80% of the plutonium was
present as insoluble or hydrolysed species in all three compartments. In the study
with orange juice, there was a dramatic increase in the amount of insoluble/hydroly-
sable plutonium in the stomach, but two-thirds of this material was resolubilised,
probably by bicarbonate, in the duodenal compartment (Taylor et al., 1985a). In a
further study, a soluble extract of raw potato was used in place of orange juice,
and approximately 50% of the plutonium was found in the soluble/hydrolysed frac-
tions of all three compartments (Taylor et al., 1985a).
(D30) The conclusions of these studies were that when plutonium is present as a
chelate that is not stable over a wide pH range, the chemical speciation changes dur-
ing passage from the mouth to the site of absorption in the small intestine. Thus, the
chemical form in which plutonium is ingested appears to be less likely to influence
absorption than the food or endogenous complexing ligands that may be present
in the stomach and duodenum (Taylor et al., 1985a).
Table D.2. Fractionation of plutonium in saliva, simulated gastric juice, and duodenal content (from
Taylor et al. 1985a)
Fraction % of total plutonium
Saliva Gastric juice Duodenal juice
Nitrate Citrate Nitrate Citrate Nitrate Citrate
Insoluble 60 29 57 87 11 18
Complexed with proteins 0 13 3 5 3 0
Low-molecular-weight complexes 24 54 36 7 84 81
Hydrolysed species 16 4 3 0 0 0
239
(D31) Hetero-ionic exchange may occur in the mouth between ions from the fluid
bathing the teeth, such as drinking water containing plutonium, and mineral ele-
ments in the enamel such as calcium, orthophosphate, and sodium (Renaud-Salis
et al., 1990).
(D32) Previous investigations of the chemical form of plutonium in potato juice
pressed from potatoes indicate that citrate and phytate (myo-inotisol hexaphos-
phate) complexed Pu(IV) added in its nitrate form (Cooper and Harrison, 1982,
1984a). Investigations performed by Bulman et al. (1993) indicated that plutonium
and americium in potatoes were present in three unidentified fractions. They postu-
lated that one of these fractions could be plutonium or americium phytate.
D.2.2. Retention
Alkali metals
Rubidium
(D33) After in-vitro contamination of cattle teeth enamel with 86Rb+, Borggreven
et al. (1977) showed that the diffusion coefficient ranged between 0.3 and 12 · 108
cm2/s. These authors showed that dental enamel behaves like an ion-selective mem-
brane with a negative fixed charge. In this situation, cations have been shown to be
more mobile than anions.
Alkaline earth elements
Radium
(D34) Two cases of human contamination by ingested 226Ra have been re-
ported. The first concerned chronic exposure to water containing 0.1 pg/l radium.
In this case, radium in the teeth was measured and ranged between 0.019 and
0.026 pg/g ash (Lucas and Krause, 1960). In another case, a woman who had
worked as a dial painter for two years and died 52 years later had concentrations
of radium in her teeth of approximately 5.1 Bq/g ash; higher than average values
for the skeleton (3 Bq/g) (Holtzman et al., 1971). The radium was deposited non-
uniformly in teeth with definite concentration patterns. After exposure to environ-
mental radium in Russia, teeth have been shown to contain between 174 and 490
mBq 226Ra/kg (wet weight) (Ponikarova et al., 1988). Other studies measured
0.014–0.029 Bq/g calcium of 226Ra in people aged 0–50 years (Neuzil and Dysart,
1984). Each of these observations relate mainly to radium absorbed into blood
and subsequently incorporated into teeth (and bone), rather than direct adsorp-
tion of ingested radium on teeth surfaces.
Strontium
(D35) Data on strontium in teeth mainly relate to environmental exposures. Mea-
surements of dietary 90Sr in teeth in Poland gave values of approximately 1.5–
9 · 102 Bq/g ash for a dietary intake estimated at approximately 45 Bq/y 90Sr
240
(Glowiak and Pacyna, 1978). As for radium, these data can be largely taken to be a
reflection of the behaviour of strontium absorbed into blood.
(D36) Spets-Happonen et al. (1998) investigated whether strontium was incorpo-
rated into plaque and enamel in vivo during a 2-week rinsing period with a chlorh-
exidine-fluoride-strontium solution. In this investigation, a total of 19 adult
participants (aged 30–55 years) rinsed their mouths twice a day for 2 weeks, first
with a placebo solution and subsequently, after a 1-week interval without rinsing,
with a chlorhexidine gluconate (0.05%)-sodium fluoride (0.04%)-strontium (100
ppm as SrCl2) rinsing solution (CXFSr). One pooled plaque sample was collected
from each participant before and on the day after the placebo and CXFSr rinsing
periods, as well as 2, 3, and 6 weeks after the completion of the CXFSr rinsing
period. Plaque samples were collected from approximal surfaces using waxed den-
tal floss. Two enamel samples were taken from each participant: one after the pla-
cebo rinsing period and another after the CXFSr rinsing period. Prior to sampling,
the enamel was lightly polished with a rotating brush and water. The enamel was
etched for 6 s with 10 ll of 2M perchloric acid to collect the sample. The strontium
content in the samples was determined by atomic absorption spectrophotometer.
The results obtained for the strontium and fluorine content in plaque are shown
in Table D.3 and Fig. D.1. The strontium content of approximal plaque was
8.4 ± 1.2 (lg/g plaque dry weight) before CXFSr rinsing. This increased four-fold
to 32.5 ± 4.7 (lg/g plaque dry weight) after the CXFSr rinsing period, and re-
mained elevated for the 6 weeks of the experiment. The strontium content of pla-
que tended to decrease during the placebo rinsing period, possibly due to the slight
acidity of the rinsing solution which may have released some loosely-bound or free
strontium and fluorine from plaque. The strontium content in enamel was not sig-
nificantly different after CXFSr rinsing. The mean strontium content was 360 ± 28
lg/g apatite after the placebo rinsing period and 398 ± 73 lg/g apatite after the
CXFSr rinsing period. The mean strontium concentration in plaque observed prior
to the rinsing periods was of the same magnitude as that reported by Schamschula
Table D.3. Strontium and fluoride content of approximal plaque (lg/g plaque dry weight) before and after
2 weeks of rinsing with placebo and chlorhexidine-fluoride-strontium (CXFSr). Source: Spets-Happonen
et al. (1998)
Time (weeks) Period of experiment Content of approximal plaque
(mean ± SD) (lg/g plaque dry
weight)
Strontium Fluoride
0 Before starting placebo rinsing 17.2 ± 2.6 60.3 ± 9.2
2 After 2 weeks of placebo rinsing 8.4 ± 1.2 42.0 ± 4.8
3 One week after rinsing with placebo 18.2 ± 6.6 51.8 ± 6.9
5 After 2 weeks of CXFSr rinsing 32.5 ± 4.7 72.8 ± 9.0
7 Two weeks after CXFSr rinsing 29.1 ± 2.3
8 Three weeks after CXFSr rinsing 31.9 ± 3.3
11 Six weeks after CXFSr rinsing 26.1 ± 2.6
SD, standard deviation.
241
50
45
40
μg/g plaque dry weight
35
30
25
20
15
10
0
-1 0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo CXFSr
Time (weeks)
Fig. D.1. Strontium and fluoride content of approximal plaque (lg/g plaque dry weight) before and after 2
weeks of rinsing with placebo and chlorhexidine-fluoride-strontium (CXFSr). Source: Spets-Happonen
et al. (1998).
et al. (1978) in samples from Papua New Guinea. Lower strontium concentrations
of 3.6 lg/g and 12.3 lg/g have been reported in samples from Australia (Schamsch-
ula et al., 1977) and the USA (Curzon, 1985), respectively. The levels of strontium
and fluorine in enamel reported by Spets-Happonen et al. (1998) are in agreement
with previous studies (Curzon, 1985; Little and Barret, 1976). In-vitro uptake of
strontium directly into plaque-free bovine enamel and, to a lesser extent, human
enamel, has been shown (Curzon and Spector, 1983) when enamel was agitated
for 10 min per day for 7 days in a solution with a strontium concentration as high
as 2000 ppm (see Table D.4).
Table D.4. Activity in teeth (113Sn) obtained from the various adsorption experiments (counts/60 s)
Medium of sorption Activity before washing Activity after washing
Tap water 39,668 38,350
Tea with sugar 24,330 21,020
Tea without sugar 23,338 20,123
Coffee with sugar 14,558 12,371
Coffee without sugar 15,212 10,980
Coffee with sugar and milk 10,826 7234
Red tea with sugar 29,454 27,953
Red tea without sugar 45,293 43,977
Chicken stock soup 24,127 22,892
242
(D37) Once absorbed, strontium is distributed throughout the body but is prefer-
entially deposited in bone and teeth (Cabrera et al., 1999). Romanyukha et al. (2002)
investigated the localisation of strontium in teeth from Techa River area residents,
using a photostimulable phosphor imaging detector. It was observed that 90Sr was
concentrated mainly on the surface of the pulp channel and in the roots, where for-
mation of the secondary dentin takes place in adults, reflecting low bone turnover in
adults. In contrast, for younger individuals with active tooth formation during the
period of intake, 90Sr was concentrated mainly in the tooth crown near the junction
of the enamel and dentin. Similar results were reported by Gould et al. (2000) and
Tolstykh et al. (2000).
Metals
Cadmium
(D38) Four days after administration of 109Cd(II) to mice in drinking water, the
retention of activity in the head was approximately 0.2% of the administered activ-
ity, whereas the carcass accounted for only 0.03% of the administered activity
(Bhattacharyya et al., 1985). These results were attributed to the retention of
cadmium on tooth surfaces. In rats, stable cadmium has been shown to accumulate
in the dental germ and in the pulp of permanent teeth (Nomura, 1980). This accumu-
lation in teeth is not sex or age dependent (Owczarcza, 1988). Stable cadmium val-
ues for young human second teeth have been found to range between 0.009 and
0.030 mg/g, and cadmium was deposited uniformly in the enamel (Cleymaet et al.,
1993).
Lead
(D39) Four days after administration of radioactive lead to mice in drinking
water, the retention of activity in the head was approximately 0.5% of the adminis-
tered activity, whereas the carcass accounted for only 0.2% of the administered activ-
ity (Bhattacharyya et al., 1985b). Lead was deposited on all the mouth surfaces. A
similar study in which rats were fed with food containing 1.75 ppm lead showed that
lead accumulated on both molars and incisors (Wesenberg, 1983). Human data con-
cerning lead accumulation after ingestion are sparse. One woman who had been
working as a dial painter for 2 years and who died 52 years later had a 210Pb con-
centration in her teeth of approximately 1.3 Bq/g ash. In that case, the radioisotope
was mainly distributed on the tooth surfaces (Holtzman et al., 1971). Other cases of
lead contamination have been reported but all are associated with environmental
exposures to lead in air, soil, or food. In these cases, it is difficult to determine the
part due to food contamination. Measurements of lead in teeth showed that the con-
centration of the element after environmental exposure can reach 3.3 mg/g (Cleymaet
et al., 1993), and the mean values ranged from 0.6 to 300 lg/g (Gulson and Wilson,
1994; Nowak, 1996; Wesenberg, 1983). It was found that lead was deposited mainly
on enamel surfaces, and the deposition was neither sex nor age dependent (Cleymaet
et al., 1993; Holtzman et al., 1971; Owczarcza, 1988).
243
Tin
(D40) The adsorption of tin ions on human teeth from water and other drinks
has been studied using the isotope 113Sn as a tracer (Helal et al., 2002). The teeth
retained a minimum amount of tin from coffee and a maximum amount from
water and tea with sugar. It has been found that adsorbed tin is not readily
removed.
Polonium
(D41) One case of human contamination after 2 years of occupational exposure
(dial painter) has been reported. In this case, the 210Po level in teeth was 1.6 Bq/g
ash (Holtzman et al., 1971). The element was mainly deposited on the tooth surfaces.
Halogens
Fluoride
(D42) Exposure of the population to fluoride through the use of fluoridated tooth-
pastes, mouthwashes, and topical gels is increasing. It has been shown that fluoride is
absorbed readily from the mouth. However, the diffusible fluoride concentration
within the mouth probably declines rapidly after ingestion due to binding by teeth,
plaque, and micro-organisms (Patten et al., 1978).
Actinides
Plutonium
(D43) Adsorption of plutonium on to mouth surfaces has been studied by Bhat-
tacharyya et al. (1985) and Renaud-Salis et al. (1990). In both cases, Pu(IV) and
Pu(VI) were given to animals via drinking water but the duration of exposure dif-
fered between experiments. Six days after acute exposure to 236Pu(VI) via drinking
water, the heads of the mice accounted for 0.5% of the ingested activity (Bhatta-
charyya et al., 1985). This value was significantly higher than the carcass value
(0.03% of ingested activity), indicating that the major part of the radionuclide
deposited in the mouth after ingestion. However, when 236Pu(IV) was given to
mice, the plutonium distributed equally between the head (0.03% of ingested activ-
ity) and the carcass (0.025%), indicating that deposition on the mouth surfaces
was valence state dependent. Similar results were obtained for rats after chronic
ingestion of contaminated drinking water (Renaud-Salis et al., 1990). These
authors demonstrated that, during ingestion, 93–97% of the whole-body 238Pu
was deposited on teeth. This corresponded to 0.1% of the administered activity
and was independent of the initial mass ingested. Retention of plutonium on teeth
surfaces was shown to be valence state dependent, but the results obtained con-
trasted with those of Bhattacharyya et al. (1985a); Pu(IV) was strongly bound
to teeth whereas Pu(VI) retention decreased dramatically with time, indicating
that Pu(VI) was less firmly bound to the teeth surfaces. In-vitro experiments using
teeth immersed in a 1010 M solution of Pu(VI) showed high levels of adsorption
of plutonium on to teeth surfaces after 5 h of exposure (Bhattacharyya et al.,
244
1985b). Thus, it appears that plutonium is readily bound to the surfaces of teeth
and that this adsorption and retention is oxidation state dependent. The results of
Taylor et al. (1985a) suggest that the chemical form of the ingested plutonium is
another important factor.
(D44) The mean concentration of 239Pu in teeth collected around the Sellafield nu-
clear fuel reprocessing plant in Cumbria and elsewhere in the UK has been reported
to be approximately 5 mBq/kg ash (O’Donnel et al., 1997). There was a suggestion of
increased levels near Sellafield but the data were limited, and variations in 239Pu con-
centrations in teeth are very likely to be attributable to differences in rainfall and
hence deposition of weapons-test fallout 239Pu.
D.2.3. Absorption
(D45) Absorption of carrier-free 18F and 125I from the mouth has been investi-
gated using rats (Gabler, 1968; Patten et al., 1978). After 1, 2, and 3.5 h, the absorp-
tion of the 125I dose was 7.3%, 12.6%, and 23.9%, respectively. Radiofluoride
absorption was 6.8% after 2.5 h (Patten et al., 1978).
D.3. Oesophagus
D.3.1. Speciation
(D46) Chemical transformations of radionuclides in the oesophagus are unlikely

to be important as the transit time is short. However, such reactions may occur to
a limited extent as the presence of oxidising and/or reducing agents on the surface
of the oesophagus has been demonstrated (Washington et al., 1997).
Chemical characteristics of the oesophagus
(D47) Frederiks and Bosh (1997) detected superoxide dismutase (SOD) extracellu-
larly at the surface of the epithelia of the trachea, oesophagus, small intestine, and
colon. SOD catalyses the disproportionation of superoxide anions into hydrogen
peroxide and oxygen.
(D48) Washington et al. (1997) monitored intra-oesophageal pH and redox poten-
tials in 18 patients with gastro-oesophageal reflux symptoms and 15 asymptomatic
controls for a 24-h period. The pH and redox electrodes were positioned 5 cm pro-
ximal to the lower oesophageal sphincter, the position of which had been determined
by manometry. Since significantly different behaviour was observed during the day
and night, the data were divided into periods of waking and sleeping. Both patients
and normal subjects showed negative redox transients that were more frequent and
pronounced at night than during the day, and which were not correlated with acid
reflux. The only parameter that was significantly different between the normal sub-
jects and the patients was the amount of nocturnal redox activity, which was lower
in patients than in normal subjects.
245
(D49) Speciation seems to have little if any effect on metals in the oesophagus.
D.3.2. Retention
(D50) No data are available on the retention of metals in the oesophagus.
D.3.3. Absorption
(D51) No data are available on the absorption of metals from the oesophagus.
D.4. Stomach
D.4.1. Speciation
(D52) Chemical reactions that change the chemical form of an ingested radionu-
clide are very likely to occur in the stomach. The chemical properties of the secre-
tions and contents of the stomach are very complex and many oxidising, reducing,
and complexing agents could interact with the chemical forms of a radionuclide
entering the stomach.
Chemical properties of the stomach
(D53) Passage through the gastrointestinal tract begins when food is briefly mixed
with saliva in the mouth and then passed down the oesophagus into the stomach.
The food partially neutralises the acidic gastric secretions, and the pH of the bulk
gastric contents rises from approximately 1 to between 3 and 5 (see Annex B). Gas-
tric secretions may be important in facilitating the absorption of some compounds
(Cooper, 1985).
(D54) Mueller and Deistler (1987) investigated the redox potential in the gastric
juice of humans. The dependence of redox potential on the pH value and the concen-
tration of nitrite was examined in fasting gastric juice samples from 132 healthy,
young volunteers. Low pH values were associated with high redox potentials, and
higher pH values (neutral) were associated with smaller redox potentials.
(D55) The redox potential was found to change to negative values in all gastroin-
testinal sections of piglets, from the time of birth to the age of 3 days. This change was
relatively small in the small intestine, but it was more than 300 mV in the stomach and
colon. Values recorded from stomach and rectum of weaned piglets were more neg-
ative than those established for animals before weaning (Schulze and Jacob, 1981).
(D56) Caballeria et al. (1987) showed that ethanol can be oxidised in the stomach.
The rate of ethanol oxidation was 19% faster during intragastric than during intrave-
246
nous infusion (P < 0.01). When measured at the prevailing lumenal ethanol concentra-
tion (145 mM) and expressed per unit body weight, the gastric alcohol-dehydrogenase
(ADH) activity represented 14% of the hepatic activity at 30 mM ethanol, suggesting
that gastric ADH activity could account for most of the increased rate of oxidation
when ethanol is given intragastrically. Thus, gastric ethanol oxidation in the rat repre-
sents a significant fraction of the total rate of ethanol oxidation and it is therefore one
of the factors that determines the bioavailability of orally administered ethanol.
(D57) Acids and bases are absorbed in different parts of the gastrointestinal tract.
The low pH of the gastric contents produced by hydrochloric acid secretion ensures
that weak acids are essentially unionised and in their lipid-soluble form. Thus, weak
acids are best absorbed from the stomach. The lowest pKa of an acid compatible
with rapid absorption is approximately 3. Strong acids (pKa < 3) do not combine
with hydrogen ions in the stomach to form the neutral lipophilic molecule. Hence,
they are not absorbed from the stomach and remain completely ionised and unab-
sorbed as they traverse the stomach (Schedl, 1984).
(D58) Contrasting with the behaviour of acids, environmental agents that are
weak bases form salts with hydrochloric acid in the stomach and are ionised; these
polar forms are not absorbed in the stomach. They are, however, absorbed in the
small intestine due to physicochemical changes in that compartment.
(D59) Kerger et al. (1997) studied hexavalent chromium [Cr(VI)] absorption in
adult males following ingestion of 5 and 10 mg Cr(VI)/l in drinking water. The data
suggested that virtually all of the ingested Cr(VI) was reduced to Cr(III) before
entering the bloodstream. Therefore, it appears that the endogenous reducing agents
within the upper gastrointestinal tract and the blood provide sufficient reducing po-
tential to prevent any substantial systemic uptake of Cr(VI) following drinking water
exposures at 5–10 mg Cr(VI)/l. Based on these data, the chemical environment in the
gastrointestinal tract and the blood appears to be effective, even under relative fast-
ing conditions, in reducing Cr(VI) to one or more forms of Cr(III).
(D60) Trivalent plutonium could be formed in the stomach by the action of die-
tary reducing agents such as ferrous ions or ascorbic acid (Cooper, 1985).
D.4.2. Retention
Retention in adults
(D61) Blake and Henning (1988) investigated the retention of 45Ca after adminis-
tration to rats in milk or as 45CaCl2 solution. They found that tissue retention of
45
Ca administered as CaCl2 was greatest at 30 min after administration, with sub-
stantial retention in the tissues of the stomach and less retention in the duodenum,
distal jejunum, and proximal ileum. A similar pattern was observed for 45Ca admin-
istered in milk, but with maximum retention after 1 h. Retention in the stomach was
not correlated with absorption at this site as measurements after ligation at the pylo-
rus showed that absorption did not occur to any measurable extent in the stomach
(Blake and Henning, 1988). It was not clear whether the observed retention repre-
sented uptake of 45Ca into the mucosal lining of the stomach.
247
Retention in juveniles
(D62) The retention of radionuclides in the stomach wall appears to depend on the
age of the animals at the time of administration. In studies performed with neonatal
and juvenile baboons, it was demonstrated that plutonium retention in the stomach
wall increased with age for the first 30 days, and then decreased during the following
weeks (Table D.5). For neptunium, retention was maximum when the animals were 4
days old at the time of ingestion (Table D.6) (Lataillade et al., 1992).
(D63) Fritsch et al. (1988) reported that plutonium retention in the stomach of
guinea pigs, baboons, and macaque at 4–7 days after administration at ages from
1 day to 5 weeks ranged between 1 · 105 and 6 · 105 (Table D.7).
238
Table D.5. Plutonium retention in the alimentary tract of baboons after ingestion of Pu citrate.a,b
Source: Lataillade et al. (1992)
Age at intake (days) 1 17 34 50 66 129 177 195 244 310
% ingested activity · 100
Stomach 0.20 0.32 3.6 1.2 0.71 1.4 0.60 1.3 0.04 0.82
Small intestine 35.0 37.1 8.8 149.0 11.4 1.8 2.5 0.10 0.09 1.1
Large intestine 1.10 0.45 0.12 0.59 0.27 0.14 0.28 0.02 0.13 0.05
Total 36.3 37.8 12.5 150.8 12.4 3.3 3.4 1.4 0.26 2.0
Measurements made on the tissue minus the contents.
a
Ingestion of 1.7–4.3 lg plutonium/kg body mass.
b
Sacrifice 4 days after ingestion.
239
Table D.6. Neptunium retention in the alimentary tract of baboons after ingestion of Np nitrate.a,b
Source: Lataillade et al. (1992)
Age at intake (days) 4 4 6 8 14 26 77 132 159
% ingested activity · 100
Stomach 1.00 0.50 0.60 0.68 0.65 0.32 0.14 0.20 0.18
Small intestine 10.6 8.6 11.5 6.2 15.6 6.2 1.9 3.3 2.4
Large intestine 2.30 0.30 1.30 0.09 0.09 0.40 0.02 0.01 0.21
Total 13.9 9.4 13.4 0.9 16.3 6.9 2.1 3.5 2.8
a
Ingestion of 0.002 lg neptunium/kg body mass.
b
Sacrifice 4 days after ingestion.
Table D.7. Plutonium retention in different parts of the alimentary tract. Source: Fritsch et al. (1988)
Species Age at intake Postintake Stomach wall Small intestine wall Large intestine wall
(days) time (days) 3
Fraction of ingested plutonium · 10
Guinea pig 2 5 0.06 1.91 0.23
Baboon 1–34 4 0.02–0.04 1.1–3.5 0.06–0.4
Macaque 30 7 0.01 0.8 0.01
238
Pu citrate, 1–2 MBq/kg, guinea pigs.
238
Pu chloride, primates.
248
D.4.3. Absorption
(D64) Although the stomach is not generally considered to be an absorptive

organ, some chemical forms of a few elements such as methyl mercury, niobium oxa-
late, or cupric nitrate can be absorbed to some extent (Eisele and Mraz, 1981; Sasser
et al., 1978; Van Campen and Mitchell, 1965).
(D65) Other elements such as ingested copper, mercury, and niobium also show
some absorption from the stomach (Eisele and Mraz, 1981; Sasser et al., 1978;
Van Campen and Mitchell, 1965). The stomach did not seem to be an important
absorption site for ingested neptunium (Fritsch et al., 1986).
D.5. Small intestine
(D66) To be absorbed in the body, ingested chemicals must pass through the
mucosal lining of the alimentary tract, with the major site of absorption being the
small intestine. The movements of toxic chemicals and radionuclides across the intes-
tinal mucosa and into the blood or lymph occur by the same processes that are
responsible for the absorption of nutrients. There are five possible processes of intes-
tinal absorption. These are active transport, passive diffusion, pinocytosis, filtration
through ‘pores’, and lymphatic absorption. Passive diffusion is the major process for
transport of foreign chemicals across the intestine. Simple diffusion is dependent on
physicochemical criteria, i.e. it is not saturable and the transfer is directly propor-
tional to the concentration gradient and to the lipid-water partition coefficient of
the substance. The greater the concentration gradient and the higher the partition
coefficient, the faster the rate of diffusion. Absorption of structurally related chem-
icals occurs independently; co-absorption does not alter absorption rates of either
chemical. In addition to lipid solubility, the rate of passive absorption is influenced
by the degree of ionisation (Schanker, 1971). For example, many weak acids and
bases are readily absorbed, whereas stronger or highly ionised acids and bases are
less readily transported, and completely ionised compounds are very slowly ab-
sorbed. In addition to the degree of ionisation, the charge of the ion may affect
absorption. For example, Eastin et al. (1980) found that the rate of intestinal absorp-
tion of chromium was greater when the dissociated chromium complex carried a neg-
ative charge.
(D67) Active transport is responsible for the absorption of substances for which
the body has a physiological requirement, e.g. absorption of specific amino acids,
sugars, and electrolytes. Compounds that are structurally similar to naturally
occurring substrates can compete for binding sites on the same transport mecha-
nism and thus be actively absorbed. For example, cobalt and manganese compete
for the iron transport system and are absorbed in the same way (Pollack et al.,
1965). A number of factors such as diet, the motility of the intestine, the action
of micro-organisms, changes in the rate of gastric emptying, age of the animal,
and dissolution rates of the substance concerned can alter the rate of absorption
of chemicals (Chhabra and Eastin, 1984). Some of these factors are discussed
below.
249
D.5.1. Speciation
(D68) Foreign chemicals entering the alimentary tract encounter a wide variety of dif-
ferent conditions on their way to the central circulatory system of the body. Their phys-
icochemical properties may change and their fate in the body will be modified by the
micro-environment to which they are exposed. However, while nutrients are degraded
by digestive enzymes, toxic chemicals are often not chemically altered in the lumen of
the upper intestine, although they must be solubilised before they can be absorbed.
(D69) If a substance is soluble and is lipophilic to some degree, it passively perme-
ates into the epithelial cell layer of the small intestine. Most substances of this type
are absorbed at the level of the upper small intestine (duodenum, jejunum) owing to
the huge surface area and the neutral pH value at this site. Irreversible biotransfor-
mation may occur during passage through the gut wall (Hoensch and Schwenk,
1984). Some substances are channelled into lymphatic vessels or secreted back into
the lumen by the action of the epithelial cells (Lauterbach, 1977).
(D70) Once substances pass into the lower small intestinal segments or into the colon,
the intestinal flora can play a role in metabolism and degradation (Smith, 1978). Fur-
thermore, in pathological conditions such as when achlorhydric gastric juices are pres-
ent, such action of gut flora may occur in the upper small intestine. Bacteria can break
hydrolytic bonds and carry out reduction and dehydrogenation reactions (Goldmann,
1978). Some substances are unstable at acidic or neutral pH values, leading to insoluble
precipitates that are eliminated in the faeces (Hoensch and Schwenk, 1984).
Chemical properties of the small intestine
pH and redox potential in the small intestine

(D71) The pH range of the gastric contents is generally 1–3.5; most commonly 1–
2.5. Gastric contents delivered into the duodenum undergo an increase in pH from
approximately 5 to 7 as the jejunum is traversed. Pancreatic, biliary, and intestinal
secretions are alkaline and the pH of intestinal contents gradually increases to 7–8
as they pass into the ileum. Colonic secretions are alkaline.
(D72) Waldron-Edward (1971) measured pH and its variations in different portions
of the rat’s small intestine. The proximal jejunal segment provided the lowest pH in
the small bowel, followed by a very slight increase on proceeding towards the more
distal segments. The stepwise progression of increasing pH continued throughout
the ileal segments, reaching a maximum of 7.4 in the distal ileum (Table D.8).
(D73) Contrasting with the behaviour of acids, environmental agents that are
weak bases form salts with hydrochloric acid in the stomach, are ionised, and these
polar forms are not absorbed in the stomach. When these salts of basic compounds
enter the small intestine, the increase of pH to 5–7 forms the free base, which is lipid
soluble. The lowest pKa for a base that permits formation of free base at pH 5–7 is
approximately 7.8. Strong bases retain the salt form, remain ionised, and are not ab-
sorbed from small or large intestine (Schedl, 1984).
(D74) The small intestine is known to capture a wide variety of ions and nutrients
by transport systems that are energised by a fundamentally similar mechanism,
250
Table D.8. pH of ligated intestinal segments in the rata (from Waldron-Edward, 1971)
Segment Isotonic saline Tris I = 0.1
Initial pH 5.55 Initial pH 7.95
II 6.2–6.6 6.8–7.4
III 5.8–6.0 6.8–7.2
IV 5.8–6.1 6.9–7.3
V 5.7–6.5 6.8–7.2
VI 6.1–6.9 7.0–7.5
VII 5.9–6.6 6.9–7.5
VIII 6.2–7.1 7.2–7.4
IX 6.6–7.5 7.2–7.6
X 7.0–7.4 7.5–7.7
a
Saline or buffer was instilled into the lumen in vivo and removed after 30 min. pH was measured at 37 C
with a glass electrode.
namely flow of Na+ into the cell down a gradient of electrochemical potential. These
Na+-dependent transport systems are themselves specific examples of a broader class
of transport systems generally designated as ‘gradient-coupled systems’. In mamma-
lian tissues, the cation involved is typically sodium, and Na+-dependent amino acid
transport is a characteristic of nearly all animal tissues (Kimmich, 1984).
Oxidising and reducing agents in the small intestine

(D75) It is well known that the contents of the small intestine are reducing (Larsen
et al., 1981). Mouse duodenum possesses mucosal surface ferricyanide reductase
activity that is correlated with the process of intestinal iron absorption. The reducing
activity, determined in vitro by measuring ferrocyanide production from ferricya-
nide, was found to be greater in duodenal fragments compared with ileal fragments
(Pountney et al., 1996).
In-vivo chemical transformations
General considerations
(D76) Soluble molecules in the lumen of the small intestine have to diffuse through
three different layers to reach the absorptive epithelial cells of the lining mucosa. The
first layer is immobile water, adjacent to the mucosa; the second layer is a protective
mucus layer; and the third layer is a proton-rich sheet called the ‘acid microclimate’,
which affects the protonation of weak and acid bases. At the neutral pH of the intes-
tinal lumen, weak acids diffuse through the first layer and the mucus layer mainly in
anionic form, whereas weak bases diffuse in protonised form. Weak acids take up a
proton at the acid microclimate layer, thus becoming lipophilic and then diffuse into
the membrane. Weak bases remain protonised and this may favour their approach to
the negatively charged membrane surface (Hoensch and Schwenk, 1984).
(D77) If a compound is absorbed and enters the submucosal space, its further fate
depends on a variety of factors. One of them is binding to macromolecules in blood.
251
Many substances, including radionuclides, can be bound non-specifically to serum

albumin or blood cells. Such associations lower the free concentration of the sub-
stance in the intercellular space and thus promote its absorption.
(D78) McHardy and Parsons (1956) have shown that the rate of absorption of
phosphate in rats, introduced into the intestine as the sodium salt, increased with
increasing pH from 4.4 to 7.9. On the other hand, Mraz (1962) found very little
change in fractional absorption of 45Ca or 85Sr on perfusing the small intestine of rats
with solutions ranging in pH from 5 to 11. The solubility of calcium and strontium
salts formed with the physiologically important buffer anions, phosphate, bicarbon-
ate, and citrate, changes rapidly as the pH increases within the physiological range
found in the rat intestine. The concentration of each of these anions also varies in dif-
ferent parts of the small intestine and from species to species. In man, the highest con-
centration of bicarbonate is 19 mEq/l in the mid-ileum (Waldron-Edward, 1971).
(D79) Lumenal pH may affect the properties of the cell membranes and therefore
influence the absorption rate of the ionic metals. Rojas and Tobias (1965) demon-
strated that phospholipid monolayers, set up as model systems analogous to cell
membranes, act as ion-exchange resins with increasing capacity to absorb Ca2+ with
increasing pH.
Effects of complexing agents naturally present in the small intestine

(D80) Phytase concentrations have been measured in the small intestine of the rat,
rabbit, guinea pig, and hamster (Cooper and Gowing, 1983). Levels varied from 0.12
units (lg phosphorus released/min)/mg protein in the rat to 0.03 units/mg protein in
the rabbit. The enzyme is localised in the brush border of the small intestine of the
rat. It is suggested that the levels and location of phytase are important factors in the
uptake of metals from metal–phytate complexes. Metal ions released in the immedi-
ate vicinity of the absorptive surface of the intestine could be absorbed before being
rendered insoluble by competing reactions such as hydrolysis.
(D81) Phytic acid decreases the bioavailability of many essential minerals by inter-
acting with multivalent cations and/or proteins to form complexes that may be insol-
uble or otherwise unavailable under physiological conditions. It forms fairly stable
chelates with almost all multivalent cations that are insoluble at approximately
pH 6–7, although pH, type, and concentration of cation have a tremendous influence
on their solubility characteristics. In addition, at low pH and low cation concentra-
tion, phytate–protein complexes are formed due to direct electrostatic interaction,
while at pH > 6–7, a ternary phytic acid–mineral–protein complex is formed that dis-
sociates at high Na+ concentrations. These complexes appear to be responsible for
the decreased bioavailability of the complexed minerals and are also more resistant
to proteolytic digestion at low pH (Cheryan, 1980).
(D82) Results indicating that the chemical form of the actinides is not as important
in their absorption by neonates as by adults might be taken to suggest that a specific
chemical form in their milk diet might be involved in their absorption early in life. It
has been postulated that milk contains complexing agents with stronger stability con-
stants than actinide–citrate complexes (Métivier et al., 1987). Lactose is cited by some
authors because it enhances absorption of minerals in adolescent animals. However,
252
in adult baboons, an enriched lactose diet did not increase neptunium absorption de-
spite ingestion of a low neptunium mass (Métivier et al., 1986). It seems probable that
a complexing agent other than lactose or citrate is present in milk. Thus, for zinc,
Duncan and Hurley (1978) described a low-molecular-weight ligand that strongly
complexes zinc. These authors reported that the content of that ligand, so called
‘zinc-binding ligand’, differed from one species to another, which may, in part, ac-
count for interspecies differences observed in plutonium absorption.
(D83) It is likely that the high uptake of radionuclides and other substances in the
neonatal small intestine is related generally to increased permeability during this per-
iod, and specifically, in some species, to the ability to take up intact gamma globulin
molecules. Since guinea pigs, like humans, monkeys, and rabbits, do not exhibit intes-
tinal permeability to antibodies (Brambell, 1970), the increased absorption of pluto-
nium and americium observed in the Bomford and Harrison study (1986) and other
studies is probably related to increased permeability to molecular species smaller than
gamma globulins. Since both actinides bind to the iron-binding plasma protein trans-
ferrin (Boocock and Popplewell, 1965; Cooper and Gowing, 1981) and since iron is
bound more strongly by the related milk protein, lactoferrin (Aisen and Liebman,
1972), it is possible that the actinides are absorbed as lactoferrin complexes.
(D84) The absorption of an element through the small intestine depends on the
chemical form of the element. Foodstuffs may contain soluble low-molecular-weight
complexes such as citrates, phytates, and other organic acids (Popplewell et al.,
1991). The NEA (1988a,b) reviewed the data and reported that there was little infor-
mation on the nature of these complexes, and noted that feeding experiments using
adult laboratory animals have shown that dietary and chemical factors (mass, oxida-
tion state, and stability of complexes) could produce large variations in absorption.
Effects on radionuclides
Alkali metals
(D85) Calcium, when present in high concentration, forms insoluble salts at neu-
tral pH with phytate (Cheryan, 1980). Calcium is an alkaline earth element.

(D86) Magnesium, when present in high concentration, forms an insoluble salt at
neutral pH with phytate (Cheryan, 1980). Dietary fibre may bind a variety of ele-
ments (including magnesium and calcium) and render them unavailable for absorp-
tion (Campbell et al., 1976; Reinhold et al., 1976).
Transition metals
Iron
(D87) Some eucaryotic organisms, including many plants, yeast, and mice, have in-
creased iron uptake during iron deficiency because the capacity to reduce Fe3+ from
the environment to Fe2+ is greatly enhanced. Wien and Van Campen (1994) compared
the in-vivo capacity to reduce intralumenal Fe3+ in iron-deficient and normal rats.
253
They showed that iron-reducing capacity was higher in iron-deficient rats. This capac-
ity was not related to ascorbic acid, glutathione, or other non-protein sulphhydryls.
Mucosal ferric reductase activity was higher in iron-deficient rats in parallel with high-
er tissue weight, but the specific activity did not differ and the higher total activity was
not associated with the brush border fraction. They concluded that the role of endog-
enous Fe3+ reduction in regulating iron absorption should be investigated in humans
and in other experimental models. In previous experiments, they investigated lumenal
factors that might participate in Fe3+ reduction. They showed that during absorption
of 59Fe, the oxidation-reduction potential became more reducing and the pH rose in
the contents. There were small but significant differences between the iron-deficient
and normal rats. In one experiment, the lumenal environment was modified by bile
duct ligation and/or intestinal perfusion prior to the absorption test. Ascorbic acid,
non-protein sulphhydryl compounds, Fe2+, and total ionisable iron were measured
in lumenal contents. Non-protein sulphhydryl concentration was positively correlated
with, and the best predictor of, iron absorption in iron-deficient rats.
(D88) Raja et al. (1992) showed that 59Fe-uptake rates in mouse duodenal frag-
ments incubated in vitro were markedly reduced by ferricyanide (oxidising agent)
and ferrozine (Fe2+chelator) in the medium; ferrocyanide had no effect. Reduction
of Fe3+, as reflected by an increase in ferrozine-(Fe2+)-chelatable iron, was observed
in the presence of the tissue fragments. The generation of Fe2+ occurred linearly with
time, was independent of the medium ferrozine concentration, and was not due to
release of reducing factors from the duodenal fragments. Fe(3+)-reducing activity
was mainly present on the mucosal surface and was localised primarily to the prox-
imal region of the small intestine. Changes in Fe3+reduction rates closely paralleled
the changes in duodenal 59Fe uptake when metabolic inhibitors or modulators of
membrane potential were included in the medium. The enhancement in duodenal
mucosal 59Fe uptake in chronic hypoxic and iron-deficient mice paralleled the
changes in the tissue reduction of medium Fe2+. Moreover, the rates of reduction
were quantitatively similar to the rates of uptake. These observations indicate that
a sequential reduction and uptake process operates for Fe3+absorption in mouse
duodenum.
Cobalt
(D89) Some metal complexes have essential biological functions, and specific up-
take mechanisms exist in the intestine. As an example, the absorption of cobalt in the
form of vitamin B12 has been shown to be much higher that that of cobalt chloride,
approximately 70% compared with 1–16%, respectively (ICRP, 1993a,b). Cobalt in
marine organisms could be present as vitamin B12. Inaba et al. (1980, 1982) reported
that the retention of cobalt in rats after oral administration in fish or marine algae
was 35% and 10%, respectively; substantially higher than when it was administered
as the chloride (1%).
Metals
(D90) Sullivan and Ruemmler (1987) showed that ferrous and ferric iron caused
three-fold and 14-fold increases, respectively, in the absorption of 109Cd in rats. In
254
contrast, while fasting increased 210Pb absorption five fold, the oxidising agents ferric
iron and quinhydrone counteracted the effect of fasting.
(D91) The presence of bile in the intestine has been shown to affect the absorp-
tion of some metals. Cikrt and Tichy (1975) found that the absorption of 203Pb
administered into the duodenum of rats as 203PbCl2 was decreased by approxi-
mately 18% when normal bile flow to the intestine was interrupted by bile duct
cannulation.
(D92) Metals such as copper, zinc, and cadmium are bound by metallothionein in
mucosal cells. The degree of binding can differ, depending on the physiological state
and diet. A low-calcium diet, for example, increases mucosal calcium-binding pro-
tein, which causes enhanced binding of both calcium and cadmium (Washko and
Cousins, 1977).
(D93) Zinc and aluminium, when present in high concentrations, will form insol-
uble salts at neutral pH with phytate (Cheryan, 1980). Some metals in trace amounts
such as cadmium, copper, lead, and zinc will also coprecipitate with calcium phytate
(Wise and Gilburt, 1981, 1982; Wise et al., 1983). These reactions, if occurring
in vivo, would reduce absorption. Similarly, dietary fibre may bind a variety of ele-
ments and render them unavailable for absorption (Campbell et al., 1976; Reinhold
et al., 1976). Potentiators of uptake have been proposed for some metals. The effec-
tiveness of human breast milk in the treatment of acrodermatitis enteropathica has
been attributed to a particularly readily absorbed form of zinc (Hurley and Lonner-
dal, 1982).
(D94) Some results suggest that the high bioavailability of zinc in human milk
results from the presence of picolinic acid, a bidentate chelating ligand that facil-
itates zinc absorption from the intestine (Evans and Johnson, 1980). Histidine,
released by the digestion of proteins, has also been implicated as an important
ligand for zinc in the lumen of the intestine (Wapnir et al., 1983). These authors
suggested that the zinc–histidine complex was absorbed by the same mechanisms
as the amino acid. Copper may also be absorbed as amino acid complexes.
However, not all metals that form complexes with amino acids are absorbed
in this form. L-histidine complexes manganese but it appears that this metal is
not absorbed as this low-molecular-weight complex (Garcia-Aranda et al.,
1983).
Non-metals
(D95) Chemical form has very little influence on the gut uptake of some non-met-
als of radiobiological importance such as sulphur and iodine. Commonly occurring
forms of both of these elements are well absorbed, with the exception of elemental
sulphur (Johnson et al., 1971) and lignin-sulphonate (Bouchard and Conrad,
1973). It has been shown that incorporation of selenium into amino acids enhances
absorption relative to the inorganic selenite. However, differences occur between ani-
mal species. In rats, the intestinal absorption of selenite and seleno-methionine are
similar at approximately 95%, whereas in humans, the absorption from selenium-la-
belled meat of approximately 80% may be higher than from selenite (approximately
35%) (Christensen et al., 1983).
255
Actinides: neptunium
Oxido-reduction
(D96) Ballou et al. (1962) reported that the oxidation state of neptunium was an
important factor in its intestinal absorption. In these studies, groups of rats gavaged
with 237Np(IV), 237Np(V), and 237Np(VI) nitrate solutions retained 0.3, 1.1, and
2.3%, respectively, at 1 day after gavage. In another study, more careful control of
oxidation state was achieved and pH 1.5 nitrate solutions were used, checked spec-
trophotometrically just prior to administration (Mahlum, 1962). Results of these
studies showed that absorption of 237Np(V) and 237Np(VI) in adult rats was 1.8 ·
103 and 2.4 · 103, respectively.
(D97) Reducing conditions in the intestine may influence the absorption of neptu-
nium. The pentavalent neptunyl ion (NpO2+) is stable at neutral pH. Administration
of milligram amounts of 237Np(V) to rats resulted in an uptake of up to 3% (Sullivan
et al., 1983). However, in the same study, only 0.04% of a 5-pg dose of 239Np(V) was
absorbed. The authors’ explanation was that small amounts of Np(V) are reduced in
the intestine to the poorly absorbed Np(IV). Consistent with this, other workers have
observed this mass effect in rats (Harrison et al., 1984) and in baboons (Métivier
et al., 1983a,b), but not in hamsters (Harrison et al., 1984).
(D98) Sullivan et al. (1984c) investigated the effect of oxidising and reducing
agents on absorption of neptunium from the gastrointestinal tract of mice and
rats. They showed that the oxidants quinhydrone and ferric ions caused an in-
crease in 237Np absorption in both fed and fasted rats. On the other hand, ferrous
iron, which is a reducing agent, decreased absorption. Similar results were ob-
tained with mice given 235Np and either ferric or ferrous iron. The effects of ferric
and ferrous iron on neptunium absorption by neonatal rats were similar to their
effect in adult animals but of lesser magnitude (Sullivan et al., 1984c). These re-
sults are consistent with the hypothesis that Np(V), when given in small quantities
to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well
absorbed than Np(V). This process could be limited, however, in the intestine of
neonates.
Complexation
(D99) The absorption of neptunium has been studied in baboons fed with different
diets (Métivier et al., 1986). A hydroxyl-acid-depleted diet decreased absorption and
retention of neptunium, but when the hydroxy acid and vitamin content was raised
with a fruit diet, an increase in total absorption was observed with a corresponding
increase in urinary excretion. This finding may be due to the formation of strong
complexes with the main hydroxy acids in fruit (ascorbate, citrate, malate, and oxa-
late), combined with the highly transferable character of these complexes and their
rapid excretion in urine (Métivier et al., 1986). Fasting causes marked increases in
the absorption of many heavy metals, including plutonium (Stather et al., 1980; Sul-
livan, 1980a,b) and neptunium (Sullivan et al., 1984a,c).
(D100) Fristch et al. (1985) studied the jejunal transfer of different soluble forms
of neptunium. They found that at 5 · 1012M, the jejunum was permeable to Np(V)
256
nitrate and as much as 2.7% of the activity in the lumen was transferred/10 cm/h. The
addition of DTPA–calcium (100 lm) did not significantly modify that value. Citrate
(1 mM) decreased transfer to 0.8%. Np(IV) was readily transformed to Np(V) when
the pH was raised to 7. The authors concluded that both citrate (1 mM) and cal-
cium–DTPA (100 lM) stabilised Np(IV), and the observed transfers, 0.3% and
0.9%, respectively, were lower than those of Np(V) in similar solutions. Tissue dis-
tribution of complexed Np(IV) varied as a function of the chelator used (Fritsch
et al., 1985).
Actinides: plutonium
Oxido-reduction
(D101) As for neptunium, plutonium absorption is influenced by its oxidation
state. It is known that tetravalent plutonium may be reduced or oxidised under con-
ditions that could be encountered in food and drink. For example, the oxidation of
Pu(IV) to Pu(VI) has been shown to occur in chlorinated drinking water (Larsen and
Oldham, 1978).
(D102) The absorption of Pu(III) is thought to be greater than that of Pu(IV)
(Weeks et al., 1956). Many studies have shown that the absorption of Pu(VI) was
only higher than that for Pu(IV) in fasted animals and/or in the presence of an oxi-
dant such as K2Cr2O2 (Larsen et al., 1981a; Stather et al., 1980; Sullivan et al.,
1979b). These results showed that the contents of the alimentary tract normally re-
duce any Pu(VI) present to Pu(IV), and that the absorption observed is then charac-
teristic of Pu(IV) (Sullivan et al., 1984b,c).
(D103) For a high ingested mass (>400 lg/kg), absorption of Pu(V) in baboons
approached 1% (Métivier et al., 1985). This high value is characteristic of the
Pu(V) oxidation state. At lower masses, lower values were obtained due to reduction
of Pu(V) by organic material (Métivier et al., 1985).
Complexation
(D104) Potatoes are known to contain two major ligands (phytate and citrate),
which both enhance gastrointestinal absorption of tetravalent plutonium (Cooper
and Harrison, 1984a).
(D105) Speciation studies on potatoes digested with a simulated human gastroin-
testinal fluid (pepsin, pancreatinin, and alpha-amylase) showed that plutonium was
associated with two unidentified chemical forms of low molecular weight, which were
neither phytate nor citrate (Bulman et al., 1993).
(D106) The presence of polymeric forms of plutonium reduces absorption (Bhat-
tacharyya et al., 1985a).
D.5.2. Retention
(D107) Intestinal retention has been shown to occur for many radionuclides. It is
most pronounced, however, in neonatal mammals.
257
Intestinal retention in adults
(D108) Measurements of 45Ca in various segments of the alimentary tract showed

that the greatest retention of calcium from milk occurred in the stomach, the duode-
num, and the distal jejunum (Blake and Henning, 1988).
(D109) Kostial et al. (1989) investigated the gut retention of 203Hg, 141Ce, and
115m
Cd in the rat. They showed that the ileum was the main site of intestinal reten-
tion of these elements in suckling rats, irrespective of the length of time after radio-
nuclide administration (2–12 days). In adults, the distribution in the gut was element
specific. Great similarities were observed between the location of mercury and that of
cerium (highest in the stomach, lowest in the small intestine). For cadmium, the
highest activity was found in the small intestine.
Intestinal retention in neonates
General considerations
(D110) Neonatal animals can retain ingested actinides in the gastrointestinal tract
to a much greater extent than adults (Bomford and Harrison, 1986; Fritsch et al.,
1986; Sullivan et al., 1984c). Actinides were mainly retained inside epithelial cells
on villi in the distal part of the small intestine of the neonatal rat and swine (Sullivan,
1980a,b; Sullivan et al., 1984b). The amounts of actinides retained seem to be closely
related to the non-specific uptake of macromolecules by the epithelial cells, which
mainly occurs in the distal part of the small intestine (Baintner, 1986). In some mam-
mals, intestinal uptake of macromolecules sharply decreases after birth during intes-
tinal closure. In other mammals, such as primates, closure seems to occur before
birth (Fritsch et al., 1988).
(D111) The levels of intestinal retention in different species appear to be related to
the extent of pinocytic activity. Table D.9 compares the retention of 238Pu in the
small intestine of rats and guinea pigs (Harrison and Fritsch, 1992).
(D112) Based on rat data, the kinetics of actinide retention in the small intestine
have been regarded as a dynamic process that involves the normal migration to and
sloughing of epithelial cells from the tip of the villi. However, in the neonatal guinea
pig, actinides appear to be retained not in but beneath the epithelial layer (Sullivan
et al., 1987). In guinea pigs, baboons, and macaque, low levels of plutonium are re-
tained mainly in macrophages in the lacteal region of the tips of the villi (Fritsch
238
Table D.9. Intestinal retention of Pu in newborn animals. Source: Harrison and Fritsch (1992)
Species Age at ingestion (days) Time after ingestion (days) Ingested activity (%) in
1a 2a 3a
Rat 6 5 0.03 5.5 16.7
12 5 0.01 4.6 36.3
Guinea pig 6 5 0.006 0.007 0.009
12 5 0.008 0.009 0.009
a
1, 2, and 3 refer to three equal lengths of small intestine.
258
et al., 1988). These different locations probably correspond to different retention

kinetics.
Specific examples of intestinal retention in juveniles
Plutonium
(D113) The retention of plutonium in the gastrointestinal wall has been compared
after administration to 2-day-old rats and guinea pigs, and in 1–34-day-old baboons
(Fritsch et al., 1988; Lataillade et al., 1992). The small intestine was the main site of
plutonium retention in each case (see Tables D.5 and D.7). In rats and primates,
most of the plutonium was retained in the distal ileum, whereas in guinea pigs, it
was more homogeneously distributed. In rats, plutonium was retained in the epithe-
lial cells of the villi (Fig. D.2). In guinea pigs and primates, retention was confined to
the macrophages under the epithelial cells in the lacteal region (Fritsch et al., 1988;
Sullivan et al., 1987) (Fig. D.3). These comparative studies show that the high level
and pattern of intestinal retention of plutonium observed in neonatal rats do not
apply to baboons and are unlikely to apply to humans.
(D114) The intestinal retention of plutonium ingested as 238Pu citrate by baboons
depends on the age at ingestion. Studies suggest that retention in the small intestine
was high for intakes at 1 day of age up to 50 days of age and decreased dramatically
in older animals (Table D.5) (Lataillade et al., 1992). More detailed studies showed
that plutonium retention in the intestine wall was greatest in the ileum after admin-
istration to animals up to 66 days old, while the duodenum was the major site of
accumulation when animals were 129 days or older at the time of administration
238
Fig. D.2. Autoradiograph showing the retention of Pu in the villi of the small intestine of newborn
baboons. Source: Fritsch et al. (1988).
259
Fig. D.3. Autoradiograph of the ileum of a guinea pig gavaged with 238Pu at 2 days after birth and killed 1
day later. Source: Sullivan et al. (1987).
(Lataillade et al., 1992). It was postulated that this high retention in the ileum of neo-
natal baboons was due to the presence of an apical canalicular system associated
with vacuoles in the epithelial cells of the villi of the ileum, shown to be present dur-
ing the early months of life.
Neptunium
(D115) As for plutonium, intestinal retention of neptunium ingested by baboons
as 239Np nitrate depends on the age of the animal at the time of ingestion (Table
D.6). The main site of retention was the small intestine with values ranging from
0.1% to 0.15% of the administered activity for intakes at 4–14 days of age, and
0.02–0.06% at 26–159 days of age. Within the intestine, deposition was highest in
the ileum at the youngest ages (Lataillade et al., 1992).
Others
(D116) Studies with isotopes of thorium, uranium, protactinium, neptunium,
americium, curium, and einsteinium showed that substantial amounts of these al-
pha-emitting radionuclides were retained in the intestines of neonatal rats, guinea
pigs, dogs, and swine after gavage (Sullivan et al., 1987).
(D117) Autoradiographs prepared after administration of 109Cd chloride to 2-day-
old rats showed that cadmium was retained in the duodenum, where it was distrib-
uted throughout the mucosa and submucosa. In contrast, measurements in piglets
showed much higher 109Cd retention in the ileum than in the duodenum (Sullivan
et al., 1984b).
(D118) Autoradiographs and radiochemical measurements of 147Pm and 238Pu
given as the chloride to both neonatal rats and swine showed the highest level of
260
Fig. D.4. Autoradiograph of the small intestine of a rat gavaged with 147Pm chloride 2 days after birth
and killed 1 day later. Note the concentration in the outer coils of the cross-section of the ileum and the
absence of 147Pm near the central segment of the duodenum. Source: Sullivan et al. (1987).
retention in the ileum (Fig. D.4) (Sullivan et al., 1984b). In guinea pigs, 147Pm was
found to be concentrated in the tips of the villi of the distal small intestine.
(D119) Inaba and Lengemann (1972) demonstrated that radiocerium administered
to suckling rats is readily taken up by the intestinal cells and cleared from the body
only when the cells have migrated up to the villi and have been sloughed into the
intestinal lumen.
D.5.3. Absorption
(D120) The intestinal absorption of radionuclides is, in general, markedly influenced

by the ingested chemical form and mass of the element, by the diet at the time of inges-
tion, and by numerous physiological parameters such as the age, gender, and health
status of the individuals. The aim of this section is to review some of these parameters
and to give some specific examples of fractional absorption for radionuclides of inter-
est. Results for individual elements are presented, wherever possible, gathered within a
chemical family. In some cases, however, experiments showed that members of the
same family of elements in the periodic table may behave biologically differently from
one another (Sullivan et al., 1984a) and these are then discussed separately.
(D121) Results for actinide absorption in neonates are presented at the end of the
section. Numerous studies have been performed aimed at understanding increased
absorption of these elements in neonates, and this subject warrants separate
consideration.
(D122) Many investigators have found that animals fed an iron-deficient diet ab-
sorb increased amounts of many other metals that may share an intestinal transport
261
system with iron (Sullivan and Ruemmler, 1988). In most cases, absorption of radio-
nuclides has been determined in animals fed an iron-replete diet. However, large
populations in both industrial and underdeveloped countries are anaemic because
of an inadequate dietary intake of iron. This is especially true during infancy or
childhood and under certain states of malabsorption (Sullivan and Ruemmler,
1988). In an iron-deficient animal, numerous binding sites are presumably available
to any metal using the same transfer proteins as iron. However, it has been shown
that iron deficiency does not result in increased absorption of all metals.
Non-metals
Tritium
(D123) Experiments with humans have shown that hydrogen in the form of deu-
terium oxide or tritiated water is rapidly and virtually completely absorbed from the
alimentary tract (Pinson and Langham, 1957). For organically bound forms of tri-
tium, absorption may be less complete, but, for radiological protection purposes,
in the absence of specific information, complete absorption is usually assumed.
Alkali metals
Rubidium
(D124) Rubidium is well absorbed from the human lower small intestine and co-
lon. Due to its chemical properties, 86Rb has been used mainly as a marker for K+
absorption in the colon. Clauss et al. (1989) investigated the basic bioelectrical prop-
erties and the transport of Na+, Rb+, and Cl in isolated caecal epithelium of the
rabbit. They showed that Na+ and Cl were absorbed, whereas Rb+ was secreted.
Rb+ secretion occurs via a transcellular route. The results showed that the rabbit cae-
cum has an epithelium with a high electrolyte transport capacity, distinctly different
from the neighbouring proximal colon, and suited to absorb the large quantities of
electrolytes that are present in the lumenal liquid.
(D125) Dorge et al. (1998) investigated lumenal rubidium uptake into different epi-
thelial cell types in isolated guinea pig distal colon. They showed that net rubidium
absorption was approximately 1.5–2.5 lmol/h/cm2 and was not influenced by inhibi-
tion of sodium transport with amiloride or by incubating both sides of the epithelium
with sodium-free solutions. Lumenal rubidium uptake preferentially occurred in
columnar surface cells, and to an insignificant degree in lower crypt cells. The pres-
ence of 5.4 mM potassium in the lumenal incubation solution reduced rubidium up-
take almost completely, indicating a much higher acceptance of the lumenal H-K-
ATPase for potassium than for rubidium.
Caesium
(D126) Hunt (1998) investigated the fractional absorption of 137Cs from cockles
(Cerastoderma edule) collected on the Irish Sea coast of the UK. He found that frac-
tional absorption was in the range of 0.08–0.43. McKay and Memmott (1991) found
that the fractional absorption of caesium adsorbed on to inorganic sedimentary
262
material was significantly less than unity. In general, though, caesium is readily ab-
sorbed and complete absorption has been assumed by the ICRP (1989a,b).Caesium
absorption has been shown to occur mainly in the ileum (Majle et al., 1991).
Calcium
(D127) The developing rat has been used in a number of investigations of the ontog-
eny of calcium absorption after ingestion of simple salts (Ghishan et al., 1980; Hallo-
ran and Delucas, 1980; Pansu et al., 1983; Taylor et al., 1962). In general, these studies
demonstrated that during the suckling period, ionic calcium is absorbed via a passive,
non-vitamin-D-dependent process (Ghishan et al., 1980; Pansu et al., 1983) that
contrasts with the adult mode of absorption which involves an active vitamin-D-
dependent process (Dostal and Toverud, 1984). Blake and Henning (1988) studied cal-
cium absorption in 14- and 28-day-old rats and compared absorption of 45Ca in milk
and 45CaCl2. They showed that for suckling rats (14 days old), transport and absorp-
tion of 45Ca from milk was slower during the first 3 h after introduction into the stom-
ach than that observed for 45Ca administered as the chloride. By 6 h after intubation,
absorption was similar in both cases and was 90% of the ingested activity. Overall effi-
ciency of 45Ca absorption from 45CaCl2 was significantly less in adult rats. It was pos-
tulated that in neonates, 45Ca from CaCl2 traverses the intestinal wall as ionic calcium
and enters the mucosa passively, perhaps via simple diffusion due to increased perme-
ability of the brush border membranes (Dostal and Toverud, 1984). In contrast, 45Ca
in milk entering the small intestine remains associated with milk protein.
Strontium
(D128) Gastrointestinal absorption of radioactive strontium has been widely stud-
ied as an indicator of calcium absorption. Sips et al. (1996) investigated the absorp-
tion of strontium in healthy volunteers after administering strontium chloride either
under fasting conditions or together with a standardised meal. Average absorption
was 25% without a meal and 19% with a meal, with intra-individual variation of
24% and 20%, respectively.
(D129) Zitterman et al. (1995) investigated strontium absorption in a group of
young females (24 years) who received an oral dose of 2.27 mmol strontium in a stan-
dardised breakfast that contained 0.625 mmol calcium. They showed that absorption
was 13.3 ± 3.1% with no effect of smoking, exercise, or the use of oral contraceptives.
Moon (1994) showed that strontium absorption was enhanced by co-absorption of
vitamin D. Gong et al. (1991) showed that complexation of strontium with alginates
from algae (Sargassum sp.) and kelp (Laminaria sp.) reduced absorption in humans
by 78 ± 9%. Gruden (1984) showed that in rats fed on a milk diet with or without the
addition of lactose and/or iron, the transileal 85Sr transfer was higher by 14–38% and
the intestinal strontium retention was lower by 6–23% than in control rats fed on
standard laboratory food.
(D130) The transport of strontium ions through enteral and renal tubular cells is
mediated by the same membrane carriers as used for calcium, and a highly significant
263
Table D.10. Strontium chloride gastrointestinal uptake in eight healthy adult men (4 h after oral
administration). Source: Sips et al. (1996)
Subject Absolute bioavailability (%)
Test 1 Test 2 Test 3
1 29 13 33
2 41 37 38
3 27 28 24
4 23 31 20
5 21 23 25
6 22 28 34
7 15 34 20
8 20 22 19
correlation has been observed between strontium and calcium absorption. Strontium
ions are less well absorbed in the intestine than calcium, but are more quickly ex-
creted in urine and into the intestine in digestive secretions (Vezzoli et al., 1998).
(D131) Sips et al. (1996) studied the absorption kinetics of orally administered
strontium in healthy male volunteers (aged 19–31 years) after administering stron-
tium chloride either under fasting conditions (Study I; n = 8 individuals) or in com-
bination with a standardised meal (Study II; n = 8 individuals). Mean absorption of
strontium was 25% without a meal and complete within 3 h after administration, and
19% with a meal and complete within 4.3 h after administration. This difference in
gastrointestinal uptake may have been caused by different calcium/strontium ratios
(1.0 in Study I and 1.8 in Study II) and/or by the influence of the meal. Sips et al.
(1996) measured mean gastrointestinal uptake of strontium after oral administration
of strontium chloride to eight healthy male volunteers under fasting conditions as
25% ± 7% (Table D.10). Total absorption was reached within 4 h.
(D132) Dahl et al. (2001) reported gender differences in the gastrointestinal
absorption of strontium. In rats and monkeys, plasma strontium levels were higher
in males than in females. The authors did not quantify this difference. In contrast, the
results obtained by Vezzoli et al. (1998) showed no clear influence of gender on
strontium absorption.
(D133) Bianchi et al. (1999) investigated the influence of 1,25-dihydroxyvitamin
D3 [1,25(OH)2D3] on calcium and strontium chloride absorption. 1,25(OH)2D3 is re-
ported to influence intestinal calcium absorption in vertebrates by at least two sep-
arate actions: a rapid action on cellular membranes and transport systems, and a
delayed action which involves gene activation and protein synthesis. There appear
to be several different mechanisms ensuring calcium entry across the brush border
membrane into the intestinal cell, as well as its translocation through the cytoplasm
and its release across the basal lateral membrane into the circulation. In 10 healthy
volunteers, five tests were performed in a crossover design with a washout period be-
tween two consecutive tests: strontium absorption without 1,25(OH)2D3 (Test A);
strontium absorption immediately after oral (Test B) or intravenous (Test C) admin-
istration of 1,25(OH)2D3; and strontium absorption 24 h after either oral (Test D) or
intravenous (Test E) administration of 1,25(OH)2D3. The concurrent administration
of 1,25(OH)2D3 and strontium (Tests B and C) did not significantly change the intes-
264
Table D.11. Strontium intestinal absorption tests in normal subjects under different conditions of
1,25(OH)2D3 administration. Source: Bianchi et al. (1999)
Test Absolute bioavailability (%)
A [no 1,25(OH)2D3] 22
B [immediately after oral 1,25(OH)2D3] 25
C [immediately after intravenous 1,25(OH)2D3] 23
D [24 h after oral 1,25(OH)2D3] 30
E [24 h after intravenous 11,25(OH)2D3] 30
tinal absorption compared with Test A, whereas strontium absorption was signifi-
cantly increased when strontium was given 24 h after either oral or intravenous
1,25(OH)2D3 (Tests D and E). The results are shown in Table D.11. It was concluded
by the authors that 1,25(OH)2D3 is only likely to influence calcium absorption sig-
nificantly via its effect on gene action and protein synthesis, independent of its
administration route. Comparison of the data in Tables D.10 and D.11 shows that
the increased strontium absorption reported by Bianchi et al. (1999) is within the
individual variation in absorption in the study of Sips et al. (1996).
(D134) In conclusion, a number of factors have been found to increase strontium
absorption, including fasting and low dietary levels of calcium, magnesium, and
phosphorus, milk diets, and vitamin D. The average value of the data presented in
Tables D.10 and D.11 for fractional absorption is 0.26.
Transition metals
Zirconium
(D135) Fletcher (1969) measured fractional absorption of zirconium in rats and
reported values in the range of 3 · 104 to 2 · 103. Shiraishi and Ichikawa (1972)
obtained values of 1 · 103 for the absorption of zirconium administered in oxalic
acid (pH 2.5) to juvenile animals (16 days old) and 3.5 · 104 in adult rats.
Hafnium
(D136) The absorption of various chemical forms of181Hf administered orally to
marmosets was found to be between 0.04 and 0.13%, was unaffected by age between
5 and 21 months, but was increased by fasting. The measured absorption of 181Hf in
Chinese hamsters and rats was similar to that of plutonium, and hafnium was sug-
gested as a possible surrogate for plutonium in human volunteer studies (Taylor
et al., 1985b).
Niobium
(D137) Studies with small animals with a number of niobium compounds have
indicated that fractional absorption is 1 · 102 or less (Fletcher, 1969; Furchner
and Drake, 1971). Mraz and Eisele (1977a) reported higher absorption of 95Nb in
oxalic acid by suckling rats than by adult rats, with values of 6 · 102 and
9 · 104, respectively. Paquet et al. (1998) investigated the fractional absorption of
niobium given to rat as the citrate, oxalate, and chloride forms, and obtained values
265
of 1.25 · 102, 0.37 · 102, and 0.24 · 102, respectively. When 95Nb oxalate was
given to 1-day-old rats, absorption was increased by a factor of 200.
Vanadium
(D138) Studies of the absorption of vanadium are scarce. Wiegmann et al. (1982)
studied the effect of aluminium on vanadium absorption in rats. They gavaged ani-
mals with 5 lmol Na3 VO4 in 1.0 ml 0.9% NaCl containing 1 37 kBq 48V. Al(OH)3
markedly decreased urinary excretion of 48V from 13% of the administered activity
to 8%, interpreted as a reduction in intestinal absorption. Hill (1980) found that
ascorbic acid reduced vanadium absorption in rats.
Chromium
(D139) Absorption of 51Cr by the adult rat was found to be less than 0.5% (Visek
et al., 1953). Absorption by 2-day-old animals was found to be 10-fold higher than in
adults (Sullivan et al., 1984b). It has been reported that many higher plants synthe-
sise an anionic chromium complex of high availability (around 30%) to rats (Starich
and Blincoe, 1983).
Molybdenum
(D140) Turnlund et al. (1995) investigated molybdenum absorption in humans.
Four young men were fed five different levels of dietary molybdenum, ranging from
22 to 1490 lg/day, for 24 days each. Molybdenum was very efficiently absorbed (88–
93% for all dietary molybdenum intake), with a suggestion that absorption was most
efficient for the highest amounts of dietary molybdenum. Molybdenum was con-
served at low intakes and excess molybdenum was rapidly excreted in the urine when
intake was high.
Manganese
(D141) Sahagian et al. (1971) performed in-vitro studies on the absorption of man-
ganese in the rat small intestine. They showed that manganese uptake was rapid and
continued during the 60 min of incubation. The absorption was enhanced by the
presence of cadmium and zinc but decreased by the presence of mercury. Manganese
transport was depressed by ascorbate, dehydroascorbate, and EDTA but enhanced
by phlorhizin and iodoacetate.
Technetium
(D142) Technetium released into the environment can reach animals in various
chemical forms, as pertechnetate (TcO4) in drinking water or deposited on the sur-
face of vegetables and forage plants, or as technetium incorporated into plants and
associated with various plant constituents. In addition to being influenced by chem-
ical speciation in the diet, absorption, metabolism, and retention of technetium in
animals are modified by the changes in speciation in the alimentary tract.
(D143) The fractional absorption of 99Tc from cockles collected on the Irish Sea
coast in the UK was investigated in a human volunteer study by Hunt (1998), and
a value of approximately 0.6 was obtained. Gerber et al. (1989) studied the absorption
266
of 99mTc given in diet either as TcO4 or incorporated into maize using rats and sheep.
The pattern of absorption, excretion, and, to a certain degree, organ distribution and
retention depended on animal species and species of technetium administered. Intes-
tinal absorption of technetium in the two forms was approximately equal in sheep,
but absorption in rats was greater after administration as pertechnetate than for tech-
netium in maize. Sullivan et al. (1979a) also showed that the absorption of technetium
by rats from labelled plant tissue was lower than that for pertechnetate.
Cobalt
(D144) Studies performed with 60Co chloride showed that when cobalt was pres-
ent in trace quantities (less than 1 lg), the fractional absorption was 0.05 or less, but
when higher masses were administered (1–12 mg), absorption ranged between 0.1
and 0.3 (Paley and Sussman, 1963; Smith et al., 1972). In contrast, the fractional
absorption of cobalt administered to rats as a Co(II)–glycine complex decreased
from 0.34 for an intake of 0.1 lg to 0.11 at intakes of 0.75 and 1 mg cobalt (Taylor,
1959, 1962). These administered amounts correspond to approximately 1 lg/kg and
10 mg/kg, respectively, and 1–12 mg administered to humans corresponds to 14–170
lg/kg. Taylor (1959,1962) also measured cobalt absorption in rats after administra-
tion of CoCl2, cobalt in cows’ milk, or lactose solutions (0.1–1 lg), and obtained val-
ues of approximately 0.3–0.4%.
(D145) The results of metabolic balance studies suggest that an intake of approx-
imately 8 lg of cobalt is needed to maintain cobalt equilibrium (Engel et al., 1967).
In addition, there is a requirement for 0.04 mg of cobalt daily in the form of vitamin
B12 (Schroeder et al., 1967). Thomson et al. (1971) studied cobalt absorption in rats
fed with 57CoCl2 and 59FeCl2. They found a direct relationship between intestinal
uptake of iron and cobalt. This suggested that iron and cobalt share at least part
of the same transport pathway, and further support for this conclusion is given by
the finding of an increase in cobalt absorption in iron-deficient rats (Pollack et al.,
1965). In humans, the results of balance studies suggest that a variable amount of
dietary cobalt, in the range of 20–95%, is absorbed from the intestine (Engel
et al., 1967). The absorption of radioactive cobaltous chloride appears to diminish
when it is administered after a meal or pre-tagged to protein (Paley and Sussman,
1963). Valberg et al. (1969) reported a value of 46% for the absorption of cobalt
in humans, and increased absorption in subjects suffering from iron deficiency.
(D146) Christensen et al. (1993) studied the fractional absorption of cobalt in 23
humans fed with soluble and insoluble cobalt compounds (8.5 nmol/day). In a con-
trolled study, it was found that the uptake of cobalt was considerably higher after
administration as the soluble chloride than the insoluble oxide. It was shown that
ingestion of controlled amounts of soluble cobalt compound resulted in significantly
higher urinary cobalt levels (P < 0.01) in females (median: 109.7 nmol/mmol creati-
nine) than in males (median: 38.4 nmol/mmol creatinine). This result suggests that
the gastrointestinal uptake of cobalt is higher for females than males.
(D147) The fractional absorption of 60Co from cockles collected on the Irish Sea
coast in the UK was investigated in a human volunteer study by Hunt (1998), and a
value of approximately 0.2 was obtained.
267
Iron
(D148) Dietary iron can be divided into two categories: haem and non-haem.
Haem, in which iron is contained in a porphyrin ring, is found in haemoglobin
and myoglobin, and accounts for over 30% of the iron in animal tissues. The intact
iron–porphyrin complex is taken up by the mucosal cells and the iron is released by
specific enzymes (Weintraub et al., 1968). The bioavailability of haem iron is rela-
tively unaffected by other dietary constituents and is greater than that of non-haem
iron. Haem iron represents 5–10% of the iron ingested in a Western diet but accounts
for over 30% of that absorbed (Weintraub et al., 1968).
(D149) The absorption of non-haem iron is influenced by components in the diet
(Cooper, 1985). Ionic iron can exist in two oxidation states, ferric (Fe3+) and ferrous
(Fe2+). Both forms are probably taken up by the mucosa, although studies with sol-
uble Fe3+ and Fe2+ complexes suggested that uptake of the latter is faster (Muir
et al., 1984). The availabilty of iron clearly depends upon its solubility, and therefore
dietary constituents that reduce ferric to ferrous ions or which complex iron and
maintain it in a soluble form may enhance absorption. Ascorbic acid is one of the
most important and probably acts in two ways, firstly by reducing ferric to ferrous
ions in the acid stomach conditions and secondly by complexation (Clydesdale, 1985;
Slatkavitz and Clydesdale, 1988). Other organic acids including lactic, citric, malic,
and tartaric acids will also promote absorption by complexing iron. For this to oc-
cur, however, the complex must either be able to donate its iron to receptors in the
microvillus membrane or pass intact into the absorptive cell.
(D150) Compounds that form insoluble iron salts will inhibit iron absorp-
tion. Examples are the tannates in tea, which are amongst the most potent inhibi-
tors of iron absorption known (Disler et al., 1975), and polyphenols in coffee
(Gillooly et al., 1983; Morck et al., 1983) and other plant tissues (Gillooly
et al., 1984). The non-digestible dietary fibres such as lignins, pectin, cellulose,
hemicellulose, and gum will also bind iron and thus inhibit uptake (Reinhold
et al., 1986).
(D151) Work on the bioavailability of iron from various diets has led to the con-
cept of an intralumenal pool of non-haem iron from which absorption takes place
(Charlton and Bothwell, 1983). This pool does not include insoluble compounds
such as ferric orthophosphate, ferric orthophosphate, ferric oxide, and ferritin
(which only partially exchanges) (Bezwoda et al., 1979). The absorption of iron from
the intralumenal pool is influenced by competition between the various promoting
and inhibiting compounds present in the intestinal lumen (Cooper, 1985). The rate
of absorption of iron is adjusted according to body iron requirements, but the virtual
absence of haem and the poor bioavailability of the non-haem iron in the diets of
many people, especially in developing countries, means that the amount that can
be absorbed is limited (Charlton and Bothwell, 1983).
Nickel
(D152) Paquet et al. (1998) investigated the absorption of 63Ni in adult and juve-
nile rats. They showed that the fractional absorption of nickel was 4.3 · 102,
5.1 · 102, and 3.3 · 102 for the citrate, oxalate, and chloride forms, respectively.
268
When the radionuclide was administered to 1-day-old animals, overall retention in-
creased by factors of up to 60 for the chloride.
Copper
(D153) Copper absorption and retention from a high-fibre and high-phytate diet
of conventional foods were investigated in eight healthy subjects (Knudsen et al.,
1996). Fractional absorption was estimated as 44 ± 7%.
(D154) In a review of available data, Wapnir (1998) estimated that the human ali-
mentary tract can absorb 30–40% of ingested copper from the typical diets consumed
in industrialised countries. He suggested that physiological differences may account
for copper deficiency in females. Changes in the fibre content of the diet may have an
indirect effect on copper bioavailability by altering the bioavailability of mineral
antagonists. Proteins and soluble carbohydrates tend to improve copper absorption
and bioavailability by enhancing its solubility and intestinal bulk flow. Organic
acids, other than ascorbic acid, or agents that form low-molecular-weight chelates
are likely to have a positive effect on overall copper absorption. Conditions associ-
ated with malabsorption of macronutrients and gastrointestinal disease can impair
copper uptake and contribute to suboptimal copper status.
(D155) In another review, Linder et al. (1998) showed that the net absorption of
dietary copper in adult humans is approximately 1 mg/day. Dietary copper joins
some 4–5 mg of endogenous copper flowing into the gastrointestinal tract through
various digestive juices. Newly absorbed copper is transported to body tissues, borne
primarily by plasma protein carriers (albumin, transcuprein, and ceruloplasmin).
Alternatively, absorbed copper reaching the liver via the hepatic portal vein can
be directly excreted via the bile in a form that is less easily re-absorbed. The concen-
trations of copper and ceruloplasmin in milk vary with lactational stage. Copper in
milk ceruloplasmin appears to be particularly available for absorption, at least in
rats.
(D156) According to Turnlund (1998), the efficiency of copper absorption varies
greatly depending on dietary intake. Changes in the efficiency of absorption help
to regulate the amount of copper retained by the body. In addition, endogenous
excretion of copper into the gastrointestinal tract depends heavily on the amount
of copper absorbed. When dietary copper is high and more is absorbed, endogenous
excretion increases, protecting against excess accumulation of copper in the body.
When intake is low, little endogenous copper is excreted, protecting against copper
depletion. Regulation is not sufficient with very low amounts of dietary copper (0.38
mg/day) and appears to be delayed when copper intake is high.
Metals
Zinc
(D157) Zinc is an essential trace element that is reported to be absorbed by both
animals and man in proportions of up to 90% of the ingested amount (Elinder and
Piscator, 1979). Other data suggested that approximately one-third as much 65Zn
was absorbed by the adult as by the neonate (Sullivan et al., 1984b). Methfessel
269
and Spencer (1973) also reported that the small intestine of mature rats (>80 days
old) absorbs less zinc than that of young rats (40 days old).
(D158) In-vitro studies by Sahagian et al. (1971) suggested that zinc uptake in the
small intestine of rats was concentration dependent and was enhanced by the pres-
ence of cadmium or mercury. Initial complexation of zinc with L-ascorbate, dehy-
droascorbate, phlorhizin, or EDTA enhanced absorption.
Cadmium
(D159) The behaviour of cadmium is expected to resemble that of zinc because
both are members of subgroup IIB and compete for common metabolic pathways
(Probst, 1979). Cadmium, however, is neither well absorbed nor rapidly excreted
(Friberg et al., 1974). Sasser and Jarboe (1977) measured cadmium retention in neo-
natal rats gavaged with 115CdCl2 at intervals between 1 and 21 days after gavage.
They reported a maximum of 11% retained in rats gavaged at 2 h after birth and
3% when gavaged at 1 day of age. Sullivan et al. (1984b) reported values of absorp-
tion for 109Cd administered as the chloride as 2% for 2-day-old rats, 1% for 9-day-
old pigs, and 0.6% for adult rats.
Mercury
(D160) Sahagian et al. (1971) performed in-vitro studies on the absorption of manga-
nese in the rat small intestine. They showed that mercury uptake was maximal within 10
min of incubation. The uptake of mercury was enhanced by the presence of cadmium.
Uptake was depressed by L-ascorbate, dehydroascorbate, phlorizin, and EDTA.
(D161) For mercury, conversion to methyl mercury by marine organism is impor-
tant (Nelson et al., 1971). Human and animal studies indicate that elemental mercury
is virtually unabsorbed, and inorganic salts exhibit 8–15% absorption whilst the up-
take of methyl mercury may be complete (Cooper, 1985).
Ruthenium
(D162) Ruthenium absorption was investigated by Cantone et al. (1994). They re-
ported a value of 0.55 ± 0.008 for the intestinal absorption of ruthenium in a male
rabbit. A study of ruthenium absorption by healthy volunteers using stable isotope
techniques gave fractional absorption values from 0.007 ± 0.002 to 0.011 ± 0.001
(Veronese et al., 2001).
Tin
(D163) Sullivan et al. (1984b) measured absorption of 113Sn in rats after adminis-
tration as the chloride and obtained values of approximately 0.01% for adults and
0.9% for 2-day-old neonates.
Halogens
Fluoride
(D164) The gastrointestinal absorption of fluoride is rapid and extensive (Patten
et al., 1978).
270
Lanthanides
Promethium
(D165) Few data are available on the absorption of promethium. Early studies by
Hamilton (1948) and Moskalev (1959) showed total retention of <0.05% for adult
rats. More recent studies performed with 147Pm administered as the chloride to rats
suggested values of 7 · 103% for adult rats and 5.4% for 2-day-old neonates (Sulli-
van et al., 1984). Similar experiments performed using pigs gave absorption values of
1.8% and 3.4% for 5-day-old and 9-day-old animals, respectively (Sullivan et al.,
1984b).
Cerium
(D166) The absorption of cerium in rats has been reported as being less than
1 · 103 (Durbin et al., 1956). Low values of fractional absorption have also been
reported for pigs (McClellan et al., 1965). Shiraishi and Ichikawa (1972) demon-
strated that 144Ce in 0.025 ml cerium chloride solution in HCl (pH 2.5) was poorly
absorbed by rats with values of 2 · 102 for 13-day-old neonates and 2 · 104 for
adults.
Actinides
Absorption in adults
Human data
(D167) The results of experiments to measure the absorption of actinides in hu-
mans are reported below. Table D.12 summarises the results of direct experimental
measurements of absorption of actinide elements. Data on the absorption of natural
uranium have also been obtained by comparing estimates of dietary intake for partic-
ular groups of people with measurements of urinary excretion. However, such studies
generally depend on the assumption that daily excretion is equal to absorption from
diet. This assumed balance may be most valid for middle-aged adults. Short-term
observations involving a small number of subjects could give misleading estimates
of absorption due to inter- and intrasubject variability in intake, uptake, excretion,
and interchange between blood and systemic deposits in bone and other tissues.
For these reasons, estimates of absorption based on such environmental data should
be viewed with caution. Similar considerations apply to the estimate by Mussalo-
Rauhamaa et al. (1984) of plutonium absorption from reindeer meat (see below).
Uranium
(D168) Information on the absorption of uranium is available from studies involv-
ing direct measurements of absorption in human volunteers, dietary balance data for
several different human groups, and measurements of absorption in a variety of lab-
oratory animals.
(D169) In the first controlled human study involving more than one subject, Hursh
et al. (1969) administered uranyl nitrate to four hospital patients. The data obtained
271
Table D.12. Fractional absorption of actinides in humans

Element Form ingested Administered Number of Absorption Reference
amount individuals (age) (·104)
Th Mock dial paint; 6 (63–83) 2 Maletskos et al.,
sulphate 1969
U Uranyl nitrate 1 100 Butterworth,
1955
U Uranyl(VI) 10.8 mg 4 (56–78) 40–600 Hursh et al.,
nitrate in 1969
Coca Cola
U U(VI) in drinking 0.2–0.3 mg 10 (23–62) 100–150 Wrenn et al.,
water 1989
U U in mineral 0.16 mg (acute 5 (35–58) 150–200 Harduin et al.,
water administration) 1994
U U in mineral 1.2 mg (81lg/ 5 (35–58) 100–150 Harduin et al.,
water day for 15 days) 1994
U Uranyl nitrate in 5 10–150 Karpas et al.,
grape fruit drink 1998
Np Np(IV) citrate 5 1–3 Popplewell
et al., 1991
Pu Cumbrian winkles 16 0.2–5 Hunt et al.,
1986, 1990
Pu Citrate 5 1–10 Ham and
Harrison, 2000
Am Cumbrian winkles 17 0.4–3 Hunt et al.,
1986, 1990
Cm Cm(IV) citrate 5 1–3 Popplewell
et al., 1991
were taken to suggest absorption in the range of 0.005–0.05. Leggett and Harrison
(1995a,b) interpreted the data as suggesting absorption of 0.004, 0.01, 0.02, and
0.06 for the four subjects. Wrenn et al. (1989) estimated absorption in 12 normal
healthy adult volunteers given drinking water high in uranium. On the basis that
40–60% of absorbed uranium was excreted in the urine in the first 3 days, Leggett
and Harrison (1995a,b) concluded that mean absorption was 0.01–0.015, maximum
absorption was in the range of 0.02–0.04, and that six subjects absorbed less than
2.5 · 103. Harduin et al. (1994) reported results for the absorption of uranium from
drinking water either administered on 1 day or over 15 days. The data for acute
administration suggested absorption of 0.005–0.05 with an average value of 0.015–
0.02. The data for 15-day administration suggested absorption of 0.003–0.02 and
average absorption of 0.01–0.015.
(D170) A number of dietary balance studies, reviewed by Wrenn et al. (1985) and
Leggett and Harrison (1995a,b), have indicated mean absorption values in the range
of 0.004–0.04, in reasonable agreement with central values of 0.001–0.024 from con-
trolled studies on human volunteers.
(D171) Urinary excretion data from uranium absorption studies on human volun-
teers (Harduin et al., 1994; Wrenn et al., 1989) and baboon data (Larsen and Orlan-
dini, 1984) (see below) are consistent with the assumption that uranium passes
through the intestinal wall with a half-time of 1–3 days.
272
Neptunium
(D172) Popplewell et al. (1991) measured the absorption of 239Np and 242Cm in
five adult male volunteers by comparing urinary excretion after oral administration
and intravenous injection. In each case, the elements were administered as the citrate
complexes and the solutions were ingested with a mid-day meal. The mean f1 value
obtained was 2 · 104 for both Np(IV) and Cm(III) with a range of 104 to 3 · 104
in both cases.
Plutonium
(D173) Three studies of the absorption of plutonium in humans have been re-
ported. In the first study, concentrations of fall-out plutonium in autopsy samples
of bone, liver, and lung from five male residents of Lappland were compared with
corresponding concentrations in tissues of people who had lived in Southern Fin-
land (Mussalo-Rauhamaa et al., 1984). The dietary intake of plutonium by the
Lapps was derived mainly from reindeer meat, especially liver, and was approxi-
mately 10–15 times greater than that in Southern Finns. The authors used the data
to estimate absorption as 8 · 104, a value which they recognised to be based on
insufficient sample analyses and uncertain assumptions concerning the exposure
of the two groups to inhaled plutonium. Hunt et al. (1986, 1990) carried out two
studies of the absorption of 239/240Pu and 241Am by eight volunteers (six men and
two women) who consumed winkles collected on the Cumbrian coast near to the
Sellafield nuclear fuel reprocessing plant. The winkles were consumed under con-
trolled conditions. The reported absorption values for plutonium ranged from
2 · 105 to 5 · 104, with a median of 1 · 104 and a mean of 2 · 104 (±1 SD),
suggesting 90% confidence limits of approximately 8 · 105 to 4 · 104. Ham and
Harrison (2000) reported measurements of the absorption of 244Pu administered
in citrate solution to five male volunteers. The absorption values obtained, based
on comparisons of urinary excretion of 244Pu after oral and intravenous administra-
tion, were 1.3 · 104, 2.4 · 104, 7.8 · 104, 8.9 · 104, and 1.2 · 103, with a mean
value of 6 · 104.
Americium
(D174) As discussed above, Hunt et al. (1986, 1990) measured the absorption of
239/240
Pu and 241Am by volunteers who consumed measured quantities of winkles
collected on the Cumbrian coast near to the Sellafield nuclear fuel reprocessing
plant. The reported absorption values for americium ranged from 4 · 105 to
3 · 104, with a mean of 1 · 104.
(D175) The data in Table D.12 show a close similarity in the absorption of tho-
rium, neptunium, plutonium, and americium with mean values within the range
from 104 to 103. The absorption of uranium is substantially greater than that
of the other actinides. This is consistent with its different solution chemistry, the
oxidation state UO2þ
2 being more resistant to hydrolysis at neutral pH than the pre-
dominant oxidation states of the other actinides [Th(IV), Np(V), Pu(IV), and
Am(III)].
273
Animal data
Protactinium
(D176) Harrison and Stather (1981) investigated the absorption of protactinium in
the hamster. They found that, after intragastric administration of 231Pa as the fluo-
ride or citrate complex, absorption was approximately 2 · 103 and 4 · 102, respec-
tively. Hamilton (1948) reported that absorption was less than 5 · 104 in rats given
protactinium by gavage in isotonic saline. Zalikin (1966) administered 233Pa in citric
acid solution to rats and reported that uptake did not exceed 1–2 · 102 and may be
as low as 6 · 105.
Thorium
(D177) Sullivan (1980a,b) reported values of 5 · 105and 6 · 104 for 228
Th
administered as the nitrate to rats and mice, respectively.
Uranium
(D178) Harrison and Stather (1981) measured the absorption of 233U in hamsters
after intragastric administration as nitrate or dioxide, and obtained values of
approximately 8 · 103 and 1 · 103, respectively. Previous studies in which dogs
were given UO2F2 (0.7 mg/kg) in water gave absorption values of approximately
2 · 103 (Fish et al., 1960).
(D179) LaTouche et al. (1987) studied the absorption of uranium given to rats as
uranyl solutions. They reported fractional absorption ranging from approximately
6 · 103 to 3 · 102, depending on the mass administered (from 0.03 to 45 mg/kg).
(D180) Animal studies provide information on the relative uptake of uranium in-
gested in different chemical forms. Absorption generally decreases with the solubility
of uranium compound, being greatest for uranium ingested as UO2(NO3)26H2O,
UO2F2, or Na2U2O7, roughly half as great for UO4 or UO3, and one to two
orders of magnitude lower for UCl4, U3O8, UO2, and UF4 (Leggett and Harrison,
1995a,b).
(D181) It seems likely that uranium is more readily absorbed from water than
from some food products including fresh vegetables and shellfish because a large
proportion of uranium in these products may be insoluble (Chassard-Bouchaud,
1982; Sheppard and Evenden, 1992). In addition, intakes in water at times when
the stomach and small intestine have a low food content may lead to greater levels
of absorption (Leggett and Harrison, 1995a,b). This conclusion was based on com-
parative experiments performed on fasted and fed animals. Sullivan and Ruemmler
(1988) showed that feeding rats an iron-deficient diet increased absorption of 233U,
administered as the nitrate, to 0.25 compared with a value of 0.07 for rats given a
normal diet.
Neptunium
(D182) The fractional absorption of neptunium in animals, depending on chemical
form, mass administered, and nutritional status, is presented in Tables D.13–D.15.
The main conclusions from these studies can be summarised as follows.
274
Table D.13. The effect of mass on the gastrointestinal absorption of neptunium in adult animals
Isotope/chemical Mass administered Animal Nutritional Fractional Reference
form (ng) species status absorption
239
Np nitrate 15 Baboon Ad libitum 8.6 · 104 Métivier et al., 1986
239
Np nitrate 66 Baboon Ad libitum 7.3 · 104
237
Np nitrate 40,000 Baboon Ad libitum 1.4 · 102
237
Np nitrate 120,000 Baboon Ad libitum 7 · 103
237
Np nitrate 500,000 Hamster Ad libitum 5 · 104 Harrison and Stather,
1981
237
Np nitrate 20 mg/kg Hamster Ad libitum 4 · 104 Harrison et al., 1984
239
Np nitrate 5 ng/kg Hamster Ad libitum 1.6 · 104
237
Np nitrate 28 mg/kg Rat Ad libitum 2.6 · 103
239
Np nitrate 2.7 ng/kg Rat Ad libitum 3 · 104
239
Np nitrate 22 pg/kg Rat Ad libitum 5 · 104 Sullivan et al., 1983c
235
Np nitrate 13–64 ng/kg Rat Ad libitum 6 · 104
237
Np nitrate 22–43 mg/kg Rat Ad libitum 2.7 · 102
237
Np nitrate 1 mg/kg Rat Fasted 26 · 104 Wirth and Volf, 1985
237
Np nitrate 10 mg/kg Rat Fasted 23 · 104
239
Np nitrate 110 pg/kg Rat Fasted 12 · 104
239
Np nitrate 369 pg/kg Rat Ad libitum 1.7 · 103 Métivier et al., 1983a,b
239
Np nitrate 29 pg/kg Rat Ad libitum 1.5 · 103
237
Np nitrate 1.9 lg/kg Rat Ad libitum 2.7 · 103
237
Np nitrate 2.1 mg/kg Rat Ad libitum 9.8 · 103
Table D.14. Nutritional influences on the absorption of neptunium by adult animals

Isotope/chemical Mass Animal Nutritional status Fractional Reference
form administered species absorption
(ng)
239
Np nitrate 50 Baboon Alcohol acid 5 · 104 Métivier et al.,
depleted 1986
239
Np nitrate 1 Baboon Alcohol acid 6 · 103
enriched (fruits)
239
Np nitrate 0.1 Baboon Milk enriched 1.5 · 104
239
Np nitrate 0.1 Baboon Potatoes 3.3 · 103
239
Np nitrate 1 Baboon Fasting, 24 h 9 · 103
239
Np nitrate 1 Baboon Fasting, 12 h 2 · 103
239
Np nitrate 2 Baboon Normal (controls) 7 · 104
239
Np bicarbonate 2.5 ng/kg Rat Normal (controls) 1.5 · 103 Harrison et al.,
1984
239
Np bicarbonate 2.5 ng/kg Rat Fasted, 8 h 2.5 · 103
237
Np nitrate 51 mg/kg Rat Iron-replete diet 4 · 102 Sullivan and
with 350 lg iron/g Ruemmler, 1988
237
Np nitrate 78 mg/kg Rat Iron-deficient diet 31 · 102
239
Np nitrate 110 pg/kg Rat Fed 2–8 · 104 Wirth and Volf,
1985
239
Np nitrate 110 pg/kg Rat Fasting, 24 h 2–32 · 104
237
Np nitrate 5 mg/kg Rat Normally fed 1.1 · 103 Sullivan et al.,
1984c
237
Np nitrate 5 mg/kg Rat Fasted, 24h 6.5 · 104
275
Table D.15. The effect of the initial chemical form of neptunium on its absorption in adult animals
Isotope/chemical Mass administered Animal Fractional Reference
form species absorption
237
Np citrate 5 mg/kg Hamster 6 · 104 Harrison and Stather, 1981
237
Np nitrate 5 mg/kg Hamster 5 · 104
239
Np nitrate 2.5 ng/kg Rat 3 · 104 Harrison et al., 1984
239
Np citrate 2.5 ng/kg Rat 1.4 · 103
239
Np phytate 2.5 ng/kg Rat 4 · 104
239
Np bicarbonate 2.5 ng/kg Rat 1.5 · 103
239
Np in liver 1.1 ng/kg Rat 1.3 · 104
239
Np bicarbonate 0.5 ng/kg Rabbit 1.2 · 103
239
Np nitrate 0.5 ng/kg Rabbit 1.8 · 103
(D183) The oxidation state of the element is a dominant factor for the absorption
of neptunium from the gut (Table D.13) Groups of rats gavaged with 237Np(IV),
237
Np(V), and 237Np(VI) nitrate solutions retained 0.3, 1.1, and 2.3%, respectively,
at 1 day after gavage (Ballou et al., 1962). Administration of milligram amounts
of 237Np(V) to rats resulted in an uptake of up to 3% (Sullivan et al., 1983c). How-
ever, in the same study, only 0.04% of a 5-pg dose of 239Np(V) was absorbed. The
authors suggested that small amounts of Np(V) are reduced in the intestine to the
poorly absorbed Np(IV). Consistent with this, other workers have observed this
mass effect in rats (Harrison et al., 1984) and baboons (Métivier et al., 1983a,b),
but not in hamsters (Harrison et al., 1984). Métivier et al. (1986) obtained an absorp-
tion value of 103 when baboons were given 15–66 ng 239Np as the nitrate, compared
with a value of 102 when the administered mass was 40–120 lg 237Np.
(D184) Nutritional status seems to be an important factor for the absorption of
neptunium from the gut (Table D.14). Wirth and Volf (1985) showed that there
was a six-fold higher absorption in fasted than in fed male adult and weanling rats.
This is in agreement with other studies (Larsen et al., 1982; Sullivan et al., 1984c).
Feeding baboons a milk-supplemented diet reduced absorption by a factor of five,
to 1–2 · 104, while a potato diet increased absorption by a similar factor (Métivier
et al., 1986). Fasting for 12 or 24 h increased absorption by factors of approximately
3 and 10, respectively.
(D185) According to Sullivan et al. (1984c), the increase in neptunium absorption
after fasting was due to the absence of a reducing environment in the gastrointestinal
tract, since the oxidant quinhydrone and ferric iron has a similar or greater effect.
Factors other than oxidation-reduction equilibrium may, of course, be involved in
the effect of fasting on absorption. The absence of food that could bind neptunium,
thereby making it unavailable for absorption, could also increase uptake (Sullivan
et al., 1984).
(D186) The initial chemical form influences the absorption of neptunium (Table
D.15). Experiments with low concentrations of 239Np have shown that absorption
for a number of different chemical forms in rats, hamsters, and rabbits was in the
range of approximately 104 to 103.
(D187) The duodenum and jejunum are the main sites of in-vivo absorption
of Np(V) (Fritsch et al., 1986). Transfer values for Np(V) nitrate in adult rats were
276
similar to values for lead (Conrad and Barton, 1978), copper, molybdate, iron (Van
Campen and Mitchell, 1965), and mercury (Sasser et al., 1978). The available data
suggest that intestinal transfer of neptunium may occur via the intercellular pathway
and that it is controlled by both the molecular weight of the neptunium compound
and its stability constant.
Plutonium
(D188) Information available includes studies in which plutonium was adminis-
tered in a single dose (Bhattacharyya et al., 1985a, 1986; Harrison et al., 1986; Larsen
et al., 1981a,b; Sullivan, 1980a,b; Sullivan et al., 1979b, 1983c), in serial doses
(Katz et al., 1955; Weeks et al., 1956), or in drinking water over a protacted period
(Stather et al., 1981).
(D189) The conclusions of these studies are that many factors such as the initial
valence state, concentration, fasting, or diet can influence absorption. Data are given
in Tables D.16–D.19 and can be summarised as follows.
(D190) The initial valence state of plutonium does not generally influence absorp-
tion (Table D.16) (Harrison, 1991; Harrison et al., 1981; Larsen et al., 1981a;
Stather et al., 1980; Sullivan et al., 1979). Most measurements of plutonium absorp-
tion have been made using Pu(IV), with some using Pu(VI) which is known to exist
in drinking water (due to the presence of chlorine). It appears, however, that while
Pu(VI) is more stable than Pu(IV) at neutral pH and could, in principle, result in
increased levels of absorption, in practice, no difference was observed when admin-
istration in the two forms was compared (Larsen et al., 1981b; Stather et al., 1980;
Sullivan et al., 1980). Reduction of Pu(VI) to Pu(IV) in the stomach or by the
Table D.16. Effect of valence state of plutonium on its absorption in adult animals
Isotope/chemical form Animal Nutritional Fractional Reference
species status absorption
237
Pu(IV) bicarbonate Hamster Normal 1.9 · 105 Stather et al., 1980
237
Pu(VI) bicarbonate Hamster Normal 2.2 · 105
237
Pu(IV) bicarbonate Hamster Fasted, 24 h 2 · 104
237
Pu(VI) bicarbonate Hamster Fasted, 24 h 1.1 · 104
237
Pu(IV) bicarbonate Mouse Fasted, 24 h 2 · 103 Larsen et al., 1981a
237
Pu(VI) bicarbonate Mouse Fasted, 24 h 1.5 · 103
238
Pu(IV) nitrate Rat Normal 1.3 · 104 Sullivan et al., 1979b
238
Pu(VI) nitrate Rat Normal 2.4 · 104
Table D.17. Effect of the ingested mass of plutonium on its absorption in adult animals
Isotope/chemical form Animal Nutritional Fractional Reference
(mass) species status absorption
236
Pu nitrate (30 pg) Rat Normal 104 Harrison and David, 1987
238
Pu nitrate (10 ng) Rat Normal 2 · 104
239
Pu nitrate (30 lg) Rat Normal 2 · 104
277
Table D.18. Effect of the nutritional status on plutonium absorption in adult animals
Isotope/chemical Animal Nutritional status Fractional Reference
form species absorption
238
Pu nitrate Rat Normal 1.1–2 · 104 Sullivan et al., 1983b
238
Pu nitrate Rat Normal + orange juice 1.4 · 103
238
Pu nitrate Rat Vitamin D deficient for 2 103
weeks
238
Pu nitrate Rat Calcium deficient for 2 3 · 103
weeks
238
Pu nitrate Rat Normal + whole milk >3 · 104a
238
Pu(IV) citrate Hamster Normal 9 · 105 Harrison et al., 1986
238
Pu(IV) citrate Hamster Fasted, 24 h after 2 · 104
administration
238
Pu(IV) citrate Hamster Fasted, 8 h before 2 · 103
administration
238
Pu(IV) citrate Hamster Fasted, 8 h before, 4 h 2 · 103
after administration
238
238
238
Pu(VI) bicarbonate Baboon Normal 1.2 · 104 Bhattacharyya et al., 1989
238
Pu(VI) bicarbonate Baboon Fasted 24 h 2.2 · 103
a
Retention only (urinary excretion data not available).
contents of the small intestine was proposed as an explanation for this absence of
effect (Larsen et al., 1981a,b).
(D191) The influence of mass on absorption has been investigated in rats given
from 30 pg to 30 lg of plutonium as the nitrate form (Table D.17). Results showed
that absorption was not affected by the mass administered, at least over the range
studied (Harrison and David, 1987). These results have been confirmed by Re-
naud-Salis et al. (1990) in rats fed with 107 to 106 g of Pu(VI) as the bicarbonate.
However, conflicting data have been obtained by Sullivan (1980a,b) who suggested
that fractional absorption of plutonium fed to rats as 237Pu nitrate (7 · 1011g) was
0.12%, six to 12 times higher than the results of Harrison and David (1987).
(D192) Nutritional status influences plutonium absorption (Table D.18). Sullivan
et al. (1983b) investigated the effect of changes in diet on the absorption by rats of
238
Pu nitrate. Compared with controls fed with normal food, absorption was in-
creased by between one and 20 times in animals fed on milk, orange juice, and a diet
deficient in vitamin D. Fasting hamsters for 8–24 h before administration of Pu(IV)
citrate increased absorption from approximately 104 to 1–2 · 103 (Harrison et al.,
1986). An extra 4-h fasting period after administration had no effect, but extending
this period to 24 h increased absorption to 5 · 103. Increased absorption of pluto-
nium by factors of five to 15 has also been observed in rats (Sullivan et al., 1979b),
mice, and baboons (Bhattacharyya et al., 1986, 1989) after fasting for 24 h.
(D193) In adult animals, the chemical form of ingested actinides is known to be an
important factor determining their absorption (Table D.19). Although absorption of
actinides increases when they are in solution, some of them are weak complex form-
278
Table D.19. Effect of the initial chemical form on plutonium absorption in adult animals
Isotope/chemical form Animal Species Fractional absorption Reference
239
Pu nitrate Hamster 2 · 105 Harrison et al., 1981
239
Pu oxide Hamster 4 · 106 Stather et al., 1979
239
Pu Na/Pu oxide Hamster 7 · 105
239
Pu citrate Hamster 104 Harrison et al., 1981
239
Pu in liver Hamster 104 Stather et al., 1979
239
Pu/238Pu in sediment Hamster 7 · 105 Harrison et al., 1981
238
Pu ferritin Hamster 6 · 105
238
Pu citrate Hamster 8 · 105 Harrison et al., 1986
238
Pu isocitrate Hamster 9 · 105
238
Pu phytate Hamster 7 · 105
238
Pu malate Hamster 6 · 105
238
Pu ascorbate Hamster 104
238
Pu in potato Hamster 3 · 103 Bulman et al., 1993
238
Pu citrate Rabbit 2 · 104 Harrison et al., 1981
238
Pu phytate Rabbit 104 Cooper and Harrison, 1982
238
Pu in grass Rabbit 4 · 105 Harrison et al., 1981
238
Pu nitrate Rat 2 · 104 Cooper and Harrison, 1984
238
Pu citrate Rat 5 · 104
238
Pu phytate Rat 103
238
Pu oxalate Rat 3 · 104
238
Pu Calgon Rat 7 · 104
238
Pu trimetaphosphate Rat 3 · 104
239
Pu nitrate Rat 1.1 · 104 Sullivan et al., 1985
239
Pu citrate Rat 5 · 104
238
Pu nitrate Rat 2.5 · 104
238
Pu citrate Rat 5.4 · 104
239
Pu in winkles Rat 9 · 104 Harrison, 1991
239
Pu in mussels Rat 2 · 103
238
Pu in potatoes Rat 103 Bulman et al., 1993
239
Pu citrate Marmoset 103 Harrison, 1991
239
Pu in potatoes Marmoset 2 · 103
ers. For example, plutonium in solution quickly hydrolyses and forms insoluble
polymers, thus preventing high absorption from the gut. On the other hand, when
plutonium is ingested as a complex with citrate or polyaminocarboxylic acids, it is
not hydrolysable and its transfer levels are potentially increased (Métivier et al.,
1985). Other naturally occurring organic molecules (isocitrate, malate, oxalate,
and ascorbate) and food additives (Calgon, trimetaphosphate) may increase pluto-
nium absorption from foods.
(D194) Phytate (myoinotisol hexakisphosphate) may be one important dietary
complexing agent for plutonium (Cooper, 1985). It occurs in a variety of foodstuffs
including grain, peas, and potatoes, and forms stable soluble complexes with pluto-
nium (Cooper and Harrison, 1984a). Phytate appears to have a pronounced effect on
plutonium uptake in some species. Rats absorbed 0.13% of the plutonium adminis-
tered as plutonium phytate, whereas rabbits absorbed only 0.01% (Cooper and Har-
rison, 1982). This difference was related to the presence of the enzyme phytase in the
small intestine mucosa (Cooper and Gowing, 1983). The enzyme is localised in the
279
microvillus membrane and it is thought to break down phytate releasing the pluto-
nium in an ionic form immediately adjacent to the absorptive surface. Thus, some
absorption can take place before being prevented by the competing reaction of
hydrolysis to form an insoluble colloid. It was concluded that such an increase above
values for inorganic forms of the element might apply to plutonium in potato and
other vegetables containing phytate (Ham et al., 1994). However, in-vitro studies
performed on phytase metabolism in human gut segments indicated that human
mucosal phytase and alkaline phosphatase digestion of phytate were insignificant
compared with that of dietary phytase in terms of the overall breakdown of phytate
in food (Sandberg and Anderson, 1988).
Americium
(D195) Compared with plutonium or neptunium, limited data are available on the
absorption of americium. The main conclusions of the studies performed to date can
be summarised as follows.
(D196) The initial chemical form influences absorption. Tables D.20 and D.21
show results obtained for the absorption of americium in hamsters, rabbits, rats,
and marmosets. For both rats and hamsters, the values for americium incorporated
in liver were lower than the values for nitrate. This might be taken to suggest that,
unlike plutonium, americium binding to organic molecules in foods will not increase
its availability for absorption.
(D197) Nutritional status influences intestinal absorption. In rats, intestinal
absorption was three times higher in animals fed an iron-deficient diet.
Absorption in neonates and juveniles

(D198) For many elements such as lead, cadmium, iron, cobalt, mercury, calcium,
strontium, cerium, niobium, manganese, cadmium, ruthenium, and actinides, it has
been shown that absorption is greater in newborn or young animals than in adults.
For all these elements, absorption in newborn animals exceeded absorption in adults
by factors of 10–1000 (Ballou, 1958; Barton, 1987; David and Harrison, 1984; Eisele
et al., 1980; Finkel and Kisielseki, 1976; Forbes and Reina, 1972; Inaba and Lenge-
mann, 1972; Kello and Kostial, 1977; Kostial et al., 1971; Matsusaka, 1971; Mraz
and Eisele, 1977a,b; Shiraishi and Ichikawa, 1972; Sikov and Mahlum, 1972; Sulli-
van, 1980a,b; Walsh, 1982).
(D199) Enhanced absorption of plutonium from the gastrointestinal tract of neo-
natal rats was first observed by Ballou (1958). It has since been shown in rats, guinea
pigs, hamsters, dogs, pigs, calves, and baboons, and extended to the actinides, nep-
Table D.20. Nutritional influences on the gastrointestinal absorption of americium by adult animals
Chemical form Mass Animal Nutritional Fractional Reference
administered species status absorption
241
Am nitrate 6.7 lg/kg Rat Iron-replete diet 1.8 · 102 Sullivan and Ruemmler,
with 350 lg iron/g 1988
241
Am nitrate 9.2 lg/kg Rat Iron-deficient diet 4.8 · 102
280
Table D.21. Influence of the initial chemical form of americium on its absorption in adult animals
Chemical form Species Fractional absorption Reference
241
Am nitrate Rat 2.2 · 104 Sullivan and Crosby, 1975
4 · 104 Ballou et al., 1978
2.6 · 104 Sullivan, 1980a,b
6.3 · 104
1.1 · 105 Sullivan et al., 1985
8 · 104 Harrison, 1991
241
Am oxide Rat 1.9 · 104 Sullivan and Crosby, 1975
9 · 105 Sullivan, 1980a,b
1.5 · 105
241
Am citrate Rat 6 · 104 Harrison, 1991
6.9 · 104 Sullivan et al., 1985
241
Am phytate Rat 4 · 104 Harrison, 1991
241
Am in potatoes Rat 2 · 103
241
Am nitrate Mouse 2.8–15 · 105 Hisamatsu and Takizawa, 1987
241
Am nitrate Hamster 5.4 · 104 Harrison et al., 1981
241
Am oxide Hamster 6 · 105 Stather et al., 1979
241
Am citrate Hamster 1.2 · 104 Harrison et al., 1981
241
Am in potatoes Hamster 3 · 103 Harrison, 1991
241
Am in liver Hamster 3.4 · 105 Harrison et al., 1981
241
Am nitrate Guinea pig 1.6 · 104 Sullivan, 1980a,b
241
Am nitrate Guinea pig 1.1–1.5 · 104
241
Am citrate Rabbit 2 · 104 Harrison et al., 1981
241
Am in foodstuff Cow 1 · 105 Gilbert et al., 1989
241
Am citrate Pig 1.15 · 105 Eisele and Erickson, 1985
241
Am citrate Pig 1.1 · 103 Eisele et al., 1987
241
Am in potatoes Monkey 6 · 104 Ham et al., 1994
241
Am in shellfish Human 0.4–2.1 · 104 Hunt et al., 1986
tunium, americium, and curium (David and Harrison, 1984; Harrison, 1982; Méti-
vier et al., 1986; Sullivan, 1980a,b; Sullivan and Gorham, 1982, 1983; Sullivan
et al., 1984c, 1985).
(D200) For rats, hamsters, and pigs, for which the effect of age has been the most
closely studied, high absorption immediately after birth decreases rapidly and ap-
proaches adult levels by the time the animals are weaned. Neptunium was the only
member of this group that was not absorbed by neonates in quantities between one
and two orders of magnitude higher than those absorbed by the adult rat (Sullivan
et al., 1984c). In baboons, it appeared that the decrease in neptunium absorption oc-
curred very rapidly in the first few days of life and was not related to weaning
(Métivier et al., 1987).
(D201) The uptake and absorption of actinides in neonates appears to be insensi-
tive to the chemical form ingested. Sullivan et al. (1985) observed that for low masses
of plutonium citrate, the higher solubility of this complex compared with the nitrate
did not result in higher absorption by neonatal rats. In addition, there were no dif-
ferences between the quantities of 238Pu, 241Am, or 244Cm retained in the intestine 1
week after gavage that could be attributed to the chemical form of the actinides
administered.
281
Table D.22. Fractional absorption of actinides in neonatal animals

Radionuclide Age at contamination Species Absorption Reference
(days)
233
U nitrate 1 Pig 34 · 102 Sullivan and Gorham, 1982
239
Np nitrate 4 Baboon 2–17 · 103 Lataillade et al., 1992
239
Np nitrate 26 Baboon 103 Lataillade et al., 1992
239
Np nitrate 159 Baboon 5 · 104 Lataillade et al., 1992
237
Np nitrate 1 Pig 6.1 · 102 Sullivan and Gorham, 1982
239
Np nitrate 2 Hamster 3 · 102 David and Harrison, 1984
239
Np nitrate 4 Hamster 2 · 102 David and Harrison, 1984
239
Np bicarbonate 2 Hamster 6 · 102 Harrison, 1991
239
Np bicarbonate 4 Hamster 2 · 102 Harrison, 1991
238
Pu citrate 1 Baboon 2 · 103 Lataillade et al., 1992
238
Pu citrate 34 Baboon 103 Lataillade et al., 1992
238
Pu citrate 195 Baboon 2 · 104 Lataillade et al., 1992
238
Pu nitrate 2 Dog 6 · 102 Sullivan and Gorham, 1982
238
Pu nitrate 1 Pig 17 · 102 Sullivan and Gorham, 1982
238
Pu citrate 0.5–1 Guinea pig 3 · 102 Bomford and Harrison, 1986
238
Pu citrate 5–15 Guinea pig 1–4 · 103 Bomford and Harrison, 1986
238
Pu citrate 20–adult Guinea pig 2–5 · 104 Bomford and Harrison, 1986
238
Pu citrate 1 Hamster 3.5 · 102 David and Harrison, 1984
238
Pu citrate 4 Hamster 1.4 · 102 David and Harrison, 1984
238
Pu citrate 7 Hamster 2 · 104 David and Harrison, 1984
238
238
238
Pu nitrate 1 Rat 2 · 102 Sullivan and Gorham, 1982
241
Am nitrate 1–4 Hamster 8–50 · 103 Harrison, 1991
241
Am citrate 0.5–1 Guinea pig 2 · 103 Bomford and Harrison, 1986
241
Am citrate 5–10 Guinea pig 2 · 103 Bomford and Harrison, 1986
241
Am citrate 15–30 Guinea pig 2–6 · 104 Bomford and Harrison, 1986
241
Am nitrate 1 Pig 2.1 · 102 Sullivan and Gorham, 1982
241
Am nitrate 1 Hamster 4.5 · 102 David and Harrison, 1984
241
Am nitrate 4 Hamster 1.7 · 102 David and Harrison, 1984
241
Am nitrate 7 Hamster 5 · 103 David and Harrison, 1984
241
241
244
Cm nitrate 1 Pig 5.6 · 102 Sullivan and Gorham, 1982
244
Cm nitrate 2 Rat 2 · 102 Sullivan, 1980a,b
244
Cm nitrate 2 Rat 2.7 · 102 Sullivan et al., 1985
244
Cm citrate 2 Rat 3.2 · 102 Sullivan et al., 1985
244
Cm oxide 2 Rat 1.7 · 102 Sullivan, 1980a,b
(D202) Table D.22 shows results obtained for the absorption of actinides in new-
born animals. For all elements, absorption decreased over the suckling period to
reach adult values by the time of weaning. In hamsters and guinea pigs, the level
of absorption in 1-day-old animals was approximately 100–200 times adult values.
Results for neptunium absorption in newborn hamsters showed similar increases
above adult values.
(D203) Studies with primates were performed with 239Np as the nitrate and
238
Pu as the citrate. Data showed that at 4 days of age, the gastrointestinal absorp-
tion of neptunium was approximately 102, i.e. approximately 20 times greater
282
than in adults. At 1 week and 4 weeks of age, absorption had fallen to values of
around 103, approximately three to four times the adult values (Lataillade et al.,
1992). Plutonium absorption was similarly increased by an order of magnitude in
1-day-old baboons. For neptunium and plutonium, absorption appeared to have
fallen to around adult values by approximately 5–6 months of age (Lataillade
et al., 1992).
(D204) The increased absorption of actinides and other elements in neonates,
and associated intestinal retention, has been related to intestinal permeability.
Intestinal permeability in neonates is important in many mammalian species in
the acquisition of passive immunity by the absorption of intact gamma globulins
in milk (Harrison, 1995). It has been suggested that this pinocytic uptake of macro-
molecules may be largely responsible for the increased absorption of actinides and
other elements. Passive immunity is acquired before birth by placental transfer of
antibodies in a number of mammalian species including guinea pigs and primates.
However, globulins are taken up by the mucosal cells of the small intestine in these
species during the first days or weeks of life but not transported through the cells
to the circulation (Lecce and Broughton, 1973). It seems reasonable to conclude
that levels of uptake and retention in human neonates will be most similar to those
observed in baboons and guinea pigs, and that the very high levels of epithelial
retention and absorption observed in rats and pigs will not apply to humans (Har-
rison and Fritsch, 1992). Further information is needed on the relationship be-
tween intestinal permeability and non-specific uptake of radionuclides and other
substances in different mammalian neonates.
D.6. Large intestine
D.6.1. Speciation
(D205) Grisham et al. (1990) measured the specific activities of oxidants including
SOD, catalase, and glutathione (GSH) peroxidase in the normal human colon. They
found low but significant amounts of all three enzymes in the mucosa, submucosa,
and muscularis/serosa of the human colon. The levels of SOD (3.6 ± 0.3 units/mg
protein), catalase (11 ± 3 units/mg), and GSH peroxidase (15.2 ± 0.8 mU/mg) repre-
sented 8%, 4%, and 40%, respectively, of corresponding values determined for hu-
man liver. The mucosal activity for SOD and catalase was associated with the
epithelial cells and not the lamina propria (mucosal interstitium).
(D206) Hornich and Chrastova (1981) measured the redox potential (Eh) in the
large intestine of newborn piglets as +111 ± 25 mV. In the postweaning period,
the Eh values decreased significantly to 173 ± 27 mV and a similar value was ob-
tained for healthy sows (214 ± 55 mV).
D.6.2. Retention
(D207) The studies of Lataillade et al. (1992) on 238Pu absorption in baboons in-
cluded measurements of retention in the large intestine. Low values of less than
283
0.01% of administered activity were obtained at the youngest ages and even lower
values were obtained in older animals.
(D208) Thompson and Hollis (1958) described experiments where insoluble parti-
cles containing 106Ru were fed to rats. The data showed that it took approximately
24 h before half of the animals had expelled all the particles. Further observations in
this experiment indicated that the prolonged retention of particles occurred in the
caecum and colon.
(D209) Colonic retention of zinc and calcium was studied after installation during
colonoscopy of 30 lmol of zinc and 6.4 mmol of calcium labelled with 65Zn and
47
Ca, and measurement of whole-body retention of the radionuclides (Sandstrom
et al., 1986). After caecal installation in nine patients, retention (day 13) of zinc
was 3.5 ± 2.1% (mean ± SD) and retention of calcium was 3.5 ± 2.7%. Application
at the hepatic flexure in four patients resulted in a mean retention (day 13) of
1.2% for zinc and 0.6% for calcium.
D.6.3. Absorption
(D210) Hebden et al (1999) investigated the regional absorption characteristics of

the distal gut, using two markers of permeability, quinine (a transcellular probe), and
51
Cr-EDTA (a paracellular probe). The permeability markers were delivered to the
undisturbed gastrointestinal tract in 39 healthy volunteers using an oral timed-
released delivery vehicle that allowed pulsed release within a particular site of the
gut. Site of release was identified using gamma scintigraphy. Absorption of quinine
and 51Cr-EDTA was assessed by measuring the percent excretion in the urine using
high-performance liquid chromatography and gamma counting, respectively. Serial
plasma samples allowed time–concentration curves for quinine to be plotted. There
was a significant trend for diminished absorption with more distal delivery of the
transcellular probe, quinine, which was: 6.26 ± 0.87% (small intestine, n = 10);
4.65 ± 0.93% (ascending colon, n = 16); and 2.59 ± 0.52% (transverse colon, n =
10) of the ingested dose excreted (P < 0.001). No such gradient was seen with the
paracellular marker, 51Cr-EDTA. These results suggest that delayed-release formu-
lations should aim for release in the distal small bowel and proximal colon if absorp-
tion is to be maximised. Absorption by the transcellular route diminishes in the more
distal colon, a fact that has implications for delayed- or sustained-release
formulations.
(D211) Colonic absorption of zinc and calcium was studied after installation dur-
ing colonoscopy of 30 lmol of zinc and 6.4 mmol of calcium labelled with 65Zn and
47
Ca (see above and Sandstrom et al., 1986). The calculated mean absorption was
4.1% for zinc and 14.1% for calcium. Under prevailing conditions, colonic absorp-
tion of zinc is relatively small compared with the uptake after oral administration.
Colonic absorption of calcium could, however, account for a substantial part of
the total calcium uptake.
(D212) Results of in-vitro studies have documented colonic absorption of lactose
in the newborn (Kien et al., 1997). A stable isotope model was developed for assess-
ing the entry rate of intact lactose into the portal circulation in newborn piglets. In
284
Experiment 1, unlabelled and [D-1-(13C)]-lactose were infused into two separate mes-
enteric veins, and in Experiment 2, labelled lactose was infused into a mesenteric vein
and unlabelled lactose was infused into the colon. The 13C-enrichment of plasma lac-
tose was assessed by high-performance liquid chromatography combined with mass
spectrometry. The isotopic estimate of the mesenteric venous infusion rate of lactose
was 91% of the theoretical. In Experiment 2, 13% of the unlabelled lactose infused
into the colon reached the portal circulation. The current study provides the first di-
rect in-vivo confirmation of colon absorption of intact lactose. The tracer model
could be used to evaluate intestinal or colonic absorption of other organic com-
pounds not endogenously synthesised, including vitamins or drugs.
D.7. Appendix
D.7.1. Fractional absorption values used by the ICRP .
(D213) Publication 30 (ICRP, 1979, 1980, 1981) recommended values for the frac-
tional absorption (f1 values) of elements and their radioisotopes, specifically applying
to occupational exposure of workers (Table D.5). Publications 56, 67, 69, and 71
(ICRP, 1989a,b, 1993a,b, 1995a,b) gave f1 values for members of the public. Adult
values for members of the public differ in some cases from those specified for workers
on the basis of data indicating that absorption of environmental forms of radionuc-
lides incorporated into food may be different and usually greater than that of the
chemical forms encountered in the workplace. Table D.6 shows the f1 values used
for ingestion of radionuclides by adult members of the public. Also shown are the
Table D.23. ICRP f1 values for workers

Element f1 value
H, F, C, Na, S (org.), Cl, K, Ge, Br, Rb, I, Cs, Hg (methyl), Tl, As 1
P, S (inorg.), Se, Mo, Tc, Re 0.8
Mg, Cu, Zn, As 0.5
Au (org.) 0.4
Ca, Sr, Te, W 0.3
Pb, Ra 0.2
S (element), Cr (VI), Mg, Fe, Co, Sb, Ba, Au, Po 0.1
Co (inorg.), Ni, Se (element, selenides), Mo (sulphide), Ru, Rh, Ag, 0.05
Cd, Bi
In, Sn, Hg (inorg.), U 0.02
Sr (titanate), Nb, W (tungstic acid), Os, Ir, Pt 0.01
Be, Pa 0.005
Zr, Hf, U (IV) 0.002
Ga, Ta 0.001
La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Ac, 0.0005
Th, Pa, Np, Pu, Am, Bk, Cf, Eu, Fm, Md
Th (oxides/hydroxides) 0.0002
Sc, Y, Pu (nitrates) 0.0001
Pu (insol. Oxides) 0.00001
285
greater values specified for 3-month-old infants. Adult values apply from 1 year of
age except in the cases indicated by footnotes to Table D.6.
(D214) Table D.23 gives f1 values used in Publication 71 (ICRP, 1995b) for the
absorption of radionuclides escalated from the lungs after inhalation. In assigning
these values, it was considered that for environmental exposures, the radionuclides
might typically be present as minor constituents of the inhaled particles, and that
therefore absorption would depend on the dissolution of the particle matrix as well
as on the chemical nature of the element. Generally, the f1 values used for Type F
materials (readily soluble) were those applied to direct ingestion. For Types M
and S, default f1 values of 0.1 and 0.01, respectively, were applied unless the f1 value
for direct ingestion was lower than these values or a lower value had been specified
previously (see Tables D.24 and D.25).
Table D.24. ICRP f1 values for members of the public

Element Adult Infant
H, C, I, Cs, S, Mo 1 1
Se 0.8 1
Zn, Tc, Po 0.5 1
Te, Ca, Sr 0.3 0.6
Ba, Ra, Pb 0.2 0.6
Co, Fe 0.1 0.6
Sb 0.1 0.2
Ru, Ni, Ag 0.05 0.1
U 0.02 0.04
Zr, Nb 0.01 0.02
Ce, Th, Np, Pu, Am, Cm 0.0005 0.005
Intermediate values for 1, 5, 10, and 15-year-old children: Ca, Sr, Pb, 0.4; Co, Ra, Ba, 0.3; Fe, 0.2. f1 is the
fraction of the total ingested that is absorbed to blood.
Table D.25. ICRP f1 values for adults for inhalation by members of the public
Element Lung absorption type
F M S
H, C, I, Cs 1 0.1 0.01
S, Se, Mo, Tc 0.8 0.1 0.01
Ca, Sr, Te 0.3 0.1 0.01
Ba, Ra, Pb 0.2 0.1 0.01
Co, Fe, Po 0.1 0.1 0.01
Sb 0.1 0.01 0.01
Ni, Ru, Ag 0.05 0.05 0.01
U 0.02 0.02 0.002
Nb 0.01 0.01 0.01
Zr 0.002 0.002 0.002
Th, Np, Pu, Am, Cm 0.0005 0.0005 0.0005
286

Absorption and Retentiono of Radionuclides

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Absorption and Retentiono of Radionuclides

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ANNEX D: ABSORPTION AND RETENTION OF RADIONUCLIDES

F. Paquet, J.D. Harrison

(D1) The biokinetics of radionuclides are determined by many physiological, bio-

D.2. Oral cavity

Redox and chemical properties of the oral cavity

Composition of human saliva

pH and oxidation potentials

Table D.1. Constituents of human saliva (from Long et al., 1971)

Table D.1 (continued)

is similar to that of whole saliva. The enhancement of OSCN levels in saliva by

Alkaline earth elements

(D46) Chemical transformations of radionuclides in the oesophagus are unlikely

Chemical characteristics of the oesophagus

(D50) No data are available on the retention of metals in the oesophagus.

Chemical properties of the stomach

(D64) Although the stomach is not generally considered to be an absorptive

D.5. Small intestine

Chemical properties of the small intestine

pH and redox potential in the small intestine

Oxidising and reducing agents in the small intestine

In-vivo chemical transformations

Many substances, including radionuclides, can be bound non-speciﬁcally to serum

Eﬀects of complexing agents naturally present in the small intestine

Alkaline earth elements

Intestinal retention in adults

(D108) Measurements of 45Ca in various segments of the alimentary tract showed

Intestinal retention in neonates

et al., 1988). These diﬀerent locations probably correspond to diﬀerent retention

Speciﬁc examples of intestinal retention in juveniles

(D120) The intestinal absorption of radionuclides is, in general, markedly inﬂuenced

Alkaline earth elements

Table D.12. Fractional absorption of actinides in humans

Table D.14. Nutritional inﬂuences on the absorption of neptunium by adult animals

Absorption in neonates and juveniles

Table D.22. Fractional absorption of actinides in neonatal animals

D.6. Large intestine

(D210) Hebden et al (1999) investigated the regional absorption characteristics of

D.7.1. Fractional absorption values used by the ICRP .

Table D.23. ICRP f1 values for workers

Table D.24. ICRP f1 values for members of the public

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