H (Z = 1) OIR-1

For ICRP Use Only 1. HYDROGEN (Z = 1)

Draft 16 January 2006

1.1. Chemical Forms in the Workplace Workers may be exposed to tritium in many chemical forms, including hydrogen gas (elemental tritium), tritiated water, methane, metal tritides, luminizing compounds, tritium-contaminated pump oils and a wide variety of tritium-containing research compounds, including DNA precursors such as [6-3H]-thymidine (Rudran, 1988; Taylor et al., 1990; Hill and Johnson, 1993). Hydrogen has only one radioactive isotope 3H, T = 12 years, that decays by emission of a single beta particle of mean energy ~5 keV. 1.2. Routes of Intake 1.2.1. Inhalation Information is available from volunteer studies with inhaled tritium gas and tritiated water. Information is also available from experimental studies of particulate forms, mainly metal tritides and luminous compounds, in rats, and in vitro. Classification of gases and vapours, absorption Types and parameter values Proposed absorption parameter values and Types, and associated f1 values for specific hydrogen (tritium) compounds are given in Tables 1.1 (gases and vapours) and 1.2 (particulate materials). Exposures to particulate forms of tritium are relatively unusual compared to exposures to gas or vapour forms, and it is therefore proposed here that gas/vapour form should be assumed in the absence of information. (a) Gases and vapours Tritiated water (HTO). Pinson and Langham (1957) demonstrated that inhaled HTO is translocated to blood completely and instantaneously, and then distributes uniformly throughout the body without changing chemical form. For HTO it is therefore assumed here that there is 100% deposition in the respiratory tract, with instantaneous (Type V) absorption. Note that absorption through skin can add significantly to uptake during exposure to HTO in the air (Section 1.2.3) Tritium gas (elemental tritium, HT). Studies in which human volunteers inhaled tritium gas (composed of 93% HT) showed that ~1% of the inhaled HT dissolved in body fluids and tissues, and that of this ~1% was subsequently converted to HTO and the rest exhaled (Peterman et al., 1985a; 1985b). These results appear to accord with the data of Pinson and Langham (1957). For HT it is therefore assumed here that there is 0.01% effective deposition in the respiratory tract with instantaneous (Type V) absorption. Tritiated methane, CH4xTx. The dosimetric implications of inhaling methane gas were examined by Phipps et al. (1990). In the absence of other experimental information they made the conservative assumption that 1% of the methane was metabolized. Recent data of Carlisle (2004) suggest this to be an overestimate, and that a value of 0.1% is more likely. This is consistent with observations for sheep by Dougherty et al. (1967) that indicated that approximately 0.3% of infused methane was converted to carbon dioxide. For tritiated methane it is therefore assumed here that there is 0.1% effective deposition in the respiratory tract with instantaneous (Type V) absorption. Unspecified organic forms. Volatile organic compounds have a wide range of solubility in body fluids. Therefore, in the absence of specific information, the default option for gases and vapours is taken. For tritium in unspecified organic forms it is assumed here

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that there is 100% deposition in the respiratory tract (with default regional distribution, Table 1.1) and Type F absorption. Unspecified tritium gases and vapours. Volatile tritiated compounds have a wide range of solubility in body fluids. Therefore, in the absence of specific information, the default option for gases and vapours is taken. For tritium in unspecified gas and vapour form it is assumed here that there is 100% deposition in the respiratory tract (with default regional distribution, Table 1.1) and Type F absorption. (b) Particulate aerosols Tritium could be released in the work environment in particulate form, and several studies of the dissolution of solid tritiated compounds have been conducted. Because of the low energy of the tritium beta particle, self-absorption within particles can significantly reduce doses, even for particles as small as 1 m diameter. Kropf et al (1998) calculated that (for erbium tritide) the fraction of beta energy that escapes was in the range 0.50.1 for particle diameters in the range 15 m. It is assumed here that for inhalation of inorganic particulate material, the biokinetics of tritium absorbed into body fluids follows that of HTO. Tritium-contaminated glass Results of 150-day in vitro studies of the dissolution in simulated lung fluid of fragments of tritium-filled glass microballoons used in laser fusion research (Cool and Maillie, 1983) were expressed as two-component exponential retention functions, with fr ~0.98, sr ~0.1 d1 and ss ~0.01 d1. Measurements on samples of three types of glass gave halftimes for the slow phase in the range 23280 d, but all were consistent with assignment to Type F. Luminous paint Balonov et al (1984, 1995) reported that following intratracheal instillation into rats of Soviet luminous powder (PS-A) the lung specific activity showed essentially no decrease within 5 months, and hence should be assigned to ICRP Publication 30 Class Y. This indicates that such compounds should be assigned to Type M or S. Results of 5-day in vitro studies of the dissolution in bovine serum of samples of commercial luminous paint powder made from tritium-labelled polystyrene (Rudran, 1988) were described as on average 12% dissolved on the first day, and about 2% of remaining activity on subsequent days, i.e., fr ~0.12, sr >1 d1 and ss ~0.02 d1, consistent with assignment to Type M. Titanium tritide Balonov et al (1984, 1995) reported that, following inhalation by rats, titanium tritide (TiT) showed slow lung clearance, and hence should be assigned to ICRP Publication 30 Class Y. This indicates that TiT should be assigned to Type M or S. Measurements were made up to 4 months after intratracheal instillation of TiT (1-m count median diameter, CMD) into rats, and simulation modelling was applied to obtain a time-dependent absorption function (fractional absorption rate) (Cheng et al., 1999): S(t) = 3.06e4.6t + 0.042 e0.093t d1 at time t (days) after intake.

H (Z = 1) OIR-1

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This can be roughly approximated using the HRTM dissolution model with fr = 0.66, sr = 1.8 d1 and ss = 0.0002 d1, consistent with assignment to Type M. (Rounded values are adopted here, Table 1.2.) A good fit can be obtained by using the bound state to provide an additional phase: fr = 0.70, sr = 5.5 d1, ss = 3.6 107 d1, fb = 0.29, and sb = 0.11 d1. However, its use, while giving a better estimate of excretion rates, may lead to some overestimation of the lung dose, because material bound in the BB and bb regions is taken to be located in the epithelium, close to the target cells. Results of a 30-day in vitro study of the dissolution in synthetic serum ultrafiltrate (SUF) of the same powder (Cheng et al., 1997) were expressed as a two-component exponential retention function, giving fr = 0.24, sr = 0.71 d1, ss = 0.02 d1. This dissolution rate is broadly similar to the absorption rate in vivo, (initially lower, but higher after a few days), and consistent with assignment to Type M. Dissolution in the same system of a sample of coarse dust (103-m CMD) was much slower, but still consistent with assignment to Type M. The results indicated that loss of tritium was related to diffusion and hence increases with the specific surface area of the particles. Zirconium tritide Measurements were made up to 6 months after intratracheal instillation of zirconium tritide (0.3-m CMD) into rats, and simulation modelling was applied to obtain a fractional absorption rate (Zhou and Cheng, 2004): S(t) = 5.4x103 e0.084t + 9.69x104 e0.007t d1 at time t (days) after intake. This can be approximated using the HRTM dissolution model with fr = 0.094, sr = 0.59 d-1 and ss = 3.5x104 d1, consistent with assignment to Type S. (Rounded values are adopted here, Table 1.2.) Results of 200-day in vitro studies of the dissolution in SUF of the same powder (Zhou and Cheng, 2004) were expressed as a two-component exponential retention function, with fr = 0.048, sr = 0.016 d1 and ss = 1.8x103 d1. This dissolution is somewhat faster than the absorption in vivo, and consistent with assignment to Type M. Carbon tritide The results of a 110-day in vitro study of the dissolution in SUF of carbon tritide (1-m CMD) samples taken from a test fusion reactor were expressed as a fractional absorption rate (Cheng et al, 2002a): S(t) = 0.251e9.57t + 2.08x103 e0.141t + 4.26x104 e0.00402t intake. d1 at time t (days) after

This can be approximated using the HRTM dissolution model with fr = 0.027, sr = 4.7 d1 and ss = 6.35x104 d1, consistent with assignment to Type S. A good fit can be obtained by using the bound state to provide an additional phase: fr = 0.44, sr = 9.6 d1, ss = 3.1 104 d1, fb = 0.41, and sb = 0.12 d1. However, its use, while giving a better estimate of excretion rates, may lead to some overestimation of the lung dose. The results of a preliminary 14-day in vitro study of the dissolution in serum simulant of coarse and fine tritium loaded carbon particles taken from another test fusion reactor were expressed as two-component exponential retention functions (Hodgson et al, 2004). For coarse particles fr = 0.05, sr = 500 d1 and ss = 6.3x103 d1, giving assignment to Type M. For fine particles fr = 0.003, sr = 500 d1 and ss = 3.6x104 d1, giving assignment to Type S. Specific values are not adopted here (Table 1.2), because only in vitro data are available.

H (Z = 1) OIR-1 Hafnium tritide

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Measurements were made up to 6 months after intratracheal instillation of hafnium tritide (1-m CMD) into rats, and simulation modelling was applied to obtain a fractional absorption rate (Zhou and Cheng, 2003): S(t) = 8.811x104 e0.765t + 1.05x105 e0.0194t d1 at time t (days) after intake. This can be approximated using the HRTM dissolution model with fr = 1.2x103, sr = 0.44 d1 and ss = 1.8x106 d1, consistent with assignment to Type S. (Rounded values are adopted here, Table 1.2.) A good fit can be obtained by using the bound state to provide an additional phase: fr = 1.7x103, sr = 0.77 d1, ss = 0.0 d1, fb = 0.31, and sb = 0.019 d1. In this case the dose coefficient is almost the same as that obtained without the bound state, or if zero absorption is assumed, but somewhat higher than obtained with default Type S. Results of 200-day in vitro studies of the dissolution in SUF of similar powders (Inkret et al., 2001; Cheng et al., 2002b) were expressed as twocomponent exponential retention functions, with fr ~1x103, sr ~0.015 d1 and ss ~2.5x106 d1. This dissolution is broadly similar to the absorption in vivo, (initially lower, but higher after a few days), and consistent with assignment to Type S. Default rapid dissolution rate for tritium The evidence of rapid uptake of tritiated gases from the lung indicates a rapid rate of absorption of order 100 d1, and this is adopted for Type F compounds. However, the studies on tritides suggest values in the range 0.45 d1, and therefore a value of 1 d1, is adopted for Type M and S compounds. Extent of binding of tritium to the respiratory tract The evidence of rapid uptake of tritiated gases from the lung indicates that that there is probably little binding of tritium. It is therefore assumed that for tritium the bound state can be neglected, i.e., fb = 0.0.

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Table 1.1. Deposition and absorption for gas and vapour compounds of hydrogen (tritium)a Absorption Chemical form/origin Tritiated water (HTO) Tritium gas (HT) Tritiated methane (CH4xTx) Unspecified organic compounds Unspecified a
a

Fraction deposited (%) 100d,e,f 0.01 100 100

e,f e,f d,e,g

Type V V V F F

f1 (i) (i) (i) 1.0 1.0

Systemic modelc HTO HTO HTO OBT HTO

0.1d,e,h

For tritium in unspecified gas or vapour form, the default option for gases and vapours is recommended: 100% total deposition in the respiratory tract; default distribution between regions (footnote e) and Type F absorption. Fraction deposited refers to how much of the material in the inhaled air remains behind after exhalation. Almost all inhaled gas molecules contact airway surfaces, but usually return to the air unless they dissolve in, or react with, the surface lining. In the case of tritium gas and methane, a small fraction is absorbed into body fluids and of that, a fraction is metabolised and the rest subsequently exhaled. HTO = Systemic model for tritiated water, Section 1.3.1. OBT = Systemic model for organically bound tritium, which is recommended for prospective use only, and not for interpretation of bioassay data, Section 1.3.2. Since instantaneous absorption to blood is assumed, calculations can be performed assuming direct injection into blood, and the regional deposition does not need to be considered. However, for completeness, the default distribution is assumed (footnote e). Default distribution between regions (20% ET2, 10% BB, 20% bb and 50% AI). Regional deposition: 20% ET2, 10% BB, 20% bb and 50% AI. Regional deposition: 0.002% ET2, 0.001% BB, 0.002% bb and 0.005% AI. Regional deposition: 0.02% ET2, 0.01% BB, 0.02% bb and 0.05% AI. Not applicable for absorption Type V, because all activity deposited in the respiratory tract is instantaneously absorbed.

e f g h i

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Table 1.2. Absorption parameter values for inhaled particulate forms of tritium and for ingested tritiuma. Absorption parameter valuesb Inhaled particulate materials Specific parameter valuese Titanium tritide Zirconium tritide Hafnium tritide Default parameter valuesf,g Glass fragments Luminous paint; all unspecified compounds Carbon tritide 1 0.1 0.001 10 1 1 0.005 0.0001 F M S 1 0.1 0.01 fr 0.7 0.09 0.001 sr (d1) 2 0.6 0.4 ss (d1) 0.0002 0.00035 0.000002 Absorption Typec (M) (S) (S) Absorption from the alimentary tract, fAd 0.1 0.01 0.01

Ingested materials Soluble forms (as assigned to Type F for inhalation) Relatively insoluble forms (Types M and S) a b c 1 0.1

Following uptake to body fluids, the systemic model for tritiated water is used, Section 1.3.1 It is assumed that for tritium the bound state can be neglected, i.e., fb = 0.0. For those materials for which specific absorption parameter values are given, the corresponding default absorption Type is given in parentheses. This is used to assign fA where a specific value is not available from experimental data. For soluble material entering the alimentary tract after inhalation (Type F), the fA value for ingested soluble forms of tritium is applied. For relatively insoluble materials (Types M and F) the default fA values for inhaled materials are applied (0.1 and 0.01, respectively). See text for summary of information on which parameter values are based, and on ranges of parameter values observed for individual materials Materials (e.g. Glass fragments) are listed here where there is sufficient information to assign to a default absorption Type, but not to give specific parameter values (see text). Default Type M is recommended for use in the absence of specific information.

e f g

1.2.2. Ingestion Tritiated water (HTO) Investigations in humans have shown that hydrogen in the form of deuterium oxide or tritiated water is rapidly and virtually completely absorbed from the gastrointestinal tract (Pinson and Langham, 1957; Wiseman, 1964; Etnier et al. 1984; Travis et al. 1984). Organic compounds For 3H ingested as organic compounds, a large proportion may be broken down in the gastrointestinal tract producing HTO. Studies using rodents indicate that 80-90% of ingested [6-3H]-thymidine is catabolized before reaching the blood and only a small proportion (<5%) is incorporated into DNA in body tissues (Lambert and Clifton, 1968; Feinendegen and Cronkite, 1977). For other forms of organic tritium compound, including biochemical substrates such as tritiated amino acids, absorption of the intact molecule and transfer to body tissues may be substantially greater (Takeda, 1982, 1991; Rochalska and Szot, 1977). Although absorption of organic tritium compounds is likely to vary substantially, it is assumed here, as in Publications 30 (1979) and 56 (1989), that absorption is complete unless specific information is available to indicate otherwise; that is, the default assumption for all organic tritium compounds is that f A= 1.

H (Z = 1) OIR-1 Metal tritides

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After oral administration of a suspension containing titanium tritide (TiT) particles to rats, the HTO concentration in body water increased during the 1-1.5 days of the residence of TiT in the gastrointestinal tract; total absorption was less than 0.1 (Balonov et al., 1984, 1995). Luminous compounds In three human volunteers who ingested a 3H-polystyrene-based luminous compound, produced 5 months before the study, mean absorption was about 1% Following oral administration of 3H labelled luminous compounds to rats, 0.5-5 % of the administered activity was absorbed; absorption was greatest for luminous compounds produced 1 to 2 years previously (Balonov et al., 1984, 1995). In each of these studies, absorbed 3H was in the form of HTO and low molecular weight organic compounds. Measurements of absorption in cats showed that absorption of 3H from luminous paints depended on the plastic substrate involved, with values of 0.007 for polystyrene, about 0.03 for silicone rubber and 0.8 for polyester (Wawerna, 1973; Hill and Johnson, 1993). Adopted fA values for ingestion For tritiated water and organic compounds, an fA of 1 is adopted in this report, although it is recognised that absorption may be substantially less than complete in the case of some organic compounds. For metal tritides and luminous paints, the available data indicate that an fA value of 0.1 is generally more appropriate. 1.2.3. Skin and wounds Tritiated water Human studies (Osborne, 1966) showed that for an adult at rest about 1% of the HTO present in 1 m3 air is absorbed through the skin per minute, and that, for a sedentary male worker, absorption through the skin contributes approximately one-third of the total HTO intake for any given atmospheric concentration. Similar assessments were made in the review by Myers and Johnson (1991) and also in ICRP Publication 66 (1994a). Tritium gas Absorption of HT through the skin appears to be minimal and HT is not converted to HTO on the skin surface (McElroy et al., 1989; Hill and Johnson, 1993). Metal tritides Eakins et al. (1975) showed that when metal surfaces that had been exposed to high concentrations of HT gas were placed in contact with human skin, substantial amounts of 3 H, in unidentified organic forms, were absorbed into the body fluids; this finding was confirmed in rats (Hutchin et al., 1965; Johnson and Dunford, 1985). When titanium tritide slabs were placed in contact with rat skin, about 10 -6 to 10-5 d-1 of the applied activity was absorbed into the blood as HTO (Balonov et al., 1984, 1995). Luminous compounds Studies with a 3H-polystyrene-based luminous paint, produced four months earlier, was applied to human skin for 6 hours about 0.2% of the tritium was absorbed (Balonov et al., 1984, 1995). The absorption coefficients increased from 0.2 % to 2.6 % with increasing age of the luminous compound (4 to 25 months). The tritium was absorbed

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into the body in the form of 3H2O and low molecular mass organic [3H]-compounds. After application to rat skin of a [3H]-silicone rubber-based luminous compound, an absorption coefficient of 2.4% was determined (Rehnberg et al., 1972). Organic Compounds Many types of organic compound, including those labeled with 3H or 11,14C, have the ability to penetrate the intact skin and become absorbed into the systemic circulation. Topical application of creams, lotions or ointments is widely used for the administration of a range of drugs, including corticosteroids, antihistamines and analgesics (BNF, 2005). The ability of an organic compound to penetrate the skin depends of many factors, including lipophilicity, molecular mass (Boss and Meinardi, 2000) and the vehicle in which the compounds dissolved or dispersed (El Maghraby et al., 2000). 3 Balonov et al., (1993) applied aqueous solutions of H-labelled glucose, amino acids (glycine, leucine, methionine and lysine) and nucleosides (thymidine and deoxycytidine) to rat skin and showed that only 1-4 % of the applied activity was absorbed into blood, mainly in unchanged chemical form. In contrast, Lockley et al. (2002, 2004) found that following application of either [14C]-ethoxyethanol or 2-butoxyethanol to rat skin 2528% of the dose was absorbed in 24 h. In other studies, the application of an ethanolic solution of catechol to rat skin resulted in the absorption of 53% of the applied dose in 72 h (Jung et al., 2003). As observed by Balonov et al (1993) some organic compounds may be absorbed into the systemic circulation in largely unchanged form, however others may undergo extensive metabolism in the dermal structures. Moss et al. (2000) applied an ethanolic solution of [3H]-triclosan (2,4,4-trichloro-2-hydroxydiphenyl ether) to rat
skin and observed that after 24 h 12% of the 3H was recovered in the faces and 1% in the urine, in the form of free triclosan or as the glucuronide or sulphate conjugates; 8% was retained in the carcass,30% in the stratum corneum and 26% could be rinsed from the skin surface. In vitro 3 studies showed that the metabolism occurred during the passage of the [ H]-triclosan through the skin, and also indicated that the penetration through rat skin was 3-4 times greater than that through human skin (Moss et al., 2000).

1.3. Systemic Distribution, Retention and Excretion 1.3.1. Tritiated water Tritiated water mixes rapidly and completely with the total body water after its entry into the blood. A fraction of the tritium in HTO becomes organically bound, and thus the retention of this fraction depends on the metabolic activity of the various tissues. For example the half-times of bound tritium in metabolically active tissues such as liver and intestine are shorter than those in skin and brain, where metabolic activity is less pronounced (Smith, 1986). Human and animal studies conducted over many weeks following intakes of HTO suggest that the loss of tritium from the body could be described by a three component exponential function (Thompson, 1953; Sanders and Reinig, 1968; Bennett, 1973; Hill and Johnson, 1993). Where, the first, and largest, compartment represents loss from the body water, the second represents tritium incorporated into organic compounds within the tissues and the third compartment represents tritium incorporated into structural, or other, very slowly turning-over tissue components. Human data indicate that the biological half-time of retention in the first compartment ranges from about 4-18 days, with an average of about 10 days (ICRP, 1987; Hill and Johnson, 1993). The half-time of the second compartment averages about 32 d with a range of 10-76 d (Hill and Johnson, 1993). The biological half-time of the third compartment in humans appears to be of the order of a few hundred days, Table 1.3.1 (Sanders and Reinig, 1968; Minder, 1969; Moghissi et al., 1971; 1972; Etnier et al., 1984; Travis et al. 1984; Stenstrm et al, 1996). In animals it may vary from a few hundred to a few thousand days (Thompson, 1952; 1953; 1954). The biological half-times which have been reported for the third, or longest, compartment for human subjects are summarized in Table 1.3.1.

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Table 1.3.1. Reported biological half-times (Tb) for the third (or longest) compartment for the excretion of 3H as tritiated water by humans. Reference Sanders & Reinig (1968) Minder (1969) Moghissi et al (1971); (1972) Rudran (1988) * Second term Studies with HTO in animals suggest that 1-5% of the HTO entering the blood becomes incorporated into the non-volatile organic components that are contained in the second and third compartments (Takeda and Kassida, 1979; Diabat and Strack, 1993). ICRP Publication 56 (ICRP, 1989) recommended a two-component model for predicting the behaviour of 3H that enters the human body as HTO in which 97% of the tritium was assumed to be eliminated with a biological half-time of 10 days and that 3% became organically bound and is eliminated with a biological half time of 40 days. However, it was recognized that a small fraction of the activity might be retained for much longer periods. This third compartment would represent tritium incorporated into structural or other very slowly turning-over tissue components. The second compartment, plus any possible third compartment, was considered likely to contribute about 10% to the committed dose (ICRP, 1989). The first term of this model is well supported by direct observations in several hundred people; however, the second term is based on empirical assumptions about the proportion of the ingested HTO that is converted into organically bound tritium and also about the biological half-time of this organically bound tritium. In order to develop a biokinetic model for HTO that could be used for both radiation protection planning and also for the interpretation of bioassay data, the human data published by Balonov et al., 1974; Snyder et al., 1968; Sanders and Reinig, 1968; Minder, 1969; Moghissi et al, 1971,1973; Rudran, 1988 and Trivedi et al, 1997 were reevaluated and a three component exponential model, with half-times of 10 days (99.00%), 40 days (0.98%) and 350 days (0.02%) to describe the retention of 3H from HTO was proposed (Taylor, 2003); the biological half-time of the small third compartment being based on the data shown in Table 1.3.1. The data used to derive this model show quite wide variations both in the observed biological half-times and, especially in the proportions of the total 3H entering the more slowly turning over compartments. This simple catenary model does not take into account HTO recycling within the body tissues, therefore, in accordance with modern ICRP practice the above half-times were used to derive transfer rates for the recycling model shown in Figure 1.3.1. The model, which is broadly similar to that of Hamby and Palmer (2001), comprises a compartment for HTO and two compartments for organically bound tritium one with short- and one with long-term retention. Excretion is via the HTO compartment only. The specific parameters for intakes of tritiated water are given in Table 1.3.2. No. of Subjects 1 (M) 1 (M) 3 (F) SK PB DH 2 (M) Tb[d] 344 139-227 280 550140 350190 131* 226* Period of Observation [d] 415 140-1000 495 1160 280 640 603

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Figure 1.3.1. The general form of the proposed model for tritiated water. This model assumes that HTO rapidly permeates into all body tissues, including more slowly turning over tissues such as fat, skeleton and brain, to achieve an instantaneous and uniform distribution of activity throughout the entire body water compartment. Studies with heavy water (D2O) intravenously injected into rabbits showed that the deuterium was distributed throughout 44% of the body mass within 2 minutes and 78% within 30 minutes; similar observations with HTO were also reported (Hevesy, 1948). Early human studies using HTO (Hevesy, 1948) showed that the radioactivity was distributed throughout 72% of the body mass within 30 minutes; this value may be compared with the ICRP reference value for the water content of the lean body mass of 73% (ICRP, 2002b). More recent human studies using D 2O or HTO have confirmed that equilibration of HTO throughout the body water pool is essentially complete within about 3 h of intake (Davies et al., 2001; La Forgia and Withers, 2002), thus dose estimates based on measurement of 3H in body water made more than 3 h after intake should not overestimate doses to brain, fat, skeleton or other tissues. [Information on urinary/faecal excretion needed] Applicability of the model The recycling model gives reasonable predictions of the retention of 3H from HTO at times up to about 100 d post intake. However, beyond this time the uncertainties associated with the model parameters become very large and serious consideration should be given to the validity of the results if it is applied for the interpretation of bioassay data beyond 100 d. Table 1.3.2. Parameters for intakes of tritiated water Initial conditions HTO Organic (short) Organic (long) 0 Fraction 1 0 0 Transfer rates HTO to Organic (short) HTO to Organic (long) HTO to urine Organic (short) to HTO Organic (long) to HTO 1.3.2. Organic compounds of tritium Soluble organic compounds of tritium entering the blood will be incorporated into body tissues to an extent that will depend on the specific chemical compound and the metabolic activity of the individual tissues. Tritium attached to oxygen, sulphur, nitrogen or phosphorus is in general readily exchangeable with the hydrogen of the body water pool. However, tritium bound to carbon will normally be released only through enzyme-mediated breakdown on the molecule in which the carbon atom is situated (Smith, 1986). The rate of such breakdown may be rapid for small molecules but very slow for carbon-bound tritium incorporated into structural proteins such as collagen, or the phospholipids of some nerve cells. Detailed information concerning the biokinetic behaviour of the tritium in all the various types of tritiated organic compounds is not d-1 3.763E-04 1.298E-05 6.891E-02 1.730E-02 1.980E-03

10

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available. However, the available information for specific compounds indicates that tritium retention in the human or animal body may vary from a few hours to many days. Biokinetic and dosimetric studies have been carried out in experimental animals, mainly rats, for more than 20 biochemical substrates (Vennart, 1969; Balonov et al. 1993; 1995), including substrates such as folic acid, cholesterol, ethylene glycol, L-lysine and L-tyrosine. The results of these studies showed that the fraction of the absorbed dose that was delivered by 3H incorporated into the organic components of the various tissues studied ranged from 2 - 7% for HTO to 44 - 96% for amino acids and DNA precursors. In view of the wide range of 3H-labelled substances that could be encountered in the workplace, and the general lack of data on their biokinetics, it is not practicable to define specific models for individual organic compounds of tritium. Applicability of the default OBT Model ICRP Publication 56, (ICRP, 1989) recommended a default model for all unknown compounds containing organically bound tritium (OBT). This model assumed that of the OBT entering the systemic compartment 50% would be metabolized to HTO and lost with a biological half-time of 10 days, and that the remaining 50% would enter into bonds with carbon and be removed with a biological half-time of 40 days. This value of 40 days for the biological half-time of HT bonds was derived from the empirical relationship between total body carbon content and daily carbon balance proposed in ICRP Publication 23 (1975). For the reasons mentioned above, this simple default model is not valid for the interpretation of bioassay data; however, it can still be used for prospective radiological protection planning purposes when compound-specific information is not available. 1.3.3. Elemental Tritium. Studies in human volunteers inhaling HT (Peterman et al., 1985a,b) showed that a very small fraction of the HT, 0.016, dissolved in the blood and body fluids, while the rest was exhaled. The dissolved HT is transported via the blood to sites, such as the gastrointestinal tract, where a very small fraction, about 1 x 10 -4 of the total inhaled tritium, may be converted to HTO and enter the body water pool. This conversion presumably results from microbial action in the large intestine, since mammalian tissues do not contain the hydrogenase enzyme necessary for the conversion of HT to HTO (Ichimasa et al., 1988). The remainder of the inhaled HT appears to be exhaled quite rapidly. On the basis of their human studies Peterman et al., (1985 a, b) concluded that the effective dose from inhaled HT derives from two major, but approximately equal contributions, the dose from the lungs and that from HTO. A multi-compartment biokinetic model for inhaled HT was developed by Dunford and Johnson, (1987) and modified by Hill and Johnson, (1993); this model incorporates a model for HTO, developed by Hill and Johnson, (1987), which differs from that described in paragraph 1.3.1. [Model still to be finalised] 1.4. Gender-related differences in biokinetics There are no a priori reasons to expect major gender-specific differences in the biochemical interactions undergone by HTO or [3H]-labelled organic compounds in the human body, or in the rates of elimination of 3H. Studies of the retention of HTO have been carried out in more than eight hundred persons, no differences between males and females in the biological half-times of retention of 3H from HTO have been reported. [References needed] Similarly, there appears to be no published information on the comparative retention of tritium from [3H]-labelled organic compounds However, genderrelated differences in the biokinetics of 3H following intake of some types of [3H]-labelled organic compound cannot be excluded; thus, when reliable gender-, or individual-specific biokinetic data are available, these should be used in preference to the default values recommended here.

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For inhalation of particulate tritium the human respiratory tract model (ICRP 1994) as well as the alimentary tract model are applied. After absorption to blood the biokinetic model for HTO is used. The recycling model for HTO, Section 3.2, can be used for calculating the dose from 3H that has entered the body as HTO, it is assumed that ingested and inhaled HTO is translocated directly and instantaneously from the site of intake to blood without considerations of nuclear transformations in either the respiratory or alimentary tracts. [Dose coefficients for HT and HTO not yet calculated] 1.6. Interpretation of monitoring data Still to be added References
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