Uranium in bone

A study by the oral route establishing a threshold for renal effects in weanling and adult rats of the same strain is needed to determine if susceptibility to uranium toxicity varies with age. Histopathological studies and urinalysis should be performed, as well as measurement of uranium in excreta for both groups. At termination in this study, uranium content should be measured in tissues, particularly bone and kidney. This will provide information on whether retention of uranium in bone is age-dependent (as assumed by analogy with calcium in PBPK models) and on whether kidney burden associated with uranium toxicity is age-related. 

Studies show that the main sites of uranium deposition ate the renal cortex and the Hvet (8). Uranium is also stored in bones deposition in soft tissues is almost negligible. Utanium(VI) is deposited mostly in the kidneys and eliminated with the urine whereas, tetravalent uranium is preferentially deposited in the Hvet and eliminated in the feces. The elimination of uranium absorbed into the blood occurs via the kidneys in urine, and most, - 84%, of it is cleared within 4 to 24 hours (8). 

The D-A model predicts the distribution of uranium and U-series isotopes across a bone section (Figs. 3 and 4). Under constant conditions Uranium is diffusing from the inner and outer surfaces of the bone, giving a u-shaped Uranium concentration profile that gradually flattens with time to a uniform uranium distribution when the bone reaches equilibrium with the uranium in the groundwater. Because the uranium is equilibrating with the outer portions of the bone section first, closed system U-series dates approach the true age of the bone towards the surfaces, but are underestimated towards the centre. Further details of the D-A model are given in the Appendix. 

In a group of uranium mill workers, there was an excess of deaths from malignant disease of lymphatic and hematopoietic tissue data from animal experiments suggested that this excess may have resulted from irradiation of lymph nodes by thorium-230, a disintegration product of uranium. Some absorbed uranium is deposited in bone. A potential risk of radiation effects on bone marrow has been postulated, but extensive clinical studies on exposed workers have disclosed no hematologic abnormalities. ... 

Edgington DN. 1967. The estimation of thorium and uranium at the submicrogram level in bone by neutron activation. Int J AppI Radiat Isot 18 11-18. 

Singh NP, Lewis LL, Wrenn ME. 1985. Uranium thorium and plutonium in bones from the general population of the United States. Comm Eur Communities Issue 9250 231-241. 

This ranking suggests that about 2.5 times as much Am and Cm may accumulate in bone than Pu or Th assuming identical chemical and physical forms in the soil. Uranium may show about a 5-fold greater relative accumulation. 

Autopsy data from individuals occupationally exposed to uranium indicates that bone is the primary site of long term retention of absorbed uranium (ICRP 1995). Inhalation exposure may also result in some retention of insoluble uranium particles in the lungs. An evaluation of the postmortem data from a uranium worker who had inhaled a total of 220 mg (147 pCi) uranium over a 3-year period found 11 pg (7 pCi) uranium in the lungs 13 years after the end of exposure. The total calculated dose equivalent from the inhaled uranium was 35 rem (0.35 Sv) (Keane and Polednak 1983). 

One site of deposition for the soluble compounds (uranyl nitrate, uranium tetrachloride, uranium hexafluoride) in animals was the skeleton, but accumulation was not seen in bone at levels below 0.25 mg U/m over a period of 2 years in rats exposed to soluble compounds (uranyl nitrate, uranium tetrachloride, uranium hexafluoride) in one study. The insoluble compounds (uranium hexafluoride, uranium dioxide) were found to accumulate in the lungs and lymph nodes after the inhalation exposure. For uranyl nitrate exposure, no retention was found in the soft tissues. Accumulation of uranium was also found in the skeleton (Stokinger 1953). The amount distributed in the skeleton has been reported to be 23 5% of the intake in dogs (Morrow et al. 1972) 28-78% in rats (Leach et al. 1984) and 34-43% in guinea pigs (Leach et al. 1984). A biological half-time of 150-200 days (Ballou et al. 1986) or 70 days (Morrow et al. 1982) in the skeleton has been reported following inhalation exposure to soluble uranium compounds (e.g., uranium hexafluoride). 

In some ways, the skeletal behavior of uranium is quantitatively similar to that of alkaline earths. It is known that the uranyl ion (U02 ) exchanges with Ca + on the surfaces of bone mineral crystals, although it does not participate in crystal formation or enter existing crystals. The early distribution of uranium in different parts of the skeleton is similar to that of calcium. Uranium initially deposits on all bone surfaces but is most highly concentrated in areas of growth. Depending on the microscopic structure of the bone of each species, uranium on bone surfaces may gradually diffuse into bone volume such... 

In a study with female mice exposed orally in feed to uranyl nitrate hexahydrate at a dosage of 462 mg U/kg/day for 36 44 weeks, average uranium accumulation was 6 pg per pair of kidneys, 46 pg/g bone and 0-0.5 pg in whole liver, respectively. No significant organ accumulation was found for the lower dose levels (Taimenbaum and Silverstone 1951). Maximal concentrations of 77 pg per pair of kidneys and 216 pg/g in bone were estimated at 50 weeks in male mice that were orally exposed to uranyl nitrate hexahydrate at 925 mg U/kg/day for 48 weeks. One mouse with small kidneys showed levels of 395 pg/pair of kidneys and 1,440 pg/g bone (Taimenbaum and Silverstone 1951). Average uranium accumulation in the kidneys and bone of male mice exposed to uranyl fluoride orally at 452 mg U/kg/day for 28 weeks was 33 pg/pair of kidneys and 145 pg/g bone at 20 weeks (Tannenbaum and Silverstone 1951). Maximal concentrations of 6 pg/pair of kidneys at 50 weeks and 29 pg/g bone at 14 weeks were found in female mice given oral uranium tetrachloride at 978 mg U/kg/day for 48 weeks (Tannenbaum and Silverstone 1951). 

Transfer of uranium across the placenta was investigated in an animal study, but no information is available for humans. In the animal study, only 0.01-0.03% of an intravenous dose of uranium to rat dams crossed the placenta (Sikov and Mahlum 1968) thus if an inhalation, oral, or dermal exposure was sufficient to raise the blood uranium level, a very limited amount of uranium might cross the placenta. No studies were located regarding uranium in breast milk. Based on the chemical properties of uranium, it seems unlikely that there would be preferential distribution from the blood to this high-fat compartment. It is not known if uranium has any effect on the active transport of calcium into breast milk. Most of the adult body burden of uranium is stored in bone (ICRP 1979, 1995, 1996). It is not known if maternal bone stores of uranium (like those of calcium and lead) are mobilized during pregnancy and lactation. 

According to USNRC Regulatory Guide 8.22, the acceptable methods for the quantification of uranium in urine must have a detection limit of 5 pg/mL and a precision of 30% (Kressin 1984). A urinary concentration >100 pg/L is indicative of recent absorption, while a concentration of <40 pg/L may be due either to slow uptake from the site of absorption or to bone mobilization (Butterworth 1955). Variations in background levels of uranium from drinking water in different locations may also result in higher or lower urinary concentrations of uranium. 

More information is needed on the absorption of various forms of uranium in young animals. Also, studies are needed on whether maternally stored bone uranium is mobilized to blood during pregnancy and lactation and whether this can increase exposure to the fetus and neonate. Child health data needs relating to exposure are discussed in Section 5.8.1, Data Needs Exposures of Children. 

Ubios AM, Guglielmotti MB, Steimetz T, et al. 1991. Uranium inhibits bone formation in physiologic Alveolar bone modeling and remodeling. Environment Research 54 17-23. 

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