Toxicity uranium

Brodsky A. 1996. Review of radiation risks and uranium toxicity with application to decisions associated with decommissioning clean-up criteria. Hebron,Connecticut RSA Publications. 

Prat, O., Berenguer, F., Malard, V., Tavan, E., Sage, N., Stein-metz, G., Quemeneur, E. (2005). Transcriptomic and proteo-mic responses of human renal HEK293 cells to uranium toxicity. Proteomics 5 297-306. 

Because natural uranium produces very little radioactivity per mass of uranium, the renal and respiratory effects from exposure of humans and animals to uranium are usually attributed to the chemical properties of uranium. However, in exposures to more radioactive uranium isotopes (e.g., and and naturally occurring and U), it has been suggested that the chemical and radiological toxicity may be additive or may potentiate in some instances. In these instances, this dual mode of uranium toxicity may not be distinguishable by end point because of the overlap of etiology and manifested effects. The mechanism of this interaction is as yet unclear. 

On the basis of the available data, the rabbit appears to be unusually susceptible to the lethal effects of uranium s metallotoxicity. The order of animal species susceptibility to acute uranium toxicity has been suggested as follows rabbit > rat > guinea pig > pig > mouse (Orcutt 1949). 

The mechanism for the renal toxicity observed in cases of adult exposure to uranium is believed to be due to the retention of uranium in the kidney. This is the result of the reabsorption of bicarbonate from the ultrafiltrate in the proximal tubule and the resulting release of the U02 ion from a bicarbonate complex. Newborn humans have relahvely inefficient tubular secretion and reabsorption compared to older children or adults, and whether this would increase or decrease the susceptibility of newborns to uranium toxicity is not known. 

No information was located regarding the modulation of the toxicity of uranium by other chemicals or vice versa. It is possible that co-exposure to other heavy metal nephrotoxicants (e.g., lead, cadmium) could have an additive effect on uranium toxicity. 

Populations susceptible to uranium toxicosis would include people with impaired renal function. People with stomach ulcers are thought to have elevated absorption of some toxic metals and might be unusually susceptible to uranium toxicity. The potential for children s susceptibility is discussed in Section 2.6. 

Methods for Reducing Toxic Effects. Uranium forms complexes with the bicarbonate ion (Cooper et al. 1982) and has been administered prophylactically after uranium exposure (Fisher et al. 1991). Bicarbonate can alkalize the blood to a degree that facilitates the excretion of uranium via the kidneys. This in turn, can prevent uptake by and deposition in critical tissues (kidney, bone). Chelation has been tested in animals and found to have a limited potential, though possibly valuable, role in reducing acute uranium toxicity. Further research is needed to validate, refute, or refine method(s) for reducing the toxic effects of uranium compounds. No verified methods for reducing the toxic effects of long-term exposure to uranium are currently available. 

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. 

Brodsky A. 1996. Radiation risks and uranium toxicity. RSA Publications, Hebron, Connecticut. 

Pavlakis N, Pollock CA, McLean G, et al. 1996. Deliberate overdose of uranium Toxicity and treatment. Nephron 72(2) 313-7. 

The minimal LOAEL of 0.05 mg/kg/day is divided by a total uncertainty factor of 30 (3 for use of a minimal LOAEL and 10 for human variability) to calculate the intermediate oral MRL. No adjustment was made for interspecies variation because the rabbit is the most sensitive mammalian species to uranium toxicity and is likely to be more sensitive than humans. 

Tuovinen, O.H. and Kelly, D.P., (1974 (a) (b) (c). Studies on the growth of Thiobacillus ferrooxidans. II. Toxicity of uranium to growing cultures and tolerance conferred by mutation, other metal cations and EDTA. Arch. Mikrobiol., 95 153—164. III. Influence of uranium, other metal ions and 2,4-dinitrophenol on ferrous iron oxidation and carbon dioxide fixation by cell suspensions, ibid, 95 165—180. IV. Influence of monovalent metal cations on ferrous iron oxidation and uranium toxicity in growing cultures, ibid, 98 167—174. 

Brodsky, A., Review of Radiation Risks and Uranium Toxicity with Application to Decisions Associated with Decommissioning Clean-up Criteria, RSA Publications, Hebron CT, 1996. 

Finally, another aspect of uranium toxicity must also be addressed, which is the teratogenic effect, that is, disturbing the proper growth and development of an embryo or fetus. This is a point of contention between the opponents of the use of DU munitions that attribute horrendous deformities in children whose parents were exposed to DU fragments or dust (HRN 2013) and other scientists who dispute these conclusions (Sztajnkrycer and Otten 2004). The dispute about the health effects of exposure to DU is discussed in Frame 4.2. 

An interesting review (Arzuaga et al. 2010) of the kidney toxicity effects of longterm exposure to natural uranium and DU states that The kidney was observed to be a target of uranium toxicity following oral and implantation exposure routes in several animal species. The interpretation and importance of the observed changes in biomarkers of proximal tubule function are important questions that indicate the need for additional clinical, epidemiological, and experimental research. ... 

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