Pharmacology of the phosphate binder, lanthanum carbonate.

Studies were conducted to compare the phosphate-binding efficacy of lanthanum carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received lanthanum carbonate, aluminum hydroxide, calcium carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum carbonate and aluminum hydroxide markedly increased excretion of [(32)P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, lanthanum carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of lanthanum carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that lanthanum carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses.

Validation and verification of the ICRP biokinetic model of 32P: the criticality accident at Tokai-Mura, Japan.

Regrettably, a criticality accident occurred at a uranium conversion facility in Tokai-mura, Ibaraki, Japan, on 30 September 1999. Radioactivities of 32P in urine, blood and bone samples of the victims, who were severely exposed to neutrons, were measured. 32P was induced in their whole bodies at the moment of the first nuclear release by the reaction 31P (n, gamma) 32P and 32S (n, p) 32P. A realistic biokinetic model was assumed, as the exchange of 32P between the extracellular fluid compartment and the soft tissue compartment occurs only through the intracellular compartment, and the model was used for preliminary calculations. Some acute excretion of 32P, caused by decomposition or elution of tissues which occurred at the time of the accident, may have happened in the victims' bodies in the first few days. The working hypotheses in the present work should initiate renewed discussion of 32P biokinetics.

Determination of 32P in urine for early estimation of the neutron exposure level for three victims of the JCO criticality accident.

In the criticality accident which occurred on 30 September 1999 at a uranium conversion facility in Tokai-mura, Japan, three workers were severely exposed to neutron and gamma-ray irradiation. Preliminary estimations of doses from blood properties and 24Na concentration in blood were 16-20, 6-10 and 1-4 gamma-ray gray-equivalent (gammaGyEq) respectively for the three workers. For apparent dose estimation, neutron-induced radionuclides in biological materials such as blood, hair and urine were measured. Accordingly, we detected 32p in urine samples. The concentration ratios of 32P in the urine for the three workers showed a similar tendency to those of 24Na in blood. This result indicated that the radioactivity of 32P in urine could be used to estimate the neutron exposure level.

Dose estimation for repeated phosphorus-32 ingestion in human subjects.

Dose estimation was conducted for internal phosphorus-32 exposure in one young male subject from repeated oral mis-ingestion for > 1 year. Since disclosure for previous continuous contamination, a series of urine samples were collected from this individual weekly for a period of >2 months. P-32 radioactivity in urine samples were measured by the acid precipitation method. Estimation for retrospective total effective dose equivalent received by this subject was conducted for cumulative internal dose estimation. A minimum of 9.4 mSv was estimated for an assumed single ingestion. As this was a rare case in radiation protection and internal radiation dosimetry, its implications were of considerable significance.

Occupational ingestion of P-32: the value of monitoring techniques to determine dose. A case report.

The purpose of this article is to described the analytical methods used to assess the internal dose from a P-32-labeled compound that was inadvertently ingested. Bioassay data, using the International Commission on Radiation Protection (ICRP)-30 model, enabled the calculation of internal dose. Whole body counting (WBC) and urinary measurement with liquid scintillation counting were utilized to estimate the amount of radioactive material deposited in body organs. This metabolic model assumes that 80% of the material ingested is absorbed through the gastrointestinal tract because P-32 is soluble. The time of the intake, a critical variable in this method, was estimated on the basis of urine contamination of clothing. Twenty-four-hour urine sampling over a 6-week period, coupled with daily WBC over the same period, was performed. Because P-32 does not emit photons, WBC relied on measuring the bremsstrahlung radiation produced as a result of interaction of beta radiation with the body's tissues. A P-32-spiked phantom was used as a control. Over the 6-week monitoring period, urinary results indicated an ingestion of 560 microCi of P-32, whereas WBC estimated on intake of 580 microCi. An assessment of the laboratory where the accident occurred indicated that approximately 600 microCi of radioactive phosphorous was missing. The total effective dose equivalent was estimated at 4.8 rem (48 mSv). On the basis of this study, the ICRP model appears to fit the data obtained from urine measurements and WBC. No symptoms were noted from the ingestion of 580 microCi. The committed organ doses were well within the occupational nonstochastic limits of 50 (0.5 Sv) permitted by the Nuclear Regulatory Commission. These results were confirmed by NUREG/CR-4884 and commercial software (CINDY). This report confirms the value of using the ICRP-30 model with urinary measurements and WBC to estimate the dose received as a result of ingestion of radioactive P-32.

Radioactivity in blood and urine following intraperitoneal instillation of chromic phosphate in patients with and without ascites.

Systemic distribution of radioactive colloidal chromic phosphate P 32 after intraperitoneal instillation was studied in 10 patients with ovarian or endometrial malignancies. Seven patients without ascites received chromic phosphate P 32 for positive peritoneal washings, rupture of the capsule of the cyst during operation, or minimal Stage III disease. Three patients received chromic phosphate P 32 for recurrent ascites after multiple abdominal paracenteses. Blood and urine radioactivity measurements were performed at selected intervals. There was a clear statistically significant difference (p less than 0.01) between chromic phosphate P 32 activity levels in whole blood, red blood cells, and plasma in patients with and without ascites.