Low Concentrations Of Radioactivity Research Articles

Preparation of Rhenium-188-Lipiodol Using Freeze-Dried Kits for Transarterial Radioembolization: An Overview and Experience in a Hospital Radiopharmacy.

Background: Rhenium-188(188Re)-lipiodol is a clinically effective, economically viable radiopharmaceutical for Selective Internal Radiation Therapy of liver cancer. Present study evaluates the performance of three freeze-dried kits with respect to the radiochemistry, quality control, and overall "ease of preparation" aspects in a hospital radiopharmacy. Materials and Methods: Freeze-dried kits of acetylated 4-hexadecyl-4,7-diaza-1,10-decanedithiol (AHDD), super six sulfur (SSS), and diethyl dithiocarbamate (DEDC), obtained commercially or received as gift, were used for the preparation of 188Re-lipiodol using freshly eluted 188Re-sodium perrhenate from commercial Tungsten-188/188Re generator following recommended procedures. Results: The overall yield of 188Re-lipiodol prepared using AHDD Kit, SSS Kit, and DEDC Kit was 74.82% ± 3.3%, 87.55% ± 4.8%, and 76.38% ± 4.6%, respectively. Observed radiochemical purity (RCP) of 188Re-lipiodol prepared using these kits was 88.65% ± 2.8%, 92.92% ± 3.0%, and 91.38% ± 3.0%, respectively. Using a modified version of the DEDC Kits, overall yield of 87.17% ± 2.7% and RCP of 95.43% ± 2.3% could be achieved. Conclusions: While all three freeze-dried kits can be used for the preparation of 188Re-lipiodol in >70% overall yield, the modified version of DEDC Kits has some advantages in terms of preparation time and volume of Rhenium-188 activity that can be added to the kit vial. The latter feature of the DEDC Kit is particularly useful for patient dose preparation with 188Re activity of low radioactive concentration.

Leaching of REY from Non-magnetic Coal Fly Ash with Acetic Acid

The escalating demand of REY in various industrial applications becomes an important issue nowadays. REY has prominent evidence to improve material properties such as high electropositive and good conductivity. In addition REY can be classified as one of renewable and clean energy resources. Due to the increasing demand of REY, exploration of alternative sources such as red mud, spent catalyst, and coal fly ash has been conducted. Coal fly ash is one of the promising alternative sources of REY in regarding to the low radioactive material concentration. The conventional method to recover REY from coal fly ash using inorganic acids produces harmful by-product to the environment. In this research, two steps experimental methods were conducted. The first step was silicate digestion which was performed using sodium hydroxide 8 M in which REY is concentrated, with solid to liquid ratio of 1:4 and temperature of 90°C for 120 minutes. The second step was leaching the REY using citric acid. The variables studied were pH, temperature and solid to liquid ratio. The optimum condition was at the temperature of 90°C, pH 1.7 and solid to liquid ratio (15%) for each element. The maximum recovery for each elements are 77.33% Lanthanum (La), 83.47 % Cerium (Ce), 88.78% Dysprosium (Dy) and 55% Neodymium(Nd). In addition, temperature does not have any significant efect at pH 3.8.

Derivation of Uncertainty in Measurement and Characteristic Limits for Low Radioactive Concentration Measurement According to ISO 11929

Derivation of Uncertainty in Measurement and Characteristic Limits for Low Radioactive Concentration Measurement According to ISO 11929

Bioavailability, Biotransformation, and Excretion of the Covalent Bruton Tyrosine Kinase Inhibitor Acalabrutinib in Rats, Dogs, and Humans

Acalabrutinib is a targeted, covalent inhibitor of Bruton tyrosine kinase (BTK) with a unique 2-butynamide warhead that has relatively lower reactivity than other marketed acrylamide covalent inhibitors. A human [14C] microtracer bioavailability study in healthy subjects revealed moderate intravenous clearance (39.4 l/h) and an absolute bioavailability of 25.3% ± 14.3% (n = 8). Absorption and elimination of acalabrutinib after a 100 mg [14C] microtracer acalabrutinib oral dose was rapid, with the maximum concentration reached in <1 hour and elimination half-life values of <2 hours. Low concentrations of radioactivity persisted longer in the blood cell fraction and a peripheral blood mononuclear cell subfraction (enriched in target BTK) relative to plasma. [14C]Acalabrutinib was metabolized to more than three dozen metabolites detectable by liquid chromatography-tandem mass spectrometry, with primary metabolism by CYP3A-mediated oxidation of the pyrrolidine ring, thiol conjugation of the butynamide warhead, and amide hydrolysis. A major active, circulating, pyrrolidine ring-opened metabolite, ACP-5862 (4-[8-amino-3-[4-(but-2-ynoylamino)butanoyl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-pyridyl)benzamide), was produced by CYP3A oxidation.Novel enol thioethers from the 2-butynamide warhead arose from glutathione and/or cysteine Michael additions and were subject to hydrolysis to a β-ketoamide. Total radioactivity recovery was 95.7% ± 4.6% (n = 6), with 12.0% of dose in urine and 83.5% in feces. Excretion and metabolism characteristics were generally similar in rats and dogs. Acalabrutinib's highly selective, covalent mechanism of action, coupled with rapid absorption and elimination, enables high and sustained BTK target occupancy after twice-daily administration.

Rhenium-188 Hydroxyethane 1,1-Diphosphonic Acid (HEDP) for Bone Pain Palliation Using BARC-HEDP Kits versus Pars-HEDP Kits: A Comparison on Preparation and Performance Aspects at Hospital Radiopharmacy.

Purpose of the Study:Rhenium-188 hydroxyethane 1,1-diphosphonic acid (HEDP) is a clinically established radiopharmaceutical for palliation of bone pain due to osseous metastases. Recently, the Bhabha Atomic Research Centre (BARC) had developed a freeze-dried kit for the preparation of rhenium-188 HEDP. The present study compares the radiochemistry aspects of indigenous BARC-HEDP kits with commercially available HEDP kits from Pars Isotope Company, Iran.Materials and Methods:Freeze-dried HEDP kits were obtained from Radiopharmaceuticals Division, BARC, and Pars Isotope Company, Iran. Following recommended procedures, rhenium-188 HEDP was prepared using freeze-dried kits from both sources using freshly eluted rhenium-188 sodium perrhenate obtained from a commercial tungsten-188/rhenium-188 generator.Results:Both kits could be used for the preparation of rhenium-188 HEDP in >95% radiochemical purity (RCP). Rhenium-188 HEDP prepared from both kits showed comparable in vitro stability as well as pharmacokinetic properties. The normal bone-to-soft tissue ratio observed for rhenium-188 HEDP prepared using BARC-HEDP kit and Pars-HEDP kit was 1.993 and 1.416, respectively.Conclusions:Both HEDP kits provided a user-friendly solution for the preparation of rhenium-188 HEDP. While Pars-HEDP-kit permits the addition of only 2 mL of rhenium-188 perrhenate solution per kit vial, BARC-HEDP-kit allows up to 5 mL. This feature permits the preparation of patient dose of rhenium-188 HEDP even with older generators providing rhenium-188 perrhenate having a low radioactive concentration (activity/mL). In addition, availability of an indigenous product is always preferable over imported options.

188W/188Re Generator System and Its Therapeutic Applications

The188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV), which can efficiently be used for imaging and calculations of radiation dose.188Re may be conveniently produced by188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent188W radionuclide indeed have been one of the major issues about the use of188Re in nuclear medicine. Since the specific activity of188W used in the generator is relatively low (&lt;185 GBq/g), the elutedRe188O4-can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically usefulRe188O4-solutions. This review summarizes the technologies developed for the preparation of188W/188Re generators, postelution concentration of the188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of188Re radiopharmaceuticals.

Column Chromatography Using Nano-Sorbent: A Viable Approach Towards Post-Processing Concentration of 125I for Medical Applications

Successful use of ion-exchange chromatographic technique using nano-zirconia (t-ZrO2), to concentrate 125I solution obtained from wet chemical distillation method to levels required for preparation of 125I brachytherapy sources, is reported. A careful scrutiny of the sorption parameters of t-ZrO2 was carried out and implemented to arrive at conditions resulting in optimum retention of 125I from its solution of low radioactive concentration on a tiny column containing t-ZrO2, followed by its elution in a small volume of eluent. The developed procedure was validated using samples containing varying amounts of 125I activity in the feed and the concentration factors (CF) of 125I > 5 could be obtained. The overall recovery of 125I was >90% with appropriate radiochemical purity. The compatibility of the product in the preparation of 125I brachytherapy sources was found to be satisfactory.

Rhenium-188: Availability from the 188W/188Re Generator and Status of Current Applications

Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting β(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.

In-vivo Radiolabelled Oxiracetam Binding to Rat Brain

The in-vivo binding of [3H]oxiracetam has been studied in brain areas of rats examined 30 min after i.c.v. injection. Soluble radioactivity accounted for more than 90% of total radioactivity in all the structures considered and was not affected by co-injection with a 1000-fold excess of unlabelled oxiracetam. Both total and bound radioactivity showed a marked regional distribution, with highest concentrations in the septum, followed by the hippocampus; the cerebral cortex, striatum and cerebellum had the lower concentrations of radioactivity. Computer-assisted quantitative autoradiography with [14C]oxiracetam confirms these findings. Analysis of [3H]oxiracetam bound to membranes indicated that, after co-injection with a 1000-fold excess of unlabelled oxiracetam, there was a significant reduction of binding only in the septum, hippocampus and cerebral cortex. These results suggest that in those cerebral structures oxiracetam binds to saturable sites.

Laboratory studies of the diffusive transport of 137Cs and 60Co through potential waste repository soils

Tests using reconstituted samples have been performed to assess the diffusive transport of 137Cs and 60Co through natural regolith materials from a region in South Australia being considered for a radioactive waste repository. A double diffusion cell apparatus made of polycarbonate resin was developed to estimate the effective diffusion ( D e) and sorption coefficients ( K d) that allowed large withdrawals from the source and collector cells and has enabled tests with low concentrations of radioactivity. An alternative to porous stainless steel filter plates has also been used to reduce uncertainty in test interpretation. Analysis of the transient data used a staged method of the Laplace transform to take into consideration the volume of the samples withdrawn from the apparatus during testing. At test completion samples were cut into slices and analysed for radionuclide concentration. Data obtained from the sliced samples confirmed that both numerical and experimental data produced acceptable mass balance. The D e values obtained in this study were of the order of 10 −6 cm 2 s −1 for both species, higher than previously published data. The K d values from the diffusion and batch sorption tests were in reasonable agreement for 137Cs, but an order of magnitude different for 60Co. The sorption of the latter radionuclide was strongly pH dependent, and this dependency during diffusion tests would benefit from further investigation.

U and Th in some brown coals of Serbia and Montenegro and their environmental impact

The objective of this paper is to determine and compare the concentrations of U and Th in soft to hard brown (lignite to sub-bituminous) coals of Serbia and Montenegro. It also presents comparison of the obtained data on U and Th concentrations with the published data on coals located in some other countries of the world. Almost the whole coal production of Serbia and Montenegro is used as feed coals for combustion in thermal power plants. Channel samples from open pit and underground mines and core samples were collected for hard and soft brown coals. For the analysis the samples were decomposed using microwave technique. Obtained solutions containing U and Th were analyzed by inductively coupled plasma mass spectroscopy (ICP-MS) using NIST standards. Concentration of U from the investigated basins and the corresponding mine fields ranges within 0.60-70.10 mg/kg, 0.65-3.20 mg/kg, 0.95-6.59 mg/kg, 1.20-6.05 mg/kg, 0.80-6.66 mg/kg, 0.18-89.90 mg/kg, 0.19-4.14 mg/kg, and 0.28-3.52 mg/kg for the Kostolac, Kolubara, Krepoljin, Sjenica, Soko Banja, Bogovina East field, Senje-Resavica and Pljevlja basins, respectively. Concentration of Th ranges within 0.20-2.60 mg/kg, 0.84-6.57 mg/kg, 1.48-6.48 mg/kg, 0.12-2.71 mg/kg, 0.13-4.95 mg/kg, 0.14-3.48 mg/kg, 0.29-3.56 mg/kg, and 0.17-1.89 mg/kg for the Kostolac, Kolubara, Krepoljin, Sjenica, Soko Banja, Bogovina East field, Senje-Resavica and Pljevlja basins, respectively. Brown coal from Senje-Resavica, Kolubara, Kostolac and Pljevlja is characterized by low U concentration. Coals form the Krepoljin, Soko Banja and Sjenica basins have slightly higher U concentrations than the mentioned group. The highest concentration of U is characteristic for the coal from the Bogovina East field. Concentration of Th in coals from Serbia and Montenegro has proved to be low. Out of all investigated coal basins, only the coal from the Krepoljin and Kolubara basins has high concentration of Th. The hydrothermally altered rocks of the Timok dacite-andesite complex, representing the basement of the Bogovina basin, could be a potential source of U, especially at the bottom part of the Lower seam of the Bogovina East field. This study shows that brown coals in Serbia and Montenegro (soft to hard brown coals or lignite to sub-bituminous) contain low levels of U (5.30 mg/kg, average value and 2.10 mg/kg geometric mean value) and Th (1.80 mg/kg, average value and 1.12 mg/kg geometric mean value). There are some obvious differences in concentration of U and Th in coals from different basins in Serbia and Montenegro. The approximate value for U and Th release mainly from power plants was 644.33 t and 983.46 t, respectively within the period 1965-2000 for the studied mines in Serbia, and 23.76 t and 15.05 t for the Potrlica mine (Montenegro) within the period 1965-1997. The coals in Serbia and Montenegro show no identifiable unfavourable impact on the surrounding environment, due to low natural radioactive concentration of U and Th, but further investigations concerning human health should be performed. Preliminary research revealed that in some Serbian coals (and, particularly, parts of the coal seam) U and Th content are rather high. Such coals should be carefully studied, as well as U and Th concentrations in ash, fly ash, waste disposals, nearby soil and ground water. Further studies should include determination of the radioactivity of all these products, and estimation of possible health impact.

K/Th/U in photomultiplier tubes and improved low-level NaI detectors

The study presented here is the first step in a program aimed at reducing significantly the background count rate of NaI scintillation units. We have investigated: (1) the residual background of a large well type NaI detector, i.e., when shielded with 10 cm of lead and operated deep underground, (2) low concentrations of primordial radioactivity in glass used for photomultiplier tubes (PMTs) and (3) the activity in whole tubes. The residual background of the NaI units is dominated by gamma radiation from potassium, thorium and uranium in the PMT, which severely limits their sensitivity. Activity in tubes made of new high purity glass was close to the detection level. The prospects of a new generation of low-level NaI detectors with these tubes are discussed.

The safety of the use of ethyl oleate in food is supported by metabolism data in rats and clinical safety data in humans

The absorption, distribution, and excretion of radiolabeled ethyl oleate (EO) was studied in Sprague–Dawley rats after a single, peroral dose of 1.7 or 3.4 g/kg body weight and was compared with a radiolabeled triacylglycerol (TG) containing only oleic acid as the fatty acid (triolein). Both test materials were well absorbed with approximately 70–90% of the EO dose absorbed and approximately 90–100% of the TG dose absorbed. At sacrifice (72 h post-dose), tissue distribution of EO-derived radioactivity and TG-derived radioactivity was similar. The tissue with the highest concentration of radioactivity in both groups was mesenteric fat. The other organs and tissues had very low concentrations of test material-derived radioactivity. Both test materials were rapidly and extensively excreted as CO 2 with no remarkable differences between their excretion profiles. Approximately 40–70% of the administered dose for both groups was excreted as CO 2 within the first 12 h (consistent with β-oxidation of fatty acids). Fecal elimination of EO appeared to be dose-dependent. At the dose of 1.7 g/kg, 7–8% of the administered dose was eliminated in the feces. At the dose of 3.4 g/kg, approximately 20% of the administered dose was excreted in the feces. Excretion of TG-derived radiolabel in the feces was approximately 2–4% for both doses. Overall, the results demonstrate that the absorption, distribution, and excretion of radiolabeled EO is similar to that of TG providing evidence that the oleic acid moiety of EO is utilized in the body as a normal dietary TG-derived fatty acid. To confirm the expected safety of EO in humans, a total of 235 subjects participated in a 12-week trial where two levels of ethyl oleate in a milk-based beverage were investigated: 8 g/day in a single serving (approximately 0.1 g/kg) and 16 g/day taken in two divided servings (approximately 0.2 g/kg). Adverse events (AEs) were recorded throughout the 12-week trial. In addition, a brief physical exam (including vital signs and body weight), ECGs, fasting serum chemistry profile, serum lipid profile, and urinalysis were performed at baseline and after study completion. Results showed the incidence of reported AEs was similar between the EO groups and the control groups. Analysis of comprehensive laboratory data revealed no EO exposure-related, clinically significant adverse changes in laboratory parameters. These studies demonstrated that EO has a highly favorable safety profile and is well tolerated in the diet.

Studies on the mechanism of cancer protection by wheat bran: effects on the absorption, metabolism and excretion of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

We examined ways in which dietary supplements of wheat bran may protect against colon cancer. The effects of supplementing the diet of female Wistar rats with 10% wheat bran on the disposition and metabolism of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) labelled with (14)C was determined. Our data show that the wheat bran had a major effect on both the distribution and metabolism of IQ. At a low dose of IQ (1 mg/kg), we unexpectedly found that up to 2 h after gavage there were higher concentrations of radioactivity in the plasma of rats fed wheat bran compared with the controls, but there were lower concentrations of radioactivity after 2 h. At a high dose of IQ (50 mg/kg), there were always lower concentrations of radioactivity in the plasma of rats fed wheat bran compared with the control rats. One of the most marked effects of wheat bran was apparently to significantly retard the metabolism of IQ in the plasma when this was fed at either dose. There were also differences between the rats fed wheat bran and the control in the concentrations and types of IQ metabolites in the urine.

Highly concentrated [ 99mTc]pertechnetate solutions from (n,γ) 99Mo/ 99mTc generators for nuclear medical use

Because of the high content of inactive molybdenum in the irradiated MoO 3, large generator columns containing alumina are needed to produce chromatographic (n,γ) 99Mo/ 99mTc generators. That results in large elution volumes containing relatively high Mo contents and low radioactive concentration on 99mTc. The present paper describes a system for concentration and purification of pertechnetate solutions involving steps of reduction, adsorption, reoxidation and elution which allows to improve the critical quality parameters of the pertechnetate solution in such a way that they meet the highest requirements.

Extending the life of a 99Tcm generator

99Tcm-pertechnetate can conveniently be concentrated 5-20-fold by passing up to 20 ml through a sequence of two (or three) disposable columns, one (or two) to remove chloride and one to concentrate the pertechnetate for subsequent elution with a small volume of saline. This procedure is useful for utilizing eluates with low radioactive concentration in applications that require high radioactive concentration.

Imaging of thrombi with tissue-type plasminogen activator rendered enzymatically inactive and conjugated to a residualizing label.

Contemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis. We have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiolabeled degradation products from the liver. The rapid clearance of unaltered or PPACK-treated t-PA was not influenced by conjugation to *I-DLT, but the release of radioiodinated degradation products into plasma after injection of *I-DLT-conjugated t-PA was markedly less than release of degradation products of directly radioiodinated t-PA. When 131I-DLT-PPACK-t-PA was infused for 15 minutes intravenously after a bolus injection of 20% in dogs with coronary, pulmonary, or carotid artery thrombi, clearance was rapid. Mean +/- SEM thrombus-to-blood ratios of radioactivity were high, ranging from 37 +/- 9:1 and 2.8 +/- 0.6:1 with carotid thrombi formed concomitantly or approximately 30 minutes before infusion of tracer, respectively, to 35:1 for concomitantly formed coronary thrombi, 42 +/- 7:1 and 8.1 +/- 0.8:1 for concomitantly formed and preformed pulmonary thrombi, respectively, and 18:1 for a preformed femoral artery thrombus. Thrombi were detectable by planar gamma scintigraphy even though image quality was affected adversely by low concentrations of radioactivity that in aggregate composed a relatively large amount of radioactivity in underlying and overlying tissues. This limitation was overcome by tomographic imaging, which was used to detect both femoral and pulmonary thrombi. Use of enzymatically inactivated t-PA coupled to a residualizing label permits rapid detection and localization of thrombi in vivo.

Absorption, distribution, excretion and metabolism of a single oral dose of [formula omitted] phosphate (TOCP) in the male rat

A single oral dose of 50 mg/kg of [ 14C]TOCP was administered in corn oil to male rats. Three animals were sacrificed at each of 2, 6 and 12 h and 1,2 and 5 days following dosing, and tissues and excreta were analyzed for 14C. Within 5 days, 63 and 36% of the dose were recovered in the urine and feces, respectively. Initially, the highest concentrations of radioactivity were observed in the gastrointestinal tract, its contents, the urinary bladder, liver and kidneys. Appreciable concentrations of 14C were detected in plasma, red blood cells, lungs and adipose tissues, while neural tissues, muscle, spleen and testes contained lower concentrations of radioactivity. Among neural tissues, the sciatic nerve contained the highest concentrations of 14C at all time points studied. The concentration of TOCP in plasma was at maximum by 6 h then declined biexponentially with terminal half-life of 46 h. The predominant metabolites in plasma were o-cresyl dihydrogen phosphate, di-ocresyl hydrogen phosphate and o-hydroxybenzoic acid (salicylic acid). Small concentrations of the neurotoxic metabolite of saligenin cyclic- o-tolyl phosphate, were detected in plasma at all but the last time point analyzed. Most of the radioactivity extracted from the livers of rats sacrificed at 2 and 4 h were metabolites. No TOCP was detected in the urine or feces collected within 3 days after dosing. The major metabolite in the urine and feces was o-cresyl dihydrogen phosphate followed by di- o-cresyl hydrogen phosphate, salicylic acid, o-hydroxybenzyl alcohol and o-cresol. This study supports the hypothesis that the insensitivity of the rat to TOCP-induced delayed neurotoxicity may be attributed, in part, to the disposition and metabolism of this chemical.

Severe chromosomal damage in mammalian cells induced by pulse labeling with small amounts of [ 3H]thymidine

Pulse labeling of cultured mammalian cells with tritiated thymidine ([ 3H]TdR; different specific activities, 2–47 Ci/mmole) for 30 min at low concentrations of radioactivity (0.2–2 μCi/ml) causes an unusually high degree of chromosomal aberrations which becomes fully evident in the cohort of cells analyzed 8 h later. The effect depends on the total amount of radioactivity. In HeLa cells up to 93% aberrant metaphases with up to 3.6 aberrations per metaphase were observed; in CHO cells the corresponding figures are 62% aberrant metaphases with 1 aberration per metaphase. The results may be valuable (i) for users of the pulse-labeling technique for analysis of cell-cycle kinetics, as this shows the technique as such may delay the labeled cohort of cells and therefore interferes with the matter under study and (ii) for risk assessment.

Distribution of 3H-soman in mice.

3H-soman (specific activity 10 Ci/mMol), a potent irreversible cholinesterase inhibitor, was administered IV to mice in a dose of one LD-50, which corresponds to 0.25 mCi/mouse. Animals were sacrificed at 5 min, 2 h and 24 h, and whole body autoradiography was performed. High levels of radioactivity in lung and skin were observed at all time intervals after injection. The central nervous system showed very low concentrations of radioactivity, which remained so for 24 h post-injection. Considerable accumulation of 3H-soman in the urine and gall-bladder, and in the intestinal lumen, may indicate these as pathways of soman excretion. Quantitative determinations of radioactivity in various tissue samples were consistent with the above-mentioned findings. It is concluded that the nature of the persistent binding of soman to lung and skin is striking, and may indicate the existence of specific sites for soman depots.