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PubMed1979

Fluorescence assay of tissue distribution of 4-demethoxydaunorubicin and 4-demethoxydoxorubicin in mice bearing solid tumors.

The tissue distribution of 4-demethoxydaunorubicin and 4-demethoxydoxorubicin was studied in comparison with that of their patient compounds, daunorubicin and doxorubicin, in mice bearing transplanted tumors. The doses administered were equal or equitoxic to those of their parent compounds. The levels of total fluorescence due to initial drugs and metabolites were determined on tissue extracts by fluorometry. After administration of equal doses of daunorubicin and 4-demethoxydaunorubicin, the calculated Cxt values of 4-demethoxydaunorubicin equivalents were higher than those for daunorubicin in all the organs tested except the heart. In animals treated with equitoxic doses, lower 4-demethoxydaunorubicin levels were found in all the organs tested. In mice treated with equitoxic doses of doxorubicin and 4-demethoxydoxorubicin, 4-demethoxydoxorubicin reached higher drug concentrations than doxorubicin in spleen and liver, whereas in all the other organs tested lower drug levels were found. The rate of drug disappearance from organs was slower in animals treated with 4-demethoxyderivatives than in those treated with their parent drugs.

Animals↗

PubMed1992

Kinetic analysis of tissue distribution of doxorubicin incorporated in liposomes in rats: I.

The purpose of this study was to perform a kinetic analysis of the tissue distribution of doxorubicin (DXR) and liposomes separately after intravenous administration of DXR entrapped in liposomes in rats. Liposomes were double labeled with 14C-DXR (L-DXR) and 3H-inulin (L-INU). Blood and tissues were sampled at specified times until 120 min. Blood clearance of L-DXR was similar to that of L-INU. Distribution of both L-DXR and L-INU into the liver was parallel and extensive, while in the heart, the pattern of distribution differed between L-DXR and L-INU after peak concentration. Time courses of tissue concentration were explained well by dividing tissue into a shallow compartment with efflux and a deep compartment without efflux. In the liver, pharmacokinetic parameters of L-DXR and L-INU were similar, and the two kinetically different compartments may correspond to different uptake processes in hepatic endocytosis. In the heart, the shallow compartment was considered to correspond to the cardiac vascular space, and the intercompartmental rate constant (k3) for L-DXR was much larger than that for L-INU. The estimated half-life for this process was 20 min. The half-life for the degradation of liposomes in blood circulation was also estimated at 20 min from data on the urinary excretion of released 3H-inulin. These results suggest that the release of DXR from liposomes may be the rate-limiting process in the tissue distribution of DXR to the heart.

Animals↗

PubMed1996

D-mannose dimer introduced human recombinant interleukin- 1 alpha, NEO IL-1 alpha, exhibits altered tissue distribution in mice.

Previous studies have demonstrated that the carbohydrate-introduced recombinant human IL-l alpha exhibited impairment in both biologic activities in all the experiments in vitro and receptor binding capacity compared with intact IL-l alpha. However, the glycosylated IL-l alpha exhibited selective activities in vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice were injected by intravenous and intraperitoneal routes with 2.0 mu g radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2 alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha exhibited higher levels than IL-l alpha in blood, heart, and liver. No significant difference was observed in brain at each time point. IV injection demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha increased twofold over that of IL-l alpha in liver at 1 h after dosing. These findings are consistent with the result of IP injection. There was no significant difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV administration. These differences in tissue distribution may contribute to the selective activities of glycosylated IL-l alpha in vivo. The results also suggest that by coupling with mannose dimer, it is possible to develop neocytokines prone to liver distribution.

Animals↗

PubMed1987

Tissue distribution and vitamin D dependence of IMCAL in the rat.

Integral membrane calcium-binding protein (IMCAL) is a vitamin D-dependent integral membrane protein that binds calcium with relatively high affinity (J. Biol. Chem. 225: 10834-10840, 1980). Specific immunoassays for IMCAL utilizing rabbit polyclonal and mouse monoclonal antibodies were developed and applied to studies of its tissue distribution and regulation by vitamin D3 and dietary calcium in the rat. The results indicate that vitamin D-dependent, cross-reactive protein is present in small intestinal mucosa, cecal mucosa, bone, kidney, brain, testis, heart, lung, spleen, and skin. Rats maintained on a low- (0.02%) compared with & high- (2.0%) calcium diet had significantly higher content of IMCAL in duodenal mucosa, cecal mucosa, bone, kidney, brain, testis, and heart. Treatment of rats on the high-calcium diet with 1,25-dihydroxyvitamin D3 increased the IMCAL content of the duodenal mucosa, cecal mucosa, and kidney. The widespread tissue distribution of vitamin D-dependent IMCAL, its close correlation in intestinal mucosa with the calcium transport mechanism, and its occurrence in isolated preparations of enterocyte plasma membranes (microvillus and basolateral membranes) suggest that the protein is involved in the regulation of calcium flux in a number of cell types.

Animals↗

PubMed2005

[Tissue distribution and excretion of bromotetrandrine in rats].

AIM: To study the tissue distribution and excretion of bromotetrandrine (W198) in rats. METHODS: The concentrations of W198 in biological samples were determined by an HPLC method with UV detection. RESULTS: After a single i.v. dose of 20 mg x kg(-1) W198 in rats, the parent drug concentrations in tissues were higher than those in blood at the same time. Parent drug was mainly distributed in lung, kidney, heart and liver, the peak levels were attained at 0.25 h and decreasing at 2 h after dosing in most tissues. After a single iv dose of 20 mg x kg(-1) W198 in rats, the excretion of the parent drug in urine, feces and bile amounted to 0. 150%, 2.1% and 0.063% of the dose, respectively. CONCLUSION: W198 was mostly distributed in lung. The parent drug excretion was less than 3% via urine, feces and bile.

Animals↗

PubMed1984

[Fundamental study on tissue distribution of ceftriaxone in the field of obstetrics and gynecology].

Fundamental study on tissue distribution of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin parenteral antibiotic, was studied and the following results were obtained. CTRX had been administered by intravenous drip infusion with 1 g to 9 cases who received simple total hysterectomy. The level of CTRX in the cubital venous serum and uterine arterial serum was determined as well as the tissue concentration in the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis. The level in the oviduct and portio vaginalis was generally high, although it was observed only in a few cases. The variation of the level in the myometrium was large. CTRX is expected to be clinically useful considering the fact that its half-life time is 8.5 hours, which is longer than that of existing cephalosporin antibiotics.

Adult↗

PubMed2006

The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans.

The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [(14)C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat and human plasma. Radioactivity and drug levels in blood, plasma, tissues, urine, and feces up to 192 hours were collected and measured. The mean terminal half-life of plasma (76 h) and blood (105 h) radioactivity was prolonged compared with that of unchanged AS (0.43 h) and dihydroartemisinin (0.75 h), an active metabolite of AS. Drug was widely distributed after 1 hour in select tissues. After 24 hours, the radioactivity rapidly declined in all tissues except spleen until 96 hours. Only 1% of total radioactivity was detected in brain tissue. AS revealed a higher binding capacity with human and rat plasma proteins (73-81%). The radioactivity in whole blood was higher (two to fourfold) than that in plasma throughout the period of the treatment, suggesting that AS binding to RBCs may relate to its powerful antimalarial activity.

Animals↗

PubMed1994

Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion.

This report describes the tissue distribution and long-term (14-day) excretion of hemoglobin cross-linked between the alpha-chains (alpha alpha Hb) with carbon 14-labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50% isovolemic exchange transfusion (ET) with solutions of 14C-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 days. Thirteen tissue types were analyzed for radioactivity by liquid scintillation counting. The highest concentration of label was found in the kidney and in tissues of the reticuloendothelial system (i.e., spleen, bone marrow, and liver). The 14C-labeled alpha alpha Hb did not appear to cross the blood-brain barrier, because radioactivity in the brain was barely detectable. The dose of 14C-labeled alpha alpha Hb (2.4 gm Hb/kg) produced an initial plasma Hb level of 4.6 gm/dl, with a half-life in the plasma of 5.0 hours. The peak concentration in kidney, spleen, and liver occurred at 24 hours after ET, when at least 92% of the 14C-labeled alpha alpha Hb in plasma had been cleared. At 48 hours, red casts were seen in a tiny number of renal tubules in some rats. By 14 days, up to 64% of the injected radioactivity had been recovered in urine and about 10% was recovered in feces. Most excretion occurred 24 to 48 hours after ET. This study demonstrated that 2 weeks were required for the metabolic degradation and elimination of a large dose of alpha alpha Hb in rats.

Animals↗

PubMed1999

Tissue distribution of cadmium in rats given minimum amounts of cadmium-polluted rice or cadmium chloride for 8 months.

To investigate the relationship between cadmium (Cd) toxicity, intestinal absorption, and its distribution to various tissues in rats treated orally with minimum amounts of Cd, 14 female rats per dose group per time point were given diets consisting of 28% purified diet and 72% ordinary rice containing Cd-polluted rice (0. 02, 0.04, 0.12, or 1.01 ppm of Cd) or CdCl(2) (5.08, 19.8, or 40.0 ppm of Cd) for up to 8 months. At 1, 4, and 8 months after the commencement of Cd treatment, seven rats per group were euthanized for pathological examinations to determine the Cd concentrations in the liver and kidneys and metallothionein (MT) in the liver, kidneys, intestinal mucosa, serum, and urine. One week before each period of 1, 4, and 8 months, the remaining seven rats in each group were administered a single dosage of (109)Cd, a tracer, to match the amounts of the designated Cd doses (about 1.2 to 2400 microg/kg body wt). They were euthanized 5 days later to determine the distribution of Cd to various tissues. No Cd-related toxic changes were observed. The concentrations of Cd in the liver and kidneys at any time point and MT in the liver, kidney, serum, and urine at 4 and 8 months increased dose-dependently, whereas MT in the intestinal mucosa did not alter markedly at any time point. The distribution rates of Cd to the liver increased dose-dependently (40% at lower doses to 60% at higher doses), whereas those to the kidney decreased dose-dependently (20% at lower doses to 10% at higher doses). The Cd retention rates 5 days after (109)Cd administration (amounts of Cd in various tissues/amounts of Cd administered) ranged from 0.2 to 1. 0% at any time point. These results suggest that the distribution of Cd to the liver and kidneys after the oral administration vary depending on the dosage levels of Cd. The difference of the distribution pattern of Cd to the liver and kidney is probably due to the difference in the form of the absorbed Cd, i.e., free ion or Cd-MT complex, although not closely related to the MT in the intestinal mucosa.

Administration, Oral↗

PubMed1978

Tissue distribution and excretion of 14C-epichlorohydrin in male and female rats.

The tissue distribution and excretion of 14C-epichlorohydrin was studied in both male and female rats following an oral dose of 10 mg/kg. Organs containing the highest concentrations of radioactive label per unit weight were the kidneys, liver, pancreas, ann spleen. With the exception of the pancreas, these are the same organs in which epichlorohydrin-induced pathologic changes have been reported by a number of investigators, indicating a direct correlation between tissue levels and target organ toxicity. The principal route of excretion was via the kidneys, 38-40% of the dose appearing in the urine during the 72 hour period of study. Fecal excretion was relatively insignificant, representing less than 4% of the administered dose. It was found that 18-21% of the administered dose appeared as 14CO2 in the expired air, the majority being excreted in the first 4 hours, suggesting a rapid and extensive biotransformation of the compound.

Animals↗

PubMed1984

Natural killer (NK) cell activity in murine muscular dystrophy. II. Age-related tissue distribution and enhanced NK activity in the thymus of dystrophic mice.

The age-related tissue distribution of natural killer (NK) cell activity in murine muscular dystrophy was investigated. Lymphoid tissues including the spleen, thymus, mediastinal (or bronchial) lymph nodes (BLN), mesenteric lymph nodes (MLN), inguinal/popliteal lymph nodes (PLN1), and axillary/brachial lymph nodes (PLN2) were obtained from various aged normal (+/+) and dystrophic (dy2J/dy2J) C57BL/6J mice. Cell suspensions were incubated with 51Cr-labeled YAC-1 lymphoma target cells in a 4-hr 51Cr-release assay. The data indicated that dystrophic mice, at all ages studied, had elevated levels of NK activity in the spleen, BLN, MLN, PLN1, and PLN2 as compared with the normal age- and sex-matched control group. The NK activity in the thymocyte population from dystrophic mice at 2 weeks of age was found to be negligible, while at 8 weeks of age it was two-fold higher than that for the normal control group. In addition, dystrophic mice had an age-related decline in NK activity in all tissues after 10 weeks of age but the activity was still elevated at 40 weeks of age as compared with the normal control group. Target cell binding studies revealed that the number of conjugate-forming cells in thymocytes from 8-week-old dystrophic mice were found to be significantly higher than that found in normal mouse thymocytes using NK-sensitive YAC-1 tumor target cells. The number of cells bound per YAC-1 target cell ranged from 1 to 3 for dystrophic mouse thymocytes as compared with 1 to 2 for the normal control group. Thus, the data indicate an elevated NK activity in all lymphoid tissues studied from dystrophic mice of different ages. In addition, the thymus from dystrophic mice at 8 weeks of age contains an enhanced number of conjugate-forming NK cells and NK activity.

Aging↗

PubMed2001

Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues.

Peptide hormones are generated by proteolytic processing of their respective protein precursors by several prohormone processing proteases. The peptide hormone PTHrP is widely expressed in normal and malignant tissues, where proPTHrP undergoes proteolytic processing to generate PTHrP peptides with distinct biological actions. In this study, the tissue distribution of the prohormone processing enzymes PTP, PC1, and PC2 were compared by immunohistochemistry in human PTHrP-producing cancer cell lines, and in mammalian neuroendocrine and other tissues from rat and bovine that contain peptide hormones. PTP, PC1, and PC2 were prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung, prostate, as well as lymphoma. These processing enzymes also showed significant expression in normal mammalian neuroendocrine tissues from bovine and rat, including pituitary, hypothalamus, adrenal medulla, pancreas, and other tissues. Most neuroendocrine tissues contained prominent levels of at least two of the three processing enzymes examined, and all tissues contained at least one of these three enzymes. Differential expression of processing enzyme proteins was also demonstrated by Western blots. The differential expression of PTP, PC1, and PC2 observed in certain cancer and normal neuroendocrine cell types postulates selective roles for these processing enzymes in different tissues for generating biologically active peptide hormones. These results support the importance of these processing enzymes in their hypothesized roles in prohormone processing.

Adrenal Medulla↗

PubMedDate not supplied

Waist-to-hip ratio and adipose tissue distribution: contribution of subcutaneous adiposity.

The waist-to-hip ratio (WHR) reflects the relative distribution of adipose tissue in the human body. However, whether this is due to the musculoskeletal structures of the waist and hip or the overlying subcutaneous adipose tissue has been disputed. We measured waist and hip girths in 11 male and 11 female cadavers, aged 55-94 years, before and after complete removal of skin and subcutaneous adipose tissue. Girths measured following removal of subcutaneous adipose tissue were termed "waist gx" and "hip gx", and their ratio "WHRx". Masses of regional adipose tissue segments were obtained by complete dissection, and the adipose mass ratios "trunk/arm-plus-leg", "trunk/leg", "internal/arm-plus-leg", and "internal/leg" were derived. As assessed by analysis of variance, WHR accounted for significant (P < 0.05) portions of the variance in all adipose mass ratios; adjustment for internal adipose mass increased the significance of all these relationships (P < 0.005). The ratio WHRx was not related to any ratio of regional adipose masses. Waist girth was related to trunk (P < 0.001) and internal (P < 0.05) adipose masses, and hip girth was related to arm-plus-leg adipose mass (P < 0.0001) and leg adipose mass (P < 0.0001), but waist gx and hip gx were not related to dependent variables. The results indicate that the ability of WHR and waist and hip girths to reflect the regional distribution of adipose tissue in the body is dependent upon the subcutaneous adipose tissue mass of the waist hip area, not its musculoskeletal constituency.

Adipose Tissue↗

PubMed2001

Heat treatment of amphotericin b modifies its serum pharmacokinetics, tissue distribution, and renal toxicity following administration of a single intravenous dose to rabbits.

The purpose of this investigation was to determine the serum pharmacokinetics, tissue distribution, and renal toxicity of amphotericin B (AmpB) following administration of a single intravenous dose (1 mg/kg of body weight) of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to New Zealand White female rabbits. FZ solutions were heated at 70 degrees C for 20 min to produce HFZ. Blood samples were obtained before drug administration and serially thereafter. After collection of the 48-h blood sample, each rabbit was humanely sacrificed and the right kidney, spleen, lungs, liver, and heart were harvested for AmpB analysis. Serum creatinine levels were measured before and 10 h after drug administration. AmpB concentrations in the serum and tissues were analyzed using high-performance liquid chromatography. FZ administration to rabbits resulted in a greater-than-50% increase in serum creatinine concentrations compared to baseline. However, HFZ administration resulted in no difference in serum creatinine concentrations compared to baseline. The AmpB area under the concentration-time curve (AUC) after HFZ administration was significantly lower than the AmpB AUC in rabbits administered FZ. However, AmpB systemic total body clearance was significantly greater in rabbits administered HFZ than in rabbits administered FZ without any differences in volume of distribution at steady state. Kidney tissue AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. Likewise, lung and spleen AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. However, liver AmpB concentrations were significantly lower in rabbits administered FZ than in rabbits administered HFZ. No significant differences in heart AmpB concentration between rabbits administered FZ and those given HFZ were found. These findings suggest that the pharmacokinetics, tissue distribution, and renal toxicity of AmpB are modified following administration of HFZ. HFZ could be an improved low-cost AmpB drug delivery system that has a potentially higher therapeutic index than FZ.

Amphotericin B↗

PubMed1989

Obesity, adipose tissue distribution and health in women--results from a population study in Gothenburg, Sweden.

The associations between generalized obesity measured as body mass index (BMI), or adipose tissue distribution, measured as the waist/hip circumference ratio (WHR), on one hand, and a number of socioeconomic, somatic as well as psychologic and mental health variables on the other, were analysed in a population study of women (1462 participants, aged 38-60 years, participation rate 90.1%). The anthropometric measurements were adjusted for their influence on each other. BMI, but not WHR, was negatively associated with socioeconomic status and education. Increased WHR correlated to a number of somatic diseases from different organ systems, including diabetes mellitus, infectious respiratory and abdominal diseases. Even more striking were strong correlations to a number of variables indicating accident proneness as well as mental disorder, and increased use of antidepressants and tranquilizers. BMI and WHR were also associated to different personality profiles. Furthermore, the use of alcohol and smoking were positively correlated to the WHR. In contrast, most of these associations were not seen with the BMI--sometimes even negative correlations were found. Exceptions were, however, varicose veins, joint problems and surgery for gall bladder disease, which were positively correlated to BMI only. Blood pressure, plasma triglycerides and uric acid were positively correlated to both BMI and the WHR, plasma cholesterol, however, only to the WHR. Obesity (high BMI) and abdominal adipose tissue distribution (high WHR) clearly show differences in their associations to various health variables. It is hypothesized that an arousal syndrome might be a contributing factor to cause symptoms of psychological maladjustment, including psychosomatic disease. Hypothetically, in parallel, an accumulation of depot fat in the abdominal depot, might follow as a consequence of neuroendocrine dysregulation of endocrine secretions.

Adipose Tissue↗

PubMed2004

Tissue distribution of AU-rich mRNA-binding proteins involved in regulation of mRNA decay.

Short lived cytokine and proto-oncogene mRNAs are destabilized by an A+U-rich element (ARE) in the 3'-untranslated region. Several regulatory proteins bind to AREs in cytokine and proto-oncogene mRNAs, participate in inhibiting or promoting their rapid degradation of ARE mRNAs, and influence cytokine expression and cellular transformation in experimental models. The tissue distribution and cellular localization of the different AU-rich binding proteins (AUBPs), however, have not been uniformly characterized in the mouse, a model for ARE mRNA decay. We therefore carried out immunoblot and immunohistochemical analyses of the different AUBPs using the same mouse tissues. We show that HuR protein, a major AUBP that stabilizes the ARE mRNAs, is most strongly expressed in the thymus, spleen (predominantly in lymphocytic cells), intestine, and testes. AUF1 protein, a negative regulator of ARE mRNA stability, displayed strong expression in thymus and spleen cells within lymphocytic cells, moderate expression in the epithelial linings of lungs, gonadal tissues, and nuclei of most neurons in the brain, and little expression in the other tissues. Tristetraprolin, a negative regulator of ARE mRNA stability, displayed a largely non-overlapping tissue distribution with AUF1 and was predominantly expressed in the liver and testis. KH-type splicing regulatory protein, a presumptive negative regulator of ARE mRNA stability, was distributed widely in murine organs. These results indicate that HuR and AUF1, which functionally oppose each other, have generally similar distributions, suggesting that the balance between HuR and AUF1 is likely important in control of short lived mRNA degradation, lymphocyte development, and/or cytokine production, and possibly in certain aspects of neurological function.

Animals↗

PubMed1997

Tissue distribution of the cytofectin component of a plasmid-DNA/cationic lipid complex following intravenous administration in mice.

Allovectin-7 is a gene therapy agent that consists of plasmid DNA (pDNA) encoding the human HLA-B7 class I and beta2-microglobulin genes (VCL-1005), complexed with the cationic lipid DMRIE Br and DOPE. A tritiated version of the cytofectin component, DMRIE Br, was synthesized by regiospecific isotope incorporation to a very high specific activity. The 3H-labeled DMRIE/DOPE mixture was complexed with VCL-1005 to produce a radiolabeled version of Allovectin-7. The VCL-1005/3H-DMRIE/DOPE complex was administered intravenously to mice, and the tissue distribution of radioactivity was analyzed 24 hr later. Excretion of radioisotope was monitored for 96 hr post dosing. At 24 hr post administration, a tissue distribution for the radioisotope of liver >> spleen > lung >> heart > brain approximately muscle approximately blood was observed. During the 96-hr period post dose, very little administered radioactivity (<17%) was excreted and the majority of the isotope (83%) remained in the animal. This is the first report on the biodistribution of the cytofectin component of a pDNA-cationic lipid complex for which the distribution of the plasmid component has also been reported.

Animals↗

PubMedDate not supplied

Pitfalls when determining tissue distributions of organophosphorus chemicals: sodium fluoride accelerates chemical degradation.

This paper describes the tissue distributions of dichlorvos, an organophosphate, and chlorpyrifos-methyl, an organophosphorothioate, in a male individual who died after ingesting an insecticidal preparation containing these chemicals and the results of an in vitro stability study on dichlorvos and chlorpyrifos-methyl in blood and buffers. Tiny amounts of dichlorvos, 0.067 and 0.027 mg/L, were detected in the vitreous humor and cerebrospinal fluid, respectively. Although dichlorvos (0.082-8.99 mg/L or mg/kg) was detected in the thoracic aortic blood, thoracic inferior vena caval blood, pericardial fluid, bile, and spleen, it was strongly suggested that it had diffused postmortem from the stomach, which contained 879 mg, because no dichlorvos was detected in the other blood samples and tissues tested. Substantial amounts (0.615-4.15 mg/L) of chlorpyrifos-methyl were detected in all blood samples, and the order of its concentrations was as follows: pulmonary vessel blood > thoracic inferior vena caval blood > blood in the right cardiac chambers > blood in the left cardiac chambers approximately thoracic aortic blood > right femoral venous blood. The total amount of chlorpyrifos-methyl in the stomach was 612 mg. However, it was strongly suggested that virtually no chlorpyrifos-methyl diffused from the stomach into surrounding fluids and tissues postmortem because no chlorpyrifos-methyl was detected in the bile and little was found in the pericardial fluids. Neither compound was detected in the urine. In vitro experiments showed that dichlorvos (10 mg/L) almost disappeared from fresh (pH 7.4) and acidified (pH 6.2) blood samples within 24 and 72 h, respectively. However, 53 and 77% of the original amount of dichlorvos in 0.05M phosphate buffers at pH 7.4 and 6.2 were detected 72 h later. Chlorpyrifos-methyl (1 mg/L) was very stable in blood samples, regardless of the pH, during the 72-h study period, but in the pH 7.4 and 6.2 phosphate buffers, approximately 80% of the original amount had degraded after 72 h. These results indicate that organophosphates are degraded more rapidly by esterase activities than by chemical mechanisms and that organophosphorothioates are hydrolyzed chemically in aqueous solutions but are very stable in biological specimens and not metabolized by esterases. When sodium fluoride was added to blood samples, dichlorvos degraded completely within 15 min, and chlorpyrifos-methyl became very unstable. Thus, when analyzing samples to detect organophosphorus chemicals, this common preservative should not be added to fluid specimens.

Aged↗