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Biomedical subjects

D E Carter

Publications and source records attributed to D E Carter.

At least 55 records · Page 3Linked to original sources
PubMed1989

Dermal absorption of phthalate diesters in rats.

This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the [14C]phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of 14C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hr decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied 14C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal and showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.

Animals↗
PubMed1989

Reaction of gallium arsenide with concentrated acids: formation of arsine.

Crystalline particles of gallium arsenide (GaAs) (approximately 2 microns in diameter) react with concentrated hydrochloric acid (HCl) (11.6 to 9 M) to form highly toxic arsine (AsH3) gas. None of the other strong acids that were investigated reacted with gallium arsenide to form AsH3. A spectrophotometric method, based on the reaction of AsH3 with silver diethyldithiocarbamate in a chloroform solution containing morpholine, was used to detect AsH3 gas dissolved in aqueous solutions and to determine the AsH3 gas that was liberated by the reaction of GaAs with HCl. Active sites on the gallium arsenide surface initiate the reaction that forms AsH3 gas. Absorption of oxygen or ions from solution on these active sites inhibits the formation of AsH3.

Arsenic↗
PubMed1989

Dissolution of crystalline gallium arsenide in aqueous solutions containing complexing agents.

Crystalline gallium arsenide (GaAs) was found to dissolve in an aqueous solution containing the inorganic anions, chloride, sulfate, bicarbonate, monohydrogen phosphate, and dihydrogen phosphate, and the organic anions, acetate and citrate. The aqueous solution was made up to resemble lung fluid (Gamble solution) and was maintained at a pH of 7.4. The concentrations of arsenic (As) and gallium (Ga) in solution and the As-GA ratio on the surface of the GaAs increased continuously as the time of contact with the aqueous solution increased. X-ray photoelectron spectroscopic studies of the GaAs surface, at various time intervals, showed that As migrated to the surface and was oxidized to a species resembling As2O3 and, finally, was dissolved. The zinc present in the crystalline GaAs also migrated to the surface.

Arsenic↗
PubMed1988

Evaluation of a self-instructional method for improving doctor-patient communication.

The purpose of the project reported here was to develop and evaluate an educational intervention to improve the interviewing skills learned in medical school. Sixty fourth-year medical students in a required ambulatory care rotation were randomly selected and randomly assigned to one of four conditions. All students interviewed a simulated patient who presented with one of five main complaints, and the interview was videotaped. Students were assigned to a control group or to one of three intervention groups: viewing a self-instruction videotape, viewing and critiquing a videotape of their interview, or both of these activities. The students assigned to the control group did not participate in any educational interventions. At the end of the intervention period, the students again interviewed a simulated patient and were videotaped. The 120 videotaped interviews were reliably rated by a scoring system developed by the project team. The postintervention interviews conducted by students in the two groups that used the self-instruction videotape received significantly higher ratings than those in the control group. These results suggest that this self-instruction intervention can improve the interviewing skills of senior medical students.

Ambulatory Care↗
PubMed1987

Metabolism and excretion of gallium arsenide and arsenic oxides by hamsters following intratracheal instillation.

The increasing use of gallium arsenide (GaAs) in the electronics industry has produced the need for pharmacokinetic and toxicologic data on GaAs. The disposition in male Syrian golden hamsters (n = 4) following intratracheal instillation of GaAs (mean volume diameter 5.8 micron), arsenic (III) oxide (arsenite), and arsenic (V) oxide (arsenate) at a dose of 5 mg/kg body weight was examined. Blood, kidney, liver, and lung samples were collected at 1, 2, and 4 days after administration. Excreta were collected daily. Urinary metabolite profiles were determined after separation on a mixed anion-cation-exchange column. Total As content was analyzed by direct hydride flame atomic absorption spectrophotometry after digestion. Arsenic blood levels after GaAs, arsenite, and arsenate administration were 0.185 +/- 0.041, 0.596 +/- 0.117, and 0.310 +/- 0.045 ppm, respectively, after Day 1. Arsenic blood levels after GaAs administration increased to 0.279 +/- 0.021 ppm on Day 2 indicating continued absorption while levels decreased for the arsenite and arsenate groups. At Day 1 the liver contained 0.565 +/- 0.036, 2.62 +/- 0.26, and 0.579 +/- 0.144% of the arsenic dose of GaAs, arsenite, and arsenate, respectively. The arsenite and arsenate were rapidly excreted in the urine with almost half the dose appearing after 4 days; in contrast, only about 5% of the GaAs was found at the corresponding time. Total recoveries, as arsenic equivalents, for the three compounds were between 75 and 80%. Ratios of the two major urinary metabolites (dimethylarsinic acid/total inorganic As species) were 1.41, 1.71, and 0.983 for GaAs, arsenite, and arsenate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1987

Pulmonary clearance and toxicity of respirable gallium arsenide particulates intratracheally instilled into rats.

Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry.

Animals↗
PubMed1986

Comparative pulmonary toxicity of gallium arsenide, gallium(III) oxide, or arsenic(III) oxide intratracheally instilled into rats.

The relative toxicity of gallium arsenide (GaAs) and its metal oxides was assessed by intratracheally instilling particulate suspensions of GaAs (100 mg/kg), equimolar gallium as Ga2O3 (65 mg/kg), or a maximally tolerated nonlethal dose of arsenic as As2O3 (17 mg/kg). Two weeks after dosing, five rats from each group were randomly selected for the biochemical determination of lung lipid, protein, DNA, and collagen (4-hydroxyproline; 4-HP) content. The pulmonary retention of gallium and/or arsenic and the concentration of these metals in blood were also determined. Lungs from the remaining rats (n = 3) were examined histopathologically. Pulmonary exposure to Ga2O3 particulates significantly (p less than 0.05) increased the total lipid content of lungs relative to that observed in the vehicle-treated control animals. This response appeared to be associated with the pulmonary retention of gallium particulates (means = 36% of the gallium dose). In contrast, As2O3 particulates were not retained in the lung. Blood arsenic concentrations were 36 ppm which represented 20% of the total arsenic administered. Treatment with As2O3 significantly elevated lung dry weight as well as protein, DNA, and 4-HP content. These data suggest that As2O3 induced an acute fibrogenic response. The intratracheal instillation of GaAs particulates produced effects similar to those observed with the individual oxides. The total lung content of lipids, protein, and DNA was significantly elevated. These biochemical changes were accompanied by significant increases in lung dry weight and lung wet weight. Lungs from rats receiving GaAs particulates retained 44% of the dose as gallium and 28% of the dose as arsenic at the end of the 14-day study. Blood arsenic concentrations were 44 ppm (7% of the arsenic dose) while gallium was not detected in blood at this time. The primary histopathological observations 14 days after the intratracheal instillation of all metal particulates were an inflammatory response and pneumonocyte hyperplasia. The biological severity of these lesions, in descending order, was GaAs greater than As2O3 much greater than Ga2O3. It must be noted, however, that As2O3 was dosed at 0.25 X moles of GaAs.

Analysis of Variance↗
PubMed1986

Examination of the differential hepatotoxicity of diallyl phthalate in rats and mice.

In this study we confirmed that diallyl phthalate (DAP) is more hepatotoxic to rats than to mice, and we demonstrated the same species difference in toxicity for allyl alcohol (AA). The data suggest that the toxicity of DAP probably results from AA cleaved from DAP. To determine if the species difference in susceptibility to hepatotoxicity resulted from differences in the disposition and metabolism of DAP, Fischer-344 rats and B6C3F1 mice were given [14C]DAP, 1, 10, or 100 mg/kg po or 10 mg/kg iv, and placed in metabolism cages for 24 hr. In rats, 25-30% of the DAP was excreted as CO2, and 50-70% appeared in the urine within 24 hr. In mice, 6-12% of the DAP was excreted as CO2, and 80-90% was excreted in the urine within 24 hr. Monoallyl phthalate (MAP), allyl alcohol, 3-hydroxypropylmercapturic acid (HPMA), and an unidentified polar metabolite (PM) were found in the urine of rats and mice dosed with DAP. The polar metabolite was present in the urine of rats dosed with DAP or AA, indicating that the compound is a metabolite of AA. There was no difference between the species in the quantity of AA excreted, but mice excreted more MAP (39 vs 33%), HPMA (28 vs 17%), and PM (20 vs 8%) than rats. Because DAP is metabolized to AA, a potent periportal hepatotoxicant, and because the mouse produced more HPMA than rats, we postulate that the differential hepatotoxicity of DAP is related to the extent of glutathione conjugation with allyl alcohol or acrolein (the active metabolite of AA).

1-Propanol↗
PubMed1986

Distribution, excretion, and metabolism of butylbenzyl phthalate in the rat.

The disposition of butylbenzyl phthalate (BBP), a widely used plasticizer, was evaluated after oral and iv administration to rats. Male Fischer-344 rats were dosed with [14C]BBP at 2, 20, 200, or 2000 mg/kg po or 20 mg/kg iv to determine the effects of dose on rates and routes of excretion. In 24 h, 61-74% of the dose was excreted in the urine and 13-19% in the feces at 2-200 mg/kg. At the 2000-mg/kg dose, 16% of the 14C was excreted in the urine and 57% in the feces. Urinary 14C was composed of monophthalate derivatives (MP: 10-42% of the dose) and glucuronides of these monophthalate derivatives (2-21% of the dose). At 4 h after iv administration of BBP (20 mg/kg), 53-58% of the dose was excreted in the bile of anesthetized rats. No parent compound was found in the bile, but monobutyl phthalate-glucuronide and monobenzyl phthalate-glucuronide (26% and 13% of the dose, respectively) and trace amounts of free monoesters (2% of the dose) and unidentified metabolites (14% of the dose) were present. Although BBP is an asymmetric diester with the potential of forming equal amounts of monobutyl phthalate (MBuP) and monobenzyl phthalate (MBeP), larger quantities of MBuP were formed (MBuP = 44% versus MBeP = 16% of the dose). The half-lives of BBP, MP, and total 14C in blood (20 mg/kg, iv) were 10 min, 5.9 h, and 6.3 h, respectively. This study indicates that BBP is rapidly metabolized and that the major route of excretion of metabolites is biliary. These metabolites are reabsorbed and ultimately eliminated in the urine.

Administration, Oral↗
PubMed1986

Excretion and tissue disposition of dichloroacetonitrile in rats and mice.

The excretion and tissue distribution of [1-14C]dichloroacetonitrile and [2-14C]dichloroacetonitrile were studied in male Fischer 344 rats and male B6C3F1 mice. Three dose levels of dichloroacetonitrile (DCAN) (0.2, 2, or 15 mg/kg) were administered to rats and two dose levels of DCAN (2 or 15 mg/kg) to mice. Daily excreta including exhaled volatiles and radiolabeled carbon dioxide (14CO2) were analyzed for radiolabeled carbon (14C) until greater than 70% of the radioactivity was excreted. At that time the animals were sacrificed and tissues were collected. Tissues and excreta were analyzed for 14C by combustion and liquid scintillation counting. Rats administered [1-14C]DCAN excreted 62 to 73% of the 14C in 6 days, with 42 to 45% in urine, 14 to 20% in feces, and 3 to 8% as CO2. Rats administered [2-14C]DCAN excreted 82 to 86% of the 14C in 48 hr, with 35 to 40% in urine, 33 to 34% as CO2, and 10 to 13% in feces. Mice administered [1-14C]DCAN excreted 83 to 85% of the 14C in 24 hr, with 64 to 70% in urine, 9 to 13% in feces, and 5 to 6% as CO2. Mice administered [2-14C]DCAN excreted 84 to 88% of the 14C in 24 hr with 42 to 43% in urine, 8 to 11% in feces, and 31 to 37% as CO2. Liver tissues retained the most 14C in all studies except the study of [1-14C]DCAN in rats, where blood contained the most 14C. These results indicate that DCAN was absorbed rapidly after oral administration in water. The differences in the route of excretion of [1-14C]DCAN compared to [2-14C]DCAN indicated that the molecule was being cleaved in the body and metabolized by different mechanisms.

Acetonitriles↗
PubMed1984

N-(2,3-dimercaptopropyl)phthalamidic acid: protection, in vivo and in vitro, against arsenic intoxication.

The ip LD50s of N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) and British Anti-Lewisite (BAL) were 0.819 and 1.48 mmol/kg, respectively, in male albino mice. The ip ED50 of DMPA and BAL for prevention of the lethal effects of 0.15 mmol NaAsO2/kg was 0.022 and 0.169 mmol/kg, respectively. DMPA increased the LD50 of sodium arsenite by approximately 2.5-fold following two ip injections of 0.20 mmol DMPA/kg. The effectiveness of DMPA in reducing the toxicity of NaAsO2 was further demonstrated by its reversal of the sodium arsenite inhibition of pyruvate dehydrogenase multienzyme complex (PDH) activity in vitro. Similarly, in an in vivo experiment in which mice received 0.10 mmol NaAsO2/kg, and 30 min later were given 0.05 or 0.10 mmol/kg DMPA, there was a rapid recovery of PDH activity. The distribution of 74As in the tissues of male New Zealand rabbits was altered following im injection of 0.20 mmol/kg DMPA. Under these conditions, the tissue concentration of 74As was significantly decreased. For all tissues tested, the 74As content decreased by at least 50% as compared to that of untreated controls. DMPA was effective also in increasing both urinary and fecal excretion of arsenic. The stability of aqueous solutions of DMPA varies with the pH of the solution. DMPA is more stable in acid solution.

Animals↗
PubMed1984

In vitro solubility and in vivo toxicity of gallium arsenide.

The in vitro solubilities of gallium arsenide (GaAs) and its metal oxides were arsenic(III) oxide greater than GaAs much greater than gallium(III) oxide. GaAs dissolution was also dependent upon the type and concentration of buffer anion. The amount of arsenic dissolved in 12 hr by various aqueous media was 0.2 M phosphate buffer greater than or equal to 0.1 M phosphate buffer greater than Krebs-Hensleit buffer greater than distilled H2O greater than HCl-KCl buffer. GaAs was apparently soluble under in vivo conditions. Blood arsenic concentrations in rats 14 days after intratracheal instillation of 10, 30, or 100 mg/kg GaAs were 5.5, 14.3, and 53.6 micrograms/ml, respectively; gallium was not detected at any doses. An increase in lung wet weight at 14 days was dose dependent with these organs retaining 17 to 42% of the dose as gallium or arsenic. Excretion of gallium and arsenic was limited to the feces. Urinary porphyrin concentrations and body weight, monitored as indices of toxicity, were significantly altered over the 14-day study. The analysis of porphyrins revealed that uroporphyrin replaced coproporphyrin as the primary urinary metabolite. Rats receiving 10, 100, or 1000 mg/kg GaAs po exhibited similar signs of toxicity. Blood arsenic concentrations at 14 days were 3.5, 6.8, and 17.6 micrograms/ml, respectively. Porphyria was increased, and body weight was decreased at 1000 mg/kg GaAs. These values were equivalent to those obtained with an intratracheal dose of 10 to 30 mg/kg GaAs. Our results showed that pulmonary and po exposure to GaAs resulted in systemic arsenic intoxication. The finding that urinary uroporphyrin concentrations were greater than coproporphyrin concentrations may serve as a sensitive indicator for GaAs exposure.

Animals↗
PubMed1984

Disposition of 1,2,3-trichloropropane in the Fischer 344 rat: conventional and physiological pharmacokinetics.

To investigate the disposition of 1,2,3-trichloropropane (TCP), [14C]-TCP was administered iv to male Fischer 344 rats. Unchanged TCP and total radiolabel were determined in tissues and excreta at varying intervals after administration. The compound was distributed and eliminated rapidly. Initial and terminal half-lives of unchanged TCP in the blood were 0.29 and 23 hr. Adipose tissue accumulated 37% of the dose within 15 min and retained more of the dose than any other tissue until 4 hr; most (69%) of the radiolabel in adipose tissue through 4 hr was unchanged TCP. After 4 hr, the liver contained the largest fraction of the dose, primarily as metabolites. Thus TCP disappeared from adipose tissue while metabolites appeared in liver and other tissues. Excretion was nearly complete (90% of the dose) in 24 hr and was predominantly via the urine (47% of the dose). Expiration was the only route by which unchanged TCP (5% of the dose) was excreted. In addition, 25% of the dose was expired as carbon dioxide. There were numerous other metabolites, none accounting for more than 10% of the dose. Nonvolatile metabolites were longer lived than the parent compound. On the basis of high water solubility, reaction with 2,4-dinitrofluorobenzene, and diminished radiolabel in bile of glycidol-treated rats, glutathione conjugation is suggested as an important metabolic route for TCP. A physiological pharmacokinetic model was developed to describe the time course of trichloropropane concentration in tissues. The model demonstrates the possibility of using physiological and pharmacokinetic data to predict concentration-time relations for toxic compounds.

Animals↗
PubMed1984

DMSA, DMPS, and DMPA--as arsenic antidotes.

meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3- dimercaptopropyl )- phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA greater than DMPS greater than DMPA greater than BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite . DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite . The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and biotransformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.

Animals↗
PubMed1984

Toxicity of a phthalate ester in the diet of a penaied shrimp.

The toxicity of di-2-ethylhexyl phthalate (DEHP), a ubiquitous environmental pollutant, was measured experimentally as a contaminant in shrimp aquaculture feeds. Diets containing 40 to 50,000 ppm DEHP were fed to Penaeus vannamei for 14 d at 4% body weight/d. DEHP concentrations in shrimp, diet, and water were measured by electron-capture gas chromatography. Whole-body residues in shrimp were 18 ppm at the highest dose, and bioconcentration factors were inversely proportional to dose. DEHP in water was less than or equal to 1.7 ppb for all dose levels. No increased mortality or histopathological alterations were observed at any dose. Absorption of DEHP by P. vannamei was measured in static 24- and 96-h bioassays. Diets enriched with [14C]DEHP to levels of 60, 600, and 6000 ppm were fed at 2% body weight/d. At all dose levels, 3.7% of total radioactivity was measured as body burden in shrimp and 40% as polar species in test water after 96 h. DEHP by oral administration was absorbed, metabolized, and excreted, and this process was linear with dose for the dose range studied.

Analysis of Variance↗
PubMed1984

Comparison of 2,2',4,4',5,5'-hexachloro[14C]biphenyl levels in different adipose tissues of dogs and monkeys.

The polychlorinated biphenyl isomer, 2,2',4,4',5,5'-hexachloro[14C]biphenyl (2,4,5-HCB) was administered as a single iv dose at 0.6 mg/kg to dogs and monkeys. Adipose tissue, which included omentum, pericardial, perirenal, peritesticular, and subcutaneous fat, and blood were collected at various termination times and analyzed for total 14C and the parent hexachlorobiphenyl (HCB). Significant differences (p less than 0.0005) in the total hexachlorobiphenyl concentration as measured by total radioactivity (14C equivalents) were noted in the various adipose tissues and in the same adipose tissues with time. Peritesticular fat was consistently lower in the concentration of 14C equivalents than the other adipose tissues, which were nearly equal. The concentrations in subcutaneous fat samples were inconsistent. Total 14C equivalent concentrations in the adipose tissues either peaked or reached a maximum at Day 1 and Day 4 for dog and monkey, respectively. However, parent HCB fat/blood ratios continually increased over the time course of the experiment, because concentrations in blood decreased more rapidly than those in adipose tissue.

Adipose Tissue↗
PubMed1983

The effect of intestinal esterase inhibition on the in vivo absorption and toxicity of Di-n-butyl phthalate.

Inhibition of intestinal mucosal esterases by S,S,S-tributylphosphorotrithioate (DEF) did not alter the gastro-intestinal absorption of di-n-butyl phthalate (DBP) in the rat. After intragastric administration of [14C]DBP to control and esterase-inhibited animals, the disappearance of 14C from the small intestine and the levels of 14C in the blood were not significantly different in the two groups over the first 4 hr. Peak blood levels of 14C occurred 2 hr after dosing in both groups of rats. The circulating [14C]butyl phthalate in the diester form accounted for less than 5% of the total 14C at 2 hr, regardless of intestinal esterase activity. The remaining 14C was associated with mono-n-butyl phthalate or more polar metabolites. These data suggest an important role for pancreatic esterases, which may be protected from DEF-mediated inhibition by storage in zymogen granules, in the metabolism and absorption of DBP.

Animals↗