Human Tissue Concentrations Research Articles

Distribution and excretion of 2,2′,4,4′,5,5′-hexabromobiphenyl in rats and man: Pharmacokinetic model predictions

A mathematical model was developed to describe the pharmacokinetics of 2,2′,4,4′,5,5′-hexabromobiphenyl (HBB) in rats and man. Rats were given single iv or multiple oral doses of [ 14C]HBB and tissue distribution and excretion data were obtained. A blood flow-limited physiological compartmental model was constructed and used to simulate the time course of HBB in rat tissues and excreta. Intestinal absorption of oral doses and reabsorption of HBB in bile could be accounted for by an effective permeability constant; a growing adipose tissue compartment was needed to properly describe the pharmacokinetics of HBB in growing rats. The model was then scaled to man by appropriately adjusting tissue volume, blood flow, and clearance and rate constant parameters. Human HBB tissue concentrations were predicted following an acute high-dose or a chronic low-dose exposure regimen, and the results compared to human data where available. As for the rat, adipose tissue had a significant effect on the HBB concentrations predicted in man. The estimated body burden t 1 2 in man was 6.5 years. It appears that at least for this compound, past exposure and present and future human tissue concentrations can be estimated by extrapolating pharmacokinetic results obtained in the rat.

Studies of trace-metal levels in human tissues--VI. Concerning the estimation of lead levels in human lung and vertebra with particular reference to formalin fixation.

The difficulties arising from the study of lead levels in lung and vertebra raise a number of matters relevant to all studies of trace element concentrations in human tissues. First, the fixation of tissues in formalin, prior to trace element analysis, should be avoided because of the likelihood of loss by leaching. Secondly, meaningful comparisons among different studies are difficult, if not impossible, to make unless standard conditions for the weight basis of expression of the results are used in preparing the tissues. Thirdly, if results are expressed as median metal concentrations, the mean concentration should also be given. Fourthly, authors must indicate the steps they have taken to ensure both the precision and accuracy of their data. Fifthly, it is desirable that there should be more consistency between different studies in the age groups used to show the relation (if any) between age and tissue metal levels. Sixthly, the value of a data set involving trace-metal levels in human tissues is enhanced if information on the tissue donors includes their smoking history. The contribution of cigarette smoking to renal cadmium levels is now well established.

Reproducibility of proton-induced elemental analysis in biological tissue sections

The reproducibility of trace element concentrations in biological tissue sections has been studied by a proton-induced X-ray fluorescence technique. With the use of beam defocusing and improved target preparations, a precision of ±20% was achieved. Applications for the simultaneous determinations of trace element concentrations in human tissues are demonstrated.

Toxicological Findings in Fatal Poisonings

Abstract Anyone who must decide whether the amount of toxic substance present in a specimen is sufficient to indicate that the substance may have been the cause of death is aware of the difficulty of finding information to guide that decision. Opinions are given concerning therapeutic and toxic concentrations in human tissues for most of the common drug and chemical poisons. These include alcohols, amitriptyline, amphetamine, arsenic, barbiturates, boron, bromides, carbon monoxide, chloral hydrate, chlordiazepoxide, cyanide, diazepam, diphenylhydantoin, ethchlorvynol, fluoride, glutethimide, heroin (morphine), imipramine, lead, LSD, marihuana, meperidine, meprobamate, methadone, methamphetamine, methaqualone, nicotine, nortriptyline, orphenadrine, paraldehyde, pentazocine, phenothiazines, propoxyphene, quinine, salicylates, and strychnine.

Lead concentrations in human tissues.

<b>Barry, P. S. L., and Mossman, D. B. (1970).</b><i>Brit. J. industr. Med.,</i><b>27,</b> 339-351. <b>Lead concentrations in human tissues.</b> A study of 69 subjects at post-mortem, four of whom had histories of occupational exposure to lead, demonstrated a marked difference in the lead concentrations between bones and soft tissues. The soft tissues of infants and young children contained low concentrations of lead, varying from 0·01 ppm in muscle to 0·46 ppm in liver. By the end of the second decade of life the concentrations of lead in most of the soft tissues showed values varying between 0·06 ppm in muscle and 1·35 ppm in liver and thereafter did not increase with advancing age. The concentrations of lead in bone were considerably greater than those in soft tissues, being about 1 ppm in infants and young children and increasing to more than 40 ppm in persons over the age of 50 years. Adult male bones contained more lead than adult females by a ratio of 3 to 2, and in both sexes the long bone contained concentrations of lead two and a half times that observed in the flat bone. No marked difference was noted in lead concentrations between the corresponding soft tissues of the two sexes. From the findings it appeared that in adults the total body burden varied widely from subject to subject. Nearly 95% was represented by the lead content in bone, of which more than 70% was in dense bone. A far lower concentration of lead was found in the bones of children than in those of adults, but there was less divergence in the lead concentrations in the soft tissues. The total lead content in the soft tissues of the majority of the subjects investigated appeared to be relatively stable and did not correlate with levels in bone. The four male subjects with known occupational exposure to lead had greater concentrations of lead in bone than those with no known occupational exposure, but no difference was noted in the soft tissues between the two groups, with the exception of the most heavily exposed subject in whom concentrations of lead in the brain were over 4 ppm and in the aorta 28 ppm. Hair and nails were found to contain relatively high concentrations of lead, approximately 20 ppm; some significance may be attached to this finding in a medico-legal context. The findings of this study would suggest that the present intake of lead among the general population is no greater than in the past.

A comparison of steroid hormone concentrations in human tissues including breast cancer.

A comparison of steroid hormone concentrations in human tissues including breast cancer.

Chromium, Cadmium and Lead in Rats:: Effects on Life Span, Tumors and Tissue Levels

Groups of 50 or more Long-Evans rats in a low metal environment and fed a diet devoid of cadmium and low in many trace metals were given 5 ppm chromium (III), cadmium or lead in drinking water from weaning until death. Life span was shortened in those fed lead and cadmium; tissue concentrations were within human ranges. Longevity of the last 10% was increased in those fed chromium; tissue concentrations were within ranges of young human beings, and females resisted an epidemic of pneumonia. Rats fed lead had fewer tumors than controls or other groups. Arteriolar sclerosis in kidneys and ventricular hypertrophy occurred largely in cadmium-fed animals; cirrhosis of the liver in all groups. Organs of controls were cadmium-free; the metal occurred in animals from another laboratory. Cadmium did not accumulate in kidneys at older ages. Older rats fed lead showed less in organs than younger ones. Chromium did not accumulate in tissues. Extension of life span by restriction of food was reproduced by restriction of lead and cadmium and feeding of chromium. Results indicate that lead and cadmium at human tissue concentrations are toxic to rats in terms of life span and longevity, whereas chromium (III) is not.

Two naturally occurring metabolites of progesterone, isolation, identifications, biologic activity and concentration in human tissue: Zander, J., Forbes, T. R., Von Munstermann, A. M., and Neher, R.: p. 337

Two naturally occurring metabolites of progesterone, isolation, identifications, biologic activity and concentration in human tissue: Zander, J., Forbes, T. R., Von Munstermann, A. M., and Neher, R.: p. 337