Biomedical subjects

P Mushak

Publications and source records attributed to P Mushak.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Quantitative analysis of total and trimethyl lead in mammalian tissues using ion exchange HPLC and atomic absorption spectrometric detection.

Measurement of total and trimethyl lead in mammalian tissue is described, using ion exchange/high performance liquid chromatography in tandem with flameless atomic absorption spectrometry for lead-specific detection. All lead forms in whole blood and homogenates of soft tissue--brain, kidney, and liver--were liberated from tissue binding by treatment with dilute (3N) HCl for a period of 18 hr. Trimethyl lead was partitioned into chloroform/ethyl acetate after media neutralization to pH of approximately 4 and saturation with sodium chloride. The extract was chromatographically analyzed on a Partisil SCX-10 cation exchange column, using 0.167M ammonium citrate in methanol:water (70:30) as mobile phase. Fractions of eluate were collected using a programmable fraction collector, and the fractions collected from 3.5 to 5.0 min were analyzed by atomic absorption spectrometry. Total lead in tissue was measured by acid wet digestion and flameless atomic absorption spectrometry. The difference in the values from both analyses provided a measure of any trimethyl lead metabolites.

Animals↗

PubMedDate not supplied

Risk and revisionism in arsenic cancer risk assessment.

Oral exposures of nonoccupational populations to environmental inorganic arsenic are associated with skin and internal cancers as well as various noncarcinogenic effects. Cancer risk assessments have been based largely on epidemiological studies of a large population exposed to inorganic arsenic in well water in Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating arsenic cancer risks outside of Taiwan, including potential use by the U.S. Environmental Protection Agency for regulatory purposes, have been expressed on various grounds. The nature and extent of such criticisms have sharpened with recent findings in the exposed Taiwanese of increased incidence of internal cancers (bladder, kidney, liver, and lung), in addition to already-observed skin cancer, coupled with a good likelihood that these findings will produce more stringent arsenic regulation in the United States and elsewhere. These criticisms collectively posit a revisionist view that: 1) cancer incidence among the Taiwanese was amplified by a number of host and environmental factors not applicable elsewhere, 2) the cancer dose-response curve may not be linear at the lower exposures elsewhere, and 3) there is a toxicokinetic and metabolic threshold to cancer risk that was exceeded by the Taiwanese. However, a number of the arguments against wide use of the Taiwanese data are flawed and subject to challenge. We explore some of these arguments and their critical evaluation, particularly as they concern certain exposure, metabolic, and nutritional determinants of the cancer risk of inorganic arsenic in the Taiwanese.

Adult↗

PubMedDate not supplied

Comparative organotin toxicity in the developing rat: somatic and morphological changes and relationship to accumulation of total tin.

The effect of the structure of organotin compounds on their toxicity and neurotoxicity to the developing rat has been studied. Oral administration was used after selection of a vehicle that gave uniform organotin solubilization as evidenced by toxicity and chemical solubility data. This vehicle was milk plus Tween-80. Eight different organotin compounds were systematically surveyed for effects in the neonatal rat. Trimethyl- and triethyltin were most toxic, and were somewhat more toxic than tri-n-propyltin. Tri-n-butyltin was somewhat less toxic, while tricyclohexyl-, triphenyl-, diethyl- and dimethyltin were least toxic. Some higher doses of trimethyl- or triethyltin caused neuropathological changes that were characteristic for each compound, these changes being absent for the other agents. Regardless of their toxicity, significant amounts of tin, as the element, were found in brain, kidney, and liver after treatment with all agents. However, detectable blood values were only obtained for trimethyl- and triethyltin.

Administration, Oral↗

PubMedDate not supplied

New directions in the toxicokinetics of human lead exposure.

An important determinant of body lead (Pb) burden and Pb toxicity in exposed humans is Pb metabolism, or more correctly, Pb toxicokinetics. It affects the former through the quantitative processes of uptake, distribution and retention/excretion and the latter via delivery of toxic doses to cellular/molecular sites of action. Pb toxicokinetics has useful application in understanding Pb's behavior in populations. Several of these applications have been studied and results are presented for the toxicokinetic basis of dose-neurotoxic effect relationships in selected longitudinal studies and the use of toxicokinetic modeling for estimation of body lead burden in early populations. Three well-known, ongoing longitudinal studies of developmental neurotoxicity--in Boston, Cincinnati, and Port Pirie, Australia--involve cohorts who differ markedly as to their pre- and postnatal lead exposure profiles. Toxicokinetic examination of these exposure differences helps to explain the temporal variability seen in blood Pb-toxic effect relationships and supports a causal role for lead. Toxicokinetic models of Pb uptake and in-vivo behavior are increasingly being considered for estimating Pb-B levels in lieu of direct measurement. A linear biokinetic model, using reliable input data for natural/prehistoric levels of Pb in sources, was applied to estimation of prehistoric/preindustrial children's blood lead. A range of 0.06 to 0.12 microgram/dl was estimated for two lead intakes. These estimates are still two orders of magnitude (85 to 165-fold) lower than the newly issued CDC toxicity guideline for children of 10 micrograms/dl. Lastly, the toxicokinetics of lead in bone, particularly its resorption with metabolic stimuli, is of concern, particularly for "baby boom" women who are either of childbearing age or approaching menopause and who had greatly elevated environmental lead exposures in the 1940s to 1970s.

Developing Countries↗