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Biomedical subjects

F E Guthrie

Publications and source records attributed to F E Guthrie.

At least 19 recordsLinked to original sources

In vitro penetration of pesticides through human newborn foreskin.

The in vitro dermal penetration of 14C-labelled parathion, fenvalerate, carbofuran, and lindane through fresh full-thickness human newborn foreskin was determined at 1, 6, 24, and 48 h. The pesticides were applied to a constant dosing area (0.031 cm2), and a fixed dose (1.18 microgram), for each of the compounds studied. 90%, or greater, of the labelled pesticides were recovered in all cases. Carbofuran showed the greatest mean penetration of 82% followed by parathion and lindane with mean penetrations of 79 and 66%, respectively. Fenvalerate exhibited a mean penetration of 9% which is significantly lower than that of the other three compounds. No difference was noted in the penetration of pesticides through human skin from blacks and whites.

Epidermis↗

A method for preparing mouse skin for assessing in vitro dermal penetration of xenobiotics.

A method is described for preparing mouse skin for assessment of in vitro penetration of dermally applied compounds. Separation of the epidermis from the dermis was attempted using a dermatome, heat, trypsin and collagenase. When mouse skin was incubated in a collagenase solution and separated using water, the hypodermis and part of the dermis were separated from the epidermis while leaving the hair follicles and hair shafts intact. Morphologically, the skins prepared for in vitro use appeared to offer similar barriers to topically applied compounds as those found in vivo.

Administration, Topical↗

Macrophage uptake of a lipoprotein-sequestered toxicant: a potential route of immunotoxicity.

An experimental system was chosen to investigate the bioactivity of a lipoprotein-sequestered toxicant at the cellular level based on recent studies demonstrating receptor-mediated uptake of lipoproteins by macrophages. Rat peritoneal exudate cell suspensions (PEC) were exposed to DDT and lipoprotein-sequestered DDT, followed by measurement of DDT uptake, metabolism, and cellular toxicity. In vitro uptake assays demonstrated that PEC suspensions treated for 10, 20, and 30 min with 2.5 microM lipoprotein-sequestered DDT had approximately a twofold increase over the amount of DDT associated with PEC treated with 2.5 microM free DDT. PEC were assayed for DDT metabolites to serve as a measure of the cellular internalization of the toxicant after treatment in vitro for 18 hr with either 1.5 microM DDT or lipoprotein-sequestered DDT. Evidence of DDT metabolism was only observed with PEC which had been treated with lipoprotein-sequestered DDT. These cells contained significantly higher amounts of DDT metabolites as compared to cells treated with unsequestered DDT (over an eightfold difference). Assays measuring macrophage phagocytic activity indicated that macrophages treated for 4.5 hr in vitro with 2.5 microM lipoprotein-sequestered DDT showed significant inhibition in their ability to phagocytize yeast particles. These results suggest that serum lipoproteins may facilitate the cellular uptake of lipoprotein-sequestered toxicants leading to altered cellular function (phagocytosis).

Animals↗

Target ricin by coupling to an anti-macrophage monoclonal antibody.

By altering the receptor binding specificity of the highly potent natural toxin ricin, a macrophage specific immunotoxin was developed. Ricin ordinarily does not demonstrate cell type specificity and is capable of binding and entering cells through galactose containing receptors resulting in rapid cell death. A murine anti-rat peritoneal macrophage IgGl monoclonal antibody, B-6, was developed to serve as a target specific carrier for ricin. By covalently binding monoclonal antibody B-6 and reversibly binding lactose to ricin, a new biologically active hybrid toxin possessing macrophage specificity was developed. When P3X63-Ag8.653 myeloma cells, which served as an nonspecific target cell type, and macrophages were treated with the ricin conjugate over a broad range of concentrations and various time periods, the conjugate demonstrated substantially greater toxicity toward macrophages than myeloma cells even though both cell types responded similarly to treatments with unconjugated ricin. It was also observed that ricin was considerably more toxic to macrophages when conjugated to monoclonal antibody B-6 than unconjugated ricin. Through ricin-antibody conjugation a high degree of specificity and toxicity can be attained potentially suitable for anti-tumor reagents and immuno-modulators.

Animals↗

A rapid spectrophotometric method for assessing macrophage phagocytic activity.

The method described provides a rapid and inexpensive in vitro assay of phagocytosis by mononuclear phagocytes. This assay utilizes yeast cells, stained with congo red, as the target particle and quantitation is performed spectrophotometrically. An attractive feature of this assay is that phagocytic activity is assessed using large sample sizes, in this case approximately 1 X 10(6) macrophages per sample, resulting in a more accurate evaluation of phagocytosis than assays dependent on microscopic quantitation.

Animals↗

Percutaneous penetration of three insecticides in rats: a comparison of two methods for in vivo determination.

Percutaneous penetration of three insecticides was studied by two methods. The indirect (excretion analysis) and direct (skin patch removal) methods for determining penetration were compared in rats. Radiolabeled solutions of parathion, carbaryl, and DDT were applied to previously shaved rats at the rate of 4 micrograms/cm2. Recoveries of radioactivity in urine, feces, application site, and various tissues were measured at intervals over a 5-day period. Urinary excretion rates were corrected for incomplete excretion by intraperitoneal applications. In the 5 days following intraperitoneal administration, the urinary excretion of parathion and carbaryl was greater than 80% while less than 5% of DDT was excreted. A good correlation was found between the indirect and direct methods utilized to determine percutaneous absorption rates with the compounds tested at the later time intervals. All compounds showed more than 85% dermal penetration within 5 days. At the early time intervals (greater than 24 h), penetration by the direct method was significantly greater for parathion and carbaryl than by the indirect method.

Animals↗

Comparative penetration of insecticides in target and non-target species.

Dermal penetration of 14C-labeled carbaryl, parathion, DDT, dieldrin and permethrin was compared in American roaches, tobacco hornworms, Japanese quail, grass frogs and mice. Insecticides were absorbed more quickly in mice (one exception) while entry into insects was generally slow. The half time penetration rates for carbaryl ranged from 6 min for frogs to 4600 min for roaches. Whereas permethrin penetrated easily into insects, other insecticides showed generally slower penetration into target organisms. Carbaryl tended to penetrate most rapidly in all species except roaches, while DDT and dieldrin tended to penetrate slowly in all organisms tested. Distribution of insecticides in the blood and liver of Japanese quail and grass frogs was surprisingly low. Insect species tended to show higher amounts in hemolymph than most other species. Excretion of radioactivity was relatively low in the frog in these experiments but was high in the quail for rapidly-metabolized compounds.

Absorption↗

In vitro uptake and transfer of chlorinated hydrocarbons among human lipoproteins.

The uptake, distribution, and exchange of chlorinated hydrocarbon insecticides (dieldrin and chlordecone) and biphenyls (2,4,5-2',4',5'-hexachlorobiphenyl and 3-chlorobiphenyl) among human lipoproteins was examined by fluorescence quenching, gel filtration, and ultrafiltration. The chlorinated hydrocarbons were rapidly taken up from solution or silica particles by lipoproteins. The distribution of chlorinated hydrocarbons among the lipoproteins was independent of the amount taken up by the lipoproteins. The partition coefficient for each lipoprotein and the serum concentration of individual lipoproteins determined the distribution pattern of chlorinated hydrocarbons among lipoproteins. The chlorinated hydrocarbons attached to albumin or one of the lipoproteins were rapidly transferred to all other lipoproteins. The exchange was complete in less than one minute. The role of rapid exchange of chlorinated hydrocarbons among lipoproteins in removal of these chemicals from blood and distribution to other tissues is discussed.

Biphenyl Compounds↗

Interaction of insecticides with human plasma lipoproteins.

The binding of chlorinated hydrocarbon, carbamate and organophosphate insecticides to human low density plasma lipoproteins (LDL) and high density plasma lipoproteins (HDL) was studied at pH 7.0 and 16 degrees C and 26 degrees C by equilibrium dialysis, difference spectra and fluorescence. The results suggest interaction to be a partitioning rather than a stoichiometric binding process. Distribution is related to lipid content and composition of the lipoproteins. The K-values vary from 3 x 10(5)M-1 for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) to less than 10 M-1 for nicotine and aldicarb, and delta G degrees tr is in the range of 7400 cal for DDT to less than 1000 cal for aldicarb and nicotine. The K and delta G degrees tr are inversely related to the water solubility of the insecticides. A significant role of plasma lipoproteins in the transport of slightly water soluble insecticides is suggested.

Humans↗

Exposure of field workers to organophosphorus insecticides: sweet corn and peaches.

Plasma and red blood cell cholinesterase levels of professional agricultural workers engaged in packing sweet corn and thinning peaches were monitored. Workers with extensive contact with mechanically harvested sweet corn (the corn had been treated one or two days before harvest with a combination of ethyl and methyl parathion) exhibited significant depression of cholinesterase. Gloves, worn by 40% of the workers, provided some protection from absorption of pesticide residues. No significant cholinesterase depression was found in workers thinning peaches which had been previously treated with parathion.

Adult↗

Exposure of field workers to organophosphorus insecticides: cotton.

The red blood cell and plasma cholinesterase (ChE) levels of cotton scouts inspecting foliage for insect infestation and damage were monitored. Group means for ChE activity were significantly depressed at one or more time(s) during four of the eight growing seasons studied. Although no symptoms of organophosphate poisoning were confirmed, several scouts exhibited ChE depressions over 50% of pre-exposure levels.

Agricultural Workers' Diseases↗