F. E. Guthrie

Comparative rates of dermal penetration of insecticides in mice

Abstract Dermal penetration of 14 radiolabeled insecticides into ICR mice was studied. Permethrin penetrated most rapidly ( T 0.5 = 5.9) while malathion penetrated least rapidly ( T 0.5 = 130 min). Within 5 min after application some toxicants were in the blood, and measurable quantities of radioactivity from the majority of toxicants tested were detected in blood, liver, and other organs 15 min after application. Within 8 hr, 4-chlorobiphenyl showed almost complete penetration as did several other compounds. Insecticides showing poor dermal penetration were absorbed to the extent of 60% or greater by 8 hr. The liver, intestine, stomach, urine, and feces contained appreciable quantities of several insecticides at intervals greater than 1 hr, but only small amounts were found in other tissues. Insecticides that were slowly excreted or metabolized tended to accumulate in the carcass suggesting a major storage role in those tissues at early time intervals. Correlations with a number of physical parameters and penetration were inconclusive.

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.

Affinities of parathion, DDT, dieldrin, and carbaryl for macromolecules in the blood of the rat and American cockroach and the competitive interaction of steroids

Abstract This investigation concerns the binding of DDT, dieldrin, parathion, and carbaryl to macromolecules of rat and roach blood. Plasma was filtered on Sephadex G-200, and the first protein peak (FPP) was used to investigate binding characteristics for the insecticides. Binding was demonstrated to be of a nonspecific hydrophobic nature, except for roach FPP and dieldrin in which, in addition to low-affinity binding, sites for high-affinity binding were also found. Competitive binding experiments were run with cholesterol, estrogen, DDT, and dieldrin. No significant competitive interactions were demonstrated.

Binding of insecticides to macromolecules in the blood of the rat and American cockroach

Abstract This investigation concerns transport of DDT, dieldrin and parathion in the blood of the rat and roach. Using gel filtration, ion-exchange chromatography, and disc gel electrophoresis, a method for the isolation of some of the plasma proteins that bind DDT and dieldrin has been demonstrated. By a variety of staining procedures, these macromolecules were shown to be of a lipoprotein nature. A tentative molecular weight of 520,000 was obtained for one of the binding proteins in roach hemolymph.

In vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice

Dermal absorption is a major portal of entry for a wide variety of potentially toxic substances. In vivo and in vitro investigations assessing penetration of topically applied xenobiotics using both human and other animals have been conducted. Current ethical considerations have drastically curtailed the testing of xenobiotics in human volunteers; consequently, dermal penetration in humans is usually estimated from in vivo tests in animals and in vitro tests using either human or animal skin. In order for in vitro penetration results to be meaningful, there needs to be close relationship with in vivo data. The objective of the present study was to investigate the relationship between in vivo and in vitro penetration of both hydrophilic and lipophilic /sup 14/C-labelled compounds in mice.

Absorption and distribution of intubated insecticides in fasted mice

Abstract Radioactive solutions of 14 C-labeled insecticides were administered by stomach needle to fasted female mice (1 mg/kg, Dublin strain). They were killed at different time intervals and the amount of radioactivity determined in the gastrointestinal tract (unabsorbed) and in selected organs. T 0.5 values of penetration (min) ranged from 8 to 17 for the carbamates tested, 24 to 78 for the organophosphorus compounds, and 15 to 62 for the chlorinated hydrocarbons. Among other insecticide groups, nicotine penetrated rapidly whereas permethrin was the least rapid of all compounds under study. The insecticides were rapidly distributed to various organs. No consistent correlations between absorption and physicochemical properties of the compounds were noted.

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.

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.

The effects of DDT and dieldrin on rat peritoneal macrophages

Abstract The effects of DDT and dieldrin on cell population, viability, and phagocytic activity on the rat peritoneal macrophages were studied. It was observed that both pesticides, at low levels of concentration, exhibited a marked effect on this cell type. At the lowest concentrations tested both pesticides produced an increase in the macrophage population which appeared to be the result of a foreign-body response. At higher concentrations of pesticide this foreign-body response appears to be inhibited. The phagocytic activity of the cells steadily decreased as the concentration of the pesticide administered increased, and a decrease in cell viability with increased pesticide exposure was also noted.

Dermal absorption of pesticides in mice

Abstract The dermal penetration of 2,4-D, cyhexatin, fenvalerate, paraquat, maleic hydrazide, and captan was determined at 1, 6, and 24 hr after application to a 1.2-cm2 area of the upperback of 7- to 8-week-old mice (1 mg/kg). The amounts of labeled pesticide were measured at the site of application and in the blood, liver, kidney, excreta, and carcass. Ninety-five percent, or greater, were recovered in all cases. These compounds were found to penetrate much slower (21% or less in 24 hr) than was shown for a group of insecticides (parathion, permethrin, carbofuran, and dieldrin, for example) in previous reports. Whereas slow penetration could be explained by low partition coefficients for most compounds, both fenvalerate and cyhexatin (high lipophilicity) were also found to have slow penetration rates. These compounds did not indicate any propensity for appreciable storage or binding in the tissues examined. The carcass contained the greatest amount of radioactivity at 24 hr. The fraction of each compound that penetrated was eliminated from the body at various rates with excretion being lowest for paraquat (50%) and highest for 2,4-D (93%) at 24 hr.