Extended summaries: Physicochemical and biophysical panel symposium enhancing pesticide action through mixtures

The following are summaries of papers presented at a meeting of the Physicochemical and Biophysical Panel of the Pesticides Group held on 14 October 1986 at the Society of Chemical Industry, 14 Belgrave Square, London SWIX8PS. The papers published here are entirely the responsibility of the authors and do not reflect the views of the Editorial Board of Pesticide Science.     

Investigation of relative rates of solvent and solute penetration through protective glove materials

Pesticides are often formulated as a concentrate in volatile organic solvents. The most important means of preventing the contamination of workers using the concentrate is by the use of protective clothing, particularly gloves. The influence of formulation solvent on solute permeation rates across selected protective glove materials has been investigated. In one of the cases studied, the solute penetrated the glove material appreciably faster than the formulation solvent. This result, therefore, questions the manner in which gloves are often selected for protection against pesticide formulations (by selecting the glove that offers the best protection against the formulation solvent rather than the active ingredient). Although this is a preliminary study, it is recommended that, to gain the maximum protective effect, all selected gloves are tested using the formulation of choice and that the permeation of all components of the formulation is monitored and reported. It may, therefore, be necessary for glove and pesticide manufacturers to re-examine the way in which these tests are carried out and the processes of product selection used.     

Predicting pesticide percutaneous penetration

It is important to be able to predict the absorption of materials through the skin, particularly if there are toxicological implications. However, for pesticides which are known to be toxic, there are ethical considerations in conducting in-vivo human evaluations of percutaneous absorption. It would therefore be desirable to obtain an indication of the amount of pesticide that can penetrate the skin from a simple knowledge of its physico-chemical properties. It has been shown that the rate of penetration of a range of drugs through intact skin can be estimated from parameters such as partition coefficient, molecular size and solubility. These parameters will be equally applicable to pesticides and the relevant mathematical expressions are discussed.     

Influence of transport on gas loss from freight containers under fumigation. Part I: Experimental investigation

The rate of gas interchange between the atmosphere within a freight container and the external air has an important influence on the effectiveness of in-container fumigation. When a container is exposed to the wind or is in motion, the rate of gas interchange may be much greater than that under static conditions. The effect of motion or wind on gas interchange was studied by observing gas loss from freight containers, both empty and loaded with rice, while stationary and while being transported by rail. The gas interchange rate was determined by measuring the rate of loss from the containers of either a combination of a fumigant, methyl bromide, and a relatively inert tracer gas, carbon monoxide, or of carbon monoxide alone. In loaded containers the difference between the loss rate constants of methyl bromide and carbon monoxide (0.29.0.03d^?1) was within the range expected for the reaction of methyl bromide with rice. After allowing for gas loss caused by changes in temperature and pressure, the component of the interchange rate constant attributable to air motion was found to be proportional to gas-tightness as measured by a steady-state pressure test, and also to the relative air speed over the container. Under conditions of varying wind and train speed, the fraction of the initial concentration of gas remaining was found to be an exponential function of wind run past the container. When wind effects were not important, it was found to be an exponential function of distance travelled.     

Calibration and verification of risk algorithms using logistic regression

The use of logistic regression is proposed as a method of verifying and calibrating disease risk algorithms. The logistic regression model calculates the log of the odds of a binary outcome as a function of a linear combination of predictors. The resulting model assumes a multiplicative (relative) relationship between the different risk factors. Computer programs for performing logistic regression produce both estimates and standard errors, thus permitting the evaluation of the importance of different predictive variables. The use of receiver operating characteristic (ROC) curves is also proposed as a means of comparing different algorithms. An example is presented using data on Sclerotinia stem rot in oil seed rape, caused bySclerotinia sclerotiorum.     

Surface characteristics of necrotrophic secondary hyphae produced by the bean anthracnose fungus, Colletotrichum lindemuthianum

During infection of bean (Phaseolus vulgaris), the hemibiotrophic anthracnose pathogen, Colletotrichum lindemuthianum, initially produces biotrophic primary hyphae that are large-diameter and entirely intracellular, followed by necrotrophic secondary hyphae that are narrower and either intercellular or intracellular. In the present study, transmission electron microscopy of infected tissues prepared by high-pressure freezing and freeze-substitution showed that secondary hyphae have much thinner cell walls (25–40 nm) than primary hyphae (100–130 nm) and are not surrounded by an extracellular matrix. Immunofluorescence labelling with a panel of monoclonal antibodies showed that glycoproteins which are present on conidia, germ-tubes, appressoria, primary hyphae and mycelium grown in vitro are absent from the surface of secondary hyphae. Chitin, detected with the lectin wheat germ agglutinin, was the only surface component shared by secondary hyphae and the other fungal cell types. The results suggest that the fungal cell surface becomes modified during necrotrophic growth, with none of the glycoproteins associated with earlier stages of the infection process being produced.     

Nonlinear mixed‐effects pharmacokinetic modeling of the novel COX‐2 selective inhibitor vitacoxib in dogs

The objective of this study was to develop a nonlinear mixed‐effects model of vitacoxib disposition kinetics in dogs after intravenous (I.V.), oral (P.O.), and subcutaneous (S.C.) dosing. Data were pooled from four consecutive pharmacokinetic studies in which vitacoxib was administered in various dosing regimens to 14 healthy beagle dogs. Plasma concentration versus time data were fitted simultaneously using the stochastic approximation expectation maximization (SAEM) algorithm for nonlinear mixed‐effects as implemented in Monolix version 2018R2. Correlations between random effects and significance of covariates on population parameter estimates were evaluated using multiple samples from the posterior distribution of the random effects. A two‐compartment mamillary model with first‐order elimination and first‐order absorption after P.O. and S.C. administration, best described the available pharmacokinetic data. Final parameter estimates indicate that vitacoxib has a low‐to‐moderate systemic clearance (0.35 L hr^?1 kg^?1) associated with a low global extraction ratio, but a large volume of distribution (6.43 L/kg). The absolute bioavailability after P.O. and S.C. administration was estimated at 10.5% (fasted) and 54.6%, respectively. Food intake was found to increase vitacoxib oral bioavailability by a fivefold, while bodyweight (BW) had a significant impact on systemic clearance, thereby confirming the need for BW adjustment with vitacoxib dosing in dogs.     

Relative skeletal distribution of proliferating marrow in the adult dog determined using 3′‐deoxy‐3′‐[18F]fluorothymidine

3′‐deoxy‐3′‐[¹⁸F]fluorothymidine (¹⁸FLT) is a radiopharmaceutical tracer used with positron emission tomography (PET), often in combination with computed tomography (CT), to image DNA synthesis, and thus, cellular proliferation. Characteristic accumulation of the tracer within haematopoietic bone marrow provides a noninvasive means to assess marrow activity and distribution throughout the living animal. The present study utilizes three‐dimensional analysis of ¹⁸FLT‐PET/CT scans to quantify the relative skeletal distribution of active marrow by anatomic site in the dog. Scans were performed on six healthy, adult (3–6 years of age), mixed‐breed dogs using a commercially available PET/CT scanner consisting of a 64‐slice helical CT scanner combined with an integrated four ring, high‐resolution LSO PET scanner. Regions of interest encompassing 11 separate skeletal regions (skull, cervical vertebral column, thoracic vertebral column, lumbar vertebral column, sacrum, ribs, sternum, scapulae, proximal humeri, ossa coxarum, and proximal femora) were manually drawn based on CT images and thresholded by standardized uptake value to delineate bone marrow activity. Activity within each skeletal region was then divided by the total skeletal activity to derive the per cent of overall marrow activity within an individual site. The majority of proliferative marrow was located within the vertebral column. Of the sites traditionally accessed clinically for marrow sampling, the proximal humerus contained the largest percentage, followed by the ossa coxarum, proximal femur, and sternum, respectively. This information may be used to guide selection of traditional marrow sampling sites as well as inform efforts to spare important sites of haematopoiesis in radiation therapy planning.