摘要:

Dermal penetration of chemicals and drugs is of concern to both toxicologists and pharmacologists. Environmental professionals try to limit exposure to chemicals using protective clothing and gloves or barrier creams to trap chemicals. Drug developers try to enhance penetration of chemicals through the skin for medical purposes. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. These models are especially useful when they are based on physiological and biochemical parameters which can be measured in the laboratory. Appropriately validated models based on conservation of mass, diffusion and chemical transport by flow can be predictive of human exposures. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) skin models to predict blood concentrations of dibromomethane in rats after skin-only vapor exposures. These new models improve the predictions of the blood concentrations especially at the beginning of the exposures. Sensitivity analysis shows that the permeability constants followed by partition coefficients have the most impact on blood concentration predictions. With proper validation the new models could be used to improve species, dose, and duration extrapolations of chemical or drug penetration. They could also be used to investigate and predict concentrations of drugs or chemicals in the skin.

ISSN:1062-936X    

DOI:10.1080/10629369608032985

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

This article describes the possibility of estimating whether or not a mixture of nonreactive volatile organic chemicals (NRVOC) is likely to elicit complaints of sensory irritation in humans. For this estimation we rely on: a) the sensory irritating potency of individual NRVOC can be estimated from a variety of physicochemical properties of these chemicals, b) at low exposure concentrations, the additivity rule can be applied using the potency of each chemical in a mixture and c) a threshold concentration exists below which no sensory irritation will occur. We used this estimating approach and we compared the results obtained with those obtained experimentally in humans exposed to a well defined mixture. The approach presented can be used to arrive at a decision as to whether or not exposure to a mixture of NRVOC is likely to result in sensory irritation complaints by humans, either in the general indoor air situation or for industrial workers.

ISSN:1062-936X    

DOI:10.1080/10629369608032986

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

Cluster significance analysis is a tool that allows the identification of ‘embedded clusters’ in QSAR datasets. It is successfully applied to an eye irritation data set to show that these data are indeed asymmetric. The method identifies five parameters that form an embedded cluster of eye irritants amongst non irritants, although full separation is not achieved. This method has considerable potential to identify potential non-linearity in toxicology data sets and for parameter reduction. It is shown also that this can be obtained relatively quickly with an analysis performed on 100,000 subsets containing the same information as an analysis on 1,000,000 subsets.

ISSN:1062-936X    

DOI:10.1080/10629369608032987

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

The toxicity of certain polycyclic aromatic hydrocarbons (PAHs) can be greatly increased by simultaneous exposure of test organisms to ultraviolet (UV) wavelengths present in sunlight. This phenomenon, commonly termed photoinduced toxicity, had been evaluated extensively in laboratory settings where only one chemical of concern was present. However, more recent studies have demonstrated that complex mixtures of PAHs present, for example in sediments, also can cause phototoxicity to a variety of aquatic species when the samples are tested in simulated sunlight. Unfortunately, because these types of samples can contain thousands of substituted and unsubstituted PAHs it is difficult, if not impossible, to use conventional analytical techniques to identify those responsible for photoinduced toxicity. The objective of the present study was to link two powerful ecotoxicology tools, toxicity-based fractionation techniques and QSAR models, to identify phototoxic chemicals in a sediment contaminated with PAHs emanating from an oil refinery. Extensive chromatographic fractionation of pore water from the sediment, in conjunction with toxicity testing, yielded a simplified set of sample fractions containing 12 PAHs that were identifiedviamass spectroscopy. Evaluation of these compounds using a recently developed QSAR model revealed that, based upon their HOMO-LUMO gap energies, about half were capable of producing photoinduced toxicity. We further evaluated the phototoxic potential of the reduced set of PAHs by determining their propensity to bioaccumulate in test organisms, through calculation of octanol-water partition coefficients for the chemicals. These studies represent a novel linkage of sample fractionation methods with QSAR models for conducting an ecological risk assessment.

ISSN:1062-936X    

DOI:10.1080/10629369608032988

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

The aim of this work was to propose methods to test mechanisms of synergistic effects of toxic agents in bees. We assumed that the fungicide prochloraz acts synergistically on deltamethrin by increasing the penetration of deltamethrin and/or inhibiting the oxidative metabolism of deltamethrin. These hypotheses were tested by using a pharmacokinetic box model. A previous experimental work showed that there was a synergy between deltamethrin and prochloraz in bees, and allowed to compare the effects of the treatment with 0.25 g ha−1deltamethrin in the presence of 25 g ha−1(Δ0.25 +P) prochloraz and the treatment with 1 g ha−1deltamethrin alone (Δ1). We postulated that cumulated mortality was proportional to the cumulated internal deltamethrin (ID2). To be consistent with the experimental data,ID2of treatment (Δ0.25 +P) had to be greater thanID2of treatment (Δ1) during the period from 2 to 8 hours. We studied in the most favourable conditions if the different hypotheses could be consistent with the experimental data. The conclusions were that published parameter values would be consistent with simulation results only in the case of an action on both metabolism and possible active transports during penetration, whereas inhibition of metabolism and increase in penetration, by increasing diffusion, would not be sufficient to explain the synergy.

ISSN:1062-936X    

DOI:10.1080/10629369608032989

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

This is a scanned image of the original Editorial Board page(s) for this issue.

ISSN:1062-936X    

DOI:10.1080/10629369608032984

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor