Biomedical subjects

J L Hermens

Publications and source records attributed to J L Hermens.

At least 19 recordsLinked to original sources

PubMed2000

Validation of negligible depletion solid-phase microextraction as a tool to determine tissue/blood partition coefficients for semivolatile and nonvolatile organic chemicals.

In the current study, negligible depletion solid-phase microextraction (nd-SPME) as a technique to determine tissue/blood (tissue/water and blood/water) partition coefficients was validated. With this method the free fraction of chemicals in water in the presence of different tissues was determined and, subsequently, the partition coefficients were calculated. Liver, blood, muscle, and fat tissues obtained from male Wistar-derived rats (U:Wu) were used without homogenization. Data obtained were compared with literature data for lindane, parathion, and paraoxon. The results show that the data in the present work differ by less than a factor of two from those reported in literature. In addition, the standard deviations obtained show that the technique is accurate. Therefore, we conclude that this accurate and automated method can be used to determine tissue/blood partition coefficients for semivolatile and nonvolatile chemicals.

Adipose Tissue↗

PubMed2000

Absorption of hydrophobic compounds into the poly(dimethylsiloxane) coating of solid-phase microextraction fibers: high partition coefficients and fluorescence microscopy images.

The use of solid-phase microextraction with poly(dimethylsiloxane) (PDMS)-coated glass fibers for the extraction and analysis of hydrophobic organic analytes is increasing. The literature on this topic is characterized by large discrepancies in partition coefficients and an uncertainty of whether highly hydrophobic analytes are retained by absorption into the fiber coating or by adsorption to the fiber surface. We applied a new method, which minimizes the impact of experimental artifacts, to determine PDMS water partition coefficients of 17 hydrophobic analytes including chlorinated benzenes, PCBs, PAHs, and p,p'-DDE. These partition coefficients are several orders of magnitude higher than some reported values. Two observations strongly suggest that the retention of hydrophobic organic substances is governed by partitioning into the PDMS coating. (1) The partition coefficients are proportional with octanol/water partition coefficients. (2) The fluorescence of fluoranthene was observed to be homogeneously distributed within the polymer coating when studied by means of fluorescence microscopy. Implications of these findings for the application of solid-phase microextraction with respect to potential detection limits, with respect to biomimetic extraction, and with respect to measurements in multicompartment systems are discussed.

Benzene↗

PubMed2000

Classifying environmental pollutants: Part 3. External validation of the classification system.

In order to validate a classification system for the prediction of the toxic effect concentrations of organic environmental pollutants to fish, all available fish acute toxicity data were retrieved from the ECETOC database, a database of quality-evaluated aquatic toxicity measurements created and maintained by the European Centre for the Ecotoxicology and Toxicology of Chemicals. The individual chemicals for which these data were available were classified according to the rulebase under consideration and predictions of effect concentrations or ranges of possible effect concentrations were generated. These predictions were compared to the actual toxicity data retrieved from the database. The results of this comparison show that generally, the classification system provides adequate predictions of either the aquatic toxicity (class 1) or the possible range of toxicity (other classes) of organic compounds. A slight underestimation of effect concentrations occurs for some highly water soluble, reactive chemicals with low log K(ow) values. On the other end of the scale, some compounds that are classified as belonging to a relatively toxic class appear to belong to the so-called baseline toxicity compounds. For some of these, additional classification rules are proposed. Furthermore, some groups of compounds cannot be classified, although they should be amenable to predictions. For these compounds additional research as to class membership and associated prediction rules is proposed.

Animals↗

PubMed2000

1-octanol/water distribution coefficient of oxolinic acid: influence of pH and its relation to the interaction with dissolved organic carbon.

The distribution of oxolinic acid (OA) between 1-octanol and buffers at a broad range of pH values was studied and found to decrease with increasing pH. The distribution coefficient to dissolved organic carbon (DOC), log DDOC, was estimated and compared with an experimentally derived log DDOC, showing the experimental value to be almost three orders of magnitude higher. Because only the neutral molecule is assumed to distribute to 1-octanol, the interaction with DOC is considered to be electrostatic in character.

1-Octanol↗

PubMed1999

Bioavailability, biodegradation, and acclimation of Tetrahymena pyriformis to 1-octanol.

Previous work has indicated that the ubiquitous freshwater ciliate Tetrahymena pyriformis acclimates to the presence of hydrophobic chemicals acting by nonpolar narcosis. Four explanations have been identified to explain this apparent acclimation: (1) genetic adaptation occurs resulting in a resistant population, (2) T. pyriformis quickly biodegrades hydrophobic chemicals resulting in a perceived acclimation response, (3) hydrophobic chemicals are not bioavailable, and (4) T. pyriformis contain an endogenous biochemical adaptation system which can quickly cause cellular changes resulting in acclimation. Results of biodegradation experiments indicated that the total extractable 1-octanol did not change over the duration of the experiments. Bioavailability experiments were performed using the solid-phase microextraction technique. Although there is a decrease in freely available concentrations of 1-octanol over a 2.5 log unit range of Tetrahymena population density, the freely available concentration is constant for the population densities used for population growth experiments. Genetic change is highly unlikely since acclimation occurs in less than the time required for one population division. It is hypothesized that the acclimation response seen in Tetrahymena results from partitioning of the chemical into the membrane followed by active changes in the membrane structure to restore homeostasis.

1-Octanol↗

PubMed1998

Role of kinetics in acute lethality of nonreactive volatile organic compounds (VOCs).

The role of kinetics in the acute inhalation toxicity of nonreactive, volatile organic compounds (VOCs), including lipophilic and hydrophilic compounds, was analyzed with a physiologically based pharmacokinetic (PB-PK) model for the rat. For 15 VOCs, a total of 23 LC50 values were retrieved from the literature. It was observed that the external exposure parameter (LC50.exposure length; in ppm.h), varied approximately 60-fold. Concentrations of compounds in the lipoid brain fraction were simulated using a kinetic model. This lead to a more than 10-fold reduction in the toxic range of the 15 VOCs. The average value for this simulated dose surrogate was 70 +/- 31 mM for all VOCs. These observations support the presumption that nonspecific, acute narcotic lethality is directly related to the extent of VOC distribution into lipoid brain constituents. The present results can be used for estimation of the acute lethality of nonreactive VOCs on the basis of kinetic simulations. In addition, the presently calculated dose surrogate for VOC lethality in rats is found to be very similar to the reported internal lethal concentrations of so-called "baseline toxicity compounds" in fish. This indicates a common mechanism of acute VOC toxicity among mammalian and aquatic species.

Alkanes↗

PubMed1998

Understanding and estimating membrane/water partition coefficients: approaches to derive quantitative structure property relationships.

In the current study we describe three approaches to derive quantitative structure property relationships (QSPRs) that give insight in the interactions that are important in membrane/water partitioning. In the first model only semiempirically (AM1) calculated descriptors are used to model membrane/water partition coefficients. Additionally, differences between the n-octanol/water and membrane/water partition coefficients are explored using a small selection of calculated descriptors. The results from both these models show that besides the partitioning between an organic phase and water, additional hydrogen-bonding parameters (epsilonLUMO, Q-, and Q+) should be taken into account. Finally, using structural fragment values, a QSPR was derived to correct the n-octanol/water partition coefficient to obtain membrane/water partition coefficients, in case that obtaining AM1 descriptors is not feasible. The QSPRs that are presented here include only alcohols, benzenes, anilines, phenols, nitrobenzenes, quinoline, esters, and amines. Due to the data limitation, the models should be regarded preliminary for other structures, and caution is necessary when modeling charged species.

Amines↗

PubMed1997

A quantitative property-property relationship (QPPR) approach to estimate in vitro tissue-blood partition coefficients of organic chemicals in rats and humans.

The present study describes quantitative property-property relationships (QPPRs) for the partitioning of organic chemicals between blood and tissue homogenates from both rats and humans. The n-octanol/water partition coefficient (K[ow]) is used as a non-biological descriptor. QPPRs for human tissue-blood partition coefficients (PCs) were derived from a dataset of 24 volatile organic compounds in blood, liver, muscle, fat, kidney and brain tissue homogenates. QPPRs were also derived for the PCs of rat tissues, using a dataset of 42 volatile organic compounds in blood, liver, muscle and fat tissue homogenates. These QPPRs were evaluated using a test set of 10 compounds for human tissues and a test set of 14 compounds for rat tissues. For both human and rat test sets, it was generally observed that most estimated PCs were within a range of 50-200% of their experimental values. The present approach is concluded to offer a rapid means for the estimation of tissue-blood PCs of compounds on the basis of K(ow) values. In addition, indications for a possible role of tissue components other than lipid and water in the tissue-blood partitioning process of compounds were observed from the calibration results of the model.

1-Octanol↗

PubMed1997

Solid phase microextraction as a tool to determine membrane/water partition coefficients and bioavailable concentrations in in vitro systems.

Solid phase microextraction (SPME) is an extraction technique that uses a polymer-coated fiber as the extraction device. After extraction, the compound of interest can be desorbed from the fiber and subsequently analyzed by GC or HPLC. One of the properties of SPME is that only the freely dissolved fraction of a chemical is available for partitioning to the extraction device. The method can be applied in a way that small amounts are extracted from the sample, which allows negligible depletion extraction. These two properties make SPME devices particularly suitable for measurements of free concentrations. In toxicological studies the free concentration is considered to be a more relevant parameter, concerning toxic effects, than the nominal concentration that is used most frequently. In the current study, the usefulness of this method to measure phospholipid/water partition coefficients and free concentrations in three different in vitro test systems (rat hepatocytes in primary culture, 9000 g and 100,000 g homogenate fractions of rainbow trout liver) was demonstrated. Results show separate relationships between phospholipid/water and n-octanol/water partition coefficients for a set of polar and nonpolar organic chemicals, respectively. These observations suggest that phospholipid/water partition coefficients may be a more suitable parameter in modeling the kinetic behavior of organic chemicals. Additionally, differences between the nominal and the actual free concentration in in vitro systems are more pronounced for more hydrophobic compounds, as was expected based on theoretical considerations. To our knowledge, the approach presented here is the first analytical method to measure toxicologically relevant concentrations in in vitro test systems in a fast and efficient way.

Animals↗

PubMed1996

Quantitative determination of total molar concentrations of bioaccumulatable organic micropollutants in water using C18 empore disk and molar detection techniques.

A highly sensitive and quantitative group parameter to determine total molar concentrations of organic micropollutants that can bioaccumulate in the lipid phase of aquatic organisms from effluents, surface water, and drinking water has been developed. C18 empore disk was used as a surrogate lipid phase. The partition process between water and C18 empore disk was employed to simulate the bioaccumulation process. After partition extraction of the water sample, the empore disk was extracted with cyclohexane, and total molar concentrations were determined in these extracts using vapor pressure osmometry (VPO) and gas chromatography/mass spectrometry (GC/MS), respectively. Total molar concentrations bioaccumulated in aquatic biota were estimated from the cyclohexane concentrations. Good accuracy for the total molar determination was obtained using VPO, due to the practically constant molar response factors (43.1 +/- 1.7 V/M) for a wide compound range and to excellent additivity of individual compound responses. Satisfying reproducibility (0-8.3%) of VPO was obtained for sample extracts. The detection limit of VPO in cyclohexane extracts corresponded to 0.60 mM in the lipid phase of aquatic biota. A minimal separation GC/MS system was developed, which enabled highly sensitive and sufficiently accurate total molar determinations. The reproducibility of the GC/MS determination for samples ranged from 0.7 to 22%. The detection limit of GC/MS in cyclohexane extracts corresponded to 0.044 mM in the lipid phase. The determined total molar concentrations in the lipid phase of aquatic biota were in the range of 0.139-168 mM for effluents, 0.26-1.34 mM for surface water systems, and < 0.044 mM for drinking water.

Chemical Phenomena↗

PubMed1994

Application of QSARs in risk management of existing chemicals.

QSAR-estimates of aquatic toxicity of relatively unreactive (narcosis-type) organic chemicals for 19 species were used to predict "no-effect-levels" (NELs) at the ecosystem level by means of several extrapolation models which were recently discussed by the Organisation for Economic Cooperation and Development (OECD). It appeared that the differences between the numerical results of these extrapolation methods, despite their different statistical assumptions, were small. Equilibrium-partitioning theory for sediment and water as well as biota and water was used to derive NELs for aquatic sediments and whole-body residues. Simple equations are given, from which NELs for water, and subsequently for sediments and whole-body residues, can be predicted on the basis of only the octanol-water partition coefficient. Actual application of the models presented absolutely requires the availability of methods to recognize chemicals that act by the unspecific mechanism of narcosis. To this end, a classification scheme, based on molecular structure, was developed. This classification scheme was applied to the approximately 2000 so-called High Production Volume Chemicals (HPVCs) listed in Annex 1 of the Council Regulation on the Evaluation and the Control of the Environmental Risks of Existing Chemicals of the European Communities. From the classification of these 2000 HPVCs it is concluded that, for a large portion of all existing chemicals, reliable QSAR estimates of aquatic toxicity can be made; this considerably speeds up the process of priority setting and risk assessment of existing chemicals. The validity of this (dual) approach was tested by a comparison of estimated NELs with actual FCC values for all compounds from the US-EPA Water Quality Guidelines list that classify as narcosis-type compounds. This comparison shows that for many existing chemicals QSARs may be used to derive quality guidelines for water, aquatic sediments and residues in aquatic biota.

Amphibians↗

PubMed1993

N-acetyltransferase activity in rainbow trout liver and in vitro biotransformation of chlorinated anilines and benzenes in fish.

1. N-acetyl transferase activity in liver homogenate of rainbow trout (Oncorhynchus mykiss) was studied. Enzyme activity depends on the concentration of cofactor, has a broad pH and temperature optimum, is not linear with protein concentration within the whole range tested, and does not decrease upon storage at -70 degrees C. 2. In vitro biotransformation of several chlorinated anilines and benzenes was studied in liver homogenates of rainbow trout and swordtail (Xiphophorus helleri). Several phase I and II products were detected in the simple in vitro biotransformation assays using different cofactors NADPH-regenerating system and acetyl-CoA, respectively. Acetylation of di-ortho substituted anilines was not observed. 3. Apparent Vmax and Km values for the acetylation of trichloroanilines have been determined using rainbow trout liver homogenate. The rate or extent of N-acetylation is related to the structure and properties of the chlorinated anilines. 4. Comparison of the data for the two species showed that there are no apparent qualitative differences in the in vitro fate of the chlorinated anilines and benzenes studied. It is concluded that results obtained for these chemicals in the in vitro biotransformation assay can be extrapolated between the taxonomic families of Salmonidae and Poeciliidae. 5. The in vitro and in vivo N-acetylation of the chlorinated anilines turned out to be strikingly similar. Therefore, simple in vitro systems may be of use in assessing the potential of chemicals to bioconcentrate.

Acetylation↗

PubMed1991

Toxicokinetics of aromatic amines in guppy, Poecilia reticulata.

In this study the elimination kinetics of several chlorinated anilines and a tetrachlorobenzene in guppy, Poecilia reticulata, have been determined. The elimination of all the chlorinated anilines in fish showed a bi-phasic pattern, whereas the elimination characteristics of the tetrachlorobenzene are in agreement with a one-compartment model. Elimination of the chlorinated anilines is faster than elimination of the tetrachlorobenzene. The small differences in octanol-water partition coefficient of these compounds can only in part describe the differences in elimination rate. The observed differences might be attributed to differing biotransformation rates.

Aniline Compounds↗

PubMed1991

Influence of survival time on the lethal body burden of 2,3,4,5-tetrachloroaniline in the guppy, Poecilia reticulata.

The lethal body burden (LBB) of 2,3,4,5-tetrachloroaniline in guppy (Poecilia reticulata), exposed for up to 14 days, has been determined at different aqueous concentrations of the test compound. It was found that the LBB is not constant during these 14 days, declining within the first 48 h to an approximately constant value. It is concluded that LBBs of organic compounds may not always be constant and may depend on survival time.

Aniline Compounds↗

PubMed1991

The application of QSARs, extrapolation and equilibrium partitioning in aquatic effects assessment for narcotic pollutants.

QSAR estimates of toxicity of relatively unreactive organic chemicals for 19 species of bacteria, algae, fungi, protozoans, coelenterates, rotifers, molluscs, crustaceans, insects, fish and amphibians were used to predict 'no-effect-levels' (NELs) at the ecosystem level by means of a recently developed extrapolation model. Equilibrium-partitioning theory for sediment and water was used to derive NELs for aquatic sediments. A simple table is given from which NELs for water and sediments can be predicted on the basis of only the octanol-water partition coefficient and molecular weight.

Animals↗

PubMed1991

Bioconcentration of chlorinated anilines and benzene in fish: preliminary results.

1. Seven chlorinated anilines and one chlorinated benzene were tested for their ability to bioconcentrate in guppies (Poecilia reticulata) under different experimental conditions. 2. Interactions between compounds in a mixture influence the bioconcentration of some chlorinated anilines. These interactions result in either an increase or a decrease of bioconcentration, depending on the compound studied. 3. Exposure concentration can have an effect on the extent of bioconcentration of some chlorinated anilines.

Analysis of Variance↗

PubMed1990

Influence of cytochrome P450 mixed-function oxidase induction on the acute toxicity to rainbow trout (Salmo gairdneri) of primary aromatic amines.

The influence of enzyme induction on the acute toxicity of aniline and 4-chloroaniline to rainbow trout (Salmo gairdneri) was investigated. For these two xenobiotics, bioactivation reactions are known to occur in mammals. Induction of cytochrome P450 mixed-function oxidase was obtained by intraperitoneal (ip) injection of trout with a mixture of polychlorinated biphenyls (Aroclor 1254). Five days after ip injection with three different doses of Aroclor 1254 (50, 100, and 200 mg/kg), benzo[a]pyrene hydroxylase activity in trout liver microsomes increased five- to sixfold. Cytochrome P450 concentrations in the microsomes were slightly, but significantly, enhanced in two of the three dose levels. The 96-hr LC50's of aniline and 4-chloroaniline were not affected by pretreatment with Aroclor 1254, suggesting that metabolic activation does not necessarily play a role in the acute toxicity of aromatic amines to fish.

Aniline Compounds↗

PubMed1990

Electrophiles and acute toxicity to fish.

Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms.

Alcohols↗