Compartmental systems. An appealing class for kinetic modeling and identification of metabolic processes

Problems which arise in quantitative studies on the kinetics of exogenous and endogenous chemical substances within the organism are examined together with approaches for their resolution. Linear and nonlinear compartmental mathematical models are presented and their relevant role for interpreting stimulus‐response experimental data is outlined. Available approaches are then discussed for the resolution of the system identification problem, including a priori and a posteriori identifiability, parameter estimation from test measurement data and optimum design of kinetic experiments. Finally, approaches to the problem of validation are reviewed.     

Ecotoxicological effects of Trichloroethene upon plankton

A case study in an experimental pond was performed to evaluate the ecotoxic effects of Trichloroethene (TRI) upon the population density and productivity of phyto‐ and zooplankton. TRI was continuously released into two pond enclosures over 11 weeks (mean concentrations 1.5 and 7.5 mg/l). The chronic chemical treatment showed distinctive toxic influences upon the biota. Following the high TRI concentration, the phytoplankton density slightly increased; the productivity per single cells, however, was significantly reduced compared to the controls and the low TRI concentration. Cryptophyceae were the most sensitive algae taxa. The density and reproductivity of Daphniae and Phyllopodae decreased by the high TRI concentration. Most of the Rotatoriae were not negatively influenced. With increasing TRI concentrations two different bacteria forms showed a mass development. Small amounts of Trichloroacetic acid were detected in both enclosures as a conversion product of TRI (～3 μg/l after 80 days treatment).     

Isolation of petroleum and chlorinated hydrocarbons from the same extract

Sequential analysis is an extremely powerful technique for complex samples analysis. For determination of petroleum and chlorinated hydrocarbons, the same sample is divided into two parts. One part is utilized to extract the petroleum hydrocarbons and the second part is used to extract the organochlorine compounds because petroleum hydrocarbons usually appear in higher concentrations and interfering with organochlorine compounds. This analysis method required more solvent, time, and more sample volume. The analytical strategy, in this paper, involves the use of effective and efficient but simple techniques for petroleum hydrocarbons and chlorinated hydrocarbons separation. A clean‐up procedure is presented, by which these compounds are isolated from aliphatic as well as polyaromatic hydrocarbons through a combination of HPLC and adsorption chromatography on a florisil microcolumn. Mass spectrometric identification was used as confirmation method. GLC equipped with ECD and FID for organochlorine and petroleum compounds analysis, respectively.     

Utility of the QSAR modeling system for predicting the toxicity of substances on the European inventory of existing commercial chemicals∗

Many chemicals are in common commercial use for which no information on the environmental fate or toxicity exists. Recent legislation requires that many substances be assessed for their toxicity to aquatic organisms within a very short time and determine which of these chemicals need to be studied in greater detail. It would be impossible to measure the acute and chronic effects of all of these compounds on a single organism, let alone a battery of different types of organisms, communities or ecosystems. Initially, the chemicals on the European Inventory of Existing Commercial Chemical Substances (EINECS) need to be screened and relative hazard to the environment determined. In response to OECD directives, there has been a great deal of activity by government and industry scientists. At the International Workshop on Advances in Environmental Hazard and Risk Assessment it was concluded that quantitative structure activity relationships (QSAR) could and should be used in the hazard assessment process. Papers published in that volume outline the advantages, disadvantages, limitations, advances and research requirements.

The QSAR, structure‐activity based chemical modeling and information system, which was developed by the US‐Environmental Protection Agency was used to predict the acute toxicity of 113 substances from the “Old Substances”; list of the German government to the four commonly used aquatic toxicity test organisms: Daphnia magna (DM), fathead minnow (FHM), rainbow trout (RBT), and blue‐gill sunfish (BG).

Of these compounds the QSAR system predicted the acute toxicity of 87 substances towards fathead minnow. For the other three species examined the QSAR system could be used to predict toxicity for 78 compounds.

The predicted toxicities were compared to observed toxicities of compounds which have been evaluated and stored in the “Aquire”; data base. Observed toxicity values were available for at least one species for 38 compounds. The toxicities of some compounds are well predicted while those of other compounds were not well predicted. Overall, the QSAR system accurately classified the acute toxicity ranges of 50%, 64%, 56% and 56% of the compounds investigated for DM, FHM, RBT and BG, respectively. Of the compounds studied 10 were very poorly predicted, of these the QSAR system overpredicted the toxicity of three, while underpredicting the toxicity of seven. Of these seven compounds, five contained amino groups.     

Regression models for some solute distribution equilibria in the terrestrial environment

Sorption coefficients (K_p) of several organochlorine insecticides (OCs) in volcanic ash silt from Central Java are presented.

Selected experimental and estimated octanol‐water partition coefficient (P) values are used to study log‐log regressions with K_p data collected from the literature (PAHs, chlorophenols, phenylureas, chloro‐s‐triazines, carbamates and organophosphorus insecticides) and those of the OCs determined in the present study. Leaching distances and bioactivities in soil are correlated with the K_p values of the pesticides, and with the organic matter and the water content of the soil.     

A modified steam distillation method for volatile acids determination in anaerobic digestors

A modified steam distillation method for the accurate determination of low levels of volatile acids found primarily in low rate anaerobic digestors has been developed. The interference of bicarbonate alkalinity is minimal with complete removal of carbon dioxide from the sample prior to distillation. This removal can be achieved by boiling the acidified sample for 30 min in an erlenmeyer flask with ground‐glass neck attached to a reflux condenser.     

Cadmium and chromium in human lung tissue in relation to smoking and lung cancer

The pulmonary Cd and Cr content was determined from 53 lung cancer patients operated for cancer and from 39 patients who died of non‐malignant diseases. The results were correlated with smoking habits, pulmonary emphysema and occupational history. Both the pulmonary Cd and Cr increased with the amount of smoking. In ex‐smokers the Cr content in lung tissue did not diminish with the time since stopping smoking, but the Cd did follow the half‐life of about 9 years. The pulmonary Cd, compared with smoking habits, behaved similarly in both the lung cancer and control patients, whereas Cr in the lung cancer patients could not be explained solely by smoking, but some of the cancer patients may have been occupationally exposed to Cr. Speciation was not studied.     

The metabolism and distribution of [14C‐phenyl]‐ethyl parathion in a tropical soil under field conditions

The persistence, distribution and metabolism of [^l4C‐phenyl]‐ethyl parathion applied to soil columns in an agricultural farm were investigated under tropical field conditions. Volatilization, soil microbial activity, moisture levels and pH were found to influence the persistence, distribution and metabolism of this pesticide in the soil. There was rapid distribution of the pesticide in the soil matrix with time resulting in high levels of bound residues which reduced the overall rate of disappearance of parathion residues from the soil. The soil was slightly acidic but the metabolites, paraoxon, p‐nitrophenol and p‐aminophenol were detected in the soil extracts 7 days after pesticide application. After 72 days, 43.7% of the applied pesticide remained in soil composed of 18.9% extractable and 24.8% bound residues. A mechanism for the metabolism of ethyl parathion in this soil is given.     

Determination of pentachlorophenol in human urine using solid phase extraction and GC‐MS analysis with stable isotope dilution

A method for the determination of pentachlorophenol (PCP) in human urine was developed. Urine samples were fortified with ¹³C₆‐IabeIed PCP and hydrolyzed with sulfuric acid prior to extraction. The urine samples were then passed through preconditioned solid phase extraction cartridges containing octadecylsilane adsorbent. The PCP was subsequently eluted from the cartridge with ethyl acetate and converted to pentachloroanisole prior to GC‐MS analysis. GC‐MS quantitation was performed using the technique of stable isotope dilution. Percent recoveries averaging 100, 97, and 111% were obtained for replicate urine samples fortified with approximately 2, 20, and 200 ng/mL of PCP, respectively. The method detection limit was estimated to be 0.2 ng/mL.     

Characterisation of cobalt‐binding proteins in occupational cobalt exposuret†

In animal experimentations cobalt is found to be carcinogenic under conditions which are comparable with a possible exposure of human beings at the workplace.^1,2 Little is known about binding and distribution of incorporated cobalt in blood.

Blood, serum and plasma of workers occupationally exposed to cobalt were analyzed concerning cobalt‐binding. The samples were focused by preparative IEF in layers of granulated gels. The cobalt concentrations in the isolated fractions were measured with the aid of flameless atomic absorption spectrometry. The whole blood samples exhibit peaks with different sizes in the pH‐5‐ and ‐7‐range. The proportion of these peaks can change with individual samples. In serum and plasma cobalt is found only in the pH‐5‐range.

When separated by gelelectrophoresis under denaturating conditions the cobalt‐fractions in all blood, serum and plasma samples shows a similar protein pattern. Several proteins with different molecular weights are detected in the pH‐5‐fractions, whereas only hemoglobin is found in the pH‐7‐fractions. In agreement with these results is the refocusing in ultrathin‐layer of polyacrylamide. Heterogeneous protein patterns are demonstrated with the pH‐5‐fractions; the pH‐7‐fractions yield only the hemoglobin pattern.

In vivo cobalt is bound to plasma proteins‐perhaps‐albumin^3,4‐and hemoglobin. Till now the chemical structure of the binding is unknown.