Review of acute chemical incidents as a first step in evaluating the usefulness of physiologically based pharmacokinetic models in such incidents.

CONTEXT. Acute chemical incidents can have substantial public health consequences in terms of morbidity and mortality. OBJECTIVE. We aimed to characterize acute chemical incidents and near-misses in the Netherlands and compare the results with previous studies. This review is a first step in evaluating whether Physiologically Based Pharmacokinetic (PBPK) models can be of value in acute chemical incidents. MATERIAL AND METHODS. Government, regional, municipal and University Hospital Institutes involved in the management of acute chemical incidents in the Netherlands were contacted, and they provided data between 2008 and 2010 on the characteristics and consequences of the incidents. The study is a retrospective epidemiological study based on data from five institutes. Incidents involving biological agents or radiation were excluded. RESULTS. A total of 764 reports were available which involved 722 incidents after cross-matching the different sources of data. Forty incidents were excluded, leaving 682 incidents for which information was available in accordance with the inclusion criteria. Of the 682 incidents included in this study, most occurred in non-industrial buildings (37%) or industrial sites (34%). The most frequently observed event types were loss of containment (60%) and fire (36%), leading to gas emission (54%), followed by spill of liquid or solid chemicals (36%). The chemicals involved were most often products of combustion (e.g. smoke, soot, particles, 25%) and volatile organic compounds (e.g. solvents, styrene, xylene, 23%), followed by inorganic gases (e.g. carbon monoxide, hydrogen, hydrogen sulphide, 13%). A minimum of 847 people experienced adverse health effects following exposure during a chemical incident, and 10 fatalities were reported. The most frequently reported symptoms were respiratory (27%), due to irritant chemicals. The number of incidents related to fire and the number of injured people were higher in this study than in previous studies; 49% of the injured were transported to hospital. DISCUSSION. This study helps to identify which chemicals are frequently involved in acute chemical incidents in the Netherlands. The results will be used in future to assess whether PBPK models may be useful for risk assessment of chemicals often involved in acute chemical incidents and for which human toxicological and kinetic data are scarce.

Indoor air exposure to volatile compounds emitted by paints: experiment and model.

To describe the evaporation of organic solvents from paints and the resulting indoor concentrations, a mathematical model and an indoor paint experiment are presented. The model describes painting in terms of an increasing area of paint during application and two compartments of paint once applied. Evaporation of organic solvents is driven by the vapor pressure of the organic solvent. The experiment revealed concentrations of n-alkanes in indoor air, during painting, and 3 days thereafter. To compare experimental results to model predictions, model parameters were measured at the start of the experiment. Diffusional exchange between paint compartments and fraction of paint applied to the upper compartment were set by expert judgment. Model predictions and experimental results were in agreement, although the timing of the concentration peak appeared difficult to predict.

Bioavailability of inorganic arsenic from bog ore-containing soil in the dog.

In some parts of The Netherlands, bog ore-containing soils predominate, which have natural arsenic levels that exceed, by a factor of 10, existing standards for maximum allowable levels of inorganic arsenic in soil. These standards are based on the assumption that in humans the bioavailability of arsenic from ingested soil is equal to that from an aqueous solution. In view of the regulatory problem that the arsenic levels of these soils present, we questioned the validity of this assumption. To obtain a more realistic estimate, the bioavailability of inorganic arsenic from soil in a suitable animal model was studied. In this report, a study performed in six dogs in a two-way cross-over design is presented. The dogs received orally, in random order, arsenic both as an intravenous solution and as arsenic-containing soil. During a 120-hr period after administration urine was collected in 24-hr fractions. Levels of arsenic were determined using a method of wet digestion, isolation and complexation of arsine, followed by molecule absorption spectrometry. Within 120 hr after intravenous administration, 88 +/- 16% of the dose was excreted renally. After oral administration of arsenic-containing soil, only 7.0 +/- 1.5% was excreted renally. From the urinary excretion data for these two routes of administration, the calculated bioavailability of inorganic arsenic from soil was 8.3 +/- 2.0%. The results from this study demonstrate the need to reconsider the present risk assessment for arsenic in soil.

Problems, related to the occurrence of organic pollutants in the indoor environment.

Evaluation of the occurrence of organic compounds in the indoor environment is needed on at least two levels: 1. Evaluation of the overall prevalence of organic compounds in the indoor air. 2. Evaluation of abnormal concentrations in the indoor air as a result of more or less special circumstances. On both levels this evaluation can be problematic as a result of missing information on exposure to, and health risks of the measured compounds. As a result of this, only general remarks can be made about the relevance of the presence of organic compounds in the indoor air. The choice of the right policy is therefore often difficult. When, as a result of special circumstances the indoor air concentrations of organic compounds are elevated as in the case of houses built on polluted soil, or houses treated with a hydrofobing agent it is as a consequence, often difficult to take effectively the proper decisions. To solve these problems, a great deal of research appears to be necessary. By using all available information produced by the analysis and new techniques like pattern and source-recognition it may be possible to do this research in a more direct way.

Methods for source characterization of organic air pollutants.

Organic compounds are becoming increasingly more of interest as air pollutants, indoor as well as outdoor. Sources emitting such compounds are numerous and of various origin. For toxicological and epidemiological examination and for deciding on remedial actions information is required on the occurrences of compounds as well as on the emitting sources. For this purpose a number of investigations have been carried out with only limited success. To increase the quality of the description of air pollution related to complaints of dwellers and to exposure evaluation analytical and mathematical methods have tested in our laboratory. Analytical methods for the determination of different groups of organic compounds and mathematical methods for defining minimum sampling strategies and for the characterization of sources are discussed and illustrated with applications dealt with in the passed years. It is concluded that the application of a combination of these methods offers a manner to better describe and understand air pollution with organic compounds.