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

Abstract

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.

Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure

“…Inhalation exposure is relevant for single exposure chemical incidents, as shown by a recent review of this kind of incidents in which inhalation represented 80% of the cases (Hunault et al, 2014). This present study is only a first step, which might be continued in the future, for example, by taking account of dermal exposure.…”

“…They are organic chemical compounds, such as benzene or formaldehyde, that evaporate at room temperature under normal, indoor atmospheric conditions. VOCs represented 23% of the exposures after acute chemical incidents, in the Netherlands, between 2008 and 2010 (Hunault et al, 2014). The Mumtaz model divides the body into seven compartments (Fig.…”

“…Physiologically based pharmacokinetic models (PBPK) may facilitate emergency risk assessment after single inhalation or oral exposure to a chemical by estimating the dose absorbed in a specific organ (Mumtaz et al, 2012;Scheepers, 2010;Hunault et al, 2014). PBPK models represent the body as a set of functional compartments (e.g., blood, brain, liver, muscle and skin, rest of the body) and simulate the pharmacokinetic profiles of chemicals in animals and humans on the basis of available information on relevant physiological, physico-chemical, and biochemical factors.…”

Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals

“…The 9 chemicals selected for investigation are: dichloromethane (DCM), benzene (BNZ), xylene (XYL), toluene (TOL), styrene (STY), 2-propanol (2-P), methanol (MeOH), trichloroethylene (TCE), and tetrachloroethylene (PCE). The selection of these chemicals was primarily based on a review of acute incidents with hazardous chemicals in the Netherlands (Hunault et al, 2014) revealing that VOCs represent about 23% of all acute releases. Another reason for selecting these nine chemicals was their frequent use as industrial solvents.…”

“…PBTK models are mathematical models that quantitatively describe the absorption, distribution, metabolism and excretion (ADME) of chemicals into the body using anatomical, physiological, biochemical and physicochemical parameters. Some recent publications have advocated in favour of the use of PBTK modeling in specific situations of human risk assessment (Scheepers, 2010;Mumtaz et al, 2012;Hunault et al, 2014). Examples of situations in which the use of PBTK models could be helpful are intoxications with delayed serious effects, repeated exposure, reverse dosimetry calculation of exposure doses in forensic cases, or interpretation of biomonitoring data.…”