A screening method for ranking chemicals by their fate and behaviour in the environment and potential toxic effects in humans following non-occupational exposure

A large number of chemicals are released intentionally or unintentionally into the environment each year. These include thousands of substances that are currently listed worldwide and several hundred new substances added annually (Mücke et al., 1986). When these compounds are used, they can reach microorganisms, plants, animals and man either in their original state or in the form of reaction and degradation products via air, water, soil or foodstuffs. Hence environmental chemicals can occur in practically all environmental compartments and ecosystems. It is not feasible to conduct assessments of human exposure and possible associated health effects for all chemicals. Even if the necessary resources were available, reliable data for a quantitative evaluation are likely to be absent in most cases. This has led to the development of schemes for prioritising compounds likely to be of environmental significance. Such schemes can be used to direct future research efforts towards the prioritised compounds. This study was commissioned by the Department of Health (DH) as part of a broader research activity that aims to identify key priority chemicals of concern to human health at routine levels of environmental exposure. The main pathways of human exposure are shown in Figure 1.1. A review of the principal prioritisation schemes used by different organisations to assess the significance of chemical release into the environment has been conducted by the MRC Institute for Environment and Health (IEH, 2003). This review showed that the approaches used by different organisations vary widely, depending on the initial reasons for which the schemes were developed. The basic information presented in the review was used to develop a simple screening method for ranking chemicals. The model used in this prioritisation scheme is outlined in Figure 1.2. The main purpose in developing the prioritisation scheme for DH was to develop a dedicated priority setting method capable of identifying chemicals in air, water, soil and foodstuffs that might pose a significant risk to human health following low level environmental exposure. The methodology was developed in order to identify compounds that required further assessment and those that had data gaps. More detailed risk assessments were conducted at a later stage on those compounds prioritised as being of high importancea. The screening methodology was developed for ‘existing chemicals’ as these are of greatest concern because data on their toxicity and/or fate and behaviour are often unknownb. The production of a priority list was designed to highlight compounds that required further regulatory measures to reduce exposure of the general population and for which an in-depth risk characterisation would be necessary to assist in the evaluation and implementation of activities for reducing environmental risks. This might include an assessment of the costs of such risks to human health and the costs of reduction measures. As the scheme also aimed to identify data gaps that might warrant further investigation, the application of default categories for chemicals with no data was also considered. The overall aim was to develop a screening methodology that is quick, clear and simple to use and that can easily be revised to take into account new information on compounds as and when it becomes available. a Benzene (IEH Report on Benzene in the Environment, R12); 4,6-dichlorocresol, hexachloro-1,3-butadiene, tetrachlorobenzene, 2,4,6-trichlorophenol (reports to DH; available from MRC Institute for Environment and Health b ‘Existing Substances’ are those that were placed in the European Union (EU) market before 1981. Prior to 1981 regulatory requirements were related to products intended for certain uses (e.g. veterinary medicines) and did not require assessment of the hazardous properties of any substance before they were released into the market. For substances placed on the market after 1981 (classified as ‘New Substances’) there is a legal requirement to conduct such assessments. Regulatory agencies require the collection of extensive documentation for safety before a chemical, for example, can be used in foods or commercial products. IEH Web Report W14, posted March 2004 at http://www.le.ac.uk/ieh/ 4 This report describes how physicochemical properties and toxicological data were incorporated into a screening model to assess the potential fate and transfer of chemicals between different environmental compartments and to predict the potential human exposure to toxic chemicals through the inhalation of contaminated air and the ingestion of water and food. It must be stressed, however, that the method devised is a simple screening process and that a more detailed assessment is necessary to determine the potential transfer through the foodchain of a chemical and the full extent of any adverse health effects. Sections 2 and 4 present the physicochemical properties, toxicological data and algorithms used to screen the compounds. Section 3 summarises the groups of chemicals that were included in the screening process. The results of the prioritisation scheme and comments on their limitations and constraints are presented in Section 5

Physiological modeling of isoprene dynamics in exhaled breath

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.Comment: 14 page

Physiological modeling of isoprene dynamics in exhaled breath

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.Comment: 14 page

Assessing Human Exposure to SVOCs in Materials, Products, and Articles : A Modular Mechanistic Framework

A critical review of the current state of knowledge of chemical emissions from indoor sources, partitioning among indoor compartments, and the ensuing indoor exposure leads to a proposal for a modular mechanistic framework for predicting human exposure to semivolatile organic compounds (SVOCs). Mechanistically consistent source emission categories include solid, soft, frequent contact, applied, sprayed, and high temperature sources. Environmental compartments are the gas phase, airborne particles, settled dust, indoor surfaces, and clothing. Identified research needs are the development of dynamic emission models for several of the source emission categories and of estimation strategies for critical model parameters. The modular structure of the framework facilitates subsequent inclusion of new knowledge, other chemical classes of indoor pollutants, and additional mechanistic processes relevant to human exposure indoors. The framework may serve as the foundation for developing an open-source community model to better support collaborative research and improve access for application by stakeholders. Combining exposure estimates derived using this framework with toxicity data for different end points and toxicokinetic mechanisms will accelerate chemical risk prioritization, advance effective chemical management decisions, and protect public health.Peer reviewe

Prediction of Partition Coefficients and Permeability of Drug Molecules in Biological Systems with Abraham Model Solute Descriptors Derived from Measured Solubilities and Water-to-Organic Solvent Partition Coefficients

Book chapter on the prediction of partition coefficients and permeability of drug molecules in biological systems with Abraham model solute descriptors derived from measured solubilities and water-to-organic solvent partition coefficients

Numerical Modeling of Chemical Compounds’ Fate and Kinetics in Living Organisms: An Inverse Numerical Method for Rate Estimation from Concentration

Emerging chemical compounds are ubiquitous in all environmental compartments and may pose a risk to biota ecosystems. The quantification and prediction of environmental partitioning of these chemicals in various environmental compartment systems (water, sediments, soil, air, biota) is an important step in the comprehensive assessment of their sources, fates, and not finally of their uptake potential by various living organisms of ecosystems