Hazard and risk assessment

An important role for the dose-response relationship and biomarkers is in risk assessment. 

Risk is a mathematical concept, which refers to the likelihood of undesirable effects resulting from exposure to a chemical. 

Risk is defined as the probability that a hazard will cause an adverse effect under specific exposure conditions and may also be defined in the following way  

Hazard is defined as the capability of a substance to cause an adverse effect. Conversely, safety may be defined as the practical certainty that adverse effects will not occur when the substance is used in the manner and quantity proposed for its use.  

As exposure increases so does the probability of harm, and therefore a reduction in 

Two types of hazards are associated with the use of chemicals—hazards that are a direct result of the physical and reactive properties of a chemical, and health hazards resulting from the biological properties. This chapter summarises hazards that are associated with working with chemicals in a laboratory, and highlights some sources of hazard information for carrying out hazard and risk assessments. 

Lack of hazard information does not mean that the consequences of handling a chemical can be disregarded. Any chemical has the capacity for harm if it is carelessly used, and for many newly synthesised materials (e.g., new synthetic reagents), hazardous properties may not be apparent or may not have been cited in the literature. The toxicity of some very reactive chemicals may not have been evalnated becanse of ethical considerations. 

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Hazard and Risk Assessment Tools The hazard and risk assessment tools used vary with the stage of the project from the early design stage to plant operations. Many techniques are available, both quahtative and quantitative, some of which are hsted in the following section. Reviews done early in projects often result in easier, more effective changes. 

Jones, D., Nomenclature for Hazard and Risk Assessment in the Process Industries, Second Edition, Rugby, Wai-wickshire, UK Institution of Chemical Engineers, 1992. 

Safe, S. (1998) Hazard and Risk Assessment of Chemical Mixtures Using the Toxic Equivalency Factor Approach. Environmental Health Perspectives, 106(Suppl. 4), 1051-1058. 

A Resources to identify chemicals of concern B Chemical toxicity C Exposure assessment tools D Hazard and risk assessment tools E Safer chemistry design tools... 

A large number of research and review papers have been published in recent years on the integration of data on physicochemical properties, in vitro derived toxicity data, and physiologically based kinetics and dynamics as a modeling tool in hazard and risk assessment [72-85]. 

Chemical Risk Analysis is a practical handbook of chemical hazard and risk assessment, and is aimed particularly (but not exclusively) at the practitioner level. Its main target audiences include ... 

The need to develop and use chiral chromatographic techniques to resolve racemates in pesticide residues will be driven by new hazard and risk assessments undertaken using data from differential metabolism studies. The molecular structures of many pesticides incorporate chiral centers and, in some cases, the activity differs between enantiomers. Consequently, in recent years manufacturers have introduced resolved enantiomers to provide pesticides of higher activity per unit mass applied. For example, the fungicide metalaxyl is a racemic mix of R- and 5-enantiomers, both having the same mode of action but differing considerably in effectiveness. The -enantiomer is the most effective and is marketed as a separate product metalaxyl-M. In future, it will not be satisfactory to rely on hazard/risk assessments based on data from metabolism studies of racemic mixes. The metabolism studies will need to be undertaken on one, or more, of the resolved enantiomers. 

As it has been shown in this chapter knowing the concentrations of chemicals in the environment is a key aspect in order to carry out meaningful hazard and risk assessment studies. Predicting concentrations of chemicals can serve as a quick and robust way to produce an acceptable screening level assessment however if further precision is desired, the complexity of real environmental scenarios can make it a cumbersome and unaffordable task. Models improvement requires not only refining their computation algorithms but also and more important, implementing new inputs and processes in order to better describe real scenarios. 

The potential for a compound to induce carcinogenicity is a crucial consideration when establishing hazard and risk assessment of chemicals and pharmaceuticals in humans [53]. To date, the standard approach to assess carcinogenicity at a regulatory level is the 2-year bioassay in rodents. According to the recent REACH... 

World Bank (1997). Environmental Hazard and Risk Assessment. In Environmental Assessment Sourcebook. Update No. 21. Washington, DC World Bank. 

Complete a hazard and risk assessment to determine if it is acceptable to commit responders to the site. 

Ecological and toxicological association of the dyestuff manufacturing industry (ETAD). E 3022 Environmental hazard and risk assessment in the context of EC directive 79/831/ from 31 May 1991. 

Throughout this book, the OECD/IPCS terms and definitions in chemical hazard and risk assessment will be used unless otherwise stated. The OECD/IPCS terms are generally concordant with those used by the US-EPA and the EU. 

Alphabetical List of Selected Generic Terms in Hazard and Risk Assessment and Their Definitions... 

Other terms often used indiscriminately for the dose-response relationship include concentration-effect relationship and dose-effect relationship. According to the joint OECD/IPCS project (OECD 2003 a), which has developed internationally harmonized generic and technical terms used in chemical hazard and risk assessment, the following definitions have been provided although consensus was not achieved ... 

As mentioned previously, the assessment of hazard and risk to humans from exposure to chemical substances is generally based on the extrapolation from data obtained in smdies with experimental animals. In the absence of comparative data in humans, a basic assumption for toxicological risk assessment is that effects observed in laboratory animals are relevant for humans, i.e., would also be expressed in humans. In assessing the risk to humans, an assessment factor is applied to take account of uncertainties in the differences in sensitivity to the test substance between the species, i.e., to account for interspecies variability (Section 5.3). If data are available from more than one species or strain, the hazard and risk assessment is generally based on the most susceptible of these except where data strongly indicate that a particular species is more similar to man than the others with respect to toxicokinetics and/or toxicodynamics. Two main aspects of toxicity, toxicokinetics and toxicodynamics, account for the namre and extent of differences between species in their sensitivity to xenobiotics this is addressed in detail in Chapter 5. 

Acute toxic effects are considered as being threshold effects, i.e., effects for which there are expected to be a threshold of substance concentration below which the effects will not be manifested. For the hazard and risk assessment, it is important to identify those dose levels at which signs of acute toxicity are observed, and the dose level at which acute toxicity is not observed, i.e., to derive a NOAEL for acute toxicity. However, it should be noted that a NOAEL is usually not derived in the classic acute toxicity smdies, partly because of the limitations in smdy design. 

Where information is available on toxic signs of acute toxicity and the dose levels at which these signs occur, then this is useful information that can aid in the hazard and risk assessment for acute toxicity. Equally, dose levels leading to no acute effects can provide useful information. 

Many of the proposed toxicity tests have been criticized for nonspecificity and lack of reproducibility. Concern has also been raised about their relevance for generating useful data for hazard and risk assessment purposes. The diversity of the possible modes of action (e.g., receptor binding. 

Concern has been raised that infants and children are at higher risk than adults from exposure to environmental chemicals. The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children has therefore been raised and the rationale for such a children-specific assessment factor has been discussed. 

Data from studies in experimental animals are the typical starting points for hazard and risk assessments of chemical substances and thus differences in sensitivity between experimental animals and humans need to be addressed, with the default assumption that humans are more sensitive than experimental animals. The rationale for extrapolation of toxicity data across species is founded in the commonality of anatomic characteristics and the universality of physiological functions and biochemical reactions, despite the great diversity of sizes, shapes, and forms of mammalian species. 

In the hazard assessment, it is important to evaluate the toxicological database with regard to its adequacy. The adequacy of a study includes its validity and its relevance. The relevance refers to what has been studied in relation to what is needed for the hazard and risk assessment, and the validity refers to how the study was performed, e.g., conforming with a particular test guideline. The validity and the relevance of a study, or a whole database, has to be considered in relation to the reliability and thus the confidence. The data for hazard assessment are described in detail in Chapter 3. 

The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children is specifically addressed in Section 5.2.1.13. The U.S. Food Quality Protection Act (FQPA) (US-EPA 1996) directed the US-EPA to apply an extra safety factor of 10 in assessing the risks of pesticides to infants and children. The US-EPA (2002) noted the overlap of areas covered by the FQPA factor and those addressed by the traditional UFs, and it was concluded that an additional UF (children-specific) is not needed in the setting of reference values because the currently available UFs (interspecies, intraspecies, LQAEL-to-NOAEL, subchronic-to-chronic, and database-deficiency) were considered sufficient to account for uncertainties in the database from which the reference values are derived. Renwick et al. (2000) concluded that the available data did not provide a scientific rationale for an additional 10-fold UF for infants and children and pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

In the following, several terms used to describe interactions between chemicals are mentioned as well as basic concepts used in the hazard and risk assessment of chemical mixmres. The description of these basic concepts, first outlined by Bliss (1939) and Placket and Hewlett (1952), are based on the publications by Konemann and Pieters (1996), Cassee et al. (1998), and Groten et al. (2001). The definitions of additivity, synergism, antagonism, and potentiation are those of Klaassen (1995) and Seed et al. (1995). 

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