Assessment factor

In considering exposure tests, whether in the form of laboratory, field or service tests it is important to consider the purpose of the test and the relevance of the data to the anti-corrosion function of the coating. Thus, in the case of paint coatings, factors such as gloss deterioration, chalking and colour retention are of considerable importance in some industries, for example the automotive industry, but perhaps of minor importance in the painting of structural steelwork. These assessment factors can nevertheless be of significance since they may be the precursors of corrosion of the basis metal. 

Gather patient history. Assess factors involved in drug selection. Inquire about social history and alcohol use. Ask the patient about drug allergies and chronic health problems such as asthma. 

Table 4 EC50 (in mg L ) used to calculate PNEC (by dividing EC50 by an assessment factor (AF) of 1,000), for fish, daphnids (Daphnia magna) and algae for some of the most ubiquitous pharmaceuticals detected in environmental waters...

Table 20. Typical assessment factors for human health risk assessment...

The objective is to predict the concentration of the substance below which adverse effects in a particular environmental compartment are not expected to occur, i.e., the predicted no effect concentration (PNEC). However, in some cases, it may not be possible to establish a PNEC, and a qualitative estimation has to be made instead. An assessment factor is applied to... 

Composite (reductive) factor by which an observed or estimated No-Observed-Adverse-Effect Level (NOAEL) is divided to arrive at a criterion or standard that is considered safe or without appreciable risk. Related terms Assessment Factor, Uncertainty Factor. 

Related terms Assessment Factor, Safety Factor. 

The risk assessment comprises an effect assessment (hazard identification and hazard characterization) and an exposure assessment. The principles for the effect assessment of the active substances are in principle similar to those for existing and new chemicals and are addressed in detail in Chapter 4. Based on the outcome of the effect assessment, an Acceptable Daily Intake (ADI) and an Acceptable Operator Exposure Level (AOEL) are derived, usually from the NOAEL by applying an overall assessment factor addressing differences between experimental effect assessment data (usually from animal studies) and the real human exposure situation, taking into account variability and uncertainty for further details the reader is referred to Chapter 5. As a part of the effect assessment, classification and labeling of the active substance according to the criteria laid down in Directive 67/548/EEC (EEC 1967) is also addressed (Section 2.4.1.8). 

For threshold effects, traditionally, a level of exposure below which it is believed that there are no adverse effects estimated, based on an approximation of the threshold termed the No-Observed-(Adverse)-Effect Level (NO(A)EL) and assessment factors this is addressed in detail in Chapter 5. This estimated level of exposure will in this book be termed tolerable exposure level. Examples, where this approach is used, include establishment of the Acceptable/Tolerable... 

The distinction between non-adverse effects and adverse effects can seem academic, but is essential in the hazard assessment in relation to, e.g., evaluation of no-effect levels and lowest-effect levels (Section 4.2.4), identification of the critical effect(s) (Section 4.2.7), and to the magnitude of the assessment factor to be used for taking into account the uncertainty due to the nature and severity of effects (Section 5.8). 

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. 

A recently pubhshed WHO/IPCS document regarding chemical-specific adjustment factors for interspecies differences and human variability (WHO/IPCS 2005) provides guidance for use of toxicokinetic data in dose-response assessment to develop the so-called Compound-Specific Assessment Factors (CSAFs) (Section 5.2.1.12). 

An assessment factor of 240 is applied to take into consideration extrapolation from LOAEL to NOAEL (a factor of 6), extrapolation from subchronic to chronic study (a factor of 2), and inter- and intraspecies variation (a factor of 4 and 5, respectively). 

Use of assessment factors seems rather controversial in this approach. 

The approach of deriving a tolerable intake by dividing the N/LOAEL, or alternatively a BMD for the critical effect(s) by an assessment factor has been described and discussed extensively in the scientihc literature. It is beyond the scope of this book to review all these references. This chapter presents an overview of pubhshed extrapolation methods for the derivation of a tolerable intake based on the assessment factor approach, i.e., limited to address effects with threshold characteristics, and is not meant to be exhaustive. The main focus is on the rationale for and the use of the assessment factors. Pertinent guidance documents and reviews for the issues addressed in this chapter include WHO/IPCS (1994, 1996, 1999), US-EPA (2002, 2004), IGHRC (2003), ECETOC (2003), KEMI (2003), Kalberlah and Schneider (1998), Vermeire et al. (1999), and Nielsen et al. (2005). 

The assessment factors generally apphed in the estabhshment of a tolerable intake from the NOAEL, or LOAEL, for the critical effect(s) are apphed in order to compensate for rmcertainties inherent to extrapolation of experimental animals data to a given human situation, and for rmcertainties in the toxicological database, i.e., in cases where the substance-specific knowledge required for risk assessment is not available. As a consequence of the variabihty in the extent and nature of different databases for chemical substances, the range of assessment factors apphed in the establishment of a tolerable intake has been wide (1-10,000), although a value of 100 has been used most often. An overview of different approaches in using assessment factors, historically and currently, is provided in Section 5.2. 

In the context of assessment factors, it is important to distinguish between the two terms variability and uncertainty. Variability refers to observed differences attributable to true heterogeneity or diversity, i.e., inherent biological differences between species, strains, and individuals. Variability is the result of natural random processes and is usually not reducible by further measurement or study although it can be better characterized. Uncertainty relates to lack of knowledge about, e.g., models, parameters, constants, data, etc., and can sometimes be minimized, reduced, or eliminated if additional information is obtained (US-EPA 2003). 

Default Assessment Factors Used or Suggested for the Establishment of a Regulatory Standard or Health-Based Guidance Value for Threshold Effects... 

These parameters are parallel to those being considered in the evaluation of the assessment factors to be applied in the establishment of a tolerable intake. 

The TGD has been revised and the second edition was published in 2003 (EC 2003). However, the human health risk characterization part was not included in this second edition. A final draft version of the human health risk characterization part was released in 2005 with a detailed guidance on, among others, the main issues to be included in derivation of the reference MOS (MOSref), which is analogous to an overall assessment factor. The individual factors contributing to the MOSref are described separately and guidance is given on how to combine these into the MOSref. The guidance provided in this draft version has been extensively used in relation to the risk assessment of prioritized substances carried out since the draft version was released however, this version is not publicly available. 

In the new EU chemicals regulation REACH, which entered into force on 1 June 2007, detailed guidance documents on different REACH elements, including risk characterization and the use of assessment factors, are currently in preparation (spring 2007). These documents will probably be available on the EU DG Environment REACH Web site (EU 2006) when published. 

Interspecies differences (animal-to-human) mouse, a default value of 7 X 3 rat, a default value of 4 X 3 rabbit, a default value of 2.4 X 3 dog, a default value of 1.4 X 3. The first factor for each species is a calculated adjustment factor, allowing for differences in basal metabolic rate (proportional to the 0.75th power of body weight). The second factor of 3 is the assessment factor applied for remaining uncertainties (Section 5.3.3), for which the default value is 3. For local skin and respiratory tract effects, the assessment factor is 3, as adjustment for differences in body size is inappropriate. 

Principally, the overall assessment factor is established by multiplication of the separate factors. The authors note that in practice it is not possible to distinguish all above-mentioned factors, and some factors are not independent of each other. Therefore, straightforward multiplication may lead... 

Vermeire et al. (1999) have published a discussion paper with focus on assessment factors for human health risk assessment. The status quo with regard to assessment factors is reviewed and the paper discusses the development of a formal, harmonized set of assessment factors. Options are presented for a set of default values and probabilistic distributions for assessment factors based on the state of the art. Methods of combining default values or probabUistic distributions of assessment factors (Section 5.11) are also described. In relation to assessment factors, the authors recommended ... 

Worst-case character of the traditional default assessment factors is considered doubtful as the 95th percentile for the proposed distributions for the interspecies (anrmal-to-human) factor and the subchronic-to-chronic duration factor are considerably higher than 10. In addition, the limited data on intraspecies (human-to-human) variation is also considered to indicate that a default factor of 10 may not be sufficient. 

Derivation of approximations of the distribution of assessment factors from historical data (based on NOAEL ratios) has limitations as the use of the NOAEL instead of the True No-Adverse-Effect Level brings along the variation (error) in the NOAELs. 

Application of assessment factors derived from currently estimated distributions of assessment factors may lead to very wide distributions of the overall assessment factor. 

Probabilistic multiplication of distributions of assessment factors is preferred above the simple multiplication of percentiles to avoid extreme conservatism. 

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