Human risk assessment discussion

This chapter considers the recently developed tools and the latest versions of the old tools. Some of the tools comprise not only the environmental compartments used on environmental risk assessment but also the human compartment necessary for human health risk assessment. For this reason, when summarizing the models, as described in the second part of this chapter, several characteristics of human compartment are discussed as well. However, a detailed description of human compartment together with a wide range of tools developed for exposure and human risk assessment is presented in the next chapter. 

Dermal absorption is influenced by several factors, e.g. the physico-chemical properties of the substance, vehicle, occlusion, concentration, exposure pattern and skin site of the body (ECETOC, 1993 Howes et al., 1996 Schaefer and Redelmeier, 1996). Despite the fact that guidance exists for the conduct of dermal absorption studies (USEPA, 1998, 2004 OECD, 2004a,b,c), there continues to be discussion on some experimental details. In order to harmonize the use of dermal absorption data in human risk assessment within the EU, a guidance document was prepared by the Commission (EC, 2002). 

No oral MRLs were calculated because of the variability in the composition of gasoline. Also, no quantitative information on adverse effects other than oc2u-globulin-mediated nephropathy in male rats was available. As discussed in Section 2.2.1.2, Renal Effects, oe globulin- mediated nephrotoxicity is not considered an appropriate end point for the derivation of MRLs for gasoline because it is unique to male rats and, thus, not relevant to human risk assessment. 

Basic problems of animal-to-human extrapolation are in the OTA s report (op. cit.) and comprehensively treated in Edward Calabrese, Principles of Animal Extrapolation (John Wiley and Sons New York, 1983). The particular problem of extrapolation of teratology data from animals to humans is concisely discussed by V. Frankos in his paper FDA perspectives in the use of teratology data for human risk assessment (Fundamental and Applied Toxicology, Vol. 5, 1985, pp 615-25). 

The detection and analysis, including quantification, of cyanobacterial toxins are essential for monitoring their occurrence in natural and controlled waters used for agricultural purposes, potable supplies, recreation and aquaculture. Risk assessment of the cyanobacterial toxins for the protection of human and animal health, and fundamental research, are also dependent on efficient methods of detection and analysis. In this article we discuss the methods developed and used to detect and analyse cyanobacterial toxins in bloom and scum material, water and animal/clinical specimens, and the progress being made in the risk assessment of the toxins. 

The final article, by S. G. Bell and G. A. Codd of the University of Dundee Department of Biological Services, is concerned with detection, analysis, and risk assessment of cyanobacterial toxins. These can be responsible for animal, fish, and bird deaths and for ill-health in humans. The occurrence of toxic cyanobacterial blooms and scums on nutrient-rich waters is a world-wide phenomenon and cases are cited from Australia, the USA, and China, as well as throughout Europe. The causes, indentification and assessment of risk, and establishment of criteria for controlling risk are discussed. 

The other main application area for predictive error analysis is in chemical process quantitative risk assessment (CPQRA) as a means of identifying human errors with significant risk consequences. In most cases, the generation of error modes in CPQRA is a somewhat unsystematic process, since it only considers errors that involve the failure to perform some pre-specified function, usually in an emergency (e.g., responding to an alarm within a time interval). The fact that errors of commission can arise as a result of diagnostic failures, or that poor interface design or procedures can also induce errors is rarely considered as part of CPQRA. However, this may be due to the fact that HEA techniques are not widely known in the chemical industry. The application of error analysis in CPQRA will be discussed further in Chapter 5. 

From a human reliability perspective, a number of interesting points arise from this example. A simple calculation shows that the frequency of a major release (3.2 x lO"" per year) is dominated by human errors. The major contribution to this frequency is the frequency of a spill during truck unloading (3 X10" per year). An examination of the fault tree for this event shows that this frequency is dominated by event B15 Insufficient volume in tank to imload truck, and B16 Failure of, or ignoring LIA-1. Of these events, B15 could be due to a prior human error, and B16 would be a combination of instrument failure and human error. (Note however, that we are not necessarily assigning the causes of the errors solely to the operator. The role of management influences on error will be discussed later.) Apart from the dominant sequence discussed above, human-caused failures are likely to occur throughout the fault tree. It is usually the case that human error dominates a risk assessment, if it is properly considered in the analysis. This is illustrated in Bellamy et al. (1986) with an example from the analysis of an offshore lifeboat system. 

There is a continuing interest in the development of biomarker assays for use in environmental risk assessment. As discussed elsewhere (Section 16.6), there are both scientific and ethical reasons for seeking to introduce in vitro assays into protocols for the regulatory testing of chemicals. Animal welfare organizations would like to see the replacement of toxicity tests by more animal-friendly alternatives for all types of risk assessment—whether for environmental risks or for human health. 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

Histological changes in the spleen related to diisopropyl methylphosphonate intake were not observed in male or female rats exposed to 1 mg/kg/day of diisopropyl methylphosphonate in their drinking water for 26 weeks (Army 1978). As discussed in Section 2.2.2.1, there is some confusion concerning the concentration units and purity of the diisopropyl methylphosphonate used in the Army (1978) study (EPA 1989), and therefore results from the Army (1978) study are considered inappropriate for human health risk assessment. No changes in spleen weight were noted in male or female mink exposed to... 

No differences were noted in the litter sizes among those treated and the controls. No differences were noted in the number of stillborn pups or in pup weights. The study authors concluded that there was no evidence of adverse diisopropyl methylphosphonate-induced reproductive effects. However, as discussed in Section 2.2.2.1, there is some confusion regarding the actual doses to which the animals were exposed in the Hardisty et al. (1977) study. Therefore, results from this study are considered inappropriate for human health risk assessment. 

As U.S. EPA continues to revise the regulatory program for incinerators in order to adequately protect human health and the environment, the omnibus permitting authority, site-specific risk assessments, and public participation issues have received greater attention. The following discusses both issues in greater detail. 

An important input to the Risk Estimation step, as shown in Figure 1, is the analysis of health effects associated with the pollutant in question. Since environmental toxicology is itself a complex and difficult field, we have confined this paper to a discussion of how dose-response estimates can be utilized within a risk assessment, with emphasis on human carcinogenesis. Thus, the scope of this paper corresponds to the four steps surrounded by a dashed line in Figure 1. 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

EMEA (2001) Discussion paper on environmental risk assessment on non-genetically modified organisms (non-GMO) containing medicinal products for human use. CPMP/ SWP/4447/00 draft corr. The European Agency for the Evaluation of Medical Products... 

Besse JP, Garric J (2010) Environmental risk assessment and prioritization stratagies for human pharmaceuticals review and discussion. In Benoit R (ed) Pharmaceuticals in the environment current knowledge and need assessment to reduce presence and impact. IWA Publishing, London... 

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