Hazard assessment human data

In this chapter the risk assessment is briefly introduced. Risk assessment is divided into four steps hazard identification, hazard characterization, exposure assessment, and risk characterization. This chapter also highlights five risk and life cycle impact assessment models (EUSES, USEtox, GLOBOX, SADA, and MAFRAM) that allows for assessment of risks to human health and the environment. In addition other 12 models were appointed. Finally, in the last section of this chapter, there is a compilation of useful data sources for risk assessment. The data source selection is essential to obtain high quality data. This source selection is divided into two parts. First, six frequently used databases for physicochemical... 

Plants used to produce PRPs should be amenable to confinement . Isolation distances were increased, and the cultivation of food and feed crops following a PRP crop was discouraged. New hazard and exposure data for human and livestock health assessment may also be required from PRP-containing traditional food or feed crops prior to the approval of field trials. Exposure risk concerns the potential for PRPs to be present in human food or animal feed, and where exposure can occur, what mechanisms are used to limit biological activity. Hazards included direct toxicity and allergenicity in humans or animals as well as hazards presented by the coproduct streams that result from processing. These latter requirements could place a major burden on proponents to prove their materials are safe prior to even confined field trials. 

The first principle in hazard assessment is to have the data correspond as closely as possible to the real-life situation that is, the nearer the model to humans, the better the quality of the prediction of any potential hazards. The second principle should now also be clear to be able to translate toxicity to hazard, and to be able to manage such hazards, it is essential to know how the agent is to be used and the marketplace it is to be part of. It is hoped that this section has made these relationships clear. 

In the absence of human data, or when the available human data are insufficiently quantitative, or are insufficiently sensitive to rule out risks, animal data will be used for hazard identification and dose-response assessment. 

The data required for the risk assessment in relation to human health can be categorized as data on the identity of the substance, its physico-chemical and toxicological properties, and on exposure. The minimum data set required for a risk assessment depends on the chemical use category (industrial chemical, pesticide, biocide, food additive, food contact material, etc.), the regulation involved, and the goal of the risk assessment. This chapter will focus on the data used in the hazard assessment. 

This chapter will describe the various types of data used in the hazard assessment process, including human data, data from laboratory animal studies, data from in vitro studies, and nontesting data that can be deducted from the physico-chemical structure of the substance. 

Human data adequate to serve as the sole basis for a hazard assessment are rare however, when available, reliable and relevant human data are preferable over animal data. 

In relation to a hazard assessment, the relative lack of sensitivity of human data may cause particular difficulty. Therefore, negative human data cannot be used to override the positive findings in animals, unless it has been demonstrated that the mode of action of a certain toxic response observed in animals is not relevant for humans. In such a case, a full justification is required. 

The aim of the hazard assessment of a chemical substance under evaluation is to assess whether exposure to the chemical might result in adverse health effects in humans, based on a critical evaluation of the available data on the inherent toxicological properties of the substance as well as the toxicological mode(s) of action/mechanisms of toxicity. 

Finally, the use of different types of information (human data, data from studies in experimental animals, in vitro test data, and other data such as, e.g., data on physico-chemical properties and (Q)SAR) in the hazard assessment for a specific endpoint is addressed in more detail. 

In the first step of the hazard assessment process, aU effects observed are evaluated in terms of the type and severity (adverse or non-adverse), the dose-response relationship, and NOAEL/LOAEL (or alternatively BMD) for every single effect in aU the available studies if data are sufficient, and the relevance for humans of the effects observed in experimental animals. In this last step of the hazard assessment, all this information is assessed as a whole in order to identify the critical effect(s) and to derive a NOAEL, or LOAEL, for the critical effect(s). It is usual to derive a NOAEL on the basis of effects seen in repeated dose toxicity studies and in reproductive toxicity studies. However, for acute toxicity, irritation, and sensitization it is usually not possible to derive a NOAEL because of the design of the studies used to evaluate these effects. For each toxicological endpoint, these aspects are further addressed in Sections 4.4 through 4.10. 

The most relevant study to base a hazard assessment and derivation of a tolerable intake upon is a study that reflects the human exposure situation as well as possible. Eor numerous substances, data are only available from acute (single exposure), subacute (14—28 days), or subchronic (90 days) animal studies. In order to derive, e.g., a TDl or RfD for such a substance, it may be necessary to base the assessment on data from a shorter duration study. An assessment factor allowing for differences in the experimental exposure duration and the duration of exposure for the population and scenario under consideration needs to be considered taking into account that, in general, the experimental NOAEL will decrease with increasing exposure duration as well as other and more serious adverse effects may appear with increasing exposure duration. 

Hazard identification is the process of collecting and evaluating information on the effects of an agent on animal or human health and well-being. In most cases, this involves a careful assessment of the adverse effects and what is the most sensitive population. The dose-response assessment involves evaluation of the relationship between dose and adverse effect. Typically, an effort is made to determine the lowest dose or exposure at which an effect is observed. A comparison is often made between animal data and any human data that might be available. Next is exposure assessment, in which an evaluation of the likely exposure to any given population is assessed. Important parameters include the dose, duration, frequency, and route of exposure. The final step is risk characterization, in which all the above information is synthesized and a judgment made on what is an acceptable level of human exposure. In the simplest terms, risk is the product of two factors hazard and exposure (i.e. hazard x exposure = risk). In real risk assessments, all hazards may not be known and exposure is often difficult to quantify precisely. As a result, the calculated risk may not accurately reflect the real risk. The accuracy of a risk assessment is no better than the data and assumptions upon which it is based. 

Cancer. Studies found no relationship between endogenous p-cresol levels in the urine and the occurrence of large bowel cancer (Bone et al. 1976) or bladder cancer (Renwick et al. 1988) in humans. There are no data available regarding the carcinogenicity of exogenous cresols in humans. No cancer bioassays have been conducted in animals, but the results of a promotion study in mice suggested that cresols can be cancer promoters. Cresols have some ability to interact with mammalian DNA in vitro, but it is impossible to assess the potential hazard to humans without more information. 

In the chemical safety report, the hazard assessment of a particular substance is based on the data set provided in the technical dossier. This contains substance-specific information on physicochemical properties as well as on toxicological and ecotoxicological hazards. One objective of the hazard assessment is the substance s hazard identification, which comprises the determination of its physicochemical and hazardous properties for the purpose of classification. Concerning human health hazards, both human and nonhuman information is taken into consideration and evaluated with respect to the classification criteria laid down in the Dangerous Substances Directive and in the CLP Regulation, respectively. However, in most cases human data do not exist, so the hazard identification has to be based on data from animal experiments. With respect to teratogenicity, this hazardous property may in principle be detected in the following toxicity studies ... 

Human health hazards assessment is the process of identifying the potential effects that chemical may have on humans who are exposed to it, and of determining the levels at which these effects may occur. Human health toxicity data are compared with data from the exposure assessment module to assess human health risk in the risk characterization module. 

Ashby, J. Clapp, M.J.L. (1995) The rodent dominant lethal assay a proposed format for data presentation that alerts to psendo-dominant lethal effects. Mutat. Res., 330, 209-218 Ashby, J., Brady, A., Elcombe, C.R., Elliott, B.M., Ishmael, J., Odnm, J., Tngwood, J.D., Kettle, S. Purchase, IF. (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. exp. Toxicol., 13 (Suppl. 2), S1-S117... 

The evaluation of dose-response relationships is a critical component of hazard characterization (OECD, 1989 ECETOC, 1992 US , 1997a IPCS, 1999). Evidence for a dose-response relationship is an important criterion in establishing a toxic reproductive effect. It includes the evaluation of data from both human and laboratory animal studies. Because quantitative data on human dose-response relationships are infrequently available, the dose-response evaluation is usually based on the assessment of data from tests performed using laboratory animals. However, if data are available in humans with a sufficient range of doses, dose-response relationships in humans can also be evaluated. 

The hazard assessment identifies the adverse effects that a chemical may cause and investigates the relationship between their magnitude and the dose to which an organism is exposed. A major source of uncertainty is the use of data from tests on laboratory animals (or plants) to investigate toxicity to other species (including humans). There are at least four reasons why there is uncertainty in the application of test data to exposures of humans and wild animals (RCEP, 2003, pp21—22 Rodricks, 1992, ppl58-179) ... 

Exposure Levels in Humans. Data regarding levels of diazinon in humans from environmental exposures (the general population, populations living near hazardous waste sites, or occupationally exposed groups) are not available. It is arguable that these levels are not knowable because of the rapid metabolism and clearance of diazinon after it enters the body (Iverson et al. 1975 Machin et al. 1975 Mount 1984 Mucke et al. 1970). Additional studies which associate levels of diazinon in the environment and levels of diazinon metabolites in body tissues would be helpful. These studies are needed to give a practical assessment of exposure risks. This information is necessary for assessing the need to conduct health studies on these populations. 

Exposure Levels in Humans. Tin has been detected in human adipose tissue (Stanley 1986), but the data are not current. No data were available on biological monitoring for tin in other tissues. Biological monitoring data, especially for populations near hazardous waste sites, would help to assess human exposure to tin. 

As discussed in the introduction to Section 2.1, there are a number of limitations in the human database for most health effects, the data are inadequate to assess the potential for humans having a particular effect. Because the human data are incomplete, hazard and risk must be extrapolated across species. A large number of adverse effects have been observed in animals, and most have been observed in every experimental animal species tested, if the appropriate dose is administered. This is illustrated in Table 2-8 for 8 major effects associated with CDD toxicity (acute lethality, hepatotoxicity, wasting syndrome, chloracne, immunotoxicity, reproductive toxicity, developmental toxicity, and cancer). With the exception of acute lethality in humans, positive responses have been observed in each tested species, when a response has been investigated. Despite the similarities in hazard response between different species, large species differences in sensitivity have been observed. Comparisons of species sensitivity demonstrate that no species is consistently sensitive or refractory for all effects and, for some effects,... 

Geographic Information System (GIS) A system that allows for the interrelation of quality data (as well as other information) from a diversity of sources based on multilayered geographical information-processing techniques, hazard (toxic) The set of inherent properties of a stressor or mixture of stressors that makes it capable of causing adverse effects in humans or the environment when a particular intensity of exposure occurs. See also risk, hazard assessment (HA) Comparison of the intrinsic ability to cause harm with expected environmental concentration. In Europe, it is typically a comparison of predicted environmental concentration (PEC) with predicted no-effect concentration (PNEC). It is normally based on a single value for effects and exposure. It is sometimes incorrectly referred to as risk assessment. 

---