Risk assessment behavior

Fig. 5 Elevated plus maze for mice. While cautiously entering the platform, the mouse displays risk assessment behavior...

Fig. 7 Results from behavioral testing in the modified hole board (see Sect. 2.2.5). While DBA/2 mice (DBA) display a more pronounced avoidance behavior towards an unprotected area as well as more risk assessment behavior than C57BL/6 (BL6) mice, no differences in term of general exploration and locomotion are found in these strains. Therefore, these strains can be considered to represent an interesting model for high and low anxiety...

Hazard identification involves gathering and evaluating data on the types of health injury or disease that may be produced by a chemical and on the conditions of exposure under which injury or disease is produced. It may also involve characterization of the behavior of a chemical within the body and the interactions it undergoes with organs, cells, or even parts of cells. Hazard identification is not risk assessment. It is a scientific determination of whether observed toxic effects in one setting will occur in other settings. 

Simple models are used to Identify the dominant fate or transport path of a material near the terrestrial-atmospheric Interface. The models are based on partitioning and fugacity concepts as well as first-order transformation kinetics and second-order transport kinetics. Along with a consideration of the chemical and biological transformations, this approach determines if the material is likely to volatilize rapidly, leach downward, or move up and down in the soil profile in response to precipitation and evapotranspiration. This determination can be useful for preliminary risk assessments or for choosing the appropriate more complete terrestrial and atmospheric models for a study of environmental fate. The models are illustrated using a set of pesticides with widely different behavior patterns. 

PBPK and classical pharmacokinetic models both have valid applications in lead risk assessment. Both approaches can incorporate capacity-limited or nonlinear kinetic behavior in parameter estimates. An advantage of classical pharmacokinetic models is that, because the kinetic characteristics of the compartments of which they are composed are not constrained, a best possible fit to empirical data can be arrived at by varying the values of the parameters (O Flaherty 1987). However, such models are not readily extrapolated to other species because the parameters do not have precise physiological correlates. Compartmental models developed to date also do not simulate changes in bone metabolism, tissue volumes, blood flow rates, and enzyme activities associated with pregnancy, adverse nutritional states, aging, or osteoporotic diseases. Therefore, extrapolation of classical compartmental model simulations... 

The relevant changes in exposure rates are also of importance for predicting the behavior of Mangrove ecosystems and environmental risk assessment for their fate. 

Typically extrapolations of many kinds are necessary to complete a risk assessment. The number and type of extrapolations will depend, as we have said, on the differences between condition A and condition B, and on how well these differences are understood. Once we have characterized these differences as well as we can, it becomes necessary to identify, if at all possible, a firm scientific basis for conducting each of the required extrapolations. Some, as just mentioned, might be susceptible to relatively simple statistical analysis, but in most cases we will find that statistical methods are inadequate. Often, we may find that all we can do is to apply an assumption of some sort, and then hope that most rational souls find the assumption likely to be close to the truth. Scientists like to be able to claim that the extrapolation can be described by some type of model. A model is usually a mathematical or verbal description of a natural process, which is developed through research, tested for accuracy with new and more refined research, adjusted as necessary to ensure agreement with the new research results, and then used to predict the behavior of future instances of the natural process. Models are refined as new knowledge is acquired. 

The risk assessment framework, first proposed in 1983 by the National Academies committee that prodnced the Red Book, has proved to be durable. Its influence has extended to other areas of risk assessment, and public health authorities who are responsible for understanding and mitigating the truly large public health problems of our time, those associated in part with certain personal behaviors, are beginning to describe their activities within that same framework. 

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

The developmental neurotoxicity guideline, accepted by OECD in 2007, has added the important aspect of behavioral effects of pre- and postnatal exposure to chemicals. This development arose from the notion that behavioral disorders in man such as anxiety, depression, phobias, autism, and attention deficit hyperactivity disorder, which appear to show increasing prevalences in western societies, may have a perinatal origin (4, 5). In the absence of causal inferences with respect to chemicals it seems nevertheless prudent to assess in a risk assessment whether such causal relations may exist. 

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