Data, in risk assessment

Notice Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment E-Docket ID No. ORD-2005-0022. Fed Reg July 28, 2005 70 (144) 43692-43693. 

Air Force. 1990. Development and validation of methods for applying pharmacokinetic data in risk assessment Volume n. Trichloroethylene. Wright-Patterson Air Force Base, OH U.S. Air Force, Air Force Systems Command, Harry G. Armstrong Medical Research Laboratory, Human Systems Division. NTIS No. AD-A237 366. 

The methodology for conducting aquatic model ecosystem studies was well established by the late 1990s. However, the use of the data in risk assessments raised a number of uncertainties regarding their interpretation and implementation [32]. Four of the uncertainties that were identified were the extent to which aquatic model ecosystem data generated in one location could be applied to another situation, the potential influence of mixtures of chemicals or stressors, whether the timing (season) of application would influence the outcome of the study, and whether differences in ecosystem properties (e.g., trophic status) might influence the results. 

Cunningham, M.L., Workshop overview use of genomic data in risk assessment, Toxicol. Sci., 73, 209, 2003. 

Two of the more interesting uses of pharmacokinetic data in risk assessment involve the neurotoxic agents lead and methylmercury (Chapter 4). In the case of lead, epidemiological studies have typically involved the development of quantitative relationships between levels of lead in the blood and adverse health effects. Other measures of lead in the body have also been used. Levels in blood are now very easy to measure, and they do carry the strong advantage that they integrate cumulative exposures from many possible sources (water, food, paint, soil, air, consumer products). Current public health targets for lead are expressed as blood concentrations, typically in pg/dL (Chapter 4). 

EuKng S et al (2011) Use of genomic data in risk assessment case study II. Evaluation of the dibutyl phthalate toxicogenomic data set. Toxicol Appl Pharmacol. doi S0041-008X(ll)00236-5 (pii)I0.I0I6/j.taap. 2011.06.014... 

The application of human data in risk assessment for children has been detailed in a number of publications (USEPA, 1991 Richter-Reichhelm et al., 2002 IPCS, 2005 Kimmel et al., 2006). In general, the risk assessor should evaluate each human study for its power and potential bias. The power of the study is the study s ability to detect an effect. It is dependent on the size of the study population, the frequency of the effect or the exposure in the population, and the level of risk to be identified. The greater the population size and the effect or exposure frequency, the greater the power of the study. In studies of low power, it is generally not possible to establish the lack of an association between an exposure and an effect, and even positive findings may be difficult to support. Metaanalysis, which combines populations from different studies, may increase the power of the overall database, but the potential for the combination of dissimilar populations must be considered in any risk assessment. 

Gundert-Remy U, Sonich-Mullin C, IPCS Uncertainty and Variability Planning Workgroup and Drafting Group (2002) The use of toxicokinetic and toxicodynamic data in risk assessment an international perspective. Sci Total Environ, 288(1-2) 3-11. 

Within this model, attention is given to the use of the data in risk assessment. The approach is very simple for compounds that show (1) no cumulative toxicity,... 

Examples of other workshops include one on the Use of Human (Epidemiology) Data in Risk Assessment workshop in conjunction with World Health Organization s International Programme of Chemical Safety (IPCS), and an Influence of Maternal Toxicity on Developmental Toxicity workshop. 

USEPA. Approaches for the application of physiologically based pharmacokinetic (PBPK) models and supporting data in risk assessment. Report number EPA/600/ R-05/043A. Washington, DC US Environmental Protection Agency, 2005. 

The initial process in the application of toxicity (dose-response) data in risk assessment is the extrapolation of findings to establish acceptable levels (AL) of human exposure. These levels may be reference values (inhalation reference concentrations, RfC or oral reference doses, RfD), minimal risk levels (MRL) values, occupational exposure limits, and so on. When the toxicity data are derived from animals, the lowest dose representing the NOAEL (preferably) or the LOAEL defines the point of departure (POD). In setting human RfD, RfC, or MRL values, the POD requires several extrapolations (see [13] and revisions). Extrapolations are often made for interspecies differences, intraspecies variability, duration of exposure, and effect level. Each area is generally addressed by applying a respective uncertainty factor having a default value of 10 their multiplicative value is called the composite uncertainty factor (UF). The UF is mathematically combined with the dose at the POD to determine the reference value ... 

Although these types of data are beginning to be incorporated into regulatory assessments, they are not always easy to collect and interpret. So, while we can expect wider use of ADME and mechanistic data in risk assessments in the future, for the present the regulatory... 

Many obvious research needs arc apparent after a pcru.sal of the anticholinesterase mixture literature. Most important is the need to conduct mixture testing in the low range of the dose-response relationship researchers need to use sensitive end points such as cholinesterase inhibition rather than lethality. Experimental design and statistical analyses are also very important to the interpretation of results. In their paper on the use of mixture data in risk assessment. 

Use of site-specific As bioavailability data in risk assessment may dramatically lower cleanup costs. The demand for site-specific soil bioavailability data will likely increase because in vivo and in vitro bioavailability methods are inexpensive compared with site cleanup based on overly conservative soil bioavailability As levels. Site-specific As availability information will lower the degree of uncertainty in risk assessment and provide scientifically derived data to aid in the selection of appropriate remedies that are cost effective and protective of human health and the environment. 

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