Risk assessment perspective

Andersen (2003) gives a comprehensive review outlining the history of PBPK modeling, emphasizes more recent applications of PBPK models in health risk assessment, and discusses the risk assessment perspective provided by modern uses of these modeling approaches. 

Kimmel GL, Clegg ED, Crisp TM (1995) Reproductive toxicity testing a risk assessment perspective. In Witorsch RJ ed. Reproductive toxicology. New York, Raven Press, pp 75-98. 

US Environmental Protection Agency. A review of ecological assessment case studies from a risk assessment perspective. Washington, DC Risk Assessment Forum, USEPA, 1993. EPA/630/R-92/005. 

Cancer risk-specific doses and screening values for end points other than cancer are essentially equivalent from a risk assessment perspective. 

As noted above, the lowest effective doses in adults and young are often similar. However, the type and severity of effects from an exposure may be very different. This becomes an important consideration, especially in evaluating prenatal animal studies. Because the developing embryo/fetus is exposed in the maternal animal, it has been argued that if maternal toxicity is observed, any developmental toxicity could be due to the compromised maternal system. However, several issues should be considered. The difference between the lowest maternally toxic dose and the developmentally toxic dose may at times be related to the relative thoroughness with which endpoints are evaluated in dams and offspring, as well as to the sensitivity of the end-points. Moreover, the severity of the effects must be considered the developmental effects may be permanent, while the maternal effects may be reversible. From a risk assessment perspective, developmental toxicity in the presence of maternal toxicity cannot be simply considered secondary to maternal toxicity and discounted (USEP A, 1991). 

Dellarco, V. L., and Baetcke, K. (2005). A risk assessment perspective application of mode of action and human relevance frameworks to the analysis of rodent tumor data. Toxicol Sci 86, 1-3. 

Weiss, B. 1998. A risk assessment perspective on the neurobehavioral toxicity of endocrine disrupters. Toxicol. Ind. Health 14(l-2) 341-59. 

U.S. Environmental Protection Agency, A Review of Ecological Assessment Case Studies from a Risk Assessment Perspective, EPA/630/R-92/ 005, U.S. Environmental Protection Agency, Washington, DC, 1993. Albone, D.J. Kibblewhite, M.G. Sansom, L.E. Morris, P.R. The Storage Stability of Oil Spill Dispersants, Warren Spring Laboratory Report LR670 (CS), Hertfordshire, UK, 1988. 

Upon reporting these results, however, the authors cautioned that "error propagation due to parameter uncertainty can be expected to be considerable." They went on to conclude that "the role of plastic in bioaccumulation of POPs is scientifically interesting but not very relevant from a risk assessment perspective. This, however, may be different for chemicals for which plastic is the main source of bioaccumulation such as additives leaching from microplastic" (p. 7818). 

Grandjean, P., White, R. E, and Weihe, P. (1996). Neurobehavioral epidemiology Application in risk assessment. Enniron. Health Perspect. 104(2), 397- 00. 

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. 

Since 1970 tlie field of healtli risk assessment Itas received widespread attention witliin both tlie scientific and regulatoiy committees. It has also attracted tlie attention of the public. Properly conducted risk assessments have received fairly broad acceptance, in part because they put into perspective the terms to. ic, Itazard, and risk. Toxicity is an inlierent property of all substances. It states tliat all chemical and physical agents can produce adverse healtli effects at some dose or under specific exposure conditions. In contrast, exposure to a chemical tliat lias tlie capacity to produce a particular type of adverse effect, represents a health hazard. Risk, however, is tlie probability or likelihood tliat an adverse outcome will occur in a person or a group tliat is exposed to a particular concentration or dose of the hazardous agent. Tlierefore, risk can be generally a function of exposure and dose. Consequently, healtli risk assessment is defined as tlie process or procedure used to estimate tlie likelihood that... 

Clewell HJ 3rd, Gentry PR, Covington TR, Gearhart JM. Development of a physiologically based pharmacokinetic model of trichloroethylene and its metabolites for use in risk assessment. Environ Health Perspect 2000 May 108 Suppl 2 283-305. 

Quantitative risk assessment is now used extensively for determination of chemical and microbial risks in food. This concept helps to systematically and scientifically judge whether certain hazardous compounds may reach unacceptable risk levels when ingested. Quantitative risk assessment can support both quality design and quality assurance but, we discuss it from the assurance perspective. In the past decade, much attention has been paid to assessment of microbial risks due to then-typical differences as compared to chemical risks ... 

Safe, S. (1998) Hazard and Risk Assessment of Chemical Mixtures Using the Toxic Equivalency Factor Approach. Environmental Health Perspectives, 106(Suppl. 4), 1051-1058. 

In terms of environmental metrics to assess processes, it is hopefully clear that a considerable testing burden exists to assess potential environmental hazards that lead to a credible risk assessment. At a first pass, one would typically screen compounds from an environmental hazard perspective to assess their tendency for persistence, bioaccumulation and toxicity. Depending on the final application of the compoimd, one might avoid commercial production of a particular compound, or one might devise processes that would use the... 

Kavlock, R.J., et al., Research needs for the risk assessment of health and environmental effects of endocrine disrupters a report of the U.S. EPA-sponsored workshop, Environ. Health Perspect., 104, 715, 1996. 

This would allow a more comprehensive ecological risk assessment, and also predict a perspective of the geoecological situation changes, in particularly, in the Northern Caspian under varying input of different pollutants into the river-sea system. 

Frankos, V (1985). FDA perspectives on the use of teratology data for human risk assessment. Fund. Appl. Toxicol. 5 615-625. 

The bio availability of organic compounds in soils/sediments to microbes, plants, and animals is important from the perspective of remediation and risk assessment. Cleanup technology (ex situ or in situ) of contaminated soils and bottom sediments requires mass transport of contaminants through the solid materials, which in turn depends on sorption/desorption kinetics. 

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