Addressing Human Variability in Risk Assessment—The Robustness of the Intraspecies Uncertainty Factor

Burin, G.J.; Saunders, Doug

doi:10.1006/rtph.1999.1351

Cited by 34 publications

(17 citation statements)

References 37 publications

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“…Biological Mechanisms of Action -Among the factors included in this review are those influencing internal dose, such as metabolic rate constants and partition coefficients. The research efforts included in this review involve compiling available data on these factors, examining general trends in variability in these factors, and assessing their general implications for exposure and risk assessment (e.g., Hattis et al 1999a,b;Burin and Saunders 1999). In addition to these efforts, researchers are also applying these factors in the context of a variety of types of exposure information to develop detailed physiologically based pharmacokinetic (PBPK) models of the disposition and mechanisms of action of specific chemicals (e.g., Wu and Schaum 2000).…”

Section: Application Of Resultsmentioning

confidence: 99%

Review of Information Resources to Support Human Exposure Assessment Models

Boyce

Garry

2002

Human and Ecological Risk Assessment: An International Journal

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Efforts to model human exposures to chemicals are growing more sophisticated and encompass increasingly complex exposure scenarios. The scope of such analyses has increased, growing from assessments of single exposure pathways to complex evaluations of aggregate or cumulative chemical exposures occurring within a variety of settings and scenarios. In addition, quantitative modeling techniques have evolved from simple deterministic analyses using single point estimates for each necessary input parameter to more detailed probabilistic analyses that can accommodate distributions of input parameters and assessment results. As part of an overall effort to guide development of a comprehensive framework for modeling human exposures to chemicals, available information resources needed to derive input parameters for human exposure assessment models were compiled and critically reviewed. Ongoing research in the area of exposure assessment parameters was also identified. The results of these efforts are summarized and other relevant information that will be needed to apply the available data in a comprehensive exposure model is discussed. Critical data gaps in the available information are also identified. Exposure assessment modeling and associated research would benefit from the collection of additional data as well as by enhancing the accessibility of existing and evolving information resources.

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Section: Application Of Resultsmentioning

confidence: 99%

Review of Information Resources to Support Human Exposure Assessment Models

Boyce

Garry

2002

Human and Ecological Risk Assessment: An International Journal

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“…In the risk assessment of food and chemicals, the concept of uncertainty or safety factors (UFs/SFs) has been used for over 50 years to convert the NOAEL into the tolerable or acceptable daily intake (TDI/ADI), a level of exposure "without appreciable health risk" (Burin and Saunders, 1999). The 100-fold UF represents the product of 2 separate 10-fold factors that allow for interspecies differences and human variability (Renwick and Lazarus, 1998).…”

Section: Discussionmentioning

confidence: 99%

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol

et al. 2017

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-3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in highrisk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

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“…The risk assessment process associated with these chemicals is limited because of the use of a variety of assumptions, particularly relating to crossspecies extrapolation, dose response, and estimated exposure levels of humans [70][71][72][73]. Thus, the need has arisen for elucidation of transspecies, chemical-specific biomarkers resulting from quantified exposures to drugs or toxic chemicals.…”

Section: Challengesmentioning

confidence: 98%

Discovery in toxicology: Mediation by gene expression array technology

Hamadeh

Bushel

Paules

et al. 2001

J Biochem & Molecular Tox

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Toxicogenomics is a term that represents the merging of toxicology with novel genomics techniques. Data generated in the new-age era of toxicology is relatively complex, requires new bioinformatics tools for adequate interpretation, and allows for the rapid generation of testable hypotheses. Hazard identification and risk assessment processes will advance from the use of genomics techniques, which will lead to greater understanding of mechanism(s) of action of toxicants, development of novel biomarkers of exposure and effect, and better identification of sensitive subpopulations.

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Addressing Human Variability in Risk Assessment—The Robustness of the Intraspecies Uncertainty Factor

Cited by 34 publications

References 37 publications

Review of Information Resources to Support Human Exposure Assessment Models

Review of Information Resources to Support Human Exposure Assessment Models

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol

Discovery in toxicology: Mediation by gene expression array technology

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