Exponent

About: Exponent is a company organization based out in Menlo Park, California, United States. It is known for research contribution in the topics: Population & Risk assessment. The organization has 1589 authors who have published 2680 publications receiving 88140 citations.

The use of toxic equivalency factor distributions in probabilistic risk assessments for dioxins, furans, and PCBs.

Abstract: Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated biphenyl (PCB) congeners have been developed by the World Health Organization (WHO). Each TEF was derived from a range of relative potency (REP) estimates obtained from in vivo and in vitro studies wherein the potency of the congener was evaluated relative to 2,3,7,8-TCDD (or some other appropriate benchmark). For most congeners, the range of REP values spans several orders of magnitude, and the degree of conservatism varies widely among the congeners. Although some TEFs are greater than the maximum REP value, others are less than the minimum. This suggests that the point estimate TEFs introduce a significant amount of variability and uncertainty into the PCB and PCDD/F risk assessment process. The use of REP data distributions, rather than point estimate TEFs, would permit a more informed evaluation of the variability and uncertainty in the attendant risk estimates. Further, a standardized method of choosing a TEF from an REP distribution would ensure a uniform degree of conservatism in the TEF values. In this analysis, distributions of REP values were derived for the coplanar PCBs and 2,3,7,8-substituted PCDD/Fs. There are 936 REP values in the WHO database; the number of values per congener ranges from 1 (1,2,3,7,8,9-HxCDF) to 117 (PCB126). Twenty REP values qualified by WHO as " " were not used. Fit tests indicate that most distributions are lognormal. Mean, standard deviation, and 50th and 95th percentile values for each REP distribution are presented. In general, the WHO TEFs for the PCDD/Fs are at the upper bound (75th percentile or greater) of the underlying REP distributions, while the PCB TEFs tend to be more representative of the central tendency of the underlying REP distribution. A simplistic weighting scheme that emphasizes long-term in vivo studies suggests that the REP distributions may not be overly sensitive to weighting techniques--that is, the statistical descriptors of the weighted distributions were similar to those of the unweighted distributions. A case study using fish tissue PCB and PCDD/F data suggests that in some settings the use of WHO TEFs may understate upper bound PCB risks relative to PCDD/F risks. A preliminary sensitivity analysis suggests that measurement endpoint, tissue-type and species (or strain) may be significant contributors to the variability and heterogeneity in the underlying REP data for some congeners. Although there are fundamental shortcomings inherent in any TEF scheme, evidence suggests that some form of REP distributions should be used in lieu of or in addition to point estimate TEFs in settings where PCBs and PCDD/Fs are commingled.

Fugacity and activity analysis of the bioaccumulation and environmental risks of decamethylcyclopentasiloxane (D5)

Abstract: As part of an initiative to evaluate commercial chemicals for their effects on human and environmental health, Canada recently evaluated decamethylcyclopentasiloxane (D5; CAS no. 541-02-06), a high-volume production chemical used in many personal care products. The evaluation illustrated the challenges encountered in environmental risk assessments and the need for the development of better tools to increase the weight of evidence in environmental risk assessments. The present study presents a new risk analysis method that applies thermodynamic principles of fugacity and activity to express the results of field monitoring and laboratory bioaccumulation and toxicity studies in a comprehensive risk analysis that can support risk assessments. Fugacity and activity ratios of D5 derived from bioaccumulation measures indicate that D5 does not biomagnify in food webs, likely because of biotransformation. The fugacity and activity analysis further demonstrates that reported no-observed-effect concentrations of D5 normally cannot occur in the environment. Observed fugacities and activities in the environment are, without exception, far below those corresponding with no observed effects, in many cases by several orders of magnitude. This analysis supports the conclusion of the Canadian Board of Review and the Minister of the Environment that D5 does not pose a danger to the environment. The present study further illustrates some of the limitations of a persistence-bioaccumulation-toxicity-type criteria-based risk assessment approach and discusses the merits of the fugacity and activity approach to increase the weight of evidence and consistency in environmental risk assessments of commercial chemicals.

Strategies and tools for preventing neurotoxicity: To test, to predict and how to do it

Abstract: A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National Research Council (NRC) of the US National Academies of Science, high-throughput in vitro tests will provide evidence for alterations in "toxicity pathways" as the best possible method of large scale toxicity prediction. The challenges to implement this proposal are enormous, and provide much room for debate. While many efforts address the technical aspects of implementing the vision, many questions around it need also to be addressed. Is the overall strategy the only one to be pursued? How can we move from current to future paradigms? Will we ever be able to reliably model for chronic and developmental neurotoxicity in vitro? This paper summarizes four presentations from a symposium held at the International Neurotoxicology Conference held in Xi'an, China, in June 2011. A. Li reviewed the current guidelines for neurotoxicity and developmental neurotoxicity testing, and discussed the major challenges existing to realize the NCR vision for toxicity testing. J. Llorens reviewed the biology of mammalian toxic avoidance in view of present knowledge on the physiology and molecular biology of the chemical senses, taste and smell. This background information supports the hypothesis that relating in vivo toxicity to chemical epitope descriptors that mimic the chemical encoding performed by the olfactory system may provide a way to the long term future of complete in silico toxicity prediction. S. Ceccatelli reviewed the implementation of rodent and human neural stem cells (NSCs) as models for in vitro toxicity testing that measures parameters such as cell proliferation, differentiation and migration. These appear to be sensitive endpoints that can identify substances with developmental neurotoxic potential. C. Sunol reviewed the use of primary neuronal cultures in testing for neurotoxicity of environmental pollutants, including the study of the effects of persistent exposures and/or in differentiating cells, which allow recording of effects that can be extrapolated to human developmental neurotoxicity.