Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study.

Cancer potencies of mineral and synthetic elongated particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of elongated particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual elongated particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the elongated particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin elongated particles significantly degrades the resultant particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of elongated particles with aspect ratios less than 8 and lengths greater than 80 µm.

In vitro determinants of asbestos fiber toxicity: effect on the relative toxicity of Libby amphibole in primary human airway epithelial cells.

Background: An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples.

Morphological and chemical mechanisms of elongated mineral particle toxicities.

Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle.

Direct application of biota-sediment accumulation factors.

In the early stages of risk assessments for sites with contaminated sediments, predictions of risks are often complicated or limited by sparse or inadequate bioaccumulation data. These limitations often require risk assessors to estimate bioaccumulation relationships in order to complete the assessments of risk. In the present study, the errors are evaluated with the simple (direct) application of field measured biota-sediment accumulation factors (BSAFs) to other species at a specific location, and to the same species and/or other species at other locations within a site and to other sites.

Organic carbon-water concentration quotients (II(SOC)S and pi(poc)S): measuring apparent chemical disequilibria and exploring the impact of black carbon in Lake Michigan.

Chemical concentration quotients measured between water and total organic carbon (TOC) in sediment (II(SOC)) or suspended particulates (pi(poc)) in southern Lake Michigan reveal up to 2 orders of magnitude differences for polychlorinated biphenyl (PCB), dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and polycyclic aromatic hydrocarbon (PAH) compounds with similar octanol-water partition coefficients (K(ow)S). Apparent disequilibria for PAHs, PCDDs, and PCDFs, determined as measured II(SOC)S or pi(poc)S divided by their organic carbon equilibrium partitioning values, are significantly greater than disequilibria of PCBs with similar K(ow)S. Apparent disequilibria, when adjusted for black carbon content by using published black carbon nonlinear partition coefficients (K(f,bc)S) and a Freundlich exponent (n(f)) value = 0.

Tissue distribution and metabolism of benzo[a]pyrene in embryonic and larval medaka (Oryzias latipes).

The need to understand chemical uptake, distribution, and metabolism in embryonic and larval fish derives from the fact that these early life stages often exhibit greater sensitivity to xenobiotic compounds than do adult animals. In this study, a 6-h acute waterborne exposure immediately after fertilization was used to quickly load the egg with benzo[a]pyrene (BaP). This exposure was used to mimic the initial egg concentration of a persistent bioaccumulative toxicant that could result from maternal transfer.

A hybrid empirical-mechanistic modeling approach for extrapolating biota-sediment accumulation factors and bioaccumulation factors across species, time, and/or ecosystems.

An approach is presented for extrapolating field-measured biota-sediment accumulation factors (BSAFs) and bioaccumulation factors (BAFs) across species, time, and/or ecosystems. This approach, called the hybrid bioaccumulation modeling approach, uses mechanistic bioaccumulation models to extrapolate field-measured bioaccumulation data (i.e.

Comparison of biota-sediment accumulation factors across ecosystems.

Sets of biota-sediment accumulation factors (BSAFs) for fish were compared across ecosystems for nonionic organic chemicals. The sets of BSAFs, when plotted against each other, in log-log space, formed linear relationships and demonstrated that the relative scaling or ranking of the individual BSAFs within a set are consistent, if not the same, across ecosystems. This behavior holds for chemicals that either are, or are not, metabolized by fish.

Biota--sediment accumulation factors for polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in southern Lake Michigan lake trout (Salvelinus namaycush).

A set of high-quality, age-specific biota-sediment accumulation factors (BSAFs) for polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) have been determined from concentrations measured with high-resolution gas chromatography/high-resolution mass spectrometry, by use of the 13C isotopic dilution technique, in lake trout and surficial (0-2 cm) sediment samples from southern Lake Michigan. BSAFs ranged from <0.1 to 18 for PCBs and from <0.

Use of multi-photon laser-scanning microscopy to describe the distribution of xenobiotic chemicals in fish early life stages.

To better understand the mechanisms by which persistent bioaccumulative toxicants (PBTs) produce toxicity during fish early life stages (ELS), dose-response relationships need to be understood in relation to the dynamic distribution of chemicals in sensitive tissues. In this study, a multi-photon laser scanning microscope (MPLSM) was used to determine the multi-photon excitation spectra of several polyaromatic hydrocarbons (PAHs) and to describe chemical distribution among tissues during fish ELS. The multi-photon excitation spectra revealed intense fluorescent signal from the model fluorophore, pentamethyl-difluoro-boro-indacene (BODIPY), less signal from benzo[a]pyrene and fluoranthene, and no detectable signal from pyrene.

Evaluation of two methods for prediction of bioaccumulation factors.

Two methods for deriving bioaccumulation factors (BAFs) used by the U.S. Environmental Protection Agency in development of water quality criteria were evaluated using polychlorinated biphenyl (PCB) data from the Hudson River and Green Bay ecosystems.

The relationship of bioaccumulative chemicals in water and sediment to residues in fish: a visualization approach.

A visualization approach is developed and presented for depicting and interpreting bioaccumulation relationships and data (i.e., bioaccumulation factors [BAFs], biota-sediment accumulation factors [BSAFs], and chemical residues in fish) using water-sediment chemical concentration XY plots.

Effects of aryl hydrocarbon receptor-mediated early life stage toxicity on lake trout populations in Lake Ontario during the 20th century.

Lake trout embryos and sac fry are very sensitive to toxicity associated with maternal exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related chemicals that act through a common aryl hydrocarbon receptor (AHR)-mediated mechanism of action. The loading of large amounts of these chemicals into Lake Ontario during the middle of the 20th century coincided with a population decline that culminated in extirpation of this species around 1960. Prediction of past TCDD toxicity equivalence concentrations in lake trout eggs (TEC(egg)s) relative to recent conditions required fine resolution of radionuclide-dated contaminant profiles in two sediment cores; reference core specific biota--sediment accumulation factors (BSAFs) for TCDD-like chemicals in lake trout eggs; adjustment of the BSAFs for the effect of temporal changes in the chemical distributions between water and sediments; and toxicity equivalence factors based on trout early life stage mortality.