Philip M. Cook

Toxic equivalency factors of polychlorinated dibenzo-p-dioxin, dibenzofuran and biphenyl congeners based on early life stage mortality in rainbow trout (Oncorhynchus mykiss)

Abstract Toxic equivalency factors (TEFs), which relate the potency of individual polychlorinated dibenzo- p -dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners to 2,3,7,8- tetrachlorodibenzo- p -dioxin (TCDD), are used to assess the risk to fish early life stage development posed by complex mixtures of these congeners in eggs. Newly fertilized rainbow trout ( Oncorhynchus mykiss ) eggs were injected with graded doses of 5 PCDD, 4 PCDF or 4 nonortho substituted PCB congeners, and sac fry mortality was used to determine TEFs. Potencies of non-ortho substituted PCBs in causing early life stage mortality were much lower than expected based on Ah receptor binding affinities in mammals and 4 mono-ortho and 5 di-ortho substituted PCB congeners did not cause rainbow trout early life stage mortality at doses of 24 300–130 000 ng/g egg. To determine if increased elimination of PCBs, relative to PCDDs and PCDFs, was responsible for the lower toxic potency of PCBs in fish compared to mammals, PCDD, PCDF and PCB congeners were injected into newly fertilized rainbow trout eggs and the percent dose remaining 35 days later at the sac fry stage of development was determined. The percent dose of various PCB congeners remaining in sac fry (62–88%) was similar to that of PCDD and PCDF congeners (78–91%), indicating that increased elimination is not responsible for the extremely low potency of the non-ortho substituted PCB congeners or for the failure of the mono- and di-ortho substituted PCB congeners to cause rainbow trout early life stage mortality.

Bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans from contaminated Wisconsin River sediment to carp

Abstract The bioavailability of 2,3,7,8-TCDD from sediment to freshwater fish was studied in laboratory exposures. Carp (10g) exposed to Wisconsin River sediment (39 pg/g) for 55 days accumulated 7.5 pg/g. Maintaining exposured fish in clean water for an additional 205 days resulted in depuration of 32–34% TCDD. These values compare to field data where sediments ranged from 30–200 pg/g and 1.5 kg carp (70 pg/g) depurated 55% in 325 days. Analysis of sediment, laboratory exposed fish, and Wisconsin River fish for other PCDDs and PCDFs showed residues of 2,3,7 and 8 substituted congeners selectively enriched.

Asbestiform amphibole minerals: detection and measurement of high concentrations in municipal water supplies.

Ashestiform amphibole minerals, which have been demonstrated to be associated with human health problems, have been detected in substantial quantities in municipal water supplies taken from western Lake Superior Water. The total concentrationl of amphibole minerals in the Duluth, Minnesota, water supply, as measured by x-ray diffraction for daily samples of suspended solids averages 0.19 milligram per liter with large fluctuations due to seasonal and climatological effects on lake circulation. Electron microscopic examination of these water samples confirms the presence of asbestiform amphibole fibers. A conservatiue estimate of the fiber count for 1973 Duluth water supply samples is (1 to 30) x 106 amphibole fibers identifiable by electron diffraction per liter of water with a mass concentration of 1 to 30 micrograms per liter.

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 particles 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. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles.

Potency of a Complex Mixture of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners Compared to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Causing Fish Early Life Stage Mortality

Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalents concentration (TEC) assumes that polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additively and via a common mechanism to cause toxicity. To test these assumptions, 11 TCDD-like congeners and three non-TCDD-like congeners were combined at ratios typically found in Lake Michigan lake trout. The potency of the mixture, expressed as TEC based on fish-specific toxic equivalency factors, was compared to TCDD for producing lake trout and rainbow trout early life stage mortality. Signs of toxicity following exposure of newly fertilized eggs to the mixture or to TCDD were indistinguishable; sac fry mortality associated with blue-sac disease, and slopes of the dose-response curves for percentage sac fry mortality versus egg TEC or versus egg TCDD were parallel. However, the mixture dose-response curves were significantly shifted to the right of the TCDD dose-response curves by 1.3- and 1.8-fold as illustrated by LD50 values. Following exposure to the mixture or TCDD, LD50S for lake trout early life stage mortality were 97 (89-110) pg TE/g egg and 74 (70-80) pg TCDD/g (LD50, 95% fiducial limits) and for rainbow trout were 362 (312-406) pg TE/g egg and 200 (148-237) pg TCDD/g egg. These data suggest that TCDD-like congeners act via a common mechanism to cause toxicity during trout early development, but may not act strictly additively when combined in a mixture of TCDD- and non-TCDD-like congeners at ratios found in Great Lakes fish. The deviation from additivity, however, is less than current safety factors of 10-fold commonly applied in ecological risk assessments, providing support for the continued use of a TE additivity model for assessing risk posed by complex mixtures of PCDDs, PCDFs, and PCBs to fish.

Integrated assessment of contaminated sediments in the lower Fox River and Green Bay, Wisconsin.

Samples of sediment and biota were collected from sites in the lower Fox River and southern Green Bay to determine existing or potential impacts of sediment-associated contaminants on different ecosystem components of this Great Lakes area of concern. Evaluation of benthos revealed a relatively depauperate community, particularly at the lower Fox River sites. Sediment pore water and bulk sediments from several lower Fox River sites were toxic to a number of test species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata, Selenastrum capricornutum, and Photobacterium phosphorum. An important component of the observed toxicity appeared to be due to ammonia. Evaluation of three bullhead (Ictalurus) species from the lower Fox River revealed an absence of preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium bioassay indicated relatively little mutagenicity in sediment extracts. Apparent adverse reproductive effects were noted in two species of birds nesting along the lower Fox River and on a confined disposal facility for sediments near the mouth of the river, and there were measurable concentrations of potentially toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in sediments from several of the study sites. Based on toxic equivalency factors and the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota from the lower Fox River/Green Bay system was due to the planar PCBs. The results of these studies are discussed in terms of an integrated assessment focused on providing data for remedial action planning.

Relative Mesothelioma Induction in Rats by Mineral Fibers: Comparison with Residual Pulmonary Mineral Fiber Number and Epidemiology

AbstractLarge differences in mesothelioma induction by various minerals were demonstrated in rats on the basis of tumor to fiber ratios. Erinoite was 500–800 times more tumorigenic and crocidolite 30–60 times more tumorigenic than chysotile. Erionite was relatively more potent when introduced intratrachealy than either asbestos. These data rank similarly to human exposure to the same mineral fibers. We propose that a factor here termed intrinsic potency probably related to surface activity overrides both fiber number and geometric configuration when fibers of strongly different tumorigenicity are compared. This potency difference may be related to differing tendencies of the respective surfaces to coordinate endogenous iron and release free radicals via the fenton reaction during the reduction from the ferric to the ferrous state. It is suggested that such potency differences may explain the failure of certain man-made fibers to induce mesothelioma from inhalation exposure because of insufficient dose rea...

Isomer dependent bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans from municipal incinerator fly ash to carp

The isomer-dependent bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) from municipal incinerator fly ash to freshwater fish was determined. It was observed that carp exposed to fly ash in a continuous-flow exposure readily accumulated select isomers of PCDDs and PCDFs. A preference for greater retention of isomers substituted in the 2, 3, 7 and 8 positions was observed. The Bioavailability Index (ratio of contaminant level in fish to level in fly ash) decreased with increasing degree of chlorination.

Uptake and depuration studies of PCDDs and PCDFs in freshwater fish

Abstract The bioavailability of PCDD/PCDFs from municipal incinerator fly ash and sediment to freshwater fish has been studied. A preference to selectively bioaccumulate PCDD/PCDF isomers substituted in the 2,3,7 and 8 positions was observed. The depuration half life of 2,3,7,8-TCDD from carp was found to be 300–325 days. The rate of depuration of PCDD/PCDFs decreased with increasing degree of chlorination.

Methodology used for a laboratory determination of relative contributions of water, sediment and food chain routes of uptake for 2,3,7,8-TCDD bioaccumulation by lake trout in Lake Ontario

A long-term laboratory exposure of lake trout to Lake Ontario sediment and smelt (food chain) provided comprehensive bioaccumulation relationships for 2,3,7,8-TCDD. The laboratory exposure was designed to investigate the rates of TCDD uptake via water, sediment, and food under simulated Lake Ontario conditions. Innovative methods of preparing sediment, dosing sediment, preparing food and feeding the fish were developed. Results indicated that bioaccumulation of 2,3,7,8-TCDD occurs primarily through the food chain and secondarily through contact with contaminated sediment. The water exposure route, even under simulated equilibrium conditions, and low suspended solids concentrations did not appear to make a significant contribution to 2,3,7,8-TCDD bioaccumulation.