James P. Meador

Bioaccumulation of Polycyclic Aromatic Hydrocarbons by Marine Organisms

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the marine environment, occurring at their highest environmental concentrations around urban centers. While they can occur naturally, the highest concentrations are mainly from human activities, and the primary sources are combustion products and petroleum. Two factors, lipid and organic carbon, control to a large extent the partitioning behavior of PAHs in sediment, water, and tissue; the more hydrophobic a compound, the greater the partitioning to these phases. These two factors, along with the octanol-water partition coefficient, are the best predictors of this partitioning and can be used to determine PAH behavior and its bioavailability in the environment. It is well known that the lipid of organisms contains the highest levels of hydrophobic compounds such as PAHs, and that organic carbon associated with sediment or dissolved in water can have the greatest influence on PAH bioavailability. Partitioning of combustion-derived PAHs between water and sediment may be much less than predicted, possibly because associations with particles are much stronger than expected. This reduced partitioning may produce erroneous results in predicting bioaccumulation where uptake from water is important. Accumulation of PAHs occurs in all marine organisms; however, there is a wide range in tissue concentrations from variable environmental concentrations, level and time of exposure, and species ability to metabolize these compounds. PAHs generally partition into lipid-rich tissues, and their metabolites can be found in most tissues. In fish, liver and bile accumulate the highest levels of parent PAH and metabolites; hence, these are the best tissues to analyze when determining PAH exposure. In invertebrates, the highest concentrations can be found in the internal organs, such as the hepatopancreas, and tissue concentrations appear to follow seasonal cycles, which may be related to variations in lipid content or spawning cycles. The major route of uptake for PAHs has been debated for years. For the more water-soluble PAHs, it is believed that the main route of uptake is through ventilated water and that the more hydrophobic compounds are taken in mainly through ingestion of food or sediment. There are many variables, such as chemical hydrophobicity, uptake efficiency, feeding rate, and ventilatory volume, which may affect the outcome. The route of uptake may be an important issue for short-term events; however, under long-term exposure and equilibrium conditions between water, prey, and sediment, the route of uptake may be immaterial because the same tissue burdens will be achieved regardless of uptake routes.(ABSTRACT TRUNCATED AT 400 WORDS)

The interaction of pH, dissolved organic carbon, and total copper in the determination of ionic copper and toxicity

Abstract The bioavailability of copper to Daphnia magna was studied in a complete three factor experiment with variable total copper (TCU), pH, and naturally-derived dissolved organic carbon (DOC). Both pH and DOC were found to be important in controlling the amount of ionic copper (for a given total copper concentration) and a model was developed which explained 94% of the variability in the data. Mortality of Daphnia magna was highly correlated with ionic copper under pH 7 at 24 and 48 hours ( r 2 = 0.90 and 0.96) and less so at higher pH suggesting that copper complexes may be contributing to the response. When toxicity was expressed in terms of ionic copper, it was concluded that a given amount of ionic copper produced more toxicity as pH increased. The 48-h SP 50 for D. magna exposed to ionic copper was in the order of 0.5 nM (0.03 ng.ml −1 ).

Crucial role of mechanisms and modes of toxic action for understanding tissue residue toxicity and internal effect concentrations of organic chemicals

This article reviews the mechanistic basis of the tissue residue approach for toxicity assessment (TRA). The tissue residue approach implies that whole-body or organ concentrations (residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration typically used in the external medium. Although the benefit of internal concentrations as dose metrics in ecotoxicology has long been recognized, the application of the tissue residue approach remains limited. The main factor responsible for this is the difficulty of measuring internal concentrations. We propose that environmental toxicology can advance if mechanistic considerations are implemented and toxicokinetics and toxicodynamics are explicitly addressed. The variability in ecotoxicological outcomes and species sensitivity is due in part to differences in toxicokinetics, which consist of several processes, including absorption, distribution, metabolism, and excretion (ADME), that influence internal concentrations. Using internal concentrations or tissue residues as the dose metric substantially reduces the variability in toxicity metrics among species and individuals exposed under varying conditions. Total internal concentrations are useful as dose metrics only if they represent a surrogate of the biologically effective dose, the concentration or dose at the target site. If there is no direct proportionality, we advise the implementation of comprehensive toxicokinetic models that include deriving the target dose. Depending on the mechanism of toxicity, the concentration at the target site may or may not be a sufficient descriptor of toxicity. The steady-state concentration of a baseline toxicant associated with the biological membrane is a good descriptor of the toxicodynamics of baseline toxicity. When assessing specific-acting and reactive mechanisms, additional parameters (e.g., reaction rate with the target site and regeneration of the target site) are needed for characterization. For specifically acting compounds, intrinsic potency depends on 1) affinity for, and 2) type of interaction with, a receptor or a target enzyme. These 2 parameters determine the selectivity for the toxic mechanism and the sensitivity, respectively. Implementation of mechanistic information in toxicokinetic-toxicodynamic (TK-TD) models may help explain time-delayed effects, toxicity after pulsed or fluctuating exposure, carryover toxicity after sequential pulses, and mixture toxicity. We believe that this mechanistic understanding of tissue residue toxicity will lead to improved environmental risk assessment.

Relating Results of Chronic Toxicity Responses to Population-Level Effects: Modeling Effects on Wild Chinook Salmon Populations

Abstract Standard toxicity tests assess the physiological responses of individual organisms to exposure to toxic substances under controlled conditions. Time and space restrictions often prohibit the assessment of population-level responses to a toxic substance. Compounds affecting various toxicity endpoints, such as growth, fecundity, behavior, or immune function, alter different demographic traits and produce different impacts on the population. Chronic effects of immune suppression, reproductive impairment, and growth reduction were examined using life history models for Chinook salmon (Oncorhynchus tshawytscha). Modeled immune suppression acted through reductions in age-specific survival, with first- and second-year survival producing the greatest changes in the population growth rate (λ). A 10% reduction in various reproductive parameters all produced a similar λ, but different sensitivity and stable age distributions. Growth reduction models incorporated effects to both survival and reproduction and produced additive effects. Overall, model output indicated that for Chinook salmon, alteration of first-year survival has the greatest relative impact on λ. Results support the importance of linking toxicity endpoints to the demographic traits that they influence and help generate toxicity tests that are more relevant for the species. Life history modeling provides a useful tool to develop testable hypotheses regarding specific and comparative population-level impacts.

Rationale and Procedures for Using the Tissue-Residue Approach for Toxicity Assessment and Determination of Tissue, Water, and Sediment Quality Guidelines for Aquatic Organisms

ABSTRACT This article describes a set of procedures for developing tissue, water, and sediment quality guidelines for the protection of aquatic life by using the tissue-residue approach (TRA) for toxicity assessment. The TRA, which includes aspects of the Critical Body Residue (CBR) approach, associates tissue concentrations of chemicals with adverse biological effects in a dose-response fashion that can be used to determine CBRs. These CBRs can then be used to develop tissue quality guidelines (TQGs), which may be translated into water or sediment guidelines with bioaccumulation factors. Not all toxicants are amenable to this type of analysis; however, some appear to exhibit relatively consistent results that can likely be applied in a regulatory framework. By examining tissue residues, variations in toxicokinetics (temporal aspects of accumulation, biotransformation, and internal distribution) are greatly reduced allowing a greater focus on toxicodynamics (action and potency) of the toxicants. The strongest feature of this approach is causality; hence, guidelines based on tissue concentrations are based on data demonstrating a causal relationship between the acquired dose and the biological effect. Because the TRA has utility for assessing the toxicity of contaminant mixtures, an approach is presented here using toxic unit values that can be used to assess the likelihood of observing toxic effects based on tissue residues.

Chemical contaminants in harbor porpoise (Phocoena phocoena) from the North Atlantic coast: Tissue concentrations and intra- and inter-organ distribution

Concentrations of chlorinated hydrocarbons (CHs), such as polychlorinated biphenyls (PCBs), were measured in subsamples taken from different anatomical locations of blubber and liver of three apparently healthy harbor porpoises (Phocoena phocoena) incidentally caught in a gill-net fishery along the northwest Atlantic coast; selected elements (e.g., mercury) were measured in subsamples of liver. The vertical distribution (skin to muscle) of contaminants within blubber was also determined. Additionally, the concentrations of CHs and elements were determined in individual samples of brain, lung, kidney, and testis to assess how the disposition of toxic chemicals may be dependent on the physiological characteristics of a specific organ. Statistical analyses of the results showed that the anatomical location of the blubber or liver sample had no significant effect on concentrations of either CHs in blubber and liver, or of selected elements in liver. However, there were statistical differences between strata of blubber (skin to muscle) for the concentrations of CHs. As expected, the results showed that the CH concentrations, based on wet weight, were considerably higher in the blubber than in the other tissues; however, the concentrations of CHs in the different tissues were more comparable when values were based on total lipid weight with the exception of the brain where lipid normalized concentrations were lower than in all other tissues: This low relative accumulation of lipophilic contaminants in the brain tissue may be due to the presence of the blood-brain barrier, or due to a lower proportion of neutral lipids, such as triglycerides, as analysis for percent lipid and for the proportion of specific lipid classes showed.

Tributyltin and the obesogen metabolic syndrome in a salmonid.

We conducted a dietary feeding study with juvenile chinook salmon (Oncorhynchus tshawytscha) to assess the potential for tributyltin (TBT) to elicit the obesogen response that has been described for mammals. The results show increases in whole-body lipid content, which is consistent with the obesogen response; however, we also observed associated parameters that were dissimilar. We found increases in body mass and alterations to several physiological parameters at doses between 0.4 and 3.5 ng/g fish/day (1.4-12 pmol/g fish/day) and reduced body mass at the highest dose after 55 days of exposure. Lipid related plasma parameters (plasma triacylglycerols, cholesterol, and lipase) exhibited monotonic increases over all doses while other values (glucose and insulin-like growth factor (IGF)) exhibited increases only for the low-dose treatments. The increases noted for several parameters in fish were opposite to those reported for the obesogen metabolic syndrome, which is characterized by a reduction in serum glucose, free fatty acids, and triglycerides. This is the first report of growth stimulation resulting from low-dose exposure to this pesticide, which is an unusual response for any animal exposed to an organic or organometallic xenobiotic. Because a number of environmental contaminants act as metabolic disruptors at very low doses, these results are noteworthy for a variety of species. Intuitively, enhanced growth and lipid storage may appear beneficial; however, for salmonids there are numerous potentially negative consequences for populations.

Comparative toxicokinetics of tributyltin in five marine species and its utility in predicting bioaccumulation and acute toxicity

Abstract The acute toxic response (LC50), bioconcentration factor (BCF), lethal tissue residue (LR50), uptake clearance constant (k1), and elimination rate constant (k2) for tributyltin (TBT) were examined and compared in four marine invertebrate and one marine fish species. The toxic response and BCFs were vastly different among the species when exposed to the dissolved compound, which was reflected in their unequal uptake clearance and elimination rate constants. Based on the dual-rate constant approach for a one compartment, first-order kinetic model (1CFOK), predicted values for both the acute toxic response and BCF based on these toxicokinetic constants were matched closely by observed values. Additionally, a strong correlation between the LC50 and BCF was found, which was expected based on their relationship to the balance between uptake and elimination and a consistent LR50 (lethal residue causing 50% mortality) among species. Predictions were made about the time to steady-state tissue concentrations with k2 values and how this would affect the results of the standard 10 day toxicity bioassay. Because acute TBT toxicity occurs at tissue concentrations 100 times lower than compounds exhibiting a narcosis mode of action, tributyltin is very toxic at low environmental concentrations, especially to organisms that have high uptake clearance and low elimination rate constants. Making predictions about toxicity based on uptake clearance and elimination rate constants in conjunction with the critical body residue will be helpful when choosing sensitive organisms for determining water and sediment quality criteria.

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions.

A Perspective on the Toxicity of Petrogenic PAHs to Developing Fish Embryos Related to Environmental Chemistry

ABSTRACT Numerous studies demonstrate polynuclear aromatic hydrocarbons (PAHs) dissolved from weathered crude oil adversely affect fish embryos at 0.5 to 23 μg/l. This conclusion has been challenged by studies that claim (1) much lower toxicity of weathered aqueous PAHs; (2) direct contact with dispersed oil droplets plays a significant role or is required for toxicity; (3) that uncontrolled factors (oxygen, ammonia, and sulfides) contribute substantively to toxicity; (4) polar compounds produced by microbial metabolism are the major cause of observed toxicity; and (5) that based on equilibrium models and toxic potential, water contaminated with weathered oil cannot be more toxic per unit mass than effluent contaminated with fresh oil. In contrast, several studies demonstrate high toxicity of weathered oil; shifts in PAH composition were consistent with dissolution (not particle ablation), embryos accumulated dissolved PAHs at low concentrations and were damaged, and assumed confounding factors were inconsequential. Consistent with previous empirical observations of mortality and weathering, temporal shifts in PAH composition (oil weathering) indicate that PAHs dissolved in water should (and do) become more toxic per unit mass with weathering because high molecular weight PAHs are more persistent and toxic than the more abundant low molecular weight PAHs in whole oil.