H.A. Leslie

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.

Tracing organophosphorus and brominated flame retardants and plasticizers in an estuarine food web

Nine organophosphorus flame retardants (PFRs) were detected in a pelagic and benthic food web of the Western Scheldt estuary, The Netherlands. Concentrations of several PFRs were an order of magnitude higher than those of the brominated flame retardants (BFRs). However, the detection frequency of the PFRs (6-56%) was lower than that of the BFRs (50-97%). Tris(2-butoxyethyl) phosphate (TBOEP), tris(isobutyl) phosphate (TIBP) and tris(2-chloroisopropyl) phosphate (TCIPP) were the dominant PFRs in sediment with median concentrations of 7.0, 8.1 and 1.8 ng/g dry weight (dw), respectively. PFR levels in the suspended particular matter (SPM) were 2-12 times higher than that in sediment. TBOEP, TCIPP, TIBP, tris(2-chloroethyl) phosphate (TCEP) and tris(phenyl) phosphate (TPHP) were found in organisms higher in the estuarine food web. The highest PFR concentrations in the benthic food web were found in sculpin, goby and lugworm with median concentrations of 17, 7.4, 4.6 and 2.0 ng/g wet weight (ww) for TBOEP, TIBP, TCIPP and TPHP, respectively. Comparable levels were observed in the pelagic food web, BDE209 was the predominant PBDE in sediment and SPM with median concentrations up to 9.7 and 385 ng/g dw, respectively. BDE47 was predominant in the biotic compartment of the food web with highest median levels observed in sculpin and common tern eggs of 79 ng/g lipid weight (lw) (2.5 ng/g ww) and 80 ng/g lw (11 ng/g ww), respectively. Trophic magnification was observed for all PBDEs with the exception of BDE209. Indications of trophic magnification of PFRs were observed in the benthic food web for TBOEP, TCIPP and TCEP with tentative trophic magnification factors of 3.5, 2.2 and 2.6, respectively (p<0.05). Most of the other PFRs showed trophic dilution in both food webs. The relative high PFR levels in several fish species suggest high emissions and substantial exposure of organisms to PFRs in the Western Scheldt.

Comparing laboratory and field measured bioaccumulation endpoints

An approach for comparing laboratory and field measures of bioaccumulation is presented to facilitate the interpretation of different sources of bioaccumulation data. Differences in numerical scales and units are eliminated by converting the data to dimensionless fugacity (or concentration-normalized) ratios. The approach expresses bioaccumulation metrics in terms of the equilibrium status of the chemical, with respect to a reference phase. When the fugacity ratios of the bioaccumulation metrics are plotted, the degree of variability within and across metrics is easily visualized for a given chemical because their numerical scales are the same for all endpoints. Fugacity ratios greater than 1 indicate an increase in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biomagnification). Fugacity ratios less than 1 indicate a decrease in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biodilution). This method provides a holistic, weight-of-evidence approach for assessing the biomagnification potential of individual chemicals because bioconcentration factors, bioaccumulation factors, biota-sediment accumulation factors, biomagnification factors, biota-suspended solids accumulation factors, and trophic magnification factors can be included in the evaluation. The approach is illustrated using a total 2393 measured data points from 171 reports, for 15 nonionic organic chemicals that were selected based on data availability, a range of physicochemical partitioning properties, and biotransformation rates. Laboratory and field fugacity ratios derived from the various bioaccumulation metrics were generally consistent in categorizing substances with respect to either an increased or decreased thermodynamic status in biota, i.e., biomagnification or biodilution, respectively. The proposed comparative bioaccumulation endpoint assessment method could therefore be considered for decision making in a chemicals management context.

Differential long-term effects of developmental exposure to polychlorinated biphenyls 52, 138 or 180 on motor activity and neurotransmission. Gender dependence and mechanisms involved

Developmental exposure to polychlorinated biphenyls (PCBs) induces motor alterations in humans by unknown mechanisms. It remains unclear whether: (a) all non-dioxin-like (NDL) PCBs are neurotoxic or it depends on the grade of chlorination; (b) they have different neurotoxicity mechanisms; (c) they affect differently males and females. The aims of this work were to assess: (1) whether perinatal exposure to 3 NDL-PCBs with different grades of chlorination, (PCBs 52, 138 or 180) affects differentially motor activity in adult rats; (2) whether the effects are different in males or females and (3) the mechanisms involved in impaired motor activity. Rats were exposed to PCBs from gestational day 7 to post-natal day 21. Experiments were performed when the rats were 4 months-old. PCB52 did not affect motor activity, PCB180 reduced it in males but not in females and PCB138 reduced activity both in males and females. PCB52 or 138 did not affect extracellular dopamine in nucleus accumbens (NAcc). PCB180 increased it both in males and females. Extracellular glutamate in NAcc was reduced by the three PCBs. Activation of metabotropic glutamate receptors (mGluRs) in NAcc increased extracellular dopamine in control rats and in those exposed to PCB52 and reduced dopamine in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs increases dopamine in females and reduces it in males. The opposite changes were observed for glutamate. mGluRs activation reduced extracellular glutamate in control rats and in those exposed to PCB52 and increased glutamate in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs reduces glutamate in females and increases it in males. The data support that different NDL-PCBs affect differently motor activity. Increased glutamate release in NAcc following activation of mGluRs would be involved in reduced dopamine release and reduced motor activity in rats exposed to PCB138 or 180.

Decabromodiphenylether and hexabromocyclododecane in wild birds from the United Kingdom, Sweden and The Netherlands: Screening and time trends

The brominated flame retardant decabromodiphenylether (DBDE) was analysed in wild birds to identify the most suitable species for monitoring time trends in DBDE contamination. This information was later used for the design of a 10-year trend study on DBDE in the European Union. DBDE was measured in muscle tissue, liver, and eggs from 10 terrestrial and four aquatic bird species. DBDE was detected in 47% of the terrestrial bird samples (nine species) and in 9% of the aquatic bird samples (six species). Peregrine falcon and sparrowhawk specimens were selected as most suitable species to determine temporal trends of DBDE. For sparrowhawks, no significant change in DBDE concentrations between 1973 and 2001 was found, although in later years more DBDE concentrations were above the detection limit. Peak DBDE levels measured in peregrines in 1995, were followed by a decline in concentrations until 2001. The same species were used for a trend study on hexabromocylcododecane (HBCD). Twenty-four percent of peregrine falcon eggs and 12% of sparrowhawk muscle samples demonstrated measurable HBCD residues. Three diastereomers of HBCD were analysed and the α-diastereomer was the predominant one in most samples. No clear time trends were observed for HBCD in either species. This study demonstrated that these DBDE and HBCD are bioavailable to birds of Northern Europe, although bioaccumulation seems to occur to a limited extent.

Do plastic particles affect microalgal photosynthesis and growth

The unbridled increase in plastic pollution of the worlds oceans raises concerns about potential effects these materials may have on microalgae, which are primary producers at the basis of the food chain and a major global source of oxygen. Our current understanding about the potential modes and mechanisms of toxic action that plastic particles exert on microalgae is extremely limited. How effects might vary with particle size and the physico-chemical properties of the specific plastic material in question are equally unelucidated, but may hold clues to how toxicity, if observed, is exerted. In this study we selected polystyrene particles, both negatively charged and uncharged, and three different sizes (0.05, 0.5 and 6μm) for testing the effects of size and material properties. Microalgae were exposed to different polystyrene particle sizes and surface charges for 72h. Effects on microalgal photosynthesis and growth were determined by pulse amplitude modulation fluorometry and flow cytometry, respectively. None of the treatments tested in these experiments had an effect on microalgal photosynthesis. Microalgal growth was negatively affected (up to 45%) by uncharged polystyrene particles, but only at high concentrations (250mg/L). Additionally, these adverse effects were demonstrated to increase with decreasing particle size.

Screening for microplastics in sediment, water, marine invertebrates and fish: Method development and microplastic accumulation

Measurements of microplastics in biota and abiotic matrices are key elements of exposure and risk assessments for this emerging environmental pollutant. We investigated the abundance of microplastics in field-collected biota, sediment and water. An improved sediment extraction method, based on density separation was developed. For analysis of microplastics in biota we found that an adapted enzymatic digestion protocol using proteinase K performed best, with a 97% recovery of spiked plastic particles and no observed degradation effects on the plastics in subsequent Raman analysis. Field analysis revealed that 8 of 9 tested invertebrate species from the North Sea and 68% of analyzed individuals of brown trout (Salmo trutta) from the Swedish West Coast had microplastics in them. Based on the number of plastic particles per kg d.w. the microplastic concentrations found in mussels were approximately a thousand-fold higher compared to those in sediment and surface water samples from the same location.

Plastic Debris Is a Human Health Issue

The global threat of highly persistent plastic waste accumulating and fragmenting in the world’s oceans, inland waters and terrestrial environments is becoming increasingly evident.1−3 Humans are being exposed to both plastic particles and chemical additives being released from the plastic debris of consumer society. This material is fragmenting, leaching and spreading throughout the biosphere, including indoor and outdoor air, soil, and water systems. What started as a marine environmental contamination issue is in fact very much a human health issue as well. What do we know so far about the impacts of this plastic debris for humans? Humans can be exposed to plastic particles via consumption of seafood and terrestrial food products, drinking water and via the air.1,4 Uptake of plastics by humans (and animals) can cause adverse health effects by at least three possible means: particle toxicity, chemical toxicity and as a pathogen and parasite vector.

Comparing laboratory‐ and field‐measured biota–sediment accumulation factors

Standardized laboratory protocols for measuring the accumulation of chemicals from sediments are used in assessing new and existing chemicals, evaluating navigational dredging materials, and establishing site-specific biota-sediment accumulation factors (BSAFs) for contaminated sediment sites. The BSAFs resulting from the testing protocols provide insight into the behavior and risks associated with individual chemicals. In addition to laboratory measurement, BSAFs can also be calculated from field data, including samples from studies using in situ exposure chambers and caging studies. The objective of this report is to compare and evaluate paired laboratory and field measurement of BSAFs and to evaluate the extent of their agreement. The peer-reviewed literature was searched for studies that conducted laboratory and field measurements of chemical bioaccumulation using the same or taxonomically related organisms. In addition, numerous Superfund and contaminated sediment site study reports were examined for relevant data. A limited number of studies were identified with paired laboratory and field measurements of BSAFs. BSAF comparisons were made between field-collected oligochaetes and the laboratory test organism Lumbriculus variegatus and field-collected bivalves and the laboratory test organisms Macoma nasuta and Corbicula fluminea. Our analysis suggests that laboratory BSAFs for the oligochaete L. variegatus are typically within a factor of 2 of the BSAFs for field-collected oligochaetes. Bivalve study results also suggest that laboratory BSAFs can provide reasonable estimates of field BSAF values if certain precautions are taken, such as ensuring that steady-state values are compared and that extrapolation among bivalve species is conducted with caution.

Flame retardants: Dust – And not food – Might be the risk

Flame retardants (FRs) are used to delay ignition of materials such as furniture and electric and electronic instruments. Many FRs are persistent and end up in the environment. Environmental studies on flame retardants (FRs) took off in the late 1990s. Polybrominated diphenylethers (PBDEs) appeared to be bioaccumulative and were found in many organisms all over the world. When PBDEs were banned or their production voluntarily terminated, alternatives appeared on the market that often had similar properties or were of more concern due to their toxicity such as halogenated phosphorus-based FRs. Here we show that in spite of the ban on PBDEs more brominated FRs are being produced, an increasing number of other FRs is being applied and FR levels in our homes are much higher than in the outdoor environment. While nowadays we live in better isolated houses and sit in front of the computer or television, on flame retarded upholstery, we are at risk due to the toxic effects of a suite of FRs. The high exposure to these substances indoors calls for better risk assessments that include mixture effects.