Per/Polyfluoroalkyl Substances (PFASs) in a Marine Apex Predator (White Shark, Carcharodon carcharias) in the Northwest Atlantic Ocean.

Per/polyfluoroalkyl substances (PFASs) are ubiquitous, highly persistent anthropogenic chemicals that bioaccumulate and biomagnify in aquatic food webs and are associated with adverse health effects, including liver and kidney diseases, cancers, and immunosuppression. We investigated the accumulation of PFASs in a marine apex predator, the white shark (Carcharodon carcharias). Muscle (N = 12) and blood plasma (N = 27) samples were collected from 27 sharks during 2018-2021 OCEARCH expeditions along the eastern coast of North America from Nova Scotia to Florida. Samples were analyzed for 47 (plasma) and 43 (muscle) targeted PFASs and screened for >2600 known and novel PFASs using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Perfluoroalkyl carboxylates with carbon chain-length C11 to C14 were frequently detected above the method reporting limits in plasma samples, along with perfluorooctanesulfonate and perfluorodecanesulfonate. Perfluoropentadecanoate was also detected in 100% of plasma samples and concentrations were estimated semiquantitatively as no analytical standard was available. Total concentrations of frequently detected PFASs in plasma ranged from 0.56 to 2.9 ng mL-1 (median of 1.4 ng mL-1). In muscle tissue, nine targeted PFASs were frequently detected, with total concentration ranging from 0.20 to 0.84 ng g-1 ww. For all frequently detected PFASs, concentrations were greater in plasma than in muscle collected from the same organism. In both matrices, perfluorotridecanoic acid was the most abundant PFAS, consistent with several other studies. PFASs with similar chain-lengths correlated significantly among the plasma samples, suggesting similar sources. Total concentrations of PFASs in plasma were significantly greater in sharks sampled off of Nova Scotia than all sharks from other locations, potentially due to differences in diet. HRMS suspect screening tentatively identified 13 additional PFASs in plasma, though identification confidence was low, as no MS/MS fragmentation was collected due to low intensities. The widespread detection of long-chain PFASs in plasma and muscle of white sharks highlights the prevalence and potential biomagnification of these compounds in marine apex predators.

Associations between total mercury, trace minerals, and blood health markers in Northwest Atlantic white sharks (Carcharodon carcharias).

The ecology and life-histories of white sharks make this species susceptible to mercury bioaccumulation; however, the health consequences of mercury exposure are understudied. We measured muscle and plasma total mercury (THg), health markers, and trace minerals in Northwest Atlantic white sharks. THg in muscle tissue averaged 10.0 mg/kg dry weight, while THg in blood plasma averaged 533 µg/L. THg levels in plasma and muscle were positively correlated with shark precaudal length (153-419 cm), and THg was bioaccumulated proportionally in muscle and plasma. Nine sharks had selenium:mercury molar ratios in blood plasma >1.0, indicating that for certain individuals the potential protective effects of the trace mineral were diminished, whereas excess selenium may have protected other individuals. No relationships between plasma THg and any trace minerals or health markers were identified. Thus, we found no evidence of negative effects of Hg bioaccumulation, even in sharks with very high THg.

Comprehensive assessment of chemical residues in surface and wastewater using passive sampling, chemical, biological, and fish behavioral assays.

Effluents from ten full-scale municipal wastewater treatment plants (WWTPs) that discharge into the Hudson River, surface waters, and wild-caught fish samples were analyzed using liquid chromatography with tandem mass spectrometry (LC/MS/MS) to examine the influence of wastewater discharge on the concentrations of contaminants of emerging concern (CECs) and their ecological impacts on fish. Analysis was based on targeted detection of 41 pharmaceuticals, and non-targeted analysis (suspect screening) of CECs. Biological effects of treated WWTP effluents were assessed using a larval zebrafish (Danio rerio) swimming behavior assay. Concentrations of residues in surface waters were determined in grab samples and polar organic chemical integrative samplers (POCIS). In addition, vitellogenin peptides, used as biomarkers of endocrine disruption, were quantified using LC/MS/MS in the wild-caught fish plasma samples. Overall, 94 chemical residues were identified, including 63 pharmaceuticals, 10 industrial chemicals, and 21 pesticides. Eight targeted pharmaceuticals were detected in 100% of effluent samples with median detections of: bupropion (194 ng/L), carbamazepine (91 ng/L), ciprofloxacin (190 ng/L), citalopram (172 ng/L), desvenlafaxine (667 ng/L), iopamidol (3790 ng/L), primidone (86 ng/L), and venlafaxine (231 ng/L). Over 30 chemical residues were detected in wild-caught fish tissues. Notably, zebrafish larvae exposed to chemical extracts of effluents from 9 of 10 WWTPs, in at least one season, were significantly hyperactive. Vitellogenin expression in male or immature fish occurred 2.8 times more frequently in fish collected from the Hudson River as compared to a reference site receiving no direct effluent input. Due to the low concentrations of pharmaceuticals detected in effluents, it is likely that chemicals other than pharmaceuticals measured are responsible for the behavioral changes observed. The combined use of POCIS and non-target analysis demonstrated significant increase in the chemical coverage for CEC detection, providing a better insight on the impacts of WWTP effluents and agricultural practices on surface water quality.

Comparative transcriptomics implicate mitochondrial and neurodevelopmental impairments in larval zebrafish (Danio rerio) exposed to two selective serotonin reuptake inhibitors (SSRIs).

Pharmaceuticals and personal care products are emerging contaminants that are increasingly detected in the environment worldwide. Certain classes of pharmaceuticals, such as selective serotonin reuptake inhibitors (SSRIs), are a major environmental concern due to their widespread use and the fact that these compounds are designed to have biological effects at low doses. A complication in predicting toxic effects of SSRIs in nontarget organisms is that their mechanism of action is not fully understood. To better understand the potential toxic effects of SSRIs, we employed an ultra-low input RNA-sequencing method to identify potential pathways that are affected by early exposure to two SSRIs (fluoxetine and paroxetine). We exposed wildtype zebrafish (Danio rerio) embryos to 100 µg/L of either fluoxetine or paroxetine for 6 days before extracting and sequencing mRNA from individual larval brains. Differential gene expression analysis identified 1550 genes that were significantly affected by SSRI exposure with a core set of 138 genes altered by both SSRIs. Weighted gene co-expression network analysis identified 7 modules of genes whose expression patterns were significantly correlated with SSRI exposure. Functional enrichment analysis of differentially expressed genes as well as network module genes repeatedly identified various terms associated with mitochondrial and neuronal structures, mitochondrial respiration, and neurodevelopmental processes. The enrichment of these terms indicates that toxic effects of SSRI exposure are likely caused by mitochondrial dysfunction and subsequent neurodevelopmental effects. To our knowledge, this is the first effort to study the tissue-specific transcriptomic effects of SSRIs in developing zebrafish, providing specific, high resolution molecular data regarding the sublethal effects of SSRI exposure.

Varying the exposure period and duration of neuroactive pharmaceuticals and their metabolites modulates effects on the visual motor response in zebrafish (Danio rerio) larvae.

Pharmaceuticals and personal care products are emerging contaminants that are increasingly detected in surface waters around the world. Despite the rise in environmental detections, measured concentrations are still typically low, raising the importance of environmental risk assessments that focus on ecologically relevant sublethal endpoints, such as altered behavior. Neuroactive pharmaceuticals, like mental health medications, pain killers, etc., may be particularly potent in this regard as they are specifically designed to cause behavioral changes without causing physiologic impairment in mammalian systems. We screened 15 different popular neuroactive pharmaceuticals, ranging from antidepressants (including 3 major antidepressant metabolites), anxiety medications, and pain killers, under three different exposure scenarios (repeated, late acute and early transient exposure) to look for behavioral effects in larval zebrafish using the visual motor response (VMR). Drugs were screened at 0, 1, 10, and 100 µg/L in the repeated exposure scenario, and at 0 and 100 µg/L in the late acute and early transient exposure scenarios. Eight of the 15 compounds tested, specifically the antidepressants amitriptyline, fluoxetine, nor-fluoxetine, paroxetine, sertraline, nor-sertraline, venlafaxine, and the antipsychotic drug haloperidol decreased swimming activity by 25% to 40% under repeated exposure conditions. Five of the compounds (amitriptyline, fluoxetine, nor-fluoxetine, paroxetine, and sertraline) also significantly decreased activity by 17% to 31% in the late acute exposure paradigm. Three compounds (fluoxetine, paroxetine and venlafaxine) significantly altered swimming activity with early transient exposure, however creating a hyperactive response and increasing activity from 24% to 28%, while haloperidol significantly decreased activity by 31%. This paper is, to our knowledge, the first to screen so many neuroactive pharmaceuticals, including major metabolites, in parallel under multiple exposure conditions. We show that antidepressants most consistently alter VMR swimming activity. Additionally, we show that major antidepressant metabolites can potentially alter behavior as much as their parent compounds. Furthermore, we show that the magnitude and direction of behavioral effect is dependent on the exposure duration and period, indicating that a more diverse experimental approach might be needed to more accurately assess the risk these compounds pose to the environment.

Fate of methoprene in temperate salt marsh ditches following aerial applications.

Aerial applications of liquid methoprene are used in salt marshes to control mosquitoes by preventing adult emergence. Despite concern about toxicity to non-target organisms, little is known about environmental concentrations after applications, nor methoprene's persistence in salt marsh environments. Aqueous and sediment samples were collected from two marshes receiving weekly applications. Aqueous samples were collected as early as 30 min after applications and as long as nine days afterwards; sediment samples were taken within hours of application and as long as 19 days post-application. Use of time-of-flight liquid chromatography - mass spectral analysis allowed for ultra-low detection limits (0.5 ng/L) in water samples. The data show loss of nearly all methoprene from 1 m deep marsh ditches within 1 day and presence but not accumulation of methoprene in marsh sediments despite repeated applications. Methoprene concentrations observed in salt-marsh mosquito ditches were below those found to be of toxicological significance in other studies.

Antioxidant responses and oxidative stress in sheepshead minnow larvae exposed to Corexit 9500® or its component surfactant, DOSS.

Large-scale use of dispersants to remediate oil spills has raised concerns about their toxicity to marine organisms. Of particular concern is oxidative stress and resulting membrane damage due to exposure to surfactants in dispersant mixtures. We investigated the potential of the dispersant Corexit 9500® and one of its major components, the anionic surfactant dioctyl sodium sulfosuccinate (DOSS), to induce oxidative stress in larval sheepshead minnows after 24 and 96h exposures, at two sublethal concentrations, the lesser being environmentally realistic for each compound. Corexit exposures elicited only minimal antioxidant responses for most antioxidant components tested, with increased glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities observed only after 96h and at the higher exposure concentration. In contrast, DOSS induced statistically significant increases in the levels of reactive oxygen species (ROS), GPx, and lipid peroxidation, as well as depleted reduced glutathione (GSH) levels at both time points and concentrations. These data indicate that short-term and environmentally realistic exposures to DOSS can impact antioxidant response capabilities, raising concern about its use in oil dispersants and other high volume use products where environmental releases are likely.

Effects of Microcystis on development of early life stage Japanese medaka (Oryzias latipes): Comparative toxicity of natural blooms, cultured Microcystis and microcystin-LR.

Freshwater cyanobacterial harmful algal blooms (CyanoHABs) caused by algae in the genus Microcystis have been increasing in frequency and severity in recent decades. Microcystis blooms threaten aquatic organisms through effects associated with the rapid increase of biomass and the production of the hepatotoxin microcystin (MC) by toxic strains. Among fish, effects of blooms are likely to be more severe for early life stages, and physiological impacts on this life stage could significantly impact recruitment and fish populations. This study explores the effects of Microcystis blooms on the development of fish using the model organism, the Japanese medaka (Oryzias latipes), under realistic exposure conditions. Medaka embryos were exposed to natural blooms collected from New York City (USA) lakes, lab cultures of Microcystis, and MC-LR solutions. Field collected samples were more toxic than lab cultures (even when compared at the same algal density or MC concentration), causing decreased survival, premature time to hatch, reduced body length, yolk sac edema, and decreased heart rate, while lab culture exposures only resulted in bradycardia. Heart rate was the most sensitive endpoint measured, being depressed in embryos exposed to both lab cultures and field collected blooms. Generalized linear model analysis indicated bradycardia was statistically associated with both cell densities of blooms and MC concentrations, while single factor analysis indicated that MC concentrations had a stronger correlation compared to cell densities. However, MC exposure could not fully explain the effects observed, as exposures to MC-LR solutions alone were not able to reduce heart rate as severely as algal exposures. Collectively, these experiments indicate that factors beyond exposure to MC or even isolated Microcystis strains influence heart rate of fish exposed to Microcystis blooms. Enhanced mortality, depressed heart rate, and abnormal development observed in response to environmentally realistic exposures of Microcystis blooms could affect success of fish at both individual or population levels.

Cytotoxicity and CYP1A inhibition in rainbow trout liver (RTL-W1) cell lines exposed to dispersant Corexit 9500 and its major surfactant components.

As part of a large study examining the toxicity of the Corexit® family of oil spill dispersants on aquatic vertebrates, we examined effects on the liver in an in vitro study using the rainbow trout liver cell line (RTL-W1). We exposed RTL-W1 cells to the dispersant Corexit 9500 and its major surfactant components and measured their cytotoxic effects as well as modulation of activity of CYP1A, one of the major enzymes responsible for organic contaminant metabolism. The anionic surfactant DOSS was found to be the most cytotoxic with a 24h EC50 of 10mg/L, as compared to 45 to 91mg/L for the non-ionic surfactants, Tween 80 and 85 and Span 80. The EC50 for Corexit was intermediate between these compounds at 29mg/L. Corexit 9500 and the non-ionic surfactants Tween 80 and 85, but not DOSS or Span 80 knocked down CYP1A activity induced by benzo[a]pyrene, a model agonist, demonstrating the potential of these compounds to compromise the ability of exposed organisms to metabolize petroleum hydrocarbons or other CYP1A substrates.

Effects of oxygenated polycyclic aromatic hydrocarbons on the early life stages of Japanese medaka.

Oxygenated polycyclic aromatic hydrocarbons (oxyPAHs) are directly discharged into the atmosphere with exhaust gas from diesel engine automobiles and industry and are also generated by photo-oxidation and/or microbial metabolism of parent polycyclic aromatic hydrocarbons (PAHs). They are widely distributed in environment, especially around urban areas. We evaluated the effects of exposure to oxyPAHs as acenaphthenequinone (ANQ), 7,12-benz(a)anthracenequinone (BAQ), 1,4-naphthoquinone (NAQ), and 9,10-phenanethrenequinone (PHQ) in Japanese medaka (Oryzias latipes) embryos. ANQ (>2720 µg/L) caused caving in the yolk sac, and BAQ (>22.4 µg/L) caused tanning of the oil droplet. Additionally, NAQ (>314 µg/L) and PHQ (>734 µg/L) stopped development of medaka embryos beginning 2 days after the start of exposure. The hatched larvae from embryos exposed to ANQ, BAQ, NAQ, or PHQ at 518, 9.86, 36.5, or 80.7 µg/L, respectively, exhibited incomplete development of the cephalic region, incomplete palate, unabsorbed and hypertrophied yolk sac, tubular heart, altered axial curvature, and poor swimming ability. These symptoms were similar to those observed in blue sac disease, which is caused by exposure to PAHs.

Toxic evaluations of sediments in Tokyo Bay, Japan, using Japanese medaka embryos.

Toxic risks of sediments collected from seven sites in Tokyo Bay were evaluated using Japanese medaka embryos. Those sediments with slight pore water were placed in grass petri dishes without overlying water. The most remarkable effect in the field sediment was to cause hatching delay in embryos, and the longest time until hatching took was 12.5 ± 1.6 days post-fertilization (dpf), although that in control group was 10.1 ± 0.7 dpf. A significant delay in hatching was observed at four sites. Because total carbon concentrations were relatively high in sediments at three of these four sites, several chemicals were expected to be residues in these sites and could cause their delay. Although extreme mortality was not observed at all sites, sediments collected from the site close to Kawasaki city induced 10 % mortality. Polycyclic aromatic hydrocarbon (PAH) concentrations were remarkably high at this site compared with other sites, and thus PAH toxicities could be causing the mortality. Concentration of heavy metals such as cadmium, copper, lead, and zinc in sediments were also determined, but no clear relationship was found between toxicities to embryos and the distribution of their concentrations.

Hypoxia depresses CYP1A induction and enhances DNA damage, but has minimal effects on antioxidant responses in sheepshead minnow (Cyprinodon variegatus) larvae exposed to dispersed crude oil.

The growing incidence of hypoxic regions in coastal areas receiving high volumes of anthropogenic discharges requires more focused risk assessment of multiple stressors. One area needing further study is the combined effect of hypoxia and oil exposure. This study examined the short-term sublethal effects of co-exposure to hypoxia and water accommodated fractions (WAF) and chemically enhanced WAFs (CEWAFs) of Southern Louisiana Crude oil on detoxification, antioxidant defenses and genotoxicity in early life stage sheepshead minnow (Cyprinodon variegatus). CYP1A induction (evaluated by measuring EROD activity), activity of a number of key antioxidant enzymes (GST, GR, GPx, SOD, CAT, and GCL), levels of antioxidants (tGSH, GSH, and GSSG), evidence of lipid peroxidation (evaluated using the TBARS assay), and DNA damage (evaluated using the comet assay) provided a broad assessment of responses. Contaminant detoxification pathways induced by oil exposure were inhibited by co-exposure to hypoxia, indicating a maladaptive response. The interactive effects of oil and hypoxia on antioxidant defenses were mixed, but generally indicated less pronounced alterations, with significant increases in lipid peroxidation not observed. Hypoxia significantly enhanced DNA damage induced by oil exposure indicating the potential for significant deleterious effects post exposure. This study demonstrates the importance of considering hypoxia as an enhanced risk factor in assessing the effects of contaminants in areas where seasonal hypoxia may be prevalent.

Hypoxia Enhances the Toxicity of Corexit EC9500A and Chemically Dispersed Southern Louisiana Sweet Crude Oil (MC-242) to Sheepshead Minnow (Cyprinodon variegatus) Larvae.

Oil exploration and production activities are common in the northern Gulf of Mexico as well as many other coastal and near coastal areas worldwide. Seasonal hypoxia is also a common feature in the Northern Gulf, and many other coastal areas, which is likely to increase in severity and extent with continuing anthropogenic nutrient inputs. Hypoxia has well established physiological effects on many organisms, and it has been shown to enhance the toxicity of polycyclic aromatic hydrocarbons (persistent components of petroleum) in fish. The goal of this study was to examine the combined effects of hypoxia and exposure to contaminants associated with oil spills. We evaluated the effects of short term (48 hr) exposures to Corexit EC9500A, water accommodated fractions (WAF), and chemically enhanced water accommodated fractions (CEWAF) prepared from Southern Louisiana Sweet Crude Oil (MC 242) on survival of sheepshead minnow (Cyprinodon variegatus) larvae held under normoxic (ambient air) or hypoxic (2 mg/L O2) conditions. Results demonstrated that hypoxia significantly enhances mortality observed in response to Corexit or CEWAF solutions. In the latter case, significant interactions between the two stressors were also observed. Our data supports the need to further evaluate the combined stresses imparted by hypoxia and exposure to petroleum hydrocarbons and dispersants.

Antimicrobial activity in the cuticle of the American lobster, Homarus americanus.

American lobster, Homarus americanus, continues to be an ecologically and socioeconomically important species despite a severe decline in catches from Southern New England and Long Island Sound (USA) and a high prevalence of epizootic shell disease in these populations. A better understanding of lobster immune defenses remains necessary. Cuticle material collected from Long Island Sound lobsters was found to be active against a broad spectrum of bacteria, including Gram-negative and -positive species. The antimicrobial activity was characterized by boiling, muffling, and size fractioning. Boiling did not significantly reduce activity, while muffling did have a significant effect, suggesting that the active component is organic and heat stable. Size fractioning with 3 and 10 kDa filters did not significantly affect activity. Fast protein liquid chromatography fractions were also tested for antimicrobial activity, and fractions exhibiting protein peaks remained active. MALDI mass spectrometry revealed peptide peaks at 1.6, 2.8, 4.6, and 5.6 kDa. The data presented suggest that one or several antimicrobial peptides contribute to antimicrobial activity present in the American lobster cuticle.

Structural disruption increases toxicity of graphene nanoribbons.

The increased utilization of graphene nanoribbons (GNRs) for biomedical and material science applications necessitates the thorough evaluation of potential toxicity of these materials under both intentional and accidental exposure scenarios. We here investigated the effects of structural disruption of GNRs (induced by low-energy bath and high-energy probe sonication) to in vitro (human cell lines), and in vivo (Oryzias latipes embryo) biological systems. Our results demonstrate that low concentration (20 µg ml(-1) ) suspensions of GNRs prepared by as little as 1 min of probe sonication can cause significant decreases in the overall metabolic state of cells in vitro, and increased embryo/larval mortality in vivo, as compared to bath sonicated or unsonicated suspensions. Structural analysis indicates that probe sonication leads to disruption in GNR structure and production of smaller carbonaceous debris, which may be the cause of the toxicity observed. These results point out the importance of assessing post-production structural modifications for any application using nanomaterials.

Genotoxicity of oxy-PAHs to Japanese medaka (Oryzias latipes) embryos assessed using the comet assay.

Polycyclic aromatic hydrocarbons (PAHs) have long been recognized as important environmental toxicants. Despite a plethora of information on the fate and effects of parent PAHs, relatively little is known about the environmental fate and toxicity of ketone- and quinone-substituted PAH oxidation products (termed oxy-PAHs), particularly in the aquatic environment. This study begins to fill that gap using embryos of the Japanese medaka (Oryzias latipes) as a model species. The genotoxic potential of two environmentally relevant oxy-PAHs, acenaphthenequinone and 7,12-benz[a]anthracenquinone, was assessed using the comet assay. We found that both oxy-PAHs could cause significant increases in DNA damage after only 48 h of exposure at the lowest concentrations tested (5 µg/L). Comparisons of the genotoxic potential between these oxy-PAHs and their corresponding parent PAHs (acenaphthene and benz[a]anthracene) and a well-known mutagenic PAH, benzo[a]pyrene, indicated similar potencies among all five of these compounds, particularly after longer (7 day) exposures. This study demonstrates the mutagenic potential of oxy-PAHs to an in vivo fish embryo model and points out the need for further study of their environmental occurrence and biologic effects.

A new PCR-based method shows that blue crabs (Callinectes sapidus (Rathbun)) consume winter flounder (Pseudopleuronectes americanus (Walbaum)).

Winter flounder (Pseudopleuronectes americanus) once supported robust commercial and recreational fisheries in the New York (USA) region, but since the 1990s populations have been in decline. Available data show that settlement of young-of-the-year winter flounder has not declined as sharply as adult abundance, suggesting that juveniles are experiencing higher mortality following settlement. The recent increase of blue crab (Callinectes sapidus) abundance in the New York region raises the possibility that new sources of predation may be contributing to juvenile winter flounder mortality. To investigate this possibility we developed and validated a method to specifically detect winter flounder mitochondrial control region DNA sequences in the gut contents of blue crabs. A survey of 55 crabs collected from Shinnecock Bay (along the south shore of Long Island, New York) in July, August, and September of 2011 showed that 12 of 42 blue crabs (28.6%) from which PCR-amplifiable DNA was recovered had consumed winter flounder in the wild, empirically supporting the trophic link between these species that has been widely speculated to exist. This technique overcomes difficulties with visual identification of the often unrecognizable gut contents of decapod crustaceans, and modifications of this approach offer valuable tools to more broadly address their feeding habits on a wide variety of species.

Severe inbreeding and small effective number of breeders in a formerly abundant marine fish.

In contrast to freshwater fish it is presumed that marine fish are unlikely to spawn with close relatives due to the dilution effect of large breeding populations and their propensity for movement and reproductive mixing. Inbreeding is therefore not typically a focal concern of marine fish management. We measured the effective number of breeders in 6 New York estuaries for winter flounder (Pseudopleuronectes americanus), a formerly abundant fish, using 11 microsatellite markers (6-56 alleles per locus). The effective number of breeders for 1-2 years was remarkably small, with point estimates ranging from 65-289 individuals. Excess homozygosity was detected at 10 loci in all bays (FIS = 0.169-0.283) and individuals exhibited high average internal relatedness (IR; mean = 0.226). These both indicate that inbreeding is very common in all bays, after testing for and ruling out alternative explanations such as technical and sampling artifacts. This study demonstrates that even historically common marine fish can be prone to inbreeding, a factor that should be considered in fisheries management and conservation plans.

Polychlorinated biphenyls, mercury, and antinuclear antibody positivity, NHANES 2003-2004.

Serum antinuclear antibody positivity (ANA) has been associated with elevated serum polychlorinated biphenyls (PCBs) among residents in PCB-polluted areas; however, associations in general populations have not been reported by congener type or with adjustment for mercury. Cross-sectional data on serum PCBs, total blood mercury, ANA, and potential confounders age, race, body mass index, menopausal status, and dietary eicosapentaenoic acid (EPA) were obtained from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) for males and females aged 12-85. PCB congeners were summed separately for dioxin-like and nondioxin-like PCBs; the former were weighted for toxic equivalent factors. Total PCBs by congener type and mercury were analyzed as both continuous log-transformed variables and as categorical quintiles. Logistic regression models were stratified by sex. There were no associations between nondioxin-like PCBs or mercury and ANA among males or females. Among females (n=114 affected and 518 unaffected), adjusting for potential confounders, the prevalence odds for ANA positivity were significantly elevated per incremental increase in log-transformed dioxin-like PCBs (odds ratio {OR}=1.66; 95% confidence interval {CI}=1.24, 2.23); the highest dioxin-like PCB quintile (>0.00425-0.04339ng/g) was significantly associated with 4.04 (95% CI=2.43, 6.70) greater prevalence odds for ANA positivity relative to the lowest quintile (Ptrend<0.001). We present novel findings of an association between low-level dioxin-like PCBs and ANA among women. No associations were observed between mercury and ANA at mercury levels common to the U.S. population.

The tissue residue approach for toxicity assessment: findings and critical reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop.

Over the past few years, the "critical body residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of tissue residues as the dose metric when defining dose-response relationships, evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "tissue residue approach for toxicity assessment" or "tissue residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using tissue residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.