Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats.

Di(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in various industrial and household plastic products, ensuring widespread human exposures. Its routine detection in human bio-fluids and the propensity of its monoester metabolite to activate peroxisome proliferator activated receptor-α (PPARα) and perturb lipid metabolism implicate it as a metabolic disrupter. In this study we evaluated the effects of DEHP exposure on hepatic levels of free CoA and various CoA esters, while also confirming the metabolic activation to CoA esters and partial ß-oxidation of a DEHP metabolite (2-ethyhexanol). Male Wistar rats were exposed via diet to 2% (w/w) DEHP for fourteen-days, following which hepatic levels of free CoA and various CoA esters were identified using liquid chromatography-mass spectrometry. DEHP exposed rats showed significantly elevated free CoA and increased levels of physiological, DEHP-derived and unidentified CoA esters. The physiological CoA ester of malonyl-CoA and DEHP-derived CoA ester of 3-keto-2-ethylhexanoyl-CoA were the most highly elevated, at eighteen- and ninety eight-times respectively. We also detected sixteen unidentified CoA esters which may be derivative of DEHP metabolism or induction of other intermediary metabolism metabolites. Our results demonstrate that DEHP is a metabolic disrupter which affects production and sequestration of CoA, an essential cofactor of oxidative and biosynthetic reactions.

Long-term hypoxia exposure alters the cardiorespiratory physiology of steelhead trout (Oncorhynchus mykiss), but does not affect their upper thermal tolerance.

It has been suggested that exposure to high temperature or hypoxia may confer tolerance to the other oxygen-limited stressor (i.e., 'cross-tolerance'). Thus, we investigated if chronic hypoxia-acclimation (>3 months at 40% air saturation) improved the steelhead trout's critical thermal maximum (CTMax), or affected key physiological variables that could impact upper thermal tolerance. Neither CTMax (24.7 vs. 25.3°C) itself, nor oxygen consumption ( [Formula: see text] ), haematocrit, blood haemoglobin concentration, or heart rate differed between hypoxia- and normoxia-acclimated trout when acutely warmed. However, the cardiac output (Q̇) of hypoxia-acclimated fish plateaued earlier compared to normoxia-acclimated fish due to an inability to maintain stroke volume (SV), and this resulted in a ~50% lower maximum Q̇. Despite this reduced maximum cardiac function, hypoxia-acclimated trout were able to consume more O2 per volume of blood pumped as evidenced by the equivalent [Formula: see text] . These results provide additional evidence that long-term hypoxia improves tissue oxygen utilization, and that this compensates for diminished cardiac pumping capacity. The limited SV in hypoxia-acclimated trout in vivo was not associated with changes in cardiac morphology or in vitro maximum SV, but the affinity and density of myocardial ß-adrenoreceptors were lower and higher, respectively, than in normoxia-acclimated fish. These data suggest that alterations in ventricular filling dynamics or myocardial contractility constrain cardiac function in hypoxia-acclimated fish at high temperatures. Our results do not support (1) 'cross-tolerance' between high temperature and hypoxia when hypoxia is chronic, or (2) that cardiac function is always the determinant of temperature-induced changes in fish [Formula: see text] , and thus thermal tolerance, as suggested by the oxygen- and capacity-limited thermal tolerance (OCLTT) theory.

What training and skills will the ecotoxicologists of the future require?

Students and academic researchers conduct a diverse range of studies that add to the growing body of ecotoxicology research. Once an academic researcher entertains an applied research topic, there is potential for that research to be used in local, state, or federal regulatory decision or action. The ability of regulatory decision makers to use academic studies to inform decisions is dependent on: 1) the relevance of the experiment to regulatory decisions, 2) the reliability of the laboratory and the study itself, and 3) quality reporting of data such that study relevance and reliability are evident. The purpose of this brief communication is to highlight actions that can be taken by Society of Environmental Toxicology and Chemistry members to enhance the usability of academic research studies in regulatory decision making by promoting training, partnerships, and communication. Integr Environ Assess Manag 2017;13:580-584. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Effect of Acute Alcohol Ingestion on Resistance Exercise-Induced mTORC1 Signaling in Human Muscle.

Duplanty, AA, Budnar, RG, Luk, HY, Levitt, DE, Hill, DW, McFarlin, BK, Huggett, DB, and Vingren, JL. Effect of acute alcohol ingestion on resistance exercise-induced mTORC1 signaling in human muscle. J Strength Cond Res 31(1): 54-61, 2017-The purpose of this project was to further elucidate the effects postexercise alcohol ingestion. This project had many novel aspects including using a resistance exercise (RE) only exercise design and the inclusion of women. Ten resistance-trained males and 9 resistance-trained females completed 2 identical acute heavy RE trials (6 sets of Smith machine squats) followed by ingestion of either alcohol or placebo. All participants completed both conditions. Before exercise (PRE) and 3 (+3 hours) and 5 (+5 hours) hours postexercise, muscle tissue samples were obtained from the vastus lateralis by biopsies. Muscle samples were analyzed for phosphorylated mTOR, S6K1, and 4E-BP1. For men, there was a significant interaction effect for mTOR and S6K1 phosphorylation. At +3 hours, mTOR and S6K1 phosphorylation was higher for placebo than for alcohol. For women, there was a significant main effect for time. mTOR phosphorylation was higher at +3 hours than at PRE and at +5 hours. There were no significant effects found for 4E-BP1 phosphorylation in men or women. The major findings of this study was that although RE elicited similar mTORC1 signaling both in men and in women, alcohol ingestion seemed to only attenuate RE-induced phosphorylation of the mTORC1 signaling pathway in men. This study provides evidence that alcohol should not be ingested after RE as this ingestion could potentially hamper the desired muscular adaptations to RE by reducing anabolic signaling, at least in men.

Comparison of Measured and Predicted Bioconcentration Estimates of Pharmaceuticals in Fish Plasma and Prediction of Chronic Risk.

Evaluation of the environmental risk of human pharmaceuticals is now a mandatory component in all new drug applications submitted for approval in EU. With >3000 drugs currently in use, it is not feasible to test each active ingredient, so prioritization is key. A recent review has listed nine prioritization approaches including the fish plasma model (FPM). The present paper focuses on comparison of measured and predicted fish plasma bioconcentration factors (BCFs) of four common over-the-counter/prescribed pharmaceuticals: norethindrone (NET), ibuprofen (IBU), verapamil (VER) and clozapine (CLZ). The measured data were obtained from the earlier published fish BCF studies. The measured BCF estimates of NET, IBU, VER and CLZ were 13.4, 1.4, 0.7 and 31.2, while the corresponding predicted BCFs (based log Kow at pH 7) were 19, 1.0, 7.6 and 30, respectively. These results indicate that the predicted BCFs matched well the measured values. The BCF estimates were used to calculate the human: fish plasma concentration ratios of each drug to predict potential risk to fish. The plasma ratio results show the following order of risk potential for fish: NET > CLZ > VER > IBU. The FPM has value in prioritizing pharmaceutical products for ecotoxicological assessments.

Bioconcentration of two basic pharmaceuticals, verapamil and clozapine, in fish.

The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 µg/L and 419 µg/L of verapamil (500 µg/L nominal) or 28.5 µg/L and 40 µg/L of clozapine (50 µg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients.

Review of laboratory-based terrestrial bioaccumulation assessment approaches for organic chemicals: Current status and future possibilities.

In the last decade, interest has been renewed in approaches for the assessment of the bioaccumulation potential of chemicals, principally driven by the need to evaluate large numbers of chemicals as part of new chemical legislation, while reducing vertebrate test organism use called for in animal welfare legislation. This renewed interest has inspired research activities and advances in bioaccumulation science for neutral organic chemicals in aquatic environments. In January 2013, ILSI Health and Environmental Sciences Institute convened experts to identify the state of the science and existing shortcomings in terrestrial bioaccumulation assessment of neutral organic chemicals. Potential modifications to existing laboratory methods were identified, including areas in which new laboratory approaches or test methods could be developed to address terrestrial bioaccumulation. The utility of "non-ecotoxicity" data (e.g., mammalian laboratory data) was also discussed. The highlights of the workshop discussions are presented along with potential modifications in laboratory approaches and new test guidelines that could be used for assessing the bioaccumulation of chemicals in terrestrial organisms.

Bioaccumulation of decamethylpentacyclosiloxane (D5): A review.

Decamethylpentacyclosiloxane (D5) is a widely used, high-production volume personal care product with an octanol-water partition coefficient (log K(OW)) of 8.09. Because of D5's high K(OW) and widespread use, it is subject to bioaccumulation assessments in many countries. The present study provides a compilation and an in-depth, independent review of bioaccumulation studies involving D5. The findings indicate that D5 exhibits depuration rates in fish and mammals that exceed those of extremely hydrophobic, nonbiotransformable substances; that D5 is subject to biotransformation in mammals and fish; that observed bioconcentration factors in fish range between 1040 L/kg and 4920 L/kg wet weight in laboratory studies using non-radiolabeled D5 and between 5900 L/kg and 13 700 L/kg wet weight in an experiment using C(14) radiolabeled D5; and that D5 was not observed to biomagnify in most laboratory experiments and field studies. Review of the available studies shows a high degree of internal consistency among findings from different studies and supports a broad comprehensive approach in bioaccumulation assessments that includes information from studies with a variety of designs and incorporates multiple bioaccumulation measures in addition to the K(OW) and bioconcentration factor.

In Silico analysis of perturbed steroidogenesis and gonad growth in fathead minnows (P. promelas) exposed to 17α-ethynylestradiol.

The multi-factorial nature of adverse reproductive effects mediated by endocrine disrupting compounds (or EDCs) makes understanding the mechanistic basis of reproductive dysfunction a highly pertinent area of research. As a consequence, a main motivator for continued research is to integrate 'multi-leveled' complexity (i.e., from genes to phenotype) using mathematical methods capable of encapsulating properties of physiological relevance. In this study, an in silico stoichiometric model of piscine steroidogenesis was augmented with a 'biomass' reaction associating the underlying stoichiometry of steroidogenesis with a reaction representative of gonad growth. The ability of the in silico model to predict perturbed steroidogenesis and subsequent effects on gonad growth was tested by exposing reproductively active male and female fathead minnows (Pimephales promelas) to 88 ng/L of the synthetic estrogen, 17α-ethynylestradiol (EE2). The in silico model was parameterized (or constrained) with experimentally quantified concentrations of selected steroid hormones (using mass spectrometry) and fold changes in gene expression (using RT-qPCR) for selected steroidogenic enzyme genes, in gonads of male and female fish. Once constrained, the optimization framework of flux balance analysis (FBA) was used to calculate an optimal flux through the biomass reaction (analogous to gonad growth) and associated steroidogenic flux distributions required to generate biomass. FBA successfully predicted effects of EE2 exposure on fathead minnow gonad growth (%gonadosomatic index or %GSI) and perturbed production of steroid hormones. Specifically, FBA accurately predicted no effects of exposure on male %GSI and a significant reduction for female %GSI. Furthermore, in silico simulations accurately identified disrupted reaction fluxes catalyzing productions of androgens (in male fish) and progestogens (in female fish), an observation which agreed with in vivo experimentation. The analyses presented is the first-ever to successfully associate underlying flux properties of the steroidogenic network with gonad growth in fish, an approach which can incorporate in silico predictions with toxicological risk assessments.

Responses to various exposure durations of levonorgestrel during early-life stages of fathead minnows (Pimephales promelas).

Pharmaceuticals are routinely detected in the environment; and several of these compounds have been extensively researched due to their potential impacts to the endocrine system of aquatic organisms. The negative reproductive consequences of synthetic progestins in teleost species have only recently been investigated. The current study examined different exposure periods that may be most sensitive for levonorgestrel (LNG) in early-life stages of fathead minnow larvae. Larvae were exposed to a single concentration of LNG (125ng/L) for different durations from fertilized egg through 28 days post hatch (dph) with growth and mRNA expression of FSH, 3ß-HSD, 20ß-HSD, and CYP19a1 measured. Regardless of the duration of exposure, LNG significantly decreased growth in the fathead minnow larvae at day 28. For both 20ß-HSD and CYP19a1, mRNA expression was decreased following LNG exposure durations ≥7 days. 3ß-HSD and FSH showed similar trends after exposure to LNG with later stages of development exhibiting decreased expression. 20ß-HSD and 3ß-HSD were the only transcripts to remain down regulated once larvae were moved to clean water after the 7-14dph LNG exposure. This study is the first to investigate the effects of exposure time to a synthetic progestin on developing fish. Future research is needed to understand what impacts these changes have on adult stages of development.

Effects of progesterone and norethindrone on female fathead minnow (Pimephales promelas) steroidogenesis.

As knowledge of contaminants capable of adversely modulating endocrine functions increases, attention is focused on the effects of synthetic progestins as environmental endocrine disrupters. In the present study, effects of exposure to a synthetic progestin (norethindrone, 168 ± 7.5 ng/L) and endogenous progestogen (progesterone, 34 ± 4.1 ng/L) on steroidogenesis in adult female fathead minnows were examined. In vivo exposure to either compound lowered expression (nonsignificant) of luteinizing hormone (LHß) levels in the brain along with significantly down-regulating the beta isoform of membrane progesterone receptor (mPRß) in ovary tissue. The correspondence between lowered LHß levels in the brain and mPRß in the ovary is suggestive of a possible functional association as positive correlations between LHß and mPR levels have been demonstrated in other fish species. In vitro exposure of ovary tissue to progesterone resulted in significantly elevated progestogen (pregnenolone, 17α-hydroxyprogesterone, and 17α,20ß-dihydroxypregnenone) and androgen (testosterone) production. Whereas in vitro exposure to norethindrone did not significantly impact steroid hormone production but showed decreased testosterone production relative to solvent control (however this was not significant). Overall, this study showed that exposure to a natural progestogen (progesterone) and synthetic progestin (norethindrone), was capable of modulating LHß (in brain) and mPRß expression (in ovary).

Levonorgestrel exposure to fathead minnows (Pimephales promelas) alters survival, growth, steroidogenic gene expression and hormone production.

Human pharmaceuticals are commonly detected in the environment. Concern over these compounds in the environment center around the potential for pharmaceuticals to interfere with the endocrine system of aquatic organisms. The main focus of endocrine disruption research has centered on how estrogenic and androgenic compounds interact with the endocrine system to elicit reproductive effects. Other classes of compounds, such as progestins, have been overlooked. Recently, studies have investigated the potential for synthetic progestins to impair reproduction and growth in aquatic organisms. The present study utilizes the OECD 210 Early-life Stage (ELS) study to investigate the impacts levonorgestrel (LNG), a synthetic progestin, on fathead minnow (FHM) survival and growth. After 28 days post-hatch, survival of larval FHM was impacted at 462 ng/L, while growth was significantly reduced at 86.9 ng/L. Further analysis was conducted by measuring specific endocrine related mRNA transcript profiles in FHM larvae following the 28 day ELS exposure to LNG. Transcripts of 3ß-HSD, 20ß-HSD, CYP17, AR, ERα, and FSH were significantly down-regulated following 28d exposure to 16.3 ng/L LNG, while exposure to 86.9 ng/L significantly down-regulated 3ß-HSD, 20ß-HSD, CYP19A, and FSH. At 2,392 ng/L of LNG, a significant down-regulation occurred with CYP19A and ERß transcripts, while mPRα and mPRß profiles were significantly induced. No significant changes occurred in 11ß-HSD, CYP11A, StAR, LHß, and VTG mRNA expression following LNG exposure. An ex vivo steroidogenesis assay was conducted with sexually mature female FHM following a 7 day exposure 100 ng/L LNG with significant reductions observed in pregnenolone, 17α,20ß-dihydroxy-4-pregnen-3-one (17,20-DHP), testosterone, and 11-ketotestosterone. Together these data suggest LNG can negatively impact FHM larval survival and growth, with significant alterations in endocrine related responses.

Exposures to a selective serotonin reuptake inhibitor (SSRI), sertraline hydrochloride, over multiple generations: changes in life history traits in Ceriodaphnia dubia.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to range from low parts per trillion to parts per billion levels in surface waters, wastewater effluents, and sediments. These low levels have led to concern for their potential long-term risks to the survival, growth, and reproduction of aquatic organisms. We investigated the acute and chronic effects of sertraline on the life history traits of Ceriodaphnia dubia over the course of three generations under environmentally realistic concentrations. Acute toxicity of sertraline in C. dubia offspring resulted in a 48h median effective concentration of 126µgL(-1). Under chronic exposure, the lowest concentration to affect fecundity and growth was at 53.4µgL(-1) in the first two generations. These parameters become more sensitive during the third generation where the LOEC was 4.8µgL(-1). The median effective concentrations (EC50) for the number of offspring per female, offspring body size, and dry weight were 17.2, 21.2, and 26.2µgL(-1), respectively. Endpoints measured in this study demonstrate that chronic exposure of C. dubia to sertraline leads to effects that occur at concentrations only an order of magnitude higher than predicted environmental concentrations. However, this study also demonstrates that multigenerational effects should be considered in chronic exposure studies because standard toxicity tests do not account for increases in sensitivity in successive generations to toxicants.

Tissue-specific bioconcentration of the synthetic steroid hormone medroxyprogesterone acetate in the common carp (Cyprinus carpio).

The steroid hormone medroxyprogesterone acetate (MPA), commonly used in oral and injectable contraceptives, has been detected in surface and wastewaters near urban and agricultural areas in several rivers of the world. The objectives of this study were to examine the accumulative potential and tissue distribution of MPA in fish. A freshwater species, the common carp (Cyprinus carpio), was exposed to 100 µg/L of MPA for a 7-day period followed by a depuration phase in which fish were maintained in dechlorinated tap water for an additional 7 days. Tissues (muscle, brain, plasma, and liver) were sampled during the uptake (days 1, 3, and 7) and depuration (day 14) phases of the experiment. Tissue-specific bioconcentration factors (BCF) ranged from 4.3 to 37.8 and uptake was greatest in the liver>brain>plasma and lowest in the muscle. From a regulatory standpoint, MPA shows little tendency to bioaccumulate in fish.

Toward improved models for predicting bioconcentration of well-metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance.

Models were developed to predict the bioconcentration of well-metabolized chemicals by rainbow trout. The models employ intrinsic clearance data from in vitro studies with liver S9 fractions or isolated hepatocytes to estimate a liver clearance rate, which is extrapolated to a whole-body biotransformation rate constant (kMET ). Estimated kMET values are then used as inputs to a mass-balance bioconcentration prediction model. An updated algorithm based on measured binding values in trout is used to predict unbound chemical fractions in blood, while other model parameters are designed to be representative of small fish typically used in whole-animal bioconcentration testing efforts. Overall model behavior was shown to be strongly dependent on the relative hydrophobicity of the test compound and assumed rate of in vitro activity. The results of a restricted sensitivity analysis highlight critical research needs and provide guidance on the use of in vitro biotransformation data in a tiered approach to bioaccumulation assessment.

Involvement of ß(3)-adrenergic receptors in in vivo cardiovascular regulation in rainbow trout (Oncorhynchus mykiss).

Currently, we have little information concerning the involvement of ß(3)-adrenergic receptors (AR) in cardiovascular regulation in fishes. The goal of this study was to investigate the effect of ß(3)-AR ligands on in vivo cardiovascular function in larval and adult rainbow trout (Oncorhynchus mykiss). In adult fish, injection of BRL(37344) (ß(3)-AR agonist) resulted in an increase in heart rate (f(H)) (~31%) while stroke volume (Sv) was reduced (-25.9%). Injection of SR(59230A) (ß(3)-AR antagonist) and propranolol (ß(1)/ß(2)-AR antagonist) resulted in increases in dorsal aorta blood pressure (P(DA)) with differing effect on cardiac variables (f(H) and Sv). To confirm specificity of the results, BRL(37344) was injected following sequential injections of phentolamine (α(1)-AR antagonist), atropine (muscarinic antagonist), propranolol and SR(59230A). While phentolamine had no effect on BRL(37344), atropine completely abolished the influence of BRL(37344) on f(H), Sv and cardiac output (Q). In larval trout, BRL(37344) (10 and 100 µM) induced a significant concentration-dependent increase in f(H) while SR(59230A) (1 and 10 µM) and propranolol (1 and 10 µM) separately caused a significant concentration-dependent decrease. These data suggest that ß(3)-ARs have an important role in regulation of cardiovascular function, and provide evidence for a potential interaction between muscarinic and adrenergic receptors in rainbow trout.

Chronic effects of carbamazepine on life-history strategies of Ceriodaphnia dubia in three successive generations.

Trace quantities of pharmaceuticals are continuously being discharged into the environment through domestic and industrial wastewater effluents, causing concern among scientists and regulators regarding potential long-term impacts on aquatic ecosystems. These compounds and their metabolites are constantly interacting with organisms at various life-cycle stages and may differentially influence the development of embryonic, larval, juvenile, and adult stages. To understand the possible cumulative effects of exposure to carbamazepine (CBZ), a multigenerational approach was taken in which survival, reproduction, respiration, growth, brood size, and biomass of Ceriodaphnia dubia were assessed at sublethal concentrations over the course of three successive generations. CBZ exposure significantly decreased fecundity at 196.7 µg/L in the F0 and F1 generations over 2 weeks and acclimatized at 264.6 µg/L in the F2 generation. Similarly, a significant decrease of neonate dry weight was observed at the 196.7 µg/L CBZ treatment in the F1 generation, and it acclimatized at 264.6 µg/L treatment level in the F2 generation. Median time to first brood release was significantly delayed at 264.6 µg/L in the F2 generation, indicating slower maturation. Results over three successive generations are not different than what one would obtain by testing simply the F0 generation. Furthermore, the effects measured were observed at concentrations two orders of magnitude higher than are environmentally relevant, and it is unlikely that CBZ poses a substantial risk to the environment regarding the end points measured in this study. However, additional research through laboratory and field multigenerational studies may be required to understand the overall risk of CBZ to other nontarget organisms.

Presence, fate and effects of the intense sweetener sucralose in the aquatic environment.

Sucralose (1,6-dichloro-1,6-dideoxy-b-D-fructo-furanosyl 4-chloro-4-deoxy-a-D-galactopyranoside), sold under the trade name Splenda, has been detected in municipal effluents and surface waters in the United States and Europe. The environmental presence of sucralose has led to interest in the possibility of toxic effects in non-target species. This review presents an environmental risk assessment of sucralose based on available data concerning its presence, fate and effects in the environment. Sucralose, which is made by selective chlorination of sucrose, is a highly stable compound, which undergoes negligible metabolism in mammals, including humans, and displays a low biodegradation potential in the environment. This intense sweetener is highly soluble in water, displays a low bioaccumulation potential and a low sorption potential to soil and organic matter, and thus is predominantly present in the water column. The predicted environmental concentration (PEC) for sucralose, based on measured data in surface waters, was determined to be 10 µg/L. Aquatic toxicity studies using standardized, validated protocols used in regulatory decision making indicate that sucralose does not alter survival, growth and reproduction of aquatic organisms (such as plants, algae, crustaceans and fish) at concentrations >9000 times higher than those detected in the environment. Some studies, using non-standardized protocols, have reported behavioral and other non-traditional responses in aquatic organisms, but the relevance of these findings for assessing adverse effects on individuals and populations will require further investigation. In terms of traditional risk assessment, the proposed predicted no effect concentration for aquatic organisms (PNEC) was determined to be 0.93 mg/L, based on the lowest no effect concentration (NOEC) from a validated chronic study with mysid shrimp and an application factor of 100. The resultant PEC/PNEC quotient was determined to be well below 1 (PEC/PNEC=0.08), thus indicating a limited risk to the environment using traditional ecological risk assessment approaches.

Field and laboratory fish tissue accumulation of the anti-convulsant drug carbamazepine.

Understanding the potential for human and veterinary pharmaceuticals to accumulate in the tissues of biota is a topic of increasing importance in the pharmaceutical risk assessment process. However, few data are available in the literature that compare the ability of laboratory bioconcentration studies to predict field tissue concentrations. To begin to address this data gap, bioconcentration factors (BCF) for carbamazepine (CBZ), a human anticonvulsant that modulates Na+ channels, were determined using laboratory experiments with Pimephales notatus and Ictalurus punctatus. These data were compared to field derived bioaccumulation factors (BAFs) for Oreochromis niloticus from the Denton, Texas Wastewater Treatment Plant. The 42 d kinetic BCFs (BCFk) for white muscle and liver of P. notatus were 1.9 and 4.6, respectively, while the white muscle, liver, brain, and plasma BCFk's of I. punctatus were 1.8, 1.5, 1.6, and 7.1, respectively. Field derived BAF values (2.5-3.8) for O. niloticus were similar to those derived in laboratory studies. Partitioning values between blood plasma and individual tissues were calculated for I. punctatus and O. niloticus, with the values indicating that tissue levels of carbamazepine are similar or slightly higher than plasma concentrations. Collectively these data suggest that the fish laboratory BCF and field derived BCF/BAF values for carbamazepine are similar and much lower than the European Union regulatory threshold of 2000 for designation of a "B" substance.