Bioconcentration factors for hydrocarbons and petrochemicals: Understanding processes, uncertainty and predictive model performance.

Fish bioconcentration factors (BCFs) are often used to assess substance-specific bioaccumulation. However, reliable BCF data are limited given the practical challenges of conducting such tests. The objectives of this paper are to describe nine rainbow trout studies performed in our lab using tailored dosing and test designs for obtaining empirical BCFs for 21 test substances; gain insights into the structural features and processes determining the magnitude and uncertainty in observed BCFs; and assess performance of six quantitative structure property relationships (QSPRs) for correctly categorizing bioaccumulation given current regulatory triggers. Resulting mean steady-state BCFs, adjusted to a 5% lipid content, ranged from 12 Lkg-1 for isodecanol to 15,448 Lkg-1 for hexachlorobenzene which served as a positive control. BCFs for hydrocarbons depended on aromatic and saturated ring configurations and position. Uptake clearances appeared to be modulated by gill metabolism and substance bioavailability, while elimination rates were likely influenced by somatic biotransformation. Current approaches for quantifying uncertainty in experimental BCFs, which take into account only variability in measured fish concentrations, were found to underestimate the true uncertainty in this endpoint with important implications for decision-making. The Vega (KNN/Read-Across) QSPR and Arnot-Gobas model yielded the best model performance when compared to measured BCFs generated in this study.

Application of the Target Lipid Model and Passive Samplers to Characterize the Toxicity of Bioavailable Organics in Oil Sands Process-Affected Water.

Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g., naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

Technical basis for using passive sampling as a biomimetic extraction procedure to assess bioavailability and predict toxicity of petroleum substances.

Solid-phase microextraction fibers coated with polydimethylsiloxane (PDMS) provide a convenient passive sampling format to characterize bioavailability of petroleum substances. Hydrocarbons absorb onto PDMS in proportion to both freely dissolved concentrations and partitioning properties of the individual constituents, which parallels the mechanistic basis used to predict aquatic toxicity in the PETROTOX model. When deployed in a non-depletive manner, combining SPME with thermal desorption and quantification using gas chromatography-flame ionization creates a biomimetic extraction (BE) procedure that has the potential to simplify aquatic hazard assessments of petroleum substances since the total moles of all hydrocarbons sorbed to the fiber can be related to toxic thresholds in target lipid of aquatic organisms. The objective of this work is to describe the technical basis for applying BE measurements to predict toxicity of petroleum substances. Critical BE-based PDMS concentrations corresponding to adverse effects were empirically derived from toxicity tests on different petroleum substances with multiple test species. The resulting species sensitivity distribution (SSD) of PDMS effect concentrations was then compared and found consistent with the previously reported target lipid-based SSD. Further, BE data collected on samples of aqueous media dosed with a wide range of petroleum substances were highly correlated to predicted toxic units derived using the PETROTOX model. These findings provide justification for applying BE in environmental hazard and risk evaluations of petroleum substances and related mixtures.

Influence of toluene co-exposure on the metabolism and genotoxicity of benzene in mice using continuous and intermittent exposures.

Benzene exposure in occupational settings often occurs with concurrent exposure to toluene, the methyl-substituted derivative of benzene. Toluene is also readily metabolized by CYP450 isozymes although oxidation primarily occurs in the methyl group. While earlier mouse studies addressing co-exposure to benzene and toluene at high concentrations demonstrated a reduction in benzene-induced genotoxicity, we have previously found, using an intermittent exposure regimen with lower concentrations of benzene (50 ppm) and toluene (100 ppm), that toluene enhances benzene-induced clastogenic or aneugenic bone marrow injury in male CD-1 mice with significantly increased CYP2E1, and depleted GSH and GSSG levels. The follow-up study reported here also used the same daily and total co-exposures but over consecutive days and compared the effects of co-exposure on genotoxicity and metabolism in CD-1 mice both with and without buthionine sulfoximine (BSO) treatment to deplete GSH. In this study the toluene co-exposure doubled the genotoxic response (as determined by the erythrocyte micronucleus test) to benzene alone. Further, GSH depletion caused a reduction in this genotoxicity in both benzene exposed and benzene/toluene co-exposed mice. The results are discussed in terms of the analyses of urinary metabolites from this consecutive day study and the intermittent exposure study as well as levels of CYP2E1, epoxide hydrolase, quinone reductase, alcohol dehydrogenase, and aldehyde dehydrogenase activities. The results suggest that the presence of glutathione is necessary for benzene genotoxicity either as a metabolite conjugate or through an indirect mechanism such as TNF-induced apoptosis.

Assessing the aquatic hazard of commercial hydrocarbon resins.

Hydrocarbon resins are used to modify polymer products to achieve desired functional properties for a diverse range of products. These complex hydrocarbon-based mixtures are typically poorly soluble in water. However, resins may leach lower-molecular-weight monomers or impurities upon contact with water, thus posing a potential hazard to the aquatic environment. The bioavailability and toxicity of leachable constituents of four solid and three liquid resins were evaluated by analyzing water-accommodated fractions prepared with each resin, using biomimetic solid phase microextraction (SPME) techniques. Liquid resins exhibited concentrations of bioavailable constituents that were sufficiently elevated to cause acute toxicity to the aquatic organism Daphnia magna. All solid resins exhibited lower bioavailable concentrations of leachable constituents that were unlikely to pose an aquatic toxicity concern. Since observed toxicity of both resin types was generally consistent with bioavailable concentrations determined using SPME fiber measurements, it is concluded that this approach provides a convenient in vitro screening tool that can help reduce the use of animal testing in environmental hazard assessment of complex hydrocarbon-based substances.

Hazard evaluation of diisononyl phthalate and diisodecyl phthalate in a Japanese medaka multigenerational assay.

Reproductive and developmental effects of diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were evaluated in a Japanese medaka (Oryzias latipes) multigeneration protocol. Each phthalate was administered via fish flake diets at a concentration of 20 microg/g (1 microg/g fish/day). Two controls were included, untreated and acetone carrier. The F(0) and F(1) generation adults were reared to sexual maturation and the test was ended prior to sexual maturation of the F(2) generation. Biochemical, individual, and population parameters were evaluated: testosterone metabolism, 7-ethoxyresorufin-o-deethylase (EROD) activity, survival, development, growth, gonadal-somatic index, histopathology, sex ratio, and fecundity. Male fish showed a two-fold induction of several testosterone metabolites in the DINP-treated group compared to the untreated control but not the acetone control. In a similar manner, in female fish only the DIDP-treated group expressed greater testosterone hydroxylase activity. There were neither sex- nor treatment-related differences in the results from the EROD assay. A statistically significant transient delay in red blood cell pigmentation was observed. The male-to-female ratio was consistent across treatments and the phenotypic and histological gender classifications were in agreement. Egg production was not significantly different among treatment groups. Neither phthalate elicited an effect on reproduction or development at various levels of biological organization.

Assessing the aquatic toxicity of complex hydrocarbon mixtures using solid phase microextraction.

Assessing the ecotoxicity of hydrocarbon mixtures is complicated by the complex nature of these mixtures. Traditional analytical methods for characterizing hydrocarbon contamination are not good predictors of potential ecotoxicity because these methods fail to characterize the bioavailability of individual hydrocarbon components. Recent research indicates that hydrocarbons act by a common narcotic mode of action and that ecotoxicity occurs when the molar concentration in organism lipid exceeds a critical threshold. Since the ecotoxicity of narcotic mixtures appears to be additive, ecotoxicity thus depends upon the partitioning of individual hydrocarbons from the environment to lipids and the total molar sum of individual hydrocarbons in lipids. These insights have led previous investigators to advance the concept of 'biomimetic' extraction as a novel analytical tool for assessing narcosis-type or 'baseline'. Drawing from this earlier work, a simple method to quantify bioavailable petroleum hydrocarbons (BPHs) in hydrocarbon-contaminated aqueous and soil/sediment samples was developed. The proposed method combines the essential features of biomimetic extraction for simulating the bioconcentration process with the analytical advantages of solid phase microextraction (SPME). The procedure for determining BPH involves two steps. The sample is first equilibrated with a SPME fiber that serves as a surrogate for organism lipids. The total moles of hydrocarbons that partition to the SPME fiber is then quantified using GC/FID. The capability of this method to predict ecotoxicity was assessed by comparing BPH measurements for hydrocarbon contaminated aqueous samples to corresponding toxicity test results for rainbow trout. Results indicate that BPH analyses correlate to the observed acute toxicity. Consequently, BPH analyses offer a promising, cost-effective screening tool for predicting aquatic toxicity of complex hydrocarbon mixtures.