The role of the Niemann-Pick disease, type C1 protein in adipocyte insulin action.

The Niemann-Pick disease, type C1 (NPC1) gene encodes a transmembrane protein involved in cholesterol efflux from the lysosome. SNPs within NPC1 have been associated with obesity and type 2 diabetes, and mice heterozygous or null for NPC1 are insulin resistant. However, the molecular mechanism underpinning this association is currently undefined. This study aimed to investigate the effects of inhibiting NPC1 function on insulin action in adipocytes. Both pharmacological and genetic inhibition of NPC1 impaired insulin action. This impairment was evident at the level of insulin signalling and insulin-mediated glucose transport in the short term and decreased GLUT4 expression due to reduced liver X receptor (LXR) transcriptional activity in the long-term. These data show that cholesterol homeostasis through NPC1 plays a crucial role in maintaining insulin action at multiple levels in adipocytes.

Sediment contamination in Lyons Creek East, a tributary of the Niagara River: part I. Assessment of benthic macroinvertebrates.

Sediments in Lyons Creek East (Welland, Ontario), a tributary of the Niagara River and part of the Niagara River Area of Concern, which exceed screening-level environmental-quality criteria for multiple contaminants, were assessed for biological impacts using information from multiple lines of evidence. An initial chemical survey indicated the primary contaminants of concern to be polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), zinc, and p,p'-DDE due to frequent exceedences of sediment guidelines. A subsequent study focused on the chemical composition of sediment, status of benthic invertebrate communities, contaminant bioaccumulation in resident benthos, and sediment toxicity to laboratory-exposed organisms. Chemical and biological conditions in the creek were compared with those in reference creeks using both multivariate (cluster analysis and ordination) and univariate (regression) techniques. Sediment PCBs (≤ 19 µg/g), PAHs (≤ 63 µg/g), and Zn (≤ 7969 µg/g) were increased above the sediment-quality guidelines along most of the creek; however, the upper 1.5 km portion of the creek was the most highly contaminated and therefore the main focus for biological study. Although severe toxicity was evident at several locations in the upper creek, resident benthic communities were minimally affected by sediment contamination. The cause of toxicity was likely related to a combination of stressors, including PCBs, PAHs, and metals. Due to its biomagnifiable nature, bioaccumulation focused on PCBs; concentrations in resident macroinvertebrates were ≤ 2 orders of magnitude greater than those found in reference creeks and were above tissue residue guidelines, indicating a potential risk for consumers of benthos. This risk was not limited to the upper 1.5 km where other effects were seen.

Long-term changes in fish mercury levels in the historically impacted English-Wabigoon River system (Canada).

The English-Wabigoon River system in Northwestern Ontario, Canada, was one of the most heavily mercury-contaminated waterways in the world due to historical discharges in the 1960s from a chlor-alkali plant. This study examines long-term (1970-2010) monitoring data to assess temporal trends in mercury contamination in Walleye, Northern Pike and Lake Whitefish, three species important for sport and subsistence fishing in this region, using dynamic linear modeling and piecewise regression. For all lakes and species, there is a significant decline (36-94%) in mercury concentrations through time; however, there is evidence that this decline is either slowing down or levelling off. Concentrations in the English-Wabigoon fish are elevated, and may still present a potential health risk to humans consuming fish from this system. Various biotic and abiotic factors are examined as possible explanations to slowing rates of decline in mercury concentrations observed in the mid-1980s.

Long-term environmental fate of perfluorinated compounds after accidental release at Toronto airport.

Perfluorooctane sulfonate (PFOS; a perfluorinated compound or PFC), its salts, and perfluorooctane sulfonyl fluoride have recently been listed in Annex B of the Stockholm Convention due to their widespread presence, persistence, and toxicity. Because of the persistent nature of PFCs, it is generally presumed that the impact of direct discharges of these chemicals on a receiving environment would be long-lasting. However, long-term environmental fate studies based on field measurements are rare. We examined spatial and long-term (9 year) temporal trends of PFCs in water, sediment, fish, and fish liver collected in 2003, 2006, and 2009 from 10 locations spanning ∼20 km in Etobicoke and Spring Creeks, where an accidental release of fire fighting foam containing PFOS from nearby Toronto International Airport occurred in 2000. Even a decade after the spill, sediment PFOS concentrations are still elevated in Spring Creek Pond which received the foam discharge; however, the major impact is relatively localized likely due to the stormwater management nature of the pond and the diluting effect of Etobicoke Creek. Fish and fish liver PFOS concentrations at a Spring Creek location downstream of Spring Creek Pond declined by about 70 and 85%, respectively, between 2003 and 2009. PFOS in water at locations further downstream in Etobicoke Creek have declined by >99.99% since the spill; however, the 2009 water and fish levels were ∼2-10 times higher than upstream locations likely due to the long-term impact of the spill as well as urbanization. The decrease in the upstream PFOS concentrations likely reflects the reduction of PFOS sources due to phased out production by 3M and regulations on the use of PFOS in fire fighting foams. Field-based sediment/water distribution coefficients (K(D)) and bioaccumulation factors (BAF) were calculated from environmental measurements. Log K(D) values were 0.54-1.65 for perfluoroalkyl sulfonates (PFASs) and 1.00-1.85 for perfluorocarboxylates (PFCAs). Log BAF(fish) ranged from 1.85 to 3.24 for PFASs and 0.88-3.47 for PFCAs, whereas log BAF(fish liver) ranged from 2.1-4.3 for PFASs and 1.0-5.0 for PFCAs.

Influence of fish size and sex on mercury/PCB concentration: importance for fish consumption advisories.

Fish advisories for polychlorinated biphenyls (total-PCBs) and mercury are often given on a length-specific basis and fish sex is usually not considered. The relationship between concentration and length is well established for mercury, however its suitability for total-PCBs and the influence of sex over the large scale covered by most monitoring programs is not well known. Here we use what is perhaps the largest consistent sport fish contaminant dataset to evaluate the relationship between total-PCB/mercury and length and sex. We evaluated seven of the most commonly consumed fishes from the Canadian Great Lakes and two Ontario (Canada) inland lakes. For mercury, the relationship between concentration and length was significant (p<0.05) in most fish species and locations. For total-PCB, this relationship was also generally significant in Chinook salmon and lake trout, which are the species with the most advisories for this compound. In contrast, significant relationships were found less often for whitefish, northern pike, smallmouth bass, walleye, and especially yellow perch. However, mercury usually drives fish consumption advisories for these species. Overall, our results support the protocol of issuing contaminant advice on a length-specific basis in fish monitoring programs with reasonable confidence when at least a moderate number of samples over the natural size range of a species are included in the analysis. Sex differences were common for walleye (males>females, p<0.05) but not other species, suggesting that an equal number of male and female walleye should be used in deriving fish advisories for walleye.

Estimating sediment quality thresholds to prevent restrictions on fish consumption: Application to polychlorinated biphenyls and dioxins-furans in the Canadian Great Lakes.

Sediment quality thresholds (SQTs) are used by a variety of agencies to assess the potential for adverse impact of sediment-associated contaminants on aquatic biota, typically benthic invertebrates. However, sedimentary contaminants can also result in elevated fish contaminant levels, triggering consumption advisories that are protective of humans. As such, SQTs that would result in fish concentrations below consumption advisory levels should also be considered. To illustrate how this can be addressed, we first calculate biota sediment accumulation factors (BSAFs) for polychlorinated biphenyls (total PCB) and polychlorinated dioxins-furans (PCDD/Fs) in the Canadian Great Lakes using measured lake sediment and fish tissue concentrations in 4 fish species, namely, lake trout, whitefish, rainbow trout, and channel catfish. Using these BSAFs and tissue residue values for fish consumption advisories employed by the Ontario Ministry of the Environment (OMOE, Canada), we derive fish consumption advisory-based SQTs (fca-SQTs) that are likely to result in fish tissue residues that are safe to eat without restriction. The PCDD/Fs fca-SQTs ranged from 6 to 128 pg toxic equivalents (TEQ)/g dry weight (dw) and were above the Canadian Council of the Ministers of the Environment (CCME) threshold effect level (TEL) of 0.85 pg TEQ/g dw. In contrast, the total PCB fca-SQTs ranged from 1 to 60 ng/g dw and were generally below the CCME's TEL of 34.1 ng/g and OMOE's lowest effect level (LEL) of 70 ng/g; however, they were consistent with the OMOE's no effect level (NEL) of 10 ng/g. The fca-SQTs derived using the BSAF as well as food chain multiplier (FCM) approach for a smaller scale system (Hamilton Harbour in Lake Ontario) corresponded well with average lakewide Lake Ontario fca-SQTs. This analysis provides approximate sediment concentrations necessary for reducing fish consumption advisories for each of the Canadian Great Lakes and emphasizes the impacts of historical lake sediment contamination on fish advisories. We believe that this approach merits consideration in sediment guideline development.

Temporal trends and spatial distribution of dioxins and furans in lake trout or lake whitefish from the Canadian Great Lakes.

Concentrations of the seventeen 2,3,7,8-substituted, most toxic congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were measured in lake trout (Salvelinus namaycush) or lake whitefish (Coregonus clupeaformis) collected between 1989 and 2003 from the Canadian Great Lakes as a part of the on-going Sport Fish Contaminant Monitoring Program of the Ontario Ministry of the Environment. These monitoring data were used to assess temporal trends and spatial variations of these compounds in the Canadian Great Lakes. Toxic equivalents (TEQs) were calculated using the measured congener concentrations and toxicity equivalency factors (TEFs) published by the World Health Organization in 1998. Five congeners, namely 2,3,7,8-TCDD, 2,3,7,8-TCDF, 1,2,3,7,8-PeCDD, 1,2,3,7,8-PeCDF, and 2,3,4,7,8-PeCDF, were the most dominant congeners among the 17 congeners analyzed. The highest TEQs were found for Lake Ontario lake trout (22-54 pg g(-1)) while the TEQs for the other Canadian Great Lakes were 60-95% lower. Non-parametric Mann-Kendall and Sen's tests performed on TEQs and PCDD/Fs standardized at a mean lake trout length of 60 cm suggest a linearly decreasing trend for PCDD/Fs in lake trout from Lakes Ontario and Huron. There was no monotonously increasing or decreasing trend found for Lake Superior lake trout. The ratios of 2,3,7,8-TCDD to 2,3,7,8-TCDF concentrations were generally constant during the 1989-2003 period with the values being in the order of Lakes Superior (0.05-0.3)

Converting Toxic Equivalents (TEQ) of dioxins and dioxin-like compounds in fish from one Toxic Equivalency Factor (TEF) scheme to another.

Toxic Equivalency Factors (TEFs) are an essential part of the Toxic Equivalent (TEQ) concept and have evolved for dioxins/dioxin-like compounds over the last two and half decades. Therefore, it is difficult to compare past and current TEQs that are reported using different TEFs without explicitly mentioning underlying congener concentrations. Using what likely is the largest known dioxin/furan (PCDD/F) and dioxin-like polychlorinated biphenyl (dl-PCB or DLP) fish database, here we present regression models that can facilitate conversion of a fish TEQ from an old to a newer TEF scheme. The results show that the mammalian PCDD/F-TEQ based on the latest TEF(WHO-05) is about 7.5% lower than that based on TEF(WHO-98). The mammalian DLP-TEQ(WHO-05) is on average 25-26% lower than almost identical DLP-TEQ(WHO-94) and DLP-TEQ(WHO-98). Total-TEQ(WHO-05) is on average 22% lower than Total-TEQ(WHO-98). According to the current toxicological standards for dioxins/furans, all previous major TEF schemes except TEF(Germany-85) and TEF(USEPA-87) were conservative (i.e., higher) in estimating TEQs. The major (> 75%) contribution to PCDD/F-TEQ(WHO-05) is from 2,3,7,8-TCDD (33%), 1,2,3,7,8-PCDD (26%), 2,3,7,8-TCDF (10%), and 2,3,4,7,8-PCDF (9%). The DLP-TEQ(WHO-05) is dominated by PCB-126 which on average contributes about 88%. The DLP-TEQ generally contribute > 70% of Total-TEQ. When reporting TEQs, we recommend that the underlying congener specific concentrations are presented, TEF scheme used is clearly stated, names of compounds included are explicitly expressed, and TEQs are identified accordingly (e.g., DLP-TEQ, PCDD/F-TEQ, Total-TEQ).

Composition of dioxin-like PCBs in fish: an application for risk assessment.

It is widely accepted that a congener-specific analysis of polychlorinated biphenyls (PCBs), rather than traditional Aroclor equivalent total PCB analysis, is required for risk assessment. This is based on the fact that environmental processes alter the original distribution of PCB congeners in Aroclors and that toxicity varies considerably among the congeners with dioxin-like PCBs (dl-PCBs) generally being among the most toxic. Using the largest known dl-PCB fish dataset, here we present a likely composition of dl-PCBs in fish. In contrast to common perception, we found that the dl-PCB composition is relatively constant (within approximately a factor of 2) regardless of fish species and total PCB level. The abundance of dl-PCBs expressed as a percentage of total PCB (25-75 quartile range) in fish is generally in the order of PCB-118 (3.0-6.2%) > PCB-105 (1.1-2.4%) > PCB-156 (0.39-0.75%) > PCB-167 (0.20-0.43%) > PCB-123 (0.11-0.26%) > PCB-157 (0.09-0.19%) = PCB-114 (0.08-0.18%) > PCB-189 (0.045-0.094%) > PCB-77 (0.018-0.093%) > PCB-126 (0.015-0.036%) > PCB-81 (0.002-0.007%) = PCB-169 (0.001-0.006%). The most toxic dl-PCB congeners PCB-126 and -169 contribute on average only 0.027 and 0.004% of total PCB, respectively. The statistically significant relationships presented between individual di-PCB and total-PCB concentrations can be used as a practical tool to estimate dl-PCBs for risk assessment purposes. A comparison of the dl-PCB pattern presented here with other studies suggests that this dl-PCB composition is applicable to fish from North America and perhaps from other geographical regions throughout the world.