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Biomedical subjects

Paul F Hoekstra

Publications and source records attributed to Paul F Hoekstra.

14 recordsLinked to original sources
PubMed2005

Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications.

Dicofol is a non-systemic acaricide/miticide currently registered in the US and Canada for use on a wide variety of crops. This agrochemical has been identified as a potential candidate substance for the United Nations Economic Commission for Europe (UN-ECE) Persistent Organic Pollutant (POP) Protocol and implicated as a potential "endocrine disrupting compound". The technical product is usually synthesized from technical DDT and consists of approximately 80% and 20% of p,p'- and o,p'-dicofol isomers. The o,p'-substituted isomer of dicofol is chiral and may have enantiomer-specific activity; however, the stereospecific activity of o,p'-dicofol has not been reported. In this study, we examined the isomer- and enantiomer-specific endocrine disruption potential of dicofol using yeast-based steroid hormone receptor gene transcription assay designed with the human estrogen receptor (hER). Estrogenic activity of (+)-17-beta estradiol (positive control), p,p'-dicofol, racemic o,p'-dicofol [(+/-)-o,p'-dicofol] and the individual o,p'-dicofol enantiomers was measured via quantification of beta-galactosidase. The (+/-)-o,p'- and p,p'-dicofol were weak estrogen mimics (EC(50): 4.2 x 10(-6) and 1.6 x 10(-6)M, respectively) relative to estradiol (3.7 x 10(-10)M). For o,p'-dicofol, the beta-galactosidase induction by (-)-o,p'-dicofol (EC(50): 5.1 x 10(-7)M) was greater than the racemic mixture. However, the (+)-o,p'-dicofol enantiomer was found to have negligible estrogenic activity. These data indicate that dicofol is a weak hER agonist due to activity of the achiral p,p'-isomer and (-)-o,p'-substituted enantiomer and emphasizes the influence of chemical structure and configuration on biological responses to exposure from chiral compounds.

Dicofol↗
PubMed2005

Spatial and temporal trends of contaminants in terrestrial biota from the Canadian Arctic.

Contaminants in the Canadian Arctic have been studied over the last twelve years under the guidance of the Northern Contaminants Program. This paper summarizes results from that program from 1998 to 2003 with respect to terrestrial animals in the Canadian Arctic. The arctic terrestrial environment has few significant contaminant issues, particularly when compared with freshwater and marine environments. Both current and historical industrial activities in the north may have a continuing effect on biota in the immediate area, but effects tend to be localized. An investigation of arctic ground squirrels at a site in the Northwest Territories that had historically received applications of DDT concluded that DDT in arctic ground squirrels livers was the result of contamination and that this is an indication of the continuing effect of a local point source of DDT. Arsenic concentrations were higher in berries collected from areas around gold mines in the Northwest Territories than from control sites, suggesting that gold mining may significantly affect arsenic levels in berries in the Yellowknives Dene traditional territory. Although moose and caribou from the Canadian Arctic generally carry relatively low contaminant burdens, Yukon moose had high renal selenium concentrations, and moose and some woodland caribou from the same area had high renal cadmium levels, which may put some animals at risk of toxicological effects. Low hepatic copper levels in some caribou herds may indicate a shortage of copper for metabolic demands, particularly for females. Similarities in patterns of temporal fluctuations in renal element concentrations for moose and caribou suggest that environmental factors may be a major cause of fluctuations in renal concentrations of some elements. Concentrations of persistent organochlorines and metals in beaver and muskrat from the Northwest Territories, and carnivores from across the Canadian Arctic were very low and considered normal for terrestrial wildlife. Two new classes of persistent fluorinated contaminants, perfluorooctane sulfonate (PFOS) and perfluoroalkyl carboxylates (PFCAs) were found in arctic carnivores and were most abundant in arctic fox and least abundant in mink. Although trace element concentrations in king and common eider ducks were low and not of toxicological concern, the number of nematode parasites in common eiders was positively correlated with total and organic mercury concentrations. Future research should focus on cadmium in moose and caribou, mercury in caribou, and emerging contaminants, with an effort to sample moose and caribou annually where possible to explore the role of naturally occurring cycles in apparent temporal trends.

Animals↗
PubMed2005

Development and application of bioaccumulation models to assess persistent organic pollutant temporal trends in arctic ringed seal (Phoca hispida) populations.

Individual- and population-based models were developed to simulate the bioaccumulation of persistent organic pollutants (POPs) over the lifetime of ringed seals (Phoca hispida) and account for the effects of age, growth, body condition and sex (including gestation, birth and lactation). Lactational transfer was described using a milk to blubber partition coefficient, which was shown to be a function of Kow (KMB=1/(1.676+1.293.10(-7).Kow) r2=0.60, n=32, p<0.001). Simulations showed that nursing mothers could transfer between 5% and 40% of their burden of low and high KMB contaminants, respectively, to their milk over 40 days of lactation. The models were calibrated using a POPs dataset for 50 seals (29 males, 21 females) from Arviat, Nunavut. They were initially calibrated for a group of eight highly recalcitrant PCB congeners (e.g. PCBs 153, 180) assuming a baseline elimination rate (ke) of about 0.03 year-1. For congeners more prone to biotransformation a satisfactory fit could only be reached by iteratively increasing ke to values ranging from 0.05 to 2.5 year-1 for PCBs 187 and 18, respectively; thus the models became a means for estimating ke. Estimated ke values were correlated with a calculated index of susceptibility to biotransformation (ke=0.0284/Rrelr2=0.98, n=20, p<0.001). This relationship was used to estimate ke values used in simulations to hind-cast temporal trends of SigmaPCB, SigmaDDT, SigmaCHL, alphaHCH, betaHCH in ringed seal populations and to predict potential future trends. Results of these simulations showed good agreement with measured concentrations in seals from two locations in the Canadian Arctic (Holman Island, NWT and Arctic Bay, Nunavut) collected between 1972 and 2001. The models show that the combined effects of rapid juvenile growth, a fast rate of population turnover and substantial capacity to eliminate many POPs result in fairly rapid responses to changes in contaminant loading, thus making ringed seals an effective choice for monitoring spatial and temporal trends of POPs in the Arctic marine ecosystem.

Adipose Tissue↗
PubMed2005

Bioaccumulation factors for PCBs revisited.

Bioaccumulation factors (BAFs) for individual polychlorinated biphenyl (PCB) congeners in Barents Sea and White Sea marine calanoid copepods were 1-3 orders of magnitude higher than BAFs in the same species in Canadian and Alaskan Arctic Ocean areas, and in freshwater plankton (Lake Ontario) reported from the mid- to early 1980s. The present study reviews variability in PCB BAFs from the North American Great Lakes and the Arctic Ocean, and discusses possible explanations for the large variation among different studies. BAFs are higher in recent arctic marine and Great Lakes studies than previously reported, and they are at least 10 times higher than those predicted from the octanol-water partition coefficient (KOW). If the recent high BAFs are realistic, it means that earlier reported BAFs are too low. This is likely due to earlier erroneously high quantification of water PCB concentrations, and it implies that bioaccumulation in zooplankton is more efficient than previously assumed. Evidence is presented supporting that also trophic transfer and biomagnification of PCBs in zooplankton leads to BAFs well above those predicted by simple equilibrium partitioning. Overall, miss-measurement of water PCB concentrations and biomagnification contribute significantly to variability in BAFs for PCBs within and among studies. This large variability of BAFs for PCBs in zooplankton illustrated in the present study is of importance for future assessments of potential new bioaccumulative chemicals that rely on measured BAFs, such as the European Union Registration, Evaluation and Authorization of Chemicals program (REACH).

Animals↗
PubMed2005

Organohalogen contaminants in delphinoid cetaceans.

This chapter reviews the global distribution, biotransformation, accumulation patterns, and mechanisms of action and the potential impacts of persistent organohalogen contaminants (PHCs) on physiological systems of cetaceans with emphasis on delphinoids. Methods used to study PHCs in stranded and free-living cetaceans are discussed, and concentrations of PHCs of stranded, hunted, by-catch, and free-ranging delphinoids are summarized. Overall, the highest concentrations of PHC contamination were found in delphinoids from industrialized areas of the Northern Hemisphere compared to the Southern Hemisphere. Nonetheless, PHCs are also found in marine mammal tissues from the Southern Hemisphere and in remote regions such as the Arctic, reflecting the global distribution and contamination of PHCs in the marine ecosystem.

Adipose Tissue↗
PubMed2005

Concentrations of selected persistent organochlorine contaminants in store-bought foods from northern Alaska.

OBJECTIVES: We address marine and terrestrial mammal blubber, liver, muscle, kidney, heart, tongue, maktak and maktaaq (epidermis and blubber from bowhead, beluga whales, respectively), and fish muscle and livers, as commonly consumed tissues in subsistence communities across northern Alaska in the context of organochlorine (OC) contamination of store-bought foods. Human exposure to contaminants from biota, as part of a subsistence diet, has been superficially evaluated in numerous studies (focused on liver and blubber), but are limited in the type of tissues analyzed, and rarely consider the contaminants in the alternatives (i.e., store-bought foods). STUDY DESIGN: Concentrations from published literature on selected persistent organochlorine contaminants (OCs) in eight tissues of the bowhead whale and other biota (1) were compared to store-bought foods evaluated in this study. RESULTS: As expected, store-bought foods had lower concentrations of OCs than some tissues of the marine mammals (especially blubber, maktak, and maktaaq). However, blubber is rarely eaten alone and should not be used to give consumption advice unless considered as a portion of the food item (i.e., maktak). This study indicates that the store-bought food alternatives have detectable OC concentrations (e.g., < 0.01 to 22.5 ng/g w.w. for hexachlorobenzene) and, in many cases, have greater OC concentrations than some subsistence food items. Many wildlife tissues had OC concentrations similar to those quantified in local store-bought food. CONCLUSIONS: Switching from the traditional diet to western store-bought foods will not always reduce exposure to OCs. However, raw blubber-based products are clearly more contaminated with OCs due to lipid content. A detailed profile of traditional/country foods and western foods consumed by subsistence communities of northern Alaska is required to address chronic exposure in more detail for the diverse sources of foods (subsistence use and commercially available) and the widely varying concentrations of contaminants reported therein. This should be combined with biomonitoring people dependent upon subsistence foods. Further assessment of essential and non-essential elements, emerging contaminants (e.g. brominated flame retardants), etc. should be conducted in order to improve our understanding of the differences and similarities between wildlife and store-bought foods.

Alaska↗
PubMed2004

Identification of long-chain perfluorinated acids in biota from the Canadian Arctic.

Recently it was discovered that humans and animals from various urban and remote global locations contained a novel class of persistent fluorinated contaminants, the most pervasive of which was perfluorooctane sulfonate (PFOS). Lower concentrations of perfluorooctanoate, perfluorohexane sulfonate, and heptadecafluorooctane sulfonamide have also been detected in various samples. Although longer perfluoroalkyl carboxylates (PFCAs) are used in industry and have been detected in fish following a spill of aqueous film forming foam, no studies have been conducted to examine the widespread occurrence of long-chain PFCAs (e.g., CF3(CF2)xCOO-, where x > 6). To provide a preliminary assessment of fluorinated contaminants, including PFCAs, in the Canadian Arctic, polar bears, ringed seals, arctic fox, mink, common loons, northern fulmars, black guillemots, and fish were collected at various locations in the circumpolar region. PFOS was the major contaminant detected in most samples and in polar bear liver was the most prominent organohalogen (mean PFOS = 3.1 microg/g wet weight) compared to individual polychlorinated biphenyl congeners, chlordane, or hexachlorocyclohexane-related chemicals in fat. Using two independent mass spectral techniques, it was confirmed that all samples also contained ng/g concentrations of a homologous series of PFCAs, ranging in length from 9 to 15 carbons. Sum concentrations of PFCAs (sum(PFCAs)) were lower than total PFOS equivalents (sum(PFOS)) in all samples except for mink. In mink, perfluorononanoate (PFNA) concentrations exceeded PFOS concentrations, indicating that PFNA and other PFCAs should be considered in future risk assessments. Mammals feeding at higher trophic levels had greater concentrations of PFOS and PFCAs than mammals feeding at lower trophic positions. In general, odd-length PFCAs exceeded the concentration of even-length PFCAs, and concentrations decreased with increasing chain length in mammals. PFOS and PFCA concentrations were much lower for animals living in the Canadian Arctic than for the same species living in mid-latitude regions of the United States. Future studies should continue to monitor all fluorinated contaminants and examine the absolute and relative toxicities for this novel suite of PFCAs.

Alkanesulfonates↗
PubMed2004

Toxicokinetics of three polychlorinated biphenyl technical mixtures in rainbow trout (Oncorhynchus mykiss).

Accumulation and depuration parameters of polychlorinated biphenyls (PCBs) in fish have been reported only for a few congeners. As well, there is little information on the ability of fish to biotransform PCBs. To address these issues, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to dietary concentrations of three Aroclor mixtures (1248, 1254, 1260) in food for 30 d followed by an additional 160 d of nonspiked food at 8 degrees C. Accumulation, depuration, and potential biotransformation of 92 PCB congeners were assessed. Half-lives (t1/2) of PCB congeners ranged from 79 to 182 d, assimilation efficiencies ranged from 40 to 50% and biomagnification factors (BMF) ranged from 2.9 to 6.9. No evidence of significant biotransformation of any PCB congeners was found. All 92 congeners fell on the same t1/2 to Kow relationship as 16 preselected PCB congeners previously shown to persist in fish and no hydroxylated PCB metabolites (OH-PCBs) were detected in the plasma after 30 d of exposure. These findings suggest that OH-PCBs observed in feral fish may be accumulated from sources other than internal metabolism of the parent congeners, at least for juvenile fish at cool temperatures. Because t1/2s in this experiment were slower than t1/2s reported in other work, water temperature also may be an important factor in determining the t1/2s of all PCB congeners in fish.

Animals↗
PubMed2003

Enantiomer-specific biomagnification of alpha-hexachlorocyclohexane and selected chiral chlordane-related compounds within an Arctic marine food web.

Concentrations of achiral and chiral organochlorine contaminants (OCs), including hexachlorocyclohexane isomers (HCH), chlordane congeners (cis- and trans-chlordane, cis- and trans-nonachlor, MC5, MC7, and U82), and related metabolites (oxychlordane [OXY] and heptachlor exo-epoxide [HEPX]), were quantified in seawater (100 L; n = 6) and biota from the coastal Beaufort-Chukchi Seas food web near Barrow (AK, USA). The biota included zooplankton (Calanus spp.; n = 5), fish species such as arctic cod (Boreogadus saida; n = 10), arctic char (Salvelinus alpinus; n = 3), and marine mammals including bowhead whales (Balaena mysticetus; liver: n = 23; blubber: n = 40), beluga whales (Delphinapterus leucas; blubber: n = 20), ringed seals (Phoca hispida; blubber: n = 20), and bearded seals (Erignathus barbatus; blubber: n = 7). The food web magnification factors (FWMFs) for HCHs and chlordane compounds ranged from 0.5 (gamma-HCH) to 6.5 (HEPX) and were expected based on known recalcitrance and biotransformation of OCs. The enantiomer fractions (EFs) of all chiral OCs were near racemic (EF = 0.50) in the seawater, zooplankton, and all fish analyzed. In contrast, the EFs for most OCs analyzed were nonracemic (EF # 0.50) in the marine mammals blubber (range: 0.09-0.79) because of enantiomer-specific biotransformation and (or) accumulation. However, EF values were not significantly correlated with isotopically determined trophic level. The EFs for all chiral OCs (except alpha-HCH) in bowhead whale liver closely approximated the values in zooplankton, suggesting that the accumulation of chiral OCs from prey into this cetacean is not enantiomer specific. However, the modification of EFs from bowhead liver to blubber suggests that this species has the ability to enantioselectively biotransform and accumulate several chiral OC compounds.

Animals↗
PubMed2003

Hydroxylated and methylsulfone-containing metabolites of polychlorinated biphenyls in the plasma and blubber of bowhead whales (Balaena mysticetus).

Bowhead whale (Balaena mysticetus) blubber (n = 20) and plasma (n = 19) samples were collected during the 1997 to 2000 Inuit subsistence harvests in Barrow, Alaska, USA, to quantify the concentrations of methylsulfone (MeSO2)-containing and hydroxylated (OH) polychlorinated biphenyl (PCB) metabolites in this cetacean. The distribution of MeSO2-PCBs in blubber was dominated by 4-MeSO2-substituted congeners, the most abundant being 4-MeSO2-CB-70, 3'-MeSO2-CB-132, and 4-MeSO2-CB-64. Mean (+/- 1 standard error) sum (sigma) MeSO2-PCBs concentrations in blubber were low (6.23 +/- 0.81 ng g(-1) lipid normalized) compared to concentrations previously reported in other marine mammals. However, similar ratios of MeSO2-PCB metabolites to parent PCB congeners among marine mammals suggest that cytochrome P450 2B-like biotransformation and other necessary enzyme-mediated processes and mechanisms that influence the formation and clearance of MeSO2-PCBs exist in the bowhead whale. Pentachlorophenol was the most abundant halogenated phenolic compound quantified in bowhead plasma (1.55 +/- 0.19 ng g(-1) wet wt). Despite indirect evidence for arene epoxidation of the biphenyl moiety inferred from MeSO2-PCB formation, sumOH-PCB concentrations in bowhead plasma were low (1.52 +/- 0.31 ng g(-1) wet wt) compared to humans and marine mammals and were comprised of only two detectable OH-PCB congeners (4'-OH-CB-130 and 4-OH-CB-187). Further research is required to elucidate the toxicokinetics and distribution of OH-PCBs in this cetacean.

Adipose Tissue↗
PubMed2002

Enantiomer-specific accumulation of PCB atropisomers in the bowhead whale (Balaena mysticetus).

Blubber (n = 40) and liver (n = 20) samples from the bowhead whale (Balaena mysticetus) were collected during the 1997-1998 Native (Inuit) subsistence harvests in Barrow, AK. Bowhead tissues and zooplankton were analyzed for polychlorinated biphenyl (PCB) concentrations and the enantiomeric fractions (EFs) of eight chiral PCB congeners (PCB-91, 95, 135, 136, 149, 174, 176, and 183) to quantify the enantiomer-specific accumulation of PCBs in this cetacean. PCB concentrations in bowhead blubber were low (mean +/- 1 SE: 610 +/- 54 ng g(-1) lipid) relative to other cetaceans. The accumulation of several chiral PCBs (PCB-91, 135, 149, 174, 176, and 183) in bowhead blubber was enantiomer-specific relative to bowhead liver and zooplankton, suggesting that biotransformation processes within the bowhead whale are enantioselective. The EFs for PCB-95 and 149 were significantly correlated with body length in male and female whales, while EFs for PCB-91 correlated with length in males only. Despite evidence for enantioselective biotransformation, all three congeners bioaccumulated in the bowhead relative to PCB-153. Results suggest that enantioselective accumulation of PCB-91, 95, and 149 is influenced by PCB concentrations, age, and/or the modification of an uncharacterized stereoselective process (or processes) during sexual maturity.

Adipose Tissue↗
PubMed2002

Enantiomer fractions of chiral organochlorine pesticides and polychlorinated biphenyls in standard and certified reference materials.

Enantiomeric ratios (ERs) and enantiomeric fractions (EFs) of a number of chiral organochlorine pesticides and PCB atropisomers were measured by chiral gas chromatography/mass spectrometry (GC/MS) in five standard (SRM) and certified (CRM) reference materials: SRM 1588a (organics in cod liver oil), SRM 1945 (organics in whale blubber), Marine Mammal Quality Assurance Exercise Control Material IV (NIST IV, organics in whale blubber), CRM trout, and CRM EC-5 (sediment). Target analytes were cis- and trans-chlordane, heptachlor exo-epoxide, oxychlordane, U82, MC5, MC6, MC7, o,p'-DDT, and PCB congeners 91, 95, 136, 149, 174, 176, and 183. Measured ERs and EFs are in close agreement with the few literature values reported for some of these analytes in SRMs and CRMs. Chiral PCB ERs and EFs measured by one-dimensional chiral GC/MS were similar to values measured using multidimensional chiral GC/MS. Non-racemic chiral compositions are in agreement with known uptake and biotransformation in the respective environmental matrices. These values should aid in the quality assurance/quality control methodologies for chiral environmental chemistry using standardized reference materials.

Adipose Tissue↗
PubMed2002

Spatial trends and bioaccumulation of organochlorine pollutants in marine zooplankton from the Alaskan and Canadian Arctic.

Planktonic copepods (Calanus glacialis and C. hyperboreus; n = 37) and water (n = 19) were collected to examine the spatial distribution and bioaccumulation of organochlorine contaminants (OCs) in the Alaskan and Canadian Arctic. The rank order of total OC (sigma OC) group concentrations in Calanus samples was toxaphene > or = sigma polychlorinated biphenyls (PCBs) > sigma hexachlorcyclohexane (HCH) > sigma DDT > sigma chlordane-related compounds (CHLOR) > sigma chlorobenzenes (ClBz). The dominant analyte was alpha-HCH in all water and zooplankton samples. The most abundant toxaphene congener in water and zooplankton samples was the hexachlorobornane B6-923. Organochlorine contaminant group concentrations in Alaskan zooplankton and water samples were lower than those in samples collected from sites in the eastern Canadian Arctic. Comparison of PCB and toxaphene congener profiles in zooplankton and water samples suggests that biotransformation by cytochrome P-4502B isozymes is low in Calanus, and limited phase I metabolism may occur. The log relationship of bioaccumulation factor (log BAF) versus octanol-water partition coefficient (log Kow) relationship was near 1:1 for OCs within the log Kow range of 3 to 6. A curvilinear model provided a better relationship between these two variables when OC compounds with log Kow > 6 were included. These results suggest that hydrophobic OCs (log Kow 3-6) in Calanus species are at equilibrium with the water concentrations and that physical partitioning, rather than biotransformation, is the major factor governing OC profiles in marine zooplankton.

Alaska↗