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Östermalm, Sweden

Kharlyngdoh J.B.,Orebro University | Pradhan A.,Orebro University | Asnake S.,Orebro University | Walstad A.,Orebro University | And 2 more authors.
Environment International | Year: 2015

Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5. α-reductases and β-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5. α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE and DPTE are potent AR antagonists and the alterations in LAT gene transcription suggest that these compounds can affect neuronal functions and should be considered as potential neurotoxic and endocrine disrupting compounds. © 2014. Source


Cermak J.,University of Waterloo | Stephenson G.,University of Waterloo | Stephenson G.,Stantec Consulting Ltd. | Birkholz D.,ALS Laboratory Group | Dixon D.G.,University of Waterloo
Environmental Toxicology and Chemistry | Year: 2013

Petroleum hydrocarbons (PHCs) act via narcosis and are expected to have additive toxicity. However, previous work has demonstrated less-than-additive toxicity with PHC distillates and earthworms. A study was initiated to investigate this through toxicity and toxicokinetic studies with the earthworm Eisenia andrei. Three petroleum distillate fractions, F2 (>C10-C16), F3a (>C16-C23), and F3b (>C23-C34), were used in two binary combinations, F2F3a and F3aF3b. In the toxicity study, clean soil was spiked with equitoxic combinations of the two distillates ranging from 0.5 to 2.5 toxic units. In the toxicokinetic study, a binary combination consisting of one concentration of each distillate was used. On a soil concentration basis, the toxicity of the binary combinations of distillates was less than additive. Accumulation of the individual distillates, however, was generally reduced when a second distillate was present, resulting in lower body burden. This is thought to be due to the presence of a nonaqueous-phase liquid at the soil concentrations used. On a tissue concentration basis, toxicity was closer to additive. The results demonstrate that tissue concentrations are the preferred metric for toxicity for earthworms. They also demonstrate that the Canada-wide soil standards based on individual distillates are likely protective. © 2013 SETAC. Source


Genuis S.J.,University of Alberta | Beesoon S.,University of Alberta | Lobo R.A.,University of Alberta | Birkholz D.,ALS Laboratory Group
The Scientific World Journal | Year: 2012

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body. © 2012 Stephen J. Genuis et al. Source


Cermak J.H.,University of Waterloo | Cermak J.H.,Environment Canada | Stephenson G.L.,University of Waterloo | Stephenson G.L.,Stantec Inc. | And 3 more authors.
Environmental Toxicology and Chemistry | Year: 2010

Canadian standards for petroleum hydrocarbons in soil are based on four distillate ranges (F1, C6-C10; F2, >C10-C16; F3, >C16-C34; and F4, >C34). Concerns have arisen that the ecological soil contact standards for F3 may be overly conservative. Oil distillates were prepared and characterized, and the toxicity of F3 and two subfractions, F3a (>C16-C23) and F3b (>C23-C34), to earthworms (Eisenia andrei), springtails (Orthonychiurus folsomi), and northern wheatgrass (Elymus lanceolatus), as well as the toxicity of F2 to earthworms, was determined. Clean soil was spiked with individual distillates and measured concentrations were determined for select tests. Results agree with previous studies with these distillates. Reported toxicities of crude and petroleum products to invertebrates were generally comparable to that of F3 and F3a. The decreasing order of toxicity was F3a > F3 > F3b with invertebrates, and F3a > F3b > F3 with plants. The toxicities of F3a and F3b were not sufficiently different to recommend regulating hydrocarbons based on these distillate ranges. The results also suggest that test durations may be insufficient for determining toxicity of higher distillate ranges, and that the selection of species and endpoints may significantly affect interpretation of toxicity test results. © 2010 SETAC. Source


Birkholz D.A.,ALS Laboratory Group
Proceedings of the 34th AMOP Technical Seminar on Environmental Contamination and Response | Year: 2011

Private laboratories often receive soil samples from industry and consultants for the purposes of hydrocarbon testing. Usually the information required pertains to hydrocarbon levels (CCME - F1-F4) and this information is employed to determine regulatory compliance and the need for reclamation. In some instances, where the observed data suggests that exceedences have occurred and reclamation is required, additional questions often arise. These include the nature of the petroleum, potential source(s) and age of the product. The rationale behind these questions is one of assigning liability and ultimately cost of cleanup. The ability to answer such questions requires the application of forensic techniques. We were provided with three soil samples from a consultant, and following analyses for total petroleum hydrocarbons (F1-F4) it was determined that regulatory exceedences had occurred and that extensive reclamation was required. The consultant requested our laboratory to provide information on the nature of the petroleum as well as the age of the product. A Phase I audit determined a potential source, however, no product was available that we could compare to. Furthermore, it was determined that these samples were extremely weathered. Our approach to answering the question of the nature of the petroleum product and age is presented and discussed. Source

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