Use of simple pharmacokinetic modeling to characterize exposure of Australians to perfluorooctanoic acid and perfluorooctane sulfonic acid

Perflurooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been used for a variety of applications including fluoropolymer processing, fire-fighting foams and surface treatments since the 1950s. Both PFOS and PFOA are polyfluoroalkyl chemicals (PFCs), man-made compounds that are persistent in the environment and humans; some PFCs have shown adverse effects in laboratory animals. Here we describe the application of a simple one compartment pharmacokinetic model to estimate total intakes of PFOA and PFOS for the general population of urban areas on the east coast of Australia. Key parameters for this model include the elimination rate constants and the volume of distribution within the body. A volume of distribution was calibrated for PFOA to a value of 170ml/kgbw using data from two communities in the United States where the residents' serum concentrations could be assumed to result primarily from a known and characterized source, drinking water contaminated with PFOA by a single fluoropolymer manufacturing facility. For PFOS, a value of 230ml/kgbw was used, based on adjustment of the PFOA value. Applying measured Australian serum data to the model gave mean+/-standard deviation intake estimates of PFOA of 1.6+/-0.3ng/kgbw/day for males and females >12years of age combined based on samples collected in 2002-2003 and 1.3+/-0.2ng/kg bw/day based on samples collected in 2006-2007. Mean intakes of PFOS were 2.7+/-0.5ng/kgbw/day for males and females >12years of age combined based on samples collected in 2002-2003, and 2.4+/-0.5ng/kgbw/day for the 2006-2007 samples. ANOVA analysis was run for PFOA intake and demonstrated significant differences by age group (p=0.03), sex (p=0.001) and date of collection (p<0.001). Estimated intake rates were highest in those aged >60years, higher in males compared to females, and higher in 2002-2003 compared to 2006-2007. The same results were seen for PFOS intake with significant differences by age group (p<0.001), sex (p=0.001) and date of collection (p=0.016).

Population variation in biomonitoring data for persistent organic pollutants (POPs) : an examination of multiple population-based datasets for application to Australian pooled biomonitoring data

Background Australian national biomonitoring for persistent organic pollutants (POPs) relies upon age-specific pooled serum samples to characterize central tendencies of concentrations but does not provide estimates of upper bound concentrations. This analysis compares population variation from biomonitoring datasets from the US, Canada, Germany, Spain, and Belgium to identify and test patterns potentially useful for estimating population upper bound reference values for the Australian population. Methods Arithmetic means and the ratio of the 95th percentile to the arithmetic mean (P95:mean) were assessed by survey for defined age subgroups for three polychlorinated biphenyls (PCBs 138, 153, and 180), hexachlorobenzene (HCB), p,p-dichlorodiphenyldichloroethylene (DDE), 2,2′,4,4′ tetrabrominated diphenylether (PBDE 47), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Results Arithmetic mean concentrations of each analyte varied widely across surveys and age groups. However, P95:mean ratios differed to a limited extent, with no systematic variation across ages. The average P95:mean ratios were 2.2 for the three PCBs and HCB; 3.0 for DDE; 2.0 and 2.3 for PFOA and PFOS, respectively. The P95:mean ratio for PBDE 47 was more variable among age groups, ranging from 2.7 to 4.8. The average P95:mean ratios accurately estimated age group-specific P95s in the Flemish Environmental Health Survey II and were used to estimate the P95s for the Australian population by age group from the pooled biomonitoring data. Conclusions Similar population variation patterns for POPs were observed across multiple surveys, even when absolute concentrations differed widely. These patterns can be used to estimate population upper bounds when only pooled sampling data are available.

The effect of ongoing blood loss on human serum concentrations of perfluorinated acids

Perfluorinated alkyl acids (PFAAs) have been detected in serum at low concentrations in background populations. Higher concentrations haven been observed in adult males compared to females, with a possible explanation that menstruation offers females an additional elimination route. In this study, we examined the significance of blood loss as an elimination route of PFAAs. Pooled serum samples were collected from individuals undergoing a medical procedure involving ongoing blood withdrawal called venesection. Concentrations from male venesection patients were approximately 40% lower than males in the general population for perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). A simple pharmacokinetic model was used to test the hypothesis that blood loss could explain why adult males have higher concentrations of PFAAs than females, and why males undergoing venesections had lower concentrations compared to males in the general population. The model application generally supported these hypotheses showing that venesection might reduce blood serum concentrations by 37% (PFOA) and 53% (PFOS) compared to the observed difference of 44% and 37%. Menstruation was modeled to show a 22% reduction in PFOA serum concentrations compared to a 24% difference in concentrations between males and females in the background population. Uncertainties in the modeling and the data are identified and discussed.

Combined effects of polyfluorinated and perfluorinated compounds on primary cultured hepatocytes from rare minnow (Gobiocypris rarus) using toxicogenomic analysis

Polyfluorinated and perfluorinated compounds (PFCs) are used in numerous commercial products and have been ubiquitously detected in the environment as well as in the blood of humans and wildlife. To assess the combined effects caused by PFCs in mixtures, gene expression profiles were generated using a custom cDNA microarray to detect changes in primary cultured hepatocytes of rare minnows exposed to six individual PFCs (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorooctane sulfonate, and 8:2 fluorotelomer alcohol) and four formulations of the PFCs mixtures. Mixtures as well as individual compounds consistently regulated a particular gene set, which suggests that these conserved genes may play a central role in the toxicity mediated by PFCs. Specifically, a number of genes regulated by the mixtures were identified in this study, which were not affected by exposure to any single component. These genes are implicated in multiple biological functions and processes, including fatty acid metabolism and transport, xenobiotic metabolism, immune responses, and oxidative stress. More than 80% of the altered genes in the PFOA- and PFOS-dominant mixture groups were of the same gene set, while the gene expression profiles from single PFOA and PFOS exposures were not as similar. This work contributes to the development of toxicogenomic approaches in combined toxicity assessment and allows for comprehensive insights into the combined action of PFCs mixtures in multiple environmental matrices. (C) 2009 Elsevier B.V. All rights reserved.

Perfluorinated compounds in the Pearl River and Yangtze River of China

A total of 14 perfluorinated compounds (PFCs) were quantified in river water samples collected from tributaries of the Pearl River (Guangzhou Province, south China) and the Yangtze River (central China). Among the PFCs analyzed, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were the two compounds with the highest concentrations. PFOS concentrations ranged from 0.90 to 99 ng/1 and < 0.01-14 ng/1 in samples from the Pearl River and Yangtze River, respectively; whereas those for PFOA ranged from 0.85 to 13 ng/l and 2.0-260 ng/l. Lower concentrations were measured for perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctanesulfoamide (PFOSA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorononaoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA). Concentrations of several perfluorocarboxylic acids, including perfluorododecanoic acid (PFDoDA), perfluorotetradecanoic acid (PFTeDA), perfluorohexadecanoic acid (PFHxDA) and perfluorooctadecanoic acid (PFOcDA) were lower than the limits of quantification in all the samples analyzed. The highest concentrations of most PFCs were observed in water samples from the Yangtze River near Shanghai, the major industrial and financial centre in China. In addition, sampling locations in the lower reaches of the Yangtze River with a reduced flow rate might serve as a final sink for contaminants from the upstream river runoffs. Generally, PFOS was the dominant PFC found in samples from the Pearl River, while PFOA was the predominant PFC in water from the Yangtze River. Specifically, a considerable amount of PFBS (22.9-26.1% of total PFC analyzed) was measured in water collected near Nanjing, which indicates the presence of potential sources of PFBS in this part of China. Completely different PFC composition profiles were observed for samples from the Pearl River and the Yangtze River. This indicates the presence of dissimilar sources in these two regions. (c) 2007 Elsevier Ltd. All rights reserved.

Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus)

Perfluorinated organic compounds (PFOCs) are emerging persistent organic pollutants (POPs) widely present in the environment, wildlife and human. We studied the cellular toxicology of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on oxidative stress and induction of apoptosis in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus). Cultured hepatocytes were exposed to PFOS or PFOA (0, 1, 5, 15 and 30 mg L-1) for 24 h, and a dose-dependent decrease in cell viability was determined using trypan blue exclusion method. Significant induction of reactive oxygen species (ROS) accompanied by increases in activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were found, while activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were decreased. Glutathione (GSH) content was reduced following treatment of PFOA and PFOS. A dose-dependent increase in the lipid peroxidation (LPO) level (measured as maleic dialdehyde, MDA) was observed only in the PFOA exposure groups, whereas LPO remained unchanged in the PFOS exposure groups. Furthermore, a significant activation of caspase-3, -8, -9 activities was evident in both PFOS and PFOA exposure groups. Typical DNA fragmentation (DNA laddering) was further characterized by agarose gel electrophoresis. The overall results demonstrated that PFOS and PFOA are able to produce oxidative stress and induce apoptosis with involvement of caspases in primary cultured tilapia hepatocytes. (c) 2007 Elsevier B.V. All rights reserved.

Perfluorinated compounds in environmental matrices of Lake Victoria Gulf

ABSTRACT One of the major ecological challenges on Lake Victoria resources is the existence of “hot spots”, caused by human waste, urban runoff, and industrial effluents. The lake is tending towards eutrophication which is attributed to the increasing human population in its watershed. A report of the levels of perfluorooctane sulfonate and perfluorooctanoic acid in environmental matrices of Lake Victoria is presented, and the management implication of perfluorinated compounds and similar potential organic pollutants examined. Two widely consumed and economically important fish species namely Lates niloticus (Nile perch) and Oreochromis niloticus (Nile tilapia) were obtained from Winam gulf of Lake Victoria, Kenya, and analysed for perfluorooctane sulfonate and perfluorooctanoic acid in muscles and liver using liquid chromatography coupled with mass spectroscopy. Variability in the concentrations of perfluorooctanoic acid or perfluorooctane sulfonate in river waters (range perfluorooctanoic acid 0.4 – 96.4 ng/L and perfluorooctane sulfonate < 0.4 – 13.2 ng/L) was higher than for Lake waters (range perfluorooctanoic acid 0.4 – 11.7 ng/L and perfluorooctane sulfonate < 0.4 – 2.5 ng/L respectively). Significant correlations were tested between perfluorinated compounds levels in sediments, fish and water. Wastewater treatment plants and other anthropogenic sources have been identified as significant sources or pathways for the introduction of perfluoroalkyl compounds into Lake Victoria ecosystem. In this study, elevated concentrations of perfluorooctanoic acid and perfluorooctane sulfonate was found in two wastewater treatment plants (WWTPs) in Kisumu, City of Kenya. An alternative analytical method to liquid chromatography/ mass spectroscopy for analysis of perfluorocarboxylic acids in abiotic and biotic matrices where high concentrations are expected is also presented. Derivatisation of the acid group to form a suitable alkyl ester provided a suitable compound for mass spectroscopy detection coupled to gas chromatography instrumental analysis. The acid is esterified by an alkyl halide i.e benzyl bromide as the alkylating agent for Perfluorocarboxylic acids quantification. The study also involved degradability measurements of emerging perfluorinated surfactants substitutes. The stability of the substitutes of perfluorinated surfactants was tested by employing advanced oxidation processes, followed by conventional tests, among them an automated method based on the manometric respirometry test and standardized fix bed bioreactor [FBBR] on perfluorobutane sulfonate (PFBS), a fluoroethylene polymer, fluorosurfactant (Zonyl), two fluoraliphaticesters (NOVEC ™ FC4430 and NOVEC ™ FC4432) and 10-(trifluoromethoxy) decane-sulfonate. Most of these emmerging surfactants are well-established in the market and have been used in several applications as alternatives to PFOS and PFOA based surfactants. The results of this study can be used as pioneer information for further studies on the sources, behaviour and fate of PFOA and PFOS and other related compounds in both abiotic and biota compartments of Lake Victoria and other lakes. Further an overview in degradation of emerging perfluorinated compounds substitutes is presented. Contribution in method development especially for acid group based fluorosurfactants is presented. The data obtained in this study can particularly be considered when formulating policies and management measures for preservation and sustainability of Lake Victoria resources.

Composti perfluorurati: Valutazione degli effetti biologici e molecolari in modelli cellulari

L’acido perfluorottanoico (PFOA) e l’acido perfluoronanoico (PFNA) sono composti perfluorurati (PFCs) comunemente utilizzati nell’industria, negli ultimi 60 anni, per diverse applicazioni. A causa della loro resistenza alla degradazione, questi composti sono in grado di accumularsi nell’ambiente e negli organismi viventi, da cui possono essere assunti in particolare attraverso la dieta. Le esistenti evidenze sugli effetti dell’esposizione negli animali, tra cui la potenziale cancerogenicità, hanno accresciuto l’interesse sui possibili rischi per la salute nell’uomo. Recenti studi sull’uomo indicano che i PFC sono presenti nel siero, con livelli molto alti soprattutto nei lavoratori cronicamente esposti, e sono associati positivamente al cancro al seno e alla prostata. Inoltre, sono state riportate proprietà estrogen-like e variazioni nei livelli di metilazione sui promotori di alcuni geni. L’esposizione in utero è stata associata positivamente a ipometilazione globale del DNA nel siero cordonale. L’obiettivo di questo studio è stato quello di indagare gli effetti dell’esposizione a questi perfluorurati su linee cellulari tumorali e primarie umane (MOLM-13, RPMI, HEPG2, MCF7,WBC, HMEC e MCF12A), appartenenti a diversi tessuti target, utilizzando un ampio range di concentrazioni (3.12 nM - 500 μM). In particolare, si è valutato: la vitalità, il ciclo cellulare, l’espressione genica, la metilazione globale del DNA e la metilazione gene specifica. Dai risultati è emerso come entrambi i perfluorurati abbiano effetti biologici: PFOA presenta un effetto prevalente citostatico, PFNA prevalentemente citotossico. L’effetto è, però, prevalente sulle linee cellulari primarie di epitelio mammario (HMEC, MCF12A), anche a concentrazioni riscontrate in lavoratori cronicamente esposti (≥31,25 µM). Dall’analisi su queste cellule primarie, non risultano variazioni significative della metilazione globale del DNA alle concentrazioni di 15,6 e 31,25 µM. Emergono invece variazioni sui geni marcatori del cancro al seno, del ciclo cellulare, dell’apoptosi, del pathway di PPAR-α e degli estrogeni, ad una concentrazione di 31,25 µM di entrambi i PFCs.

Valutazione della presenza di contaminanti perfluoroalchilici in alimenti destinati al consumo umano

Le sostanze perfluoralchiliche (PFAS), composti fluorurati ampiamente utilizzati negli ultimi anni in diverse applicazioni industriali e commerciali, sono ritrovati diffusamente nell’ambiente e in diverse specie animali. Recentemente i PFAS hanno destato preoccupazione anche per la salute umana. Il rischio di esposizione è principalmente legato alla dieta (i prodotti ittici sembrano essere gli alimenti più contaminati). Lo scopo di questo lavoro è stato quello di valutare la presenza del perfluorottanosulfonato (PFOS) e dell’acido perfluorottanoico (PFOA), in diverse matrici alimentari: latte vaccino commercialmente disponibile in Italia, latte materno italiano, diverse specie di pesce commercialmente disponibili in Italia e 140 branzini di diverse aree (principalmente Mediterraneo). I campioni di latte sono stati trattati con estrazione liquido-liquido seguita da due fasi di purificazione mediante cartucce SPE prima dell’iniezione nell’UPLC-MS/MS. L’analisi del latte vaccino ha evidenziato una contaminazione diffusa di PFOS, ma a basse concentrazioni (fino a 97 ng/L), mentre il PFOA è stato ritrovato raramente. In questo studio, in grado di individuare anche i livelli delle ultra-tracce, sono state osservate nel latte materno concentrazioni di 15-288 ng/L per il PFOS e di 24-241 ng/LPFOA. Le concentrazioni e le frequenze più alte, per entrambi i PFAS, sono stati ritrovate in campioni di latte forniti da donne primipare, suggerendo un rischio di esposizione per i primogeniti. Il metodo utilizzato per i campioni di pesce era basato su un’estrazione con solvente organico seguita da due fasi di purificazione: una con i sali e una con fase solida dispersiva. L’estratto, analizzato in UPLC-MS/MS, ha confermato la contaminazione di questa matrice a livelli significativi, ma anche l’alta variabilità delle concentrazioni misurate. Il monitoraggio monospecie ha mostrato una contaminazione rilevante (PFOS 11,1- > 10000 ng/L; PFOA < 9-487 ng/L), soprattutto nei branzini pescati, rispetto a quelli allevati.

Temporal variations of perfluoroalkyl substances and polybrominated diphenyl ethers in alpine snow

The occurrence and temporal variation of 18 perfluoroalkyl substances (PFASs) and 8 polybrominated diphenyl ethers (PBDEs) in the European Alps was investigated in a 10 m shallow firn core from Colle Gnifetti in the Monte Rosa Massif (4455 m above sea level). The firn core encompasses the years 1997-2007. Firn core sections were analyzed by liquid chromatography-tandem mass spectrometry (PFASs) and gas chromatography-mass spectrometry (PBDEs). We detected 12 PFASs and 8 PBDEs in the firn samples. Perfluorobutanoic acid (PFBA; 0.3-1.8 ng L(-1)) and perfluorooctanoic acid (PFOA; 0.2-0.6 ng L(-1)) were the major PFASs while BDE 99 (

Caracterização microbiológica, química e presença de poluentes orgânicos em amostras de lodo de esgoto de São Paulo

Objetivou-se com este trabalho avaliar o potencial agrícola do lodo de esgoto produzido no estado de São Paulo, bem como, verificar a possibilidade de interação entre a composição química e a abundância relativa de bactérias no lodo. Foram realizadas coletas de amostra de lodo de esgoto em 19 estações de tratamento de esgoto, em três épocas distintas. Nas amostras provenientes das três épocas foram determinados as concentrações dos 16 hidrocarbonetos policíclicos aromáticos (HPAs) listados como prioritários no monitoramento ambiental pela USEPA (acenafteno, acenaftileno, antraceno, benzo(a)antraceno, benzo(a)pireno, benzo(b)fluoranteno, benzo(ghi)perileno, benzo(k)fluoranteno, criseno, dibenzo(a,h)antraceno, fenantreno, fluoranteno, fluoreno, indeno(1,2,3-cd)pireno, naftaleno e pireno). Nas amostras da segunda época de coleta, além da presença de HPAs, determinou-se as concentrações de poluentes orgânicos emergentes (hormônios, produtos farmacêuticos e produtos de uso industrial), realizou-se a caracterização completa segundo a Resolução CONAMA 375/2006 (umidade, pH, N-Kjeldahl e inorgânico, carbono orgânico, cálcio, potássio, fósforo, magnésio, enxofre, boro, cobre, ferro, níquel, manganês, molibdênio, selênio, zinco, alumínio, arsênio, bário, cádmio, cromo, chumbo, mercúrio e sódio) e a caracterização da comunidade bacteriana através de metodologia independente de cultivo (sequenciamento illumina). Os macronutrientes em maiores concentrações no lodo de esgoto são: N > Ca > S > P > Mg > K. Os elementos inorgânicos Ni e Zn apresentaram concentração superior à máxima permitida para utilização agrícola pela resolução Conama 375/2006 em 1 e 3 amostras, respectivamente. A substância inorgânica que mais limita o enquadramento do lodo de esgoto como adubo orgânico (Instrução Normativa 27/2006) é o Hg. Os compostos benzilparabeno, bisfenol AF (BPAF), ácido perfluorooctanoico (PFOA) e tetrabromobisfenol A (TBBPA) não foram detectados. Por outro lado, cimetidina, metilparabeno, bisfenol A (BPA) e triclocarban foram detectados nas 19 amostras avaliadas. O composto presente em maior concentração é o triclocarban. As concentrações de hidrocarbonetos policíclicos aromáticos são baixas, de acordo com a norma Europeia. Os filos Proteobacteria e Bacteroidetes estão presentes em maior abundância relativa. Existe uma comunidade bacteriana núcleo nas estações de tratamento de esgoto do estado de São Paulo, composta por 81 gêneros, presentes nas 19 ETEs avaliadas, dos quais, os que estão em maior abundância relativa são Treponema, Clostridium, Propionibacterium, Syntrophus e Desulfobulbus. A elevação do pH a valores próximos de 12 reduz a diversidade microbiana. Considerando a abundância relativa e a composição química do lodo de esgoto, as estações podem ser agrupadas em três grupos distintos, sendo que um deles é influenciado principalmente pelos teores de Ca, Zn e Cu, o outro pelos teores de Fe e S e o terceiro grupo que foi influenciado pelos demais fatores avaliados.

Levels of 12 perfluorinated chemicals in pooled Australian serum, collected 2002-2003, in relation to age, gender, and region

Pooled serum samples from 3802 Australian residents were analyzed for four perfluoroalkylsulfonates, seven perfluoroalkylcarboxylates, and perfluorooctanesulfonamide (PFOSA). Serum was collected from men and women of five different age groups and from rural and urban regions in Australia. The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 20.8 ng/mL) followed by perfluorooctanoic acid (PFOA, 7.6 ng/mL), perfluorohexane sulfonate (PFHxS, 6.2 ng/mL), perfluorononanoic acid (PFNA, 1.1 ng/mL), and PFOSA (0.71 ng/mL). Additional four PFCs were detected in 5-18 % of the samples at concentrations near the detection limits (0.1-0.5 ng/mL). An increase in PFOS concentration with increasing age in both regions and genders was observed. The male pool levels of some of the age groups compared to females were higher for PFOS, PFOA, and PFHxS. In contrast, PFNA concentrations were higher in the female pools. No substantial difference was found in levels of PFCs between the urban and rural regions. The levels are equal or higher than previously reported serum levels in Europe and Asia but lower compared to the U. S. A. These results suggest that emissions from production in the Northern Hemisphere are of less importance for human exposure.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.