Decline in perfluorooctane sulfonate and perfluorooctanoate serum concentrations in an Australian population from 2002 to 2011.

Some perfluoroalkyl and polyfluoroalkyl substances (PFASs) have become widespread pollutants detected in human and wildlife samples worldwide. The main objective of this study was to assess temporal trends of PFAS concentrations in human blood in Australia over the last decade (2002-2011), taking into consideration age and sex trends. Pooled human sera from 2002/03 (n=26); 2008/09 (n=24) and 2010/11 (n=24) from South East Queensland, Australia were obtained from de-identified surplus pathology samples and compared with samples collected previously from 2006/07 (n=84). A total of 9775 samples in 158 pools were available for an assessment of PFASs. Stratification criteria included sex and age: <16 years (2002/03 only); 0-4 (2006/07, 2008/09, 2010/11); 5-15 (2006/07, 2008/09, 2010/11); 16-30; 31-45; 46-60; and >60 years (all collection periods). Sera were analyzed using on-line solid-phase extraction coupled to high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Perfluorooctane sulfonate (PFOS) was detected in the highest concentrations ranging from 5.3-19.2 ng/ml (2008/09) to 4.4-17.4 ng/ml (2010/11). Perfluorooctanoate (PFOA) was detected in the next highest concentration ranging from 2.8-7.3 ng/ml (2008/09) to 3.1-6.5 ng/ml (2010/11). All other measured PFASs were detected at concentrations <1 ng/ml with the exception of perfluorohexane sulfonate which ranged from 1.2-5.7 ng/ml (08/09) and 1.4-5.4 ng/ml (10/11). The mean concentrations of both PFOS and PFOA in the 2010/11 period compared to 2002/03 were lower for all adult age groups by 56%. For 5-15 year olds, the decrease was 66% (PFOS) and 63% (PFOA) from 2002/03 to 2010/11. For 0-4 year olds the decrease from 2006/07 (when data were first available for this age group) was 50% (PFOS) and 22% (PFOA). This study provides strong evidence for decreasing serum PFOS and PFOA concentrations in an Australian population from 2002 through 2011. Age trends were variable and concentrations were higher in males than in females. Global use has been in decline since around 2002 and hence primary exposure levels are expected to be decreasing. Further biomonitoring will allow assessment of PFAS exposures to confirm trends in exposure as primary and eventually secondary sources are depleted.

Evaluation of dioxin-like chemicals in pooled human milk samples collected in Australia.

DESIGN: Human milk samples were collected and analysed for the levels of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and selected dioxin-like polychlorinated biphenyls (PCBs). In total, 157 individual samples collected during 2002 and 2003 as well as 24 samples collected in 1993 were analysed as 20 pools. RESULTS: PCDDs, PCDFs and dioxin-like PCBs were detected in all pooled samples. For samples collected during 2002/2003, the TEQ(DFP) ranged from 6.0 to 15.2 pg TEQ g(-1) lipid with an average of 9.0 pg TEQ g(-1) lipid. The average lipid content was 3.7+/-0.5%. No systematic differences were observed in the levels of PCDDs, PCDFs and PCBs in human milk samples collected from different regions of Australia during 2002/2003. For samples collected in 1993 and analysed as pools, the mean level, expressed as TEQ(DFP) was 16+/-1.4 pg TEQ g(-1) lipid. The average lipid content was 3.9+/-0.7%. CONCLUSION: The levels of PCDDs, PCDFs and dioxin-like PCBs in the human milk of Australian women are both low compared to international levels and similar across all regions of Australia. Consistent with world-wide trends, the levels of PCDDs, PCDFs and dioxin-like PCBs have decreased over a 10 year period from 1993 to 2003 by approximately 40%.

Evaluation of age, gender and regional concentration differences for dioxin-like chemicals in the Australian population.

The results of this study provide a measure of the levels of dioxin-like compounds (polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls) in pooled blood serum collected throughout Australia in 2003. De-identified samples selected from surplus pathology samples were stratified on the basis of gender, region and age. In total 9090 samples were collected and analysed as 96 pools. Dioxin-like chemicals were detected in all strata. The mean and median levels expressed as TEQ values for all pooled samples were 10.9+/-1.0 pg TEQ g(-1) lipid and 8.3 pg TEQ g(-1) lipid. For males and females the mean levels were 10.4+/-0.6 pg TEQ g(-1) lipid and 11.5+/-1.5 pg TEQ g(-1) lipid, respectively. A direct relationship of increasing dioxin-like chemical levels with increasing age was observed and could be described by the following equation: Levels in blood expressed as pg TEQ g(-1) lipid = 3.3 exp(0.0251 age) (r2 = 0.87). No significant differences were observed in the levels of dioxin-like chemicals in samples collected from males and females. In addition, the levels of dioxin-like chemicals across the five regions were similar within each age range. In summary, the levels of dioxin-like chemicals in the Australian population are low compared to international levels and are similar across all regions of Australia within each designated age range. The levels of these chemicals increase with age and can be estimated if the age of an individual is known.

Age-related changes in adenosine in rat coronary resistance vessels.

1. The vasodilator effects of adenosine receptor agonists, isoprenaline and histamine were examined in perfused heart preparations from young (4-6 weeks) and mature (12-20 weeks) rats. 2. Adenosine induced a biphasic concentration-dependent decrease in KCl (35 mM) raised coronary perfusion pressure in hearts from young and mature rats, suggesting the presence of both high- and low-affinity sites for adenosine receptors in the two age groups tested. In heart preparations from mature rats, vasodilator responses to adenosine were significantly reduced compared with responses observed in young rats. 3. Responses to 5'-N-ethylcarboxamidoadenosine (NECA) and 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) were reduced in preparations from mature rats, whereas the vasodilator actions of N6-cyclopentyladenosine (CPA) and N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not change with age. 4. The results presented in this study suggest that several adenosine receptor subtypes mediate vasodilator responses in the coronary circulation of the rat and that a reduction in response to adenosine with age may be due to changes in the high-affinity receptor site.

A biphasic response to adenosine in the coronary vasculature of the K(+)-arrested perfused rat heart.

Biphasic vasodilatory responses to adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) were observed in the coronary vasculature of K(+)-arrested perfused rat hearts. Dose-response data for both agonists were best represented by two-site models. For adenosine, two sites with negative log ED50 (pED50) values of 8.1 +/- 0.1 (mean +/- S.E.M) and 5.2 +/- 0.1 were obtained, mediating 31 +/- 2% and 69 +/- 2% of the total response. In the presence of 8-phenyltheophylline, the vasodilatory response to adenosine remained best fitted to a two-site model with pED50 values of 7.0 +/- 0.2 and 5.4 +/- 0.2. The relative contribution of each site to the total response remained unchanged. For NECA, pED50 values of 9.6 +/- 0.1 and 6.8 +/- 0.2 were obtained, representing 48 +/- 3% and 52 +/- 3% of the sites, respectively. In contrast, ATP produced a monophasic response with a pED50 value of 8.8 +/- 0.1. These results provide evidence of adenosine receptor and response heterogeneity in the in situ coronary vasculature.

A method to evaluate the response of the coronary circulation of perfused rat heart to adenosine.

Exogenous adenosine causes a monophasic dilation of the coronary vessels in paced, perfused rat heart preparations. Because levels of endogenous adenosine in paced hearts may mask the presence of high potency adenosine receptors, we have developed a method to measure coronary vascular responses in a potassium-arrested heart. Hearts from adult male, Wistar rats were perfused at a constant flow rate of 10 mL/min in the nonrecirculating, Langendorff mode, using Krebs-Henseleit buffer. After 30 min, coronary perfusion pressure was 44 +/- 1 mmHg (mean +/- SEM). Hearts were then perfused with a modified Krebs-Henseleit buffer containing 35 mM potassium. Coronary perfusion pressure increased by 84 +/- 3 mmHg. Adenosine-induced reductions in coronary perfusion pressure were expressed as a percentage of the maximal increase in pressure produced by modified Krebs-Henseleit buffer from the equilibration level. A concentration-response curve for adenosine (n = 6) was biphasic and best described by the presence of two adenosine receptors, with negative log EC50 values of 8.8 +/- 0.3 and 4.3 +/- 0.1, representing 29 +/- 3 and 71 +/- 3%, respectively, of the observed response. Interstitial adenosine sampled by microdialysis during potassium arrest was 25% of the concentration found in paced hearts. Endogenous adenosine in nonarrested hearts may obscure the biphasic response of the coronary vessels to adenosine.

Synthesis and adenosine receptor affinity of a series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine.

Pyrazolo[3,4-d]pyrimidines are pyrazolo analogues of purines. They have been shown to be a general class of compounds which exhibit A1 adenosine receptor affinity. Two series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine have been synthesized. The first involved substitution of the N1-position while the second involved substitution of the N5-position. Both alkyl and aryl substituents were examined. All compounds were tested for A1 adenosine receptor affinity by using a (R)-[3H]-N6-(phenylisopropyl)adenosine binding assay. The 3-chlorophenyl group showed the greatest activity in the N1-position and the butyl group produced the greatest activity in the N5-position. Combination of the best substituent in each of these positions enhanced the overall activity. The most potent compound was 4-amino-5-N-butyl-1-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-6(5H)- one with an IC50 of 6.4 x 10(-6) M. Selectivity at the receptor subclasses was examined by performing an A2 adenosine receptor affinity assay with [3H]CGS 21680. This series of compounds were slightly less potent at A2 receptors. 4-Amino-5-N-butyl-1-(3-chlorophenyl-1H-pyrazolo[3,4-d]pyrimidin-6(5H)-one was the most potent compound with an IC50 of 19.2 x 10(-6) M.