Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model.

Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.

Hand Wipes: A Useful Tool for Assessing Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) through Hand-to-Mouth and Dermal Contacts.

The indoor environment contributes considerably to human exposure to poly- and perfluoroalkyl substances (PFASs). This study estimated the human exposure to PFASs from the indoor environment through hand-to-mouth and dermal contacts using hand wipes. An analytical method was developed to determine 25 PFASs in hand wipe samples collected as a composite sample from both hands of 60 adults. Polyfluoroalkyl phosphate esters (PAPs) were the predominant PFASs in the hand wipe samples (medians between 0.21 and 0.54 ng per sample). Positive and significant correlations were observed between PAPs, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) in hand wipes. Low frequency of daily hand washing (≤8 times day-1) was associated with 30-50% higher concentrations of PFOS, PFOA, and 8:2diPAP in hand wipes. Further, significant correlations between paired hand wipes and house dust samples were observed for PFOS, PFOA, and 6:2diPAP. Also, a significant correlation between PFOS in hand wipes and EtFOSE in indoor air was found. This finding indicates either a common source of exposure or a transformation of EtFOSE to PFOS in the environment or on the hands. The contributions of direct and indirect exposure to perfluoroalkyl acids (PFAAs) showed that PFOA contributed the highest exposure to adults via hand-to-mouth and dermal contacts, followed by PFOS. The median of estimated daily intakes via hand-to-mouth and dermal contacts (for hands only) for PFOA were 0.83 and 0.50 pg·kg bw-1·day-1, respectively. This study gives a first indication that PFAS concentrations in hand wipes can be used as a proxy for the exposure to PFASs from indoor environments, but further studies are needed to confirm this.

Presence and leaching of bisphenol a (BPA) from dental materials.

BPA has been reported to leach from some resin based dental restorative materials and materials used for orthodontic treatment. To confirm and update previous findings, especially in light of the new temporary lower threshold value for tolerable daily BPA intake, we have investigated the leaching of BPA from 4 composite filling materials, 3 sealants and 2 orthodontic bonding materials. The materials were either uncured and dissolved in methanol or cured. The cured materials were kept in deionized water for 24 hours or 2 weeks. Samples were subsequently analyzed by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS-MS). The composite filling material Tetric EvoFlow® and the fissure sealant DELTON® showed significantly higher levels of BPA leaching compared to control samples for all test conditions (uncured, 24 h leaching and 2 weeks leaching). There were no significant differences in amount of leached BPA for any of the tested materials after 24 hours compared to 2 weeks. These results show that BPA is still released from some dental materials despite the general concern about potential adverse effects of BPA. However, the amounts of BPA were relatively low and most likely represent a very small contribution to the total BPA exposure.

Persistent and emerging pollutants in the blood of German adults: Occurrence of dechloranes, polychlorinated naphthalenes, and siloxanes.

Human biomonitoring is a valid method to determine exposure, identify time trends, and monitor the effects of restrictions and measures. To characterize the recent exposure of Germans to persistent or emerging substances, we analyzed 4 dechloranes, 33 polychlorinated naphthalenes (PCNs), and 3 cyclic volatile methyl siloxanes (cVMS) in 42 plasma samples. The samples were collected from blood donors on a random selection. The median values of both Dechlorane Plus (DDC-CO) isomers were 1.23ng/gl.w. for anti- and 0.77ng/gl.w. for syn-DDC-CO. The two other dechloranes were found at lower levels. The median level of ∑-PCNs was 575pg/gl.w. (range: 101-1406pg/gl.w.). On average, the levels of PCNs in plasma were dominated by the congeners CN73, CN66/67, and CN51, which were responsible for approximately 71% of the total amount of PCNs. The cVMS octa-, deca-, and dodecamethylcyclotetrasiloxane could be determined in only some samples, with maximum values of 0.73, 0.48, and 0.79µg/l, respectively. Regarding dechloranes, our results are similar to those from other western countries but slightly lower than results from China. The levels of PCNs in German blood are similar to those observed in the U.S.A., but considerably lower than those reported for Korea. Using a preliminary TEF (toxic equivalency factor), the mean TEQ of the 9 quantifiable PCNs in Germany was low (0.36pg TEQ/gl.w.). The PCN levels in our study group are lower compared to previous studies.

Role of dietary patterns for dioxin and PCB exposure.

Dietary patterns were related to intake and blood concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and selected non-dioxin-like-PCBs (ndl-PCBs). Intake calculations were based on an extensive food frequency questionnaire and a congener-specific database on concentrations in Norwegian foods. The study (2003) applied a two-step inclusion strategy recruiting representative (n=73) and high consumers (n=111) of seafood and game. Estimated median intakes of sum PCDD/PCDFs and dl-PCBs of the representative and high consumers were 0.78 and 1.25 pg toxic equivalents (TEQ)/kg bw/day, respectively. Estimated median intakes of ndl-PCBs (sum chlorinated biphenyl (CB)-28, 52, 101, 138, 153, 180) were 4.26 and 6.40 ng/kg bw/day. The median blood concentrations of PCDD/PCDFs/dl-PCBs were 28.7 and 35.1 pg TEQ/g lipid, and ndl-PCBs (sum of CB-101, 138, 153 and 180) 252 and 299 ng/g lipid. The Spearman correlations between dietary intake and serum concentration were r=0.34 (p=0.017) for dl-compounds and r=0.37 (p<0.001) for ndl-PCBs. Oily fish was the major source of dl-compounds and ndl-PCBs in high and representative consumers. Four dietary patterns were identified by principal component analysis. Two were related to high intakes, one dominated by oily fish ((Omega-3)), the other by fish liver and seagull eggs ("northern coastal"). Only the latter was closely associated with high blood concentrations of dioxins and PCBs.