Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.

Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard. As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose-response data (Gollapudi et al., 2013), here we present analyses of 1-ethyl-1-nitrosourea (ENU) and 1-methyl-1-nitrosourea (MNU) dose-response data and additional approaches for the determination of genetic toxicity point-of-departure (PoD) metrics. We previously described methods to determine the no-observed-genotoxic-effect-level (NOGEL), the breakpoint-dose (BPD; previously named Td), and the benchmark dose (BMD10 ) for genetic toxicity endpoints. In this study we employed those methods, along with a new approach, to determine the non-linear slope-transition-dose (STD), and alternative methods to determine the BPD and BMD, for the analyses of nine ENU and 22 MNU datasets across a range of in vitro and in vivo endpoints. The NOGEL, BMDL10 and BMDL1SD PoD metrics could be readily calculated for most gene mutation and chromosomal damage studies; however, BPDs and STDs could not always be derived due to data limitations and constraints of the underlying statistical methods. The BMDL10 values were often lower than the other PoDs, and the distribution of BMDL10 values produced the lowest median PoD. Our observations indicate that, among the methods investigated in this study, the BMD approach is the preferred PoD for quantitatively describing genetic toxicology data. Once genetic toxicology PoDs are calculated via this approach, they can be used to derive reference doses and margin of exposure values that may be useful for evaluating human risk and regulatory decision making.

Evaluation of impact of shale gas operations in the Barnett Shale region on volatile organic compounds in air and potential human health risks.

Shale gas exploration and production (E&P) has experienced substantial growth across the U.S. over the last decade. The Barnett Shale, in north-central Texas, contains one of the largest, most active onshore gas fields in North America, stretching across 5000 square miles and having an estimated 15,870 producing wells as of 2011. Given that these operations may occur in relatively close proximity to populated/urban areas, concerns have been expressed about potential impacts on human health. In response to these concerns, the Texas Commission on Environmental Quality established an extensive air monitoring network in the region. This network provides a unique data set for evaluating the potential impact of shale gas E&P activities on human health. As such, the objective of this study was to evaluate community-wide exposures to volatile organic compounds (VOCs) in the Barnett Shale region. In this current study, more than 4.6 million data points (representing data from seven monitors at six locations, up to 105 VOCs/monitor, and periods of record dating back to 2000) were evaluated. Measured air concentrations were compared to federal and state health-based air comparison values (HBACVs) to assess potential acute and chronic health effects. None of the measured VOC concentrations exceeded applicable acute HBACVs. Only one chemical (1,2-dibromoethane) exceeded its applicable chronic HBACV, but it is not known to be associated with shale gas production activities. Annual average concentrations were also evaluated in deterministic and probabilistic risk assessments and all risks/hazards were below levels of concern. The analyses demonstrate that, for the extensive number of VOCs measured, shale gas production activities have not resulted in community-wide exposures to those VOCs at levels that would pose a health concern. With the high density of active wells in this region, these findings may be useful for understanding potential health risks in other shale play regions.

Authenticity and positivity strivings in marriage and courtship.

We proposed that married persons would want their spouses to see them as they saw themselves but that dating persons would want their relationship partners to evaluate them favorably. A survey of 176 married and dating couples tested these predictions. Just as married persons were most intimate with spouses whose evaluations verified their self-views, dating persons were most intimate with partners who evaluated them favorably. For married people with negative self-views, then, intimacy increased as their spouses evaluated them more negatively. Marriage apparently precipitates a shift from a desire for positive evaluations to a desire for self-verifying evaluations.

When does introspection bear fruit? Self-reflection, self-insight, and interpersonal choices.

Whereas earlier research suggests that the fruits of introspection may promote error and misperception, this research suggests that thinking about the self may sometimes foster self-insight. Participants who had opportunity to reflect on themselves were particularly inclined to display self-insight by (a) rating feedback that confirmed their self-views as self-descriptive (Experiments 1 and 3), (b) rating themselves in ways that matched their friends' appraisals of them (Experiment 2), and (c) choosing a self-verifying interaction partner rather than an overly favorable one (Experiment 4). These effects were moderated by the nature of the introspective activity (Experiment 3) and by its duration (Experiment 4). Implications of these findings for the nature of self-knowledge and the worlds people construct around themselves are discussed.

The fleeting gleam of praise: cognitive processes underlying behavioral reactions to self-relevant feedback.

We propose that a preference for favorable social feedback (i.e., self-enhancement) requires only that feedback be characterized as favorable or unfavorable but that a preference for self-confirming feedback (i.e., self-verification) is based on a more elaborate set of cognitive operations that requires both the characterization of feedback and a subsequent comparison of that feedback to a representation of self stored in memory. Study 1 set the stage for testing this hypothesis by showing that depriving people of processing resources interfered with their tendency to access their self-conceptions. In Studies 2 and 3, participants who were deprived of resources preferred the favorable, self-enhancing evaluator, whereas control participants displayed a preference for the self-verifying evaluator, even if that evaluator was relatively unfavorable.