Next generation risk assessment: an ab initio case study to assess the systemic safety of the cosmetic ingredient, benzyl salicylate, after dermal exposure.

We performed an ab initio next-generation risk assessment (NGRA) for a fragrance ingredient, benzyl salicylate (BSal), to demonstrate how cosmetic ingredients can be evaluated for systemic toxicity endpoints based on non-animal approaches. New approach methodologies (NAMs) used to predict the internal exposure included skin absorption assays, hepatocyte metabolism, and physiologically based pharmacokinetic (PBPK) modeling, and potential toxicodynamic effects were assessed using pharmacology profiling, ToxProfiler cell stress assay, transcriptomics in HepG2 and MCF-7 cells, ReproTracker developmental and reproductive toxicology (DART) assays, and cytotoxicity assays in human kidney cells. The outcome of the NGRA was compared to that of the traditional risk assessment approach based on animal data. The identification of the toxicologically critical entity was a critical step that directed the workflow and the selection of chemicals for PBPK modeling and testing in bioassays. The traditional risk assessment and NGRA identified salicylic acid (SA) as the "toxdriver." A deterministic PBPK model for a single-day application of 1.54 g face cream containing 0.5% BSal estimated the Cmax for BSal (1 nM) to be much lower than that of its major in vitro metabolite, SA (93.2 nM). Therefore, SA was tested using toxicodynamics bioassays. The lowest points of departure (PoDs) were obtained from the toxicogenomics assays. The interpretation of these results by two companies and methods were similar (SA only results in significant gene deregulation in HepG2 cells), but PoD differed (213 µM and 10.6 µM). A probabilistic PBPK model for repeated applications of the face cream estimated the highest Cmax of SA to be 630 nM. The resulting margins of internal exposure (MoIE) using the PoDs were 338 and 16, which were more conservative than those derived from external exposure and in vivo PoDs (margin of safety values were 9,705). In conclusion, both traditional and ab initio NGRA approaches concluded that the daily application of BSal in a cosmetic leave-on face cream at 0.5% is safe for humans. The processing and interpretation of toxicogenomics data can lead to different PoDs, which can subsequently affect the calculation of the MoIE. This case study supports the use of NAMs in a tiered NGRA ab initio approach.

Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin.

Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes in vivo and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin.

Metabolism and plasma protein binding of 16 straight- and branched-chain parabens in in vitro liver and skin models.

Parabens are alkyl esters of 4-hydroxybenzoic acid (4-HBA), with short-chain parabens used as antimicrobials in cosmetics. We investigated the impact of chain structure on skin and liver metabolism. Incubations with primary human hepatocytes and human liver S9 indicated that methyl-, ethyl-, propyl- and butylparaben were rapidly metabolized to similar metabolites, including 4-HBA plus the corresponding alcohols. Liver and EpiSkin™ S9 were used to investigate the metabolism of 16 short and long straight- and branched-chain parabens. The rate of hydrolysis generally decreased with increasing chain length in liver S9, whereas the reverse was true for EpiSkin™ S9. Chain length also correlated with the number of metabolites, with more oxidized metabolites detected from longer chain parabens. The identity of the alcohol group impacted metabolism the most, in terms of the rate of metabolism and the contribution of cofactors. The majority of parabens (13/16) exhibited high plasma protein binding (PPB) (>90%); whereas, 4-HBA PPB was 38%. PPB was related to the LogP of the parabens. In conclusion, the major and common paraben metabolite in PHH, liver S9 and EpiSkin™ S9 was 4-HBA. The rate of metabolism, type of metabolite and contribution of hydrolysis was tissue-specific (liver, skin) and was influenced by the chain length (and hence LogP), structural isomeric form (straight vs branched), and/or the identity of the alkyl group. SHORT ABSTRACT: We investigated how the chain structure of parabens affects their metabolism by liver and EpiSkin™ S9. The major and common metabolite in primary human hepatocytes, liver S9 and EpiSkin™ S9 was 4-HBA plus the corresponding alcohols. The rate of metabolism, type of metabolite and contribution of hydrolysis was tissue-specific and influenced by the chain length, structural isomeric form (straight vs branched), and/or the identity of the alkyl group. Most parabens exhibited high PPB (>90%), whereas the PPB of 4-HBA was 38%.

Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids.

A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin and isolated human skin layers for 50 compounds relevant to cosmetics ingredients. K values were measured in dermatomed skin, isolated dermis, whole epidermis, intact stratum corneum (SC), delipidized SC and SC lipids by direct measurements of the radioactivity in the tissue layers/lipid component vs. buffer samples. D determinations were made in dermatomed skin, isolated dermis, whole epidermis and intact SC using a non-linear regression of the cumulative receptor fluid content of radiolabeled compound, fit to the solution of Fick's 2nd Law. Correlation analysis was completed between K, D, and physicochemical properties. The amount of interindividual (donor) and intraindividual (replicate) variability in the K and D data was characterized for each skin layer and chemical. These data can be further used to help inform the factors that influence skin bioavailability and to help improve in silico models of dermal penetration.

Use of human liver and EpiSkin™ S9 subcellular fractions as a screening assays to compare the in vitro hepatic and dermal metabolism of 47 cosmetics-relevant chemicals.

The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients.

Comparison of the metabolism of 10 cosmetics-relevant chemicals in EpiSkin™ S9 subcellular fractions and in vitro human skin explants.

An understanding of the bioavailability of topically applied cosmetics ingredients is key to predicting their local skin and systemic toxicity and making a safety assessment. We investigated whether short-term incubations with S9 from the reconstructed epidermal skin model, EpiSkin™, would give an indication of the rate of chemical metabolism and produce similar metabolites to those formed in incubations with human skin explants. Both have advantages: EpiSkin™ S9 is a higher-throughput assay, while the human skin explant model represents a longer incubation duration (24 hours) model integrating cutaneous distribution with metabolite formation. Here, we compared the metabolism of 10 chemicals (caffeine, vanillin, cinnamyl alcohol, propylparaben, 4-amino-3-nitrophenol, resorcinol, 4-chloroaniline, 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline and 2-acetyl aminofluorene) in both models. Both models were shown to have functional Phase 1 and 2 enzymes, including cytochrome P450 activities. There was a good concordance between the models with respect to the level of metabolism (stable vs. slowly vs. extensively metabolized chemicals) and major early metabolites produced for eight chemicals. Discordant results for two chemicals were attributed to a lack of the appropriate cofactor (NADP+ ) in S9 incubations (cinnamyl alcohol) and protein binding influencing chemical uptake in skin explants (4-chloroaniline). These data support the use of EpiSkin™ S9 as a screening assay to provide an initial indication of the metabolic stability of a chemical applied topically. If required, chemicals that are not metabolized by EpiSkin™ S9 can be tested in longer-term incubations with in vitro human explant skin to determine whether it is slowly metabolized or not metabolized at all.

Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic-relevant chemicals. The penetration of finite doses (10 µL/cm2 ) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 µg/cm2 . The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although there were some exceptions, particularly of low DD chemicals. While there was some variability due to cell outliers and donor variation, the overall reproducibility was very good. As six chemicals had to be applied in 100% ethanol due to low aqueous solubility, we compared the penetration of four chemicals with similar physicochemical properties applied in ethanol and phosphate-buffered saline. Of these, the DD of hydrocortisone was the same in both solvents, while the DD of propylparaben, geraniol and benzophenone was lower in ethanol. Some chemicals displayed an infinite dose kinetic profile; whereas, the cumulative absorption of others into the RF reflected the finite dosing profile, possibly due to chemical volatility, total absorption, chemical precipitation through vehicle evaporation or protein binding (or a combination of these). These investigations provide a substantial and consistent set of skin penetration data that can help improve the understanding of skin penetration, as well as improve the prediction capacity of in silico skin penetration models.

Facilitating physical activity and reducing symptoms in patients with knee osteoarthritis: study protocol of a randomized controlled trial to test a theory-based PrevOP-psychological adherence program (PrevOP-PAP).

BACKGROUND: The present randomized controlled trial, which is crossed with the "PREVenting the impairment of primary Osteoarthritis by high impact long-term Physical exercise regimen" Main Medical Trial (PrevOP-MMT), aims to evaluate a psychological adherence program (PrevOP-PAP), and is designed to support persons with knee osteoarthritis (OAK) in the uptake and maintenance of regular physical activity to reduce OAK symptoms. The PrevOP-PAP is based on the Health Action Process Approach (HAPA), a social-cognitive theory predicting health behavior change in individuals, extended here by social network characteristics and social exchange processes. It is expected that participants with OAK receiving the PrevOP-PAP will maintain higher levels of regular physical activity throughout a 24-month period and consequently report lower levels of OAK symptoms than participants of an active control condition. METHODS: A total of N = 240 participants with medically verified moderate OAK will be randomly assigned to an intervention condition (PrevOP-PAP-I; 50%) or an active control condition (PrevOP-PAP-CTRL). The PrevOP-PAP-I includes a motivational intervention, repeated self-regulation interventions, and a network creation intervention delivered over 12 months. Modes of intervention delivery include a paper-pencil motivation leaflet with a quiz, a computer-assisted face-to-face intervention, four computer assisted phone-based interventions, and activity calendars. The PrevOP-PAP-CTRL includes the motivational intervention only. Primary outcome will be OAK symptoms. Secondary outcomes include objectively and subjectively measured physical activity and indicators of quality of life. Other outcomes are HAPA-derived self-regulatory indicators as well as proposed social network and social exchange mechanisms of health behavior change. Assessments take place at baseline, 6 months, 12 months, 18 months, and 24 months following baseline. DISCUSSION: Based on the extended HAPA, this study seeks to reveal the self-regulatory and social mechanisms of the uptake and maintenance of physical activity and their relation to disease symptoms in persons with OAK. The design and evaluation of this program are intended to become a yardstick for future development and implementation of digitalized psychological adherence programs in this population. TRIAL REGISTRATION: German Clinical Trials Register; also available at http://apps.who.int/trialsearch/ ; registration number: DRKS00009677 ; date of registration: 26 January 2016.

Sex differential mediation effects of planning within the health behavior change process.

OBJECTIVE: Previous research demonstrates that planning mediates the relationship between intention and health behavior change, but evidence is inconclusive, and possible sex differences within the intention-planning-behavior-chain are understudied so far. The current study, therefore, aims to disentangle this by addressing potential sex differences in the mediating role of planning in the health behavior change process. METHOD: Three longitudinal studies were conducted in Germany between 2009 and 2011 (Study 1: 245 women, 216 men; Study 2: 156 women, 37 men; Study 3: 82 women, 84 men). In each study, intention (predictor), planning (mediator), and sex (moderator) were assessed to predict changes in (1) fruit and vegetable intake, (2) physical activity, and (3) sun protection. A moderated mediation model was specified to test whether the conditional direct effect of intention on health behavior change and/or the conditional indirect effect of intention on health behavior change through planning was different for men and women. RESULTS: Similar patterns of sex differential effects emerged within the intention-planning-behavior-chain across all three studies. The conditional indirect effect of intention on health behavior change through planning was meaningful for men but not for women for all three health behaviors. Thus, planning acted as a mediator between intention and health behavior change only for men. CONCLUSION: The study contributes to the understanding of the inconclusive evidence on the role of planning as mediator between intention and health behavior change and sheds some light of possible sex differences that qualify this mediation. The findings suggest that women and men may not similarly benefit from health behavior change modification techniques involving planning strategies. Future theoretical developments and interventions should take this into account.

A strategy for systemic toxicity assessment based on non-animal approaches: The Cosmetics Europe Long Range Science Strategy programme.

When performing safety assessment of chemicals, the evaluation of their systemic toxicity based only on non-animal approaches is a challenging objective. The Safety Evaluation Ultimately Replacing Animal Test programme (SEURAT-1) addressed this question from 2011 to 2015 and showed that further research and development of adequate tools in toxicokinetic and toxicodynamic are required for performing non-animal safety assessments. It also showed how to implement tools like thresholds of toxicological concern (TTCs) and read-across in this context. This paper shows a tiered scientific workflow and how each tier addresses the four steps of the risk assessment paradigm. Cosmetics Europe established its Long Range Science Strategy (LRSS) programme, running from 2016 to 2020, based on the outcomes of SEURAT-1 to implement this workflow. Dedicated specific projects address each step of this workflow, which is introduced here. It tackles the question of evaluating the internal dose when systemic exposure happens. The applicability of the workflow will be shown through a series of case studies, which will be published separately. Even if the LRSS puts the emphasis on safety assessment of cosmetic relevant chemicals, it remains applicable to any type of chemical.

Fruit and Vegetable Intake: the Interplay of Planning, Social Support, and Sex.

PURPOSE: Intention and planning are important predictors of dietary change. However, little attention has been given yet to the relationship between them as a function of other social-cognitive factors and their interplay with socio-demographics such as sex. METHODS: In an observational study (1520 women, 430 men) with two measurement points in time, intention (predictor), planning (mediator), social support (first moderator), and sex (second moderator) were assessed to predict changes in diet separately for fruit and vegetable intake. RESULTS: All predictors had a main effect on fruit intake but no interactions emerged. For vegetable intake, the mediation-chain was qualified by a three-way interaction: for women, the lower the perceived social support, the more the translation of planning into behavior; for men, the higher the perceived social support, the more the translation of planning into behavior. CONCLUSIONS: Even though intention and planning are predictors of dietary change, they operate differently under specific conditions (level of social support), for specific subgroups (men vs. women), and for different target behaviors (fruit vs. vegetable intake). These results suggest to further examine the mechanisms by which intentions are translated into behavior via planning.

Comparison of the Skin Penetration of 3 Metabolically Stable Chemicals Using Fresh and Frozen Human Skin.

BACKGROUND: The Cosmetics Europe ADME Task Force is developing in vitro and in silico tools for predicting skin and systemic concentrations after topical application of cosmetic ingredients. There are conflicting reports as to whether the freezing process affects the penetration of chemicals; therefore, we evaluated whether the storage of human skin used in our studies (8-12 weeks at -20°C) affected the penetration of model chemicals. METHODS: Finite doses of trans-cinnamic acid (TCA), benzoic acid (BA), and 6-methylcoumarin (6MC) (non-volatile, non-protein reactive and metabolically stable in skin) were applied to fresh and thawed frozen skin from the same donors. The amounts of chemicals in different skin compartments were analysed after 24 h. RESULTS: Although there were some statistical differences in some parameters for 1 or 2 donors, the penetration of TCA, BA, and 6MC was essentially the same in fresh and frozen skin, i.e., there were no biologically relevant differences in penetration values. Statistical differences that were evident indicated that penetration was marginally lower in frozen than in fresh skin, indicating that the barrier function of the skin was not lost. CONCLUSION: The penetration of the 3 chemicals was essentially unaffected by freezing the skin at -20°C for up to 12 weeks.

Intervention Engagement Moderates the Dose-Response Relationships in a Dietary Intervention.

Behavioral interventions could lead to changes in behavior through changes in a mediator. This dose-response relationship might only hold true for those participants who are actively engaged in interventions. This Internet study investigated the role of engagement in a planning intervention to promote fruit and vegetable consumption in addition to testing the intervention effect on planning and behavior. A sample of 701 adults (mean = 38.71 years, 81% women) were randomly assigned either to a planning intervention (experimental group) or to one of 2 control conditions (untreated waiting list control group or placebo active control group). Moderated mediation analyses were carried out. Significant changes over time and time × group effects revealed the effectiveness of the intervention. The effect of the intervention (time 1) on changes in behavior (time 3; 1 month after the personal deadline study participants set for themselves to start implementing their plans) was mediated by changes in planning (time 2; 1 week the personal deadline). Effects of planning on behavior were documented only at a moderate level of intervention engagement. This indicates an inverse U-shaped dose-response effect. Thus, examining participants' intervention engagement allows for a more careful evaluation of why some interventions work and others do not.

Self-efficacy, planning, and preparatory behaviours as joint predictors of physical activity: A conditional process analysis.

OBJECTIVE: Planning can bridge the gap between intentions and action, but what bridges the gap between planning and action? This study helps to answer the question by disentangling the interrelationships between self-efficacy, planning and preparatory behaviours in predicting physical activity. Preparatory behaviours are tested as a working mechanism of planning. Moreover, it is tested whether the utility of preparatory behaviours depends on an individual's level of self-efficacy. METHODS: A survey assessed planning, self-efficacy and preparatory behaviours for physical activity. Adults (N = 166) provided data at two measurement points. In a longitudinal model, preparatory behaviours were specified as a mediator between planning and physical activity. Self-efficacy was specified as a possible moderator at two points in the model. RESULTS: Preparatory behaviours mediated the relationship between planning and physical activity. An interaction between self-efficacy and preparatory behaviours on physical activity was found, indicating that individuals with low self-efficacy beliefs were more active if they engaged more frequently in preparatory behaviours. CONCLUSION: Planning seems to stimulate preparatory behaviours, which in turn make future physical activity more likely. Furthermore, as performing preparatory behaviours represent a step forward towards the enactment of behavioural goals, preparatory behaviours may be particular beneficial for individuals afflicted by self-doubts regarding physical activity.

The interplay of intention, autonomy, and sex with dietary planning: A conditional process model to predict fruit and vegetable intake.

OBJECTIVES: Dietary intentions are supposed to engender planning processes, which in turn stimulate dietary behaviour change. However, some studies failed to find such mediation effects, which suggest more complex and not yet unravelled relationships between these factors. One explanation may be that mediation works better under certain circumstances or only for specific subgroups. This study addresses this reasoning by examining autonomy beliefs and sex as putative moderators of the hypothesized mediation chain. DESIGN AND METHODS: In a longitudinal design with three measurement points in time (1 week and 1 month apart), 912 women and 214 men were surveyed. Planning, intention, dietary autonomy beliefs, and sex were used to predict fruit and vegetable intake within a conditional process model designed to identify mechanisms of change. RESULTS: The intention-planning-behaviour chain was qualified by a triple interaction involving autonomy beliefs and sex as moderators between intention and planning. Higher dietary autonomy resulted in higher levels of planning fruit and vegetable intake. For men, even in case of higher intention, at least medium levels of autonomy beliefs were necessary to facilitate planning processes. For women, already lower levels of autonomy beliefs can engender postintentional planning strategies and seem to even compensate lower intention. CONCLUSIONS: Intention and planning are key predictors of dietary change. However, these variables work better under specific conditions (with a sufficient level of autonomy), and differently in subgroups (men vs. women). These results may explain the inconsistent findings of previous studies on the mediating effect of planning and allow for a better description of the mechanisms by which intentions may influence behaviour. Statement of contribution What is already known on this subject? The adoption of health-enhancing dietary behaviours can be facilitated by intentions and planning. Planning to eat more fruit and vegetable helps to translate intentions into actual consumption. Fruit and vegetable intake levels are higher in women than in men. What does this study add? Dietary intentions engender more likely planning processes when perceived autonomy concerning food consumption is high. Dietary autonomy beliefs and sex moderate the intention-planning-behaviour chain. Among men, dietary planning is highest when both intentions and autonomy are high.

Preparing for physical activity: pedometer acquisition as a self-regulatory strategy.

When people intend and plan to perform higher levels of physical activity, they do not start on impulse without preparing. Thus, preparation is a behavioral construct positioned between planning and target behavior. This may be reflected by the acquisition of sports equipment as well as monitoring devices such as pedometers. The research questions are who takes such preparatory action, whether picking up a complimentary pedometer can be predicted by self-efficacy and outcome expectancies, and whether this kind of preparatory action facilitates subsequent physical activity. A longitudinal physical activity survey was conducted with 143 university students who were offered a complimentary pedometer. Collecting this free gift served as indicator of preparatory behavior. Outcome expectancies and self-efficacy beliefs were specified as predictors of this behavior. Two weeks later, physical activity differences between the groups were determined. Collecting the pedometer was associated with higher levels of physical activity at follow-up. Outcome expectancies failed to predict the pedometer collection, but self-efficacy did. An interaction between these two factors indicated that self-efficacy compensated for low outcome expectancies. Pedometer acquisition signifies a preparatory action that is facilitated by self-efficacy. Positioned between planning and target behavior, they constitute a proximal self-regulatory step towards health behavior change.

Self-regulation prompts can increase fruit consumption: a one-hour randomised controlled online trial.

OBJECTIVE: The purpose was to examine whether a 1-h intervention would help increase fruit consumption in motivated individuals and to study the role of self-regulatory mechanisms in the behaviour change process, with a particular focus on dietary planning and action control. METHODS: A randomised controlled trial compared a 1-h online intervention with controls in 791 participants. Dependent variables were fruit intake, planning to consume and dietary action control. RESULTS: Experimental condition by time interactions documented superior treatment effects for the self-regulation group, although all participants benefited from the study. To identify the contribution of the intervention ingredients, multiple mediation analyses were conducted that yielded mediator effects for dietary action control and planning. CONCLUSIONS: A very brief self-regulatory nutrition intervention was superior to a control condition. Dietary planning and action control seem to play a major role in the mechanisms that facilitate fruit intake.

Positive experience, self-efficacy, and action control predict physical activity changes: a moderated mediation analysis.

OBJECTIVES: Experiencing positive consequences of one's physical activity is supposed to facilitate further activity. This motivational outcome might be generated by an increase in perceived self-efficacy. In addition to such a mediator effect, we examine whether this applies generally or only under conditions of volitional control. For this purpose, perceived action control was considered as a putative moderator. DESIGN AND METHOD: N = 193 students participated in a study with three measurement points in time. At baseline, positive experience with previous physical activity was measured as a predictor of physical activity. Two weeks later, self-efficacy and action control variables were assessed as putative mediator and moderator, respectively. After another 2 weeks, physical activity was measured as the outcome. A moderated mediation model was specified with baseline physical activity and sex as covariates. RESULTS: Self-efficacy was found to mediate between initial positive experience and later physical activity, and this mediation was moderated by action control. CONCLUSIONS: Participants' perceptions of positive experience were associated with their subsequent self-efficacy fostering physical activity. However, persons with low levels of action control did not translate positive experience into physical activity via self-efficacy. STATEMENT OF CONTRIBUTION: What is already known on this subject? Numerous studies have shown that exercise-specific self-efficacy predicts subsequent physical activity. Prior positive experience with physical activity is suggested to be associated with exercise-specific self-efficacy. Furthermore, action control was found to be beneficial for the maintenance of physical activity. What does this study add? This study unveils the mechanisms between these social-cognitive determinants: our longitudinal results suggest that the mediation of positive experience and subsequent physical activity via self-efficacy is moderated by action control. Persons with low levels of action control did not translate positive experience into physical activity via self-efficacy.

A dietary planning intervention increases fruit consumption in Iranian women.

The study examined whether a dietary planning intervention would help increase fruit consumption among Iranian women focusing on self-regulatory mechanisms in behavior change. We conducted a randomized controlled trial to compare a planning intervention with a control condition in 165 Iranian women (aged 17-48years). Dependent variable was fruit intake, and dietary planning served as the mediator. After baseline assessment (T1) the intervention group received a leaflet on fruit consumption with a planning sheet. Changes were assessed at 3-weeks (T2) and at 3-months follow-ups (T3). Findings showed that the dietary planning intervention led to an increase in fruit intake. Age moderated this mediation. Changes in dietary planning mediated between intervention and fruit consumption in middle aged women. Dietary planning seems to play a role in the mechanism that facilitates fruit intake among Iranian women. This mediation by planning was found in middle aged women (30-48 years old), but not in young adult women (17-29 years old).