An assessment of the ECETOC TRA Consumer tool performance as a screening level tool.

BACKGROUND: The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) Consumer tool was developed to fill in a methodology gap for a high throughput, screening level tool to support industry compliance with the European Union's Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. OBJECTIVE: To evaluate if the TRA Consumer tool has met its design of being a screening level tool (i.e., one which does not under-predict potential exposures). METHODS: The TRA Consumer tool algorithms and defaults were reviewed and performance benchmarked vs. other consumer models and/or empirical data. Findings from existing reviews of the TRA consumer tool were also considered and addressed. RESULTS: TRA predictions based on its default inputs exceeded measured exposures when available, typically by orders of magnitude, and were generally greater than or similar to those of other consumer exposure tools. For dermal exposure from articles, there was no evidence that a diffusivity approach would provide more appropriate exposure estimates than those of the TRA. When default values are refined using more specific data, the refined values must be considered holistically to reflect the situation being modeled as some parameters may be correlated. SIGNIFICANCE: This is the first evaluation of the ECETOC TRA consumer tool in its entirety, considering algorithms, input defaults, and associated predictions for consumer products and articles. The evaluation confirmed its design as a screening level tool. IMPACT STATEMENT: The ECETOC TRA Consumer tool has been widely applied to generate exposure estimates to support chemical registrations under the EU REACH regulation. This evaluation supports the appropriateness of the TRA as a screening level exposure assessment tool. It also warrants additional measurements of consumer exposure, especially for article use scenarios, to aid the development of consumer exposure tools and chemical risk assessment.

The European exposure science strategy 2020-2030.

Exposure science is an emerging and rapidly growing field dedicated to all aspects concerning the contact between chemical, biological, physical or psycho-social stressors and human and ecological receptors. With that, exposure science plays a central role in protecting human and ecosystem health, and contributes to the global transition towards a green and sustainable society. In Europe, however, exposure science is currently not sufficiently recognised as a scientific field, resulting in inefficient uptake into policies. In response, the wider European exposure science community developed elements and actions under the auspices of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe), for identified priority areas, namely education, exposure models, exposure data, human biomonitoring, and policy uptake. In the present document, we synthesize these strategic elements into an overarching 'European Exposure Science Strategy 2020-2030', following three strategic objectives that focus on acknowledging exposure science as an independent and interconnected field, harmonizing approaches and tools across regulations, and exploring collaboration, education and funding mechanisms. To operationalise this strategy, we present concrete key actions and propose initiatives and funding options for advancing the underlying science, cultivating broader education and cross-sector exposure knowledge transfer, and fostering effective uptake of exposure information into policy. We aim at anchoring European efforts in the global exposure science context, with a special focus on the interface between scientific advancements, application in decision support, and dissemination and training. This will help to develop exposure science as a strong scientific field with the ultimate goal to successfully assess and manage various stressors across sectors and geographic scales.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

A framework for chemical safety assessment incorporating new approach methodologies within REACH.

The long-term investment in new approach methodologies (NAMs) within the EU and other parts of the world is beginning to result in an emerging consensus of how to use information from in silico, in vitro and targeted in vivo sources to assess the safety of chemicals. However, this methodology is being adopted very slowly for regulatory purposes. Here, we have developed a framework incorporating in silico, in vitro and in vivo methods designed to meet the requirements of REACH in which both hazard and exposure can be assessed using a tiered approach. The outputs from each tier are classification categories, safe doses, and risk assessments, and progress through the tiers depends on the output from previous tiers. We have exemplified the use of the framework with three examples. The outputs were the same or more conservative than parallel assessments based on conventional studies. The framework allows a transparent and phased introduction of NAMs in chemical safety assessment and enables science-based safety decisions which provide the same level of public health protection using fewer animals, taking less time, and using less financial and expert resource. Furthermore, it would also allow new methods to be incorporated as they develop through continuous selective evolution rather than periodic revolution.

Building a European exposure science strategy.

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a 'European Exposure Science Strategy' 2020-2030, which is aligned with advances in science and technology.

Evaporation of decamethylcyclopentasiloxane (D5) from selected cosmetic products: Implications for consumer exposure modeling.

Consumer exposure to leave-on cosmetics and personal care products (C&PCPs) ingredients of low or moderate volatility is often assumed to occur primarily via dermal absorption. In reality they may volatilize from skin and represent a significant source for inhalation exposure. Often, evaporation rates of pure substances from inert surfaces are used as a surrogate for evaporation from more complex product matrices. Also the influence of partitioning to skin is neglected and the resulting inaccuracies are not known. In this paper we describe a novel approach for measuring chemical evaporation rates from C&PCPs under realistic consumer exposure conditions. Series of experiments were carried out in a custom-made ventilated chamber fitted with a vapor trap to study the disposition of a volatile cosmetic ingredient, decamethylcyclopentasiloxane (D5), after its topical application on either aluminum foil or porcine skin in vitro. Single doses were applied neat and in commercial deodorant and face cream formulations at normal room (23°C) and skin temperature (32°C). The condition-specific evaporation rates were determined as the chemical mass loss per unit surface area at different time intervals over 1-1.25h post-dose. Product weight loss was monitored gravimetrically and the residual D5 concentrations were analyzed with GC/FID. The release of D5 from exposed surfaces of aluminum occurred very fast with mean rates of 0.029 mg cm(-2)min(-1) and 0.060 mg cm(-2)min(-1) at 23°C and 32°C, respectively. Statistical analysis of experimental data confirmed a significant effect of cosmetic formulations on the evaporation of D5 with the largest effect (2-fold decrease of the evaporation rate) observed for the neat face cream pair at 32°C. The developed approach explicitly considers the initial penetration and evaporation of a substance from the Stratum Corneum and has the potential for application in dermal exposure modeling, product emission tests and the formulation of C&PCPs.

The probabilistic aggregate consumer exposure model (PACEM): validation and comparison to a lower-tier assessment for the cyclic siloxane D5.

Current practice of chemical risk assessment for consumer product ingredients still rarely exercises the aggregation of multi-source exposure. However, focusing on a single dominant source/pathway combination may lead to a significant underestimation of the risk for substances present in numerous consumer products, which often are used simultaneously. Moreover, in most cases complex multi-route exposure scenarios also need to be accounted for. This paper introduces and evaluates the performance of the Probabilistic Aggregate Consumer Exposure Model (PACEM) applied in the context of a tiered approach to exposure assessment for ingredients in cosmetics and personal care products (C&PCPs) using decamethylcyclopentasiloxane (D5) as a worked example. It is demonstrated that PACEM predicts a more realistic, but still conservative aggregate exposure within the Dutch adult population when compared to a deterministic point estimate obtained in a lower tier screening assessment. An overall validation of PACEM is performed by quantitatively relating and comparing its estimates to currently available human biomonitoring and environmental sampling data. Moderate (by maximum one order of magnitude) overestimation of exposure is observed due to a justified conservatism built into the model structure, resulting in the tool being suitable for risk assessment.

Aggregate dermal exposure to cyclic siloxanes in personal care products: implications for risk assessment.

Consumers who use personal care products (PCPs) are internally exposed to some of the organic components present of which some may be detected in exhaled air when eliminated. The aim of this study was the quantitative determination of octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in end-exhaled air to study dermal absorption of substances in PCPs. We exposed the forearm of fifteen healthy volunteers for 60min to pure D4 or D5 and to commercial products containing D4 and D5. Inhalation uptake was kept to a minimum by keeping the forearm in a flow cabinet during dermal exposure and supplying filtered air to the breathing zone of the volunteer during the post-exposure period. End-exhaled air was collected using a breath sampler (Bio-VOC), transferred to carbograph multi-bed adsorbent tubes and analyzed by thermal desorption gas chromatography mass spectrometry (TD-GC-MS). In the end-exhaled air of non-exposed volunteers background concentrations of D4 (0.8-3.5ng/L) and D5 (0.8-4.0ng/L) were observed. After exposing the volunteers, the level of D4 and D5 in end-exhaled air did not or barely exceed background concentrations. At t=90min, a sharp increase of the D4/D5 concentration in end-exhaled air was observed, which we attributed to the inhalation of the substances during a toilet visit without using inhalation protection devices. When this visit was taken out of the protocol, the sharp increase disappeared. Overall, the results of our study indicate that dermal absorption of D4 and D5 contributes only marginally to internal exposure following dermal applications. As in our study inhalation is the primary route of entry for these compounds, we conclude that its risk assessment should focus on this particular exposure route.

Concentrations of cyclic volatile methylsiloxanes in European cosmetics and personal care products: prerequisite for human and environmental exposure assessment.

Low molecular weight cyclic volatile methylsiloxanes (cVMSs) are widely employed as emollients and carrier solvents in personal care formulations in order to acquire desired performance benefits owing to their distinctive physicochemical properties. Under current European legislation cosmetic ingredients such as cVMSs are required to be labeled on the product package only qualitatively, while for the assessment of environmental and consumer exposure quantitative information is needed. The aim of this study was therefore to measure concentrations of three cVMSs, namely octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) in 51 cosmetics and personal care products (C&PCPs) that are currently available on the European market. The list of selected articles comprised a variety of hair and sun care products, skin creams and lotions, deodorants including antiperspirants, liquid foundations and a toothpaste. The target compounds were extracted from the products with different organic solvents dependent on the product matrix, followed by gas chromatography analysis with flame ionization detection (GC-FID). D5 was the predominant cVMS with the highest mean and median concentrations in all the C&PCP categories. The median concentrations of D5, D6 and D4 were 142, 2.3 and 0.053 mg/g in deodorants/antiperspirants (n = 11); 44.6, 30.0mg/g and below the limit of quantification (

Usage patterns of personal care products: important factors for exposure assessment.

Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment. To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs. Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire. The prevalence of use varied by gender, age, level of education and skin type. A high frequency of use was observed for some products (e.g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day. The frequency of use for other PCPs varied over a wide range. The amounts of use varied largely between and within different product groups. Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts. The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night. As expected, the participants used several PCPs simultaneously. The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs.