REACH Worker Exposure Assessments: Ensuring Meaningful Health Risk Communication.

OBJECTIVES: Within the chemical legislation, REACH was implemented in order to improve safe working conditions with hazardous substances. Literature and real-life experiences by those concerned have shown that there are still gaps with a need for improved risk communication. This study elaborated on how information provided by REACH is understood and acted on by down- and upstream users, and how it can be further improved. METHODS: An extensive literature study including 21 studies and 13 tools was carried out. The outcomes were discussed and further supplemented by means of 18 interviews concerning 37 internal safety and REACH documents to build six different use cases representing different Dutch downstream companies. For the upstream perspective also 2 sector organizations and 2 registrants were interviewed. Three online workshops were organized in order to share insights and gather input on international recognition, potential suggestions and further recommendations with 30 participants from nine different EU countries. RESULTS: Although the methods to collect the data differed between the different stages of the study, the general results from all three stages elucidated similar themes in the data and each of the stages used the results from the previous stage as a starting point. Recurring themes concerned the (i) complexity of documents, (ii) deficiencies as experienced by SMEs in REACH, (iii) feedback and responsibilities in the supply chain, and (iv) the cooperation between REACH and OSH. DISCUSSION: The study at hand revealed that even though there are currently several activities to improve communication on safe-use of chemicals, communication on safe-use in the scope of REACH should be improved. This includes e.g. the future involvement of actual end-users in activities and development related to communication of safe-use information in the scope of REACH including feedback, less complicated and complex documents and clear communication concerning legislations and updates of documents. Furthermore, the issues recognized in the Netherlands are mostly also recognized by international workshop participants, thereby indicating international benefits in various areas by means of improved communication. CONCLUSIONS: The study confirmed that many of our generic conclusions were already part of the shared knowledge in the REACH community, but that it is very valuable that this knowledge has been explicated, validated and reported in a structured way in the present project. Besides uncovering some crucial aspects that offer potential improvements regarding risk communication, this study offers possible solutions and next steps to be taken.

Extrapolating the Applicability of Measurement Data on Worker Inhalation Exposure to Chemical Substances.

Measured data are generally preferred to modelled estimates of exposure. Grouping and read-across is already widely used and accepted approach in toxicology, but an appropriate approach and guidance on how to use existing exposure measurement data on one substance and work situation for another substance and/or work situation is currently not available. This study presents a framework for an extensive read-across of existing worker inhalable exposure measurement data. This framework enables the calculation of read-across factors based on another substance and/or work situation by first evaluating the quality of the existing measurement data and then mapping its similarity or difference with another substance and/or work situation. The system of read-across factors was largely based on the determinants in ECETOC TRA and ART exposure models. The applicability of the framework and its proof of principle were demonstrated by using five case studies. In these case studies, either the 75th percentiles of measured exposure data was observed to lie within the estimated 90% confidence intervals from the read-across approach or at least with the increase in the geometric mean of measured exposure, geometric mean of estimated exposure also increased. Testing and re-evaluation of the present framework by experts in exposure assessment and statistics is recommended to develop it further into a tool that can be widely used in exposure assessment and regulatory practices.

Dermal Advanced REACH Tool (dART)-Development of a Dermal Exposure Model for Low-Volatile Liquids.

This article describes the development of a mechanistic model for underpinning the dermal Advanced REACH Tool (dART), an extension of the existing ART model and its software platform. It was developed for hand exposure to low volatile liquids (vapour pressure ≤ 10 Pa at 20°C) including solids-in-liquid products. The model is based on an existing conceptual dermal source-receptor model that has been integrated into the ART framework. A structured taxonomy of workplace activities referred to as activity classes are adopted from ART. Three key processes involved in mass transport associated with dermal exposure are applied, i.e. deposition, direct emission and contact, and transfer. For deposition, the model adopts all the relevant modifying factors (MFs) applied in ART. In terms of direct emission and contact (e.g. splashes) and transfer (e.g. hand-surface contacts), the model defines independent principal MFs, i.e. substance-related factors, activity-related factors, localized- and dispersion control and exposed surface area of the hands. To address event-based exposures as much as possible, the model includes crucial events during an activity (e.g. hand immersions) and translates objective information on tools and equipment (manual or automated) to probable events (e.g. splashes) and worker behaviours (e.g. surface contacts). Based on an extensive review of peer-reviewed literature and unpublished field studies, multipliers were assigned to each determinant and provide an approximated (dimensionless) numerical value. In the absence of (sufficient) evidence, multipliers were assigned to determinants based on assumptions made during discussions by experts in the consortium. A worked example is presented to illustrate the calculation of hand exposure for a specific scenario. The dART model is not yet implemented in the ART software platform, and a robust validation of the model is necessary to determine its predictive ability. With advancing knowledge on dermal exposure and its determinants, this model will require periodic updates and refinements, in addition to further expansion of the applicability domain of the model.

Validation of the dermal exposure model in ECETOC TRA.

The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information.From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative.The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a factor of 34 in this data set, while factors of five to ten were used in the model estimations. There was also an effect of the sampling method in the measured data on the exposure levels. Exposure cases where sampling was done via an interception method, such as gloves, on average showed a factor of six higher 75th percentiles of measured values than exposure cases where sampling was done via a removal method, such as hand washing. This may partly be responsible for the apparent underestimation of dermal exposure by the model at high exposure values. However, there also appeared to be a relation between expected exposure level (as indicated by the model estimate) and the choice of sampling method.In this study, solid substances used in liquid products were treated as liquids with negligible volatility. The results indicate that the ECETOC TRA dermal exposure model performs equally well for these substances as for liquids. There were suggestions of a difference in performance of the model between solids and liquids.For several parts of the ECETOC TRA dermal model, no or hardly any measured dermal exposure data were available. Therefore, gathering of more dermal exposure levels is recommended, specifically for situations not yet sufficiently covered in the present data set.

Experimental estimation of migration and transfer of organic substances from consumer articles to cotton wipes: Evaluation of underlying mechanisms.

The aim of this work was to identify the key mechanisms governing transport of organic chemical substances from consumer articles to cotton wipes. The results were used to establish a mechanistic model to improve assessment of dermal contact exposure. Four types of PVC flooring, 10 types of textiles and one type of inkjet printed paper were used to establish the mechanisms and model. Kinetic extraction studies in methanol demonstrated existence of matrix diffusion and indicated the presence of a substance surface layer on some articles. Consequently, the proposed substance transfer model considers mechanical transport from a surface film and matrix diffusion in an article with a known initial total substance concentration. The estimated chemical substance transfer values to cotton wipes were comparable to the literature data (relative transfer ∼ 2%), whereas relative transfer efficiencies from spiked substrates were high (∼ 50%). For consumer articles, high correlation (r(2)=0.92) was observed between predicted and measured transfer efficiencies, but concentrations were overpredicted by a factor of 10. Adjusting the relative transfer from about 50% used in the model to about 2.5% removed overprediction. Further studies are required to confirm the model for generic use.

The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity.

Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for relevant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This paper describes the implementation of ITS mutagenicity and carcinogenicity in the public OSIRIS webtool. The data requirements of REACH formed the basis for these ITS. The main goal was to implement procedures to reach a conclusion on the adequacy and validity of available data. For the mutagenicity ITS a quantitative Weight of Evidence approach based on Bayesian statistics was developed and implemented. The approach allows an overall quality assessment of all available data for the five types of mutagenicity data requirements: in vitro bacterial mutagenicity, in vitro and in vivo chromosome aberration, in vitro and in vivo mammalian mutagenicity. For the carcinogenicity ITS a tool was developed to evaluate the quality of studies not conforming (entirely) to guidelines. In a tiered approach three quality aspects are assessed: documentation (reliability), study design (adequacy) and scope of examination (validity). The quality assessment is based on expert and data driven quantitative Weight of Evidence.

A structured approach to Exposure Based Waiving of human health endpoints under REACH developed in the OSIRIS project.

Exposure Based Waiving (EBW) is one of the options in REACH when there is insufficient hazard data on a specific endpoint. Rules for adaptation of test requirements are specified and a general option for EBW is given via Appendix XI of REACH, allowing waiving of repeated dose toxicity studies, reproductive toxicity studies and carcinogenicity studies under a number of conditions if exposure is very low. A decision tree is described that was developed in the European project OSIRIS (Optimised Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-Test and Test Information) to help decide in what cases EBW can be justified. The decision tree uses specific criteria as well as more general questions. For the latter, guidance on interpretation and resulting conclusions is provided. Criteria and guidance are partly based on an expert elicitation process. Among the specific criteria a number of proposed Thresholds of Toxicological Concern are used. The decision tree, expanded with specific parts on absorption, distribution, metabolism and excretion that are not described in this paper, is implemented in the OSIRIS webtool on integrated testing strategies.

Classification of occupational activities for assessment of inhalation exposure.

There is a large variety of activities in workplaces that can lead to emission of substances. Coding systems based on determinants of emission have so far not been developed. In this paper, a system of Activity Classes and Activity Subclasses is proposed for categorizing activities involving chemical use. Activity Classes share their so-called 'emission generation mechanisms' and physical state of the product handled and the underlying determinants of emission. A number of (industrial) stakeholders actively participated in testing and fine-tuning the system. With the help of these stakeholders, it was found to be relatively easy to allocate a large number of activities to the Activity Classes and Activity Subclasses. The system facilitates a more structured classification of activities in exposure databases, a structured analysis of the analogy of exposure activities, and a transparent quantification of the activity emission potential in (new) exposure assessment models. The first use of the system is in the Advanced REACH Tool.

Exposure-based waiving under REACH.

Within the REACH framework, but also within OECD, there is understanding that for reasons of animal welfare, costs and logistics, it is important to limit the number of tests to be conducted. Exposure-based waiving (EBW) is a potentially important element in testing strategies. This publication describes criteria for exposure-based waiving as foreseen in the REACH regulation and gives more detail to the REACH requirements for exposure-based waiving The principle behind any EBW is that there are situations when human or environmental exposures are so low or infrequent that there is a very low probability that the acquisition of additional effect information may lead to an improvement in the ability to manage risk. EBW therefore is risk-based and needs thorough knowledge on exposure as well as on effects criteria. Both elements are discussed: exposure models are analysed and the uncertainty in their predictions discussed as well as no-effect criteria such as the threshold of toxicological concern. Examples of EBW are provided for environmental, consumer and worker exposure. REACH only allows EBW in a limited number of cases with constraints on tonnage levels, types of tests to be waived and the need for a thorough ES and exposure assessment throughout the life cycle of a chemical and for all human exposure routes and environmental pathways. EBW will only be considered a real option by industry if a cost-benefit analysis shows an advantage, which may heavily depend on the weighing factor one applies for the non-use of experimental animals.

Cross-validation and refinement of the Stoffenmanager as a first tier exposure assessment tool for REACH.

OBJECTIVES: For regulatory risk assessment under REACH a tiered approach is proposed in which the first tier models should provide a conservative exposure estimate that can discriminate between scenarios which are of concern and those which are not. The Stoffenmanager is mentioned as a first tier approach in the REACH guidance. In an attempt to investigate the validity of the Stoffenmanager algorithms, a cross-validation study was performed. METHODS: Exposure estimates using the Stoffenmanager algorithms were compared with exposure measurement results (n=254). Correlations between observed and predicted exposures, bias and precision were calculated. Stratified analyses were performed for the scenarios "handling of powders and granules" (n=82), "handling solids resulting in comminuting" (n=60), "handling of low-volatile liquids" (n=40) and "handling of volatile liquids" (n=72). RESULTS: The relative bias of the four algorithms ranged between -9% and -77% with a precision of approximately 1.7. The 90th percentile estimate of one out of four algorithms was not conservative enough. Based on these statistics and analyses of residual plots the underlying algorithm was adapted. Subsequently, the calibration and the cross-validation dataset were merged into one dataset (n=952) used for calibrating the adapted Stoffenmanager algorithms. This new calibration resulted in new exposure algorithms for the four scenarios. CONCLUSIONS: The Stoffenmanager is capable of discriminating among exposure levels mainly between scenarios in different companies. The 90th percentile estimates of the Stoffenmanager are verified to be sufficiently conservative. Therefore, the Stoffenmanager could be a useful tier 1 exposure assessment tool for REACH.

'Stoffenmanager', a web-based control banding tool using an exposure process model.

In the scope of a Dutch programme to reinforce the working conditions policy on hazardous substances, an internet-based tool was developed to help small- and medium-sized companies to handle hazardous substances with more care. The heart of this tool, called the Stoffenmanager, is a risk banding scheme. It combines a hazard banding scheme similar to that of COSHH Essentials and an exposure banding scheme based on an exposure model originally presented by Cherrie et al. (1996) and further developed by Cherrie and Schneider (1999). The exposure model has been modified to allow non-expert users to understand and use the model. Exposure scores are calculated based on categorization of determinants of emission, transmission and immission. These exposure scores are assigned to exposure bands. The comparison of exposure bands and hazard bands leads to a risk band or priority band. Following the evaluation of the priority of tasks done with products, generic exposure control measures can be evaluated for their possibility to lower the risks. Relevant control measures can be put into an action plan and into workplace instruction cards. The tool has several other functionalities regarding registration and storage of products. The exposure model in the Stoffenmanager leads to exposure scores. These have been compared with measured exposure levels. The exposure scores correlated well with measured exposure levels. The development of the Stoffenmanager has facilitated a whole range of further developments of useful tools for small- and medium-sized enterprises.

Exposure scenarios for workers.

The new European chemicals legislation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) requires the development of Exposure Scenarios describing the conditions and risk management measures needed for the safe use of chemicals. Such Exposure Scenarios should integrate considerations of both human health and the environment. Specific aspects are relevant for worker exposure. Gathering information on the uses of the chemical is an important step in developing an Exposure Scenario. In-house information at manufacturers is an important source. Downstream users can contribute information through direct contact or through their associations. Relatively simple approaches (Tier 1 tools, such as the ECETOC Targeted Risk Assessment and the model EASE) can be used to develop broad Exposure Scenarios that cover many use situations. These approaches rely on the categorisation of just a few determinants, including only a small number of risk management measures. Such approaches have a limited discriminatory power and are rather conservative. When the hazard of the substance or the complexity of the exposure situation require a more in-depth approach, further development of the Exposure Scenarios with Tier 2 approaches is needed. Measured data sets of worker exposure are very valuable in a Tier 2 approach. Some downstream user associations have attempted to build Exposure Scenarios based on measured data sets. Generic Tier 2 tools for developing Exposure Scenarios do not exist yet. To enable efficient development of the worker exposure part of Exposure Scenarios a further development of Tier 1 and Tier 2 tools is needed. Special attention should be given to user friendliness and to the validity (boundaries) of the approaches. The development of standard worker exposure descriptions or full Exposure Scenarios by downstream user branches in cooperation with manufacturers and importers is recommended.

Task-based dermal exposure models for regulatory risk assessment.

The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of new measurements of dermal exposure together with detailed contextual information. This article describes the development of a set of generic task-based models capable of predicting potential dermal exposure to both solids and liquids in a wide range of situations. To facilitate modelling of the wide variety of dermal exposure situations six separate models were made for groupings of exposure scenarios called Dermal Exposure Operation units (DEO units). These task-based groupings cluster exposure scenarios with regard to the expected routes of dermal exposure and the expected influence of exposure determinants. Within these groupings linear mixed effect models were used to estimate the influence of various exposure determinants and to estimate components of variance. The models predict median potential dermal exposure rates for the hands and the rest of the body from the values of relevant exposure determinants. These rates are expressed as mg or microl product per minute. Using these median potential dermal exposure rates and an accompanying geometric standard deviation allows a range of exposure percentiles to be calculated.

Default values for assessment of potential dermal exposure of the hands to industrial chemicals in the scope of regulatory risk assessments.

Dermal exposure needs to be addressed in regulatory risk assessment of chemicals. The models used so far are based on very limited data. The EU project RISKOFDERM has gathered a large number of new measurements on dermal exposure to industrial chemicals in various work situations, together with information on possible determinants of exposure. These data and information, together with some non-RISKOFDERM data were used to derive default values for potential dermal exposure of the hands for so-called 'TGD exposure scenarios'. TGD exposure scenarios have similar values for some very important determinant(s) of dermal exposure, such as amount of substance used. They form narrower bands within the so-called 'RISKOFDERM scenarios', which cluster exposure situations according to the same purpose of use of the products. The RISKOFDERM scenarios in turn are narrower bands within the so-called Dermal Exposure Operation units (DEO units) that were defined in the RISKOFDERM project to cluster situations with similar exposure processes and exposure routes. Default values for both reasonable worst case situations and typical situations were derived, both for single datasets and, where possible, for combined datasets that fit the same TGD exposure scenario. The following reasonable worst case potential hand exposures were derived from combined datasets: (i) loading and filling of large containers (or mixers) with large amounts (many litres) of liquids: 11,500 mg per scenario (14 mg cm(-2) per scenario with surface of the hands assumed to be 820 cm(2)); (ii) careful mixing of small quantities (tens of grams in <1l): 4.1 mg per scenario (0.005 mg cm(-2) per scenario); (iii) spreading of (viscous) liquids with a comb on a large surface area: 130 mg per scenario (0.16 mg cm(-2) per scenario); (iv) brushing and rolling of (relatively viscous) liquid products on surfaces: 6500 mg per scenario (8 mg cm(-2) per scenario) and (v) spraying large amounts of liquids (paints, cleaning products) on large areas: 12,000 mg per scenario (14 mg cm(-2) per scenario). These default values are considered useful for estimating exposure for similar substances in similar situations with low uncertainty. Several other default values based on single datasets can also be used, but lead to estimates with a higher uncertainty, due to their more limited basis. Sufficient analogy in all described parameters of the scenario, including duration, is needed to enable proper use of the default values. The default values lead to similar estimates as the RISKOFDERM dermal exposure model that was based on the same datasets, but uses very different parameters. Both approaches are preferred over older general models, such as EASE, that are not based on data from actual dermal exposure situations.

RISKOFDERM: risk assessment of occupational dermal exposure to chemicals. An introduction to a series of papers on the development of a toolkit.

Dermal exposure to industrial chemicals during work is of major concern in the risk assessment of chemicals. Current approaches in procedures for European legislation are not based on experimental data on dermal exposures in workplaces because these are lacking. A large project, with four interrelated work parts, was funded by the European Commission (DG Research) in order to overcome large parts of this problem. The 4 year project is now in its final year and an overview is given of an important part of the project: the development of a risk assessment and risk management toolkit for dermal exposure. Five other papers in this issue deal with various aspects of this development.

Removing pesticides from the hands with a simple washing procedure using soap and water.

Crop activities lead to dermal exposure of workers to pesticides. The efficacy of hand washing as a control measure is unknown. The efficacy of water and soap was studied for some pesticides and exposure situations. Pre-washing contamination levels in field studies were calculated from foliar residues by models using transfer factors. Between 24.5% and 50.7% of the calculated prewashing contamination was removed in two field studies with three pesticides, with coefficients of variation between 43% and 72%. In a human volunteer study, on average 45.8% and 85.7% was removed for two pesticides (coefficients of variation 6% and 7%). No influence of 'washing vigour' was found and efficacy did not depend on pre-washing contamination levels. The combination of field studies and laboratory experiments was successful, partly compensating for weaknesses in both approaches.

A proposal for evaluation of exposure data.

There is a growing need for transparency concerning ways in which existing exposure data are weighted for their relative value and quality. Currently, this evaluation is largely subjective and is dependent on the quality of the judgement of the individual assessor or expert group. In this paper some general guidelines are presented for a quality assessment procedure. Such a predetermined procedure potentially enhances the consistency among different assessors and assessments and facilitates harmonization of assessment procedures. The guidelines are presented in the context of a decision tree with four decision rules for data quality, i.e. 'availability of occupational hygiene information', 'variability and precision issues', 'internal validity' and 'external validity'. These methodological issues are considered to be the most important aspects of data quality and will be discussed in this paper. The decision tree eventually results in three quality classes, i.e. exposure data providing sufficient information, supplementary information and data which should be excluded from the exposure assessment process. The guidelines should not be used in a rigid manner but have to be interpreted in the light of the particular circumstances and purposes of the assessment.