Scientific governance and the process for exposure scenario development in REACH.

The primary process established by the European Commission to address the science needed to define key REACH concepts and to help rationally implement REACH's ambitions is enshrined in a series of activities known as the REACH Implementation Projects (RIPs). These are projects that aim to define the methodology that could be used, and present the basis for guidance on the actual principles and procedures that may be (are proposed to be) followed in the development of the required documentation that ensures the safe use of chemicals. In order to develop soundly based and equitable regulation, it is necessary that science governance using established and accepted scientific principles must take a leading role. The extent to which such governance is embraced will be determined by many factors, but notably the process adopted to enable scientific discussion to take place. This article addresses the issues of science as they have impacted on the exemplification of the Exposure Scenario concept under REACH. The current RIP activities have created a non-adversarial process in which the key stakeholders are able to discuss the key REACH challenges. But the RIP activities will be finalised before REACH comes into force. A suitable mechanism should perhaps now be identified to ensure that this positive spirit of scientific discussion and collaboration can continue to benefit REACH and those that it serves well into the future.

From dermal exposure to internal dose.

Exposure scenarios form an essential basis for chemical risk assessment reports under the new EU chemicals regulation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). In case the dermal route of exposure is predominant, information on both exposure and dermal bioavailability is necessary for a proper risk assessment. Various methodologies exist to measure dermal exposure, providing quantitative or semiquantitative information. Although these studies may provide very specific and relevant information, it should be realized that case by case in-depth exposure assessment would be a very expensive process. Dermal bioavailability data are most often obtained from in vitro studies or animal experiments. For the design of studies, which generate data relevant for chemical risk assessment, detailed information on the exposure conditions is crucial (skin surface exposed, exposure duration, dose and physical state of the chemical). Results from non-testing methods for skin absorption, such as (Q)SARs, have been used only to a very limited extent for regulatory purposes. Suggestions are made in order to extend the use these methods to dermal risk assessment of chemical substances, thereby improving the practicability of REACH.

Occupational exposure during application and removal of antifouling paints.

Exposure data on biocides are relatively rare in published literature, especially for secondary exposure. This is also the case for antifouling exposure. Therefore, a field study was carried out measuring exposure to antifouling paints. Both primary exposure (rolling and spraying) and secondary exposure (during sand blasting) were studied. Exposure during rolling was measured in boatyards where paints containing dichlofluanid (DCF) were applied. Spraying was measured in dockyards (larger than boatyards) where paints containing copper were applied. Furthermore, during sand blasting the removal of old paint layers containing copper was measured. A total of 54 datasets was collected, both for inhalation and dermal exposure data. For paint and stripped paint bulk analyses were performed. The following values are all arithmetic means of the datasets. Inhalation of copper amounted to 3 mg m-3 during spraying and to 0.8 mg m-3 during sand blasting. Potential body exposure loading amounted to 272 mg h-1 copper during spraying and 33 mg h-1 during sand blasting. For dichlofluanid the inhalation exposure loading was 0.14 mg m-3 during rolling, whereas the potential body exposure loading was 267 mg h-1 and potential hand exposure loading 277 mg h-1. The results for primary exposure compare well to the very few public data available. For the secondary exposure (sand blasting) no comparable data were available. The present study shows that the exposure loading should be considered more extensively, including applicable protective gear. In this light the findings for the potmen during sand blasting suggest that personal protective equipment should be (re)considered carefully.

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.

An experimental study to investigate the feasibility to classify paints according to neurotoxicological risks: occupational air requirement (OAR) and indoor use of alkyd paints.

The concept of occupational air requirement (OAR), representing the quantity of air required to dilute the vapor concentration in the work environment resulting from 1 l product to a concentration below the occupational exposure limit (OEL), was considered to have potential to discriminate between paints that can and cannot be used safely. The OAR is a simple algorithm with the concentration of volatile organic compound (VOC) in the paint, a discrete evaporation factor and the neurotoxicological effects-based OEL. Conceptually, OAR categories of paints for construction and maintenance applications could be identified that can be applied manually without exceeding OELs with no appreciable room ventilation. Five painters volunteered in an exposure study aimed at testing the OAR approach in practice. Total exposure to VOC was assessed in 30 experiments during the application of 0.5 l of paint in a defined 'standard indoor paint job'. Fifteen paints were prepared, reflecting differences in solvents (percentage, volatility, toxicity) with a range of OAR levels from 43 to 819 m(3)/l. Exposure was assessed by personal air sampling (PAS). In addition, real-time air monitoring was performed. All tests were conducted at minimum ventilation rate (< or=0.33 h(-1)). PAS results were expressed as percentage of the nominal OEL and ranged from 8 to 93% for high solids and from 38 to 168% for conventional paints. In general, higher VOC contents resulted in higher exposure. High volatile paints showed a statistically significant faster increase of VOC concentration with time compared with paints containing low volatile solvents. A significant relationship between OAR value and exposure was observed (R(2) = 0.73). The experiments indicate that OAR-based classification of paints predicts and discriminates risk levels for exposure to neurotoxic paint-solvents in indoor painting fairly well.

Dermal absorption of chlorpyrifos in human volunteers.

OBJECTIVE: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). METHODS: Two dermal, single, doses of CPF were applied in two study groups (A and B) each comprising three apparently healthy male volunteers who gave their written informed consent. The clinical part of the study was conducted in compliance with the ICH Guideline and the EC principles of good clinical practice (GCP). An approximately 0.5 ml dilution of CPF in ethanol was applied to an area of approximately 100 cm(2) of the volar aspect of the forearm, resulting in doses of either 5 mg (A) or 15 mg (B) of CPF per study subject. Duration of dermal exposure was 4 h, after which the non-absorbed fraction was washed off. The following samples were collected at pre-determined intervals for the determination of either CPF or its metabolite TCP: dosing solutions, wash-off fractions and urine samples collected up to 120 h after dosing. RESULTS: A relatively large fraction of CPF (42%-67% of the applied dose) was washed off from the exposed skin area. Application of either 5 mg (A) or 15 mg CPF (B) resulted in the total urinary excretion of 131.8 microg (A) or 115.6 microg (B) of TCP 120 h after dosing. This indicated that 4.3% of the applied dose has been absorbed (A), while in group (B) no significant increase in urinary TCP (115.6 microg) was established. The latter indicates that an increase in the dermal dose at a fixed area does not increase absorption, which suggests that the percutaneous penetration rate was constant. Further, it was observed that the clearance of CPF by the body was not completed within 120 h, suggesting that CPF or TCP was retained by the skin and/or accumulated in the body. A mean elimination half-life of 41 h was established. CONCLUSION: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects.

Reliability of a semi-quantitative method for dermal exposure assessment (DREAM).

Valid and reliable semi-quantitative dermal exposure assessment methods for epidemiological research and for occupational hygiene practice, applicable for different chemical agents, are practically nonexistent. The aim of this study was to assess the reliability of a recently developed semi-quantitative dermal exposure assessment method (DREAM) by (i) studying inter-observer agreement, (ii) assessing the effect of individual observers on dermal exposure estimates for different tasks, and (iii) comparing inter-observer agreement for ranking of body parts according to their exposure level. Four studies were performed in which a total of 29 observers (mainly occupational hygienists) were asked to fill in DREAM while performing side-by-side observations for different tasks, comprising dermal exposures to liquids, solids, and vapors. Intra-class correlation coefficients ranged from 0.68 to 0.87 for total dermal exposure estimates, indicating good to excellent inter-observer agreement. The effects of individual observers on task estimates were estimated using a linear mixed effect model with logged DREAM estimates as explanatory variable; "task", "company/department", and the interaction of "task" and "company/department" as fixed effects; and "observer" as a random effect. Geometric mean (GM) dermal exposure estimates for different tasks were estimated by taking the exponent of the predicted betas for the tasks. By taking the exponent of the predicted observer's intercept (exp(omega i)), a multiplier (M(O)) was estimated for each observer. The effects of individual observers on task estimates were relatively small, as the maximum predicted mean observers' multiplier was only a factor 2, while predicted GMs of dermal exposure estimates for tasks ranged from 0 to 1226, and none of the predicted individual observers' multipliers differed significantly from 1 (t-test alpha = 0.05). Inter-observer agreement for ranking of dermal exposure of nine body parts was moderate to good, as median values of Spearman correlation coefficients for pairs of observers ranged from 0.29 to 0.93. DREAM provides reproducible results for a broad range of tasks with dermal exposures to liquids, solids, as well as vapors. DREAM appears to offer a useful advance for estimations of dermal exposure both for epidemiological research and for occupational hygiene practice.

Variability of task-based dermal exposure measurements from a variety of workplaces.

INTRODUCTION: The RISKOFDERM project collected task-based estimates of potential dermal exposure from a wide range of industries and services from around Europe. A formal statistical analysis was carried out to explore the main components of variability in dermal exposure levels. The central research question was to what extent dermal exposure levels could be explained by generic grouping variables like 'exposure scenarios' and 'dermal exposure operation units' (DEOs) (grouping of scenarios on the basis of similarity in exposure patterns). METHODS: Mixed effect linear models were used to estimate variance components of potential dermal exposure for DEOs or scenarios and for factories, workers and time. In addition within- and between-worker variance components were estimated for single groups of workers performing a specific scenario in a specific location with potential dermal exposure to a specific agent. RESULTS: Variability in potential dermal exposure is very large. Differences in geometric mean potential dermal exposure can range over 3-5 orders of magnitude both for DEOs and scenarios. The range depends on how dermal exposure is expressed (amount or rate). Both DEOs and scenarios explain a considerable amount of variability, but large differences in dermal exposure still existed within DEOs and scenarios. In contrast, between-worker variability in mean potential dermal exposure is minimal for a given scenario carried out within a specific location with exposure to a particular agent. Temporal variability, however, is considerable, most likely due to the event-based nature of the dermal exposure process. CONCLUSION: The classification of tasks in DEOs and scenarios has proven to be useful since large differences in average dermal exposure estimates exist between DEOs and between scenarios. However, large differences also exist between scenarios within a DEO and even within a scenario. These differences are governed by local conditions determined by the actual handling of the agent, the agent's physical and chemical properties, its intrinsic toxicity, control measures taken and training and attitude of workers. For the time being, actual dermal exposure measurements and a better understanding of actual determinants of dermal exposure seem to be a necessity in order to evaluate dermal exposure hazards properly.

Dermal exposure during filling, loading and brushing with products containing 2-(2-butoxyethoxy)ethanol.

INTRODUCTION: Limited quantitative information is available on dermal exposure to chemicals during various industrial activities. Therefore, within the scope of the EU-funded RISKOFDERM project, potential dermal exposure was measured during three different tasks: filling, loading and brushing. DEGBE (2-(2-butoxyethoxy)ethanol) was used as a 'marker' substance to determine dermal exposure to the products that workers were handling. METHODS: Potential whole body exposure was measured using self-constructed cotton sampling pads on 11 body locations. Cotton gloves were used to determine the contamination of both hands. Bulk samples were collected to determine the concentration of DEGBE so as to be able to calculate exposure to the handled product. RESULTS: A total of 94 task-based measurements were performed, 30 on filling, 28 on loading and 36 on brushing, which resulted in potential dermal hand exposure to the handled product of 4.1-18 269 mg [geometric mean (GM) 555.4, n = 30], 0.3-27745 mg (GM 217.0, n = 28) and 11.3-733.3 mg (GM 98.4, n = 24) for each of the scenarios, respectively. Potential whole body exposure to the product during filling and loading ranged from 1.67 to 155.0 (GM 15.2, n = 9) and

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.

DREAM: a method for semi-quantitative dermal exposure assessment.

This paper describes a new method (DREAM) for structured, semi-quantitative dermal exposure assessment for chemical or biological agents that can be used in occupational hygiene or epidemiology. It is anticipated that DREAM could serve as an initial assessment of dermal exposure, amongst others, resulting in a ranking of tasks and subsequently jobs. DREAM consists of an inventory and evaluation part. Two examples of dermal exposure of workers of a car-construction company show that DREAM characterizes tasks and gives insight into exposure mechanisms, forming a basis for systematic exposure reduction. DREAM supplies estimates for exposure levels on the outside clothing layer as well as on skin, and provides insight into the distribution of dermal exposure over the body. Together with the ranking of tasks and people, this provides information for measurement strategies and helps to determine who, where and what to measure. In addition to dermal exposure assessment, the systematic description of dermal exposure pathways helps to prioritize and determine most adequate measurement strategies and methods. DREAM could be a promising approach for structured, semi-quantitative, dermal exposure assessment.