This work aimed at improving the empirical database of time (i.e., exposure duration), interspecies and intraspecies extrapolation when deriving occupational exposure limits (OELs). For each extrapolation step, a distribution was derived, which can be used to model the associated uncertainties. For time and interspecies extrapolation, distributions of ratios of dose descriptors were derived from studies of different length or species. National Toxicology Program (NTP) study data were manually assessed, and data from REACH (Registration, Evaluation and Authorisation of Chemicals) registration dossiers were evaluated semi‐automatically. Intraspecies extrapolation was investigated by compiling published studies on human toxicokinetic and toxicodynamic variability. A new database was established for toxicokinetic differences in interindividual susceptibility, including many inhalation studies. Using NTP data produced more reliable results than using REACH data. The geometric mean (GM) for time extrapolation subacute/chronic agreed with previous evaluations (GM = 4.11), whereas the GM for subchronic/chronic extrapolation was slightly higher (GM = 2.93) than the GMs found by others. No significant differences were observed between systemically and locally acting substances. Observed interspecies differences confirmed the suitability of allometric scaling, with the derived distribution describing remaining uncertainty. Distributions of intraspecies variability at the 1% and 5% incidence level had medians of 7.25 and 3.56, respectively. When compared with assessment factors (AFs) currently used in the EU, probabilities that these AFs are protective enough span a wide range from 10% to 95%, depending on the extrapolation step. These results help to select AFs in a transparent and informed way and, by allowing to compare protection levels achieved, to harmonise methods for deriving OELs.

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Frameworks for deriving occupational exposure limits (OELs) and OEL‐analogue values (such as derived‐no‐effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.

Evaluating chemical exposures from consumer products is an essential part of chemical safety assessments under REACH and may also be important to demonstrate compliance with consumer product legislation. Modelling of consumer exposure needs input information on the substance (e.g. vapour pressure), the product(s) containing the substance (e.g. concentration) and on consumer behaviour (e.g. use frequency and amount of product used). This feasibility study in Germany investigated methods for conducting a consumer survey in order to identify and retrieve information on frequency, duration, use amounts and use conditions for six example product types (four mixtures, two articles): hand dishwashing liquid, cockpit spray, fillers, paints and lacquers, shoes made of rubber or plastic, and ball-pens/pencils. Retrospective questionnaire methods (Consumer Product Questionnaire (CPQ), and Recall-Foresight Questionnaire (RFQ)) as well as protocol methods (written reporting by participants and video documentation) were used. A combination of retrospective questionnaire and written protocol methods was identified to provide valid information in a resource-efficient way. Relevant information, which can readily be used in exposure modelling, was obtained for all parameters and product types investigated. Based on the observations in this feasibility study, recommendations are given for designing a large consumer survey.

It was the scope of this project to collate, compile and summarise the scientific literature on the toxicity of methyl mercury, inorganic mercury and total mercury in humans and experimental animals published since 2002 and not evaluated in former JECFA risk assessments. Epidemiological data on MeHg toxicity confirmed former findings on an association between prenatal exposure and developmental neurotoxicity. Recent findings also support an influence of methyl mercury on the cardiovascular and immune system. Existing epidemiological data reveal several shortcomings limiting their suitability for risk assessment. Developmental neurotoxicity seems to be the most critical effect of MeHg in animals. A LOAEL of 0.01 mg/kg b.w. per day has been reported in young mice for locomotor activity exposed in utero. Rats seem to be less sensitive towards this endpoint: a NOAEL of 0.04 mg/kg b.w. per day has been reported in this species for locomotor activity. Systemic effects other than neurotoxicity have been mostly observed at higher doses than those producing neurotoxicity. No qualified epidemiological data appropriate for the evaluation of the toxicity of inorganic mercury after oral intake have been identified due to several limitations of the studies, e.g. small study group, insufficient control for confounders, inadequate exposure assessment. Toxicological studies in experimental animals widely confirmed former findings with respect to the target organs (neuro-, liver-, kidney-, immune-and reproductive toxicity, oxidative stress). The animal studies indicate that there might be relevant toxicological effects (developmental toxicity, liver toxicity) of inorganic mercury at dose levels similar or below the BMDL 10 value used for the derivation of the existing PTWI. However, due to some limitations of the studies no final conclusions can be drawn from these studies and the findings need further confirmation.