Outline on risk assessment programme of existing substances in the European Union

Various programmes have been developed by national and international organisations to improve chemical safety of existing substances. The European Union Programme came into force on 4 June 1993. This programme gives a legal requirement that the manufacturer or the importer has to deliver data on substances produced or imported. The risk assessment process in the EU provides that every member state formally selects priority substances. To perform the risk characterisation for a priority substance, exposure assessment and the dose (concentration)-response (effect) assessment are conducted. Comparing the information on exposure to the effects identified by a hazard identification of the substance the risk assessor has to decide whether there is or there is no need for further information or testing or whether there is need for limiting the risks. The draft risk assessment report is sent to the OECD as European contribution to the programme on existing substances for discussion with OECD-member countries. A final decision on the substance is performed by the member states of the European Union.     

Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: Ethylene oxide

An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO.     

Risk assessment of local dermal effects and skin sensitisation under the EU Chemicals Regulation REACH: a proposal for a qualitative, exposure scenario specific, approach

Within the framework of REACH, an assessment regarding local dermal effects and skin sensitisation should be performed for substances. Quantitative hazard information for these effects is often not available. Furthermore, it is difficult to relate the way in which animals are exposed in dermal toxicity studies directly to dermal exposure in practice. In the absence of quantitative information, a qualitative assessment for dermal effects is the most reasonable option. The qualitative approach as proposed in the REACH guidance recommends only general risk management measures (RMM) for three categories with a low, moderate and high identified hazard, without specifying which RMM are needed for a specific exposure scenario. We propose to differentiate frequency of exposure based on differences in activities and to compare measured and estimated local skin exposure levels with rules of thumb for evaluation of control of risks per hazard category. For workers, specific RMM regimes are assigned to each combination of hazard category and process category (PROC). For consumers, a strategy in which RMM are arranged from product-integrated measures to the use of personal protective equipment (PPE) is presented. Our approach may be transferred into automated assessment tools like Chesar and CEFIC GES.     

An assessment of dietary exposure to glyphosate using refined deterministic and probabilistic methods

Glyphosate is a herbicide used to control broad-leaved weeds. Some uses of glyphosate in crop production can lead to residues of the active substance and related metabolites in food. This paper uses data on residue levels, processing information and consumption patterns, to assess theoretical lifetime dietary exposure to glyphosate.Initial estimates were made assuming exposure to the highest permitted residue levels in foods. These intakes were then refined using median residue levels from trials, processing information, and monitoring data to achieve a more realistic estimate of exposure. Estimates were made using deterministic and probabilistic methods. Exposures were compared to the acceptable daily intake (ADI)—the amount of a substance that can be consumed daily without an appreciable health risk.Refined deterministic intakes for all consumers were at or below 2.1% of the ADI. Variations were due to cultural differences in consumption patterns and the level of aggregation of the dietary information in calculation models, which allows refinements for processing. Probabilistic exposure estimates ranged from 0.03% to 0.90% of the ADI, depending on whether optimistic or pessimistic assumptions were made in the calculations. Additional refinements would be possible if further data on processing and from residues monitoring programmes were available.     

Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole

The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1′-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL₁₀) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL₁₀ value of 3 times the BMDL₁₀ for safrole. Based on an estimated BMDL₁₀ for apiol of 5.7–15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10⁻⁵ mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000–385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.