Towards a more effective REACH legislation in protecting human health.

There is growing evidence indicating the substantial contribution of man-made products to an increase in the risk of diseases of civilization. In this article, the Belgian Scientific Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Committee gives a critical view on the working of REACH. The current regulatory framework needs to further evolve taking into account data generated using modern science and technology. There is a need for improved assessment process not only before but also after entering the market. Objectivity, transparency, and the follow-up after market access can be optimized. Additionally, no guidance documents exist for regulation of mixture effects. Further, the lengthiness before regulatory action is a big concern. Decision-making often takes several years leading to uncertainties for both producers and end users. A first proposed improvement is the implementation of independent toxicity testing, to assure objectivity, transparency, and check and improve compliance. A "no data, no market" principle could prevent access of hazardous chemicals to the market. Additionally, the introduction of novel testing could improve information on endpoints such as endocrine disrupting abilities, neurotoxicity, and immunotoxicity. An adapted regulatory framework that integrates data from different sources and comparing the outputs with estimates of exposure is required. Fast toxicology battery testing and toxicokinetic testing could improve speed of decision-making. Hereby, several improvements have been proposed that could improve the current REACH legislation.

Assessment of human exposure to environmental sources of lead arising from the lead battery manufacturing and recycling sector in Europe: demonstration of a tiered approach in a case study.

BACKGROUND: Standard approaches for the assessment of Man via the Environment exposure are designed to be conservative. However, propagating these exposures into health impact assessment might lead to questionable socio-economic costs. OBJECTIVE: The objective of this study was to develop a novel tiered modelling approach to assess human exposure to lead (Pb) via the environment. METHOD: The approach starts in Tier 1 from EUSES modelling approach, modified with metal specific transfer factors. The generic Tier 2 approach uses the higher tier model GPM for air quality, and dietary exposure modelling based on EFSA's Comprehensive Food Database, in combination with crop specific transfer factors. Tier 3 considers additional site-specific information such as proximity of inhabitants and agricultural activities in relation to industrial sites. RESULTS: This tiered modelling approach was applied to a case study of 50 lead battery manufacturing and recycling sites across Europe. Data sets from general population human biomonitoring studies were used to compare the predicted additional bioburden of Pb resulting from lead battery manufacturing and recycling. The higher tier assessments were able to demonstrate a >20-fold reduction in modelled Pb exposure compared to default assumptions made in Tier 1. SIGNIFICANCE: Leading to better estimates for socio-economic costs in health impact assessment.

An in vitro air-liquid interface inhalation platform for petroleum substances and constituents.

The goal is to optimize and show the validity of an in vitro method for inhalation testing of petroleum substances and their constituents at the air-liquid interface (ALI). The approach is demonstrated in a pilot study with ethylbenzene (EB), a mono-constituent petroleum substance, using a human alveolar epithelial cell line model. This included the development and validation of a generation facility to obtain EB vapors and the optimization of an exposure system for a negative control (clean air, CA), positive control (nitrogen dioxide), and EB vapors. The optimal settings for the VITROCELL® 24/48 system were defined. Cytotoxicity, cell viability, inflammation, and oxidative stress were assessed in A549 after exposure to EB vapors. A concentration-dependent significant decrease in mean cell viability was observed after exposure, which was confirmed by a cytotoxicity test. The oxidative stress marker superoxide dismutase 2 was sig­nificantly increased, but no concentration-response was observed. A concentration-dependent significant increase in pro-inflammatory markers C-C motif chemokine ligand 2, interleukin (IL)6, and IL8 was observed for EB-exposed A549 cells compared to CA. The data demonstrated consistency between in vivo air concentrations at which adverse respi­ratory effects were observed and ALI-concentrations affecting cell viability, provided that the actual measured in vitro delivery efficiency of the compound was considered. It can be concluded that extrapolating in vitro air concentrations (adjusted for delivery efficiency and absorption characteristics and applied for testing cell viability) to simulate in vivo air concentrations may be a promising method to screen for acute inhalation toxicity.

"Establishing target and intervention guidance values for indoor air in dwellings and publicly accessible buildings: The Flemish approach".

Indoor air quality has been recognized by the Flemish authorities as an important policy field in view of protection of public health. In 2018, the revised Flemish Indoor Air Decree (Belgisch Staatsblad, 2018), entered into force in Flanders and is applicable for dwellings and publicly accessible buildings (PAB). The Decree is based on three pillars, 1) creating awareness on the importance of good indoor air quality for health, 2) a service for indoor air dwelling examination in case of health complaints that are likely provoked by bad indoor air, and 3) target and intervention guidance values for chemical, physical and biotic factors in the indoor environment. The target guidance values are set up as a measurable concentration of a chemical, physical or biotic factor in the indoor environment corresponding to a quality level which should be achieved as much as possible. For chemical factors, this level corresponds to a concentration where negative impact on health of the occupants due to the indoor environment is not expected. An intervention guidance value is a measurable concentration of a chemical, physical or biotic factor in the indoor environment requiring a remediation action because the concentrations might provoke a health risk for the occupants of the indoor environment. Target and intervention guidance values for indoor air in Flanders have been established for 23 substances, mainly Volatile Organic Compounds (VOCs), NO2, PM2.5 and asbestos. The indoor air target and intervention guidance values for these substances are based on chronic exposure since they are designed to be health protective for prolonged use of the indoor environments by the occupants, including vulnerable populations. Both a threshold-based approach, and specific for carcinogenic substances, a non-threshold-based approach is included. In this paper, we provide an overview of the methods for establishing the indoor air target and intervention guidance values for substances in the Flemish Indoor Air Decree along with the resulting values.

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.

Determination of contamination pathways of phthalates in food products sold on the Belgian market.

As numerous studies have indicated that food ingestion is the most important exposure pathway to several phthalates, this study aimed to determine possible contamination pathways of phthalates in food products sold on the Belgian market. To do this, concentrations of eight phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP), dicyclohexyl phthalate (DCHP), di(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP)) were determined in 591 foods and 30 packaging materials. In general, the four most prominent phthalates in Belgian food products were DEHP, DiBP, DnBP and BBP. Special attention was given to the origin of these phthalates in bread, since high phthalate concentrations (especially DEHP) were determined in this frequently consumed food product. Phthalates seemed to occur in Belgian bread samples due to the use of contaminated ingredients (i.e. use of contaminated flour) as well as due to migration from phthalate containing contact materials used during production (e.g. coated baking trays). Also the results of the conducted concentration profiles of apple, bread, salami and two cheese types revealed the important role of processing - and not packaging - on phthalate contents in foods.

Hazard property classification of waste according to the recent propositions of the EC using different methods.

Hazard classification of waste is a necessity, but the hazard properties (named "H" and soon "HP") are still not all defined in a practical and operational manner at EU level. Following discussion of subsequent draft proposals from the Commission there is still no final decision. Methods to implement the proposals have recently been proposed: tests methods for physical risks, test batteries for aquatic and terrestrial ecotoxicity, an analytical package for exhaustive determination of organic substances and mineral elements, surrogate methods for the speciation of mineral elements in mineral substances in waste, and calculation methods for human toxicity and ecotoxicity with M factors. In this paper the different proposed methods have been applied to a large assortment of solid and liquid wastes (>100). Data for 45 wastes - documented with extensive chemical analysis and flammability test - were assessed in terms of the different HP criteria and results were compared to LoW for lack of an independent classification. For most waste streams the classification matches with the designation provided in the LoW. This indicates that the criteria used by LoW are similar to the HP limit values. This data set showed HP 14 'Ecotoxic chronic' is the most discriminating HP. All wastes classified as acute ecotoxic are also chronic ecotoxic and the assessment of acute ecotoxicity separately is therefore not needed. The high number of HP 14 classified wastes is due to the very low limit values when stringent M factors are applied to total concentrations (worst case method). With M factor set to 1 the classification method is not sufficiently discriminating between hazardous and non-hazardous materials. The second most frequent hazard is HP 7 'Carcinogenic'. The third most frequent hazard is HP 10 'Toxic for reproduction' and the fourth most frequent hazard is HP 4 "Irritant - skin irritation and eye damage". In a stepwise approach, it seems relevant to assess HP 14 first, then, if the waste is not classified as hazardous, to assess subsequently HP 7, HP 10 and HP 4, and then if still not classified as hazardous, to assess the remaining properties. The elements triggering the HP 14 classification in order of importance are Zn, Cu, Pb, Cr, Cd and Hg. Progress in the speciation of Zn and Cu is essential for HP 14. Organics were quantified by the proposed method (AFNOR XP X30-489) and need no speciation. Organics can contribute significantly to intrinsic toxicity in many waste materials, but they are only of minor importance for the assessment of HP 14 as the metal concentrations are the main HP 14 classifiers. Organic compounds are however responsible for other toxicological characteristics (hormone disturbance, genotoxicity, reprotoxicity…) and shall be taken into account when the waste is not HP 14 classified.

Environmental hazard and risk characterisation of petroleum substances: a guided "walking tour" of petroleum hydrocarbons.

Petroleum substances are used in large quantities, primarily as fuels. They are complex mixtures whose major constituents are hydrocarbons derived from crude oil by distillation and fractionation. Determining the complete molecular composition of petroleum and its refined products is not feasible with current analytical techniques because of the huge number of molecular components. This complex nature of petroleum products, with their varied number of constituents, all of them exhibiting different fate and effect characteristics, merits a dedicated hazard and risk assessment approach. From a regulatory perspective they pose a great challenge in a number of REACH processes, in particular in the context of dossier and substance evaluation but also for priority setting activities. In order to facilitate the performance of hazard and risk assessment for petroleum substances the European oil company association, CONCAWE, has developed the PETROTOX and PETRORISK spreadsheet models. Since the exact composition of many petroleum products is not known, an underlying assumption of the PETROTOX and PETRORISK tools is that the behaviour and fate of a total petroleum substance can be simulated based on the physical-chemical properties of representative structures mapped to hydrocarbon blocks (HBs) and on the relative share of each HB in the total mass of the product. To assess how differing chemical compositions affect the simulated chemical fate and toxicity of hydrocarbon mixtures, a series of model simulations were run using an artificial petroleum substance, containing 386 (PETROTOX) or 160 (PETRORISK) HBs belonging to different chemical classes and molecular weight ranges, but with equal mass assigned to each of them. To this artificial petroleum substance a guided series of subsequent modifications in mass allocation to a delineated number of HBs belonging to different chemical classes and carbon ranges was performed, in what we perceived as a guided "walking tour" through the chemical space of petroleum substances. We show that the PETROTOX and PETRORISK predictions reflect changes in mass distribution introduced to selected HBs by affecting hazard and risk estimates in correspondence with what is expected based on physical-chemical properties of individual constituents in the corresponding HBs.

Phthalates dietary exposure and food sources for Belgian preschool children and adults.

Numerous studies have indicated that for phthalates, the intake of contaminated foods is the most important exposure pathway for the general population. Up to now, data on dietary phthalate intake are scarce and - to the authors' knowledge - not available for the Belgian population. Therefore, the purpose of this study was: (1) to assess the long-term intake of the Belgian population for eight phthalates considering different exposure scenarios (benzylbutyl phthalate (BBP); di-n-butyl phthalate (DnBP); dicyclohexyl phthalate (DCHP); di(2-ethylhexyl) phthalate (DEHP); diethyl phthalate (DEP); diisobutyl phthalate (DiBP); dimethyl phthalate (DMP), di-n-octyl phthalate (DnOP)); (2) to evaluate the intake of BBP, DnBP, DEP and DEHP against tolerable daily intake (TDI) values; and (3) to assess the contribution of the different food groups to the phthalate intake. The intake assessment was performed using two Belgian food consumption databases, one with consumption data of preschool children (2.5 to 6.5 years old) and another of adults (≥15 years old), combined with a database of phthalate concentrations measured in over 550 food products sold on the Belgian market. Phthalate intake was calculated using the 'Monte Carlo Risk Assessment' programme (MCRA 7.0). The intake of DEHP was the highest, followed by DiBP. The intake of BBP, DnBP and DEP was far below the TDI for both children and adults. However, for DEHP, the 99th percentile of the intake distribution of preschoolers in the worst case exposure scenario was equal to 80% of the TDI, respectively. This is not negligible, since other exposure routes of DEHP exist for children as well (e.g. mouthing of toys). Bread was the most important contributor to the DEHP intake and this may deserve further exploration, since the origin of this phthalate in bread remains unclear.