Substances Of Very High Concern Research Articles

Food contact substances and chemicals of concern: a comparison of inventories

Food contact materials (FCMs) are intended to be in contact with food during production, handling or storage. They are one possible source of food contamination, because chemicals may migrate from the material into the food. More than 6000 FCM substances appear on regulatory or non-regulatory lists. Some of these substances have been linked to chronic diseases, whilst many others lack (sufficient) toxicological evaluation. The aim of this study was the identification of known FCM substances that are also considered to be chemicals of concern (COCs). The investigation was based on the following three FCM lists: (1) the 2013 Pew Charitable Trusts database of direct and indirect food additives legally used in the United States (or Pew for short), (2) the current European Union-wide positive list for plastic FCMs (or Union for short), and (3) the 2011 non-plastics FCM substances database published by EFSA (or ESCO for short). These three lists of food contact substances (Pew, Union, ESCO lists) were compared with the Substitute It Now! (SIN) list 2.1, which includes chemicals fulfilling the criteria listed in article 57 of Regulation (EC) No. 1907/2006 (REACH), and the TEDX database on endocrine-disrupting chemicals. A total of 175 chemicals used in FCMs were identified as COCs. Fifty-four substances present on the SIN list 2.1 were also found on the Union and/or ESCO lists. Twenty-one of those 54 substances are candidates for Substances of Very High Concern (SVHC), and six of these 21 are listed on Annex XIV and intended for phase-out under REACH. In conclusion, COCs used in FCMs were identified and information about their applications, regulatory status and potential hazards was included.

Consideration of criteria required for assignment of a (skin) sensitiser a substance of very high concern (SVHC) under the REACH regulation

The identification, characterisation, risk assessment and risk management of materials that cause allergic sensitisation is an important requirement for human health protection. It has been proposed that for some chemical and protein allergens, and in particular for those that cause sensitisation of the respiratory tract (associated with occupational asthma), it may be appropriate to regard them as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). We have argued previously that categorisation of sensitising agents as SVHC should be used only in exceptional circumstances. In the present article, the subject of SVHC is addressed from another perspective. Here the information that would be required to provide a compelling case for categorisation of a skin sensitising substance as a SVHC is considered. Three skin sensitising chemicals have been identified to serve as working examples. These are chromate, a potent contact allergen, and the skin sensitisers formaldehyde and isoeugenol. The key criterion influencing the decision regarding a skin sensitiser being categorised as SVHC is the extent to which impacts on the quality of life are reversible. Consequently, SVHC categorisation for skin sensitising chemicals should be used only in exceptional circumstances.

Semipolar polycyclic aromatic compounds: Identification of 15 priority substances and the need for regulatory steps under REACH regulation

Semipolar polycyclic aromatic compounds (sPACs) are frequently found in association with homocyclic polycyclic aromatic hydrocarbons (PAHs) in substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) from coal or crude oil and products derived thereof. However, major information deficiencies exist with regard to their prevalence and their toxicological and ecotoxicological potential, persistency, and bioaccumulation characteristics. Therefore, in this work, the environmental concern and relevance of sPACs was addressed in a general, stepwise approach. First, a large list of sPACs was collected and subsequently refined by assessing their persistence, bioaccumulation, and toxicity (PBT) properties by quantitative structure-activity relationship (QSAR) methods and their relevance by determining their respective frequency of occurrence. In this way, 15 priority sPACs were identified. These 15 priority sPACs were further characterized in detail with respect to their ecotoxicological properties, environmental behavior, carcinogenicity, and genotoxicity attributes. All of these 15 substances were quantified in distillate or product samples. In the next step, some principles for nomination of indicator substances, indicative for the overall content of sPACs, are derived. Data gaps on ecotoxicological endpoints preclude final conclusions, but the respective necessary supplemental tests were identified. Five of the 15 sPACs were tentatively characterized as potential substances of very high concern (SVHC) for the environment. The overall results of this study also clearly show that regulatory risk management of homocyclic PAHs within the European Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) does not address the environmental concern created by sPACs within UVCBs from coal or crude oil. The study proves the need for additional regulatory steps under REACH and suggests indicator substances for their enforcement.

Categorisation of protein respiratory allergens: The case of Subtilisin

Characterisation of the relative sensitizing potency of protein and chemical allergens remains challenging, particularly for materials causing allergic sensitization of the respiratory tract. There nevertheless remains an appetite, for priority setting and risk management, to develop paradigms that distinguish between individual respiratory allergens according to perceptions of the hazards and risks posed to human health. One manifestation thereof is recent listing of certain respiratory allergens as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). Although priority setting is a laudable ambition, it is important the process is predicated on evidence-based criteria that are transparent, understood and owned. The danger is that in the absence of rigorous criteria unwanted precedents can be created, and confidence in the process is compromised. A default categorisation of sensitisers as SVHC requiring assessment under the authorisation process is not desirable. We therefore consider here the value and limitations of selective assignment of certain respiratory allergens as being SVHC. The difficulties of sustaining such designations in a sound and equitable way is discussed in the context of the challenges that exist with respect to assessment of potency, and information available regarding the effectiveness of exposure-based risk management.

Determination of tris (2-chloroethyl) phosphate in leather by gas chromatography-mass spectrometry coupled with mixed-mode sorbent solid phase extraction

Leather is one of the important exporting products to European Union (EU), and tris(2-chloroethyl) phosphate (TCEP) is a commonly used flame retardant in leather and leather products. Recently, TCEP has been classified as a kind of substance of very high concern (SVHC) by EU for its carcinogenicity and reproductive toxicity. But to date, there is not a recognized method for the determination of TCEP in leather and leather products due to the serious matrix interferences and relatively low recovery of TCEP. In this work, a home-made mixed-mode sorbent (Silica-WCX) with carboxyl and alkyl groups was tested as the sorbent of solid phase extraction (SPE) to extract TECP from leather. The results demonstrated that, making the carboxyl groups protonized under acidic condition, Silica-WCX exhibited better extraction performance towards TCEP over some frequently used commercial sorbents tested. After the optimization of the SPE conditions based on Silica-WCX, a method of gas chromatography/mass spectrometry (GC-MS) was established for the determination of TCEP in leather samples. The linear range for TCEP ranged from 0.10 to 100.0 μg/L and the limit of quantification (LOQ, S/N = 10) was 44.46 ng/kg. The recoveries of TCEP spiked in samples at varied levels were in the range of 91.45%-99.98% with the relative standard deviations (RSDs) of 4.33%-5.97%. The method is simple, sensitive and reliable for the analysis of TCEP in leather and leather products.

Polycyclic aromatic hydrocarbon levels in European catfish from the upper Po River basin

Polycyclic aromatic hydrocarbons (PAHs) are a major concern in environmental studies as many of them have been labeled as probable carcinogens by the International Agency for Research on Cancer (IARC 1983). Due to their lipophilic properties and resistance to degradation, PAHs can accumulate in organic tissue. As a consequence, alarming concentrations of these compounds have been found in many aquatic species. The European catfish (Silurus glanis) is a top food chain predator that is considered to be a reliable bio-indicator of environmental pollution. From 2009 to 2011, 54 specimens of S. glanis were captured from four different sites covering the area of the Po River basin (Northern Italy). Fish muscles were analyzed in the laboratory to determine the levels of nine PAHs, namely naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, pyrene, benz[a]anthracene, chrysene, and benz[a]pyrene (BaP), which were detected by high-performance liquid chromatography (HPLC). The total average concentration of PAHs was 26.90 ± 49.50 ng g(-1) (min 0.60, max 275.75 ng g(-1)). Analysis showed that 9.20% of the fish muscles exceeded the maximum levels of 2 ng g(-1) set for BaP by European regulations (Commission Regulation (EC), 2006). Values measured for benz[a]pyrene ranged from 0.05 to 8.20 ng g(-1) (mean 1.07 ± 1.58 ng g(-1)). Chrysene and benz[a]anthracene, both considered potential human carcinogens (PAH2), were found at levels of 4.40 and 0.05 ng g(-1) (mean values), respectively. The highest mean concentration was recorded for anthracene (12.92 ng g(-1)), which has been recently included in the list of substances of very high concern (SVHC) as reported by the European Chemicals Agency (ECHA 1-9, 2009).

Substances of very high concern: Challenge to risk management system, capability and fundamental research of chemicals in China

Enhancing environmental and health risks of the chimerically available chemicals have been revealed nowadays while their benefit to the society was significantly shown. The risk management of Substances of Very High Concern (SVHCs), the key field for reaching 2020 goal of global risk reduction strategy of chemicals, has been a main point of risk assessment and sound management of the chemicals. China will be the major area of risk management of SVHCs at a global scale in the future, based on the status of global industrial transfer and innovation development, stages of economic and social growth, and available environmental monitoring data. In the past, the China’s risk management system of chemicals laid the predominant stress on the risk controlling and emergency preplan of hazardous chemicals, and the risk management of SVHCs deficit in sound foundation of regulation and legislation oriented by its environmental and health risk. Therefore, more obstacles will be encountered in the risk management of SVHCs in China due to the lack of advanced technological renovation and corresponding experience in risk administration. The researches on strategic and systematic risk assessment of chemicals relevant to SVHCs are insufficient at present because they are less forward-looking, well organized and practicable, even though some breakthroughs on SVHCs researches, including persistent organic pollutants and heavy metal, have been already achieved.

PBT borderline chemicals under REACH

The European chemicals legislation REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) defines criteria to identify substances of very high concern (SVHC). Within these, the property combinations ‘persistent, bioaccumulative and toxic’ (PBT) and ‘very persistent and very bioaccumulative’ (vPvB) are of specific priority. In Annex XIII, the determination of SVHC by ‘weight-of-evidence’ is also underlined, e.g. elevated pollutant concentrations in biota ‘compared to levels in their surrounding environment’, which may result from long-range transport potential (LRTP). Nevertheless, LRTP is not included explicitly, although substances may represent an environmental hazard to the intrinsic value of sensitive remote regions as highlighted in the Guidance for the implementation of REACH. Here, it is also recommended to include ‘borderline cases’, i.e. substances where one or more of the P, B and T criteria are not met but an equivalent concern is given by other information, in particular LRTP. We define substances as potential borderline cases, which fail one of the criteria (vP or vB, P or B or T) that have to be evaluated to identify SVHC by less than 10% and are, at the same time, identified to show high LRTP, and apply this definition to prioritize potential SVHC out of the list of 5,306 compounds registered in 2012 under REACH. Eight compounds can be identified as vPvB and less than 2% as PBT compounds out of 1,022 organic, non-ionic substances. In addition, 13 borderline chemicals are contained in the list, which are characterized by LRTP. Three compounds fail one of the vPvB/PBT criteria by less than 10% only and show LRTP which strongly indicates that they should be considered as SVHC. Sensitivity analysis shows a rather stable classification around the arbitrarily fixed 10% value. It is concluded that several LRTP screening methods should be applied to reduce the uncertainty in LRTP determination.

Regulating Substances of Very High Concern

Regulating Substances of Very High Concern

Five years REACH

Editorial On June, 1st, we celebrated five years experience since the European REACH Regulation [1] entered into force. The experience is mainly positive: In nearly 29,000 technical dossiers for approximately 5,900 substances, registrants submitted a huge amount of information on uses, properties, hazards, toxicological and ecotoxicological effects to the European Chemicals Agency (ECHA) in Helsinki. These registrations include all substances with a manufacturing or import volume of more than 1,000 tons per year and registrant, all substances that are carcinogenic, mutagenic or toxic for reproduction which are intended to stay on the EU-market, and some more important chemicals. It was a really hard challenge for companies to meet the deadline for registration and the REACH information requirements. Although we, and also ECHA [2] are not completely satisfied with the quality of many dossiers and the way the information requirements were interpreted, we’d like to congratulate the world-wide chemical industry for managing this challenge in time. The task for authorities is to prioritise substances for regulatory activities. For ECHA this is the dossier evaluation, for Member States authorities the substance evaluation and for all authorities elaborating proposals to identify substances of very high concern (SVHC), and candidates for authorisation and restrictions. Some of these tasks are already in the beginning (e.g. substance evaluation), others are ongoing, (e.g. the identification of SVHC). By September, 1st, 84 SVHC are included in the candidate list, and 14 substances are included in Annex XIV and therefore will be subject for authorisation in future. To elaborate the proposals and to agree the measures in the Member State Committee was not an easy task – and therefore we congratulate also the Member States authorities, and especially ECHA. Reflecting five years experiences, we see options for some improvements. Among other suggestions, the most important is to strengthen the role of ECHA: As a last

Are chemicals in articles an obstacle for reaching environmental goals? — Missing links in EU chemical management

It is widely acknowledged that the management of risks associated with chemicals in articles needs to be improved. The EU environmental policy states that environmental damage should be rectified at source. It is therefore motivated that the risk management of substances in articles also takes particular consideration to those substances identified as posing a risk in different environmental compartments.The primary aim of the present study was to empirically analyze to what extent the regulation of chemicals in articles under REACH is coherent with the rules concerning chemicals in the Sewage Sludge Directive (SSD) and the Water Framework Directive (WFD). We also analyzed the chemical variation of the organic substances regulated under these legislations in relation to the most heavily used chemicals.The results show that 16 of 24 substances used in or potentially present in articles and regulated by the SSD or the WFD are also identified under REACH either as a substance of very high concern (SVHC) or subject to some restrictions. However, for these substances we conclude that there is limited coherence between the legislations, since the identification as an SVHC does not in itself encompass any use restrictions, and the restrictions in REACH are in many cases limited to a particular use, and thus all other uses are allowed.Only a minor part of chemicals in commerce is regulated and these show a chemical variation that deviates from classical legacy pollutants. This warrants new tools to identify potentially hazardous chemicals in articles. We also noted that chemicals monitored in the environment under the WFD deviate in their chemistry from the ones regulated by REACH.In summary, we argue that to obtain improved resource efficiency and a sustainable development it is necessary to minimize the input of chemicals identified as hazardous to health or the environment into articles.

Identification of substances with potential for long-range transport as possible substances of very high concern

According to the European legislation, REACH, organic compounds are considered as substances of very high concern (SVHC) if they are persistent, bioaccumulative and toxic (PBT). A substance's long-range transport potential (LRTP) may also pose a risk to remote regions. This is, however, not yet explicitly included. For identification of compounds, which are not PBT according to REACH criteria, but show LRTP, we investigated 22,438 compounds from the Canadian Domestic Substance List (CDSL). The CDSL was searched for organic, neutral compounds. Substance properties were estimated with EPI Suite v4.00. Next, the substance list was edited in two ways: (1) The half-life criterion in air for LRTP as defined in the Stockholm Convention was applied. (2) For all compounds, indicators for persistence and LRTP were calculated with the multimedia model ELPOS v2.2. Applying the half-life criterion, we identified 594 substances, which are prone to LRT but are not PBT (non-PBT-L substances). In contrast, investigations with ELPOS lead to a shorter list of 188 substances, which are non-PBT-L substances. Finally, the list was compared with potential Arctic contaminants identified in previous literature. Our results show that there is a large number of organic chemicals which would not be considered as SVHC since they are not, at the same time, persistent, bioaccumulative and toxic according to REACH criteria. Nevertheless, they show LRTP according to different screening approaches and thus a potential hazard to remote regions.

공산품 중 프탈레이트류 함유량 분석법에 관한 국내외 표준의 검증 연구

생식독성 및 내분비계 장애물질로 분류되는 프탈레이트가 근자에 유럽 신화학물질관리제도(REACH)의 허가대상 고위험성 물질(SVHC) 목록 및 유럽의 전기전자제품에 함유된 유해물질 규제인 RoHS II의 최우선 고려 물질 등으로 규제가 강화되면서 IEC TC 111에서 분석법 표준화가 진행되고 있으며 KS 개정도 이루어지고 있다. 본 고에서는 프탈레이트 분석법의 KS 개정 및 한국 NC에서 제안하여 진행되고 있는 IEC 62321에 프탈레이트 분석법을 추가함에 있어 기술적 자료로 사용될 수 있도록 현존하는 국가별 표준의 용매 추출 전처리를 비교 및 검증해 보았다. PVC (polyvinyl chloride)에서의 DEHP (diethylhexyl phthalate)의 추출 효율은 메탄올, 톨루엔, 디클로로메테인. 헥세인 순으로 46.9%에서 95.3%까지 증가하였다. DBP (dibutyl phthalate), BBP (butylbenzyl phthalate) 및 DEHP의 속슬렛을 사용한 추출 시간은 6시간이 최적임이 입증되었고, PVC, nitro cellulose, ABS (acrylonitrile butadiene styrene), and EPDM (ethylene propylene diene monomer) rubber 등의 매트리스로부터의 추출 효율도 90%~99%로 측정되었다. 용매추출에 이은 GC-MS 분석법의 검출한계는 용액 및 고분자 샘플에서 각각 0.08 ~0.3 <TEX>${\mu}g/mL$</TEX> 및 8~30 mg/kg으로 산출되었다. 공산품에서 프탈레이트를 분석하는 국가표준에서 용매 추출 전처리를 사용하는 EN 14372, ASTM D 7083, 일본 후생노동성 시험법(MHLW 0906-4) 및 KS M 1991을 비교한 결과 4개 국가별 표준 모두 98%~99%의 추출효율을 가짐이 검증되었다. 또한, 국내에서 유통되는 어린이 장난감, 전기 코드, 매니큐어의 공산품 3종에서 프탈레이트 함유 여부를 분석한 결과 DBP 및 DEHP가 22~1,910 mg/kg 범위로 검출되었다. As phthalates classified as toxic to reproduction category 2 and endocrine disrupting chemicals were more strictly regulated as Substances of Very High Concern (SVHC) for authorization in under EU REACH and considered as priority substances in RoHS II, standardization of phthalate testing method is now being proposed in IEC 62321 of IEC TC 111 and the 2nd revision of KS M 1991 is also finished. In order to assist standardization activities related to phthalating testing, solvent extraction part of existing national standards were compared and verified. Recovery of DEHP (diethylhexyl phthalate) from PVC (polyvinyl chloride) by Soxhlet extraction increased in the order of methanol, toluene, dichloromethane and hexane from 46.9% to 95.3% as measured by GC-MS. Optimum extraction time was verified to be 6 hours using hexane. Recovery of DBP (dibutyl phthalate), BBP (butylbenzyl phthalate), and DEHP from different matrixes such as PVC, nitro cellulose, ABS (acrylonitrile butadiene styrene). and EPDM(ethylene propylene diene monomer) rubber were evaluated to be more than 90% up to 99%. The detection limits of phthalates in solvent extraction followed by GC-MS analysis were 0.08~0.3 <TEX>${\mu}g/mL$</TEX> in solution and 8~30 mg/Kg in polymeric samples. GC-MS analyses of phthalates were carried out using different solvent extraction based on the EN 14372, ASTM D 7083, Japanese test method (MHLW 0906-4) and KS M 1991, proving that equivalent recoveries ranging from 98%~99% were obtained. DBP and DEHP were detected in three consumer products such as a child toy, a power cable and manicure with the amount of 22~1,910 mg/kg.

Verification of a REACH Environmental Prioritization System Against Regulatory Risk Indices

ABSTRACT A prioritization method that was developed to rank chemical substances on the basis of their environmental impact was applied to 230 new substance notifications from earlier European chemical legislation (67/548/EEC). The method encompasses three steps: (1) assigning an environmental hazard score, (2) assigning an environmental exposure score, and (3) combining these two scores into one priority score. In this study, the resulting scores ranged between 4 (highest priority) and 15 (lowest priority). The scores were compared with results from risk assessments available for 138 of the 230 substances. For most substances in these assessments, a priority score of 12 or higher was associated with no or limited risk, while a score of 11 or lower represented high risk or led to the conclusion that risk reduction measures were required. This categorization applied to all but 15 of the 138 substances. The method was also used for ranking the first 15 Substances of Very High Concern (SVHC) under REACH regulation, to compare the priority scores of new substances to those of the SVHC. In sum, the prioritization method seems to be valuable to identify substances of concern with respect to the environment.

Perfluorooctanoic acid (PFOA) — main concerns and regulatory developments in Europe from an environmental point of view

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are the most investigated substances of the group of per- and polyfluorinated chemicals (PFCs). Whereas for PFOS regulatory measures are already in force on international level (inclusion in Stockholm Convention on Persistent Organic Pollutants) such activities are missing for PFOA. The environmental concerns of PFOA, which are summarized in the present study, underline the necessity of regulatory measures on an international level for PFOA. Since it seems more likely to agree on a regulation within the European Union first, a regulatory strategy based on the European chemicals regulation REACH (EC No. 1907/2006), is discussed in the present study. PFOA is persistent in the environment, ubiquitous present in surface waters, and subject to long-range transport. It accumulates in biota, especially in top predators. PFOA is increasingly analyzed in food items, and in drinking water. PFOA’s intrinsic properties such as its persistency (P), its potential for bioaccumulation (B) and its toxicity (T) suggest that PFOA is a promising candidate for being identified as a Substance of Very High Concern (SVHC) under REACH. Because of the dispersive occurrence of PFOA in the environment, the presence in imported products, and the use of PFCs, which can degrade to PFOA in various consumer products, a restriction under REACH seems to be the most effective regulatory measure to minimize human and environmental exposure to PFOA in the European Union. Due to its intrinsic properties, PFOA fulfills the REACH PBT-criteria. The next regulatory step will be the identification of PFOA and its ammonium salt (APFO) as SVHC according to REACH and the addition to the REACH Candidate List. As a second step, a restriction proposal will be prepared to include both substances and precursors into REACH Annex XVII.

국제환경규제 유해물질의 최근 동향 및 국내 수출기업에 미치는 영향

2000년 중반기 이후, 산업 경쟁력에서 환경 규제, 특히 제품 함유 유해물질 규제가 EU를 중심으로 점차 강화되어 큰 영향을 미쳐왔고, 이는 1990년 초 섬유산업에서 시작하여 전기전자산업을 거쳐 전 산업으로 확장되고 있다. 본 총설에서는 EU의 제품 함유 유해물질 규제 흐름을 알아보고, EU에서 규제하고 있는 유해물질의 종류, 규제 사유, 관련 근거 및 법령을 주요 섬유제품 에코라벨인 Oeko-Tex Standard, 전기전자 제품의 RoHS (Restriction of the use of certain hazardous substances in electrical and electronic equipment) 및 REACH (Registration, Evaluation and Authorization of CHemicals)의 SVHC (Substances of Very High Concern, 고위험성 물질)를 중심으로 고찰해 보면서 NGO (Non-Governmental Organization) 단체들의 활동으로 도출되고 있는 ChemSec (the International Chemical Secretariat)의 SIN (Substitute It Now) list와 그 의미를 조사해보았다. 또한, 국내 수출기업이 국제시장에서 받고 있는 클레임 사례를 통해 규제 유해물질이 시장에 주는 영향을 살펴보고, 유해물질로 인한 국제환경규제의 단기 및 중장기 대응 방안을 고찰해 보기로 한다. Starting with textile products in the middle of 1990, environmental requirements on prohibition of hazardous substances in products have been led by EU member countries and expanded to electrical and electronic equipment with implementaion of RoHS (Restriction of the use of certain hazardous substances in electrical and electronic equipment) in 2006. Under EU REACH (Registration, Evaluation and Authorization of CHemicals), the concept of SVHC (Substances of Very High Concern) and resulting regulatory duties regarding it have been introduced to the supply chain of almost all industry sectors. In this technical review, kinds of hazardous substances, reasons for restrictions and related directives and regulations are reviewed with its influence on the international market. Suggestions are made how to cope with environmental regulations as well as mid-to-long term market strategy to secure global market competitiveness.

Are these liquids explosive? Forensic analysis of confiscated indoor fireworks

Complete forensic analysis of several confiscated liquids and gels putatively used as firework components was achieved by combining Raman, FTIR spectroscopy, and scanning electron microscopy combined with energy-dispersive spectroscopy (SEM-EDS). The chemical composition of the liquids was consistent with their use as indoor fireworks. Alcohols (methanol and isopropyl alcohol) were used to solubilise compounds producing coloured flames. Boric acid, recently introduced in the list of Substances of Very High Concern (SVHC) for the REACH Regulation of the European Union, was found in one of the samples.

The Story of the Button on the Jacket—Substances of Very High Concern in Complex Products

AbstractSubstances of Very High Concern (SVHC) are subject to specific rules in the REACH regulation. For example, once the concentration of SVHCs in articles exceeds 0,1% weight by weight notification to ECHA and communication in the supply chain is obligatory. However, many products are in fact complex articles, consisting of many articles sometimes with SVHCs. The calculation of the concentration of SVHC in complex articles is open for interpretation due to the lack of clear definitions in the legal text of REACH. Two formulas, one defended by ECHA and the other by six Member States exist. Each has its advantages and disadvantages. The choice is not clear cut. is article tries to shed light on the issues and gives a beginning of a solution.

Modelling physico-chemical properties of (benzo)triazoles, and screening for environmental partitioning

(Benzo)triazoles are distributed throughout the environment, mainly in water compartments, because of their wide use in industry where they are employed in pharmaceutical, agricultural and deicing products. They are hazardous chemicals that adversely affect humans and other non-target species, and are on the list of substances of very high concern (SVHC) in the new European regulation of chemicals – REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances). Thus there is a vital need for further investigations to understand the behavior of these compounds in biota and the environment. In such a scenario, physico-chemical properties like aqueous solubility, hydrophobicity, vapor pressure and melting point can be useful. However, the limited availability and the high cost of lab testing prevents the acquisition of necessary experimental data that industry must submit for the registration of these chemicals. In such cases a preliminary analysis can be made using Quantitative Structure-Property Relationships (QSPR) models. For such an analysis, we propose Multiple Linear Regression (MLR) models based on theoretical molecular descriptors selected by Genetic Algorithm (GA). Training and prediction sets were prepared a priori by splitting the available experimental data, which were then used to derive statistically robust and predictive (both internally and externally) models. These models, after verification of their structural applicability domain (AD), were used to predict the properties of a total of 351 compounds, including those in the REACH preregistration list. Finally, Principal Component Analysis was applied to the predictions to rank the environmental partitioning properties (relevant for leaching and volatility) of new and untested (benzo)triazoles within the AD of each model. Our study using this approach highlighted compounds dangerous for the aquatic compartment. Similar analyses using predictions obtained by the EPI Suite and VCCLAB tools are also compared and discussed in this paper.

QSAR classification of estrogen receptor binders and pre-screening of potential pleiotropic EDCs

Endocrine disrupting chemicals (EDCs) are suspected of posing serious threats to human and wildlife health through a variety of mechanisms, these being mainly receptor-mediated modes of action. It is reported that some EDCs exhibit dual activities as estrogen receptor (ER) and androgen receptor (AR) binders. Indeed, such compounds can affect the normal endocrine system through a dual complex mechanism, so steps should be taken not only to identify them a priori from their chemical structure, but also to prioritize them for experimental tests in order to reduce and even forbid their usage. To date, very few EDCs with dual activities have been identified. The present research uses QSARs, to investigate what, so far, is the largest and most heterogeneous ER binder data set (combined METI and EDKB databases). New predictive classification models were derived using different modelling methods and a consensus approach, and these were used to virtually screen a large AR binder data set after strict validation. As a result, 46 AR antagonists were predicted from their chemical structure to also have potential ER binding activities, i.e. pleiotropic EDCs. In addition, 48 not yet recognized ER binders were in silico identified, which increases the number of potential EDCs that are substances of very high concern (SVHC) in REACH. Thus, the proposed screening models, based only on structure information, have the main aim to prioritize experimental tests for the highlighted compounds with potential estrogenic activities and also to design safer alternatives.