Rüdel et al. Environ Sci Eur (2020) 32:5 https://doi.org/10.1186/s12302-019-0286-x

COMMENTARY Open Access Persistent, mobile and toxic substances in the environment: a spotlight on current research and regulatory activities Heinz Rüdel1* , Wolfgang Körner2, Thomas Letzel3, Michael Neumann4, Karsten Nödler5 and Thorsten Reemtsma6,7

Abstract Certain persistent and polar substances may pose a hazard to drinking water resources. To foster the knowledge exchange in this feld the Working Group Environmental Monitoring of the German Chemical Society (GDCh) Divi- sion Environmental Chemistry and Ecotoxicology discussed at their meeting in December 2018 the signifcance and relevance of persistent, mobile and toxic chemicals (PMT substances) in the environment. Five oral contributions highlighted not only various aspects such as the identifcation of potential PMT substances based on certain proper- ties and their possible regulation under the European REACH regulation, but also current developments in the analy- sis of PMT substances and results from environmental monitoring. The data presented prove that many persistent and mobile substances can be detected in surface waters. Once detected, it can be complex and costly to identify sources and reduce inputs, as a case study on 1,4-dioxane in Bavarian surface waters shows. The same applies to the removal of polar substances from raw water for drinking water production. Today, scientifc advances in analytical methods make it easier to identify and quantify even very polar substances in water samples. In addition to the targeted analy- sis of critical chemicals, non-target screening is playing an increasingly important role. This opens up the possibility of detecting substances in water samples that have not previously been investigated in routine monitoring and testing their relevance for humans and the environment. However, the list of potentially occurring PM substances that have not yet been investigated is still very long. Further methodological improvements seem necessary here. In view of the evidence for the presence of PMT substances in the environment (e.g., trifuoroacetic acid and 1,4-dioxane) and the potential risks for drinking water abstraction, it seems important under consideration of the precautionary principle to identify and prioritise relevant REACH-registered substances. The assessment should be based on the intrinsic proper- ties and the emission potential of the compounds. The implementation of a detailed proposal made at European level to regulate PMT and very persistent and very mobile (vPvM) substances in the context of REACH would ensure that chemicals identifed as being substances of very high concern according to the PMT and vPvM criteria are subject to authorisation in future. Keywords: Persistence, Mobility, Toxicity, Water resources, Drinking water, Water production, Risk assessment, REACH regulation, Polar compounds, Non-target analysis

Background Substances with a specifc combination of intrinsic sub- stance properties might pose a hazard to drinking water *Correspondence: [email protected] resources. Te combination of the two intrinsic substance 1 Fraunhofer Institute for Molecular Biology and Applied Ecology properties persistence (P) and mobility (M) increases the (Fraunhofer IME), Auf dem Aberg 1, 57392 Schmallenberg, Germany Full list of author information is available at the end of the article probability for PM substances to pass natural barriers

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like river banks and artifcial barriers in water treatment substances registered under REACH already today can facilities. Especially critical are substances that have pose a signifcant risk to drinking water quality. toxic properties, too (PMT substances). Consequently, a A chemical substance emitted into the environment contamination potentially becomes irreparable. In addi- poses a threat to the drinking water resources, if it is tion, substantial analytical challenges exist related to the transported from the point of emission through soil lay- detection and quantifcation of mobile (polar) substances ers, river banks, aquifers, and other natural or even arti- in water samples during routine monitoring. fcial barriers. Te time scales for this transport can vary Te Working Group Environmental Monitoring of the from a few days in the case of surface water sources, to German Chemical Society (GDCh) Division Environ- 1 or 2 weeks for river bank fltration, or few years for mental Chemistry and Ecotoxicology discussed at their remote groundwater extraction wells. Important factors meeting in December 2018 the signifcance of persis- are the scale of environmental emissions, and whether tent, mobile and toxic chemicals (PMT substances) in the substance, or its transformation products, are suf- the environment. To gather information on the current ciently persistent in the environment and enough mobile knowledge on PMT substances experts were invited to in the aquatic environment. Te German Environment present results from analytical research, environmen- Agency (UBA) proposes to name such substances in tal monitoring and regulation. Five oral contributions the regulatory context of REACH persistent, mobile highlighted various aspects spanning from chemical risk and toxic (PMT) substances or very persistent and very assessment to analytical approaches regarding the detec- mobile (vPvM) substances [2–5]. tion of PMT substances. Te same intrinsic substance properties that lead to persistence in the environment and mobility in the PMT and vPvM substances under REACH (M. aquatic environment might lead to a breakthrough in Neumann, UBA) drinking water treatment facilities. Tey may not be Te EU REACH Regulation (EC) No. 1907/2006 is in removed by flters or by technical degradation proce- force since 2007. REACH intends to ensure a high level dures. Persistent and mobile substances can circulate of protection for human and environment health. Under in the water cycle and cause irreparable contamination. REACH, industry must demonstrate in their registration Terefore, it seems no sustainable solution to rely on ret- dossiers the safe use of substances over their entire life rospective and costly advanced water treatment technol- cycle. Tis includes to take into account the precaution- ogy to protect or remediate drinking water, particularly ary principle and to substitute substances of very high because even costly treatments are not completely efec- concern (SVHCs) and critical uses of chemicals. To date, tive in removing persistent and mobile substances. approx. 22,400 substances have been registered under A substantial analytical challenge exists related to REACH by over 14,800 enterprises. In contrast, authori- the detection and quantifcation of mobile substance in ties have to date identifed 197 substances as SVHCs of water samples. Conventional methods using gas chro- which 43 substances already entered the authorisation matography (GC) and reversed phase liquid chroma- regime under REACH. By now, restrictions were imple- tography (RPLC) are not able to detect and quantify the mented for 69 substances under REACH. most mobile substances, such as those that are very polar, Ensuring that the drinking water sources are secure ionisable or ionic, resulting in high water solubility and from any threats caused by chemicals is of the utmost low n-octanol–water partition coefcients (KOW), or low importance. Te EU Drinking Water Directive (98/83/ pH-dependant n-octanol–water distribution coefcients EC) and the EU Groundwater Directive (2006/118/EC) (DOW). Tis has recently been described as the analytical explicitly demand protection against chemical contami- and monitoring gap [6], and is illustrated in the third con- nation. In contrast, an increasing number of chemicals tribution (see “Protection of water resources from traces are detected in the aquatic environment. A literature of mobile substances” section). review (25 studies from 2000 to 2018; [1]) showed that Te hazard posed by persistent chemicals that are already 333 chemicals were detected in groundwa- mobile in the aquatic environment has been well known ter and/or drinking water. Of these 333 chemicals, 142 since decades. REACH currently lacks criteria for intrin- (43%) corresponded to substances that were registered sic substance properties that indicate a potential drinking under REACH (as of May 2017) of which 32 were also water contaminant. Consequently, there is a regulatory used as pharmaceuticals and fve were also used as pes- gap between the requirements of the drinking water ticides. Te proportion of substances registered under directive and REACH to fulfl the precautionary pro- REACH is even higher (53%) if only those substances tection of the drinking water resources. Terefore, it detected above 0.1 µg L­ −1 are considered. Tis shows that was deemed necessary to scientifcally and technically develop PMT/vPvM criteria under REACH. Rüdel et al. Environ Sci Eur (2020) 32:5 Page 3 of 11

Te German Environment Agency (UBA) since 2010 less than 3.0 as very mobile (vM). Te intrinsic substance has funded research projects and since 2017 has per- property of mobility in the aquatic environment is on its formed two written consultations and several workshops. own insufcient to imply a hazard due to enrichment in Neumann and Schliebner [5] present the result of this the source of drinking water [5]; rather, substances that scientifc and technical development of the PMT/vPvM are persistent and mobile are potential SVHCs. REACH criteria under REACH (refer to Fig. 1 for a scheme of the and European Chemicals Agency’s (ECHA) guidance assessment procedure). documents point to the use of KOC as the central intrinsic Te persistence criterion (P) and very persistent crite- substance property to describe mobility (e.g., [8]). Water rion (vP) are taken directly from Annex XIII of REACH solubility is considered not to be a suitable property to [7]. Te main advantage is that it is consistent with exist- set a threshold for the assessment of mobility. Te princi- ing regulatory defnitions of P and vP. Tis means that pal reasons are difculties when assessing ionic and ion- no additional workload is caused for registrants by the isable substances, in which water solubility is dependent PMT/vPvM assessment since an assessment of P and vP on counter ions [1]. Te cut-of value of log KOC 3.0 for within the PBT/vPvB assessment has to be performed for vM is supported by scientifc literature to be protective any registration above 10 t ­a−1. of groundwater and is currently utilised by the Ground- Te indication (screening) criterion for mobility is that water Watch List coordinated by the EU Common Imple- the lowest log DOW over the pH range of 4–9 is less than mentation Strategy Working Group Groundwater for 4.5. Again, the main reasons are the compatibility to the identifying potential groundwater contaminants [9, 10]. screening for B and vB properties and the reduction of In addition, the cut-of value of log KOC 4.0 for M is sci- the workload under REACH for registrants. For neutral entifcally justifed for the protection against bank fltra- and non-ionisable substances over a specifed pH range tion breakthrough [5]. the DOW has the same value as the KOW. Te criteria for toxicity (T) are mainly already set out Te assessment criterion for the mobility is the low- in Annex XIII, 1.1.3 of REACH for the PBT/vPvB assess- est organic carbon–water partition coefcient (log KOC) ment [7]. Beyond these, there might be cases, where it is over the pH range of 4–9: if the log KOC is less than 4.0 a necessary to identify persistent and mobile substances substance is assessed as mobile (M) and if the log KOC is with other hazardous properties posing a risk to human health and the environment. Tese additional toxicity (T) criteria are: classifcation as carcinogenic (category 2), germ cell mutagenic (category 2), or for efects on or via lactation according to Regulation EC No 1272/2008 [11]; the Derived-No-Adverse-Efect-Level (DNEL) −1 −1 is ≤ 9 µg kg day­ (oral, long term, general popula- tion); or the substance acts as an endocrine disruptor in humans and/or wildlife species according to the WHO/ IPCS defnition of an endocrine disruptor. Te evaluation approach proposed by UBA consists of two steps [5]. In the frst step, the identifcation of PMT and vPvM substances is done by comparing the intrinsic substance properties with the PMT/vPvM criteria. Te second step, the emission characterisation, includes rec- ommendations for risk management measures (RMM) or the use of safe alternatives to minimise emissions and to protect the drinking water resources. Analogously to other hazardous substances under REACH, regulatory measures for PMT/vPvM substances may only need to be considered by authorities, if registrants and downstream users do not put the necessary RMM into place. Te two most relevant regulatory instruments of authorities under REACH are the authorisation regime and the restriction. A restriction limits or prohibits Fig. 1 Overview of the assessment procedure for identifying PMT/ the use of a substance if this would pose an unaccepta- vPvM substances registered under REACH [5]. For defnitions refer to ble risk to human health or the environment. Under the text. N/A, not applicable REACH such risks are identifed by the Risk Assessment Rüdel et al. Environ Sci Eur (2020) 32:5 Page 4 of 11

Committee (RAC) of the ECHA. In principle, the use of a only one example of substances that can interfere with substance is allowed, unless there is a restriction for cer- drinking water supply. tain (or all) uses. In order to protect the drinking water resources, pro- An authorisation means that it is permitted and active (i.e., emission-related) protection is necessary, so approved to use a substance in a certain way. In the that it becomes possible to identify critical substances authorisation regime the use of a substance is prohib- at an early stage—ideally before their use or during the ited, unless there is an approval for a specifc use. Within approval or registration process. However, this is a huge REACH a substance to be included into the authorisation challenge against the backdrop of the large number of regime must frst be identifed as an SVHC. According registered and pre-registered compounds (see section to REACH Article 57 (f) [7], this would be the case if for “PMT and vPvM substances under REACH (M. Neu- a PMT/vPvM substance the equivalent level of concern mann, UBA)”). Terefore, a risk-based prioritisation of as for PBT/vPvB substances were demonstrated. Under critical substances relevant for water supply was carried REACH this decision is to be taken on the basis of the out at TZW. On the basis of intrinsic properties, entry intrinsic substance properties by the Member States pathways/scenarios, and consumption volumes of the Committee (MSC). Te substance is then placed on the substances, the probability of occurrence in drinking Candidate List. If the substance is fnally included in water and the associated risk were evaluated. Annex XIV of the REACH regulation, its use is prohib- Aim of the project, funded by DVGW (German Tech- ited and subject to approval. nical and Scientifc Association for Gas and Water) with In an ongoing research project on the behalf of UBA the short title Hot-Target-approach, was to identify the PMT/vPvM criteria were applied to all substances drinking water-relevant chemicals with highest priority registered under REACH (as of May 2017) [1]. To date, for drinking water supply out of a substance pool of about approximately 260 PMT/vPvM substances have been 10,400 environmentally relevant substances from various identifed within this research project. Te substance list databases. During the evaluation of the substance data- will be prioritised according to the type of use and the bases synergies with other projects were built up. Among resulting risk of emission. others, the STOFF-IDENT database (HS Weihenstephan- Triesdorf, LfU Bavaria, TU Munich, and Zweckverband Relevance of organic micropollutants for drinking Landeswasserversorgung) [13] was used and informa- water supply (K. Nödler, TZW) tion on REACH substances, drug and plant protection A recent example demonstrates the relevance of organic products (both active substances and transformation micropollutants for drinking water supply: In 2016, con- products) as well as and biocides was compiled. In addi- centrations of more than 20 µg L­ −1 trifuoroacetate (TFA) tion, information from water suppliers was taken into were detected in the bank fltrate of the river Neckar account and scientifc literature (i.e., occurrence studies) (Germany) [12]. Tis caused nationwide attention and led evaluated. One difculty with the intersection of the data to further analyses of the occurrence of TFA in surface, sources was that the substance data sets partly referred to ground and drinking water. It was shown that the Rhine diferent substance forms (e.g., free acid vs. anion/cation is also infuenced by the identifed point source at the or salt). Te InChIKey (International Chemical Identi- Neckar and that this afects drinking water supply more fer) proved to be the most suitable identifcation feature than 300 km downstream. TFA is the anion of trifuoro- for the comparison and harmonisation of the data. As a acetic acid which, according to the REACH database, is general recommendation, InChIKeys should be system- marketed in Europe with a tonnage of 1000–10,000 t ­a−1 atically added in chemical databases as unique substance (e.g., as raw material or solvent). Natural sources may identifers in order to guarantee that in the future search also exist but only seem to be relevant in the marine and retrieval of data from existing databases will be uni- environment. In contrast, TFA was identifed as a trans- vocally linked to the chemical structure of a compound. formation product of a large variety of substances (pro- In the frst step of the risk-based prioritisation, worst pellants and refrigerants, pesticides, pharmaceuticals). case criteria were used for the screening of substances In the substance assessment of the herbicide furtamone, from the Hot-Target basic database without resort- TFA was identifed as a so-called non-relevant metabo- ing to experimental data and production/consumption lite (German health orientation value 1 µg L−1 until the volumes. Tus, parameters for mobility and technical end of 2016, 3 µg L−1 since January 2017). On the basis removability of substances during drinking water treat- of the available data, TFA can be assessed as persistent ment as well as the biological half-lives of substances and highly mobile in the water cycle and its detection in were estimated using diferent QSARs (ACD/Percepta drinking water is not surprising at all. However, TFA is (ACD/Labs) and ChemAxon for the calculation of log DOW; US EPA’s BIOWIN for biodegradation assessment) Rüdel et al. Environ Sci Eur (2020) 32:5 Page 5 of 11

and other theoretical approaches (e.g., read across). In compounds were log DOW < 4.5 and < 60% of the cationic addition, during the frst screening, the hazard poten- species of the compound (both to be evaluated at pH 8) to tials of the substances were assessed on the basis of any consider removal by hydrophobic interactions and cation conspicuous structural features. During the subsequent exchange, respectively. Further criteria are the particular refnement, a detailed assessment of the Hot-Target- consideration of small molecules (i.e., molecular mass candidates (i.e., drinking water-relevant substances that of ≤ 200 Da) and of data on biological degradation (model cannot be removed by ozonation and/or activated carbon based on US EPA‘s BIOWIN; https​://www.epa.gov/tsca- treatment and from which potential hazards emanate) scree​ning-tools​/epi-suite​tm-estim​ation​-progr​am-inter​ was carried out on the basis of experimental data (if avail- face). Volatility and water solubility, on the other hand, able). Screening and refnement procedures are explained are not included in the evaluation. in a more detailed manner in the following sections. In order to assess the toxicological relevance, the Hot-Target-approach initially uses—if available—exist- Screening criteria ing assessments of the substances to be prioritised (e.g., To assess the mobility of substances in the subsurface, drinking water guideline values, health orientation val- the criteria of previous works were examined: Provided ues, classifcations as carcinogenic, mutagenic and repro- that there is no valid experimental KOC data, the sorption duction-toxic (CMR) substances, data from international estimation is mostly carried out via the KOW (or KOW/KOC lists of carcinogenic substances or from available REACH relations). However, the KOW is not always sufcient for assessments). A software-supported search for conspicu- an evaluation of sorption. For example, for ionic or ion- ous features in the chemical structures was carried out isable substances, the mobility of organic acids may be for the screening of hitherto unevaluated substances underestimated, whereas the mobility of organic bases (with regard to possible genotoxic and non-genotoxic that can be retained by cation exchange processes may be carcinogenicity) with the Toxtree application (http:// overestimated for raw water typically within a pH range toxtr​ee.sourc​eforg​e.net/). of 6–9. A statistical evaluation from 2010 showed that For the evaluation of the potential removal of sub- about half of the substances registered under the REACH stances by ozonation, an automated database query was regulation are ionisable compounds [14]. performed for structural characteristics with known To assess the drinking water relevance of organic com- favourable reaction kinetics (e.g., molecules with C–C pounds, the potential removal by sorption (e.g., during double bonds or aniline-N are considered as reactive river bank passage) was taken into account. Terefore, [15]). Te evaluation of potential removability of sub- the speciation of the compound has to be consid- stances by activated carbon treatment is based on hydro- ered: Te selected criteria for drinking water relevant phobicity. Te cut-of value (i.e., removable: compounds

Hot-Target-candidates (760 substances)

low 1 2 low concern hazard probability concern potenal of (experi- exposure 1 2 mental) 1 2

1 2

Hot-Target-substance Fig. 2 Scheme for the evaluation of the substances identifed as Hot-Target-candidates (modifed from [17]) Rüdel et al. Environ Sci Eur (2020) 32:5 Page 6 of 11

identifcation of the main source(s) may be complex and with a log DOW ≥ 2.5) was derived by meta-analysis of in- house small-scale flter tests [16]. the implementation of efcient mitigation strategies is delayed [19]. Refned procedure In general, the availability of technical solutions for By applying the selected screening criteria, it was pos- the elimination of PM substances during drinking water sible to identify 760 substances as potentially drinking purifcation must not replace any strategies for resource water relevant priority substances, for which the usual protection, as the formation of harmful by-products dur- technical risk management measures are unlikely to be ing, e.g., ozonation is a potential threat [20]. Tis state- successful. Tese Hot-Target-candidates were subjected ment is very well in line with requirements of article to a substance-per-substance evaluation in a refned pro- 7(3) of the European Water Framework Directive, which cedure (Fig. 2). Te hazard potential of each substance states that Member States shall ensure the necessary pro- was evaluated on the basis of experimental data (if avail- tection for the bodies of water identifed with the aim of able). To assess the probability of exposure, entry path- avoiding deterioration in their quality in order to reduce ways/scenarios and consumption volumes as well as the level of purifcation treatment required in the produc- available experimental data on mobility and (bio-)degra- tion of drinking water [21]. dation were taken into account. Green light on any cri- Te report on the Hot-Target-approach is available via terion (i.e., very low probability of exposure or very low the DVGW [17]. hazard potential) indicates very low risk. Te respective compound is not high priority and, thus, considered as Protection of water resources from traces of mobile false-positive result of the screening procedure. In case substances (T. Reemtsma, UFZ) of lacking or inconsistent experimental data, the traf- Some PM compounds have been known as surface water fc light was set to yellow (i.e., medium exposure/hazard contaminants, e.g. pyrazole, TFA or 1,4-dioxane, but potential). monitoring methods that enabled the detection of larger Nine substances that are critical with regard to both cri- numbers of highly polar trace substances from water are teria (i.e., red light twice: high concern at hazard and expo- not well developed (analytical gap) [6]. In addition to this sure level) were classifed as Hot-Target-substances with analytical gap there is also a protection gap for PM sub- priority A: 1,4-dioxane, trichloroethene, trichloromethane, stances: since they are very mobile in the aquatic envi- 2,4-dinitrophenol, tris(2-chloroethyl)phosphate (TCEP), ronment and hardly degraded microbially, the barriers 1,2-dichloropropane, trichloroacetic acid, 1,2-dichloroeth- in partially closed water cycles are not efective and the ane, and 1,2-dimethoxyethane (monoglyme). Further 80 concentrations of PM compounds are reduced by dilu- chemicals were identifed as Hot-Target-substances with tion only. priority B (i.e., no green light on any level: no clear relief at As part of the Water JPI initiative of the EU, the hazard and/or exposure level). European project PROMOTE with partners from fve Several important aspects of the presented approach should be highlighted. First of all, the availability of robust experimental data is often insufcient for a proper assessment. Furthermore, as the precautionary princi- 40% ple needs to be considered, anthropogenic substances in 8.4% drinking water are undesirable, even if there is no indi- 8.0% cation for toxicological concerns. Persistence alone is a 0.1% major cause of concern and possible risks may be identi- PM substances without fed long time after the compounds’ use [18]. Terefore, 43% emission assessment the use of persistent substances should be strictly limited to essential applications and the development of readily PM substances with emission potenal (936 chemicals) degradable substitutes has to be top priority. Further- more, current assessments do usually not include the precursors of PM substances with emission potenal (174 chemicals) potential formation of persistent and mobile transfor- PM substances without expected emissions (872 chemicals) mation products from precursor molecules. Te pres- ence of multiple primary (i.e., discharge of the compound precursors of PM substances without expected emission potenal (182 chemicals) itself) and secondary (i.e., from the degradation of pre- PM substances without emission assessment (3 chemicals) cursor molecules) sources of such compounds in drink- Fig. 3 Classifcation of PM substances and precursors of PM ing water catchments is an upcoming challenge for the substances from the REACH process according to emission drinking water sector and regulatory frameworks, as the probability (data from [23]) Rüdel et al. Environ Sci Eur (2020) 32:5 Page 7 of 11

countries has pursued two approaches to reduce the concentrations ranging from the low ng L­ −1 up to µg ­L−1 knowledge gap on PM compounds. Firstly, 14,000 sub- range [27]. stances registered according to the REACH regulation With regard to drinking water preparation, some of the were prioritised with regard to their PM characteris- detected organic PM substances are neither removed by tics starting from the registration data [22]. About 2200 “conventional” processes nor by advanced treatment with REACH-registered substances were evaluated as persis- activated carbon or ozone. Tis group comprises, e.g. tri- tent and mobile because of their properties or because fuoromethane sulfonic acid, xylene sulfonic acid, cyano- they form transformation products with such properties. guanidine, 2-acrylamino-2-methylpropanesulfonic acid, Subsequently, the emission potential for these substances melamine, and acesulfame. Tese results indicate that was also estimated [23] based on the marketed tonnage current technical and environmental barriers are not suf- in Europe as well as on their use characteristics (release fcient to safely eliminate all PM chemicals. Tis suggests into the environment vs. use in closed systems). Te that, indeed, a protection gap exists for drinking water. application of this model led to a list of about 1100 PM Tis gap should be known more precisely and measures substances for which a release into the environment was need to be developed to improve the protection of our considered relevant (Fig. 3) [23]. Compounds on this list water resources. may be included into future suspect screening activities Since 2019, the investigations on the occurrence of or selected for the development of targeted methods for PM substances in the water cycle and on possibilities of PM compounds. their removal are being continued at a national level in a Although the list of 1100 PM compounds is more than project funded by the German Federal Ministry for Edu- an order of magnitude larger than the list of Hot-Target- cation and Research (BMBF) also coordinated by UFZ substances of Nödler et al. [17] and section “Relevance (Project PROTECT; http://www.ufz.de/prote​ct). of organic micropollutants for drinking water supply (K. Nödler, TZW)” above, not all compounds from that list Identifcation and detection of very polar are also included here. Tis is primarily due to the fact components in aqueous environmental samples (T. that the PM list focusses on REACH chemicals, while Letzel, TU Munich) the Hot-Target list started with a more diverse spectrum Anthropogenic organic trace substances reach the envi- of contaminants, including also pharmaceuticals and ronment via diferent input paths where difuse as well pesticides. as point sources play a role. Sewage treatment plants Secondly, three project partners have improved ana- (STPs) are the most important point sources for these lytical methods based on liquid chromatography–mass substances [28]. Te usual monitoring spectrum for the spectrometry (LC–MS) methods for highly polar sub- investigation of STP efuents only covers a limited num- stances. Tey used hydrophilic interaction liquid chro- ber of substances (target analysis). Non-target screening matography (HILIC; [24, 25]), mixed-mode liquid approaches now ofer the possibility to identify further chromatography (MMLC; [26]) and supercritical fuid relevant substances. Both procedures together open up chromatography (SFC; [27]). In this way they could sig- the possibility of determining a comprehensive spectrum nifcantly extend LC–MS methods towards more polar of substances occurring in water bodies. contaminants. Te methods were used to determine the Te organic trace substances can have very diferent occurrence, frequency of detection and semi-quantita- polarities, which thus require diferent analytical meth- tive concentrations of 64 PM substances in water sam- ods. Te serial RPLC–HILIC coupling has proven to be ples (mostly surface water, groundwater, bank fltrate) optimal for the simultaneous analysis of very polar, polar from Spain, France, the Netherlands and Germany [27]. and non-polar substances [29]. Studies were carried out, 33% of the target analytes were present in at least 50% of for example, in a river before and after the introduction the analysed water samples. Tese included some previ- of discharges of an STP as well as directly in the efu- ously known polar trace substances such as melamine, ent. For this purpose, 24-h composite samples were used. tris(1,3-dichloro-2-propyl)phosphate), acesulfame and Initially, the samples were concentrated on a C18-HILIC epsilon-caprolactam. Te predominant number of posi- solid phase. Te analyses were then carried out using tive fndings, however, concerned industrial chemicals RPLC–HILIC and atmospheric pressure interface-time that had not previously been reported to occur in envi- of fight-MS coupling (API-ToF/MS). Te HILIC method ronmental water samples, such as 1,3-diphenylguanidine, separates substances with log DOW < 0, the RPLC sub- p-toluenesulfonic acid, trifuoromethane sulfonic acid, stances with log DOW > 0. 2-acrylamino-2-methylpropanesulfonic acid, xylene- In the meantime a large number of data on relevant sulfonic acid and cyanoguanidine. Te results revealed substances have been compiled, which are also publicly that PM compounds occurred in the water cycle in available in the database STOFF-IDENT (https​://www. Rüdel et al. Environ Sci Eur (2020) 32:5 Page 8 of 11

lfu.bayer​n.de/stoff dent​/). Tis continuously updated Case study: 1,4‑dioxane in Bavarian water bodies— database with so far more than 11,000 entries contains, analysis, sources, emission reduction (W. Körner, e.g., REACH-registered chemicals, active substances of LfU Bavaria) drugs, biocides and plant protection products as well as 1,4-Dioxane is a persistent and mobile substance occur- known transformation products of these compounds and ring in wastewater treatment efuents and the aquatic other relevant substances potentially occurring in waters. environment and clearly meets the PMT criteria [30]. During the exemplary investigation of STP efuents Te chemical is used as a solvent in numerous areas. and upstream/downstream sampling points using RPLC– UBA has set a human health-based guidance value for HILIC/ToF–MS, several hundred features (characterised drinking water of 5 µg L­ −1 for lifelong intake [31]. In by retention time and accurate MS data) were detected. spring 2016, 1,4-dioxane was found in river bank fltrate Tese were then further characterised in a more com- near the mouth of a tributary to the river Danube dur- plex workfow by using the FOR-IDENT platform (https​ ing investigations for the LfU project Climate change and ://water​.for-ident​.org) and the STOFF-IDENT database. water supply in Bavaria (unpublished results). As a result, Tis includes blank value correction as well as the assign- LfU developed a modifed headspace method coupled to ment of suitable structures to the MS data and a fltering/ gas chromatography mass spectrometry (GC–MS) for prioritisation of the data with regard to the log DOW value the determination of 1,4-dioxane in water in summer range. Te selected features are then checked manually. 2016, which achieves a limit of determination of 0.2 µg Te verifcation of the substances is done by compari- ­L−1, and since May 2017 even of 0.1 µg ­L−1. Te method son with available standards and by a tandem MS confr- has been used for the determination of 1,4-dioxane in mation analysis. However, the assignment is not always the Danube and its tributaries. Using this rapid method, possible, because isomers are not separated or several four dischargers of 1,4-dioxane were identifed at the chemical structures may ft to one feature. tributary mentioned above. Te two dischargers with the With this methodology, 54 suggestions could be largest loads are manufacturers of polyester fbres, where made from 462 features (partly identifed by match- 1,4-dioxane is formed in an acid-catalysed side reaction ing MS data with databases of substances already of ethylene glycol. tested). 32 of these substances were fnally confrmed In February 2017, a mobile plant for the treatment of by measurements of available standards. Examples are the complete dioxane-containing wastewater with cata- N,N′-ethylenedi(diacetamide), 2,2,6,6-tetramethyl-4-pi- lytic oxidation with Fenton’s reagent and UV irradiation peridone or melamine as industrial chemicals, gabapen- in a batch process was installed at one of the two plants, tin as a drug or adenine, which is a biogenic substance which was replaced by a stationary plant in August 2018. but also produced and used industrially (data not yet Te dioxane load has been demonstrably reduced by published). Polarity-enhanced chromatographic meth- 95–98% with both systems. Te other polyester manu- ods such as RPLC–HILIC/ToF–MS and SFC/ToF–MS facturer also installed an additional mobile wastewater close the gap for the analysis of very polar molecules and treatment plant in April 2017, but this was only suf- are expected to be increasingly used in environmental cient for 30% of the dioxane-containing wastewater. In monitoring in the future. Further examples for detected November 2018, a distillation plant for all dioxane-con- proven vP substances are maleic acid, betaines (e.g., also taining wastewater from the plant was commissioned at contained in personal care products such as shower gels), that site, and the dioxane-containing distillates are now metformin, tenofovir or taurine. As polar substances, subsequently incinerated. After a start-up phase, a reduc- 2-butylaminoethanol, piperidine or diisopropylamine tion of the dioxane load by 90–98% is achieved. were found. However, it was also possible to determine As third dioxane source a paper mill was identifed. routinely many amino acids, which are to be regarded as Recently, the company identifed an auxiliary substance substances occurring naturally in waters. which contained 1,4-dioxane. A dioxane-free replace- Tese investigations demonstrate that the now possible ment substance has successfully been introduced. separation of very polar molecules by polarity-enhanced Dioxane inputs were also caused by a plant producing analytical separation techniques already opens up a chemical products for the textile industry. Technical deeper insight into the diversity of molecules occurring hydrochloric acid, which is used to neutralise wastewa- in waters. For further monitoring of new substances by ter, was identifed here as the dioxane source. Te acid a target screening, isotope-labelled internal standards are stemmed from three technical processes and contained typically used and the quantitative results of diferent real about 2 g ­L−1 1,4-dioxane. It was replaced by dioxane- samples are determined. In the short-to-medium term, free technical hydrochloric acid in 2017. Since then, diox- this will form a sound basis for interpreting the relevance ane emissions have decreased by over 90%. of (very) polar molecules in the aquatic environment. Rüdel et al. Environ Sci Eur (2020) 32:5 Page 9 of 11

With the measures already implemented at the four In addition to the targeted analysis of critical chemicals, plants, a signifcant reduction of the dioxane mass fow non-target screening is gaining an increasingly important was measured as early as mid-2018. Terefore, 1,4-diox- role. Tis opens up the possibility of detecting substances ane concentrations of about 5 µg ­L−1, as observed in the in water samples that have not previously been covered dry winter of 2016/2017 near the river mouth, did not in the routine monitoring, and to test their relevance for occur any longer, even in the extremely dry summer of human health and the environment. However, the list of 2018. potentially occurring but not yet tested PM substances As a further important source of 1,4-dioxane at another is still very long. Here, further methodological improve- tributary of the Danube, a company has been identifed ments seem necessary. which manufactures diferent surfactant products and In view of the evidence for the occurrence of PMT sub- precursors, including those based on ethoxylate (unpub- stances in the environment (e.g., TFA and 1,4-dioxane) lished results). Due to acid-catalysed side reactions of and the potential risks for drinking water production, it ethylene glycol and diethylene glycol these production seems important in terms of the precautionary principle processes also result in 1,4-dioxane. By August 2018, to identify and prioritise REACH-registered substances various measures, including the separation of wastewa- as relevant for environment monitoring due to the intrin- ter containing dioxane and subsequent incineration, had sic substance characteristics P and M and their emission reduced total dioxane emissions at this site by more than potential. Te proposal made at the European level to 50%. regulate PMT and vPvM substances in the context of the Bavaria-wide, from October 2016 to mid-2017, more REACH regulation would ensure that chemicals identi- than 40 surface water monitoring sites were analysed for fed as of very high concern according to these criteria 1,4-dioxane every 4 weeks. In 2018, this monitoring was would be subject to an authorisation in future. continued with 19 measuring points and the drains of Te current state of research on PMT substances will the four STPs to which the dischargers described above be presented in January 2020 at an international work- are connected. In 2019 and 2020, 1,4-dioxane monitor- shop co-organised by the NORMAN network in Leipzig ing is continued with 13 measuring points plus four STP (https​://www.norma​ndata​.eu/?q=node/354). Members efuents. It will be supplemented by a targeted search for of the GDCh-Working Group Environmental Monitoring sources at a tributary of the Danube where only tempo- of the German Chemical Society will be supporting this rarily high 1,4-dioxane concentrations occur. Moreover, meeting. an attempt will be made to trace the cause for irregular detection of 1,4-dioxane concentrations in the river Main Abbreviations upstream of the city of Bamberg, which is still unknown API: atmospheric pressure interface; CMR: carcinogenic, mutagenic and repro- despite an extensive sampling campaign. duction-toxic; DOW: n-octanol–water distribution coefcient; DVGW: Deutscher Verein des Gas- und Wasserfaches e.V. (German Technical and Scientifc Te experiences gained in Bavaria since 2016 reveal Association for Gas and Water); EU: European Union; GC: gas chromatogra- that regular and targeted monitoring can contribute phy; GC–MS: gas chromatography–mass spectrometry; GDCh: Gesellschaft decisively to identify emission sources for 1,4-dioxane in Deutscher Chemiker (German Chemical Society); HILIC: hydrophilic interaction liquid chromatography; InChIKey: International Chemical Identifer; K : soil water bodies, to justify and demand emission-reducing OC organic carbon–water partition coefcient; KOW: n-octanol–water partition measures, and to demonstrate and monitor the efective- coefcient; LfU Bavaria: Bavarian Environment Agency (Bayerisches Landesamt ness of these measures. für Umwelt); MMLC: mixed-mode liquid chromatography; N/A: not applicable; NORMAN: Network of reference laboratories, research centres and related organisations for monitoring of emerging environmental substances; PM: persistent and mobile; PMT: persistent, mobile and toxic; REACH: Registration, Conclusions Evaluation, Authorisation and Restriction of Chemicals (EU Regulation); RMM: risk management measures; RPLC: reversed phase liquid chromatography; Meanwhile many investigations prove that PM sub- SFC: supercritical fuid chromatography; STP: sewage treatment plant; SVHC: stances are detectable in surface waters. Once detected, it substance of very high concern; TFA: trifuoroacetate; ToF/MS: time of fight- can be very costly to identify their sources and to reduce mass spectrometry; TU Munich: Technical University of Munich; TZW: DVGW- Technologiezentrum Wasser; UBA: Umweltbundesamt (German Environment inputs, as the case study on 1,4-dioxane in Bavarian Agency); UFZ: Helmholtz Centre for Environmental Research (Umwelt- waters reveals. Te same applies to the removal of criti- forschungszentrum); UV: ultraviolet; vPvM: very persistent and very mobile. cal polar substances from raw water for drinking water Acknowledgements processing. However, the toxicity of many PM substances Regarding section PMT and vPvM substances under REACH (M. Neumann, is still unclear [1, 30]. Tis issue needs further considera- UBA): This study was contracted for the Environmental Research of the Federal tion, especially in the case of PM substance fndings close Ministry for the Environment, Nature Conservation, and Nuclear Safety in Ger- many, from 2016 to 2019 as project No. FKZ 3716 67 416 0 to H.P.H. Arp and to drinking water production. S.E. Hale from NGI—Norwegian Geotechnical Institute under the title REACH: Today, advances of analytical methods make it easier to Improvement of guidance and methods for the identifcation and assessment quantify even strongly polar substances in water samples. of PMT/vPvM substances. Rüdel et al. Environ Sci Eur (2020) 32:5 Page 10 of 11

Authors’ contributions Germany. https​://www.umwel​tbund​esamt​.de/sites​/defau​lt/fles​/medie​ HR initiated this contribution and conceived the conclusions. WK, TL, MN, KN n/1410/publi​katio​nen/2019-11-29_texte​_127-2019_prote​cting​-sourc​ and TR contributed specifc sections (author names given in headings). All es-drink​ing-water​-pmt.pdf. Accessed 20 Dec 2019 authors read and approved the fnal manuscript. 6. Reemtsma T, Berger U, Arp HPH, Gallard H, Knepper TP, Neumann M, Quintana JB, de Voogt P (2016) Mind the Gap: persistent and mobile Funding organic compounds—water contaminants that slip through. Environ The preparation of this manuscript was not funded by third parties. Sci Technol 50:10308–10315 7. European Parliament and Council (2006) Regulation (EC) No 1907/2006 Availability of data and materials of the European Parliament and of the Council of 18 December 2006 Data are either original data from the authors’ institutions and/or are from the concerning the Registration, Evaluation, Authorisation and Restriction references given. of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation Ethics approval and consent to participate (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well Not applicable. as Council Directive 76/769/EEC and Commission Directives 91/155/ EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Ofcial Journal L 396, Consent for publication 30.12.2006, pp 1–849 Not applicable. 8. ECHA (2017) Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specifc guidance. Version Competing interests 6.0, July 2017. ISBN 978-92-9495-970-6. European Chemicals Agency All authors declare that they have no competing interests. (ECHA), Helsinki, Finland https​://echa.europ​a.eu/docum​ents/10162​ /13632​/infor​matio​n_requi​remen​ts_r7a_en.pdf. Accessed 20 Dec 2019 Author details 9. Kozel R, Wolter R (2018) Voluntary Groundwater Watch List Concept 1 Fraunhofer Institute for Molecular Biology and Applied Ecology (Fraunhofer & Methodology. Based on fnal draft 12.3, endorsed by CIS Working IME), Auf dem Aberg 1, 57392 Schmallenberg, Germany. 2 Unit Analysis Group—Groundwater (WG GW). Common Implementation Strategy of Organic Compounds, Bavarian Environment Agency (LfU), Bürger- for the Water Framework Directive and Floods Directive, p 38. https​:// meister‑Ulrich‑Strasse 160, 86179 Augsburg, Germany. 3 Analytical Research circa​bc.europ​a.eu/d/d/works​pace/Space​sStor​e/63f48​ec1-6da8-4b5b- Group, Chair of Urban Water Systems Engineering, Technical University aed7-71e01​8324d​71/Groun​dwate​r%20wat​ch%20lis​t.pdf. 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