Dr Hans Sanderson
Aarhus University, Department of Environmental Science
4000 Roskilde, Denmark
Scott Belanger, Research Fellow, The Procter & Gamble Company, Mason OH USA, firstname.lastname@example.org
Monica Lam, Senior Scientist, The Procter & Gamble Company, Mason OH USA, email@example.com
Kristin Connors, Scientist, The Procter & Gamble Company, Mason OH USA, firstname.lastname@example.org
Martin Hansen, Senior Scientist, Aarhus University, 4000 Roskilde, DK, email@example.com
Anna M Brun, PhD student, Aarhus University, 4000 Roskilde, DK, firstname.lastname@example.org
Objectives: Our overall aim is to support the development of methods to allow accurate and precise aquatic environmental risk assessment of cationic polymers. This will lay the foundation for regulatory acceptance based on improved methods for regulatory assessment and compliance testing of polymers. However, there are significant gaps in the knowledge base. How can we reliably measure the aquatic exposure for these charged compounds? How do we describe environmental exposures and control lab testing exposure concentrations, when dissolved organic carbon (DOC) species such as humic acids can reduce the apparent toxicity of cationic polymers by one or two orders of magnitude? How can we consistently test and describe the toxicity of cationic polymers, which are not expected to pass biological membranes? How do we characterize their impacts in a modern context of the CLP definition substances hazard and toxicity properties? How do we describe the dose-response for materials that are expected to affect the outer membranes of aquatic organisms and functionalities? This proposal seeks to assess a group of closely related but understudied model cationic polymers that are widely used in industry. The level of cationicity is lower than many others that are studied (e.g., wastewater treatment plant flocculating agents) and are probably somewhat more challenging to model. We will determine if these polymers continue the trends established in QSARs of higher nitrogen-containing polymers in order to generalize toxicity and physical-chemical patterns. There are many pertinent and challenging questions regarding cationic polymers. The iTAP project will assess in a realistic and consistent way the environmental threat posed by cationic polymers. Below are the main objectives of the iTAP project, which will be address in the subsequent work packages:
Objective 1) Review: We will assess the various methods and tools currently available in the literature to measure or predict the toxicity and fate properties of cationic polymers (e.g., standard guidelines, sampling and analytical methods, SAR equations, fate models, etc.). We will review various physical chemical properties believed to demonstrate a correlation with effects (e.g., molecular weight, charge density, N-content, #C-N bonds, etc.) and propose which parameters to use in SAR equation development.
Objective 2) Exposure: Clarify the methodological scheme that should/shall be followed when assessing the environmental hazards of cationic polymers environmental hazards. We will assess the definition of the characteristics of appropriate dilution waters (i.e., OECD dilution water, tap water, tap water supplemented with humic acids, or river water) for standards and modified ecotoxicity tests. We will provide recommendations on methods for the appropriate monitoring of bioavailable concentrations, and discuss proposition of mitigation factors to be used when deriving classification from tests run with well-characterized river water or organic carbon amendments. We will discuss proposition of mitigation factors to be used when deriving PNECaqua from results derived from relevant OECD test guidelines. We will attempt to clarify whether or not the toxicity mitigation is similar to, a subset of, or independent of that typically considered in equilibrium partitioning.
Objective 3) Aquatic toxicity: We will update and organize the knowledge base on the aquatic toxicity of cationic polymers. Specifically, we will use the freshwater algae and cyanobacteria growth inhibition test (OECD 201) building on the work of Nolte et al (2017), the water flea acute test (OECD 202) and the reproduction test (OECD 211), lastly, the fish embryo acute toxicity test (OECD 236).
Objective 4) Aquatic risk: We will address environmental risks thorough description of the bulk approach (ECETOC, 2003) and review of exposure models’ applicability to cationic polymers (e.g. EUSES).
ECETOC. Sorptive substances, in: Environmental Risk Assessment of Difficult Substances, Technical Report No. 88, pp. 33-52. European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium.
Project Website: www.projects.au.dk/itap
Problem statement: Polymers have been historically excluded from registration and evaluation under REACH. Recently, there has been increased interest in including at least some classes of polymers, such as cationic polymers, into regulatory programmes. Cationic polymers have been identified as a class of polymers of environmental concern due to their sorptive capacities and environmental toxicity profile.
Cationic polymers can be inherently difficult to test substances due to their sorptive capabilities. The standard aquatic testing and assessment guidelines used to fulfill regulatory requirements have been historically developed to address soluble organic molecules and may not necessarily be applicable to polymers. Further, definitions of polymers under registered CASNOs are broad and encompass distributions of varying qualities. Significant knowledge gaps in appropriate testing methodologies and assay interpretation remain. Integrating aquatic hazard data into a standard environmental risk assessment represents additional challenges. iTAP therefore promotes an innovative chemical testing agenda by developing methods, tools, and approaches to better describe toxicity and risk.
Solutions and findings: iTAP project focused on 3 polyquarternium (PQ) families (6, 10, 16) due to their widespread industrial use. Individual com-pounds were selected to represent the breadth of characteristics possible within PQ classes, including high and low molecular weights and charge densities. Experimental work on the extremes of each of the three groups was prioritized to better clarify the contribution to the observed effects from charge density and molecular weight, as these are assumed to be the most significant descriptors including environmental interactions.
PQ-6, -10, and -16 can be considered “difficult to test substances” that require extra care in preparation of stock solutions (stirring, timing prior to test, du-ration of stirring) and pre-sorbing of exposure apparatus. From our analysis, it is clear charge density plays a role in toxic potency, however other aquatic toxicity descriptors may also be relevant. Water quality, especially organic carbon content and water hardness, are able to alter bio- and toxicologically available concentrations of the test materials and therefore modulate observed aquatic toxicity. Variations in these parameters may also influence in-tra- and inter-laboratory reproducibility of test results. Thorough documentation of water quality should accompany all cationic polymer environmental toxicity studies to ensure reproducible and comparable results. Robust test material characterization, including charge density and molecular weight, should be performed.
Physical effects were observed in all trophic levels tested including: clumping of algae, sticking effects in daphnia (e.g., inability to shed carapace, adhering to other individual in test beakers), and chorion perturbations in the fish embryo toxicity (FET) assay. It was unclear if these physical effects were the driving force behind the observed toxicity. Due to the size of the polymers, it is presumed these materials are unable to cross biological membranes. We therefore assume the toxicity was not caused by systemic intra-cellular mechanisms. The effects we saw were not traditional dissolved compound systemic intra-cellular toxicity but rather more based on extra-cellular physical impairment of the organisms. This suggests further exploration of particle-based toxicity is warranted in addition to dissolved phase toxicity. Learnings can be leveraged from this area of research with other compounds. Further research is needed to determine the relative importance of physical (external) effects verses dissolved phase toxicity. Physical effects still may be ecologically meaningful as some cationic polymers are discharged via wastewater treatment where they are neither 100% sorbed to solids nor fully biodegraded – if at all. Development of material specific novel assessment methods may be relevant to explore with regards to toxicity testing of cationic polymers – and polymers in general for that matter.
The results from the iTAP project align with previous observations from the literature. Traditional environmental risk assessment includes acute toxicity tests with Daphnia magna¸ algae Raphidocelis subcapitata, and a standard fish species. According to a 1997 analysis by US EPA, algae are the most sensitive trophic level to cationic polymers. iTAP results further demonstrate the sensitivity of algae. The FET assay aligned with acute fish toxicity data. Thus, animal alternative methods may be relevant in cationic polymer assessments.
There are no robust and sensitive analytical methods for PQ-6, -10, and -16. Despite significant investment, we were unable to develop and validate a novel analytical methodology during this project. However, significant progress was made. More work and time are required to overcome this challenge in the coming years. During method development, significant cationic polymer absorption was observed. Additional research is recommended to under-stand if sorption challenges are more critical during stock solution preparation or during the in-life portion involving sample wells and plates. Surface area to volume ratios may be an important consideration to further under-stand and mitigate sorption. All environmental hazard studies conducted in this project reflect nominal exposure concentrations.
It is clear there is no ‘one size fits all’ cationic polymer hazard and risk assessment – these need to be further developed as outlined in the ECETOC (2021) report 133-3. QSARs are critically important in any regulatory programme and material specific models needs to be developed for these materials. The new models will need to be developed in accordance with the OECD QSAR development guidelines and will in all likelihood be multivariate, as we have shown. Moreover, further guidance will be needed for categorization and read-across of polymers.
Conclusions and value: We have promoted the innovative testing agenda on cationic polymers and documented the challenges and solutions regarding the testing, modelling and risk assessment of PQ-6, -10, and -16. We have highlighted these in the scientific and technical discourse. It is clear among stakeholders that cationic polymers and polymers in general represent challenges. The work of iTAP is world leading in terms of the technical and scientific scrutiny we have presented and thus lays an important foundation for regulatory and business decision making. The findings are presented in the present report and references to publications in prep, in press and already published are included.
Final thoughts and next steps: It is evident that significant challenges remain to ensure sound cationic polymer hazard and risk assessment. Many methodological issues still need to be addressed in this topic area ahead. Work is continuing with the US EPA and Environment and Climate Change Canada on developing QSARs for polymers. iTAP will be chairing a session on polymers at the SETAC-Europe conference in May 2022 in Copenhagen with ECHA. New opportunities will be further explored to expand the work with a focus on testing, modelling, categorization, and assessment of polymers. Polymers represent thousands of different compounds with wide differences in substitution, functionalization, and properties. It is clear many polymers will enter into chemical registration programmes, such as REACH. This will challenge the market the management of the testing and assessment of these important and diverse large macromolecule compounds. Hence, more work must be foreseen – the iTAP project has highlighted some of the most important areas needing further innovation.
Anna Magdalene Brun Hansen og Hans Sanderson. Kationiske polymerer – en risiko for det akvatiske miljø? En introduktion til iTAP-projektet omkring risikovurdering af kationiske polymerer.
Hans Sanderson, Kabiruddin Khan, Anna M. Brun Hansen, Kristin Connors, Monica W. Lam, Kunal Roy, Scott Belanger. Environmental Toxicity (Q)SARs for Polymers as an Emerging Class of Materials in Regulatory Frameworks, with a Focus on Challenges and Possibilities Regarding Cationic Polymers, 17 January 2020.
Sanderson et al. 2020. Chapter 28. Environmental toxicity (Q)SARs for polymers as an emerging class of materials in regulatory frameworks, with a focus on challenges and possibilities regarding cationic polymers. Kunal Roy (Ed.). Ecotoxicological QSARs, Methods in Pharmacology and Toxicology. Springer.
ECETOC report 133-3: Case studies putting the ECETOC conceptual framework for polymers risk assessment CF4 polymers into practice – Case Study 2 – cationic polymers. Sanderson et al. (2021): https://www.ecetoc.org/publication/tr-133-3-case-studies-putting-the-ecetoc-conceptual-framework-for-polymer-risk-assessment-cf4polymers-into-practice/
QSAR Modeling of Aquatic Toxicity of Cationic Polymers. Sanderson et al. Chapter 22 page 433-451 in Chemometrics and Cheminformatics in Aquatic Toxicology, First Edition. Edited by Kunal Roy. ISBN:9781119681595© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc. https://doi.org/10.1002/9781119681397.ch22;
Khan, Sanderson and Roy (2021). QSTR and interspecies-QSTR modelling for aquatic toxicity data gap filling of cationic polymers. Computational Toxicology, https://doi.org/10.1016/j.comtox.2021.100181
Sanderson et al 2020, Ecotoxicological QSARs Springer Methods in Pharmacology and Toxicology, Chapter 28, pp. 681-709; ISBN: 978-1-0716-0149-5; DOI: https://doi.org/10.1007/978-1-0716-0150-1:
Sanderson, Brun Hansen, Belanger, Connors, and Lam. Can Polymers Represent an Aquatic Risk—What’s Known and Unknown? IEAM Blog. April 2020.
MS’s In prep:
- PQ review (Connors et al 2022)
- PQ analytical metods review (Lam et al 2022)
- PQ Algae tox (Connors, Hansen et al 2022)
- PQ Invertebrate tox (Connors, Arndt et al 2022)
- PQ Fish (FET) tox (Rawlings, Connors et al 2022)
External sessions and workshops – organized and hosted
SETAC-EU – Copenhagen session on polymers chaired and organized by iTAP with ECETOC and ECHA
SETAC-EU – virtual – session on polymers chaired and organized by iTAP with ECETOC – online workshop on toxicity testing
Invited presentation of iTAP to the US EPA polymer assessment group– with a focus on QSARs
SETAC-EU Dublin/Virtual – session on polymers chaired and organized by iTAP.
Invited presentation of iTAP to the Environment and Climate Change Canada polymer assessment group – with a focus on QSARs
SETAC-NA Toronto – session on polymers chaired and organized by iTAP as well as stakeholder workshop on analytical methods
Invited presentation of iTAP to the Danish EPA polymer assessment group
Algal toxicity of cationic polyquaternium polymers. Connors K, Brill J, Brun Hansen A, Sanderson H, Belanger S. SETAC Europe, Copenhagen.
Understanding ecotoxicological responses of fish embryos to cationic polymers. Connors K, Rawlings J, Belanger S. SETAC Europe, Copenhagen.
Modelling cationic polymers aquatic toxicity. Sanderson H, Connors K, Roy K, Hosin Khan P, Belanger S. SETAC Europe, Copenhagen.
Cationic polyquaternium acute toxicity and toxicity mitigation in D. magna: implications for chronic toxicity testing and the ACR. Arndt D, Brill J, Brun Hansen A, Woods H, Connors K, Sanderson H, Belanger S. SETAC Europe, Copenhagen.
Khan, Sanderson and Roy. QSTR and interspecies-QSTR modelling for aquatic toxicity data gap filling of cationic polymers. Poster. QSAR 2021 – virtual
Roy, Sanderson and Khan. QSTR modelling for aquatic toxicity of cationic polymers Poster. QSAR 2021 – virtual.
Sanderson et al. Presentation of iTAP findings with a focus on QSARs. Cefic LRI Annual Meeting – online participation.
Cationic polymers – aquatic toxicity and modelling challenges. Sanderson H, Roy K, Pathan M, Brun Hansen A, Lam M, Connors KA, Belanger SE. SETAC Europe, virtual.
Cationic polymer environmental toxicity: a critical data review. Connors KA, Brun Hansen A, Arndt D, Rawlings J, Lam M, Sanderson H, Belanger SE. SETAC Europe, virtual.
Cationic polyquaterniums induce variable toxicity to daphnids depending on charge and molecular weight. Arndt D, Brill J, Brun Hansen A, Connors K, Lam M, Sanderson H, Belanger SE. SETAC Europe, virtual.
Toxicity of cationic polymers to fish embryos. Connors KA, Rawlings J, Lam M, Belanger SE. SETAC Europe, Seville/virtual.
Evaluation of the Chronic Toxicity of Polyquaternium-6 to Daphnia magna. Woods. Brun Hansen A, Brill J, Connors K, Sanderson H. SETAC Europe, virtual.
Algal toxicity of polyquaterniums – do’s, don’ts, and interesting results.
Evaluation of the chronic toxicity of polyquaternium-6 to Daphnia magna. Woods H, Brun Hansen A, Brill J, Connors K, Sanderson H. SETAC Europe, virtual.
Hope H. Woods: Master’s Thesis at Copenhagen University (IFRO): Evaluation of the chronic toxicity of polyquaternium-6 to Daphnia magna
Toxicity of cationic polymers to fish embryos. Connors K, Rawlings J, Sun Y, Karb M, Brill J, Brun Hansen A, Lam M, Sanderson H, Belanger S. 2020. SETAC Europe, virtual.
Cationic polymers – aquatic toxicity and modelling challenges. Sanderson H, Brun Hansen AM, Brill JL Rawlings JM, Sun Y, Lam M , Connors KA, Belanger SE. 2020 SETAC Europe, virtual.
Environmental concern of cationic polymers: a literature review. A. Brun, J.M. Rawlings, J. Brill, M. Lam; M. Hansen, S.E. Belanger, H. Sanderson, K.A. Connors. 2020 SETAC Europe, virtual.
Katarzyna Chmielińska: Master’s Thesis at Copenhagen University (IFRO). Polymers in REACH – a confrontation of stakeholders. Alliances and conflicts within parties affected by regulatory activities concerning a place for polymers in REACH regulation.
Overview of aquatic risk assessment polymers – evidence from cationic polymers. Sanderson H, Brun Hansen AM, Brill JL, Rawlings JM, Sun Y, Lam M , Connors KA, Belanger SE. 2019. SETAC NA. Toronto, CA.
Application of standard tests to non-standard compounds – the aquatic toxicity of cationic polymers. Brun Hansen AM, Rawlings J, Brill J, Lam M, Hansen M, Connors K, Belanger S, Sanderson H. 2019. SETAC NA. Toronto, CA.
Progress in understanding the ecotoxicology of cationic polymers: evidence with Polyquat 10’s. Brill J, Rawlings J, Connors K, Belanger S, Lam M, Brun Hansen A, Sanderson H. 2019. SETAC NA. Toronto, CA.
Improved aquatic Testing and Assessment of cationic Polymers (iTAP). Sanderson H., Belanger S., Connors K., Lam M., Rawlings J., Brill J., Hansen M., Hansen A. 20th Cefic-LRI Annual Workshop, November 2019, Brussels, BE.
Aquatic toxicity of cationic polymers. Hansen M., Rawlings J., Brill J., Lam M., Connors K., Belanger S., Sanderson H. SETAC Europe 29th Annual Meeting, May 2019, Helsinki, FI.
Hansen A. The challenges in aquatic risk assessment of cationic polymers. Scientific seminar, Technical University of Denmark, May 2019, Lyngby, DK.
Monica Lam. Towards a Robust Quantitative Analytical Method for Aquatic Effects Testing of Cationic Polymers. SETAC Europe 29th Annual Meeting, May 2019, Helsinki, FI.
Jessica L. Brill. Progress in understanding the ecotoxicology of cationic polymers: evidence with Polyquat 10’s. SETAC Europe 29th Annual Meeting, May 2019, Helsinki, FI.
Hansen A. Application of standard tests to non-standard compounds: the aquatic toxicity of cationic polymers. SETAC North America 40th Annual Meeting, November 2019, Toronto, ON, CA.
Sanderson H. Overview of aquatic risk assessment of polymers: evidence from cationic polymers. SETAC North America 40th Annual Meeting, November 2019, Toronto, ON,
Sanderson H., Belanger S., Connors K., Lam M., Rawlings J., Brill J., Hansen M., Hansen A. Improved aquatic Testing and Assessment of cationic Polymers (iTAP). 20th Cefic-LRI Annual Workshop, November 2019, Brussels, BE.
Hansen M., Rawlings J., Brill J., Lam M., Connors K., Belanger S., Sanderson H. Aquatic toxicity of cationic polymers. SETAC Europe 29th Annual Meeting, May 2019, Helsinki, FI.
iTAP team. Analytical challenges with environmental testing of polymers and other difficult chemistries. November 2019.
Click here to download the workshop flyer.
Click here for the workshop report.
Can Polymers Represent an Aquatic Risk—What’s Known and Unknown? IEAM Blog. April 2020.