Environmental hazard of cationic polymers relevant in personal and consumer care products: A critical review.

Historically, polymers have been excluded from registration and evaluation under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program, the European chemical management program. Recently, interest has increased to include polymers. A tiered registration system has been envisioned and would begin with classes of polymers of greater interest based on certain properties. Cationic polymers are one such class. There is a pressing need to understand the quality and limitations of historical cationic polymer studies and to identify key sources of uncertainty in environmental hazard assessments so we can move toward scientifically robust analyses. To that end, we performed a critical review of the existing cationic polymer environmental effects literature to evaluate polymer characterization and test methodologies to understand how these parameters may affect test interpretation. The relationship between physicochemical parameters, acute and chronic toxicity, and relative trophic level sensitivity were explored. To advance our understanding of the environmental hazard and subsequent risk characterization of cationic polymers, there is a clear need for a consistent testing approach as many polymers are characterized as difficult-to-test substances. Experimental parameters such as dissolved organic carbon and solution renewal approaches can alter cationic polymer bioavailability and toxicity. It is recommended that OECD TG 23 "Aqueous-Phase Aquatic Toxicity Testing of Difficult Test Substances" testing considerations be applied when conducting environmental toxicity assays with cationic polymers. Integr Environ Assess Manag 2023;19:312-325. © 2021 SETAC.

Crumpling of silver nanowires by endolysosomes strongly reduces toxicity.

Fibrous particles interact with cells and organisms in complex ways that can lead to cellular dysfunction, cell death, inflammation, and disease. The development of conductive transparent networks (CTNs) composed of metallic silver nanowires (AgNWs) for flexible touchscreen displays raises new possibilities for the intimate contact between novel fibers and human skin. Here, we report that a material property, nanowire-bending stiffness that is a function of diameter, controls the cytotoxicity of AgNWs to nonimmune cells from humans, mice, and fish without deterioration of critical CTN performance parameters: electrical conductivity and optical transparency. Both 30- and 90-nm-diameter AgNWs are readily internalized by cells, but thinner NWs are mechanically crumpled by the forces imposed during or after endocytosis, while thicker nanowires puncture the enclosing membrane and release silver ions and lysosomal contents to the cytoplasm, thereby initiating oxidative stress. This finding extends the fiber pathology paradigm and will enable the manufacture of safer products incorporating AgNWs.

The role of charge in the toxicity of polymer-coated cerium oxide nanomaterials to Caenorhabditis elegans.

This study examined the impact of surface functionalization and charge on ceria nanomaterial toxicity to Caenorhabditis elegans. The examined endpoints included mortality, reproduction, protein expression, and protein oxidation profiles. Caenorhabditis elegans were exposed to identical 2-5nm ceria nanomaterial cores which were coated with cationic (diethylaminoethyl dextran; DEAE), anionic (carboxymethyl dextran; CM), and non-ionic (dextran; DEX) polymers. Mortality and reproductive toxicity of DEAE-CeO2 was approximately two orders of magnitude higher than for CM-CeO2 or DEX-CeO2. Two-dimensional gel electrophoresis with orbitrap mass spectrometry identification revealed changes in the expression profiles of several mitochondrial-related proteins and proteins that are expressed in the C. elegans intestine. However, each type of CeO2 material exhibited a distinct protein expression profile. Increases in protein carbonyls and protein-bound 3-nitrotyrosine were also observed for some proteins, indicating oxidative and nitrosative damage. Taken together the results indicate that the magnitude of toxicity and toxicity pathways vary greatly due to surface functionalization of CeO2 nanomaterials.

Multigeneration impacts on Daphnia magna of carbon nanomaterials with differing core structures and functionalizations.

Several classes of contaminants have been shown to have multigenerational impacts once a parental generation has been exposed. Acute and chronic toxicity are described for several types of nanomaterials in the literature; however, no information is available on the impact of nanomaterials on future generations of organisms after the exposure is removed. In the present study, the authors examined the impacts of carbon nanomaterials (CNMs), including fullerenes (C60), single-walled carbon nanotubes (SWCNTs), and multiwalled carbon nanotubes (MWCNTs) with neutral, positive, and negative functional groups to F1 and F2 generation daphnids after an F0 exposure. Data from the present study indicate that multigenerational toxicity is present with certain nanomaterial exposures and is highly dependent on the surface chemistry of the nanomaterial. Many CNMs that showed toxicity to exposed F0 daphnids in previous experiments did not induce multigenerational toxicity. Certain nanomaterials, however, such as C60-malonate, SWCNTs, SWCNT-CONH2 , and MWCNTs, caused a significant decrease in either survival or reproduction in F1 daphnids; and SWCNT-CONH2 decreased reproduction out to the F2 generation. Impacts of nanomaterials on F1 and F2 size were small and lacked clear patterns, indicating that CNMs have minimal multigenerational impacts on size. Industries should take into account how surface chemistry influences nanomaterial toxicity to future generations of organisms to create sustainable nanomaterials that do not harm freshwater ecosystems.

Molecular interactions of nanomaterials and organisms: defining biomarkers for toxicity and high-throughput screening using traditional and next-generation sequencing approaches.

The toxicity of nanomaterials depends on the basic interaction of the chemistry of the material with the molecular pathways in an organism. To design safe and sustainable nanomaterials, more detailed information on the molecular interaction and biochemical machinery that is altered in an organism upon contact with a nanomaterial is needed. There are a multitude of papers now on the toxicity of nanomaterials to various model organisms from human to ecological models, but many focus on acute high dose exposures and research on the toxicity of other chemicals has shown that the dose of a chemical can have a tremendous impact on the pathways that are affected within the organism. The most common pathways investigated in nanotoxicity experiments are related to oxidative stress, yet oxidative stress can be a temporary and natural response to an insult without a negative outcome. There are a multitude of other potential mechanisms that may be triggered in response to a toxin at sublethal exposures. Here we present a review documenting the evidence to date on the indicators of the molecular response to nanomaterials from in vitro and in vivo studies. Alternative pathways as indicated by single biomarker, global gene expression studies and next generation sequencing approaches are discussed as well as the impacts of nanomaterial type, dose, and the types of system studied. Specific mechanisms that are impacted by a nanomaterial can be used as the basis of better high-throughput methods for evaluating how nanomaterial chemistry impacts toxicity and support models to predict the toxicity of future nanomaterials.

Core structure and surface functionalization of carbon nanomaterials alter impacts to daphnid mortality, reproduction, and growth: acute assays do not predict chronic exposure impacts.

There are currently over ninety products incorporating carbon nanomaterials (CNMs) on the market today for a variety of applications. Modifications in core structure and surface chemistry of manufactured nanomaterials are used to optimize nanomaterials for specific uses. However, there is a notable lack of information on how core structure and surface chemistry may alter toxicity in low-level, chronic exposures. This paper examines the effects of twelve CNMs that differ in their core structure and surface chemistry to Daphnia magna over a 21-day chronic exposure. Overall, nanomaterials with a carbon nanotube core were more toxic to daphnids than fullerenes, with the one exception of fullerenes with a gamma-cyclodextrin surface chemistry. Acute mortality was not a good predictor of chronic effects as none of the CNMs induced toxicity at tested concentrations after 48 h, yet chronic assays indicated significant differences in mortality, reproduction, and growth realized after 21 days. Our results indicate that (1) acute exposure assays do not accurately describe the impact of CNMs to biological systems, (2) chronic exposures provide valuable information that indicates the potential for different modes of action for nanomaterials of differing chemistries, and (3) core structure and surface chemistry both influence particle toxicity.

Functionalization impacts the effects of carbon nanotubes on the immune system of rainbow trout, Oncorhynchus mykiss.

Recent studies have demonstrated the potential for manufactured nanomaterials to reach the aquatic environment. There is a need to determine if these materials will have an impact on aquatic species and at what level of exposure. In addition there is a need to develop models to test the potential effects of the multitude of particle types in production on aquatic vertebrates. The purpose of this research was to determine the impact of manufactured nanomaterials on the immune system of an aquatic vertebrate model, the rainbow trout (Oncorhynchus mykiss). We investigated how structure and type of functionalization of manufactured nanomaterials could affect immunotoxicity. To assess immunotoxicity, we used a well-studied trout macrophage primary cell culture system in conjunction with the expression of IL-1ß and IFNα for proinflammatory and antiviral gene expression. There was a significant difference among the different carbon nanotube-based nanomaterials in their level of stimulation of IL-1ß in macrophage cells and the dose at which they became stimulatory. At concentrations that were sublethal to cells, almost all nanomaterials were stimulatory at some concentration. Single-walled nanotubes and multi-walled nanotubes that were differentially functionalized to be water-soluble, varied in their effects; specifically the concentrations at which they were stimulatory and they were more stimulatory to IL-1ß expression compared with unfunctionalized nanotubes. Each functionalized nanotube type caused a dose-dependent response with the lowest exposures (0.05-1.0 µg/ml) having no stimulatory response and at the highest concentrations (5 µg/ml and 10 µg/ml) stimulating a response similar to the positive LPS positive control. Anionic functionalized multi-walled nanotubes and zwitterionic single-walled nanotubes were stimulatory at the lowest dose (0.5 µg/ml). Sodium deoxycholate, often used to suspend nanomaterials, was also tested and was as stimulatory to the immune cells as the nanomaterials. This study is the first report of the effects of nanomaterials on the function of the immune system in a nonmammalian vertebrate. Since the innate immune system is the first to respond to the intrusion of foreign material, analysis of the effects of nanomaterials on cells of the innate immune system should provide valuable information on how these materials are perceived and affect an animal. Ultimately such research will provide the means to determine which nanomaterials are most harmful to aquatic species and how particles may be altered or functionalized to decrease their toxicity.

Toxicity biomarker expression in daphnids exposed to manufactured nanoparticles: changes in toxicity with functionalization.

In previous work we have shown that the toxicity of nanomaterials to Daphnia spp. differs with the type of nanoparticle either due to the core of the particle or to the way in which a particle suspension is prepared. The purpose of this study was to investigate the toxicity and antioxidant response of Daphnia pulex in relation to a change in surface functionalization of nanomaterials with the same core material, nC60. Despite the lack of acute toxicity for various nC60 suspensions up to 100 ppm concentration, there was a significant production of the toxicity biomarkers glutathione-S-transferase and catalase, at lower concentrations indicating changes in reactive oxygen species. Nanoparticle functionalization significantly affected this response. Oxidative stress markers appear to be a good predictor of potential future toxicity of nanomaterials. Functionalization alters both toxicity and oxidative stress in whole organism assays.