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.

Environmental risk assessment of polycarboxylate polymers used in cleaning products in the United States.

Polycarboxylate polymers have been common components of consumer and institutional cleaning products for decades. With interest heightened in the potential environmental impact of polymers, the American Cleaning Institute, the industry trade association of the cleaning products industry in the United States, is reassessing the state of the science regarding the environmental safety of polymers in cleaning products. In this case study, acrylic acid homopolymers and acrylic acid-maleic acid copolymers are evaluated using historical ecotoxicity data that have been reported over the past three decades. The evaluation includes an environmental exposure assessment that is based on recent information regarding the occurrence of those ingredients in cleaning products and market sales data for cleaning products sold in the United States. The ecotoxicity of polycarboxylate polymers is generally low. Consequently, the potential environmental risks associated with their use in cleaning products in the United States are low even when applying very conservative assumptions to the environmental exposure assessment. In addition, there are recent supporting conclusions from assessments by the governments of Australia and Canada that polycarboxylate polymers are polymers of low concern, and the U.S. Environmental Protection Agency has included a number of polycarboxylate polymers among the ingredients on its Safer Chemical Ingredients List based on their low hazard profile.

Probabilistic exposure assessment of DEEDMAC using measured effluent and sludge concentrations from 41 wastewater treatment plants across the United States.

The cationic surfactant diethyldialkylester dimethyl ammonium chloride (DEEDMAC) is an active ingredient in liquid fabric softeners and, as such, is disposed of down the drain after consumer use. A monitoring program was conducted across the continental United States to measure the concentration of DEEDMAC in the effluent and sludge from 41 wastewater treatment plants (WWTPs). The concentration in the effluent ranged from 32.4 to 2660ng/L, with a mean and standard deviation of 232±450ng/L. The concentration in the sludge ranged from 0.707 to 314mg/kg dw, with a mean and standard deviation of 29.2±50mg/kg dw. The distribution of measured effluent concentrations was combined with a distribution of mixing zone dilutions factors to predict the distribution of DEEDMAC concentrations in mixing zones and sediments under mean flow and 10-year, 7 consecutive day lowest flow (7Q10 low flow) conditions. Additionally, the distribution of measured sludge concentrations was combined with a distribution of land applied sludge volumes and US tilling practices to obtain a predicted distribution of DEEDMAC concentrations in sludge amended soils. The 90th percentile concentrations of DEEDMAC in mixing zones and sediments under mean flow conditions was 10.3ng/L and 451ng/kg, respectively. The 90th percentile concentration in sludge amended soils was 1.92mg/kg. These predicted exposure concentrations were compared to published eco-toxicity data and showed that DEEDMAC has a wide margin of safety and poses negligible ecologic risk to aquatic, sediment, or terrestrial compartments.

Sensitivity to Chronic Methamphetamine Administration and Withdrawal in Mice with Relaxin-3/RXFP3 Deficiency.

Methamphetamine (METH) is a highly addictive psychostimulant, and cessation of use is associated with reduced monoamine signalling, and increased anxiety/depressive states. Neurons expressing the neuropeptide, relaxin-3 (RLN3), and its cognate receptor, RXFP3, constitute a putative 'ascending arousal system', which shares neuroanatomical and functional similarities with serotonin (5-HT)/dorsal raphe and noradrenaline (NA)/locus coeruleus monoamine systems. In light of possible synergistic roles of RLN3 and 5-HT/NA, endogenous RLN3/RXFP3 signalling may compensate for the temporary reduction in monoamine signalling associated with chronic METH withdrawal, which could alter the profile of 'behavioural despair', bodyweight reductions, and increases in anhedonia and anxiety-like behaviours observed following chronic METH administration. In studies to test this theory, Rln3 and Rxfp3 knockout (KO) mice and their wildtype (WT) littermates were injected once daily with saline or escalating doses of METH (2 mg/kg, i.p. on day 1, 4 mg/kg, i.p. on day 2 and 6 mg/kg, i.p. on day 3-10). WT and Rln3 and Rxfp3 KO mice displayed an equivalent sensitivity to behavioural despair (Porsolt swim) during the 2-day METH withdrawal and similar bodyweight reductions on day 3 of METH treatment. Furthermore, during a 3-week period after the cessation of chronic METH exposure, Rln3 KO, Rxfp3 KO and corresponding WT mice displayed similar behavioural responses in paradigms that measured anxiety (light/dark box, elevated plus maze), anhedonia (saccharin preference), and social interaction. These findings indicate that a whole-of-life deficiency in endogenous RLN3/RXFP3 signalling does not markedly alter behavioural sensitivity to chronic METH treatment or withdrawal, but leave open the possibility of a more significant interaction with global or localised manipulations of this peptide system in the adult brain.

Interactions of soy protein fractions with high-methoxyl pectin.

A protein-binding technique was employed to visualize, using scanning electron microscopy, the soy protein as well as the association between HMP and soy protein fractions. Image analysis indicated that at pH 7.5 and 3.5 soy protein isolate showed a bimodal distribution of sizes with an average [ d(0.5)] of about 0.05 microm, but at pH 3.8 the proteins formed larger aggregates than at high pH. Addition of HMP at pH 3.8 changed the surface charge of the particles from +20 to -15 mV. A small addition of HMP caused bridging of the pectin between soy protein aggregates and destabilization. With sufficient HMP, the suspensions showed improved stability to precipitation. The microscopy images are the first direct evidence of the interactions between soy proteins with high-methoxyl pectin (HMP).

Aqueous photochemical reaction kinetics and transformations of fluoxetine.

Fluoxetine (FLX) was shown to be photoreactive in sunlit surface waters. FLX degraded in deionized water when exposed to simulated sunlight with a half-life of 55.2+/-3.6 h(-1). Photodegradation products were identified using high performance liquid chromatography-UV (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS-MS) using electrospray (ES) ionization. Defluorination of the trifluoromethyl group in FLX and in fluometuron and flutalanil,two other compounds containing this functional group, is suggested to be a common direct photolysis pathway for trifluoromethylated compounds. Products resulting from O-dealkylation of FLX were also observed. The rate of degradation was faster in synthetic field water where .OH was the likely dominant oxidant in the system. The bimolecular rate constant for the reaction between FLX and .OH was measured as (8.4+/-0.5) x 10(9) and (9.6 +/-0.8) x 10(9) M(-1) s(-1) using two different methods of competition kinetics. Indirect photodegradation reactions could lead to the production of hydroxylated and O-dealkylated compounds. Although direct photolysis could potentially limitthe persistence of FLX in surface waters, its degradation by indirect photolysis would proceed faster. Thus, this latter process could be important in the elimination of FLX in surface waters.

Aquatic persistence of eight pharmaceuticals in a microcosm study.

The persistence of eight pharmaceuticals from multiple classes was studied in aquatic outdoor field microcosms. A method was developed for the determination of a mixture of acetaminophen, atorvastatin, caffeine, carbamazepine, levofloxacin, sertraline, sulfamethoxazole, and trimethoprim at microg/L levels from surface water of the microcosms using solid phase extraction and high-performance liquid chromatography-ultraviolet (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS-MS). Half-lives in the field ranged from 1.5 to 82 d. Laboratory persistence tests were performed to determine the relative importance of possible loss processes in the microcosms over the course of the study. Results from dark control experiments suggest hydrolysis was not important in the loss of the compounds. No significant differences were observed between measured half-lives of the pharmaceuticals in sunlight-exposed pond water and autoclaved pond water, which suggests photodegradation was important in limiting their persistence, and biodegradation was not an important loss process in surface water over the duration of the study. Observed photoproducts of several of the pharmaceuticals remained photoreactive, which led to further degradation in irradiated surface waters.

Microcosm evaluation of the effects of an eight pharmaceutical mixture to the aquatic macrophytes Lemna gibba and Myriophyllum sibiricum.

Pharmaceuticals have been detected in surface waters of the US and Europe, originating largely from two sources, sewage effluent and agricultural runoff. These compounds often occur as mixtures leading to potential combined effects. In order to investigate the effects of a realistic pharmaceutical mixture on an ecosystem, a study utilizing 15 of 12,000 L aquatic microcosms treated with eight common pharmaceuticals (atorvastatin, acetaminophen, caffeine, sulfamethoxazole, carbamazepine, levofloxacin, sertraline, and trimethoprim) at total (summed) molar concentrations of 0, 0.044, 0.608, 2.664, and 24.538 micromol/L (n = 3) was conducted. Phytotoxicity was assessed on a variety of somatic and pigment endpoints in rooted (Myriophyllum sibiricum) and floating (Lemna gibba) macrophytes over a 35-day period. EC10, EC25 and EC50 values were calculated for each endpoint exhibiting a concentration-dependent response. Generally, M. sibiricum and L. gibba displayed similar sensitivity to the pharmaceutical mixture, with phytotoxic injury evident in both species, which was concentration dependent. Through single compound 7-day daily static renewal toxicity tests with L. gibba, the sulfonamide antibiotic sulfamethoxazole, the fluoroquinolone antibiotic levofloxacin and the blood lipid regulator atorvastatin were found to be the only compounds to elicit phytotoxic effects in the concentration range utilized (0-1000 microg/L). Atorvastatin concentration was highly correlated to decreased pigment content in L. gibba, likely inhibiting the known target enzyme HMGR, the rate-limiting enzyme in isoprenoid biosynthesis. Hazard quotients were calculated for both microcosm and laboratory studies; the highest HQ values were 0.235 (L. gibba) and 0.051 (L. gibba), which are below the threshold value of 1 for chronic risks. The microcosm data suggest that at an ecological effect size of >20%, biologically significant risks are low for L. gibba and M. sibiricum exposed to similar mixtures of pharmaceutical compounds. For M. sibiricum and L. gibba, respective minimum differences of 5 and 1%, were detectable, however, these effect sizes are not considered ecologically significant.

Effects of pharmaceutical mixtures in aquatic microcosms.

Pharmaceuticals have a wide range of biological properties and are released into the environment in relatively large amounts, yet little information is available regarding their effects or potential ecological risks. We exposed outdoor aquatic microcosms to combinations of ibuprofen (a nonsteroidal anti-inflammatory drug), fluoxetine (a selective serotonin reuptake inhibitor), and ciprofloxacin (a DNA gyrase-inhibiting antibiotic) at concentrations of 6, 10, and 10 microg/L, respectively (low treatment [LT]); 60, 100, and 100 microg/L, respectively (medium treatment [MT]); and 600, 1,000, and 1,000 microg/L, respectively (high treatment [HT]). We maintained these concentrations for 35 d. Few responses were observed in the LT; however, effects were observed in the MT and HT. Fish mortality occurred in the MT (<35 d) and in the HT (<4 d). Phytoplankton increased in abundance and decreased in diversity (number of taxa) in the HT, with consistent trends being observed in the MT and LT. Zooplankton also showed increased abundance and decreases in diversity in the HT, with consistent trends being observed in the MT. Multivariate analyses for zooplankton and phytoplankton suggested interactions between these communities. Lemna gibba and Myriophyllum spp. showed mortality in the HT; growth of L. gibba was also reduced in the MT. Bacterial abundance did not change in the HT. All responses were observed at concentrations well below the equivalent pharmacologically active concentrations in mammals. Although the present data do not suggest that ibuprofen, fluoxetine, and ciprofloxacin are individually causing adverse effects in surface-water environments, questions remain about additive responses from mixtures.

PhetoFate: a new approach in accounting for the contribution of indirect photolysis of pesticides and pharmaceuticals in surface waters.

A new approach was developed to account for the contribution of indirect photolysis of pesticides and pharmaceuticals in which laboratory test conditions are similar to those prevalent in the aqueous environment. Rates of photolysis as a function of water composition were investigated for several aquatic contaminants. Using the laboratory-based test system, PhotoFate, the dependence of phototransformation rates on concentrations of natural water constituents that are radical producers and scavengers (nitrate, colored dissolved organic matter, bicarbonate) was studied. Mean half-lives of the model compounds in the presence of water constituents were compared to their direct photolysis half-lives to assess the contribution of photosensitized reactions to their fate in surface waters. Reactions mediated by .OH were predominant in waters with high nitrate concentrations. Colored dissolved organic matter (cDOM) acted mainly as a radiation filter and had a more important role in scavenging radicals than in their production. However, in low nitrate waters, the contribution of cDOM-derived reactive intermediates to the degradation of parent compounds became more apparent