Green Chemistry in the Synthesis of Pharmaceuticals.

The principles of green chemistry (GC) can be comprehensively implemented in green synthesis of pharmaceuticals by choosing no solvents or green solvents (preferably water), alternative reaction media, and consideration of one-pot synthesis, multicomponent reactions (MCRs), continuous processing, and process intensification approaches for atom economy and final waste reduction. The GC's execution in green synthesis can be performed using a holistic design of the active pharmaceutical ingredient's (API) life cycle, minimizing hazards and pollution, and capitalizing the resource efficiency in the synthesis technique. Thus, the presented review accounts for the comprehensive exploration of GC's principles and metrics, an appropriate implication of those ideas in each step of the reaction schemes, from raw material to an intermediate to the final product's synthesis, and the final execution of the synthesis into scalable industry-based production. For real-life examples, we have discussed the synthesis of a series of established generic pharmaceuticals, starting with the raw materials, and the intermediates of the corresponding pharmaceuticals. Researchers and industries have thoughtfully instigated a green synthesis process to control the atom economy and waste reduction to protect the environment. We have extensively discussed significant reactions relevant for green synthesis, one-pot cascade synthesis, MCRs, continuous processing, and process intensification, which may contribute to the future of green and sustainable synthesis of APIs.

Understanding ecotoxicological drivers and responses of freshwater green algae, Raphidocelis subcapitata, to cationic polyquaternium polymers.

Cationic polymer (CP) ecotoxicity is important to understand and investigate as they are widely used in industrial and consumer applications and have shown toxic effects in some aquatic organisms. CPs are identified as "polymers of concern" and are to be prioritized in upcoming regulatory reviews, (e.g., REACH). Algae have generally been found to be the most sensitive trophic level to CP. This study aimed at elucidating the magnitude of cationic polyquaternium toxicity towards algae and to understand key toxicological drivers. A suite of polyquaterniums with varying charge density (charged nitrogen moieties) and molecular weight were selected. Highly charged polyquaternium-6 and -16 were toxic towards the freshwater green microalgae Raphidocelis subcapitata with ErC50-values ranging between 0.12 and 0.41 mg/L. Lower charge density polyquaternium-10 materials had much lower toxicity with ErC50 > 200 mg/L, suggesting that charge density is an important driver of algal toxicity. These levels of toxicity were in line with historic CP data in literature. Algal agglomeration was observed in all tests but was not linked with impacts on algal growth rate. However, agglomeration can pose challenges in the technical conduct of tests and can impair interpretation of results. The toxicity mitigation potential of humic acid was also explored. The addition of 2-20 mg/L humic acid completely mitigated PQ6 and PQ16 toxicity at concentrations higher than clean water ErC50-values. CP toxicity mitigation has also been observed in fish and invertebrate tests, suggesting that CP mitigation should be accounted for in all trophic levels within an environmental safety framework.

Acute toxicity of organoarsenic chemical warfare agents to Danio rerio embryos.

During the 20th century, thousands of tons of munitions containing organoarsenic chemical warfare agents (CWAs) were dumped into oceans, seas and inland waters around the world. As a result, organoarsenic CWAs continue to leak from corroding munitions into sediments and their environmental concentrations are expected to peak over the next few decades. There remains, however, a lack of knowledge about their potential toxicity to aquatic vertebrates, such as fish. The aim of this study was to fill in this gap in research, by investigating the acute toxicity of organoarsenic CWAs on fish embryos, using the model species, Danio rerio. To estimate the acute toxicity thresholds of organoarsenic CWAs (Clark I, Adamsite, PDCA), a CWA-related compound (TPA), as well as four organoarsenic CWA degradation products (Clark I[ox], Adamsite[ox], PDCA[ox], TPA[ox]), standardized tests were performed following the OECD no. 236 Fish Embryo Acute Toxicity Test guidelines. Additionally, the detoxification response in D. rerio embryos was investigated by analysing the mRNA expression of five genes encoding antioxidant enzymes (CAT, SOD, GPx, GR and GST). During the 96 h of exposure, organoarsenic CWAs induced lethal effects in D. rerio embryos at very low concentrations (classified as 1st category pollutants according to GHS categorization), and were therefore deemed to be serious environmental hazards. Although TPA and the four CWA degradation products caused no acute toxicity even at their maximum solubility, the transcription of antioxidant-related genes was altered upon exposure to these compounds, indicating the need for further testing for chronic toxicity. Incorporating the results of this study into ecological risk assessments will provide a more accurate prediction of the environmental hazards posed by CWA-related organoarsenicals.

Biocide Runoff from Building Facades: Degradation Kinetics in Soil.

Biocides are common additives in building materials. In-can and film preservatives in polymer-resin render and paint, as well as wood preservatives are used to protect facade materials from microbial spoilage. Biocides leach from the facade material with driving rain, leading to highly polluted runoff water (up to several mg L-1 biocides) being infiltrated into the soil surrounding houses. In the present study the degradation rates in soil of 11 biocides used for the protection of building materials were determined in laboratory microcosms. The results show that some biocides are degraded rapidly in soil (e.g., isothiazolinones: T1/2 < 10 days) while others displayed higher persistence (e.g., terbutryn, triazoles: T1/2 ≫ 120 days). In addition, mass balances of terbutryn and octylisothiazolinone were determined, including nine (terbutryn) and seven (octylisothiazolinone) degradation products, respectively. The terbutryn mass balance could be closed over the entire study period of 120 days and showed that relative persistent metabolites were formed, while the mass balances for octylisothiazolinone could not be closed. Octylisothiazolinone degradation products did not accumulate over time suggesting that the missing fraction was mineralized. Microtox-tests revealed that degradation products were less toxic toward the bacterium Aliivibrio fischeri than their parent compounds. Rain is mobilizing these biocides from the facades and transports them to the surrounding soils; thus, rainfall events control how often new input to the soil occurs. Time intervals between rainfall events in Northern Europe are shorter than degradation half-lives even for many rapidly degraded biocides. Consequently, residues of some biocides are likely to be continuously present due to repeated input and most biocides can be considered as "pseudo-persistent"-contaminants in this context. This was verified by (sub)urban soil screening, where concentrations of up to 0.1 µg g-1 were detected for parent compounds as well as terbutryn degradation products in soils below biocide treated facades.

Environmental Safety of the Use of Major Surfactant Classes in North America.

This paper brings together over 250 published and unpublished studies on the environmental properties, fate, and toxicity of the four major, high-volume surfactant classes and relevant feedstocks. The surfactants and feedstocks covered include alcohol sulfate or alcohol sulfate (AS), alcohol ethoxysulfate (AES), linear alkylbenzene sulfonate (LAS), alcohol ethoxylate (AE), and long-chain alcohol (LCOH). These chemicals are used in a wide range of personal care and cleaning products. To date, this is the most comprehensive report on these substance's chemical structures, use, and volume information, physical/chemical properties, environmental fate properties such as biodegradation and sorption, monitoring studies through sewers, wastewater treatment plants and eventual release to the environment, aquatic and sediment toxicity, and bioaccumulation information. These data are used to illustrate the process for conducting both prospective and retrospective risk assessments for large-volume chemicals and categories of chemicals with wide dispersive use. Prospective risk assessments of AS, AES, AE, LAS, and LCOH demonstrate that these substances, although used in very high volume and widely released to the aquatic environment, have no adverse impact on the aquatic or sediment environments at current levels of use. The retrospective risk assessments of these same substances have clearly demonstrated that the conclusions of the prospective risk assessments are valid and confirm that these substances do not pose a risk to the aquatic or sediment environments. This paper also highlights the many years of research that the surfactant and cleaning products industry has supported, as part of their environmental sustainability commitment, to improve environmental tools, approaches, and develop innovative methods appropriate to address environmental properties of personal care and cleaning product chemicals, many of which have become approved international standard methods.

Collaborative approaches to greenhouse gas inventory in higher education: Insights from the Universities Denmark Group.

The challenges faced by universities and private industry in estimating their emissions for decarbonisation are similar, but the task of linking emissions to university operations, namely procurement, is complex and time-consuming due to the wide range and types of purchases. Here, participatory action research is used to address these challenges, with a group of Danish universities to investigate the functions and improve the completeness of university GHG inventories. The research enabled knowledge sharing and collaboration, leading to a better understanding of the complexities and possibilities of GHG inventories. The main conclusions drawn from discussions are that the GHG inventory should serve multiple functions; an inward-facing decision support material, and an externally-facing communication tool. EXIOBASE, an environmentally extended input-output model, was identified as a useful tool for future inventories, particularly in procurement, due to its comprehensive spend-based assessment of purchases also relevant to universities. With more universities adopting spend-based practices, the presented conclusions shed light on potential risks of this method that have not yet been discussed in this context. A consensus on methodological trade-offs, relevant activities, and data considerations for a GHG inventory are reached and reflected on. As suppliers can increasingly deliver product specific climate related information, a data ontology is needed to appropriately incorporate supplier-specific data into consistent inventories without conflicting with methodological principles and upholding proprietary requirements of suppliers. Addressing challenges identified through this collaborative investigation will expand on the dialogue in the literature and help shape how universities conduct and use GHG inventories. Keywords: Sustainable university; Action Research; Consequential Attributional; GHG Protocol.

Occurrence and sorption properties of arsenicals in marine sediments.

The content of total arsenic, the inorganic forms: arsenite (As(III)) and arsenate (As(V)), the methylated forms: monomethylarsonic acid and dimethylarsinic acid (DMA), trimethylarsenic oxide, tetramethylarsenonium ion and arsenobetaine was measured in 95 sediment samples and 11 pore water samples from the Baltic Sea near the island of Bornholm at depths of up to 100 m. As(III+V) and DMA were detected in the sediment and As(III+V) was detected in the sediment pore water. Average total As concentration of 10.6 ± 7.4 mg/kg dry matter (DM) in the sediment corresponds to previously reported values in the Baltic Sea and other parts of the world. Existing data for on-site measurements of sorption coefficients (Kd) of arsenicals in marine and freshwater sediments show large variability from <1 to >1,000 L/kg. In this work, calculated sorption coefficients (Kd and Koc) for As(III+V) showed significant correlation with depth, dissolved oxygen (DO), salinity and sediment classification; for depths <70 m, salinity <11 %, DO >9 mg/L and sand/silt/clay sediments the Kd was 118 ± 76 L/kg DM and for depths >70 m, salinity >11 %, DO < 9 mg/L and muddy sediments the Kd was 513 ± 233 L/kg DM. The authors recommend using the found Kd value for arsenic in marine sediments when conditions are similar to the Baltic Sea. At locations with significant anthropogenic point sources or where the local geology contains volcanic rock and sulphide mineral deposits, there may be significantly elevated arsenic concentrations, and it is recommended to determine on-site Kd values.

Preliminary studies on model development for rodent toxicity and its interspecies correlation with aquatic toxicities of pharmaceuticals.

Environmental toxicity due to pharmaceuticals has been an issue of serious concern for long time. Development of chemometric models with reliable predictive power has been considered as an effective tool for the design of new drug agents with reduced or without ecotoxic potential. Considering a higher degree of similarity in genetic homology towards drug receptor with mammals, we have used a dataset of 194 compounds with reported rodent, fish, daphnia and algae toxicity data for extrapolation of their toxicity towards humans. Allowing for rodents as the most surrogate to human physiology, attempts have also been made to develop interspecies correlation models keeping rodent toxicity as dependent variable so that any drug without reported rodent toxicity can be predicted using fish, daphnia or algae toxicity data which can be consequently extrapolated to human toxicity. The developed models have been subjected to multiple validation strategies. Acceptable results have been obtained in both cases of direct and interspecies extrapolation quantitative structure-activity relationship models.

Suspect and non-target screening of semi-volatile emerging contaminants in indoor dust from Danish kindergartens.

Indoor dust is a sink of hundreds of organic chemicals, and humans may potentially be exposed to these via indoor activities. This study investigated potentially harmful semi-volatile organic contaminants in indoor dust from Danish kindergartens using suspect and non-target screening on gas chromatography (GC)-Orbitrap, supported by target analyses using GC-low resolution mass spectrometry (LRMS). A suspect list of 41 chemicals with one or more toxicological endpoints, i.e. endocrine disruption, carcinogenicity, neurotoxicity and allergenicity, known or suspected to be present in indoor dust, was established including phthalate and non-phthalate plasticizers, flame retardants, bisphenols, biocides, UV filters and other plastic additives. Of these, 29 contaminants were detected in the indoor dust samples, also including several compounds that had been banned or restricted for years. In addition, 22 chemicals were tentatively identified via non-target screening. Several chemicals have not previously been detected in Danish indoor dust. Most of the detected chemicals are known to be potentially harmful for human health while hazard assessment of the remaining compounds indicated limited risks to human. However, children were not specifically considered in this hazard assessment.

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 impact of the explosion of the Nord Stream pipelines.

Armed conflicts have, in addition to severe impacts on human lives and infrastructure, also impacts on the environment, which needs to be assessed and documented. On September the 26th 2022, unknown perpetrators deliberately ruptured the two gas pipelines Nord Stream 1 and 2 with four coordinated explosions near a major chemical munition dump site near the Danish island of Bornholm in the Baltic Sea. While the massive release of natural gas into atmosphere raised serious concerns concerning the contribution to climate change-this paper assesses the overlooked direct impact of the explosions on the marine ecosystem. Seals and porpoises within a radius of four km would be at high risk of being killed by the shockwave, while temporary impact on hearing would be expected up to 50 km away. As the Baltic Proper population of harbour porpoises (Phocoena phocoena) is critically endangered, the loss or serious injury of even a single individual is considered a significant impact on the population. The rupture moreover resulted in the resuspension of 250000 metric tons of heavily contaminated sediment from deep-sea sedimentary basin for over a week, resulting in unacceptable toxicological risks towards fish and other biota in 11 km3 water in the area for more than a month.

Investigation of long-term hazards of chemical weapon agents in the environment of Sardasht area, Iran.

The present study aimed to investigate the persistence and existence of chemical warfare agents (CWAs) and related dissipation products in the environment of Sardasht area, Iran. Three types of environmental samples including water, soil, and native local plant materials were collected and analyzed. Gas chromatography-mass spectrometry in the electron impact ionization mode has been developed for the separation, screening, identification, and qualification of chemicals after the sample preparation methods. The initial results revealed that no trace of related compounds or CWAs was detected in the soil and water samples. However, trace amounts of some degradation products of blistering agents like mustard gas (HD) and lewisite were found in a tree wood from a house subjected to chemical attack as well as in barley samples (a mixture of leaves and root) collected from an agricultural field in the area indicating chronic low exposure to the environment and people. In order to validate the applied extraction procedures, ethylene glycol was spiked to some of the samples including groundwater, surface soil, grape, and alfalfa plants. All the recoveries were in the range of 83.6-107.4% with the relative standard deviations varying from 4.9% to 12.4% (n = 3) successfully.

Understanding Ecotoxicological Responses of Fish Embryos and Gill Cells to Cationic Polymers.

Cationic polymers are considered by the scientific and regulatory communities as a group of greater interest amongst the polymers in commerce. As a category, relatively little hazard information is available in the public literature. Very few examples exist of published, high-quality polymer characterization and quantification of exposure. In the present study we describe a series of fish embryo toxicity (FET) and fish gill cytotoxicity assays used to establish a baseline understanding of several representative polyquaternium categories (PQ-6, PQ-10, PQ-16) in animal alternative models, accompanied by high-quality analytical characterization. Materials were chosen to encompass a range of molecular weights and charge densities to determine the influence of test material characteristics on toxicity. Both chorionated and dechorionated FET assays were generally similar to published acute fish toxicity data. Toxicity was correlated with cationic polymer charge density, and not with molecular weight, and was a combination of physical effects and likely toxicity at the site of action. Toxicity could be ameliorated by humic acid in a dose-dependent manner. Fish gill cytotoxicity results were orders of magnitude less sensitive than FET test responses. Environ Toxicol Chem 2022;41:2259-2272. © 2022 SETAC.

Presence and risk assessment of pharmaceuticals in surface water and drinking water.

Trace amounts of pharmaceuticals have been detected in surface waters in the nano- to microgram per liter range, and in drinking water in the nanogram/L range. The environmental risks of pharmaceuticals in surface waters have been evaluated and generally found to be low if the wastewater is treated before release to the environment. The human health risks of trace amounts of pharmaceuticals in drinking water have however not been evaluated in any great depth. Preliminary screening level assessments suggest risk to be low--but the public and decision-makers are concerned and would like the matter investigated more thoroughly, especially with regards to mixture effects, chronic long-term effects and sensitive sub-populations. The World Health Organization is currently evaluating the need for credible health based guidance associated with low concentrations of pharmaceuticals in drinking water. The aim of this paper is to summarize the state-of-the-science and the ongoing international debate on the topic.

Acute aquatic toxicity of arsenic-based chemical warfare agents to Daphnia magna.

Sea dumping of chemical warfare (CW) took place worldwide during the 20th century. Submerged CW included metal bombs and casings that have been exposed for 50-100 years of corrosion and are now known to be leaking. Therefore, the arsenic-based chemical warfare agents (CWAs), pose a potential threat to the marine ecosystems. The aim of this research was to support a need for real-data measurements for accurate risk assessments and categorization of threats originating from submerged CWAs. This has been achieved by providing a broad insight into arsenic-based CWAs acute toxicity in aquatic ecosystems. Standard tests were performed to provide a solid foundation for acute aquatic toxicity threshold estimations of CWA: Lewisite, Adamsite, Clark I, phenyldichloroarsine (PDCA), CWA-related compounds: TPA, arsenic trichloride and four arsenic-based CWA degradation products. Despite their low solubility, during the 48 h exposure, all CWA caused highly negative effects on Daphnia magna. PDCA was very toxic with 48 h D. magna LC50 at 0.36 µg × L-1 and Lewisite with EC50 at 3.2 µg × L-1. Concentrations at which no immobilization effects were observed were slightly above the analytical Limits of Detection (LOD) and Quantification (LOQ). More water-soluble CWA degradation products showed no effects at concentrations up to 100 mg × L-1.

Use of a (quantitative) structure-activity relationship [(Q)SAR] model to predict the toxicity of naphthenic acids.

Naphthenic acids (NA) are a complex mixture of carboxylic acids that are natural constituents of oil sand found in north-eastern Alberta, Canada. NA are released and concentrated in the alkaline water used in the extraction of bitumen from oil sand sediment. NA have been identified as the principal toxic components of oil sands process-affected water (OSPW), and microbial degradation of lower molecular weight (MW) NA decreases the toxicity of NA mixtures in OSPW. Analysis by proton nuclear magnetic resonance spectroscopy indicated that larger, more cyclic NA contain greater carboxylic acid content, thereby decreasing their hydrophobicity and acute toxicity in comparison to lower MW NA. The relationship between the acute toxicity of NA and hydrophobicity suggests that narcosis is the probable mode of acute toxic action. The applicability of a (quantitative) structure-activity relationship [(Q)SAR] model to accurately predict the toxicity of NA-like surrogates was investigated. The U.S. Environmental Protection Agency (EPA) ECOSAR model predicted the toxicity of NA-like surrogates with acceptable accuracy in comparison to observed toxicity values from Vibrio fischeri and Daphnia magna assays, indicating that the model has potential to serve as a prioritization tool for identifying NA structures likely to produce an increased toxicity. Investigating NA of equal MW, the ECOSAR model predicted increased toxic potency for NA containing fewer carbon rings. Furthermore, NA structures with a linear grouping of carbon rings had a greater predicted toxic potency than structures containing carbon rings in a clustered grouping.

Acute aquatic toxicity of sulfur mustard and its degradation products to Daphnia magna.

Sulphur mustard (HD) was the most widely produced chemical warfare agent (CWA) in the history of chemical warfare (CW). Simultaneously, the loads of HD account as by far the largest fraction of the sea-dumped CW. Nowadays its presence in the marine ecosystems recognized as a serious threat for marine users and maritime industries. Although, during over a decade of research much has been done to assess the environmental threats linked with underwater chemical munitions. There are, however, essential gaps in scientific knowledge including scarce information about the aquatic toxicity thresholds of HD and its degradation products. Standardized biotests were performed according to the Organisation for Economic Co-operation and Development (OECD) Test No. 202: Daphnia sp. Acute Immobilisation Test guidelines. Obtained results provide a solid foundation for comparison and categorisation of threats of HD and its degradation products. With the D. magna LC50 aquatic acute toxicity threshold at as low as 224 ± 12 µg × L-1, 1,2,5-trithiepane is very toxic, being one of the most toxic CWA degradation products that have been investigated up to date. It exhibits stronger effects than 1,4,5-oxadithiepane and diluted HD that turn out to be toxic. In total, the toxicity of 7 compounds has been estimated. Whenever possible, toxicity thresholds were compared with previously existing data originating from different biotests and mathematical modelling.

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action.

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

Environmental properties of long chain alcohols. Part 1: Physicochemical, environmental fate and acute aquatic toxicity properties.

This paper summarises the physicochemical, biodegradation and acute aquatic ecotoxicity properties of long chain aliphatic alcohols. Properties of pure compounds are shown to follow somewhat predictable trends, which are amenable to estimation by quantitative structure-activity relationships ((Q)SARs). This allows predictions of data relating to human and environmental safety profiles and patterns. These alcohols have been shown to be rapidly degradable under standard conditions up to C(18). Furthermore, evidence suggests that longer chain lengths are also rapidly biodegradable. While logK(ow) values suggest possible bioaccumulation potential, available data suggest that these substances are not as bioaccumulative as estimations would predict. For acute aquatic toxicity, solubility limits the possibility of effects being appropriately observed and become increasingly challenging above C(12). Further, a model has been developed for multi-component mixtures which give an excellent account of aquatic ecotoxicity allowing for the prediction of acute effects of un-tested mixtures.

An overview of hazard and risk assessment of the OECD high production volume chemical category--long chain alcohols [C(6)-C(22)] (LCOH).

This review summarizes the findings of the assessment report for the category, long chain alcohols (LCOH) with a carbon chain length range of C(6)-C(22) covering 30 substances, and >1.5million tonnes/year consumed globally. The category was evaluated under the Organization for Economic Co-operation and Development (OECD) high production volume chemicals program in 2006. The main findings of the assessment include: (1) no unacceptable human or environmental risks were identified; (2) these materials are rapidly and readily biodegradable; (3) a parabolic relationship was demonstrated between carbon chain length and acute and chronic aquatic toxicity; (4) category-specific (quantitative) structure-activity relationships were developed enabling prediction of properties across the entire category; (5) LCOH occur naturally in the environment in an equilibrium between synthesis and degradation; (6) industry coming together and sharing resources results in minimizing the need for additional animal tests, produces cost savings, and increases scientific quality of the assessment.