Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern.

Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.

Formaldehyde Vapor Characteristics in Varied Decontamination Environments.

INTRODUCTION: This effort investigated formaldehyde vapor characteristics under various environmental conditions by the analyses of air samples collected over a time-course. This knowledge will help responders achieve desired formaldehyde exposure parameters for decontamination of affected spaces after a biological contamination incident. METHODS: Prescribed masses of paraformaldehyde and formalin were sublimated or evaporated, respectively, to generate formaldehyde vapor. Adsorbent cartridges were used to collect air samples from the test chamber at predetermined times. A validated method was used to extract the cartridges and analyze for formaldehyde via liquid chromatography. In addition, material demand for the formaldehyde was evaluated by inclusion of arrays of Plexiglas panels in the test chamber to determine the impact of varied surface areas within the test chamber. Temperature was controlled with a circulating water bath connected to a radiator and fan inside the chamber. Relative humidity was controlled with humidity fixed-point salt solutions and water vapor generated from evaporated water. RESULTS: Low temperature trials (approximately 10°C) resulted in decreased formaldehyde air concentrations throughout the 48-hour time-course when compared with formaldehyde concentrations in the ambient temperature trials (approximately 22°C). The addition of clear Plexiglas panels to increase the surface area of the test chamber interior resulted in appreciable decreases of formaldehyde air concentration when compared to an empty test chamber. CONCLUSION: This work has shown that environmental variables and surface-to-volume ratios in the decontaminated space may affect the availability of formaldehyde in the air and, therefore, may affect decontamination effectiveness.

Decontamination of Bacillus Spores with Formaldehyde Vapor under Varied Environmental Conditions.

Introduction: This study investigated formaldehyde decontamination efficacy against dried Bacillus spores on porous and non-porous test surfaces, under various environmental conditions. This knowledge will help responders determine effective formaldehyde exposure parameters to decontaminate affected spaces following a biological agent release. Methods: Prescribed masses of paraformaldehyde or formalin were sublimated or evaporated, respectively, to generate formaldehyde vapor within a bench-scale test chamber. Adsorbent cartridges were used to measure formaldehyde vapor concentrations in the chamber at pre-determined times. A validated method was used to extract the cartridges and analyze for formaldehyde via liquid chromatography. Spores of Bacillus globigii, Bacillus thuringiensis, and Bacillus anthracis were inoculated and dried onto porous bare pine wood and non-porous painted concrete material coupons. A series of tests was conducted where temperature, relative humidity, and formaldehyde concentration were varied, to determine treatment efficacy outside of conditions where this decontaminant is well-characterized (laboratory temperature and humidity and 12 mg/L theoretical formaldehyde vapor concentration) to predict decontamination efficacy in applications that may arise following a biological incident. Results: Low temperature trials (approximately 10°C) resulted in decreased formaldehyde air concentrations throughout the 48-hour time-course when compared with formaldehyde concentrations collected in the ambient temperature trials (approximately 22°C). Generally, decontamination efficacy on wood was lower for all three spore types compared with painted concrete. Also, higher recoveries resulted from painted concrete compared to wood, consistent with historical data on these materials. The highest decontamination efficacies were observed on the spores subjected to the longest exposures (48 hours) on both materials, with efficacies that gradually decreased with shorter exposures. Adsorption or absorption of the formaldehyde vapor may have been a factor, especially during the low temperature trials, resulting in less available formaldehyde in the air when measured. Conclusion: Environmental conditions affect formaldehyde concentrations in the air and thereby affect decontamination efficacy. Efficacy is also impacted by the material with which the contaminants are in contact.

Survey of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho-polychlorinated biphenyls in US meat and poultry, 2012-13: toxic equivalency levels, patterns, temporal trends and implications.

The US Department of Agriculture (USDA) conducts a statistically based survey of the domestic meat supply (beef, pork, chicken and turkey) to determine current levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho-polychlorinated biphenyls (no-PCBs) every 5 years. Fat samples for each slaughter class were collected from US federally licensed slaughter facilities. The samples were processed and analysed for 17 PCDD/Fs and three no-PCBs. The sum of PCDD, PCDF and no-PCB toxic equivalencies (sum-TEQ) calculated using 2005 toxic-equivalency factors for all slaughter classes ranged from non-detect (n.d.) to 6.47 pg TEQ g-1 lipid. The median sum-TEQs, when n.d. = 0.5 LOD, for beef, pork, chicken and turkey were 0.66, 0.12, 0.13 and 0.34 pg TEQ g-1 lipid respectively. A comparison of the current survey with the previous three surveys shows a declining trend, with decreasing differences between medians; differences between the median sum-TEQs from 2007-08 and 2012-13 were -10%, -29%, -33% and -25% for beef, pork, chicken and turkey respectively. Several beef samples underwent further characterisation and congener patterns from these beef samples suggested pentachlorophenol treated wood as the likely exposure source. US consumer exposure to these compounds is relatively low and no slaughter class contributed more than 26% to the US Environmental Protection Agency (USEPA) chronic oral reference dose of 0.7 pg TEQ kg-1 bw day-1.

Catalase has a key role in protecting cells from the genotoxic effects of monomethylarsonous acid: a highly active metabolite of arsenic.

Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. The authors' studies are centered on identifying a reactive species involved in the genotoxicity of arsenic using a catalase (CAT) knockout mouse model that is impaired in its ability to breakdown hydrogen peroxide (H2 O2 ). The authors assessed the induction of DNA damage using the Comet assay following exposure of mouse Cat(+/) (+) and Cat(-) (/) (-) primary splenic lymphocytes to monomethylarsonous acid (MMA(III) ) to identify the potential role of H2 O2 in mediating cellular effects of this metalloid. The results showed that the Cat(-) (/) (-) lymphocytes are more susceptible to MMA(III) than the Cat(+/) (+) lymphocytes by a small (1.5-fold) but statistically significant difference. CAT activity assays demonstrated that liver tissue has approximately three times more CAT activity than lymphocytes. Therefore, Comet assays were performed on primary Cat(+/) (+) , Cat(+/) (-) , and Cat(-) (/) (-) hepatocytes to determine if the Cat(-) (/) (-) cells were more susceptible to MMA(III) than lymphocytes. The results showed that the Cat(-) (/) (-) hepatocytes exhibit higher levels of DNA strand breakage than the Cat(+/) (+) (approximately fivefold) and Cat(+/) (-) (approximately twofold) hepatocytes exposed to MMA(III) . Electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as the spin-trap agent detected the generation of ·OH via MMA(III) when H2 O2 was present. These experiments suggest that CAT is involved in protecting cells against the genotoxic effects of the ·OH generated by MMA(III) .

A transgenic Drosophila model for arsenic methylation suggests a metabolic rationale for differential dose-dependent toxicity endpoints.

The mechanisms by which exposure to arsenic induces its myriad pathological effects are undoubtedly complex, while individual susceptibility to their type and severity is likely to be strongly influenced by genetic factors. Human metabolism of arsenic into methylated derivatives, once presumed to result in detoxification, may actually produce species with significantly greater pathological potential. We introduce a transgenic Drosophila model of arsenic methylation, allowing its consequences to be studied in a higher eukaryote exhibiting conservation of many genes and pathways with those of human cells while providing an important opportunity to uncover mechanistic details via the sophisticated genetic analysis for which the system is particularly well suited. The gene for the human enzyme, arsenic (+3 oxidation state) methyltransferase, was introduced into nonmethylating Drosophila under inducible control. Transgenic flies were characterized for enzyme inducibility, production of methylated arsenic species, and the dose-dependent consequences for chromosomal integrity and organismal longevity. Upon enzyme induction, transgenic flies processed arsenite into mono and dimethylated derivatives identical to those found in human urine. When induced flies were exposed to 9 ppm arsenite, chromosomal stability was clearly reduced, whereas at much higher doses, adult life span was significantly increased, a seemingly paradoxical pair of outcomes. Measurement of arsenic body burden in the presence or absence of methylation suggested that enhanced clearance of methylated species might explain this greater longevity under acutely toxic conditions. Our study clearly demonstrates both the hazards and the benefits of arsenic methylation in vivo and suggests a resolution based on evolutionary grounds.