Kinetics and distribution of benzalkonium compounds with different alkyl chain length following intravenous administration in rats

Kera, Hitomi; Fuke, Chiaki; Usumoto, Yosuke; Nasu, Ayako; Maeda, Kazuho; Mukai, Moe; Sato, Wakana; Tanabe, Momoka; Kuninaka, Hikaru; Ihama, Yoko

doi:10.1016/j.legalmed.2020.101821

Cited by 7 publications

(10 citation statements)

References 27 publications

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“…12 The relatively large quantity of BACs in feces could reflect the use of BACs in food-processing settings and subsequent oral intake. If BAC exposure occurs by inhalation, possible explanations include relatively brief plasma half-lives (1.8−3.7 h for C 12 , C 14 , and C 16 BAC in rats) 51 and/or formation of BAC−bile acid ion pair complexes 52 that undergo P-glycoprotein efflux transport at the bile canalicular membrane of hepatocytes and ultimately deposit into the intestinal lumen. Additional studies, however, are required to further characterize the various transport and excretion pathways involved in the QAC disposition.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans

Nguyen,

Seguin,

Ross

et al. 2024

Environ. Sci. Technol.

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The COVID-19 pandemic has led to significantly increased human exposure to the widely used disinfectants quaternary ammonium compounds (QACs). Xenobiotic metabolism serves a critical role in the clearance of environmental molecules, yet limited data are available on the routes of QAC metabolism or metabolite levels in humans. To address this gap and to advance QAC biomonitoring capabilities, we analyzed 19 commonly used QACs and their phase I metabolites by liquid chromatography–ion mobility–tandem mass spectrometry (LC–IM–MS/MS). In vitro generation of QAC metabolites by human liver microsomes produced a series of oxidized metabolites, with metabolism generally occurring on the alkyl chain group, as supported by MS/MS fragmentation. Discernible trends were observed in the gas-phase IM behavior of QAC metabolites, which, despite their increased mass, displayed smaller collision cross-section (CCS) values than those of their respective parent compounds. We then constructed a multidimensional reference SQLite database consisting of m/z, CCS, retention time (rt), and MS/MS spectra for 19 parent QACs and 81 QAC metabolites. Using this database, we confidently identified 13 parent QACs and 35 metabolites in de-identified human fecal samples. This is the first study to integrate in vitro metabolite biosynthesis with LC–IM–MS/MS for the simultaneous monitoring of parent QACs and their metabolites in humans.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans

Nguyen,

Seguin,

Ross

et al. 2024

Environ. Sci. Technol.

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“…QACs in circulation may bind plasma proteins, such as albumin and α-1-acid glycoprotein; ,− however, plasma half-lives of BACs C12, C14, and C16, dosed via IV bolus to rats, are somewhat brief (1.8–3.7 h) and volumes of distribution are high (5.6–6.7 L/kg), suggesting that partitioning into tissues is favored over retention in plasma. IV-administered BACs accumulated in heart, lung, spleen, and kidney, which was consistent with earlier findings by Xue et al , No parent BACs were detected in urine, confirming urine is not a preferred excretory pathway for the parent BACs.…”

Section: Human Exposurementioning

confidence: 99%

Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern

Arnold,

Blum,

Branyan

et al. 2023

Environ. Sci. Technol.

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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.

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“…Due to this, BZK is used as an antiseptic in consumer rubs and washes for topical solutions [ 4 ]. BZK contains the structure [C 6 H 5 CH 2 N(CH 3 ) 2 R]Cl where R is a mixture of alkyl chains: n -C 8 H 17 , n -C 10 H 21 , n -C 12 H 25 , n -C 14 H 29 , and n -C 16 H 33 [ 5 , 6 ]. The length of the carbon chain is important in determining whether BZK will kill specific classes of microbes.…”

Section: Introductionmentioning

confidence: 99%

MALDI-TOF imaging analysis of benzalkonium chloride penetration in ex vivo human skin

Morse,

Hite,

Wamer

et al. 2024

PLoS ONE

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Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions.

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Kinetics and distribution of benzalkonium compounds with different alkyl chain length following intravenous administration in rats

Cited by 7 publications

References 27 publications

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans

Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern

MALDI-TOF imaging analysis of benzalkonium chloride penetration in ex vivo human skin

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