Filling gaps between exposure modeling and the analysis of urinary biomarkers using personal air monitoring: An intervention study of permethrin used in home insecticide spray.

Permethrin is one of the most widely used active ingredients in spray-type home insecticides. However, indoor permethrin exposure resulting from the use of home insecticides is not well-characterized, as measured permethrin concentrations in indoor environmental and biological media with a known application rate are scarce. We conducted an intervention study with four participants for seven days. We conducted personal air monitoring and collected 24-h urine samples in which we quantified time-weighted average (TWA) permethrin concentrations in indoor air (Cair ) and urinary concentrations of two permethrin metabolites, 3-phenoxybenzoic acid (3-PBA) and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis/trans-DCCA). We also estimated (1) TWA Cair using a simple indoor air model and (2) urinary excreted (UE) mass using a simple excretion model with both estimated and measured TWA Cair . Measurements of TWA Cair from personal air monitoring were lower than those estimated from the indoor model by a factor of 2.9 to 49.4. The ratio of estimated to measured UE mass ranged 3.5-18.2 when using estimated TWA Cair and 1.1-2.9 when using measured TWA Cair . Smaller ratios in estimating internal permethrin exposure from personal air monitoring suggest that personal air monitoring could reduce uncertainties in permethrin exposure assessment resulting from the use of spray-type insecticides.

Exposure to permethrin used as a home insecticide: A case study comparing model predictions and excretion of metabolites.

Pyrethroids have been widely used as an active ingredient in home insecticide products since the 1960 s. Although their occurrence in indoor environments has been studied, the contribution of home insecticide application to the aggregate exposure to pyrethroids is not well known. The objective of this study was to estimate the consumer exposure to permethrin, a representative pyrethroid, via the use of home insecticide spray during the summer season using biomonitoring and personal exposure modeling. Exposure to permethrin was assessed by analyzing its urinary metabolites, 3-phenoxybenzoic acid (3-PBA) and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropan carboxylic acid (cis/trans-DCCA), for a group of consumers (n = 27). The levels of metabolites were also compared with those predicted by a screening exposure model considering personal exposure parameters. The levels of metabolites in 15 participants increased significantly (p < 0.05) with the application of home insecticide products, thereby suggesting that the heavy use of home insecticides during summer could be an important exposure route of permethrin in addition to other sources, such as food consumption. The total amount of excreted 3-PBA and cis/trans-DCCA was lower than the amount estimated by the exposure model for most participants by a factor of 0.9-861.0. These differences could be attributed to the rapid loss of permethrin after application, including sorption to indoor surfaces, reaction with indoor substances, individual biological variations, and ventilation during application. However, the screening exposure model used for the initial safety assessment of biocidal products generally performed well because it did not underestimate the personal exposure to permethrin during the application of home insecticide spray.

Liposome leakage and increased cellular permeability induced by guanidine-based oligomers: effects of liposome composition on liposome leakage and human lung epithelial barrier permeability.

Over the decades, guanidine-based oligomer groups have been one of the most widely used antimicrobial agents. Reportedly, these cationic oligomers cause serious damage to microorganisms but have low toxicity to humans. However, public concerns regarding the guanidine group have rapidly grown after the fatal misuse of these oligomers as humidifier disinfectants, which resulted in thousands of fatalities in South Korea. Herein, we investigated liposome leakage and cellular permeability changes caused by polyhexamethylene guanidine (PHMG) and polyhexamethylene biguanide (PHMB), both representative guanidine-based oligomers. The leakage of zwitterionic liposomes, induced by cationic oligomers, was more extensive than that of negative liposomes, indicating that oligomer adsorption onto lipid head groups via electrostatic interaction cannot fully explain the induced lipid membrane damage. Furthermore, lipid packing parameters, including intrinsic curvature, cholesterol content, and lipid phases, affected liposome leakage, particularly for PHMG. Cellular permeability tests were performed using an A549 cell monolayer model and a respiratory 3D tissue model, revealing that PHMG and PHMB damaged cell membranes and reduced cell barrier function. Furthermore, liposome leakage induced by PHMG and PHMB was higher in human lung surfactant-mimicking liposomes than that observed in Escherichia coli-mimicking liposomes. These results indicated that human cells are susceptible to guanidine-based oligomers. Considering that the interaction of oligomers and cell membranes is a major mechanism of toxicity initiation, this study provides crucial insights into the action of these disinfectants on mammalian cells.

Characteristics of Exposure to Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) among Humidifier Disinfectant-Associated Lung Injury (HDLI) Patients in South Korea.

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography-mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 µg/m3 for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p < 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development.

Experimental determination of indoor air concentration of 5-chloro-2-methylisothiazol-3(2H)-one/ 2-methylisothiazol-3(2H)-one (CMIT/MIT) emitted by the use of humidifier disinfectant.

A mixture of 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT) had been used as an active ingredient in humidifier disinfectants (HDs). Owing to its high reactivity, the atmospheric concentration of CMIT/MIT, following its use in HD, would be lower than expected assuming that it is removed by ventilation only. In order to evaluate the exposure concentration of CMIT/MIT used as an HD, room-scale chamber studies were conducted under plausible use of three different HD doses at air change rates (ACR) of 0.3, 0.5, and 1.0 h-1. Atmospheric CMIT/MIT was sampled using two serial impingers containing deionized water after the attainment of steady state. Water samples in which CMIT/MIT was dissolved were concentrated using a cosolvent evaporation method with efficiencies of 35.5 and 77.9% for CMIT and MIT, respectively. The estimated air concentration, assuming that all the CMIT/MIT is absorbed in deionized water, increased linearly with increasing emission rate, but was independent of the ACR. This indicates that the removal rate of CMIT/MIT via chemical reactions is more than the removal rate by ventilation. Further investigations on homogeneous and heterogeneous chemical reactions of CMIT/MIT under ambient conditions are necessary to understand the actual exposure concentration of the mixture in HD.

The fate of two isothiazolinone biocides, 5-chloro-2-methylisothiazol-3(2H)-one (CMI) and 2-methylisothiazol-3(2H)-one (MI), in liquid air fresheners and assessment of inhalation exposure.

There exist public concerns regarding the two most widely used isothiazolinones (5-chloro-2-methylisothiazol-3(2H)-one (CMI) and 2-methylisothiazol-3(2H)-one (MI)) in various consumer products because they cause allergic responses in dermatitis and are potentially harmful when inhaled. Hydrolysis and photolysis tests for CMI and MI at pH 4, 7, and 9 were performed to evaluate their stability. While MI did not degrade under the test conditions, CMI slightly degraded at pH 9 via hydrolysis and at pH 4 via photolysis. To better understand human exposure to MI and CMI during the use of consumer products, the vaporization rates of MI and CMI from two commercial air fresheners were quantified in a custom-made chamber. The evaporation of MI was almost negligible over 7 d, whereas a significant amount of CMI evaporated over the same period. Because the volume of air freshener decreases over time due to evaporation of water, the MI concentration in the product increased by a factor of 1.8-2.2. The air concentration of CMI was predicted using a ConsExpo model using a fixed weight fraction (model 1) and a new model that reflects changes in the concentrations of active ingredients and the product volume over time (model 2). The concentration determined using model 1 reached a steady-state value of 0.032 µg L(-1), whereas that predicted using model 2 increased consistently. Inhalation exposure was also assessed using two exposure scenarios: a room and a car. Both calculated values of margin of exposure were much higher than 300, indicating a negligible inhalation risk.

Isolation and identification of a sibutramine analogue adulterated in slimming dietary supplements.

A suspected sibutramine analogue was detected in a slimming functional food by an ultra performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (UPLC-ESI-TOF/MS) method. The ultraviolet (UV) spectrum of this suspected compound showed close similarity to that of sibutramine. The sample was extracted with 70% MeOH and isolated by semi-preparative column chromatography. The structure of this compound was identified by spectroscopic analyses (nuclear magnetic resonance [NMR] technique, mass and tandem mass etc.). The structure of the unknown compound was demonstrated to be [(±)-dimethyl-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N,N,3-trimethylbutan-1-amine (molecular formula C17H25NCl2) and named as chloro-sibutramine. Compared with sibutramine, it has one more chlorine atom than the 3-cholorophenyl group so was switched to 3,4-dichlorophenyl. Until now, chloro-sibutramine was isolated for the first time from the undeclared ingredient included in dietary supplements. Although the safety of chloro-sibutramine is unknown, there is a potential health risk to consumers because of a similar skeleton to sibutramine. For public health, this sibutramine analogue has been included in the inspection list of illegal adulterants in Korea.