Pulmonary toxicity of sodium dichloroisocyanurate after intratracheal instillation in sprague-dawley rats.

In water, sodium dichloroisocyanurate (NaDCC), a source for chlorine gas generation, releases free available chlorine in the form of hypochlorous acid, a strong oxidizing agent. NaDCC has been used as a disinfectant in humidifiers; however, its inhalation toxicity is a concern. Seven-week-old rats were exposed to NaDCC doses of 100, 500, and 2500 µg·kg-1 body weight by intratracheal instillation (ITI) to investigate pulmonary toxicity. The rats were sacrificed at 1 d (exposure group) or 14 d (recovery group) after ITI. Despite a slight decrease in body weight after exposure, there was no statistically significant difference between the control and NaDCC-treated groups. A significant increase in the total protein level of the bronchoalveolar lavage fluid (BALF) was observed in the exposure groups. Lactate dehydrogenase leakage into the BALF increased significantly (p < 0.01) in the exposure groups; however, recovery was observed after 14 d. The measurement of cytokines in the BALF samples indicated a significant increase in interleukin (IL)-6 in the exposure group and IL-8 in the recovery group. Histopathological examination revealed inflammatory foci and pulmonary edema around the terminal bronchioles and alveoli. This study demonstrated that ITI of NaDCC induced reversible pulmonary edema and inflammation without hepatic involvement in rats.

Acute Toxicity in the Rat Lung Induced by Intratracheal Instillation of Glycolic Acid.

BACKGROUND/AIM: Inhalation toxicity tests of glycolic acid, which is used in many household products, have been reported, but the pulmonary toxicity of glycolic-acid has not been confirmed. Here, the lung damage caused by glycolic acid was investigated in rats. MATERIALS AND METHODS: An intratracheal instillation test was performed with glycolic acid in male rats. Bronchoalveolar lavage fluid (BALF) and histopathological analysis were conducted to identify the pulmonary toxicities. RESULTS: Intratracheal instillation of glycolic acid caused weight loss in animals and increased the content of lactate dehydrogenase, total protein, polymorphonuclear neutrophils, and inflammatory cytokines in BALF. In addition, pulmonary edema, alveolar/interstitial inflammation, and necrosis and desquamation of bronchial/bronchiolar epithelia were confirmed via histopathological examination. CONCLUSION: Exposure to glycolic acid can be harmful and toxic to the lungs.

Updated general exposure factors for risk assessment in the Korean population.

BACKGROUND: There has been an increasing need to update the recommended values of Korean exposure factors for adults aged 19 and older, as using exposure factors developed over a decade ago could reduce risk assessment reliability. OBJECTIVE: Exposure factor data have been compiled and standardized using the latest national statistical reports and academic literature, as well as studies conducted from 2016 to 2018. METHODS: The updated data contained anthropometric parameters, inhalation rates, food and drinking water ingestion rates, and time-activity patterns and provided technical information on Koreans' exposure factors classified by sex, age group, per capita and general population, and doer-only for various exposure assessments. RESULTS: Although the average life expectancy, body weight, body surface area, and inhalation rate increased slightly compared to the 2007 Korean Exposure Factor Handbook, differences various in food consumption were remarkable. Because of Asians' similar food preferences, the intake rate of grain products and vegetables in Koreans, Chinese, and Japanese contributed much toward total intake. Koreans spent half their times outdoors compared to Americans and Chinese. SIGNIFICANCE: This study provided the currently updated exposure factor information for Koreans and could be compared with recommendations provided by exposure factor resources in various countries. IMPACT STATEMENT: Exposure to environmental pollutants may significantly vary depending on the exposure factors related to human behaviors and characteristics. Therefore the exposure factors need to be continuously updated along with more extensive survey areas and improved measurement methods. We utilized the existing data with the aim to develop general exposure factors for risk assessment in Korean aged ≥19 years. Measurements and questionnaire surveys were also performed if there were no existing data. This study provided the currently updated exposure factor information for Koreans and could be compared to those of other countries.

Comparison of the exposure assessment of di(2-ethylhexyl) phthalate between the PBPK model-based reverse dosimetry and scenario-based analysis: A Korean general population study.

Di (2-ethylhexyl) phthalate (DEHP), classified as a reproductive toxicant, is a ubiquitous pollutant in foodstuffs, dust, and commercial products. In this study, to provide a useful cross-check on the accuracy of the exposure assessment, the estimated daily intake of DEHP was compared using reverse dosimetry with a physiologically-based pharmacokinetic (PBPK) model and a scenario-based probabilistic estimation model for six subpopulations in Korea. For reverse dosimetry analysis, the concentrations of urinary DEHP metabolites, namely mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl)phthalate (MEOHP), from three human biomonitoring program datasets were used. For the scenario-based model, we evaluated the various exposure sources of DEHP, including diet, air, indoor dust, soil, and personal care products (PCPs), and also determined its levels based on the literature review and measurements of indoor dust. The DEHP exposure doses using both exposure assessment approaches were similar in all cases, except for the 95th percentile exposure doses in toddlers (1-2 years) and young children (3-6 years). The PBPK-reverse dosimetry estimated daily intakes at the 95th percentile ranged between 22.53 and 29.90 µg/kg/day for toddlers and young children. These exceeded the reference dose (RfD) of 20 µg/kg bw/day of the US Environmental Protection Agency (EPA) based on the increased relative liver weight. Although, food was considered the primary source of DEHP, contributing to a total exposure of 50.8-75.1%, the effect of exposure to indoor dust should not be overlooked. The occurrence of high levels of DEHP in indoor dust collected from Korean homes suggests the use of a wide variety of consumer products containing DEHP. Furthermore, more attention should be paid to the high exposure levels of DEHP, especially in young children. Therefore, it is necessary to perform continuous monitoring of the indoor dust, consumer products, and the body burden of children.

1,2,3-benzotriazole adversely affects early-life stage of Oryzias latipes.

1,2,3-benzotriazole (BT) is used in large amounts around the world and is one of the substances derived from household chemicals that are of concern for risk when discharged to aquatic environments. Therefore, several studies have been conducted on the aquatic toxicity effects of BT, but the chronic impact assessment studies to evaluate the developmental effects on the early-life stage of fish are insufficient. In this study, the acute toxicity test and subchronic toxicity test (fish, early-life stage toxicity test, ELS test) using embryos of Japanese medaka (Oryzias latipes) were performed to evaluate the acute toxicity, developmental toxicity, growth (indicated by total length and weight at the end of the test), and histopathological effect of BT. In the short-term toxicity test on embryo and sac-fry stage, toxicity value was calculated to be 41 mg/L (NOEC). Based on this value, the exposure concentration of the ELS test was determined as 0.04, 0.4, 4 and 40 mg/L, and total exposure duration was 42 days. At the highest concentration group (40 mg/L), failure of swim bladder inflation and decrease of survival and size (total length and weight) were observed. Moreover, in the histopathological analysis, abnormal findings were detected in swim bladders from the 40 mg/L group such as inflammation and tumor changes. On the other hands, condition index (weight-length relationships, CI) was statistically significantly lower in all exposed groups compared to the control group. NOEC for the survival of BT was calculated to be 4 mg/L. LOEC for CI was 0.04 mg/L, which means BT inhibited weight gain relative to its length on larvae of medaka.

Effect of benzotriazole on oxidative stress response and transcriptional gene expression in Oryzias latipes and Danio rerio embryo.

Emerging contaminants (EC) such as benzotriazole are being released into the environment in various ways, therefore it is necessary to understand how organisms are affected by EC. In this study, we exposed medaka (Oryzias latipes) and zebrafish (Danio rerio) during their embryonic period (1 day after hatching) to benzotriazole to investigate its effects on oxidative stress (ROS, GSH, GST, SOD, CAT and MDA) and changes in gene expression patterns. In both medaka and zebrafish, the influence of oxidative stress was confirmed through an increased MDA level and changes in the ROS and GSH levels. Antioxidant enzymes such as GST, CAT, and SOD were affected by benzotriazole; however, medaka and zebrafish showed different patterns in the effects by benzotriazole. Results of oxidative stress genes expression showed that medaka had either no influence or had a decrease in the gene expression profile, whereas zebrafish had a statistically significant increase in the expression of some genes. The cyp1a gene expression was increased in both species. However, vtg gene expression was increased only in zebrafish but decreased in medaka, indicating no estrogenic effects in medaka. Apoptosis genes showed changes in expression in both the species but was these changes were not dose-dependent. However, zebrafish caspase-9 gene expression was increased in all of the exposed groups, suggesting the effects on the intrinsic pathway associated with caspase-9. In conclusion, the results indicate that the toxic effects of benzotriazole differ at various levels in the two small fish medaka and zebrafish embryos.

Advantages of omics technology for evaluating cadmium toxicity in zebrafish.

In the last decade, several advancements have been made in omics technologies and they have been applied extensively in diverse research areas. Especially in toxicological research, omics technology can efficiently and accurately generate relevant data on the molecular dynamics associated with adverse outcomes. Toxicomics is defined as the combination of toxicology and omics technologies and encompasses toxicogenomics, toxicoproteomics, and toxicometabolomics. This paper reviews the trend of applying omics technologies to evaluate cadmium (Cd) toxicity in zebrafish (D. rerio). Cd is a toxic heavy metal posing several environmental concerns; however, it is being used widely in everyday life. Zebrafish embryos and larvae are employed as standard models for many toxicity tests because they share 71.4% genetic homology with humans. This study summarizes the toxicity of Cd on the nerves, liver, heart, skeleton, etc. of zebrafish and introduces detailed omics techniques to understand the results of the toxicomic studies. Finally, the trend of toxicity evaluation in the zebrafish model of Cd based on omics technology is presented.

Integrated multi-omics analysis reveals the underlying molecular mechanism for developmental neurotoxicity of perfluorooctanesulfonic acid in zebrafish.

Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1-20 µM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 µM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.

Comparative Cytotoxicity Study of PM2.5 and TSP Collected from Urban Areas.

Ambient particulate matter 2.5 (PM2.5) and total suspended particles (TSPs) are common airborne pollutants that cause respiratory and cardiovascular diseases. We investigated the differences of cytotoxicity and mechanism between PM2.5 and TSP activity in human alveolar epithelial A549 cells. Atmospheric samples from the central district of Seoul were collected and their chemical compositions were analyzed by inductively-coupled plasma mass spectrometry and ion chromatography. PM2.5 and TSP contained high concentrations of heavy metals (Cu, Fe, Zn, and Pb). The most abundant ions in PM2.5 were SO42-, NH4+, and NO3-. A549 cells were exposed to PM2.5 and TSP (25-200 µg/mL) for 24 h. TSP was more cytotoxic than PM2.5 per unit mass. PM2.5 induced oxidative stress, as evidenced by increased levels of a glutamate-cysteine ligase modifier, whereas low-concentration TSP increased hemeoxygenase-1 levels. PM2.5 and TSP did not affect c-Jun N-terminal kinase expression. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in PM2.5- and TSP-treated cells decreased significantly in the cytosol and increased in the nucleus. Thus, Nrf2 may be a key transcription factor for detoxifying environmental airborne particles in A549 cells. TSP and PM2.5 could activate the protective Kelch-like ECH-associated protein 1/Nrf2 pathway in A549 cells.

Ecological Risk Assessment of Amoxicillin, Enrofloxacin, and Neomycin: Are Their Current Levels in the Freshwater Environment Safe?

Veterinary pharmaceuticals may cause unexpected adverse effects on non-target aquatic species. While these pharmaceuticals were previously identified as priority compounds in ambient water, their ecological risks are relatively unknown. In this study, a series of chronic toxicity tests were conducted for these pharmaceuticals using algae, two cladocerans, and a fish. After a 21-d exposure to amoxicillin, enrofloxacin, and neomycin, no observed effect concentration (NOEC) for the reproduction of Daphnia magna was detected at 27.2, 3.3, and 0.15 mg/L, respectively. For the survival of juvenile Oryzias latipes following the 40-d exposure, NOEC was found at 21.8, 3.2, and 0.87 mg/L, respectively. Based on the results of the chronic toxicity tests and those reported in the literature, predicted no-effect concentrations (PNECs) were determined at 0.078, 4.9, and 3.0 µg/L for amoxicillin, enrofloxacin, and neomycin, respectively. Their hazard quotients (HQs) were less than 1 at their average levels of occurrence in ambient freshwater. However, HQs based on the maximum detected levels of amoxicillin and enrofloxacin were determined at 21.2 and 6.1, respectively, suggesting potential ecological risks. As the potential ecological risks of these veterinary pharmaceuticals at heavily contaminated sites cannot be ignored, hotspot delineation and its management are required.

Prediction of acute inhalation toxicity using cytotoxicity data from human lung epithelial cell lines.

Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two-dimensional (2D) cell culture models. We investigated the conventional submerged 2-D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC50 ) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC50 ) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC50 , but without IC50 , data to obtain the IC50 values. A weak correlation was observed between the IC50 and LC50 of all substances. Semi-volatile organic compounds (SVOCs) and non-VOCs (NVOCs) (16 substances) with a water solubility of ≥1 g/L were strongly correlated between 24-h IC50 and 4-h LC50 , and this had an excellent predictive ability to distinguish between Categories 1-3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2-D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of ≥1 g/L in SVOCs and NVOCs.

Comprehensive pulmonary toxicity assessment of cetylpyridinium chloride using A549 cells and Sprague-Dawley rats.

Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half-maximal inhibitory concentration (IC50 ) of 5.79 µg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high-exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF-α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration-dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity.

In Vitro and In Vivo Evaluation of the Toxic Effects of Dodecylguanidine Hydrochloride.

The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC50: 0.39 µg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m3 for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-ß1, IL-1ß, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC50 of DGH in rats after exposure for 4 h was estimated to be >68 mg/m3. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health.

Behavioral characteristics to airborne particles generated from commercial spray products.

Commercial spray products are commonly used in daily life and airborne particles generated by these products may cause adverse health effects. Our study was aimed to characterize the behaviors of airborne particles from spray products and to determine the deposition loss rate. Four categories of spray products with highly frequent use - air fresheners, fabric deodorants, window cleaners, and a bathroom cleaner - were selected for the study. The products were applied in a cleanroom according to the instructions for use. Airborne particles (10-10,000 nm) were measured within the breathing zone of a user with a scanning mobility particle sizer and an optical particle spectrometer. Additionally, filter sampling was performed to examine the morphological characteristics of the particles using a field emission-scanning electron microscope (FE-SEM). The initial concentration and particle size distribution varied among different spray types and products. Two propellant-type air fresheners that we tested showed a high initial concentration of smaller sized particles. However, one of these and all hand-pressure type propellants showed a low initial concentration in all size ranges. We observed that particles in nucleation mode (10-31.6 nm) decreased and aggregated particles shifted to accumulation mode (100-1,000 nm) over time. The FS-SEM analysis confirmed the aggregation of nano-sized particles for all products. The deposition loss rates of various particle sizes depended on the initial concentration and distribution of particle sizes. For two air fresheners with high initial concentrations, the loss rate of small-sized particles was higher than that of the other products whereas the particle loss rate of large-sized particles was higher, regardless of initial concentration. The results of this study can give us useful information in the behaviors of airborne particles in the consumer spray products and resulting exposure assessment especially in the application to the exposure modeling of spray products.

Physicochemical characteristics of colloidal nanomaterial suspensions and aerosolized particulates from nano-enabled consumer spray products.

Physicochemical properties between colloidal engineered nanomaterials (ENMs) and aerosols released from consumer spray products were characterized. A dynamic light scattering (DLS), transmission electron microscopy (TEM), and inductively coupled plasma mass spectrometer (ICP-MS) were used to evaluate the suspended ENMs in the products. Direct-reading instruments, TEM, and ICP-MS were used to characterize the properties of aerosolized ENMs. The aerosolized organic compounds with ENMs were assumed to be vaporized for a short time after spraying. The median diameter of ENMs in product solutions measured by DLS was about 200-350 nm, while individual particle was confirmed from 3 to 50 nm by TEM. The size of aerosolized ENMs was ranged from 7 to 44 nm, and their aggregates were about 100-1000 nm in near distance. Some inorganic substances including raw nanomaterials were also found in the aerosol. The particles released from the propellant sprays were identified in far distance, while they were not found in far distance when pump sprays were used. The number concentration from the propellant sprays increased up to 6000 particles/cm3 /g at near distance and dispersed to far distance, while the most of droplets emitted from pump sprays were settled down near sprayer's location. We found other metals besides labeled ENMs are included in each product and the characteristics of the particles are different when they are sprayed.

Development of General Exposure Factors for Risk Assessment in Korean Children.

There has been an increasing need for the risk assessment of external environmental hazards in children because they are more sensitive to hazardous chemical exposure than adults. Therefore, the development of general exposure factors is required for appropriate risk assessment in Korean children. This study aimed to determine the general exposure factors among Korean children aged ≤18 years. We developed the recommended exposure factors across five categories: physiological variables, inhalation rates, food and drinking water intake, time-activity patterns, and soil and dust ingestion. National databases were used, and direct measurements and questionnaire surveys of representative samples were performed to calculate the inhalation rate, water intake, and soil ingestion rate. With regard to the time-activity patterns, the daily inhalation rates ranged from 9.49 m3/day for children aged 0-2 years to 14.98 m3/day for those aged 16-18 years. This study found that Korean children spent an average of 22.64 h indoors, 0.63 h outdoors, and 0.73 h in-transit on weekdays. The general exposure factors of Korean children were studied for the first time, and these results could be used to assess children's exposure and risk. They also suggest the differences compared with the results of international results.

Concentration- and Time-Dependent Effects of Benzalkonium Chloride in Human Lung Epithelial Cells: Necrosis, Apoptosis, or Epithelial Mesenchymal Transition.

Benzalkonium chloride (BAC), an antimicrobial agent in inhalable medications and household sprays, has been reported to be toxic to pulmonary organs. Although cell membrane damage has been considered as the main cytotoxic mechanism of BAC, its concentration- and time-dependent cellular effects on lung epithelium have not been fully understood. In the present study, human lung epithelial (H358) cells were exposed to 0.2-40 µg/mL of BAC for 30 min or 21 days. Cell membranes were rapidly disrupted by 30 min exposure, but 24 h incubation of BAC (4-40 µg/mL) predominantly caused apoptosis rather than necrosis. BAC (2-4 µg/mL) induced mitochondrial depolarization, which may be associated with increased expression of pro-apoptotic proteins (caspase-3, PARP, Bax, p53, and p21), and decreased levels of the anti-apoptotic protein Bcl-2. The protein expression levels of IRE1α, BiP, CHOP, and p-JNK were also elevated by BAC (2-4 µg/mL) suggesting the possible involvement of endoplasmic reticulum stress in inducing apoptosis. Long-term (7-21 days) incubation with BAC (0.2-0.6 µg/mL) did not affect cell viability but led to epithelial-mesenchymal transition (EMT) as shown by the decrease of E-cadherin and the increase of N-cadherin, fibronectin, and vimentin, caused by the upregulation of EMT transcription factors, such as Snail, Slug, Twist1, Zeb1, and Zeb2. Therefore, we conclude that apoptosis could be an important mechanism of acute BAC cytotoxicity in lung epithelial cells, and chronic exposure to BAC even at sub-lethal doses can promote pulmonary EMT.

Adverse effects of perfluoroalkyl acids on fish and other aquatic organisms: A review.

Perfluoroalkyl acids (PFAAs) have been widely used in many industrial and consumer products. They have been detected ubiquitously in ambient water along with other environmental matrices, and their adverse effects on aquatic organisms have been a subject of active investigation. Here, we intended to summarize and synthesize the existing body of knowledge on PFAA toxicity through an extensive literature review, and shed light on areas where further research is warranted. PFAA toxicity appears to be influenced by the sex and developmental stages of aquatic organisms, but not significantly by exposure route. PFAA-induced aquatic toxicity could be classified as metabolism disturbance, reproduction disruption, oxidative stress, developmental toxicity, thyroid disruption, etc. At the molecular level, these responses can be initiated by key events, such as nuclear receptor activation, reactive oxygen species induction, or interaction with a membrane, followed by a cascade of downstream responses. PFAA-induced toxicity involves diverse metabolic processes, and therefore elucidating crosstalk or interactions among diverse metabolic pathways is a challenging task. In the presence of other chemicals, PFAAs can function as agonists or antagonists, resulting in different directions of combined toxicity. Therefore, mixture toxicity with other groups of chemicals is another research opportunity. Experimental evidence supports the trans-generational toxicity of PFAAs, suggesting that their long-term consequences for aquatic ecosystems should become of concern. A recent global ban of several PFAAs resulted in an increasing dependence on PFAA alternatives. The lack of sufficient toxicological information on this emerging group of chemicals warrant caution and rigorous toxicological assessments.

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats.

BACKGROUND/AIM: The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. MATERIALS AND METHODS: We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid. RESULTS: Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. CONCLUSION: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

Prediction of the skin sensitization potential of didecyldimethylammonium chloride and 3,7-dimethyl-2,6-octadienal and mixtures of these compounds with the excipient ethylene glycol through the human Cell Line Activation Test and the Direct Peptide Reactivity Assay.

In commercial products such as household deodorants or biocides, didecyldimethylammonium chloride (DDAC) often serves as an antimicrobial agent, citral serves as a fragrance agent, and the excipient ethylene glycol (EG) is used to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances are still being debated. Moreover, mixtures of DDAC or citral with EG have not been evaluated for SS potency. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) and Direct Peptide Reactivity Assay (DPRA) served to address these issues. On three independent runs of h-CLAT, DDAC and citral were predicted to be sensitizers while EG was predicted to be a non-sensitizer and also by the DPRA. Mixtures of DDAC or citral with EG at ratios of 7:3 and 1:4 w/v were all positive by the h-CLAT in terms of SS potential but SS potency was mitigated as the proportion of EG increased. Citral and its EG mixtures were all positive but DDAC and its EG mixtures were all negative by the DPRA, indicating that the DPRA method is not suitable for chemicals with pro-hapten characteristics. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.