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1.
Environ Toxicol Chem ; 43(6): 1320-1331, 2024 Jun.
Article En | MEDLINE | ID: mdl-38661473

Apis mellifera was used as a model species for ecotoxicological testing. In the present study, we tested the effects of acetone (0.1% in feed), a solvent commonly used to dissolve pesticides, on bees exposed at different developmental stages (larval and/or adult). Moreover, we explored the potential effect of in vitro larval rearing, a commonly used technique for accurately monitoring worker exposure at the larval stage, by combining acetone exposure and treatment conditions (in vitro larval rearing vs. in vivo larval rearing). We then analyzed the life-history traits of the experimental bees using radio frequency identification technology over three sessions (May, June, and August) to assess the potential seasonal dependence of the solvent effects. Our results highlight the substantial influence of in vitro larval rearing on the life cycle of bees, with a 47.7% decrease in life span, a decrease of 0.9 days in the age at first exit, an increase of 57.3% in the loss rate at first exit, and a decrease of 40.6% in foraging tenure. We did not observe any effect of exposure to acetone at the larval stage on the capacities of bees reared in vitro. Conversely, acetone exposure at the adult stage reduced the bee life span by 21.8% to 60%, decreased the age at first exit by 1.12 to 4.34 days, and reduced the foraging tenure by 30% to 37.7%. Interestingly, we found a significant effect of season on acetone exposure, suggesting that interference with the life-history traits of honey bees is dependent on season. These findings suggest improved integration of long-term monitoring for assessing sublethal responses in bees following exposure to chemicals during both the larval and adult stages. Environ Toxicol Chem 2024;43:1320-1331. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Acetone , Ecotoxicology , Larva , Animals , Bees/drug effects , Larva/drug effects , Larva/growth & development , Acetone/toxicity , Pesticides/toxicity , Life Cycle Stages/drug effects , Solvents/toxicity , Environmental Pollutants/toxicity , Life History Traits
2.
Arch Toxicol ; 98(2): 471-479, 2024 Feb.
Article En | MEDLINE | ID: mdl-38127129

Many workers can be exposed simultaneously to heat and volatile chemicals. In a controlled human exposure study, it was observed that an increase in ambient temperature was associated with increased blood concentrations for acetone and toluene. Based on the expected changes in physiological parameters that occur with an increase in ambient temperature, we aimed to develop a PBPK model for acetone and toluene that could account for the impact of temperature on the kinetics of these solvents. Changes in temperature-dependent physiological parameters (i.e. blood flows, cardiac output, alveolar ventilation) based on recent measurements in volunteers were introduced in the PBPK models to simulate observed blood concentrations for different temperature exposure conditions. Because initial simulations did not adequately predict solvent kinetics at any temperature, the most sensitive parameter (alveolar ventilation; Qp) was, therefore, optimized on experimental acetone blood concentrations to obtain a relationship with temperature. The new temperature-dependent Qp relationship gave Qp values consistent with the literature and estimated a mean increase of 19% at 30 °C (wet bulb globe temperature) compared to 21 °C. The integration of a new temperature-dependent Qp relationship in the PBPK toluene model yielded adequate simulations of the experimental data for toluene in blood, exhaled air and urine. With further validation with other solvents, the temperature-dependant PBPK model could be a useful tool to better assess the risks of simultaneous exposure to volatile chemicals and heat stress and interpret biomonitoring data in workers as well as in the general population. TRN: NCT02659410, Registration date: January 15, 2016.


Acetone , Toluene , Humans , Acetone/toxicity , Heat-Shock Response , Models, Biological , Solvents/toxicity , Toluene/toxicity , Toxicokinetics
3.
Int J Environ Health Res ; 32(7): 1447-1468, 2022 Jul.
Article En | MEDLINE | ID: mdl-33678072

Upon Seeking natural and safe alternatives for synthetic medicines to treat many chronic diseases, seaweeds have offered a promising resource to produce numerous bioactive secondary metabolites. Through in vivo investigations, Turbinaria decurrens acetone extract (AE) revealed its antidiabetic activity against alloxan-induced diabetic rats. Treatment of rats with T. decurrens AE at 300 and 150 mg/Kg doses revealed antihyperglycemic activity by reducing the elevated blood glucose level. A remarkable decrease in the liver, kidney functions, and hyperlipidemia related to diabetes were also detected. Administration of the same extract also showed a recovery in body weight loss, total protein, albumin, and haemoglobin levels compared with untreated diabetic rats. Furthermore, treatment of rats with the same extract improved liver and pancreas histopathological disorders related to diabetes. These effects may be attributed to the presence of bioactive phytochemicals and antioxidant components in T. decurrens AE mainly cyclotrisiloxane, hexamethyl, and cyclic diterpene 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol alcohol). Besides, other valuable secondary metabolites, as phenols, flavonoids, alkaloids, terpenoids, steroid and glycosides, which were documented and published by the same authors in a previous study. The obtained results in the present study recommended using T. decurrens AE in developing medicinal preparations for treatment of diabetes and its related symptoms.


Alloxan , Diabetes Mellitus, Experimental , Acetone/therapeutic use , Acetone/toxicity , Alloxan/therapeutic use , Alloxan/toxicity , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/toxicity , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats
4.
Drug Chem Toxicol ; 45(4): 1915-1922, 2022 Jul.
Article En | MEDLINE | ID: mdl-34844486

In this study, the genotoxic activity of acetone and aqueous extracts of two species of genus Artemisia (Artemisia vulgaris L. and Artemisia alba Turra), and possible role of their polyphenolic composition in the observed activities were investigated. Polyphenolic contents were evaluated by high-performance liquid chromatography (HPLC-PDA), while the genotoxic activity was tested using cytokinesis block micronucleus (CBMN) assay on human peripheral blood lymphocytes (PBLs) in vitro. HPLC-PDA showed that both A. alba extracts were richer in polyphenolic contents than A. vulgaris extracts. The acetone A. alba extract was the richest of polyphenolic content where we detected six phenolic acids and two flavonoids. CBMN assay showed that aqueous extract of A. vulgaris significantly increased micronucleus (MN) frequency in the PBLs treated with all tested concentrations (10, 50, 100, and 250 µg/mL), while A. alba did not significantly affect the mean MN frequency. Further, both acetone extracts were genotoxic in all tested concentrations, except the lowest tested (10 µg/mL) of A. alba. All tested extracts affected the nuclear division index (NDI) except the aqueous A. alba extract (p < 0.05). Based on our results, we can conclude that both acetone and aqueous A. vulgaris extracts and A. alba acetone extract were genotoxic in PBLs in vitro. A. alba aqueous extract was not genotoxic and cytotoxic in tested concentrations. We suggest that the aqueous extract of A. alba can be used in treatment, which has been confirmed by traditional medicine, but with a high dose of caution and not in high concentrations.


Artemisia , Acetone/toxicity , Artemisia/chemistry , DNA Damage , Flavonoids/analysis , Flavonoids/toxicity , Humans , Plant Extracts/chemistry , Plant Extracts/toxicity
5.
Environ Sci Pollut Res Int ; 28(45): 64552-64560, 2021 Dec.
Article En | MEDLINE | ID: mdl-34312749

Petroleum hydrocarbons are important characteristic pollutants in the process of oil exploitation in the Yellow River Delta (China), and they cause a potential hazard to the surrounding ecological environment. The research on eco-toxicological effects of petroleum-derived products still needs to be studied in depth. This paper describes the physiological indices of wheat (Triticum aestivum L.) seeds and seedlings under independent stresses of acetone, 2-pentanone, and 2-hexanone to determine the toxicological effects of ketones derived from petroleum products on typical crops. The experimental results indicated that ketones with concentrations lower than 0.4 mg·cm-2 and 800 mg·kg-1 the germination of wheat seeds and the growth of seedlings were promoted to 113.32-127.27% and 105.41-126.39%, respectively, thus exhibiting low-dose excitatory effects. However, when the concentration was higher than 0.4 mg·cm-2 and 800 mg·kg-1, germination and seedlings' growth were significantly reduced to 7.14-2.12% and 35.09-13.33%, respectively. At the same time, acetone had a greater impact on the growth of wheat seed roots, the malondialdehyde (MDA), and chlorophyll contents in leaf tissues. The low concentration of acetone had a significant promoting effect on the activity of α-amylase in wheat seeds. 2-Pentanone reduced the electrical conductivity of wheat seed extract, and it significantly promoted the catalase (CAT) activity at low concentrations. 2-Hexanone had a strong inhibitory effect on wheat germination and growth. This study provided new research results to determine the toxic effects of petroleum-derived products and provided a basis for the environmental management of such substances.


Germination , Seedlings , Acetone/toxicity , Methyl n-Butyl Ketone , Pentanones , Seeds , Triticum
6.
Regul Toxicol Pharmacol ; 120: 104840, 2021 Mar.
Article En | MEDLINE | ID: mdl-33321148

In 2017, JECFA requested reproductive and developmental toxicity studies to finalize an acceptable daily intake for solvent rosemary extracts. Thus, an OECD 421 reproductive/developmental toxicity study was conducted using an acetone rosemary extract that complied with JECFA and EFSA food additive specifications. Rosemary extract was provided to rats at dietary concentrations of 0 (control), 2100, 3600, or 5000 mg/kg, for 14 days before mating, during mating, and thereafter (throughout gestation and up to Lactation Day 13 for females) until necropsy. General toxicity (clinical signs, body weight, food consumption) and reproductive/developmental outcomes (fertility and mating performance, estrous cycles, anogenital distance, thyroid hormones, reproductive organ weights, thyroid histopathology) were assessed. There were no signs of general toxicity and no effects on reproduction; thus, the highest concentration tested (equivalent to mean daily intakes of 316 or 401 mg/kg bw/day [149 or 189 mg/kg bw/day carnosol and carnosic acid] for males and females, respectively) was established as the no-observed-adverse-effect level for general and reproductive toxicity. Dose-related reductions in T4 were observed for Day 13 pups (not seen on Day 4) but were not accompanied by thyroid weight changes or histopathological findings; further investigations are required to determine the biological relevance of these T4 reductions.


Acetone/toxicity , Genitalia/drug effects , Plant Extracts/toxicity , Reproduction/drug effects , Rosmarinus , Animals , Animals, Newborn , Developmental Disabilities/chemically induced , Developmental Disabilities/pathology , Drug Evaluation, Preclinical/methods , Female , Genitalia/physiology , Male , No-Observed-Adverse-Effect Level , Organ Size , Plant Extracts/isolation & purification , Pregnancy , Rats , Reproduction/physiology
7.
J Neuroinflammation ; 17(1): 122, 2020 Apr 20.
Article En | MEDLINE | ID: mdl-32312281

BACKGROUND: Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. METHODS: Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. RESULTS: AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1ß, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. CONCLUSIONS: Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.


Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Inflammasomes/metabolism , Pruritus/metabolism , Skin/metabolism , Spinal Cord/metabolism , Acetone/toxicity , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Animals , Apoptosis Regulatory Proteins/antagonists & inhibitors , Chronic Disease , Ether/toxicity , Female , Genetic Vectors/administration & dosage , Male , Mice , Mice, Inbred C57BL , Pruritus/chemically induced , Pruritus/pathology , Skin/drug effects , Skin/pathology , Spinal Cord/drug effects , Spinal Cord/pathology
8.
Cancer Prev Res (Phila) ; 13(6): 551-562, 2020 06.
Article En | MEDLINE | ID: mdl-32161072

Sulforaphane (SFN), a potent antioxidant and antiinflammatory agent, has been shown to protect against cancers especially at early stages. However, how SFN affects UVB-mediated epigenome/DNA methylome and transcriptome changes in skin photodamage has not been fully assessed. Herein, we investigated the transcriptomic and DNA methylomic changes during tumor initiation, promotion, and progression and its impact and reversal by SFN using next-generation sequencing (NGS) technology. The results show that SFN reduced tumor incidence and tumor number. SFN's protective effects were more dramatic in the early stages than with later stages. Bioinformatic analysis of RNA sequencing (RNA-seq) data shows differential expressed genes and identifies the top canonical pathways related to SFN treatment of UVB-induced different stages of epidermal carcinogenesis. These pathways include p53 signaling, cell cycle: G2-M DNA damage checkpoint regulation, Th1, and Th2 activation pathway, and PTEN signaling pathways. The top upstream regulators related to UVB and SFN treatment as time progressed include dextran sulfate, TP53, NFE2L2 (Nrf2), IFNB1, and IL10RA. Bioinformatic analysis of Methyl-seq data shows several differential methylation regions induced by UVB were attenuated by SFN. These include Notch1, Smad6, Gnai3, and Apc2 Integrative analysis of RNA-seq and DNA-seq/CpG methylome yields a subgroup of genes associated with ultraviolet B (UVB) and SFN treatment. The changes in gene expression were inversely correlated with promoter CpG methylation status. These genes include Pik3cd, Matk, and Adm2 In conclusion, our study provides novel insights on the impact of SFN on the transcriptomic and DNA methylomic of UVB-induced different stages of skin cancer in mice.


Anticarcinogenic Agents/therapeutic use , DNA Methylation/drug effects , Epigenome/drug effects , Isothiocyanates/therapeutic use , Neoplasms, Radiation-Induced/prevention & control , Skin Neoplasms/prevention & control , Sulfoxides/therapeutic use , Transcriptome/drug effects , Ultraviolet Rays/adverse effects , Acetone/toxicity , Animals , CpG Islands/drug effects , DNA, Neoplasm/genetics , Disease Progression , Female , Gene Expression Regulation, Neoplastic/genetics , Mice , Mice, Hairless , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/genetics , Promoter Regions, Genetic , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/genetics , RNA-Seq , Radiation-Sensitizing Agents/toxicity , Random Allocation , Skin Neoplasms/etiology , Skin Neoplasms/genetics
9.
J Appl Toxicol ; 40(4): 483-492, 2020 04.
Article En | MEDLINE | ID: mdl-31736102

Carrier solvents are used frequently in toxicity testing to assist hydrophobic chemicals into solution, but such solvents may have toxic effects on test subjects. Amphibians are model organisms in toxicity studies; however, little is known about the direct effects of solvents on native amphibians. Following modifications to standardized guidelines for native species, we used acute 96-hour exposures to assess the direct effects of three common solvents on survival, differences in morphology and occurrence of abnormalities of northern leopard frog larvae (Lithobates pipiens). The solvents, dimethyl sulfoxide (DMSO), ethanol (ETOH) and acetone (ACE) were used at nominal concentrations ranging from 1 to 100 µL/L. We also conducted a 30-day exposure to assess the direct chronic effects of DMSO at 1 and 5 µL/L, on larval growth, development and sex differentiation, but found no effects. Acute exposure to solvents also had no effect on the survival of larvae, but we found significant abnormalities in tadpoles acutely exposed to 100 µL/L ACE. Acute exposure to DMSO and ETOH had further concentration-dependent effects on larval morphological traits. Our study suggests that DMSO and ETOH at ≤20 µL/L may be used as solvents in amphibian ecotoxicological studies, but ACE should be limited to ≤50 µL/L in ecotoxicity studies and perhaps much less (≤10 µL/L) in studies with other amphibians, based on a review of existing literature. We emphasize pilot studies when using solvents on acute and chronic ecotoxicity tests, using native amphibians.


Acetone/toxicity , Dimethyl Sulfoxide/toxicity , Ecotoxicology , Embryo, Nonmammalian/drug effects , Ethanol/toxicity , Rana pipiens/embryology , Solvents/toxicity , Toxicity Tests , Animals , Dose-Response Relationship, Drug , Embryonic Development/drug effects , Female , Male , Risk Assessment , Sex Differentiation/drug effects , Time Factors
10.
Ecotoxicol Environ Saf ; 183: 109589, 2019 Nov 15.
Article En | MEDLINE | ID: mdl-31509929

A microbial fuel cell (MFC) was successfully developed as a toxicity biomonitoring system to enable a quick response to wastewater with unknown toxicity in toxic events. The objective was to quantitatively assess the toxicity of wastewater by a rapid method. Different concentrations of formaldehyde were introduced into the anode chamber, which led to different stages of voltage change. A relationship between the linear slope of the voltage drop stage and the formaldehyde concentration was established through dose-response fitting results. This relationship makes it possible to convert an unknown toxicity of wastewater into the equivalent concentration of formaldehyde. The minimum detection limit in this study was 13 mg/L formaldehyde equivalents. As the toxicity of the wastewater increased, the test time could be reduced to as low as 921 s or even shorter, with a detection error of 3-12 mg/L. By using this evaluation method, oxidized tail gas scrubber wastewater was identified as the main toxic wastewater component in a phenol acetone production plant.


Bioelectric Energy Sources , Biological Monitoring/methods , Biosensing Techniques/methods , Wastewater/toxicity , Acetone/toxicity , Electrodes , Formaldehyde/toxicity , Models, Theoretical , Phenol/toxicity , Wastewater/chemistry
11.
Bull Exp Biol Med ; 167(4): 521-524, 2019 Aug.
Article En | MEDLINE | ID: mdl-31502124

The effects of inhalation exposure to a mixture containing acetone, acetaldehyde, and ethanol in concentrations typical of closed environment in space vehicles on the structure of mesenteric lymph nodes in F1 male mice were studied by histological technique. The long-term exposure to modeled atmosphere led to pronounced structural changes in these nodes that were clearly seen on day 22 and increased by day 36 of the experiment. The thickness of the capsule and trabeculae of mesenteric lymph nodes as well as diameter of lymphatic sinuses did not differ from the control values up to day 8, but then increased on days 22-70. Starting from day 22, the thickness of the medullary cords decreased and attained the minimum to the end of the experiments, which can indicate depletion of immunocytopoiesis and inhibition of humoral immunity. The present data are important for the space medicine, because they indicate structural changes in the peripheral lymphoid organs, the key elements of immune system.


Lymph Nodes/drug effects , Space Flight , Acetaldehyde/toxicity , Acetone/toxicity , Animals , Ethanol/toxicity , Immunity, Humoral/drug effects , Male , Mice
12.
Int Wound J ; 16(6): 1330-1338, 2019 Dec.
Article En | MEDLINE | ID: mdl-31446674

There are many chemicals that can cause burns. Although they are generally acidic and basic in nature, there are more than one million known chemical compounds, of which 300 have been declared highly hazardous chemical substances by the National Fire Protection Society. Chemical burns account for approximately 10.7% of all burn injuries and 30% of deaths because of burns. Chemicals can be classified as acid, alkali, organic, and inorganic compounds. Acids act by denaturing and coagulating proteins. Alkaline burns cause deeper burns than acid burns.


Burns, Chemical/etiology , Acetic Acid/toxicity , Acetone/toxicity , Air Bags/adverse effects , Burns, Chemical/pathology , Caustics/toxicity , Cyanoacrylates/toxicity , Humans , Hydrocarbons/toxicity , Hydroquinones/toxicity , Sodium Hydroxide/toxicity
14.
Behav Brain Res ; 360: 303-311, 2019 03 15.
Article En | MEDLINE | ID: mdl-30543902

Peripheral neuropathy is a common adverse effect observed during the use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the modulatory effect of bone marrow derived mesenchymal stem cells (BM-MSCs) on pregabalin (PGB) treatment in PTX-induced peripheral neuropathy. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i.p) 4 times every other day. Rats were then treated with PGB (30 mg/kg/day, p.o.) for 21 days with or without a single intravenous administration of BM-MSCs. At the end of experiment, behavioral and motor abnormalities were assessed. Animals were then sacrificed for measurement of total antioxidant capacity (TAC), nerve growth factor (NGF), nuclear factor kappa B p65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and active caspase-3 in the sciatic nerve. Moreover, protein expressions of Notch1 receptor, phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) were estimated. Finally, histological examinations were performed to assess severity of sciatic nerve damage and for estimation of BM-MSCs homing. Combined PGB/BM-MSCs therapy provided an additional improvement toward reducing PTX-induced oxidative stress, neuro-inflammation, and apoptotic markers. Interestingly, BM-MSCs therapy effectively prevented motor impairment observed by PGB treatment. Combined therapy also induced a significant increase in cell homing and prevented PTX-induced sciatic nerve damage in histological examination. The present study highlights a significant role for BM-MSCs in enhancing treatment potential of PGB and reducing its motor side effects when used as therapy in the management of peripheral neuropathy.


Antineoplastic Agents, Phytogenic/toxicity , Cell- and Tissue-Based Therapy/methods , Mesenchymal Stem Cells/physiology , Motor Disorders/etiology , Motor Disorders/therapy , Paclitaxel/toxicity , Pregabalin/therapeutic use , Receptor, Notch1/metabolism , Sciatic Neuropathy , Acetone/toxicity , Analysis of Variance , Animals , Antioxidants/metabolism , Caspase 3/metabolism , Disease Models, Animal , Hyperalgesia/physiopathology , Hyperalgesia/therapy , Interleukin-6/metabolism , Janus Kinases/metabolism , Male , Nerve Growth Factor/metabolism , Rats , Rats, Wistar , Rotarod Performance Test , STAT Transcription Factors/metabolism , Sciatic Neuropathy/chemically induced , Sciatic Neuropathy/complications , Sciatic Neuropathy/therapy , Time Factors , Tumor Necrosis Factor-alpha/metabolism
15.
J Toxicol Sci ; 43(7): 407-422, 2018.
Article En | MEDLINE | ID: mdl-29973473

The Short Time Exposure (STE) test method is an in vitro method for assessing the eye irritation potential of chemicals and is used to classify the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 1 and No Category (NC). The method has been adopted by the Organisation for Economic Co-operation and Development (OECD) as test guideline (TG) 491 since 2015. While this method can be used to classify GHS NC, it is not suitable for testing highly volatile substances and solids other than surfactants. Here we evaluated highly volatile substances to expand the applicability domain. According to TG 491, acetone, ethanol, iso-propanol, and methyl acetate as highly volatile substances resulted in false negatives. Saline was selected as a solvent of these false negatives. In this study, mineral oil was used as the solvent, because these false negatives were amphiphilic. Based on this change, four highly volatile substances were correctly evaluated. The predictive performance for classifying GHS NC was then verified using a substance dataset constructed in reference to the Draize eye test Reference Database and STE Summary Review Document. The accuracy and false-negative rate were 86.6% (194/224) and 3.8% (3/80), respectively. Collectively, the applicability domain was expanded by changing the solvent to mineral oil for highly volatile substances, and the predictive performance for the new applicability domain including highly volatile substances was excellent. The STE test method is suitable to classify GHS NC, indicating its applicability as a test method in a bottom-up approach.


Animal Testing Alternatives/methods , Cell Survival/drug effects , Cornea/drug effects , Irritants/toxicity , Volatile Organic Compounds/toxicity , 2-Propanol/toxicity , Acetates/toxicity , Acetone/toxicity , Animals , Cells, Cultured , Cornea/cytology , Ethanol/toxicity , False Negative Reactions , Mineral Oil , Rabbits , Sodium Chloride , Solvents , Surface-Active Agents , Time Factors , Toxicity Tests, Acute/methods
16.
Pain ; 159(11): 2201-2213, 2018 Nov.
Article En | MEDLINE | ID: mdl-29939958

Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. We subjected mice to chronic itch by repetitive cutaneous treatment with acetone and diethylether followed by water (AEW) that models "dry skin." After 3 to 4 weeks AEW treatment, the mice developed behavioral phenotypes of anxiety and depression assessed by a battery of behavioral paradigms, such as light-dark box and forced swim test. These behavioral symptoms of mood disturbance were independent of cutaneous barrier disruption, but correlated well with the degree of the irritating itch sensation. Although AEW mice showed normal circadian hypothalamic-pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was dampened, including impaired endocrine stress responsivity, altered neuroendocrine-immune interaction, and blunted corticosterone response to both dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.


Diterpenes/therapeutic use , Hypothalamo-Hypophyseal System/drug effects , Mood Disorders/etiology , Pituitary-Adrenal System/diagnostic imaging , Pruritus/drug therapy , Pruritus/pathology , Acetone/toxicity , Adaptation, Ocular/drug effects , Animals , Disease Models, Animal , Feeding Behavior/drug effects , Fever/etiology , Food Preferences , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Pruritus/chemically induced , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Corticotropin-Releasing Hormone/metabolism , Stress, Psychological/complications , Time Factors
17.
Mutat Res ; 803-805: 17-21, 2017 10.
Article En | MEDLINE | ID: mdl-28759748

We evaluated DNA damage levels of different categories of workers exposed to hazards inside electronics factories in Southern China. To find out the most dangerous risk factor, a cross-sectional study was conducted on a total of 584 exposed subjects and 138 controls in an electronics factory in Southern China, where the electronics industry is prevalent. The exposed hazards included isopropanol (IPO), lead, noise, video display terminals (VDT), lead in a high-temperature (high-temp) environment, and IPO in a high-temp environment. DNA damage detection was performed by the micro-whole blood comet assay using peripheral blood. DNA damage levels were estimated by percent tail DNA (%T). Linear regression models were used to test DNA damage differences between exposed groups and control group with adjustments for potential confounding factors. The level of DNA damage was more significant in both lead in a high-temp and IPO in a high-temp environment groups than in that of the controls (p<0.05). The differences remained significant after stratifying by smoking status (p<0.05). There were no significant differences between groups exposed to IPO, lead, noise, VDT environment and controls. In conclusion, we identified potential risk factors for DNA damage to electronics workers. Special attention should be paid to workers exposed to IPO and lead in a high-temp environment.


DNA Damage/drug effects , Hazardous Substances/toxicity , Manufacturing Industry , Occupational Exposure/adverse effects , 2-Propanol/toxicity , Acetone/toxicity , Adolescent , Adult , Benzene/toxicity , China , Comet Assay , Cross-Sectional Studies , Female , Hot Temperature , Humans , Lead/toxicity , Linear Models , Male , Surveys and Questionnaires , Toluene/toxicity , Xylenes/toxicity , Young Adult
18.
J Occup Environ Med ; 59(5): 467-473, 2017 05.
Article En | MEDLINE | ID: mdl-28486343

OBJECTIVE: The objective of this study was to examine whether fractional exhaled nitric oxide (FeNO) and spirometry can be used as indices to evaluate adverse health effects of low-concentrated chemical inhalation exposure, mainly to formaldehyde. METHODS: Thirty-three subjects (pathology technicians) and 30 controls (workers without handling any chemicals in the same hospitals) participated in this study. All participants underwent FeNO measurement and spirometry before and after 5 days of work. RESULTS: FeNO significantly increased in the subjects with a history of asthma (P < 0.05), whereas forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) decreased in the subjects (P < 0.05). Furthermore, work duration and pre-work levels of FEV1 in the subjects had a significant association. CONCLUSION: The results suggest that FeNO, FVC, and FEV1 represent effective health-effect indices of low-concentrated chemical inhalation exposure.


Fixatives/toxicity , Formaldehyde/toxicity , Medical Laboratory Personnel , Nitric Oxide/analysis , Occupational Exposure/adverse effects , Pathology Department, Hospital , Physicians , Acetone/toxicity , Adult , Aged , Asthma/physiopathology , Benzene Derivatives/toxicity , Breath Tests , Case-Control Studies , Female , Forced Expiratory Volume , Humans , Inhalation Exposure/adverse effects , Male , Medical Laboratory Personnel/organization & administration , Middle Aged , Pathology Department, Hospital/organization & administration , Peak Expiratory Flow Rate , Personnel Staffing and Scheduling , Physicians/organization & administration , Spirometry , Time Factors , Vital Capacity , Xylenes/toxicity , Young Adult
19.
Neuroreport ; 28(9): 518-526, 2017 Jun 14.
Article En | MEDLINE | ID: mdl-28410268

Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice. Furthermore, a single injection of BoNT/A reduced the expression of the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), and the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) at both transcriptional and translational levels in the dorsal root ganglia (DRG) in mice. Pretreatment of BoNT/A also attenuated chronic itch induced by acetone-diethylether-water treatment and abolished the upregulation of TRPA1 in the DRG. Thus, it was suggested that downregulation of the expression of TRPA1 and TRPV1 in the DRG may contribute toward the long-term anti-itch effects of a single injection of BoNT/A in mice and BoNT/A treatment may serve as an alternative strategy for anti-itch therapy.


Botulinum Toxins, Type A/therapeutic use , Down-Regulation/drug effects , Ganglia, Spinal/drug effects , Neuromuscular Agents/therapeutic use , Pruritus/drug therapy , TRPA1 Cation Channel/genetics , TRPV Cation Channels/genetics , Acetone/toxicity , Animals , Chloroquine/toxicity , Chronic Disease , Disease Models, Animal , Dose-Response Relationship, Drug , Formaldehyde/toxicity , Ganglia, Spinal/metabolism , Male , Mice , Motor Activity/drug effects , Pain/chemically induced , Pain/drug therapy , Pruritus/chemically induced , Pruritus/pathology , TRPA1 Cation Channel/metabolism , TRPV Cation Channels/metabolism , Time Factors , p-Methoxy-N-methylphenethylamine/toxicity
20.
Environ Toxicol Chem ; 36(10): 2631-2639, 2017 10.
Article En | MEDLINE | ID: mdl-28337778

Carrier solvents are often used in aquatic toxicity testing for test chemicals with hydrophobic properties. However, the knowledge of solvent effects on test organisms remains limited. The present study aimed to determine the biochemical effects of the 4 common solvents methanol, ethanol, acetone, and dimethyl sulfoxide (DMSO) on 2 test species, Lemna minor and Raphidocelis subcapitata, by applying Fourier transform infrared spectroscopy (FTIR) coupled with multivariate analysis to select appropriate solvents for toxicity testing. The results showed biochemical variations associated with solvent treatments at different doses on test species. From the infrared spectra obtained, the structures of lipid membrane and protein phosphorylation in the test species were found to be sensitive to the solvents. Methanol and ethanol mainly affected the protein secondary structure, whereas acetone and DMSO primarily induced alterations in carbohydrates and proteins in the test species. The FTIR results demonstrated that methanol and ethanol showed higher biochemical alterations in the test species than acetone and DMSO, especially at the high doses (0.1 and 1% v/v). Based on the growth inhibition displayed and FTIR spectroscopy, acetone, and DMSO can be used as carrier solvents in toxicity testing when their doses are lower than 0.1% v/v. Environ Toxicol Chem 2017;36:2631-2639. © 2017 SETAC.


Araceae/drug effects , Chlorophyta/drug effects , Solvents/toxicity , Acetone/toxicity , Araceae/growth & development , Chlorophyta/growth & development , Dimethyl Sulfoxide/toxicity , Discriminant Analysis , Ethanol/toxicity , Methanol/toxicity , Multivariate Analysis , Principal Component Analysis , Solvents/chemistry , Spectroscopy, Fourier Transform Infrared , Toxicity Tests
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