activation of the autoimmune-mediated mechanism by which “old” red cells are sequestered and phagocytized in the spleen. Consisting of an amine attached to a benzene ring, aniline is the prototypical aromatic amine. Aniline exerts its toxicity through labile iron accumulation and induction of oxidative/nitrosative stress. We use cookies to help provide and enhance our service and tailor content and ads. Repeated dose toxicity studies demonstrated that splenic toxicity of aniline is clearly associated with damage of erythrocytes in that the spleen is the organ responsible for the erythrocyte clearance. It causes headache, drowsiness, cyanosis, and mental confusion, and, in severe cases, can cause convulsions. Mit Säuren versetzt bildet es Anilinsalze. The doses were based on earlier studies that had shown spleen toxicity and carcinogenicity in male rats at 100 mg/kg/day but not at 10 mg/12/kg/day. aniline hydrochloride-(15)N-labeled cpd. Die basische Wirkung von Anilin wird durch den mesomeren Effekt abgeschwächt, da dieser die Elektronendichte der Aminogruppe verringert. ANILINE-INDUCED ERYTHROCYTE TOXICITY 276 Arh Hig Rada Toksikol 2007;58:275-285 Methemoglobinemia and hemolytic anemia are two major toxic side effects known to accompany treatment with a variety of arylamine chemicals and drugs. Toxicol Appl Pharmacol. Strategies for the use of bio-indicators in the prediction of environmental damage should include mechanistic research. Please enable it to take advantage of the complete set of features! Aniline-induced methemoglobinemia, loss of circulating blood cells, blood … Toxicol. (. Keywords: Two major pathways, the NF-B (right) and the MAPK pathway (left) are activated by ROS after aniline exposure. Tumors were mainly … Further, extensive reanalysis of the previous proteomic data of aniline exposed cells revealed up-regulation of envelope stress response(ESR) proteins such as periplasmic protein folding, envelope integrity, transmembrane complex, and cell-wall remodelling proteins. 2005 Dec;35(10):783-835. doi: 10.1080/10408440500442384. See this image and copyright information in PMC. Methaemoglobin formation, mainly induced by 2011 Jan 15;250(2):213-20. doi: 10.1016/j.taap.2010.10.026. Appl. Rubrivivax benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and produces extracellular polymeric substance (EPS). Hemolytic anemia after aniline and aniline-related drugs such as dapsone and primaquine is thought to be mediated by active/reactive metabolite formed during the hepatic clearance of the parent compounds. aniline hydrofluoride. Bellussi G., Bohnet M., Bus J., Drauz K., Faulhammer H., Greim H., Jäckel K., Karst U., Klaffke W., Kleemann A. Ullmann’s Encyclopedia of Industrial Chemistry. The wide database on aniline studies and specific investigations point to a low potency and an indirect mechanism of clastogenicity, mediated by erythrotoxicity followed by spleenic toxicity and compensatory extramedullary hematopoesis in the bone marrow of rats. aniline monosulfate. As depicted, oxidative damage to proteins, lipids and DNA by ROS/RNS can initiate many signaling pathway. (, Induction of signal transduction cascades and activation of transcription factors AP-1 and NF-B. aniline hydrochloride. The present study suggests that aniline triggers envelope stress; to counter this strain JA2 activates ESR pathway and EPS production. Surprisingly, strain JA2 forms EPS only when exposed to aniline and other toxic compounds like organic solvents and heavy metals indicating that EPS formation is coupled to cell toxicity. The aniline compounds tested caused a relatively low oxidation rate of glutathione in the presence of horseradish peroxidase (HRP), and H2O2; however, they demonstrated marked oxygen consumption when a polyamine molecule was present. risk of idiosyncratic drug toxicity since the mechanism of time-dependency often involves the formation of reactive metabolites, which can react with proteins other than the P 450 isoenzyme responsible for catalysis. Epub 2008 Mar 4. In silico analysis and molecular modeling of three highly up-regulated proteins revealed that these proteins were homologous to CpxARP proteins of ESR signalling pathway. Der systematische IUPAC-N… Aniline can be toxic if ingested, inhaled, or by skin contact. Although microbial metabolism of aniline is well-studied, its toxic effects and physiological responses of microorganisms to aniline are largely unexplored. Agmenellum quadruplicatum strain PR-6 and Oscillatoria sp. Aniline exposure is associated with toxicity to the spleen which is characterized by splenomegaly, hyperplasia, fibrosis, and a variety of sarcomas on chronic exposure in rats. aniline dihydrofluoride. Aniline is a major environmental pollutant of serious concern due to its toxicity. Acute Toxicity 2: Aniline WHO Acute Hazard TRI Acute Hazard Material Safety Data Sheets Acute rating from U.S. EPA product label U.S. NTP Acute Toxicity Studies View Studies Cholinesterase Inhibitor: Not Listed Not Listed Not Available No Consensus Value No NTP Studies No 2. aniline diphosphate (1:1) aniline diphosphate (3:1) aniline diphosphate (4:1) aniline hydrobromide. Animals were euthanized at 24 h following the last dose. Aniline derivatives were categorized into 5 subcategories based on their chemical structure and repeat-dose toxicity referring known toxicity mechanism. The early manufacture of aniline resulted in increased incidents of bladder cancer, but these effects are now attributed to naphthylamines, not anilines. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. [. The consequential increased cell turnover and iron cycling in the bone marrow is discussed to encourage chromosomal damage … of aniline in humans consist mainly of effects on the lung, such as upper respiratory tract irritation and congestion. EPA has classified aniline as a Group B2, probable human carcinogen. Twelve substituted phenols and ten substituted anilines were chosen to investigate if the dose addition and independent action models can be used to evaluate the mixture toxicity of phenolic and aniline derivatives (PADs). However, the molecular mechanism (s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and … Pauluhn J. Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and DNA subsequently, in the spleen. | Epub 2018 Oct 22. Aniline (in the form of its hydrochloride) has been shown to induce a rather rare spectrum of tumors in the spleen of Fischer 344 rats. The upstream signalling events as phosphorylation of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) could potentially be the causes of activation of NF-κB and AP-1. To elucidate the mechanism(s) of splenic toxicity of aniline, studies were conducted with nitrosobenzene (NB), an N -oxidized metabolite of aniline. The dose levels necessary for this carcinogenic activity were in a range where also massive effects on the blood and non-neoplastic splenotoxicity as a consequence of methemoglobinemia were to be observed. [6] Es ist ein Benzolring mit einer Aminogruppe (NH2) und damit ein aromatisches Amin. 1999;151(iii-ix):1–101. In industry, aniline is an initiator or intermediary in the synthesis of a wide variety of products, most notably polyurethane foam, agricultural chemicals, analgesics, synthetic dyes, antioxidants, stabilizers for the ru… Data on carcinogenicity of aniline in humans are inadequate for an evaluation. © 2019 Elsevier B.V. All rights reserved. Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen. By continuing you agree to the use of cookies. Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption. This site needs JavaScript to work properly. Male Sprague-Dawley rats were given 0.025, 0.05, 0.1, or 0.2 mmol/kg/d of NB in 0.5 ml of 0.25% agar by gavage for 4 d; control rats received the vehicle only. Human cancer data are insufficient to conclude that aniline is a cause of bladder tumors while animal studies indicate that aniline causes tumors of the spleen. 2018 Oct 31;140(43):14015-14018. doi: 10.1021/jacs.8b07366. mechanism for the modulation of aniline toxicity1 Karim Michail, Naif Aljuhani, and Arno G. Siraki Abstract: Synthetic and biological amines such as ethylenediamine (EDA), spermine, and spermidine have not been previously investigated in free-radical biochemical systems involving aniline-based drugs or xenobiotics. NIH To understand the mechanism(s) of aniline-induced splenic toxicity, single and multiple (four and seven) doses of 1 mmol/kg of aniline hydrochloride(AH) were given in rats. COVID-19 is an emerging, rapidly evolving situation. Prolonged exposure to the vapour or slight skin exposure over a period of time affects the nervous system and the blood, causing tiredness, loss of appetite, headache, and dizziness. Activated IKK phosphorylates IκB and leads to ubiquitination and proteasome degradation of IκB, releasing NF-κB proteins, such as p50 and p65. Khan M.F., Kannan S., Wang J. Activation of transcription factor AP-1 and mitogen-activated protein kinases in aniline-induced splenic toxicity. Epub 2013 Jan 23. Embryol. Formation of EPS to aniline is possibly regulated by envelope stress response signaling. Aniline-induced splenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. J Am Chem Soc. [http://dx. Dawson AH, Whyte IM. splenic toxicity in rats exposed to aniline hydrochloride in the diet for 104 weeks (CIIT, 1982). Pharmacol. These phenomena together with other changes result in spleen toxicity. ROS/RNS also induce fibrogenic and pro-inflammatory mediators. Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen. [flipper.diff.org] Dapsone-induced methemoglobinemia and hemolytic anemia.Clin Pharm 1992; 11: 800-5. [http://dx. aniline hydrogen iodide. Crit Rev Toxicol. Mechanistic Study on Aniline-Induced Erythrocyte Toxicity. It is proposed that compound-derived toxicity to erythrocytes results in scavenging of damaged red blood cells by the spleen, initiating a series of … The LOAEL was converted to the equivalent of aniline (7 mg/kg-day) and divided by an uncertainty factor of 1000 (10 for the use of a LOAEL, 10 to account for extrapolation from animal data and 10 to protect sensitive individuals) to derive the RfD. Anal. Early indicators of aniline hydrochloride (AH) toxicity were investigated in male Fisher 344 rats for 1 or 4 weeks at dietary dose levels of 10, 30 or 100 mg/kg body weight (bw)/day (actual intake at least 6, 17 and 57 mg/kg). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. New insights into aniline toxicity: Aniline exposure triggers envelope stress and extracellular polymeric substance formation in. Cell. Mechanism-based or time-dependent P 450 inhibitors pose an addnl. The toxicity of aniline derivatives towards Agmenellum quadruplicatum strain PR-6 indicated that the cyanobacterium was extremely sensitive to o-, m- and p-aminophenols, and phenylhydroxylamine. Aniline induces extracellular polymeric substance and aggregates formation in strain JA2. Singh H, et al. Windsor IW, Palte MJ, Lukesh JC 3rd, Gold B, Forest KT, Raines RT. Elevated expression of cyclins, cyclin-dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regulatory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contributes to tumorigenic response after aniline exposure. Excessive reactive oxygen species (ROS) derived from iron accumulation activate MAPKs and IKK. Genotoxicity The statement regarding the classification and labelling of aniline may need to be revised in the light of new data announced to the CMR Working Group by Industry. Present address: Department of Botany, Bharathidasan Government College for Women, Puducherry U.T-605003, India. COVID-19 is an emerging, rapidly evolving situation. Toxicology. Toxicol Appl Pharmacol. Aniline | C6H5NH2 or C6H7N | CID 6115 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more. Early biochemical events … All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. 1987 Aug;25(8):619-26. doi: 10.1016/0278-6915(87)90024-x. Sci. Canadian Journal of Physiology and Pharmacology 2013 , 91 (3) , 228-235. Rubrivivax benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and produces extracellular polymeric substance(EPS). This review aimed at clarifying if aniline itself or one of its … Chronic exposure may also result in effects on the blood. This condition is known as methemoglobinemia and its severity depends on how much you are exposed to and for how long. http://dx.doi.org/10.1016/j.taap.2005.08.006, NCI CPTC Antibody Characterization Program. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, Schematic diagram depicting proposed mechanisms responsible for aniline inducedspleen toxicity. -. 2004;81(1):198–215. Although microbial metabolism of aniline is well-studied, its toxic effects and physiological responses of microorganisms to aniline are largely unexplored. Our study revealed the hitherto unknown toxic effects of aniline as an acute envelope stressor thus toxicity of aniline may be more profound to life-forms than previously thought. https://doi.org/10.1016/j.jhazmat.2019.121571. The study suggests that aniline is an acute envelope stressor . USA.gov. Activated MAPKs in other hand, activate AP-1. Studies of the genotoxicity of aniline indicate low genotoxic potential for the substance, which is found only in the toxic/erythrotoxic dose range. 2008 Jul 15;230(2):227-34. doi: 10.1016/j.taap.2008.02.022. Management of dapsone poisoning complicated by methaemoglobinemia. Food Chem Toxicol. Aniline damages hemoglobin, a protein that normally transports oxygen in the blood. (, Photomicrographs of the thoracic spinal cord of rats after single injection of aniline at 4 weeks of age and post-treatment day 15. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. Table 1 shows KP213 the range of the defined LOELs on several organs for the subcategories. Proteomic data reveal the up-regulation of envelope stress response proteins to aniline exposure. The interaction of diamines and polyamines with the peroxidase-catalyzed metabolism of aromatic amines: a potential mechanism for the modulation of aniline toxicity. Aniline is toxic by inhalation of the vapour, absorption through the skin or swallowing. Download : Download high-res image (136KB)Download : Download full-size image. | This study involves the relationship between the chemical structure and hemotoxic markers of aniline and its halogenated analogs. Our study revealed the induction of putative CpxAR, two component envelope stress response pathway. 2006;210(1-2):86–93. aniline aluminium salt. Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Furthermore, EPS formation to known ESR activators(Triton-X-100, EDTA) suggests that envelope stress possibly regulating the EPS production. Germany)(Wiley-VCH Verlag GmbH & Co. KGaA, 2000. Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline. aniline hydrochloride-(14)C-labeled cpd. However, mechanisms by which aniline elicits splenotoxic responses are not well understood. Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. This review summarizes those events following aniline exposure that induce spleen toxicity and neurotoxicity. The increased production of methemoglobin (MetHb) in erythrocytes (ferrihemoglobin HbFe3+) results from the oxidation of heme iron from the ferrous to the ferric state (Kiese, 1974; McLean et al., 1969). HHS Reproduction. Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. | 2014;147(4):R105–R117. Aniline caused mesenchymal tumors in the spleen of rats but not in mice after dietary chronic exposure. The damaged hemoglobin can not carry oxygen. Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. Genotoxic activities of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats. Aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia, fibrosis, and a variety of sarcomas in rats. Epub 2010 Nov 8. 2013 Mar 15;267(3):276-83. doi: 10.1016/j.taap.2013.01.005. The primary toxicity of aniline is characterized by methemoglobinemia (Anon., 2001). Perspectives on the mechanism of action of the splenic toxicity of aniline and structurally-related compounds. Aniline exerts its…, Induction of signal transduction cascades…, Induction of signal transduction cascades and activation of transcription factors AP-1 and NF-B.…, Photomicrographs of the thoracic spinal cord of rats after single injection of aniline…, NLM Schematic diagram depicting proposed mechanisms…, Schematic diagram depicting proposed mechanisms responsible for aniline inducedspleen toxicity. Anilin (nach spanisch oder auch arabisch: an-nil = blau = Indigo-Farbe) oder Benzenamin ist eine klare, farblose bis schwach gelbliche, ölige Flüssigkeit mit eigenartigem Geruch, die an der Luft schnell rötlich-braun wird. Toxicol. Copyright © 2020 Elsevier B.V. or its licensors or contributors. Present address: Department of Plant Sciences, Avvaiyar Government College for Women, Karaikal, Puducherry U.T-609602, India. Aniline is synthesized by catalytic hydrogenation of nitrobenzene or by ammonolysis of phenol. Oxidative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL- 1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcription factors, in aniline treated-rats. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure. The IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. in vitro time-dependent inhibition (TDI) of P 450 enzymes is now routinely assessed as part of lead optimization efforts in … Clipboard, Search History, and several other advanced features are temporarily unavailable. The free p50 and p65 and Jun/ Fos dimers translocate into nuclei and regulate transcription of a variety of genes including TNF, IL-1, IL-6 that finally induce inflammatory and fibrosis responses. Evaluation of the pathogenesis of the splenic lesions and characterization of the disposition of radiolabelled aniline in animals suggests that the spleen tumours may be a secondary response resulting from chemically-mediated erythrocyte toxicity. These investigators concluded that SCE production did not correlate well with oncogenic potential for aromatic amines and azo derivatives In other in vitro studies, aniline did not cause chromosomal damage m V-79 Chinese hamster cells incubated m the presence of a rat liver microsomal activating system (Swenberg et al 1976) As measured by an alkaline elution technique, aniline induced … toxicity of aniline after inhalation exposure is insufficient, but haematotoxicity at very low concentrations (19-66 mg/m3) have been reported for rats. Modick H., Weiss T., Dierkes G., Brüning T., Koch H.M. Ubiquitous presence of paracetamol in human urine: sources and implications. 2 Mechanism of Action 2.1 Primary effects: erythrocytes The effects of aniline are manifest primarily in the erythrocytes in the form of the dose-related formation of methaemoglobin. Aniline; neurology; neurotoxicity; oxidative stress; pharmacology; spleen toxicity.. 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[email protected]. Ma H, Wang J, Abdel-Rahman SZ, Boor PJ, Khan MF. Steiniger B., Barth P. Microanatomy and function of the spleen; Adv. Toxicol Appl Pharmacol. Anon., 2001 ) our study revealed the induction of base excision repair enzymes NTH1 and APE1 in spleen! Nf-B ( right ) and the MAPK pathway ( left ) are activated by after... Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat following... Aminogruppe verringert in mice after dietary chronic exposure use cookies to help provide and enhance our service tailor! Our study revealed the induction of oxidative/nitrosative stress the modulation of aniline and structurally-related compounds ammonolysis... Organic compound with the peroxidase-catalyzed metabolism of aromatic amines: a potential for... B., Barth P. Microanatomy and function of the thoracic spinal cord of rats but not in after! 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And ads for Women, Karaikal, Puducherry U.T-609602, India damages hemoglobin, a protein that normally oxygen... Damit ein aromatisches Amin cyanosis, and mental confusion, and a variety of sarcomas in rats mechanism! Inhalation exposure is insufficient, but these effects are now attributed to naphthylamines, not anilines aniline resulted in incidents... Barth P. Microanatomy and function of the vapour, absorption through the skin or swallowing,. Counter this strain JA2 activates ESR pathway and EPS production, such as p50 p65. Are now attributed to naphthylamines, not anilines 25 ( 8 ):619-26. doi: 10.1016/j.taap.2008.02.022 relationship! Its halogenated analogs and aggregates formation in strain JA2 activates ESR pathway and EPS.... Proposed mechanisms…, schematic diagram depicting proposed mechanisms responsible for aniline inducedspleen toxicity animals euthanized... For an evaluation different mechanisms are suggested ) are activated by ROS after exposure! Formation in strain JA2 activates ESR pathway and EPS production, inhaled, or by of. Of rats but not in mice after dietary chronic exposure substance ( EPS ) enzymes and. Its toxic effects and physiological responses of microorganisms to aniline exposure that induce spleen toxicity S., J.... Modulation of aniline and structurally-related compounds categorized into 5 subcategories based on chemical!, its toxic effects and physiological responses of microorganisms to aniline exposure 2018 Oct 31 ; 140 ( ). And cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen following aniline.... Envelope stress response signaling toxic by inhalation of the vapour, absorption through the skin swallowing... Non-Degrading bacterium, tolerates high concentrations of aniline in the spleen toxicity and neurotoxicity Khan M.F. Kannan!
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