Aniline-induced methemoglobinemia, loss of circulating blood cells, blood … Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen. The damaged hemoglobin can not carry oxygen. Aniline can be toxic if ingested, inhaled, or by skin contact. Toxicol. Toxicol Appl Pharmacol. 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. This study involves the relationship between the chemical structure and hemotoxic markers of aniline and its halogenated analogs. https://doi.org/10.1016/j.jhazmat.2019.121571. [http://dx. (. Aniline induces extracellular polymeric substance and aggregates formation in strain JA2. (, Induction of signal transduction cascades and activation of transcription factors AP-1 and NF-B. Epub 2010 Nov 8. 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. The consequential increased cell turnover and iron cycling in the bone marrow is discussed to encourage chromosomal damage … 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. Toxicol Appl Pharmacol. The primary toxicity of aniline is characterized by methemoglobinemia (Anon., 2001). -. Epub 2008 Mar 4. 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. Crit Rev Toxicol. Aniline caused mesenchymal tumors in the spleen of rats but not in mice after dietary chronic exposure. 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. 2018 Oct 31;140(43):14015-14018. doi: 10.1021/jacs.8b07366. 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. 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. Proteomic data reveal the up-regulation of envelope stress response proteins to aniline exposure. Steiniger B., Barth P. Microanatomy and function of the spleen; Adv. 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). Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen. Present address: Department of Plant Sciences, Avvaiyar Government College for Women, Karaikal, Puducherry U.T-609602, India. Khan M.F., Kannan S., Wang J. Activation of transcription factor AP-1 and mitogen-activated protein kinases in aniline-induced splenic toxicity. 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. 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. Anal. Cell. NIH 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. The present study suggests that aniline triggers envelope stress; to counter this strain JA2 activates ESR pathway and EPS production. 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. 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. This site needs JavaScript to work properly. Aniline derivatives were categorized into 5 subcategories based on their chemical structure and repeat-dose toxicity referring known toxicity mechanism. Mit Säuren versetzt bildet es Anilinsalze. Pharmacol. Aniline is a major environmental pollutant of serious concern due to its toxicity. [http://dx. 2014;147(4):R105–R117. Activated MAPKs in other hand, activate AP-1. Toxicol. Methaemoglobin formation, mainly induced by 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 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. COVID-19 is an emerging, rapidly evolving situation. 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. 1987 Aug;25(8):619-26. doi: 10.1016/0278-6915(87)90024-x. 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. Windsor IW, Palte MJ, Lukesh JC 3rd, Gold B, Forest KT, Raines RT. Sci. Food Chem Toxicol.  |  splenic toxicity in rats exposed to aniline hydrochloride in the diet for 104 weeks (CIIT, 1982). See this image and copyright information in PMC. of aniline in humans consist mainly of effects on the lung, such as upper respiratory tract irritation and congestion. 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. 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. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. 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. Strategies for the use of bio-indicators in the prediction of environmental damage should include mechanistic research. aniline hydrofluoride. 2011 Jan 15;250(2):213-20. doi: 10.1016/j.taap.2010.10.026. Modick H., Weiss T., Dierkes G., Brüning T., Koch H.M. Ubiquitous presence of paracetamol in human urine: sources and implications. The IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. Chronic exposure may also result in effects on the blood. aniline dihydrofluoride. Perspectives on the mechanism of action of the splenic toxicity of aniline and structurally-related compounds. 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. [flipper.diff.org] Dapsone-induced methemoglobinemia and hemolytic anemia.Clin Pharm 1992; 11: 800-5. Studies of the genotoxicity of aniline indicate low genotoxic potential for the substance, which is found only in the toxic/erythrotoxic dose range. Consisting of an amine attached to a benzene ring, aniline is the prototypical aromatic amine. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure. COVID-19 is an emerging, rapidly evolving situation. Embryol. Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption. activation of the autoimmune-mediated mechanism by which “old” red cells are sequestered and phagocytized in the spleen. Download : Download high-res image (136KB)Download : Download full-size image. By continuing you agree to the use of cookies. Management of dapsone poisoning complicated by methaemoglobinemia. Furthermore, EPS formation to known ESR activators(Triton-X-100, EDTA) suggests that envelope stress possibly regulating the EPS production. aniline hydrochloride-(15)N-labeled cpd. These phenomena together with other changes result in spleen 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. 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-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. 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). 2008 Jul 15;230(2):227-34. doi: 10.1016/j.taap.2008.02.022. 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. All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. 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. Table 1 shows KP213 the range of the defined LOELs on several organs for the subcategories. Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. Excessive reactive oxygen species (ROS) derived from iron accumulation activate MAPKs and IKK. The interaction of diamines and polyamines with the peroxidase-catalyzed metabolism of aromatic amines: a potential mechanism for the modulation of aniline toxicity. Mechanism-based or time-dependent P 450 inhibitors pose an addnl. [. 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 early manufacture of aniline resulted in increased incidents of bladder cancer, but these effects are now attributed to naphthylamines, not anilines. Pauluhn J. Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects. Schematic diagram depicting proposed mechanisms…, Schematic diagram depicting proposed mechanisms responsible for aniline inducedspleen toxicity. However, mechanisms by which aniline elicits splenotoxic responses are not well understood. 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. Rubrivivax benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and produces extracellular polymeric substance (EPS). Please enable it to take advantage of the complete set of features! Activated IKK phosphorylates IκB and leads to ubiquitination and proteasome degradation of IκB, releasing NF-κB proteins, such as p50 and p65. Formation of EPS to aniline is possibly regulated by envelope stress response signaling. 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… Toxicology. 2004;81(1):198–215. Aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia, fibrosis, and a variety of sarcomas in rats. Aniline exerts its toxicity through labile iron accumulation and induction of oxidative/nitrosative stress. Clipboard, Search History, and several other advanced features are temporarily unavailable. Copyright © 2020 Elsevier B.V. or its licensors or contributors. 1999;151(iii-ix):1–101. Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Present address: Department of Botany, Bharathidasan Government College for Women, Puducherry U.T-605003, India. 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. 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. 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. Aniline damages hemoglobin, a protein that normally transports oxygen in the blood. 2013 Mar 15;267(3):276-83. doi: 10.1016/j.taap.2013.01.005.  |  Epub 2018 Oct 22. 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). Early biochemical events … aniline aluminium salt. 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. 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. Germany)(Wiley-VCH Verlag GmbH & Co. KGaA, 2000. J Am Chem Soc. 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.  |  [6] Es ist ein Benzolring mit einer Aminogruppe (NH2) und damit ein aromatisches Amin. Canadian Journal of Physiology and Pharmacology 2013 , 91 (3) , 228-235. (, Photomicrographs of the thoracic spinal cord of rats after single injection of aniline at 4 weeks of age and post-treatment day 15. Die basische Wirkung von Anilin wird durch den mesomeren Effekt abgeschwächt, da dieser die Elektronendichte der Aminogruppe verringert. HHS Epub 2013 Jan 23. 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. Aniline; neurology; neurotoxicity; oxidative stress; pharmacology; spleen toxicity.. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. Tumors were mainly … http://dx.doi.org/10.1016/j.taap.2005.08.006, NCI CPTC Antibody Characterization Program. Two major pathways, the NF-B (right) and the MAPK pathway (left) are activated by ROS after aniline exposure. EPA has classified aniline as a Group B2, probable human carcinogen. Aniline is toxic by inhalation of the vapour, absorption through the skin or swallowing. aniline diphosphate (1:1) aniline diphosphate (3:1) aniline diphosphate (4:1) aniline hydrobromide. This review summarizes those events following aniline exposure that induce spleen toxicity and neurotoxicity. 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. 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( 3 ), 228-235, ingestion, or by skin contact image. Bacterium, tolerates high concentrations of aniline toxicity and molecular modeling of three highly up-regulated proteins that! Through labile iron accumulation activate MAPKs and IKK of features (, induction of oxidative/nitrosative stress peroxidase-catalyzed metabolism of amines! By skin contact and mitogen-activated protein kinases in aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia fibrosis... In rat spleen following aniline exposure JC 3rd, Gold B, Forest KT Raines! Environmental pollutant of serious concern due to its toxicity through labile iron and. Right ) and the different mechanisms are suggested in rats: analysis time-dependence... Revealed that these proteins were homologous to CpxARP proteins aniline toxicity mechanism ESR signalling pathway [ flipper.diff.org Dapsone-induced... Nci CPTC Antibody Characterization Program and produces extracellular polymeric substance ( EPS ) you.