Showing papers on "Morpholine published in 1998"

Structural Optimization Affording 2-(R)-(1-(R)-3,5-Bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a Potent, Orally Active, Long-Acting Morpholine Acetal Human NK-1 Receptor Antagonist

Abstract: Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17) This modified compound is a potent, long-acting hNK-1 receptor antagonist as evidenced by its ability to displace [125I]Substance P from hNK-1 receptors stably expressed in CHO cells (IC50 = 009 +/- 006 nM) and by the measurement of the rates of association (k1 = 28 +/- 11 x 10(8) M-1 min-1) and dissociation (k-1 = 00054 +/- 0003 min-1) of 17 from hNK-1 expressed in Sf9 membranes which yields Kd = 19 +/- 12 pM and a t1/2 for receptor occupancy equal to 154 +/- 75 min Inflammation in the guinea pig induced by a resiniferatoxin challenge (with NK-1 receptor activation mediating the subsequent increase in vascular permeability) is inhibited in a dose-dependent manner by the oral preadmininstration of 17 (IC50 (1 h) = 0008 mg/kg; IC90 (24 h) = 18 mg/kg), indicating that this compound has good oral bioavailbility and peripheral duration of action Central hNK-1 receptor stimulation is also inhibited by the systemic preadministration of 17 as shown by its ability to block an NK-1 agonist-induced foot tapping response in gerbils (IC50 (4 h) = 004 +/- 0006 mg/kg; IC50 (24 h) = 033 +/- 0017 mg/kg) and by its antiemetic actions in the ferret against cisplatin challenge The activity of 17 at extended time points in these preclinical animal models sets it apart from earlier morpholine antagonists (such as 4), and the piperidine antagonists 2 and 3 and could prove to be an advantage in the treatment of chronic disorders related to the actions of Substance P In part on the basis of these data, 17 has been identified as a potential clinical candidate for the treatment of peripheral pain, migraine, chemotherapy-induced emesis, and various psychiatric disorders

A Superior, Readily Available Enantiopure Ligand for the Catalytic Enantioselective Addition of Diethylzinc to alpha-Substituted Aldehydes.

Abstract: The lithium perchlorate-induced ring opening of (S)-triphenylethylene oxide (3) with secondary amines (piperidine (a), N-methylpiperazine (b), N-phenylpiperazine (c) and morpholine (d)) takes place in a stereospecific and completely regioselective manner to afford (R)-2-(dialkylamino)-1,1,2-triphenylethanols (4a-d). These amino alcohols catalytically induce the addition of diethylzinc to benzaldehyde with high enantioselectivity at 0 degrees C and at room temperature. Ligand 4a, which provides the highest enantioselectivity at 0 degrees C, has been studied in the addition of Et(2)Zn to a family of 20 representative aliphatic and aromatic aldehydes 5a-t. For a 17-membered set of alpha-substituted substrates (5a-m,q-t), including ortho-, meta-, and para-substituted benzaldehydes, the naphthaldehydes, alpha,beta-unsaturated and aliphatic (cyclic and acyclic) aldehydes, the mean enantiomeric excess of the resulting alcohols 6a-m,q-t is 97%, whereas for three alpha-unsubstituted specimens (5n-p) the addition takes place with an enantioselectivity of 92-93%.

Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolone-3-yl and 2-benzothiazolone-3-yl)acetic acid derivatives.

Abstract: Sixteen (2-benzothiazolone-3-yl and 2-benzoxazolone-3-yl) acetic acid derivatives 5 have been tested for anti-nociceptive and anti-inflammatory activity in this study. 4- [2-(6-Benzoyl-2-benzoxazolone-3-yl) acetyl] morpholine (5c), 4-(2- [ 6-(2-chloro-benzoyl)-2-benzoxazolone-3-yl]acetyl]morpholine (5d), 1-[2-(5-chloro-2-benzoxazolone-3-yl)acetyl]pyrrolidine (5f), methyl (6-methyl-2-benzoxazolone-3-yl) acetate (5k) and N,N-diethyl-2-(2-benzothiazolone-3-yl)acetamide (5m) have shown more potent anti-nociceptive activity than others. Among these compounds, 5c, 5d and 5m have exhibited good anti-inflammatory activity, with 5f, and to a lesser extent, the other molecules displaying some toxic potential.

Degradation of morpholine by an environmental Mycobacterium strain involves a cytochrome P-450.

Abstract: A Mycobacterium strain (RP1) was isolated from a contaminated activated sludge collected in a wastewater treatment unit of a chemical plant. It was capable of utilizing morpholine and other heterocyclic compounds, such as pyrrolidine and piperidine, as the sole source of carbon, nitrogen, and energy. The use of in situ1H nuclear magnetic resonance (1H NMR) spectroscopy allowed the determination of two intermediates in the biodegradative pathway, 2-(2-aminoethoxy)acetate and glycolate. The inhibitory effects of metyrapone on the degradative abilities of strain RP1 indicated the involvement of a cytochrome P-450 in the biodegradation of morpholine. This observation was confirmed by spectrophotometric analysis and1H NMR. Reduced cell extracts from morpholine-grown cultures, but not succinate-grown cultures, gave rise to a carbon monoxide difference spectrum with a peak near 450 nm, which indicated the presence of a soluble cytochrome P-450. 1H NMR allowed the direct analysis of the incubation medium containing metyrapone, a specific inhibitor of cytochrome P-450. The inhibition of morpholine degradation was dependent on the morpholine/metyrapone ratio. The heme-containing monooxygenase was also detected in pyrrolidine- and piperidine-grown cultures. The abilities of different compounds to support strain growth or the induction of a soluble cytochrome P-450 were assayed. The results suggest that this enzyme catalyzes the cleavage of the C—N bond of the morpholine ring.

Morpholine Degradation Pathway of Mycobacterium aurum MO1: Direct Evidence of Intermediates by In Situ 1H Nuclear Magnetic Resonance

Abstract: Recent studies have shown the biodegradative abilities of Mycobacterium species: they are able to metabolize xenobiotics such as polycyclic aromatic hydrocarbons (4, 10, 13, 14, 29), chlorophenols (11), trichloroethylene (33), vinyl chloride (12), amines (6), and isonicotinate (18). Mycobacterium spp. were also found to attack the heterocyclic, secondary amine morpholine (C4H9NO), which had been considered to be persistent for many years. This chemical has great industrial importance and a wide range of applications (22); it is used in the manufacture of rubber additives and also as a very versatile solvent, as an anticorrosive agent, and in the production of various drugs and pesticides. Its high solubility in water and its high potential for N nitrosation, which gives the potent mutagen and carcinogen N-nitrosomorpholine (9, 21, 27), make this xenobiotic of special interest from an environmental point of view. Knapp et al. (15) first discovered two strains of Mycobacterium (MorD and MorG) that were able to utilize morpholine as a sole source of carbon, nitrogen, and energy. A few years later, Dmitrenko et al. (5) isolated a strain of Arthrobacter, and Cech et al. (3) found a strain of Mycobacterium aurum MO1 that had morpholine degradation properties. Knapp’s group studied other Mycobacterium strains isolated from activated sludges (1, 16, 17). In the companion paper (24), we describe another Mycobacterium strain that is able to degrade morpholine. More recently, a few studies were carried out in order to understand the morpholine biodegradation process and its regulation. Swain et al. (28) proposed a hypothetical pathway for the biodegradation of morpholine by Mycobacterium chelonae (Fig. ​(Fig.1)1) that could proceed via 2-(2-aminoethoxy)acetate and glycolate and/or ethanolamine. Mazure and Truffaut (19) described the degradation of morpholine by M. aurum MO1. They proposed that M. aurum grown on morpholine could degrade intermediary compounds via the ethanolamine and glycolate routes. Depending on the morpholine concentration in the medium, one pathway could be used while the other was inhibited. FIG. 1 Hypothetical morpholine biodegradation pathway of M. chelonae proposed by Swain et al. (28). CoA, coenzyme A. However, to date, no tool for the direct detection of intermediates, or even of morpholine, has been available. Only indirect strategies were developed, such as chemical oxygen demand, optical density, or NH3 measurements, growth on intermediates, or in vitro enzyme assays. Consequently, only hypothetical pathways were proposed, and limited interpretations of various experiments were made. In this work we describe the degradation of morpholine by M. aurum MO1 by using in situ 1H nuclear magnetic resonance (1H-NMR) spectroscopy. This technique has been previously applied in medical fields for analyzing biological fluids (20, 23) and also for studying microbial physiology with extracts or culture medium (8, 30, 31). More recently, Gaines et al. (7) described the first use of 1H-NMR spectroscopy to monitor the catabolism of mixtures of aromatic compounds by Acinetobacter calcoaceticus grown in fully deuterated medium. This method is very interesting and allowed the identification and quantification of metabolites which accumulated during growth by rendering invisible the fully deuterated microbial cultures. However, it cannot be used in all circumstances, because it requires specialized growth medium and large quantities of D2O. In this work, we studied the degradative metabolism of M. aurum MO1 by directly analyzing the incubation medium in H2O. Our method, using normal water, can be more generally used and does not perturb the system being studied (the deuterated compounds can affect the enzymatic reactions). 1H-NMR spectroscopy is both qualitative and quantitative, so it allowed us to establish unambiguously some steps of morpholine degradation by this strain.

Genistein complexes with amines: structure and properties

Abstract: New amine complexes of genistein in the crystal and the solution state have been studied by X-ray crystallography and by 1H and 13C NMR spectroscopy. The gas-phase structures have been modelled with ab initio quantum chemical calculations. The morpholine–genistein hydrogen bonded complex has been investigated by all the above methods whereas the triethylamine, morpholine and piperazine complexes have been investigated with 1H NOE and 13C NMR spectroscopy. The X-ray results show the genistein–morpholine complex to be formed as a result of proton transfer from the genistein OH group at position C7 to the morpholine nitrogen atom. This complex also has the lowest total energy when compared to other possible complexes. The NMR measurements in solution indicate that the protonated amine is in fast exchange between various interaction sites, the most stable complex being formed at position C7 as in the crystal. The ab initio quantum mechanical calculations show that this position is also the best for interactions. The 13C NMR chemical shifts calculated theoretically are in agreement with experimental values.

Synthesis and Characterisation of Amine Adducts of Tri(4-bromophenyl) boroxine, Tri(3-nitrophenyl)boroxine, and Tri(3-aminophenyl)boroxine; Molecular Structure of 3-Picoline·tri(4-bromophenyl)boroxine

Abstract: Twenty five 1:1 adducts of the triarylboroxines (4-BrC6H4)3B3O3 (PBB) (3-NO2C6H4)3 B3O3 (MNB), and (3-NH2C6H4)3B3O3 (MAB) with N donor ligands (cyclohexylamine, 4-picoline, 3-picoline, piperidine, morpholine, isobutylamine, triethylamine, pyridine, of ligand and triarylboroxine in Et2O at room temperature. All 25 adducts have been characterised by elemental analysis, Mpt, IR and by 1H and 13C NMR. MNB and 4 of its adducts have been characterised by 11B MAS NMR. In solution variable temperature 1H NMR of selected PBB derivatives and of MNB-cyclohexylamine indicate that a ligand dissociation-recombination process is occuring with ΔG+ of ca. 39–54 kj·mol 1. The crystal and molecular structure of 3-picoline PBB has been determined by a single-crystal X-ray diffraction study. The colourless compound crystallises in the orthorhombic space group (Pbca) with a = 14.1710(10), b = 15.446(5), and c = 22.418(7) A, with Z = 8, calculated density = 1.737 Mg/M3, and final R values [I > 2 σ(I)] of R1 = 0.0376, and wR 2 =...

Degradation of morpholine and thiomorpholine by an environmental Mycobacterium involves a cytochrome P450. Direct evidence of intermediates by in situ NMR

Abstract: A strain of Mycobacterium sp. RP1 was isolated from a contaminated activated sludge. It was capable of utilizing morpholine, a waste of chemical industry, as sole source of carbon, nitrogen and energy. The kinetic of biodegradation of morpholine was followed directly on the incubation medium using in situ 1 H NMR. This technic allowed to identify two intermediates of the degradative pathway: glycolate and 2-(2-aminoethoxy)acetate. The inhibitory effects of metyrapone on the degradative abilities of the strain RP1 indicated the involvement of a cytochrome P 450. This observation was confirmed by spectrophotometric analysis and 1 H NMR. Metyrapol, a known metabolite of metyrapone, was also found to be an inhibitor. The same study of degradation of thiomorpholine showed the formation of sulfoxide, which confirmed the presence of a cytochrome P 450.

Copolymerization of ε-Caprolactone with (3S)-3-[(Benzyloxycarbonyl)methyl]morpholine-2,5-dione and the 13C NMR Sequence Analysis of the Copolymer

Abstract: (3S)-3-[(Benzyloxycarbonyl)methyl]morpholine-2,5-dione (BMD) has been successfully copolymerized with e-caprolactone for a wide range of mole fractions in the feed. The sequence analysis of the cop...

Synthesis, toxicological, and pharmacological assessment of derivatives of 2-aryl-4-(3-arylpropyl)morpholines.

Abstract: The synthesis of nine original morpholine derivatives, i.e. 2-aryl-4-(3-arylpropyl)morpholines, is described. The structure of all synthesised derivatives was proved by IR and 1H-NMR, and some of them by 13C-NMR. Acute toxicity studies of the compounds were performed on mice. A comparative pharmacological study of the in vivo effects on the central nervous system was undertaken using the screening tests: hexobarbital induced sleeping time: locomotor activity; and behaviour despair (for antidepressive activity). The most active compound 4-(2-benzoylethyl)-2-phenyl-3-methyl) morpholine 4e was studied for MAO-A and MAO-B inhibition in vitro in rat brain mitochondria preparations.

Thiomorpholine and morpholine oxidation by a cytochrome P450 in Mycobacterium aurum MO1. Evidence of the intermediates by in situ 1H NMR.

Abstract: Spectrophotometric assays of Mycobacterium aurum MO1 cells extracts gave evidence of a soluble cytochrome P450, involved in the degradative pathway of morpholine, a waste product from the chemical industry. In order to get further information, the kinetics of the biodegradation of the sulfur analogue thiomorpholine was monitored by using in situ nuclear magnetic resonance (NMR). This technique allowed the identification of two intermediates: the sulfoxide of thiomorpholine resulting from S-oxidation and thiodiglycolic acid owing to ring cleavage. The S-oxidation (S → SO) represents one of the well-known reactions catalyzed by cytochromes P450. The inhibitory effect of metyrapone, a cytochrome P450 inhibitor, on the thiomorpholine and morpholine degradative abilities of M. aurum MO1 confirmed the involvement of a cytochrome P450. These results and the decrease of the rate of formation of the first intermediate during the morpholine degradation, 2-(2-aminoethoxy) acetate, proved the key role of the cytochrome P450 in the early events of the biodegradation, i.e, in the C–-N bond cleavage.

S,n-substituierte diene und s,n-subtituierte tetraene aus mono(thio)subtituierten 2-nitrodienverbindungen

Abstract: Mono(thio)substituted nitrodienes 1a-b give the compounds 7a and 7b cohen treated with piperazine. S, N-substituted nitrodiene 3a was obtained from the reaction of la with p-phenylendiamine. Under the same conditions the compounds la-b and benzidine give the compounds 5a-b. The compounds la-b from the reaction with aniline in ether yielded 9s-b. Mono(thio)substituted nitrodienes la-b give 11a-b by the reaction with piperidine in ether. 13a-c are prepared by the reaction of compounds la-c with morpholine.

The synthesis and antitumor activity of metal complexes of amine-carboxyborane adducts

Abstract: The amine carboxyborane metal complexes, tetrakis - μ - (trimethylamine - boranecarboxylato)acetonitrile dicopper(II) and his-μ-(morpholine-boranecarboxylato)zinc(II) dihydrate demonstrated cytotoxic activity against human Tmolt 3 , HeLa-S 3 and MB-9812 cell growth. Tetrakis-μ-(trimethylamine-boranecarboxylato)-acetonitrile dicopper(II) and bis - μ - (morpholine - boranecarboxylato)zinc (II) dihydrate inhibited L 1210 DNA, RNA and protein syntheses, with greatest inhibitory effects on DNA synthesis. The reduction in DNA synthesis correlates well with inhibition of de novo purine synthesis and the key enzymes involved in this pathway, i.e. IMP dehydrogenase and PRPP amido transferase. These compounds were also observed to induce DNA strand scission but did not appear to intercalate between base pairs of DNA, alkylate bases or cause cross-linking of the strands of DNA. Tetrakis-μ-(trimethylamine - boranecarboxylato)acetonitrile dicopper(II) also demonstrated the ability to inhibit L 1210 DNA topoisomerase II activity.

Vilsmeier formylation of tert-anilines: dibenzo[b,f][1,5]diazocines and quinazolinium salts via the ‘t-amino effect’1

Abstract: The attempted Vilsmeier ortho-formylation of p-substituted N,N-dimethylanilines 1 with N-formyl-N-alkylarylamides 2 unexpectedly gives dibenzo[b,f][1,5]diazocines 5 in 26–74% yield. This reaction proceeds by Vilsmeier formylation ortho to the dimethylamino group of 1 followed by hydride migration from the N-methyl group to the newly formed iminium CH group, followed by intramolecular cyclisation, a new example of the ‘t-amino effect’. Similar formylation of cyclic tert-anilines such as 4-tolyl-pyrrolidines 6a,e,g, -piperidines 6b,f,h, -perhydroazepines 6c,i and -morpholine 6d, however, shows a different chemistry giving diformylated enamines 7 as the major products (12–60%). A small amount of diazocines 8 (1–13%) with a substituted benzyl at the nitrogen and N-formylated diazocines 9 are also isolated in some cases. When N-formyl-1,2,3,4-tetrahydroquinoline is used as the Vilsmeier reagent, normal formylation is observed, while use of aliphatic Vilsmeier reagents such as DMF and N-formylmorpholine give quinazolinium salts 16 and 17, also by way of the ‘t-amino effect’. The key feature in these formylations is the hydride transfer from the α-position of a tertiary amine to an unsaturated ortho-substituent CHNR2+, the ‘t-amino effect’.

Fungicide mixtures based on pyride amides and morpholine derivatives or piperidine derivatives

Abstract: The invention relates to fungicide mixtures containing, as active components, a) an amide compound of formula (I) A-CO-NR1R2, wherein A represents an aryl group or an aromatic or non-aromatic, 5- or 6-structured heterocyclic compound having 1 to 3 heteroatoms selected from O, N, S; whereby the aryl group or the heterocyclic compound can optionally comprise 1, 2 or 3 substituents selected independently of one another from alkyl, halogen, CHF?2?, CF3, alkoxyl, haloalkoxyl, alkylthio, alkyl sulfinyl and alkyl sulfonyl; R?1? represents a hydrogen atom; R2 represents a phenyl group or cycloalkyl group optionally containing 1, 2 or 3 substituents selected independently of one another from alkyl, alkenyl, alkynyl, alkoxyl, alkenyloxyl, alkynyloxyl, cycloalkyl, cycloalkenyl, cycolalkyloxyl, cycloalkenyloxyl, phenyl and halogen, whereby the aliphatic and cycloaliphatic radicals can be partially or completely halogenated and/or the cycloaliphatic radicals can be substituted by 1 to 3 alkyl groups, whereby the phenyl group can contain 1 to 5 halogen atoms and/or 1 to 3 substituents selected independently of one another from alkyl, haloalkyl, alkoxyl, haloxyl, alkylthio and haloalkylthio, and whereby the amidic phenyl group is optionally condensed with a saturated 5-structured ring which is optionally substituted by one or more alkyl groups and/or can comprise a heteroatom selected from O and S, and b) a morpholine derivative or piperidine derivative (III) selected from the group of compounds (IIa), (IIb), (IIc), (IId) and (IIe). The active components are provided in a synergistically effective quantity.

Preconcentration of Indium(III) from Complex Materials After Adsorption of Its Morpholine-4-dithiocarbamate on Naphthalene or Using Morpholine-4-dithiocarbamate-cetyltrimethylammonium Bromide-naphthalene Adsorbent

Abstract: A highly selective, sensitive and rapid differential pulse polarographic method has been developed for the estimation of trace amounts of indium in standard alloy, ore, synthetic and environmental samples. The morpholine-4-dithiocarbamate of indium(III) is adsorbed on microcrystalline naphthalene in the pH range 3.5–6.4. The metal complex is desorbed with HCl and determined with a differential pulse polarograph (DPP). This metal may alternatively be quantitatively retained on morpholine-4-dithiocarbamate-cetyltrimethylammonium bromidenaphthalene adsorbent packed in a column at a flow rate of 0.5–5.0 ml/min and determined similarly. The detection limit is 0.10 ppm at the minimum instrumental setting (signal to noise ratio = 2). Indium has been determined in the concentration range 0.70–15.0 ppm with a correlation factor of 0.9996 and a relative standard deviation of 0.76% (n = 8). In the column method, the linearity is maintained in the concentration range 0.70–8.5 ppm with a correlation factor of...

Antibacterial effect of some 2,6-disubstituted 4-anilinoquinazolines.

Abstract: Two synthetic 2,6-disubstituted 4-anilinoquinazolines exerted a significant effect on the G+ bacteriaBacillus subtilis andStaphylococcus aureus. None of 12 tested derivatives influencedEscherichia coli, Proteus mirabilis andPseudomonas aeruginosa. Derivatives having the aromatic ring non-substituted or substituted by bromine, the pyrimidine ring by phenyl, morpholine or piperidine and the aniline skeleton non-substituted or substituted by methyl or amino group exterted a considerable antibacterial activity.

Conversion of a 1,2,3-dithiazole into a 3H-pyrrole-3-thione and a 3H-pyrrol-3-ylidenephosphorane

Abstract: Treatment of the readily available dicyanomethylenedithiazole 1 with excess of morpholine or triphenylphosphine gives the 3-azacyclopentadienethione (3H-pyrrole-3-thione) 5 and the 3-azacyclopentadienylphosphorane (3H-pyrrol-3-ylidenephosphorane) 16 respectively. Both products are deeply coloured and highly stabilised by extensive electron delocalisation: 1H and 13C NMR spectra show that rotation of the morpholine groups in 5 is hindered. Structure 16, the first azacyclopentadienylphosphorane reported, is proved by X-ray crystallography. Mechanisms are reported for these transformations in which the initial step is considered to be opening of the dithiazole ring of 1 by nucleophilic attack by the amine or the phosphine at the central heteroatom.

Morpholine and its derivatives as vapour phase corrosion inhibitors for mild steel

Abstract: Morpholine and its derivatives such as carbonate, borate and phosphate were synthesized llnd evaluated as vapour-phase corrosion inhihitors (VPIs) for mild steel usin~ wei~ht loss and visual observation methods under continuous condensation test (CCT). From the results the perfornlance of mOI"pholine and its derivatives as VI'I for mild steel is comparatively a'isessed.

Photopolymerization of methyl methacrylate using a morpholine–sulfur dioxide charge‐transfer complex as the photoinitiator

Abstract: Photopolymerization of the vinyl monomer (M) of methyl methacrylate (MMA) was kinetically studied by using near-UV/visible light at 40°C and employing a morpholine (MOR)-sulfur dioxide (SO 2 ) charge-transfer(C-T complex as the photoinitiator. The rate of polymerization (R P ) was found to be dependent on the morpholine: sulfur dioxide mole ratio; the 1: 2 (MOR-SO 2 ) complex acted as the latent initiator complex C which underwent further complexation with the monomer molecules to give the actual initiating complex I. Using the 1: 2 (MOR-SO 2 ) C-T complex as the latent initiator, the observed kinetics may be expressed as R P [MOR-SO 2 ] 0.27 [M] 1.10 . Benzoquinone behaved as a strong inhibitor. Polymers obtained tested positive for the incorporation of a sulphonate-type end group. Polymerization followed a radical mechanism. Kinetic nonideality as revealed by a low initiator exponent and monomer exponent of greater than unity was explained on the basis of a prominent primary radical termination effect.

Risk Assessment of Morpholine (Tetrahydro-2H-1, 4-Oxazine): A Time for Reevaluation of Current Occupational Exposure Standards?

Abstract: Morpholine (tetrahydro-2H-1, 4-oxazine; Chemical Society No. 110-91-8), a cyclic secondary amine, is a high volume production chemical with annual worldwide production exceeding 10,000 tonnes per year. It is an important intermediate for rubber-processing chemicals, and is used as a component of laundry detergents and in the textile industry. The compound is also used to control corrosion in steam condensate systems. In both experimental animals and humans the primary acute and chronic effects are irritation of mucous membranes at high levels of exposure, consistent with the strong alkaline properties of morpholine. Available data do not provide enough evidence for the carcinogenicity of morpholine in exposed workers or in studies in experimental animals. It was found that exposure of workers to morpholine vapors may cause a transient edema of the cornea of the eye, leading to the so-called glaucopsia in workers exposed for several hours. Unfortunately, there are no data available on the...