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Morpholine

HCID 8083
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Basic information

CAS
110-91-8
Standard SMILES
C1COCCN1
InChIKey
YNAVUWVOSKDBBP-UHFFFAOYSA-N
Molecular formula
C4H9NO
Average molar mass
87.12 g/mol
Monoisotopic mass
87.06841391

Overview

Morpholine appears as a colorless liquid with a fishlike odor. Flash point 100 °F. Corrosive to tissue. Less dense than water and soluble in water. Vapors heavier than air. Used to make other chemicals, as a corrosion inhibitor, and in detergents.

Names & identifiers

Preferred name
Morpholine
IUPAC
morpholine
English name
Morpholine
Molecular formula
C4H9NO
Molecular weight
87.12

Names & synonyms

MORPHOLINE110-91-8Diethylene oximide1-Oxa-4-azacyclohexaneTetrahydro-1,4-oxazineDiethylenimide oxideDiethyleneimide oxideDiethylene imidoxideDrewamineTetrahydro-2H-1,4-oxazineTetrahydro-p-oxazinep-Isoxazine, tetrahydro-
Show more names
MORPHOLIN1,4-Oxazinanbasf238NA 2054Morphorin
Tetrahydro-1,4-isoxazineBASF 2382H-1,4-Oxazine, tetrahydro-4H-1,4-Oxazine, tetrahydro-DTXSID20256888B2ZCK305ONSC-9376DTXCID305688

Database identifiers

CAS
110-91-8
PubChem CID
8083
DTXSID
DTXSID2025688
ChEMBL
CHEMBL276518
ChEBI
CHEBI:34856
UNII
8B2ZCK305O
EC Number
203-815-1
Nikkaji
J2.453H

Properties

Computed structural propertiesFilling in

XLogP
-0.9
Topological polar surface area
21.3 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
2
Rotatable bonds
0
Heavy atoms
6
Formal charge
0
Complexity
34.5

Experimental & physicochemical properties

Chemical Classes · 2 items

Nitrogen Compounds -> Morpholines

Corrosives

CosmeticsCosmetic ingredients (Morpholine) -> CIR (Cosmetic Ingredient Review)
pHStrong base
SpringerMaterials Properties15N nuclear magnetic resonance spectrum
LogP · 4 items

log Kow = -0.86

-0.86

-0.86

-0.66

Odor · 3 items

Characteristic amine

Penetrating

Weak, ammonia- or fish-like odor

Food AdditivesBOILER WATER ADDITIVE -> FDA Substance added to food
Density · 6 items

1 at 68 °F (USCG, 1999)

1.007 at 20 °C/4 °C

Bulk density = 8.34 lb/gal at 20 °C

Relative density (water = 1): 1.0

1.007

1.007 @ 20°C

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 6 items

Danger

H226: Flammable liquid and vapor [Warning Flammable liquids]

P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P303+P361+P353, P304+P340, P305+P354+P338, P316, P317, P321, P330, P362+P364, P363, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

Danger

H226 (> 99.9%): Flammable liquid and vapor [Warning Flammable liquids]

P210, P233, P234, P240, P241, P242, P243, P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P303+P361+P353, P304+P340, P305+P354+P338, P316, P317, P321, P330, P362+P364, P363, P370+P378, P390, P391, P403+P235, P405, P406, and P501 (click each P-code to see the statement)

Hazard information

Regulatory Information · 5 items

Chemical: Morpholine

Morpholine is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Morpholine are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

REACH registered substance: Morpholine (EC: 203-815-1)

Morpholine: HSNO Approval: HSR001204 Approved with controls

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Other Safety InformationIMAP assessments - Morpholine: Human health tier II assessment
DOT LabelCorrosive Flammable Liquid
Fire Hazards · 3 items

FLAMMABLE. Flashback along vapor trail may occur. Vapor may explode if ignited in an enclosed area. Irritating vapors are generated when heated. Vapor is heavier than air and may travel some distance to source of ignition and flash back. (USCG, 1999)

Chemistry & industry

Pharmacology

Mechanism of Action · 2 items

The irritating and corrosive properties of morpholine are due to its basicity. The mechanism of action of its systemic effects is not known.

Morpholine fungicides have been shown to act by inhibiting several enzymes of sterol biosynthesis.

Biological Half-LifeAfter ip admin of 125 mg/kg (14)C-morpholine (50 uCi)/animal, the blood plasma half-lives in the rat, hamster, and guinea pig were 115, 120, and 300 min, respectively.
Metabolism/Metabolites · 5 items

There is ample evidence that this substance can be nitrosated to the carcinogenic N-nitrosomorpholine (NMOR) by reactions ... within the human body ... NMOR may be formed following concomitant administration of morpholine and nitrite or nitrous oxide under physiological conditions.

Immunostimulation of rats by intraperitoneal treatment with E. coli lipopolysaccharide (LPS; 1 mg/kg) led to a large increase in urinary nitrate and urinary metabolites of NMOR (N-nitrosomorpholine) when morpholine (80 umol/kg) and L-arginine (400 umol/kg) were injected intraperitoneally. The replacement of LPS with nitrate (330 umol/kg intraperitoneal) did not increase urinary metabolites of NMOR. This result is consistent with endogenous nitrosation of morpholine by nitrogen oxide (NO) from oxidation of the guanido group of arginine by induced NO synthase.

In vitro nitrosation of morpholine has been reported. NMOR (N-nitrosomorpholine) was formed when morpholine was added to human saliva. Additionally, a new type of metabolite, N-cyanomorpholine, was identified in human saliva.

A method /was developed/ to monitor the in vivo formation of NMOR (N-nitrosomorpholine) by measuring N-nitroso (2-hydroxyethyl)glycine, its major urinary metabolite. The formation of NMOR was measured in F-344 rats over wide range of doses of morpholine (38.3 - 0.92 umol) and sodium nitrite (191 - 4.8 umol). According to estimates ..., 0.5 to 12% of the morpholine, depending on the dose, was nitrosated.

For more Metabolism/Metabolites (Complete) data for Morpholine (11 total), please visit the HSDB record page.

Absorption, Distribution and Excretion · 5 items

The results of a variety of in vivo and in vitro experiments suggested that the kidneys were the primary route of elimination of morpholine in the rabbit. Morpholine was not bound to serum proteins and was excreted 90% unchanged. The concentration of [14C]morpholine in the renal cortex was 6.6 times the concentration in the blood, and in the renal medulla was 15.3 times the concentration in the blood after 30 min after the intravenous injection of single boluses of labeled compound. The chemical appeared to be distributed mainly to the extracellular space, and its rate of elimination was enhanced by acidification of the urine.

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Compound notes

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Viscosity
2.23 cP at 20 °C
Color/Form · 3 items

Colorless liquid

Mobile liquid

Colorless liquid [Note: A solid below 23 degrees F].

Solubility · 6 items

Soluble (NTP, 1992)

Solluble in organic solvents

Immiscible with concn sodium hydroxide soln; miscible with acetone, benzene, ether, castor oil, methanol, ethanol, ethylene glycol, 2-hexanone, linseed oil, turpentine, pine oil; miscible with water with evolution of some heat

In water, 1.00X10+6 mg/L /miscible/

1000 mg/mL

Solubility in water: miscible

CorrosivityCorrosive to metals

Physicochemical properties

Melting point
-7 · -7--5 °C (lit.)
Boiling point
126 · 126.0-130.0 °C 129 °C (lit.)
Density
0.996 g/mL · 0.996 g/mL at 25 °C (lit.)
vapor density
3 · 3 (vs air)
vapor pressure
31 mm · 31 mm Hg ( 38 °C)
refractive index
20 · n20/D 1.454(lit.)
Flash point
96 °F · 96 °F
storage temp.
30 °C · Store below +30°C.
solubility
water: miscible
form
Liquid
pka
8.33 · 8.33(at 25℃)
color
15 · APHA: ≤15
Specific Gravity
0.996 · 0.996
Odor
Characteristic amine-like odor
PH
11.2 · 11.2 (H2O)(undiluted)
explosive limit
1.4 · 1.4-15.2%(V)
Water Solubility
MISCIBLE
FreezingPoint
-4.9 ℃ · -4.9℃
Specific Heat Capacity
1.89 J/ · Cp(liquid): 1.89 J/(g·K), at 25℃
Sensitive
Hygroscopic
Merck
14 · 14,6277
BRN
102549 · 102549
Henry's Law Constant
1.9 · 1.9×102 mol/(m3Pa) at 25℃, Nguyen (2013)
Exposure limits
20 ppm · ACGIH:TLV-TWA 20 ppm (71 mg/m3)OSHA:PEL-TWA 20 ppm (70 mg/m3)NIOSH:REL-TWA 20 ppm; REL-STEL 30 ppm
Dielectric constant
7.3 · 7.3(25℃)
Stability
Stable. Flammable. Incompatible with strong oxidizing agents, strong acids, acid chlorides, acid anhydrides. Hygroscopic.
Major Application
cleaning productscosmeticsenvironmentalfood and beveragespersonal care
Cosmetics Ingredients Functions
BUFFERING
Cosmetic Ingredient Review (CIR)
Morpholine (110-91-8)
InChI
1S/C4H9NO/c1-3-6-4-2-5-1/h5H,1-4H2
InChIKey
YNAVUWVOSKDBBP-UHFFFAOYSA-N
SMILES
C1COCCN1
LogP
-0.86 · -0.860
CAS DataBase Reference
110 · 110-91-8(CAS DataBase Reference)
Substances Added to Food (formerly EAFUS)
MORPHOLINE
FDA 21 CFR
173.31 · 173.310; 175.105; 176.180;176.210; 178.3300
EWG's Food Scores
4 · 4-8
FDA UNII
8 B2ZCK305O · 8B2ZCK305O
NIST Chemistry Reference
Morpholine(110-91-8)
IARC
3 · 3 (Vol. 47, 71) 1999
EPA Substance Registry System
Morpholine (110-91-8)
UNSPSC Code
41116107 · 41116107
NACRES
24 · NA.24
Symbol(GHS)
2 · GHS02,GHS05,GHS06,GHS08
Signal word
Danger
Hazard statements
311 · H311+H331-H302-H314-H370-H372-H402-H226
Precautionary statements
501 · P501-P273-P260-P270-P240-P210-P233-P243-P241-P242-P271-P264-P280-P370+P378-P308+P311-P361+P364-P303+P361+P353-P301+P330+P331-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P403+P233-P403+P235-P405
PPE
Faceshields, Gloves, Goggles, type ABEK (EN14387) respirator filter
Hazard Codes
C
Risk Statements
10 · 10-20/21/22-34
Safety Statements
23 · 23-36-45
RIDADR
2054 · UN 2054
OEB
A
OEL
20 ppm · TWA: 20 ppm (70 mg/m3), STEL: 30 ppm (105 mg/m3) [skin]
WGK Germany
3 · 3
RTECS
6475000 · QD6475000
Autoignition Temperature
590 °F · 590 °F
TSCA
TSCA listed
HS Code
2934 · 2934 99 90
HazardClass
8 · 8
PackingGroup
I
Storage Class
3 · 3 - Flammable liquids
Hazard Classifications
3 DermalAcute · Acute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 4 OralEye Dam. 1Flam. Liq. 3Repr. 2Skin Corr. 1B
Hazardous Substances Data
110 · 110-91-8(Hazardous Substances Data)
Toxicity
50 orally · LD50 orally in female rats: 1.05 g/kg (Smyth)
IDLA
1 · 1,400 ppm [10% LEL]
REACH Registrations
Active
Excepted Quantities
Not Permitted as Excepted Quantity

· Flammable/combustible material.

Flammable. Gives off irritating or toxic fumes (or gases) in a fire. Above 35 °C explosive vapour/air mixtures may be formed.

Fire PotentialA very dangrous fire hazard when exposed to flame, heat, or oxidizers.
Health Hazards · 2 items

VAPOR: Irritating to eyes, nose and throat. If inhaled, will cause nausea, headache, or difficult breathing. LIQUID: Irritating to skin and eyes. (USCG, 1999)

· May cause toxic effects if inhaled or ingested.

Hazards Summary · 1 item

Liver damage is prominent in animals exposed to high concentrations. Skin, eye, and respiratory irritation, but no chronic health effects, were reported after occupational exposure. [ACGIH] Corrosive to skin; [Quick CPC] A corrosive substance that can cause pulmonary edema; [ICSC]

DOT ID and Guide · 2 items

2054 132

2054 132

FDA Requirements · 2 items

Morpholine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.

Morpholine is an indirect food additive for use only as a component of adhesives.

Reactive GroupAmines, Phosphines, and Pyridines
EC ClassificationSymbol: C; R: 10-20/21/22-34; S: (1/2)-23-36-45
UN ClassificationUN Hazard Class: 8; UN Subsidiary Risks: 3; UN Pack Group: I

Safety & protection

Fire Fighting · 2 items

Excerpt from ERG Guide 132 [Flammable Liquids - Corrosive]:

Use water spray, powder, alcohol-resistant foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

First Aid Measures · 4 items

Fresh air, rest. Half-upright position. Artificial respiration may be needed. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Give one or two glasses of water to drink. Do NOT induce vomiting. Refer for medical attention .

Accidental Release Measures · 2 items

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

First Aid · 3 items

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

General First Aid:

(General first aid procedures)

Safe StorageFireproof. Separated from strong oxidants and acids. Dry.
Firefighting HazardsVapor is heavier than air and may travel some distance to source of ignition and flash back.
Exposure Control and Personal Protection · 2 items

· Wear positive pressure self-contained breathing apparatus (SCBA).

5.0 [ppm]

Fire Fighting Procedures · 3 items

Use dry chemical, carbon dioxide, or alcohol foam extinguishers. Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Containers may explode in fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode.

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, carbon dioxide or dry chemical.

Use flooding quantities of water as fog or spray, dry chemical, "alcohol resistant" foam, or carbon dioxide. Use water spray to keep fire-exposed containers cool.

Storage Conditions · 5 items

Before entering confined space where this chemical may be present, check to make sure that an explosive concentration does not exist. Morpholine must be stored to avoid contact with strong acids, such as nitric acid, and strong oxidizers, such as chlorine dioxide, bromine, nitrates, and permanganates, since violent reactions occur.

Separate from oxidizing materials and acids. Store in a cool, dry, well ventilated location. Outside or detached storage is preferred. Inside storage should be in a standard flammable liquids storage warehouse, room, or cabinet.

Morpholine should be protected from atmospheric moisture and carbon dioxide. As morpholine corrodes copper, aluminum, zinc, and galvanized surfaces, the compound should be stored in iron or steel containers, preferably located outdoors, above ground, and surrounded by dykes to contain spills or leaks.

Keep containers closed and store in a cool, dark place.

Unstable if stored in copper or zinc containers.

Cleanup Methods · 5 items

Spill handling: evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Establish forced ventilation to keep levels below explosive limit. Absorb liquids in vermiculite, dry sand, earth, peat, carbon, or a similar material and deposit in sealed containers. Keep this chemical out of a confined space, such as a sewer, because of the possibility of an explosion, unless the sewer is designed to prevent the build-up of explosive concentrations. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations.

Environmental considerations - land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder, or commercial sorbents.

Environmental considerations - water spill: Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction hoses.

Environmental considerations - air spill: Apply water spray or mist to knock down vapors.

For more Cleanup Methods (Complete) data for Morpholine (7 total), please visit the HSDB record page.

Nonfire Spill ResponseExcerpt from ERG Guide 132 [Flammable Liquids - Corrosive]:
Disposal Methods · 5 items

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Package lots. Distill for reuse or package and label for disposal by burning.

Small quantities. Wear eye protection, laboratory coat, and rubber gloves. Dissolve the morpholine (1 mL) in 50 mL of 3 M sulfuric acid (prepared by slowly adding 8 mL of concentrated sulfuric acid to 21 mL or water). Weigh 10 g of potassium permanganate and stir small portions of the solid into the morpholine solution over a period of about 1 hr. Stir the mixture at room temperature for 48 hr, and then neutralize the solution by adding solid sodium carbonate or a 10% solution of sodium hydroxide. Add solid sodium bisulfite until solution is colorless. Decant the clear liquid into the drain and discard any brown solid with regular refuse.

Incineration is acceptable and the preferred method of disposal; however, nitrogen oxide emission controls may be required to meet environmental regulations. Morpholine is also broken down by activated sludge and this is a possible method of disposal under controlled conditions.

For more Disposal Methods (Complete) data for Morpholine (7 total), please visit the HSDB record page.

Toxicology

Interactions · 5 items

A group of seven female Sprague-Dawley rats /were fed/ 5 g morpholine together with 5 g nitrite/kg diet for 12 weeks. After 39 weeks, all of the animals developed hepato-cellular adenomas, six out of the seven hepatocellular carcinomas, two hemangioendotheliomas of the liver, one a cyst-adenocarcinoma of the liver, and one a renal adenoma. Rats fed morpholine or nitrite alone did not develop tumors.

Pregnant rats /were fed/ on a diet containing various concentrations of morpholine, sodium nitrite, and NMOR (N-nitrosomorpholine) ... Hepatocellular carcinoma and hemangio-sarcomas of the liver and angiosarcoma of the lungs were the most common tumors observed in the rats. The neoplasms induced by nitrite and morpholine were morphologically similar to those induced by NMOR. High concentrations (1000 mg/kg) of morpholine and nitrite together were carcinogenic to rats. When the morpholine concentration was reduced and the nitrite concentration remained high, the incidence of hepatic cell carcinomas decreased with a linear dose-response relationship. When morpholine concentration remained high, with decreasing nitrite concentration, the number of hepatic tumors was sharply reduced. This agrees with the observation in vitro that the nitrosation of morpholine depends on the square of the nitrite concentration.

Groups of 40 male MRC Wistar rats were treated for 2 yr with either 10 g morpholine/kg diet and drinking-water containing 3 g sodium nitrite/L, or with drinking-water containing 0.15 g NMOR/L. In both cases, one group of rats was also given sodium ascorbate (22.7 g/kg diet). The results of treatment with morpholine plus nitrite or with NMOR were similar to those reported /in the feeding experiments/. When ascorbate was present, the liver tumors induced by morpholine plus nitrite had a longer induction period (93 vs 54 weeks) and a slightly lower incidence (49% vs 65%). However, ascorbate did not affect liver tumor induction by preformed NMOR. Of those treated with morpholine, nitrite, and ascorbate, 21/39 animals developed forestomach tumors. In a similar study using Syrian hamsters, a high morpholine, high nitrite diet (1000 mg/kg) induced liver cancer in some animals. In contrast, hamsters fed NMOR in the diet seemed to have greater resistance to tumor induction.

Bis(2,2-dimethyl-4-methanesulfonic acid sodium salt-1,2-dihydroquinoline)-6,6'-methane (MIDQ-DA) inhibited liver necrosis induced in rats by simultaneous admin of morpholine and sodium nitrite.

For more Interactions (Complete) data for Morpholine (17 total), please visit the HSDB record page.

Target OrgansEyes, skin, respiratory system, liver, kidneys
Ecotoxicity Values · 5 items

LC50; Species: Brachydanio rerio (zebra fish); Conditions: 22 °C, pH 7.5, hardness 250 mg/L CaCO3, no aeration; Concentration: >1000 mg/L for 96 hr

LC50; Species: Leuciscus idus melanotus (golden orfe); Conditions: 20 °C, pH 8, hardness 220-320 mg/L CaCO3, continual aeration; Concentration: 285 mg/L for 48 hr (95% confidence level: 250-340 mg/L)

LC50; Species: Leuciscus idus melanotus (golden orfe); Conditions: 20 °C, pH 8, hardness 220-320 mg/L CaCO3, continual aeration; Concentration: 240 mg/L for 48 hr (95% confidence level: 100-301 mg/L);

LC50; Species: Salmo gairdneri (rainbow trout); Conditions: 15 °C, pH 7.4, hardness 20 mg/L CaCO3, >95% oxygen saturation; Concentration: 380 mg/L for 96 hr (95% confidence level: 375-460 mg/L)

For more Ecotoxicity Values (Complete) data for Morpholine (19 total), please visit the HSDB record page.

Environmental Fate · 3 items

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 7.4(SRC), determined from a log Kow of -0.86(2) and a regression-derived equation(3), indicates that morpholine is expected to have very high mobility in soil(SRC). The pKa of morpholine is 8.49(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of cationic morpholine from moist soil surfaces will not occur since ions do not volatilize(SRC). Volatilization of the neutral form of morpholine from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 10.1 mm Hg(6), and assigned value for water solubility of 1.0X10+6 mg/L (miscible)(6). Morpholine is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(6). The theoretical BOD using activated sludge in the Japanese MITI test was 0% after 2 weeks(7). Results from longer biodegradation screening tests indicate morpholine is biodegradable in activated sludge with degradation rates of 87% to greater than 90% within 28 to 31 days, respectively; lag periods ranging from 7 to 21 days were observed for these tests(8,9). In a study investigating morpholine-degrading bacteria, it was noted that these bacteria were slow to become established, and could only be done so in biological treatment plants with a mean solids retention times of more than 8 days(10). Therefore, morpholine is expected to be biodegradable in environments where morpholine-degrading organisms are present and after acclimation to these organism is achieved(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 7.4(SRC), determined from a log Kow of -0.86(2) and a regression-derived equation(3), indicates that morpholine is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.49(4) indicates morpholine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), measured BCF values of less than 0.3 to 0.65 and less than 2.8(7), suggest that bioconcentration in aquatic organisms is low(SRC). Only 3 out of 58 river die-away tests failed to biodegrade morpholine or failed to contain morpholine-degrading bacteria. Lag periods of approximately 6 to 50 days were observed(8). These data indicate that biodegradation in aquatic environments will vary depending on conditions(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), morpholine, which has a vapor pressure of 10.1 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase morpholine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.8 hours(SRC), calculated from its rate constant of 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Morpholine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Food Survey Values · 1 item

An average morpholine concentration in baked ham obtained from a local market (n = 5) in Kobe City, Japan was 0.20 ppm, testing date not specified. It was not detected in fish sausage (n = 5), cod roe (n = 3), spinach (n = 2 ), or miso (n = 2) (detection limit = 0.01 ppm)(1). During a study analyzing naturally-occurring secondary amines in locally purchased food, morpholine was detected in the following food items at concentrations of ppm: 0.5 in baked ham, 0.4 in frankfurters, 0.2 in evaporated milk, 1 in coffee (average of two brands; per dry weight), trace amounts (<0.1) in tea, 0.4 in canned beer, <0.2 in bottled beer, and <0.7 in wine(2).

Adverse EffectsOccupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
Exposure Routes · 2 items

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

Toxicity Summary · 2 items

The safety of this ingredient has not been documented and substantiated. The CIR Expert Panel cannot conclude that Morpholine is safe for use in cosmetic products until such time that the appropriate safety data have been obtained and evaluated.

Ingredients for which the data are insufficient and their use in cosmetics is not supported

Ecotoxicity Excerpts · 5 items

/AQUATIC SPECIES/ The toxicity threshold of morpholine for aerobic bacteria (after 16 hr) was 310 mg/L and for green-blue algae (after 193 hr), 1.7 mg/L. Inhibition of protozoa started at a morpholine concentration of 12 mg/L, and growth of algae was inhibited from 4.1 mg/L.

/AQUATIC SPECIES/ In a 192 hr test, the onset of inhibition by morpholine (in distilled water, pH 7.0) of cell multiplication (here defined as 3% in population growth) in the green alga Scenedesmus quadricauda in a turbidity test was noted at a concentration of 4.1 mg/L.

/AQUATIC SPECIES/ Selenastrum capricornutum grows exponentially without a lag phase in the presence as well as in the absence of morpholine, the growth being inhibited first at a concentration of 100 mg/L. The inhibition was most marked after 6 days, shortly before reaching the stationary phase; the no-observed-effect level (NOEL) was 10 mg/L ... Algal growth /in the same species was evaluated/ by measuring in vivo the fluorometric units at 48, 72, 96 hr, and 7 days. A 96 hr EC50 of 28 mg/L was determined.

/AQUATIC SPECIES/ Exposure of rainbow trout to 5.7 times 10 (-10) M (5 times 10 (-5) mg/L) morpholine during smolting period did not influence the subsequent neural response to this substance when tested immediately and 12 months after smolting. Perfusion of the olfactory organs with 1% morpholine for 10 min irreversibly inhibited the olfactory responsiveness to odorants.

/PLANTS/ 4.4 +/- 0.9 mol morpholine/cu m (383 mg/L) lowers the percentage germination of lettuce seeds (Lactuca sativa) by 50% of the control value. The seeds were kept on agar for 3 days in sealed plastic containers at a temperature of 30 °C.

Plant ConcentrationsMorpholine was detected in the medicinal plant roots obtained from a local market in Ibadan, Nigeria(1).
Signs and Symptoms · 5 items

Burning sensation. Cough. Laboured breathing. Shortness of breath. Symptoms may be delayed.

MAY BE ABSORBED! Redness. Pain. Skin burns. Blisters.

Redness. Pain. Blurred vision. Severe deep burns.

Abdominal pain. Burning sensation. Cough. Diarrhoea. Nausea. Shock or collapse. Vomiting.

irritation eyes, skin, nose, respiratory system; visual disturbance; cough; In Animals: liver, kidney damage

Medical Surveillance · 1 item

The following medical procedures should be made available to each employee who is exposed to morpholine at potentially hazardous levels: 1. Initial Medical Screening: Employees should be screened for history of certain medical conditions which might place the employee at increased risk from morpholine exposure. /These include/ chronic respiratory disease ... liver disease ... kidney disease ... eye disease ... /and/ skin disease. 2. Periodic Medical Examination: Any employee developing the above-listed conditions should be referred for further medical examination.

Regulatory information

FDA Requirements · 2 items

Morpholine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.

Morpholine is an indirect food additive for use only as a component of adhesives.

Atmospheric Standards · 1 item

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Morpholine is produced, as an intermediate or a final product, by process units covered under this subpart.

Safety data

OEB
A
OEL
TWA: 20 ppm (70 mg/m3), STEL: 30 ppm (105 mg/m3) [skin]
PPE
Faceshields, Gloves, Goggles, type ABEK (EN14387) respirator filter
wgk
3
IDLA
1,400 ppm [10% LEL]
tsca
TSCA listed
rtecs
QD6475000
ridadr
UN 2054
hs_code
2934 99 90
Toxicity
LD50 orally in female rats: 1.05 g/kg (Smyth)
risk_code
10-20/21/22-34
Signal word
Danger
Symbol(GHS)
GHS02,GHS05,GHS06,GHS08
hazard_code
C
safety_code
23-36-45
hazard_class
8
Storage Class
3 - Flammable liquids
packing_group
I
Hazard statements
H311+H331-H302-H314-H370-H372-H402-H226
Excepted Quantities
Not Permitted as Excepted Quantity
REACH Registrations
Active
Hazard Classifications
Acute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 4 OralEye Dam. 1Flam. Liq. 3Repr. 2Skin Corr. 1B
Autoignition Temperature
590 °F
Precautionary statements
P501-P273-P260-P270-P240-P210-P233-P243-P241-P242-P271-P264-P280-P370+P378-P308+P311-P361+P364-P303+P361+P353-P301+P330+P331-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P403+P233-P403+P235-P405
Hazardous Substances Data
110-91-8(Hazardous Substances Data)

Morpholine is well absorbed after oral and dermal administration and inhalation. Distribution studies showed that in rabbits, following inhalation or injection, the highest concentrations of morpholine were found in the kidney, whereas, in rats, high concentrations were found in muscle. In mice, rats, hamsters, guinea-pigs, and rabbits, almost all ingested or intravenously or intraperitoneally injected morpholine was excreted unchanged in the urine. In guinea-pigs, the metabolite N-methylmorpholine-N-oxide was identified. Only 0.5% was eliminated as CO2.

Female New Zealand rabbits (number not given) were exposed to morpholine (905 mg/ci m) for 5 hr by nose-only inhalation. At the end of the exposure, the animals were sacrificed and the tissue and body fluids analyzed. Concentrations of morpholine were highest in urine (324 mg/L) and kidney (118 mg/kg), the other tissues having concentrations below 40 mg/kg.

Elimination of (14)C from labeled morpholine (intraperitoneal injection) through expired air is minimal. In rats, experiments have shown that only about 0.5% of the dose of radioactively labelled morpholine is exhaled as (14)CO2. In rabbits 0.0008% of the administered dose was (14)CO2.

For more Absorption, Distribution and Excretion (Complete) data for Morpholine (14 total), please visit the HSDB record page.

Cellular LocationsCytoplasm

Uses & manufacturing

Uses · 6 items

CIR ingredient: Morpholine

Used as a solvent for resins, waxes, casein and dyes; morpholine compounds are used as emulsifiers, corrosion inhibitors, antioxidants, plasticizers, pesticides, antiseptics, etc. [Merck Index]

Plastic Composites Manufacturing [Category: Industry]

For morpholine (USEPA/OPP Pesticide Code: 054701) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Morpholine is used as a separating agent for volatile amines; an intermediate for textile lubricants; in the synthesis of rubber accelerators and pharmaceuticals. It is also used as a solvent, as a boiler water additive, and in the formulation of waxes, polishers, and cleaners.

Solvent for resins, waxes, casein, dyes

Impurities · 2 items

When produced from diethylene glycol, commercial morpholine is more than 99% pure, being contaminated particularly by N-ethylmorpholine and ethylenediamine.

Impurities in cosmetic grade morpholine have been reported to include arsenic (up to 3 mg/kg) and lead (up to 20 mg/kg).

U.S. Imports(1977) AT LEAST 4.54X10+7 G
U.S. Production · 6 items

2023: 1,000,000 - <2,500,000 lb

(1974-81) Stable at about 11,000 tons/yr (US)

(1978) PROBABLY GREATER THAN 4.54X10+6 G

(1982) PROBABLY GREATER THAN 6.81X10+6 G

(1992) 19,752,000 Kg

For more U.S. Production (Complete) data for Morpholine (7 total), please visit the HSDB record page.

Consumer UsesNot Known or Reasonably Ascertainable
Industry UsesIntermediate
Methods of Manufacturing · 4 items

Morpholine is prepared by condensation of ethylene oxide with ammonia...

Dehydration of diethanolamine by strong acid at elevated temperature (Former method)

Prepd by dehydrating diethanolamine

Morpholine can be obtained from diethanolamine by cyclization with sulfuric acid or via diethanolamine hydrochloride or from di(2-chloroethyl) ether and ammonia. Industrially more important is the amination of diglycol under hydrogen pressure and over a cobalt or nickel catalyst.

Formulations/PreparationsThe compound is marketed under the name of "Morpholine". It is distributed as an anhydrous liquid and as 40% and 88% solutions with water.
Household ProductsInformation on 66 consumer products that contain Morpholine in the following categories is provided:
General Manufacturing Information · 6 items

Soap, Cleaning Compound, and Toilet Preparation Manufacturing

Morpholine: ACTIVE

Morpholine is listed by the Cosmetic Ingredient Review as an ingredient used in cosmetics, although there are insufficient data to substantiate safety. Morpholine is listed in Annex II of the EEC Cosmetics Directive. Annex II lists compounds that must not be used in cosmetic formulations. In Germany, the use of morpholine in cosmetic preparations has been forbidden since 1985 and in the EU since 1986.

Because water and morpholine have similar volatilities and the latter is an anticorrosion agent, it is useful in steam cycles, aqueous hydraulic liquids, and similar systems.

An aqueous solution of morpholine (2 M) can be used for removing carbon dioxide, hydrogen sulfide, or hydrogen cyanide from gases.

/Morpholines are/ a group of systemic fungicides active against powdery mildew of cereals, including dodemorph and tridemorph. /Morpholines/

Applications · 6 items

Uses(1) For medicine, it used as the raw materials for rubber accelerator and fluorescent whitening agent. (2) Morpholine is the intermediates of fungicide dimethomorph and flumorpholine and organophosphate insecticide phosalphos. (3) Morpholine is Mainly used for the production of rubber vulcanization accelerator, but also for surfactant, textile auxiliaries, pharmaceuticals, pesticide synthesis. (4) Morpholine also used as a catalyst for polymerization of butadiene, corrosion inhibitors, optical bleach, the goods are dyes, resins, wax, early glue, casein and other solvents. At present, the total production of morpholine in the world is 3-4 million t/a. (5) Morpholine salts are also widely used. Morpholine salts like morpholine hydrochloride (10024-89-2) are the organic synthesis of intermediates. Morpholine fatty acid salt can be used as the coating agent of fruits or vegetables epidermal coating agent, and it could inhibit the base respiration and prevent the epidermis from evaporation of water and epidermal atrophy. (6) Morpholine is the main raw materials of accelerator NOBS. for analysis reagents and resins, wax, shellac and other solvents, used in the production of sodium sulfate. Water glass and ultramarine. Also used in the manufacture of glass. Paper. Detergent. Soap. Dye. Synthetic fiber. Tanning. Medicine and ceramics industries. Analysis reagents, such as nitrogen determination, dehydrating agent. (7) Morpholine is used for the analysis of reagents and resins, wax, casein, shellac and a variety of solvents solvent. (8) Morpholine could produce salt after reacting with inorganic acid, and it also could produce salt or amide after reacting with organic acid. It also can be alkylated, and it also could come up a ketone reaction or Willgerodt reaction with ethylene oxide.

DescriptionMorpholine is a colorless liquid with a weakammonia or fish-like odor. The odor threshold is 0.01 ppm.Molecular weight = 87.14; Specific gravity (H2O:1) 51.007; Boiling point = 128.9℃; Freezing/Meltingpoint 5 25℃; Vapor pressure 5 6 mmHg at 20℃; Flashpoint 5 37℃. Autoignition temperature 5 310℃. Explosivelimits: LEL 5 1.4%; UEL 5 11.2%. Hazard Identification(based on NFPA-704 M Rating System): Health 3,Flammability 3, Reactivity 0. Soluble in water

UsesMorpholine is made by dehydrating ethanolamines. Its main use is as a rubber accelerator in manufacturing tires. This process requires high temperature (300°F) and pressure, which increase the hazards. Morpholine is also used as a boiler water additive, brightener for detergents, and corrosion inhibitor, in the preservation of book paper, in waxes and polishes, and in organic synthesis.

UsesSolvent for resins, waxes, casein, dyes; morpholine compounds used as corrosion inhibitors, insecticides, antiseptics, intermediate for rubber-processing chemicals; corrosion inhibitors; waxes and polishes; optical brighteners

UsesRubber accelerator, solvent, additive to boilerwater, waxes and polishes, optical brightener fordetergents, corrosion inhibitor, preservation of bookpaper, organic intermediate (catalyst, antioxidants,pharmaceuticals, bactericides, etc.).

General DescriptionAn aqueous solution with a fishlike odor. Corrosive to tissue and moderately toxic by ingestion and inhalation.

Upstream & downstream products

Upstream raw materials

Diethylene glycol4-ChlorobenzaldehydeDiethanolamine1,4-DioxaneHydrogenSodium hydroxideSulfuric acidAmmonia

Downstream products

4-(5-Nitropyridin-2-yl)morpholine2-MORPHOLIN-4-YL-PYRIMIDINE-5-CARBALDEHYDE4-MORPHOLINOBENZYLAMINE6-MORPHOLINONICOTINALDEHYDEETHYL 2-AMINO-4-METHYLTHIOPHENE-3-CARBOXYLATEETHYL 3-PYRIDYLACETATEMORPHOLIN-4-YL-ACETIC ACID6-MORPHOLINONICOTINOYL CHLORIDE6-MORPHOLINONICOTINIC ACID2-MORPHOLINOBENZOIC ACID2-MORPHOLIN-4-YL-ISONICOTINIC ACID4-MORPHOLINECARBOXAMIDINE4-Acryloylmorpholine2-AMINO-6-METHYL-4,5,6,7-TETRAHYDRO-BENZO[B]THIOPHENE-3-CARBOXYLIC ACID ETHYL ESTERAcetylmorpholine4-(MORPHOLINE-4-SULFONYL)-PHENYLAMINE2-CHLORO-3-(4-MORPHOLINYL)QUINOXALINEMethyl 3-(morpholinomethyl)benzoate ,98%3-Amino-6-morpholinopyridine2-AMINO-1-MORPHOLIN-4-YL-ETHANONE HCL1-(4-AMINO-2,6-DICHLOROPHENOXY)-3-MORPHOLINOPROPAN-2-OL2-(Morpholinothio)benzothiazole4-Morpholinophenylboronic acidAdefovir dipivoxil6-MORPHOLINONICOTINOHYDRAZIDE6-MORPHOLINONICOTINONITRILEMORPHOLINE-4-CARBOTHIOAMIDE3-MORPHOLINOPHENOL1-[2-(MORPHOLIN-4-YL)-ETHYL]-PIPERAZINE4-(Morpholinomethyl)aniline2-(CHLOROMETHYL)-5-METHYLTHIENO[2,3-D]PYRIMIDIN-4(3H)-ONE(6-MORPHOLINO-3-PYRIDINYL)METHANOL4-Methylmorpholine N-oxide monohydrate3-Morpholinobenzaldehyde2-(MORPHOLINE-4-CARBONYL)-BENZOIC ACID4-(3-MORPHOLINOPROPOXY)-3,5-DICHLOROBENZENAMINE4-Formylmorpholine4-Bromophenethyl alcohol5-BROMO-2-(MORPHOLIN-4-YL)PYRIMIDINE4-(2-MORPHOLINOETHOXY)-3,5-DICHLOROBENZENAMINE
Additional notes · 1 item

DefinitionChEBI: Morpholine is an organic heteromonocyclic compound whose six-membered ring contains four carbon atoms and one nitrogen atom and one oxygen atom that lies opposite to each other; the parent compound of the morpholine family. It is a saturated organic heteromonocyclic parent and a member of morpholines. It is a conjugate base of a morpholinium.