Beta-Propiolactone

Hazardous Air Pollutants (HAPs)

Other Classes -> Lactones

Carcinogens

PUNGENT

SLIGHTLY SWEETISH

Slightly sweet odor.

1.146 at 68 °F (EPA, 1998) - Denser than water; will sink

1.1460 @ 20 °C/4 °C

Density (at 20 °C): 1.1 g/ml

Relative density of the vapour/air-mixture at 20 °C (air = 1): 1.0

1.15

1.1460 @ 20°C

A COLORLESS LIQUID

Colorless liquid.

10 to 50 mg/mL at 66 °F (NTP, 1992)

SOL IN WATER: 37% VOL/VOL; MISCIBLE WITH ALCOHOL, ACETONE, ETHER, CHLOROFORM

PROBABLY MISCIBLE WITH MOST POLAR ORG SOLVENTS & LIPIDS

water solubility = 3.70X10+5 mg/l @ 25 °C

Solubility in water, g/100ml at 25 °C: 37 (good)

158 °F (EPA, 1998)

74 °C

165 °F (74 °C) (closed cup)

74 °C c.c.

165 °F

165 °F

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

324 °F at 760 mmHg decomposes (EPA, 1998)

Decomposes (155ºC)

61 °C @ 20 MM HG

BP: 162 °C @ 760 MM HG (DECOMP); 150 °C @ 750 MM HG (DECOMP); DIPOLE MOMENT: 3.8

323 °F (decomposes)

162 °C @760 [mm Hg]

Danger

H315: Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P264, P264+P265, P271, P280, P284, P302+P352, P304+P340, P305+P351+P338, P316, P318, P320, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P264, P264+P265, P271, P280, P284, P302+P352, P304+P340, P305+P351+P338, P316, P318, P320, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Chemical: 2-Oxetanone

Hazard Traits - Carcinogenicity; Ocular Toxicity; Respiratory Toxicity

Status: Active Update: 01-07-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/21395

Propiolactone: HSNO Approval: HSR003070 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.)

Containers may explode. When heated to decomposition, it emits acrid smoke and fumes. Stable when stored at 41F. Avoid storing in areas of exposure to the direct rays of the sun and in areas of high fire hazard. Tends to polymerize on storage. Avoid elevated temperatures. (EPA, 1998)

Combustible. Above 74 °C explosive vapour/air mixtures may be formed.

beta-Propiolactone is used for vaccines, tissue grafts, surgical instruments, and enzymes, as a sterilant of blood plasma, water, milk, and nutrient broth, and as a vapor-phase disinfectant in enclosed spaces. Acute (short-term) inhalation exposure to beta-propiolactone causes severe irritation of the eyes, nose, throat, and respiratory tract in humans. Acute dermal exposure may cause irritation of the skin, blistering, or burns in humans. Contact with the eyes may cause permanent corneal opacification. Burns of the mouth and stomach may occur in humans following acute exposure via ingestion. No information is available on the chronic (long-term), reproductive, developmental, or carcinogenic effects of beta-propiolactone in humans. Squamous cell carcinomas of the forestomach have been reported in orally exposed rats. In dermally exposed rodents, skin tumors have been observed. The International Agency for Research on Cancer (IARC) has classified beta-propiolactone as a Group 2B, possible human carcinogen.

Causes permanent corneal opacification when tested in the rabbit eye and scarring when tested on mouse skin; Avoid contact because of its carcinogenic potential; [ACGIH] Causes second degree burns after a few minutes of skin exposure; [CHRIS] Corrosive to the eyes; [ICSC] Irritating to the skin and eyes; Very toxic by inhalation; Inhalation of high concentration may cause chemical pneumonitis; [MSDSonline] Causes liver injury in high-dose animal studies; [HSDB]

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. beta-Propiolactone (57-57-8) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s154bpro.pdf]

Wear air mask, goggles or face shield, rubber gloves, and protective clothing to prevent all skin contact. Cool exposed containers with water.

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

Fresh air, rest. Artificial respiration may be needed. Refer immediately for medical attention.

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 .

Warning: Propiolactone, beta- is an animal carcinogen. Toxicity potential via inhalation and ingestion is high. May cause death or permanent injury after very short exposures to small quantities. Propiolactone, Beta- also is an irritant; effects may be delayed.

(General first aid procedures)

MATERIALS WHICH ARE TOXIC AS STORED OR WHICH CAN DECOMPOSE INTO TOXIC COMPONENTS ... SHOULD BE STORED IN A COOL WELL VENTILATED PLACE, OUT OF THE DIRECT RAYS OF THE SUN, AWAY FROM AREAS OF HIGH FIRE HAZARD, AND SHOULD BE PERIODICALLY INSPECTED. INCOMPATIBLE MATERIALS SHOULD BE ISOLATED ... .

SHOULD BE STORED @ LOW TEMP (O °C)

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

... SUBSTITUTION OF LESS IRRITATING SUBSTANCES ... REDESIGN OF OPERATIONS ... PREVENT CONTACT, PROVISION OF A PHYSICAL BARRIER AGAINST CONTACT, PROPER WASHING FACILITIES, WORK CLOTHING AND STORAGE FACILITIES, PROTECTIVE CLOTHING, AND BARRIER CREAMS.

... MEASURES SHOULD BE TAKEN TO PREVENT CONTACT WITH SKIN OR EYE, ESPECIALLY WITH BETA-LACTONES. /LACTONES/

A PERSONAL MONITORING BADGE WAS DEVELOPED FOR THE DETECTION OF THE DIRECT-ACTING, ALKYLATING CARCINOGEN BETA-PROPIOLACTONE @ ATMOSPHERIC CONCN OF 6 PPB FOR 24 HR & 0.6 PPM FOR 0.25 HR IS DISCUSSED.

For more Preventive Measures (Complete) data for BETA-PROPIOLACTONE (18 total), please visit the HSDB record page.

WHILE BETA-PROPIOLACTONE CAUSES LIVER NECROSIS AND RENAL TUBULAR DAMAGE WHEN GIVEN BY ITSELF INTRAVENOUSLY, IF IT IS ALLOWED TO REACT WITH PROTEINS BEFORE INJECTION, THE TOXICITY IS SAID TO BE VERY MUCH REDUCED.

The ability of UV-A light (320-400 nm) to induce cellular transformation in vitro and to modify chemical carcinogen-induced cellular transformation was investigated in BALB/c 3T3 cell cultures. When administered as a series of nontoxic exposures, UV-A alone was found to induce cellular transformation as a linear function of the numbers of UV-A exposures. Possible interactions of UV-A with environmentally encountered chemical carcinogens were studied by examining the effects of UV-A light exposures on cellular transformation in cells exposed to the direct acting carcinogen, beta-propiolactone, an alkylating agent, with a standard initiation/promotion protocol. Twenty-four hours after a single treatment with 2.5 ug/ml of beta-propiolactone, cells were exposed to 3.0 kJ/sq m of UV-A light. UV-A exposures were repeated weekly for up to 5 weeks, after which cells were fixed, stained and dishes were scored for type III transformed foci. Weekly exposures to UV-A alone for 5 weeks induced approximately 3 foci/dish. Treatment with beta-propiolactone alone induced approximately 1 focus/dish (background was 0.17 foci/dish). A combination of the two treatments resulted in a marked increase in the yield of transformed foci/dish, with the UV-A enhancement increasing with increasing numbers of exposures (approximately 10 foci/dish after a single exposure to beta-propiolactone and five UV-A exposures). These results suggest a synergistic interaction between beta-propiolactone and subsequent UV-A exposures in the induction of in vitro neoplastic transformation.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the lumen of the GI tract and thus prevent these carcinogens from attacking tissues of the host. Sodium 4-mercaptobenzene sulfonate is a potent nucleophile and was found to react rapidly in vitro with the direct-acting carcinogen beta-propiolactone. In further investigations sodium 4-mercaptobenzene sulfonate was shown to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA-100 to beta-propiolactone and a second direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoquanidine. Subsequent experiments were performed to determine if sodium 4-mercaptobenzene sulfonate would inhibit beta-propiolactone induced carcinogenesis in vivo. In the first of these, sodium 4-mercaptobenzene sulfonate was administered by oral intubation to female A/J mice 5 min before oral administration of beta-propiolactone. Under these conditions inhibitions of carcinogenesis of the forestomach occurred. In a second experiment, sodium 4-mercaptobenzene sulfonate was given by rectal intubation 5 min before beta-propiolactone also administered intrarectally. Administration of beta-propiolactone intrarectally produced adenomatous polyps of the large intestine. The occurrence of these neoplasms was inhibited by the prior administration of sodium 4-mercaptobenzene sulfonate. These results suggest that sodium 4-mercaptobenzene sulfonate has the capacity to trap direct-acting carcinogens and to inhibit the occurrence of beta-propiolactone induced neoplasia.

Using a two-step carcinogenesis protocol, SENCAR mice were initiated with 25 ug 7,12-dimethylbenz(a)anthracene and were then treated twice weekly with either (a) 0.5 mg beta-propiolactone or (b) 1 ug fluocinolone acetonide followed in 30 min by 0.5 mg beta-propiolactone. The tumor incidence for the group receiving fluocinolone acetonide prior to beta-propiolactone was significantly greater than for beta-propiolactone alone (p< 0.0005). Under these experimental conditions beta-propiolactone alone showed neither promoting activity nor complete carcinogenic activity. These results were not anticipated, but the reasons for their occurrence are being explored.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the stomach. Sodium thiosulfate is a potent nucleophile and in initial experiments was found to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA100 to the direct-acting carcinogens beta-propiolactone and styrene oxide. In in vitro experiments sodium thiosulfate was shown to maintain its nucleophilicity in the acid pH range. It reacted with beta-propiolactone as rapidly at pH 2 as at pH 7.4. Thus sodium thiosulfate has the prerequisite attributes to inhibit the carcinogenic effects of electrophiles in the stomach. Experiments were performed in which sodium thiosulfate was administered by oral intubation to female A/J mice 5 min before oral administration of beta-propiolactone. Under these conditions, inhibition of formation of the forestomach tumors occurred. The data obtained suggest that use of nucleophiles to protect against direct-acting carcinogens is a potential strategy for chemoprevention.

TERRESTRIAL FATE: The important environmental fate processes for beta-propiolactone in the terrestrial environment are expected to be hydrolysis and volatilization. beta-Propiolactone has an aqueous hydrolysis half-life of approximately 3.5 hr at 25 °C(2); therefore, relatively rapid hydrolysis can be expected to occur in moist soils. beta-Propiolactone has a vapor pressure of 3.4 mm Hg at 25 °C(1); therefore, significant evaporation from dry surfaces may occur. Although high soil mobility can be predicted, concurrent hydrolysis should preclude the importance of leaching(SRC).

AQUATIC FATE: The dominant environmental fate process for beta-propiolactone in water is hydrolysis since it has a half-life of approximately 3.5 hr at 25 °C(1,SRC). The hydrolysis half-life at 5 °C is approximately 33 hr(2,SRC).

ATMOSPHERIC FATE: Based upon a vapor pressure of 3.4 mm Hg at 25 °C(1), beta-propiolactone can be expected to exist entirely in the gas-phase in the ambient atmosphere(2,SRC). Gas-phase beta-propiolactone may be degraded in the ambient atmosphere by reaction with photochemically produced hydroxyl radicals; the half-life for this reaction can be estimated to occur at the relatively slow rate of 45 days in an average atmosphere(3,SRC). Beta-propiolactone is very water soluble (37 % v/v at 25 °C)(1), therefore, physical removal from air by wet deposition processes such as rainfall may be possible(SRC).

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

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

Burning sensation. Cough. Sore throat. Headache. Nausea. Shortness of breath. Vomiting.

Redness.

Redness. Pain. Burns.

See Inhalation.

Skin irritation, blistering, burns; corneal opacity; frequent urination; dysuria; hematuria (blood in the urine); [potential occupational carcinogen]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

DESIRABLE THAT PERSONS WORKING WITH LACTONES UNDERGO REGULAR MEDICAL EXAMINATIONS WITH SPECIAL ATTENTION TO THE DEVELOPMENT OF ANY SKIN LESIONS. ... /LACTONES/

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. beta-Propiolactone is included on this list.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Propiolactone, beta- is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 lbs.

When employed under conditions of maximum effectiveness, propiolactone is approximately 25 more active as a vapor phase disinfectant than formaldehyde, 4000 times more active than ethylene oxide and 50000 times more active than methyl bromide. It has been shown to be mutagenic by inducing cell transformation, chromosomal aberrations and chromatoid exchange. Propiolactone has been shown to be mutagenic in both somatic and germ cells.

Propiolactone is an alkylating agent that acts through alkylation of carboxyl- and hydroxyl- groups. The lactone ring splits either at the first or third carbon. Propiolactone reacts with polynucleotides and DNA, mainly at N7 of guanine and N1 of adenine to form carboxyethyl derivatives. It also forms adducts with N3 of cytosine and thymine.

Chemical mutagens 6-N-hydroxylaminopurine and propiolactone induce Lys2 mutants with high frequency in diploid yeast Saccharomyces cerevisiae. 6-N-hydroxylaminopurine induces such mutants even in tetraploid strains. The genetic analysis of mutants was performed. It is known that propiolactone induces mutants by means of mutation-mitotic segregation mechanism, while 6-N-hydroxylaminopurine induces mutants through novel mechamism both allele mutation. Manifestation of such mechanism is the null fertility after meiosis of diploid mutants induced by 6-N-hydroxylaminopurine.

Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was 50 to 100 times more reactive with all the nucleophiles than beta-butyrolactone whereas gamma-butyrolactone was completely inactive. The rate of alkylation by lactones was guanosine greater than RNA= denatured DNA greater than double-stranded DNA. The type of the adducts formed were characterized by fluorescence and ultraviolet spectroscopy. Similar alkylation products were formed by the two lactones. The main sites alkylated were N-1 at adenosine, N-3 at cytidine and N-7 at guanosine. The results suggest that the carcinogenic potency of the lactones correlates with their reactivity rather than with specificity of the adducts formed.

The half-life of propiolactone in water is of 225 minutes.

No reports found; [TDR, p. 1048]

Propiolactone is completely hydrolyzed after 3 hours of being in an aqueous solution and this time can be even faster in the presence of cellular debris and cell culture media. When in water, the lactone ring opens at the alkyl and acyl bonds. The degradation products of propiolactone are not toxic.

BETA-PROPIOLACTONE CAN REACT WITH CHLORIDE ION TO FORM 3-CHLOROPROPIONIC ACID, ESPECIALLY IN BLOOD PLASMA.

BETA-HYDROXYPROPIONIC ACID, THE HYDROLYSIS PRODUCT OF BETA-PROPIOLACTONE, FAILED TO PRODUCE EITHER LOCAL SARCOMAS IN SC STUDY IN RATS ... OR SKIN TUMORS AFTER APPLICATIONS TO SKIN OF MICE.

Substances used on inanimate objects that destroy harmful microorganisms or inhibit their activity. Disinfectants are classed as complete, destroying SPORES as well as vegetative forms of microorganisms, or incomplete, destroying only vegetative forms of the organisms. They are distinguished from ANTISEPTICS, which are local anti-infective agents used on humans and other animals. (From Hawley&apos;s Condensed Chemical Dictionary, 11th ed)

THE LD50 BY SKIN APPLICATION IS LESS THAN 5 ML/KG IN THE GUINEA PIG, INDICATING CONSIDERABLE ABSORPTION.

BETA-PROPIOLACTONE BINDS IN VIVO TO DNA, RNA & PROTEINS OF MOUSE SKIN. DEGREE OF TUMOR-INITIATING ACTIVITY IS PROPORTIONAL TO EXTENT OF DNA BINDING BUT NOT TO EXTENT OF RNA OR PROTEIN-BINDING. MAJOR RNA & DNA BINDING PRODUCT IS 7-(2-CARBOXYETHYL)GUANINE. S-2-CARBOXYETHYLCYSTEINE ... FOUND IN ACID HYDROLYSATE OF PROTEIN ... .

beta-Propiolactone is used for vaccines, tissue grafts, surgical instruments, and enzymes, as a sterilant of blood plasma, water, milk, and nutrient broth, and as a vapor-phase disinfectant in enclosed spaces. Its sporicidal action is used against vegetative bacteria, pathologic fungi, and viruses. beta-Propiolactone is also used as a chemical intermediate.

Used as a sterilant in medicine for biological pharmaceuticals and surgical instruments; also used as a disinfectant and chemical intermediate; [ACGIH]

Regulated as a carcinogen: See 29CFR1910.1013 (Code of Federal Regulations pertaining to the manufacturing, processing, repackaging, releasing, handling, and storing of this chemical).

Using Disinfectants or Biocides [Category: Clean]

VERSATILE INTERMEDIATE IN ORGANIC SYNTHESIS; DISINFECTANT

Used as a sporicide to sterilize water, milk, nutrient broths, and vaccines.

(1972) 2.2X10+10 GRAMS

(1975) PROBABLY LESS THAN 4.54X10+5 GRAMS