β-Propiolactone

72.06

72.06

200-340-1

6RC3ZT4HB0

0555

758422|21626

2810

DTXSID8021197

C44339

A COLORLESS LIQUID|Colorless liquid.

2932209090

26.3

0.46 (estimated)

Liquid

1.1460 g/cm³ @ Temp: 20 °C

-33.4 °C

61 °C @ Press: 20 Torr

158 °F

1.445

H2O: 37 g/100 mL

2-8°C

Vapour pressure, Pa at 25°C: 453

2.5

Inhalation-rat LC50: 25 ppm/6 hours; peritoneal-mouse LD50: 405 mg/kg

Flammable; spicy and irritating smoke is released in the fire; rapid hydrolysis in water

vol% in air: 2.9

PUNGENT

VERY HIGH CHEMICAL REACTIVITY DUE TO PRESENCE OF STRAINED FOUR-MEMBERED LACTONE RING|DECOMP IN WATER & ALCOHOL

Slow reaction with water to form beta- hydroxypropionic acid.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

BETA-PROPIOLACTONE is an ester. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides. This chemical may be incompatible with alkalis.

LOWER FLAMMABLE LIMIT: 2.9%|Class IIIA Combustible Liquid: Fl.P. at or above 140°F and below 200°F.

I

6.1

UN 3382 6.1/PG 1

3

45-26-36/38

53-45-99

RQ7350000

T+

Warehouse low temperature, ventilated, dry; moisture-proof

Explosive when mixed with air

STABLE WHEN STORED AT +5 DEG C IN GLASS CONTAINERS

P201-P260-P284-P305 + P351 + P338-P310

H315-H319-H330-H350

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/

Acetates, halogens, thiocyanates, thiosulfates [Note: May polymerize upon storage].

beta-Propiolactone is an indirect food additive for use only as a component of adhesives.

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]

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.|Carcinogens, Corrosives, Mutagens, Flammable - 2nd degree

|Danger|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P260, P264, P271, P280, P281, P284, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P320, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|Aggregated GHS information provided by 69 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P284, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P320, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|H227: Combustible liquid [Warning Flammable liquids]|P201, P202, P210, P260, P261, P264, P270, P271, P280, P281, P284, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P320, P321, P330, P332+P313, P362, P370+P378, P403+P233, P403+P235, P405, and P501

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

Avoid contact with liquid. Keep people away. Stop discharge. Avoid inhalation. (EPA, 1998)

Skin: Wear appropriate personal protective clothing to prevent skin contact. Eyes: Wear appropriate eye protection to prevent eye contact. Wash skin: The worker should immediately wash the skin when it becomes contaminated. The worker should wash daily at the end of each work shift. Remove: Work clothing that becomes wet or significantly contaminated should be removed and replaced. Change: Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premise. Provide: Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection. Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.] (NIOSH, 2016)|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/|Wear appropriate personal protective clothing to prevent skin contact.|Wear appropriate eye protection to prevent eye contact.|Eyewash fountains should be provided in areas where there is any possbility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection.|For more Personal Protective Equipment (PPE) (Complete) data for BETA-PROPIOLACTONE (7 total), please visit the HSDB record page.|(See protection codes)

FIRE HAZARD: MODERATE, WHEN EXPOSED TO HEAT OR FLAME ... .

LOWER EXPLOSIVE LIMIT: 2.9%|Explosive limits , vol% in air: 2.9-?

USE ALCOHOL FOAM.

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/

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.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

Workers' exposure to beta-propiolactone is to be controlled through the required use of engineering controls, work practices, & personal protective equipment, incl respirators. Identified as an occupational carcinogen without establishing a PEL.

NIOSH considers beta-propiolactone to be a potential occupational carcinogen.|NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concn.

Personal protection: self-contained breathing apparatus. Collect leaking liquid in sealable containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

Separated from food and feedstuffs. Cooled. Well closed. Ventilation along the floor.

A harmful contamination of the air can be reached rather quickly on evaporation of this substance at 20 °C on spraying.

The substance is severely irritating to the eyes. The substance is irritating to the skin and respiratory tract.

This substance is probably carcinogenic to humans.

NO open flames. Above 74 °C use a closed system and ventilation.

AVOID ALL CONTACT!

Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety goggles or eye protection in combination with breathing protection.

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.

| 0 - Materials that, under emergency conditions, would offer no hazard beyond that of ordinary combustible materials.| 2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.| 0 - Materials that in themselves are normally stable, even under fire conditions.

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.

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.

highly toxic

Based on experimental trials, it has been determined that propiolactone is a human carcinogen. The results have shown the generation of tumors in several tissues and from different administration routes.

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.

LC50 RAT INHALATION 250 PPM/30 MIN|LC50 RAT INHALATION 25 PPM/6 HR|LD50 RAT YOUNG IV 225 + OR - 55 MG/KG, SCORED @ 24 HR|LD50 GUINEA PIG SKIN APPLICATION < 5 ML/KG

Health professionals (eg, physicians, nurses) could possibly be exposed during preparation and administration of the pharmaceuticals. Workers involved in the formulation of the products may also be exposed to beta-propiolactone. The possibility of exposure also exists from contact with sterilized instruments, from ingestion of liquids sterilized with the compound, or from transfusion of blood plasma sterilized with it.|Occupations at greatest risk of possible exposure included disinfectant workers and makers of viricidal agents, acrylic plastics, and resins.

Propiolactone is highly bound to proteins showing an almost 2-fold binding increase when compared to DNA and RNA.

beta-Propiolactone has not been reported to occur as such in nature(1).

beta-Propiolactone may be present in waste streams from plants where it is made or used(1).

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 rate constant for the aqueous hydrolysis of beta-propiolactone at 25 °C has been experimentally measured to be 5.5-5.68X10-5 /sec(1); this corresponds to a half-life of 3.39-3.59 hr(SRC). The aqueous hydrolysis rate constant at 5 °C has been measured to be 0.35X10-3 /min(2) which corresponds to a half-life of 33 hr(SRC). The aqueous hydrolysis product is 3-hydroxypropionic acid(1). The rate constant for the gas-phase reaction between beta-propiolactone and hydroxyl radicals can be estimated to be 3.56X10-13 cu cm/molecule-sec at 25 °C which corresponds to a half-life of 45 days in an average atmosphere containing 5X10+5 OH radicals/cu cm(3,SRC). Beta-propiolactone does not absorb UV light significantly above 270 nm; therefore, direct photolysis in the environment should not occur(4). The reaction half-lives of beta-propiolactone with respect to ozone and peroxy radicals have been estimated to be in excess of 1 yr(4).

The rapid aqueous hyrolysis of beta-propiolactone precludes the importance of bioconcentration. (SRC)

The rapid aqueous hyrolylsis of beta-propiolactone precludes the importance of leaching. (SRC)

The rapid aqueous hyrolysis of beta-propiolactone precludes the importance of leaching. (SRC)

Beta-propiolactone is used as a chemical intermediate in organic synthesis and has been used as sterilant for the sterilization of blood plasma, vaccines, tissue grafts, surgical instruments, enzymes, water, milk, and nutrient broth(1,2). The sterilization applications are apparently no longer used(1,2); therefore, human exposure from these uses may not occur(SRC). Occupational exposure may be possible through inhalation and dermal contact at sites where beta-propiolactone is used as a chemical intermediate(SRC).|NIOSH (NOHS Survey 1972-1974) has statistically estimated that 575 workers are potentially exposed to beta-propiolactone in the USA(1).

Propiolactone was used for vaccines, tissue grafts, surgical instruments, and enzymes, as a sterilant of blood plasma, water, milk and nutrient broth as a vapor-phase disinfectant in enclosed spaces. Its sporicidal action is used against vegetative bacteria, pathologic fungi, and viruses. It is no longer used in medical procedures or in food.

Because production of skin cancer is felt to be the overriding consideration in the toxic potential of BPL, all contact with liquid BPL should be avoided.

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.

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's Condensed Chemical Dictionary, 11th ed) (See all compounds classified as Disinfectants.)

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 ... .

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.

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

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.

Impurities in fresh and aged commercial samples include acrylic acid, acrylic anhydride, acetic acid and acetic anhyride in amounts of less than 1%.

The toxicity potential of this material via inhalation or ingestion is high; may cause death or permanent injury after very short exposures to small quantities. It is a carcinogen. (EPA, 1998)

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. Signs and Symptoms of Propiolactone, Beta- Exposure: Acute exposure to propiolactone, beta- may include irritation to skin, eyes, mouth, esophagus, GI tract, and respiratory tract. Liver and kidney injury, dyspnea (difficult or labored breathing), and convulsions may also be noted. Emergency Life-Support Procedures: Acute exposure to propiolactone, beta- may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to propiolactone, beta-. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures. 4. Rush to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to propiolactone, beta-. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Remove contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin thoroughly with soap and water. 6. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures. 7. Rush to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. DO NOT induce vomiting. 4. Following ingestion, immediately dilute with 4 to 8 ounces (120 to 140 mL) of milk or water not to exceed 15 mL/kg in a child). 5. Rush to a health care facility. (EPA, 1998)|(See procedures)

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.

In the event of an emergency, remove the victim from further exposure, send for medical assistance, and initiate emergency procedures. If a worker had contact with beta-propiolactone, OSHA requires that that the worker shower as soon as possible, unless contraindicated by physical injuries.|Where there is any possibility of worker's eyes being exposed to beta-propiolactone, an eye-wash fountain should be provided within the immediate work area for emergency use. If beta-propiolactone gets into the eyes, flush them immediately with large amounts of water for 15 minutes, lifting the lower and upper lids occasionally. Get medical attention as soon as possible. Contact lenses should not be worn when working with this chemical.|Where there is any possibility of a worker's body being exposed to beta-propiolactone, facilities for quick drenching of the body should be provided within the immediate work area for emergency use. If beta-propiolactone gets on the skin, wash it immediately with soap and water. If beta-propiolactone penetrates the clothing, remove the clothing immediately and wash the skin with soap and water. Get medical attention promptly.

SKIN BURNS IN HUMAN/S/ RESULT FROM CONTACT FOR TWENTY MIN WITH 40% SOLN IN WATER.|... VERY READILY HYDROLYZED TO 3-HYDROXY-PROPIONIC ACID WHICH IS INACTIVE. IT WAS THEREFORE CONCLUDED THAT AS USED IN STERILIZATION PROCEDURES BETA-PROPIOLACTONE WAS NOT CARCINOGENIC. HOWEVER ... FACT REMAINS THAT ... UNALTERED LACTONE IS A CARCINOGEN AND THEREFORE HUMAN CONTACT MUST BE AVOIDED.|The vapor /of propiolactone/ is unbearable to human beings at concentrations greater than 0.1 mg/l of air. The immediate irritation appears to be great enough to prevent people from working in the presence of vapor concentrations which might be injurious.|Short-term (acute): Exposure to beta-propiolactone can cause irritation and blistering of the skin, hair loss, and scarring. Eye contact with liquid beta-propiolactone can cause permanent corneal opacification.

beta Propiolactone

The substance can be absorbed into the body by inhalation and by ingestion.|inhalation, skin absorption, ingestion, skin and/or eye contact

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

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

Redness.

Redness. Pain. Burns.

Kidneys, skin, lungs, eyes

MORE THAN 85% IS USED IN CAPTIVE CONSUMPTION FOR ACRYLATES; LESS THAN 15% IS USED AS A STERILANT (1972)

2-Oxetanone: ACTIVE

Propanolide is determined in air using gas chromatography/flame ionization detection. Nitrogen is used as carrier gas. The limit of detection is 0.1 ppb.|Propanolide has been determined in soil extracts by gas chromatography of the bromophenacylate derivatives using mass spectrometric detection.

Hazardous Air Pollutants (HAPs)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Fire Hazards -> Carcinogens, Corrosives, Mutagens, Flammable - 2nd degree