National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Propiolactone
• 2-OXETANONE (9CI)

Human Toxicity Excerpts

• SKIN BURNS IN HUMAN/S/ RESULT FROM CONTACT FOR TWENTY MIN WITH 40% SOLN IN WATER. [Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 859]**PEER REVIEWED**
  
• ... 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. [Sax, N.I. Dangerous Properties of Industrial Materials. 4th ed. New York: Van Nostrand Reinhold, 1975., p. 284]**PEER REVIEWED**
  
• 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. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 766]**PEER REVIEWED**
  
• 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. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. ]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• WHEN UNDILUTED BPL OR BPL IN CORN OIL OR IN ACETONE SOLUTIONS AT INDIVIDUAL DOSES OF FROM 0.8 MG TO 100 MG WAS APPLIED 1 TO 6 TIMES ON THE SKIN OF MICE, ALL SHOWED SKIN IRRITATION RANGING FROM ERYTHEMA TO HAIR LOSS AND SCARRING. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 497]**PEER REVIEWED**
  
• THE ACUTE ORAL AND INTRAPERITONEAL TOXICITY IS HIGH IN RATS (ORALLY, THE UNDILUTED MATERIAL HAS AN APPROX LD50 OF 50-100 MG/KG AND ABOUT THE SAME INTRAPERITONEALLY). THE SYMPTOMS COME ON RAPIDLY AND CONSIST OF TWITCHING, GASPING, CONVULSIONS, AND COLLAPSE. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1824]**PEER REVIEWED**
  
• ... BETA-PROPIOLACTONE CAUSES LIVER NECROSIS AND RENAL TUBULAR DAMAGE WHEN GIVEN BY ITSELF INTRAVENOUSLY. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1824]**PEER REVIEWED**
  
• DROP OF PROPIOLACTONE APPLIED TO RABBIT'S EYE CAUSED IMMEDIATE PAIN, GRAYING OF THE CORNEA, & MIOSIS. ... OPACIFICATION WAS PERMANENT. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 766]**PEER REVIEWED**
  
• WEEKLY /ORAL/ DOSES OF 10 MG BETA-PROPIOLACTONE IN 0.5 ML TRICAPRYLIN GIVEN TO FEMALE SPRAGUE-DAWLEY RATS FOR 487 DAYS PRODUCED SQUAMOUS CELL CARCINOMAS OF FORESTOMACH IN 3/5 RATS. NO SUCH TUMORS ... IN 5 CONTROLS GIVEN WEEKLY DOSES OF 0.5 ML TRICAPRYLIN ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 262 (1974)]**PEER REVIEWED**
  
• WEEKLY PAINTING OF 0.3 ML OF 2.5% SOLN ... IN ACETONE FOR 52 WK TO 10 STOCK "S" MICE PRODUCED PAPILLOMAS (1ST ... @ 27 WK) IN 5/9 ... SURVIVING FOR 55 WK. TWO TUMORS UNDERWENT MALIGNANT CHANGE TO SQUAMOUS CELL CARCINOMAS BY 40 WK, & TUMORS IN 2 OTHER MICE ... REGARDED AS "PROBABLY MALIGNANT". [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 262 (1974)]**PEER REVIEWED**
  
• TWICE-WEEKLY SC INJECTIONS OF 20 UG ... IN 0.1 ML ARACHIS OIL INTO MICE OF TUCK NUMBER 1 STRAIN OVER 81 WK RESULTED IN DEVELOPMENT OF LOCAL TUMORS IN 10/20 ANIMALS SURVIVING APPEARANCE OF FIRST TUMOR @ 43 WK. CONTROLS GIVEN ARACHIS OIL OVER 72 WK EXHIBITED 1 MAMMARY ADENOMA AMONG 19 SURVIVORS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 263 (1974)]**PEER REVIEWED**
  
• FOUR GROUPS, EACH OF 30 MALE SWISS MICE ... WEEKLY /SKIN/ APPLICATIONS OF 100 MG BETA-PROPIOLACTONE AS 0.25, 0.8, 2.5, OR 5% SOLN IN ACETONE FOR LIFE. ... /90 CONTROLS/ ... RECEIVED ACETONE ... ALONE. PAPILLOMAS DEVELOPED ... IN 12, 15, 18 & 21 MICE IN EACH OF ... 4 GROUPS ... PAPILLOMAS DEVELOPED IN ... 11/90 /MICE IN THE CONTROL GROUP/. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 262 (1974)]**PEER REVIEWED**
  
• FOLLOWING WEEKLY SC INJECTIONS OF 0.73 MG ... IN 0.05 ML TRICAPRYLIN FOR 503 DAYS TO 30 FEMALE ICR/HA SWISS MICE, 3 ... DEVELOPED SQUAMOUS PAPILLOMAS @ INJECTION SITE, & 18 ... DEVELOPED MALIGNANT TUMORS (9 FIBROSARCOMAS, 3 ADENOCARCINOMAS & 6 SQUAMOUS CELL CARCINOMAS) @ INJECTION SITE. NO LOCAL TUMORS ... IN 110 CONTROLS ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 263 (1974)]**PEER REVIEWED**
  
• FOLLOWING TWICE-WEEKLY SC INJECTIONS ... 90 DAYS, TOTALLING 440 MG/KG BODY WT IN 6 MALES & 480 MG/KG ... IN 6 FEMALES /RATS/ DOSED IN 22 & 24 ML/KG BODY WT ARACHIS OIL, RESPECTIVELY, LOCAL SARCOMAS ... IN 5/6 MALES & IN 4/6 FEMALES ... LOCAL SARCOMAS /13/48 CONTROLS TWICE-WEEKLY INJECTIONS OF OIL TOTALLING 70-397 ML/KG, 97-300 DAYS/ ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 264 (1974)]**PEER REVIEWED**
  
• FOLLOWING TWICE-WEEKLY SC INJECTIONS OF 0.1 OR 1 MG ... IN ARACHIS OIL OR 2 MG IN WATER IN GROUPS OF 10 MALE WISTAR RATS FOR 34, 44 & 33 WK, RESPECTIVELY, INJECTION-SITE SARCOMAS ... IN 4/4, 10/10 & 2/4 ... @ 25-31 WK. ... OBSERVED UP TO 55 WK. NO LOCAL SARCOMAS ... IN 6 CONTROLS GIVEN REPEATED INJECTIONS OF 0.5 ML ARACHIS OIL ... 54 WK. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 264 (1974)]**PEER REVIEWED**
  
• SINGLE DOSE OF 100 MG/KG BODY WT ... IN OIL ... 35 MALE & 33 FEMALE B6AF1 MICE, 9-11 DAYS AFTER BIRTH, PRODUCED LYMPHOMAS IN 8.8% OF SUCKLING MALES & 20% OF SUCKLING FEMALES, COMPARED WITH 0% IN ... CONTROLS GIVEN OLIVE OIL ... . HEPATOMAS ... IN 22/34 MALES & 0/30 FEMALES COMPARED WITH 1/25 & 0/25 IN OLIVE OIL-TREATED CONTROLS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 265 (1974)]**PEER REVIEWED**
  
• BETA-PROPIOLACTONE INHIBITS DNA SYNTHESIS IN VIVO IN MOUSE SKIN ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 265 (1974)]**PEER REVIEWED**
  
• 24 HR AFTER SINGLE IV INJECTION OF 100 MG/KG INTO MALE & FEMALE RATS, BREAKS FOUND IN CHROMOSOMES OF METAPHASE MARROW CELLS LOW (8.8% VERSUS 5.0% IN CONTROLS). 55 CHROMOSOMES WERE PREFERENTIALLY DAMAGED. 200 MG/KG INCR INCIDENCE TO 11.3%. MULTIPLE (5) IV INJECTIONS (100 MG/KG EACH) GIVEN IN 6 WK PERIOD TO RATS INDUCED 2 NEOPLASMS (CHLORO-LEUKEMIA & MAMMARY FIBROADENOMA) AMONG 37 ANIMALS FOLLOWING 12-13 MO. NO SIGNIFCANT CHROMOSOMAL CHANGES OBSERVED. CARCINOGENIC & CLASTOGENIC EFFECTS OF BETA-PROPIOLACTONE IV ARE LOW IN RATS & NOT COMPARABLE IN MAGNITUDE TO THOSE OF BENZO(A)PYRENE. [REES ET AL; J ENVIRON PATHOL TOXICOL 2 (6): 1475-85 (1979)]**PEER REVIEWED**
  
• Using SHEL:CF1,SPF mice, 50 of each sex were treated with 0.2 ml of a freshly prepared 2% solution of beta-propiolactone in acetone twice per week from 6 weeks of age for 2 years. All dead and dying animals were autopsied as well as all animals still alive at 2 years. These animals, when compared to the acetone treated controls, had significantly depressed mean body weights and shortened mean survival times for both sexes. The neoplastic lesions (microscopically confirmed) included squamous cell carcinomas and dermal fibrosarcomas with metastases, (40/50 for males and 37/50 females). There was no evidence of skin tumors distant from application site, or of an increase in systemic neoplasms. There was a lower incidence of certain age-related tumors due to the shorter survival time. [Zakova N et al; Food Chem Toxicol 23: 1081-9 (1985)]**PEER REVIEWED**
  
• In rats, acute oral administration or ip injection of beta-propiolactone caused muscular spasms, respiratory difficulty, convulsions, and death. Acute iv injection caused kidney tubule and liver damage. Subcutaneous injection of beta-propiolactone in rats and mice produced cancer at the sites of administration. Single intraperitoneal injections in suckling mice produced lymphatic tumors and liver cancer. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. ]**PEER REVIEWED**
  
• beta-Propiolactone has been tested on preimplantation mouse embryos for possible genotoxic effects. Tests were performed at different stages of meiosis (late prophase I, diakinesis/metaphase I, anaphase I, telophase I/prophase II and metaphase II) by injecting females at various times after the induction of superovulation. Male and female derived chromosome complements from first-cleavage embryos were analysed before syngamy for cytogenetic abnormalities. A higher proportion of diploid oocytes, produced by the non-extrusion of the first or second polar body, was found after fertilization when the compound was administered immediately before metaphase I or II. No obvious effect was detected at any other time of beta-propiolactone exposure. Based on these results, several possible modes of action for beta-propiolactone are postulated. [Santal'o J et al; Mutat Res 189 (4): 407-16 (1987)]**PEER REVIEWED**
  
• The relationship between the carcinogenic activity of beta-propiolactone, methylmethane sulfonate, ethylchloroformate, dichloroacetyl chloride and propylene oxide which spanned six orders of magnitude was investigated. All products were given by inhalation to male Sprague-Dawley rats were found to induce nasal cancer with the exception of propylene oxide when given to rats for a period of 30 days in concentrations that were inversely proportional to the hydrolysis rates of the corresponding products. The incidence of nasal cancer was high in rats treated with 5 and 10 ppm beta-propiolactone and 50 ppm methylmethane sulfonate. A low incidence of nasal tumors was recorded in animals treated with 20 ppm beta-propiolactone for 5 days and in animals treated with the highest concentrations of dichloroacetyl chloride and ethylchloroformate (6 and 2 ppm, respectively). A dose dependent tumorigenic response was recorded for 10 and 5 ppm beta- propiolactone. A strong carcinogenic effect at the level of the nasal epithelium was obtained for animals treated with 5 and 10 ppm beta-propiolactone. Animals treated with propylene oxide did not show any tumors, but two rats had lung adenoma; controls had no such tumors. /It was/ concluded that a relationship exists between the carcinogenic action of selected reactive electrophilic agents and their rate of hydrolysis. [Sellakumar AR et al; J NCI 79 (2): 285-90 (1987)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LC50 RAT INHALATION 250 PPM/30 MIN [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 497]**PEER REVIEWED**
  
• LC50 RAT INHALATION 25 PPM/6 HR [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 497]**PEER REVIEWED**
  
• LD50 RAT YOUNG IV 225 + OR - 55 MG/KG, SCORED @ 24 HR [REES ET AL; J ENVIRON PATHOL TOXICOL 2 (6): 1475-85 (1979)]**PEER REVIEWED**
  
• LD50 GUINEA PIG SKIN APPLICATION < 5 ML/KG [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1834]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• THE LD50 BY SKIN APPLICATION IS LESS THAN 5 ML/KG IN THE GUINEA PIG, INDICATING CONSIDERABLE ABSORPTION. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1834]**PEER REVIEWED**
  
• 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 ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 265 (1974)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• BETA-PROPIOLACTONE CAN REACT WITH CHLORIDE ION TO FORM 3-CHLOROPROPIONIC ACID, ESPECIALLY IN BLOOD PLASMA. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 265 (1974)]**PEER REVIEWED**
  
• 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. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V4 265 (1974)]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.