Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 107-02-8 Toxicity Effects

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

Names (NTP)

  • Acrolein
  • 2-PROPENAL (9CI)
  • ACRALDEHYDE

Human Toxicity Excerpts

  • IT IRRITATES SKIN, MUCOUS MEMBRANES. VAPORS CAUSE LACRIMATION. WEAK SENSITIZER; INHALATION MAY CAUSE ASTHMATIC REACTION. [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 20]**PEER REVIEWED**
  • ... /INHALATION CAUSES/ IRRITATION OF NOSE & THROAT, TIGHTNESS OF CHEST, & SHORTNESS OF BREATH, NAUSEA & VOMITING. BRONCHOPULMONARY EFFECT IS VERY SEVERE; EVEN IF VICTIM RECOVERS FROM ACUTE EXPOSURE, THERE WILL BE PERMANENT RADIOLOGICAL & FUNCTIONAL DAMAGE. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 50]**PEER REVIEWED**
  • Exposure to 1 ppm (2.3 mg/cu m) acrolein vapor in air causes lacrimation & marked eye, nose & throat irritation within a period of 5 min. Acrolein is a severe pulmonary irritant & powerful lachrymogen at a concn of 3 ppm (7 mg/cu m) & greatly irritates the conjunctiva & mucous membranes of upper resp tract. At higher concn it ... causes injury to lung; Resp insufficiency may persist for at least 18 mo after exposure. A 10 min exposure to 350 mg/cu m was lethal. [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. V36 147 (1985)]**PEER REVIEWED**
  • ... Skin contact with liquid acrolein /has been described/ as causing irritation, erythema, & edema, & a splash in the eye as causing blepharoconjunctivitis, lid edema, fibrinous or purulent discharge, & corneal injury, which ... may be deep & long-lasting. ... Severe damage is possible as from alkali burns ... . [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 49]**PEER REVIEWED**
  • INHALATION OF AIR CONTAINING 10 PPM ACROLEIN MAY BE FATAL IN A FEW MIN. [National Research Council. Prudent Practices for Handling Hazardous Chemicals in Laboratories. Washington, DC: National Academy Press, 1981., p. 107]**PEER REVIEWED**
  • Acrolein ... is a well-established respiratory irritant. [USEPA; Subst Risk Notice, 8(e) p.232 (1978) EPA 560/11-80-008]**PEER REVIEWED**
  • Intense lacrimation & nasal irritation ordinarily give adequate warning of inhalation, but exposed patients should be observed for 24 hr for a slowly developing pulmonary edema. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-186]**PEER REVIEWED**
  • Acrolein increases airway resistance and tidal volume and decreases respiratory frequency. [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1676]**PEER REVIEWED**
  • Aldehydes increase airflow at concentrations below those that decrease respiratory frequency. /Aldehydes/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1676]**PEER REVIEWED**
  • The ability of the highly reactive aldehyde acrolein to affect growth, membrane integrity, differentiation, and thiol status and to cause DNA damage has been studied at serum and thiol free conditions using cultured human bronchial epithelial cells. Acrolein markedly decreases colony survival at 3 uM whereas about 10 fold higher concentrations are required to increase membrane permeability, measured as uptake of trypan blue dye. Acrolein at uM concentrations also causes epithelial cells to undergo squamous differentiation as indicated by decreased clonal growth rate, dose dependent increased formation of cross linked envelopes, and increased cell planar surface area. Acrolein causes a marked and dose dependent cellular depletion of total and specific free low molecular weight thiols as well as protein thiols. Exposure to acrolein did not cause oxidation of glutathione indicating that thiol depletion occurred by direct conjugation of reduced glutathione to acrolein without concomitant generation of active oxygen species. Furthermore, acrolein is genotoxic and causes both DNA single strand breaks and DNA protein cross-links in human bronchial epithelial cells. The results indicate that acrolein causes several cytopathic effects that relate to multistage carcinogenesis in the human bronchial epithelium. [Grafstrom RC et al; Cancer Res 48(7): 1717-21 (1988)]**PEER REVIEWED**
  • ... The purpose of this study was to: (a) compare the relative abilities of phosphoramide mustard and acrolein to induce cytogenetic damage and cytotoxicity in cultured human lymphocytes; (b) assess the efficacy of 2-mercaptoethanesulfonic acid to attenuate the cytogenetic damage and cytotoxicity induced by cyclophosphamide, acrolein, phosphoramide mustard, and diethyl-4'-hydroperoxycyclophosphamide, an activated acrolein generating compound; and (c) determine if concanavalin A stimulated T-lymphocytes, which differentiate into suppressor cells upon lectin activation, exhibit any heightened cytogenetic sensitivity compared to a variety of cultured mammalian cells during exposure to phosphoramide mustard or acrolein as reported by other investigators. Purified mononuclear leukocytes were stimulated with concanavalin A and exposed to cyclophosphamide (0.5-2.0 mM) without and exogenous activation system, acrolein (0.001-40.0 uM), phosphoramide mustard (0.0014-27.1 uM), or diethyl-4'-hydroperoxycyclophosphamide (0.1-100.0 uM) in the presence or absence of 2-mercaptoethansulfonic acid (1, 5, or 10 mM). All four compounds induced significant concentration related increases in the sister chromatid exchange frequency, but only phosphoramide mustard was clastogenic. On an induced sister chromatid exchange/uM basis, phosphoramide mustard was 130 and 193 times more potent than were diethyl-4'-hydroperoxycyclophosphamide and acrolein respectively. 2-Mercaptoethanesulfonic acid protected against the cytogenetic damage and cytotoxicity induced by the four compounds, but it was particularly effective against acrolein and diethyl-4'-hydroperoxycyclophosphamide by abolishing sister chromatid exchange induction completely. Sister chromatid exchanges and chromosome aberrations differed considerably in their induction kinetics in lymphocytes exposed to phosphoramide mustard, and these disparities suggested an uncoupling of the two phenomena. Although sister chromatid exchange induction was not consistently associated with cytotoxicity with the four agents, chromosome aberration induction coincided with an inhibition of cell cycle kinetics in phosphoramide mustard treated cells. The exceptionally high sister chromatid exchange frequency of up to 21 times baseline in cells exposed to phosphoramide mustard indicates that T-supressor lymphocytes stimulated with concanavalin A may be particularly sensitive to the DNA-damaging effects of phosphoramide mustard. Finally, these data suggest that the anticarcinogenicity of 2-mercaptoethanesulfonic acid correlates with its ability to attenuate cytogenetic damage and cytotoxicity induced by reactive cyclophosphamide metabolites. [Wilmer JL et al; Cancer Res 46(1): 203-10 (1986)]**PEER REVIEWED**
  • The possible use of the degree of inhibition of glutathione-S-transferase activity as a biological marker for determining exposure to chemicals such as acrolein, styrene oxide, propylene oxide, ethylene dibromide, and ethylene dichloride was explored. Glutathione-S-transferase activity was studied in vitro in human erythrocytes or as the purified enzyme. While glutathione-S-transferase activity was inhibited by all these compounds, acrolein was the most inhibitory. A dose dependent inhibition was evident in each case not only for inactivation of erythrocyte glutathione-S-transferase in situ but for inhibition of purified erythrocyte glutathione-S-transferase as well. Concentrations inhibiting 50% of the activity (I50) ranged from around 10(-3) to 10(-4) M. Some of the I50 values for the compounds used in this study were relatively high. It was stated that the concentrations of these chemicals in the blood of chronically exposed industrial workers may not reach these levels. It is suggested that further studies be made to evaluate the usefulness of inhibition of erythrocyte glutathione-S-transferase by these agents. [Ansari GAS et al; Toxicol Lett 37 (1): 57-62 (1987)]**PEER REVIEWED**
  • ... Is a severe pulmonary irritant and lacrimating agent with a piercing, disagreeable, acrid odor. It is ciliastatic and capable of causing direct tissue damage ... [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 982]**PEER REVIEWED**
  • ... Toxic effects of acrolein exposure include sensory irritation, enzymatic inhibition, elevated liver alkaline phosphatase, protein synthesis inhibition, weight loss, and death. Acrolein is a suspected carcinogen ... May possess immunotoxic potential... Can induce pulmonary edema. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 982]**PEER REVIEWED**
  • Severe irritation of the eyes, skin, mucous membranes; abnormal pulmonary function; delayed pulmonary edema, chronic respiratory disease. [Montgomery, J.H.; Agrochemicals Desk Reference 2nd ed. Lewis Publishers, Boca Raton, FL 1997, p. 3-4]**PEER REVIEWED**
  • Acrolein is a major contributor to the irritative quality of cigarette smoke ... [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1676]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • When swallowed, /acrolein/ produces severe gastrointestinal distress with pulmonary congestion & edema. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-186]**PEER REVIEWED**
  • SUBACUTE INHALATION TOXICITY OF ACROLEIN WAS EXAM IN 4 GROUPS OF 20 HAMSTERS, 12 RATS, & 4 RABBITS EACH EXPOSED 6 HR/DAY, 5 DAYS/WK FOR 13 WK AT CONCENTRATIONS OF 0, 0.4, 1.4, & 4.9 PPM. THE HIGHEST CONCENTRATION CAUSED DEATH IN RATS, OCULAR & NASAL IRRITATION, GROWTH DEPRESSION & METAPLASIA & HYPERPLASIA OF THE LINING OF THE RESP TRACT IN ALL SPECIES. THE LOWEST EXPOSURE LEVEL (0.4 PPM) PRODUCED NO TOXIC EFFECTS IN RABBITS OR HAMSTERS. [FERON VJ ET AL; TOXICOLOGY 9 (1-2): 47-58 (1978)]**PEER REVIEWED**
  • Groups of pure bred beagle dogs, squirrel monkeys (Saimiri sciurea), guinea pigs, & Sprague-Dawley derived rats were exposed to 0.7 & 3.7 ppm (1.6 & 8.5 mg/cu m) acrolein vapor for 8 hr/day on 5 days/wk for 6 consecutive weeks; squamous metaplasia & basal cell hyperplasia in the trachea were observed in dogs & monkeys, & squamous metaplasia of the lung in 7/9 monkeys. [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. V36 144 (1985)]**PEER REVIEWED**
  • ANIMAL EXPT INDICATE THAT ACROLEIN ... /DESTROYS/ RESPIRATORY TRACT MUCOUS MEMBRANES TO SUCH AN EXTENT THAT RESPIRATORY FUNCTION IS FULLY INHIBITED WITHIN 2-8 DAYS. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 50]**PEER REVIEWED**
  • ACROLEIN: ... AFFECTS ALKALINE PHOSPHATASE & TYROSINE-ALPHA-KETOGLUTARATE TRANSAMINASE ACTIVITIES IN RATS 5-12 HR AFTER INJECTION (3 MG/KG 20 HR BEFORE SACRIFICE) OR INHALATION. ... DATA SUGGESTED ... ACROLEIN STIMULATES PITUITARY-ADRENAL SYSTEM, LEADING TO HYPERSECRETION OF GLUCOCORTICOIDS ... /WHICH STIMULATE SYNTH OF ENZYME PROTEINS/. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 555]**PEER REVIEWED**
  • Acrolein has ... been reported to cause alterations in lung & liver biochemistry, incl significant reduction in microsomal mixed-function oxidase activity, in rats given 2 ip injections of 5 mg/kg body wt acrolein. A single ip injection of 3 mg/kg body wt acrolein to male Holtzman rats ... caused a prolongation of ... pentobarbital & hexobarbital sleeping time. In vitro studies ... total destruction of liver & lung microsomal the reduced form of nicotinamide-adenine dinucleotide phosphate cytochrome c reductase by 1.5 to 6 mM (0.084 to 3.3 mg/ml) acrolein, total loss of nonprotein sulfhydryl content & partial loss of protein sulfhydryl content in these organs /have been observed/. Depletion of sulfhydryl (21-63%) in the resp mucosa of male Fisher 344 rats after inhalation of 0.1 to 5 ppm (0.23 to 11.5 mg/cu m) acrolein vapor has ... been reported. [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. V36 144 (1985)]**PEER REVIEWED**
  • Two groups of 18 male & female Syrian golden hamsters, 6 wk old, were exposed to 0 or 4 ppm (0 or 9.2 mg/cu m) acrolein vapor (purity unspecified) for 7 hr/day on 5 days/wk for 52 weeks. Six animals per group were killed at 52 wk & the remainder at 81 wk. Survival was similar in treated & control animals. No tumor of resp tract was found in any 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. V36 142 (1985)]**PEER REVIEWED**
  • ... ACROLEIN INDUCED MUTATIONS IN DROSOPHILA MELANOGASTER (2.23% COMPARED TO 0.19% IN CONTROLS). ... RESULTS REPORTED ... INDICATE THAT ACROLEIN IS MUTAGENIC IN AN ESCHERICHIA COLI STRAIN DEFICIENT IN DNA POLYMERASE WITHOUT METABOLIC ACTIVATION. [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. V19 486 (1979)]**PEER REVIEWED**
  • IT WAS ... NEGATIVE IN BACK-MUTATION TEST (SPOT TEST) WITH 2 YEAST STRAINS, 1 SENSITIVE TO BASE SUBSTITUTION (S211) & 1 TO FRAMESHIFT MUTATION (S128). [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. V19 487 (1979)]**PEER REVIEWED**
  • ... /Acrolein/ added ... to an in vitro rat embryo culture at 5 ug/ml (equimolar to a teratogenic dose of cyclophosphamide) ... /produced/ no growth retardation or increase in defects. At twice the dose the cmpd was lethal. ... Growth retardation but no structural defects at 100 & 150 uM concentrations /were observed/ when rat embryos were exposed in vitro. ... [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 9]**PEER REVIEWED**
  • Acrolein (practical grade), stabilized with 0.2% hydroquinone ... & dissolved in 25 ul of 0.9% sodium chloride, was injected at doses of 0.001, 0.01, 0.1, 1.0 & 10 umol/egg (0.006 to 56 ug/egg) into ... air space or the yolk sac of 3-day-old White Leghorn SK 12 strain chick embryos. On day 14 of incubation, the embryos were examined for ... viability & malformations. Dose-related lethality was observed ... . No clear evidence of teratogenic potential was found. [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. V36 145 (1985)]**PEER REVIEWED**
  • Dose-related incr in embryolethality, but not in malformations (4/69 fetuses at high dose, compared to 2/121 in control group were malformed, but this difference was not significant), was found when groups of New Zealand white rabbits were injected iv on day 9 of gestation with 3, 4.5 or 6 mg/kg body wt acrolein (stabilized with 0.2% hydroquinone). The high dose killed 6/16 rabbits, compared to 0/13 controls. ... Direct injections into yolk sac of 10, 20 or 40 ul of a 0.84% soln of acrolein in physiological saline into day-9 embryos resulted in a dose-related incr in ... resorptions (63% in high-dose group compared to 21.2% in controls) & malformations (23.3% in high-dose group compared to 3% in controls). The defects in high-dose group incl hypoplastic & asymmetrical cervical & thoracic vertebrae, shortened extremities & a ventricular septal defect. [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. V36 145 (1985)]**PEER REVIEWED**
  • Signs of ... /toxicity in mallard ducks given oral LD50 doses of acrolein/. Regurgitation, reluctance to leave the swimming pond, slow responses, ataxia, geotaxia, imbalance, phonation, wing tremors, running & falling, asthenia, myasthenia, & withdrawal. Treatment levels as low as 3.33 mg/kg /orally/ produced /these/ signs /in mallards/. Signs appeared as soon as 10 min & persisted up to 36 days after treatment. Mortalities occurred as soon as 32 min; However, several mortalities occurred several days after treatment. /Sample purity: 92%/ [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984., p. 8]**PEER REVIEWED**
  • Repeated inhalation by chickens of 50 & 200 ppm (115 & 450 mg/cu m) acrolein vapor for 5 min/day for 1 to 27 days produced concentration-dependent decreases in the numbers of ciliated & goblet cells & mucous glands in the trachea, & lymphocytic inflammatory lesions in the tracheal mucosa. [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. V36 144 (1985)]**PEER REVIEWED**
  • Lesions occurring in the respiratory tract of mice after exposure to 10 sensory irritants, incl acrolein, at a concn which elicited a respiratory rate decr of 50% (RD50 of acrolein= 1.7 ppm), were compared with respect to type and severity. After exposure of mice for 6 hr/day for 5 days, the respiratory tract was examined for histopathological changes. All irritants produced lesions in the nasal cavity with a distinct anterior-posterior severity gradient. The lesions ranged from slight epithelial hypertrophy or hyperplasia to epithelial erosion, ulceration, and necrosis with variable inflammation of the subepithelial tissues. [Buckley LA et al; Toxicol Appl Pharmacol 74 (3): 417-29 (1984)]**PEER REVIEWED**
  • Groups of Fischer 344 rats were exposed to either filtered air, 0.4, 1.4, or 4.0 ppm acrolein for 62 days (6 hr/day, 5 days/wk). Mortality was observed only in the 4.0 ppm chamber, where 32 of 57 male rats died, but none of the 8 exposed females died. The lungs of the 4.0 ppm group were heavier than those of the larger control animals. Relative to controls, there was a 20% incr in total dry lung wt while the percent dry wt decr 1.5% in the high dose group. Lung connective tissue content was incr as a result of subchronic acrolein exposure. The amount of elastin per unit dry wt was 173% of control values in the animals exposed to 4.0 ppm acrolein. Collagen levels were elevated in both the 1.4 and 4.0 ppm groups, 113 and 137%, respectively, of control values. Histologically, the 4.0 ppm animals demonstrated bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema. Exposure related lesions were observed in only 3 of the 31 rats examined from the 1.4 ppm chamber and in none of the animals exposed to 0.4 ppm acrolein. [Kutzman RS et al; Toxicology 34 (2): 139-51 (1985)]**PEER REVIEWED**
  • Continuous 90 day exposure at 0.22 ppm caused inflammation in liver, lung, kidneys, and heart of monkeys, guinea pigs, and dogs. Exposure to 1.8 ppm caused squamous cell metaplasia and basal cell hyperplasia of the trachea in monkeys. [Lyon JP et al; Toxicol Appl Pharmacol 17 (3): 726-32 (1970) as cited in USEPA; Chemical Hazard Information Profile: Acrolein p.11 (1980) EPA 560/11-80-011]**PEER REVIEWED**
  • Inhibition of cell multiplication starts at 0.44 mg/l in protozoa (Uronema parduczi Chatton-Lwoff); At 0.21 mg/l in bacteria (Pseudomonas putida); And at 0.04 mg/l in algae (Microcystis aeruginosa). The lowest observed avoidance concn in insects was above 0.1 mg/l for mayfly nymphs (Ephemerella walkeri); 0.1 mg/l for rainbow trout (Salmo gairdneri). The incipient Median Threshold Limit (TLm) for fathead minnow was 84 ug/l in a flow through bioassay; The maximum acceptable toxicant concentration was 11.4 ug/l. [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 158]**PEER REVIEWED**
  • The pathologic and immunotoxic effects of acrolein were studied using 4 groups of male Sprague-Dawley rats. Rats were exposed to 0, 0.17, 1.07, or 2.98 ppm of acrolein for 6 hr/day, 5 days/wk for 3 wk. From each treatment group (N= 40), 12 rats were used for spleen and lung associated lymph node blastogenesis using the T-cell mitogen, phytohemaglutinin P, and the B-cell mitogen, Salmonella typhimurium. Ten additional rats received an intratracheal challenge of sheep erythrocytes after which lung associated lymph node cells were assayed for plaque formation. The remaining 18 rats were evaluated for host resistance to Listeria monocytogenes. Histological examination of nasal turbinates of the rats exposed to 2.98 ppm revealed exfoliation, erosion and necrosis of respiratory epithelium, and squamous metaplasia. The lung did not demonstrate significant histopathology. A decrease in body weight gain was observed only for rats exposed to 2.98 ppm. In vitro pulmonary immune response as determined by the hemolytic plaque assay, and lymphocyte response to phytohemaglutinin P and Salmonella typhimurium were not affected by any of the acrolein exposures. Acrolein exposure did not affect resistance to Listeria. [Leach CL et al; Toxicol Lett 39 (2-3): 189-98 (1987)]**PEER REVIEWED**
  • Acrolein is formed when fat is overheated and has the typical smell of "burning fat". ... A poodle, shut up for half an hour in a small unventilated kitchen with a chip pan of boiling fat, was seen next day to have swollen tonsils, blood from the nostrils and a temperature of 39.4 deg C. 24 hr later there was slight dyspnea, the pulse was faint, the tongue cyanosed and the eyes congested and discharging pus. It collapsed and died soon afterwards. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 81]**PEER REVIEWED**
  • Embryologic and teratogenic effects of acrolein over a narrow concentration range in cultured rat embryos were assessed. On the tenth day of gestation, pregnant Sprague-Dawley rats were etherized and the uterus was removed. Embryos were dissected free of maternal tissue and cultured in either a serum or serum free medium; dissolved acrolein was added. After 42 hours of culture time, embryos were examined for viability and morphology. For embryos cultured in serum, 100% mortality was observed at 140 uM acrolein. Significance in number of embryo deaths was reached at 120 uM; median effective concentration (EC50) for embryo deaths was 115 uM. Significant increases in embryo malformations were detected with doses as low as 80 uM; the EC50 for malformations was 137 uM. Malformations of the brain, heart, somites, facial area, and forelimb buds occurred most frequently. Doses of 80 uM acrolein and greater produced significant decreases in embryo growth and development. Yolk sac diameter, crown rump length, head length, number of somites, protein content, and total morphological score decreased significantly at 120 uM compared to controls. In embryos cultured in a serum free medium, acrolein was totally embryolethal at 20 uM; EC50 for acrolein induced mortality was 8.3 uM. Malformations occurred in 67, 80, and 100% of the embryos in the 5, 10, and 15 uM dose groups, respectively. The EC50 for acrolein induced malformations was 2.8 uM. Malformations included reduced left forelimb bud, blebs of the maxillary, nasal or optic region, protrusions of the body, hindlimbs or head area, cardiac malformations, head abnormalities, incomplete turning, and irregular somites. At 5 and 10 uM acrolein, there was a significant decrease in yolk sac diameter, crown rump and head length, somite number, and morphological score. [Slott VL, Hales BF; Teratol 34 (2): 155-63 (1986)]**PEER REVIEWED**
  • The mutagenic potential of acrolein has been studied with a wide range of in vitro and in vivo genetic toxicity assays. The data often have been conflicting, especially with the Ames assay. This study was undertaken to assess the mutagenic potential of acrolein using the CHO/HGPRT assay, both with and without metabolic activation. This assay system was chosen because it provides eukaryotic DNA as the target and is capable of detecting a range of mutational events. Because of its considerable toxicity, acrolein was tested over a very narrow dose range of 0.2-2 nl/ml without exogenous activation and 0.5-8 nl/ml with rat S-9 activation. Multiple assays were performed under both conditions. The results indicated that while acrolein was clearly very cytotoxic, it did not induce a significant mutagenic response in the presence or absence of metabolic activation. [Parent RA et al; J Appl Toxicol 11 (2): 91-6 (1991)]**PEER REVIEWED**
  • The effect of systemic administration of acrolein, a constituent of cigarette smoke and a metabolite of cyclophosphamide, on the urinary bladder epithelium of 8 week old male F344 rats was investigated. The animals were injected with single dose of acrolein at 25 mg/kg by intragastric intubation or ip injection. The 25 mg/kg dose level proved extremely toxic. The mortality rate was 42% for both groups. Rats administered acrolein intragastrically had severe erosive hemorrhagic gastritis. Rats treated ip had severe localized peritonitis. Surviving animals were sacrificed at 24 or 48 hours after administration and shown to have focal simple hyperplasia of the urinary bladder after 2 days. In a second set of studies groups of 10 week old male F344 rats were given acrolein via intraperitoneal injection at doses of 0.5, 1, 2, 4, or 6 mg/kg divided into up to three doses. Rats were injected with tritiated thymidine 7 days after the first treatment, and bladders were processed for autoradiographic evaluation. Sufficient acrolein reached the urinary bladder to induce a proliferative response following ip administration as determined by autoradiography. [Sakata T et al; J Environ Path Toxicol Oncology 9 (2): 159-70 (1989)]**PEER REVIEWED**
  • The carcinogenic effects of chronic exposure to acrolein, acrolein diethylacetal, acrolein oxime, and allyl alcohol were tested in rats and hamsters. Each compound was administered at various doses up to near the maximum tolerated dose in drinking water to groups of 20 male or female F344 rats for up to 2 years. Acrolein was not given to hamsters because it proved to be too toxic for administration in an adequate dose. The other compounds were given at doses of 2 mg/wk by gavage to male Syrian golden hamsters. One group of each species was maintained as untreated controls, and a group of rats was given acetaldoxine as a control for possible carcinogenicity of oximes. Animals that survived the treatments were allowed to die naturally or were killed when moribund, and they were necropsied and lesions examined histologically. There was little or no effect of any of the treatments on mortality of the rats compared with the controls. The only suggestion of a possible carcinogenic effect was an unusually high incidence of five adenomas and two hyperplastic nodules of the adrenal cortex in the group of 20 rats treated with the highest concentration (625 ppm) of acrolein. The incidence of common neoplasms was very similar to the incidence in the controls. Three hamsters had adenomas of the pancreatic ducts, which were not seen in untreated hamsters. Approximately half of the hamsters treated with acrolein diethylacetal or acrolein oxime that survived early toxicity died with neoplasms. It was concluded that, considering the relatively small size of the test groups, it is not certain that acrolein and its derivatives are not carcinogenic, although it appears that any carcinogenic effect of these compounds will be weak. [Lijinsky W, Reuber MD; Toxicol Ind Health 3 (3): 337-45 (1987)]**PEER REVIEWED**
  • Acrolein has been shown to form cyclic deoxyguanosine adducts when it reacts with DNA in vitro. In this study, a recently developed immunoassay for these adducts to study their formation in DNA from Salmonella typhimurium exposed to acrolein /was utilized/. Acrolein deoxyguanosine adducts were formed in a dose dependent fashion in Salmonella tester strains TA100 and TA104, reaching levels as high as 5 umol adduct/mol deoxyguanosine. Using the liquid preincubation assay, acrolein induced mutations were also found in strains TA100 and TA104. The correlation between acrolein deoxyguanosine adduct concentration and acrolein induced mutations in TA100, which contains GC base pairs at the site of reversion, suggests that the acrolein deoxyguanosine adduct is a promutagenic lesion. That mutations are also seen in TA104 which contains AT base pairs at the site of reversion suggest that adducts of bases other than deoxyguanosine may also be important in the mutagenic activity of acrolein. [Foiles PG et al; Carcinogenesis 10 (1): 87-90 (1989)]**PEER REVIEWED**
  • The effects of acrolein were studied on the chick embryos of 48 and 72 hr of incubation. Acrolein was dissolved in physiological saline and injected into the air sacs of the eggs at doses ranging from 0.001 to 0.1 mg per egg. The controls received an equal amount of saline only (0.1 ml per egg). All the embryos including controls were examined at day 13. In all, 600 eggs were utilized for this investigation. At 48 hr incubation, the percentage survival ranged from 80 to 0 as the dosage of acrolein was increased. Embryonic mortality following 72 hr incubation did not increase significantly at any dose level. Gross malformations such as short and twisted limbs, everted viscera, microphthalmia, short and twisted neck, and hemorrhage over the body were observed. The frequency and the type of gross abnormalities did not vary much in the 48 or 72 hr treated groups. The incidence of malformation in the controls was low. The results of this study indicate that acrolein is embryotoxic at higher doses and moderately teratogenic to chick embryogenesis. [Chibber G, Gilani SH; Environ Res 39 (1): 44-9 (1986)]**PEER REVIEWED**
  • An animal model was used to study the effects of early administration of intramuscular corticosteroids on mortality and lung histopathology induced by a component of smoke. Thirty-six rabbits (mean weight, 2.7 kg) were exposed to acrolein vapor for 15 min; 30 min later the animals were divided into 3 treatment groups. One group received saline placebo intramuscularly at 12 hr intervals, a second group was treated intramuscularly with 100 mg methylprednisolone at 12 hr intervals, and a third group was treated with a single 100 mg dose of methylprednisolone followed by doses of saline at 12 hr intervals. The animals were studied for a 72 hr period. There was a significantly lower mortality in the 2 steroid-treated groups than in the nontreated group. A scoring system was developed for evaluating observed histologic changes in the lung. No correlation was seen between survival and histologic score or between score and treatment. High scores for particular histologic features did not explain mortality nor did they predominate in untreated animals; vascular congestion was found to be greater in the steroid-treated group. The beneficial effects of steroids in reducing mortality after inhalation of a common smoke constituent was not associated with any evidence of attenuation of lung damage. [Beeley JM et al; Am Rev Respir Dis 133 (2): 191-6 (1986)]**PEER REVIEWED**
  • ... Acrolein at concn of 1x10-4 to 1x10-10 M was phytotoxic to tobacco tissue cultures. [Kearney, P.C., and D. D. Kaufman (eds.) Herbicides: Chemistry, Degredation and Mode of Action. Volumes 1 and 2. 2nd ed. New York: Marcel Dekker, Inc., 1975., p. 817]**PEER REVIEWED**
  • Acrolein is a direct-acting mutagen in prokaryotic and eukaryotic systems... [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 3]**PEER REVIEWED**

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Human Toxicity Values

  • TCLo Man inhalation 1 ppm [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**

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Non-Human Toxicity Values

  • LD50 Rat oral 46 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**
  • LD50 Rat sc 50 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**
  • LD50 Mouse sc 30 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**
  • LD50 Rabbit oral 7 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**
  • LD50 Rabbit skin 562 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 13]**PEER REVIEWED**
  • LC50 Sprague-Dawley rat (combined sexes) 26 ppm/1 hr [Ballantyne B et al; Hum Toxicol 8(3): 229-35 (1989)]**PEER REVIEWED**
  • LC50 Sprague-Dawley rat (combined sexes) 8.3 ppm/4 hr [Ballantyne B et al; Hum Toxicol 8(3): 229-35 (1989)]**PEER REVIEWED**
  • LD50 Cat inhalation 11 ppm/3-10 hr [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 308]**PEER REVIEWED**
  • LD50 Cat inhalation 18-92 ppm/3-4 hr [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 308]**PEER REVIEWED**
  • LD50 Cat inhalation 690-1150 ppm/2 hr [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 308]**PEER REVIEWED**
  • LD50 Rat inhalation 130 ppm/30 min [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 310]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • IT CAN ... BE ABSORBED PERCUTANEOUSLY ... [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-186]**PEER REVIEWED**
  • In goat and hen, no acrolein was detected in tissues or excreta, or in goat milk or hen eggs following administration of high doses. [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium, 11 th ed., British Crop Protection Council, Surrey, England 1997, p. 19]**PEER REVIEWED**

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Metabolism/Metabolites

  • ... The excretion of acrolein metabolites in urine of adult female Wistar rats /was observed/ after a single oral admin of 10 mg/kg body wt acrolein in corn oil. S-carboxyethyl-N-acetylcysteine (S-carboxyethylmercapturic acid) & S-(propionic acid methyl ester) mercapturic acid were reported to be the major metabolites. [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. V36 146 (1985)]**PEER REVIEWED**
  • MALE CFE ALBINO RATS METABOLIZED 10.5% OF A SC DOSE OF 1 ML OF A 1% SOLN OF ACROLEIN IN ARACHIS OIL TO N-ACETYL-S-(3-HYDROXYPROPYL)-L-CYSTEINE, WHICH WAS ISOLATED FROM THE URINE. [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. V36 146 (1985)]**PEER REVIEWED**
  • Acrolein is metabolized in vitro by liver & lung microsomes to glycidaldehyde. [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. V36 142 (1985)]**PEER REVIEWED**
  • Acrolein is a suspected carcinogen because of its 2,3-epoxy metabolite ... [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 982]**PEER REVIEWED**

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TSCA Test Submissions

  • Acrolein (CAS # 107-02-8) was evaluated for acute oral toxicity in groups of 10 male CD-1 mice administered single doses of 0.0, 11.0, 13.2, 15.84, and 19.0 mg/kg by oral gavage (10 ml/kg in deionized water). Treatment was associated with lethargy, squinting of eyes, rough coats, hunching, and piloerection. Several survivors of 14-day post-gavage observation also had blackening, necrosis, and breakage of nails. Reduced weight gains (-11.6% - 28.6%) persisted at all dose levels to 14th-day end of study. All treatment-related mortality (22/50) occurred within 2 days of dosing and was consistent with an oral LD50 (by Karber probit analysis) in male mice of 13.9 (95% confidence limit, 12.8 - 15.1) mg/kg. Upon necropsy, the study lethalities exhibited reddened lungs and hemorrhagic stomachs and intestines. Other than 1 male of a 13.2 mg/kg dose with reddened lungs, the study survivors showed minimal pathological changes on terminal sacrifice.[SRI Intl; Acute Oral LD50 of Acrolein in Male Mice; BSC Project Number 11479; 12/30/82; EPA Document No. 88-920000355; Fiche No. OTS0534806]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for mutagenicity in the Salmonella Liquid Suspension Mutant Fraction Assay. Relative to negative control, concentrations of 1, 3, 10, 20, and 40 ug/ml induced no concentration-related mutagenicity (increased mutant fraction, or number of mutants/viable cell) in duplicate assays with 5 Salmonella strains, either with or without rat liver metabolic activation.[SRI Intl; Salmonella Liquid Suspension Mutant Fraction Assay, BSC Project Number 10258; 12/30/80; EPA Document No. 88-920000355; Fiche No. OTS0534806]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for acute oral toxicity in groups of 10 nonfasted male rats albino administered doses of 0, 31.6, 39.8, 50, and 63 mg/kg by oral gavage. Based on a method of Thompson, treatment was associated with an oral LD50 for male rats of 46 (39 - 56) mg/kg. Doses of 46 mg/kg administered to rats in a 0.05% aqueous dilution (instead of 0.5%) killed only 1/10 rats in a subsequent trial. Study lethalities had congested and mottled livers, hemorrhagic peritoneums, and hemorrhagic and injected stomachs.[Union Carbide Chem & Plas Co; Acute and Subacute Oral Toxicity of Acrolein; 11/08/49; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107/02-8) was evaluated for acute oral toxicity in groups of 5 male New Zealand albino rabbits fed single doses of 3.16, 6.3, 12.6, and 25.2 mg/kg (1% in water). Treatment was associated with mortality consistent with an oral LD50 in rabbits of 7.1 (3.1 to 16.7) mg/kg. No further information was provided. Study lethalities had pale and mottled livers, injected, congested and hemorrhagic stomachs, and pale and friable kidneys.[Union Carbide Chem & Plas Co; Acute and Subacute Oral Toxicity of Acrolein; 11/08/49; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for repeated dose oral toxicity in groups of 10 Sherman strain rats exposed to concentrations of 0, 1, and 10 ppm in the drinking water (approximate doses of 0, 0.17, and 1.5 mg/kg/day) for 30 days. Treatment was associated with decreased fluid ingestion, reduced mean weight gain in surviving rats, and increased relative kidney weights (10 ppm), with no increased toxic mortality or pathology. Histopathological evaluation of small intestine, kidney, and liver revealed no treatment-related changes. Two day trial with exposures to 0, 30, 100, 300, and 1000 ppm in the drinking water versus fluid imbibed in groups of 10 rats revealed that reduced fluid intake is significantly related to acrolein concentrations. [Union Carbide Chem & Plas Co; Acute and Subacute Oral Toxicity of Acrolein; 11/08/49; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for acute inhalation toxicity in Sprague-Dawley rats (5/sex/group) administered single dynamically-generated exposures to mean vapor concentrations of 0, 14, 22, 24, 31, and 81 ppm for 1 hour or 0, 4.8, 7.0, 9.1, and 12.1 ppm for 4 hours. Exposures were associated with clinical signs of toxicity at all exposure levels, including lacrimation, periocular, perinasal, and perioral wetness and encrustation, unkempt fur, labored breathing, lethargy, and stomach distention. Body weights or bodyweight gains were universally depressed during post-exposure Week 1 and, during Week 2, in 22 and 24 ppm groups of 1-hour exposures and 12.1, 9.1, and 7.0 ppm groups of 4-hour exposures. Treatment-related mortality occurred primarily from Day 1 through Day 6 and, based on a Thompson moving average method, was consistent with all-sex inhalation 1-hour and 4-hour LC50s (with 95% confidence limits), respectively, of 26 (24-27) ppm and 8.3 (7.0-9.9) ppm. Upon necropsy, gross lesions were identified only in study lethalities and included perinasal and perioral encrustation, mottled discoloration of lungs and liver, clear fluid-filled trachea and thoracic cavity, reddened submandibular lymph nodes, gas-filled stomach and intestines, and opaque or cloudy eyes.[Union Carbide Chem & Plas Co; Acute Inhalation Toxicity of Acrolein Vapor by One and Four Hour Exposures; 02/02/87; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for mutagenicity in the Chinese Hamster Ovary (CHO) Mutation test. Selected based on preliminary cytotoxicity tests, concentrations of 0.0 (ethanol solvent control), 0.2, 0.5, 1.0, 2.0, and 4.0 x 10(-5)% (v/v), both in the presence and the absence of S9 metabolic activation, produced statistically significant (Student's t-test, p < 0.01) mutagenicity (mutants/10(6) cells/viable cells). Significantly increased CHO mutagenicity, ranging from 56.2 (2.0 x 10(-5)%) to 200.00 (0.5 x 10(-5)%) mutants/10(6) viable cells without metabolic activation and 18.6 (0.2 x 10(-5)%) to 190.9 (2.0 x 10(-5)% mutants/10(6) viable cells, did not correlate to concentrations, however, and positive results were not obtained in either Sister Chromatid Exchange or Unscheduled DNA Synthesis tests. While acrolein mutagenicity was statistically indicated in the CHO Mutation test, a dose-response relationship was not demonstrated.[Union Carbide Chem & Plas Co; Acrolein (inhibitor-free) In Vitro Mutagenesis Studies -3-Test Battery; 06/29/81; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for clastogenicity in the Sister Chromatid Exchange (SCE) test. Selected based on preliminary cytotoxicity tests, 6 staggered acrolein concentrations between 0.0% (negative culture, ethanol solvent, and positive controls) and 3.0 x 10(-5)% (v/v) without S9 metabolic activation and between 0.0% and 10.0 x 10(-5)% with metabolic activation, respectively, induced no statistically significant (Student's t-test) dose-related increments in Chinese Hamster ovary (CHO) cell SCE frequency (SCE/cell, mean SCE/chromosome of 20 cells/culture) after 5-hour and 2-hour incubations. Statistically significant increases in SCE were observed at doses of 0.8 x 10(- 5)% (p < 0.05) and 5.0 x 10(-5)% (p < 0.01), respectively, in cultures without and with S9 metabolic activation; however, based on a lack of a dose-response relationship, study authors concluded that acrolein does not induce SCE-derived mutagenicity in vitro.[Union Carbide Chem & Plas Co; Acrolein (inhibitor-free) In Vitro Mutagenesis Studies -3-Test Battery; 06/29/81; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for mutagenicity in an Unscheduled DNA Synthesis (UDS) Assay with rat hepatocytes. Selected based on preliminary cytotoxicity tests, 12 acrolein concentrations from 0.00 (ethanol solvent control, 2 positive controls) to 30.0 x 10(-5)% added to rat liver cells cultured in the presence of 3H-thymidine and hydroxyurea for 2 hours were associated a statistically significant (p < 0.05, Duncan's Multiple Range Analysis) increase in nuclear-bound label per 10(6) viable hepatocytes at a dose of 0.6 x 10(5)%. Further, both nuclear-bound label and DNA-bound label from DNA precipitated per 10(6) viable hepatocytes/dose exposed at toxicity levels allowing at least 50% survival were consistently numerically greater than values obtained from historical and solvent controls. A lack of dose-related statistically significant increases in either nuclear- and/or DNA-bound label led authors to conclude this study was inconclusive regarding acrolein-induced unscheduled DNA synthesis in rat hepatocytes in vitro.[Union Carbide Chem & Plas Co; Acrolein (inhibitor-free) In Vitro Mutagenesis Studies -3-Test Battery; 06/29/81; EPA Document No. 86-920000742; Fiche No. OTS0535072]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) with several other chemicals was evaluated for sensory (upper airway) irritation in a modified Alarie Mouse Sensory Irritation Test. Four each male Swiss Albino CD-1 mice were administered dynamic head only exposures to vapor concentrations of 0.0 to 8.7 ppm in air over 10 minutes to characterize type response as either immediate and persisting, immediate with accommodation (ameliorated with time), or immediate and progressive during exposures. Concentrations below 2 ppm produced a linear response (breaths/minute/animal) curve, while maximal responses (decreased respiration rate) occurred after 10 minutes' exposure, thus indicating a progressive response to exposure without physiological accommodation or compensation; an RD50 (linear regression determination of that concentration causing 50% reduction of respiratory rate) was 1.27 ppm (R=0.89; 95% CL 1.07-1.52 ppm). Response data were not provided.[E I Dupont De Nemours & Co Inc; Mouse Sensory Irritation Method Verification, Haskell Laboratory Report No. 209-80; 04/19/80; EPA Document No. 86-870001049; Fiche No. OTS0514951]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for acute inhalation toxicity in groups of 5 each male and female Syrian golden hamsters administered low dynamic whole-body exposures to vapor concentrations of 11.2, 23.3, 30.0, and 30.4 ppm in air for 4 hours. During all exposures, the animals kept their eyes shut and exhibited lachrymation, dyspnea, nasal secretion, and, late in the exposure, inflating of cheek pouches. Treatment was also associated with significantly dose-related mortality between 24 hours and 12 days post exposure, consistent with an LC50 (by a method of Litchfield and Wilcoxon) of 25.4 ppm (58 mg/m3 air) with a calculated LCt50 of 101 ppm-hour.[Dow Chem Co; Acute Inhalation Toxicity of Acrolein in Hamsters (Final Report); 08/01/71; EPA Document No. 88-920001468S; Fiche No. OTS0536144]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for acute inhalation toxicity in male Sprague-Dawley Spartan rats (7/exposure group) administered single dynamically generated whole-body exposures to average analytic vapor concentrations of 14.5, 41.5, 93.5, and 251 ppm for up to 30 minutes. During exposures and a 15-minute post-exposure venting period, the animals were observed continuously for behavioral anomalies and sensory irritation, including altered reflexes, eye and/or nasal irritation, and or respiratory irregularities. Treatment was associated with clinical signs of toxicity including teary and squinted eyes, nasal discharge, labored breathing, gasping, and prostration at all levels of exposure; treatment also dampened righting, blink, and pain reflexes at exposures of 41.5 ppm or greater. Bodyweights were low normal based on comparison with historical controls, and mortality was consistent with a 30-minute LC50 of 60 ppm. Additionally, severity, time to onset, progression, and duration of the toxic response were each correlated with dose. Immediate necropsy of study lethalities upon their discovery revealed treatment-related gross pathology including congestion of nasal turbinates (41.5 ppm), failure of lungs to collapse on incision with a dark mottled and congested appearance of apical and cardiac regions of the lungs (41.5 ppm, 1/7), accumulations of exudate around nose and mouth (93.5 ppm, 7/7; 251 ppm, 7/7), mucopurulent or mucohemorrhagic rhinitis (93.5 ppm, 7/7; 251 ppm, 7/7), pulmonary congestion and hemorrhage (93.5 ppm, 7/7; 251 ppm, 7/7), gaseous distention of the stomach (93.5 ppm, 7/7; 251 ppm, 7/7), congestion of liver and kidneys (93.5 ppm, 7/7; 251 ppm, 1/7), pulmonary edema (251 ppm), and hydrothorax (251 ppm). None of 7/7 terminally sacrificed survivors of a 14.5 ppm exposure exhibited any treatment-related gross pathology, while survivors of 41.5 ppm exposures had catarrhal rhinitis on Day 15 terminal necropsy.[Dow Chem Co; A Study of the Inhalation Toxicity of Acrolein (Final Report); 01/12/76; EPA Document No. 88-920001478S; Fiche No. OTS0536154]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for subchronic inhalation toxicity in Syrian golden hamsters (10/sex/group) administered dynamic whole-body exposures to vapor concentrations of 0, 0.4, 1.4, and 4.9 ppm in air for 6 hours/day, 5 days/week over 13 weeks. Treatment with high and mid-level exposures was associated with clinical signs of toxicity, including restlessness, insomnia, eye irritation, nasal discharge, salivation, and statistically significant (p < 0.05, Student's t-test) and persistent reductions in bodyweight (4.9 ppm). Treatment-related mortality consisted of a solitary 4.9 ppm male killed in moribund condition in Week 12. Elevations in hemoglobin and hematocrit values, as well as erythrocyte and lymphocyte counts, were statistically significant (p < 0.05, Wilcoxon analysis) in 4.9 ppm females, while the high-exposure female neutrophil count was significantly depressed. Serum biochemistry values appeared unaffected in both males and females, as urinalyses were unremarkable relative to controls. Increased relative kidney, brain, gonad, and lung weights reached statistical significance in high dose animals of both sexes, while relative heart weights were significantly increased in 4.9 ppm females only. Examination of major organs on terminal necropsy (on the day following a final exposure) revealed no gross changes attributable to treatment, other than subcutaneous edema, ascites, epididymal abscesses, gastric ulcer, and pale kidneys and liver of the high-exposure male lethality. Histological evaluation of head, larynx, trachea, and pulmonary lobes of each animal revealed cellular changes of the nasal cavity, larynx, and trachea, including moderate rhinitis, necrosis, and hyper- and metaplasia of respiratory and olfactory epithelium, primarily in the 4.9 ppm group. Females of 4.9 ppm exposures also exhibited slight hyperplastic appearance of the vocal cords and surrounding tissues and near universal focal hyper- and metaplasia of the tracheal epithelium. A few males also showed tracheal hyper- and metaplasia. No histopathological changes attributable to acrolein exposure were identified in the bronchi or lungs, and, among the 4.9 ppm males and females examined, no other organ systems showed histological manifestation of acrolein vapor toxicity. Only the premature high exposure study lethality exhibited amyloidosis of the kidneys, liver, and adrenals, testicular atrophy, as well as inflammatory changes in many organs.[Dow Chem Co; Sub-chronic (90-Day) Inhalation Toxicity Study with Acrolein in Hamsters; 10/01/74; EPA Document No. 86-920000855S; Fiche No. OTS0535413]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for mutagenicity in the Reverse Mutation Test using 5 strains of Salmonella typhimurium cultured both in the presence and the absence of mammalian metabolic activation with acrolein concentrations of 0 (negative and positive controls), 0.001, 0.01, 0.1, and 1.0 ug/plate (a dose of 10 ug was toxic in preliminary screening tests) for 48 hours. None of the 5 Salmonella typhimurium strains produced sufficiently increased revertants/plate over negative control to indicate a acrolein mutagenicity and no dose-related response was demonstrated.[Goodyear Tire & Rubber Co; Mutagenicity Evaluation of Acrolein; 10/26/79; EPA Document No. 86-920001016; Fiche No. OTS0533562]**UNREVIEWED**
  • Acrolein (CAS # 107-02-8) was evaluated for mutagenicity in a quantitative overlay assay using 5 strains of Salmonella typhimurium cultured both in the presence and the absence of Aroclor-induced rat liver microsomal enzyme with acrolein concentrations of 0 (solvent and positive controls), 1, 3, 5, 10, 20, 30, and 50 ug/plate for 48 hours. None of the 5 Salmonella typhimurium strains produced sufficiently increased revertants/plate over negative control, either with or without mammalian metabolic activation, to indicate a acrolein mutagenicity. No toxicity was observed under these test conditions, although preliminary screening had shown toxicity associated with exposures to 25 to 39 ug/plate. [Monsanto Co; Mutagenicity Plate Assay - Acrolein (Final Report); 06/13/77; EPA Document No. 86-920000169; Fiche No. OTS0534374]**UNREVIEWED**

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Footnotes

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

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