Acrolein, stabilized appears as a colorless to yellow volatile liquid with a disagreeable choking odor. Flash point below 0°F. Initially irritating to the eyes and mucous membranes. Very toxic by inhalation. Less dense than water (7.0 lb / gal). Vapors heavier than air. Used to make other chemicals, plastics, and as a herbicide. Rate of onset: Immediate Persistence: Minutes to hour Odor threshold: 1 ppm Source/use/other hazard: Herbicide; tox and corrosive fumes.
颜色/状态：
Colorless or yellowish liquid
气味：
Extremely sharp; extremely acrid, pungent, burnt sweet; hot fat
Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and their molar sum (sigmaAcrolein) with diabetes using data from investigated 2027 adults who participated in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA-IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-beta, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and sigmaAcrolein with evidence of a dose-response relationship (p<0.05). The highest 3rd and 4th quartiles of CEMA compared to the lowest quartile were significantly associated with higher HOMA-IR, HOMA-beta and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and sigmaAcrolein were positively and significantly associated with HOMA-IR, HOMA-beta and fasting insulin. ...
The carcinogenic potential of acrolein per se has not been adequately determined. However, glycidaldehyde, a metabolite of acrolein, is considered to be carcinogenic.
Acrolein is oxidized to acrylic acid by aldehyde dehydrogenase. Acrolein can also be converted to glycidaldehyde by microsomal enzymes, and the latter compound was hydrolyzed to glyceraldehyde by epoxide hydrolase. Acrolein was also conjugated with reduced glutathione to yield the corresponding mercapturic acid.
... Acrolein is metabolized by conjugation with glutathione and excreted in the urine as mercapturic acid metabolites. Acrolein forms Michael adducts with ascorbic acid in vitro, but the biological relevance of this reaction is not clear. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis.
Acrolein can be absorbed though oral, inhalation, or dermal routes. In the liver and kidneys, acrolein forms conjugates with glutathione, cysteine, N-acetylcysteine, and/or thioredoxin. Acrolein can also be transformed into acrylic acid by liver cytosol or microsomes, or it can be oxidized to glycidaldehyde by lung or liver microsomes. Acrolein metabolites are excreted in the urine. (L121)
IDENTIFICATION AND USE: Acrolein is a colorless or yellowish liquid. Acrolein is a biocide currently registered as an herbicide to control aquatic weeds in irrigation canals, as a burrow fumigant to control rodents, and as a microbiocide to eliminate slime-forming microbes in oil drilling operations, pulp and paper mills, and in industrial cooling towers. It has activity as a molluscicide, but is not currently registered for use against mollusks. It is an intermediate for synthetic glycerol, polyurethane and polyester resins, methionine, and pharmaceuticals. In World War I, it was used as a tear gas under the name Papite. HUMAN EXPOSURE AND TOXICITY: The threshold levels of acrolein causing irritation and health effects are 0.7 mg/ cu m for odor perception, 0.13 mg/cu m for eye irritation, 0.3 mg/cu m for nasal irritation and eye blinking, and 0.7 mg/cu m for decreased respiratory rate. Potential symptoms of overexposure are irritation of eyes, skin and mucous membranes; decreased pulmonary function; delayed pulmonary edema; chronic respiratory disease. Intense lacrimation and nasal irritation ordinarily give adequate warning of inhalation, but exposed patients should be observed for 24 hr for a slowly developing pulmonary edema. Acrolein is ciliastatic and capable of causing direct tissue damage similar to that reported for formaldehyde. Acrolein has a relatively short half-life and exerts its greatest effects on the upper and lower respiratory tract. Acrolein is also a weak sensitizer and may elicit asthma-type reactions. Accidental exposure to vapors of acrolein produced burns of the cheeks and eyelids in a male subject. ANIMAL STUDIES: Exposure of rats to airborne concentrations of acrolein of 100-40,000 ppm for short periods of time (<1 hour) caused death ranging from minutes to 11 days. Death was attributed to obstruction of trachea and bronchi, pulmonary edema, or hemorrhage. In animals and humans the reactivity of acrolein effectively confines the substance to the site of exposure, and pathological findings are also limited to these sites. Acrolein reacts directly with protein and non-protein sulfhydryl groups and with primary and secondary amines. Acrolein is a cytotoxic agent. In vitro cytotoxicity has been observed as low as 0.1 mg/liter. The substance is highly toxic to experimental animals and humans following a single exposure via different routes. The vapor is irritating to the eyes and respiratory tract. Liquid acrolein is a corrosive substance. At higher single exposure levels, degeneration of the respiratory epithelium, inflammatory sequelae, and perturbation of respiratory function develop. In general, body weight gain reduction, decrement of pulmonary function, and pathological changes in nose, upper airways, and lungs have been documented in most species exposed to concentrations of 1.6 mg/cu m or more for 8 hr/day. Pathological changes include inflammation, metaplasia, and hyperplasia of the respiratory tract. Significant mortality has been observed following repeated exposures to acrolein vapor at concentrations above 9.7 mg/ cu m. In experimental animals acrolein has been shown to deplete tissue glutathione and in in vitro studies, to inhibit enzymes by reacting with sulfhydryl groups at active sites. There is limited evidence that acrolein can depress pulmonary host defenses in mice and rats. The reduction in removal of bacteria from the alveolar spaces may result from the destruction of functionality of alveolar macrophages present in the respiratory epithelium. Inhalation studies with acrolein revealed that this aldehyde has significant cardiovascular activity at concentrations below those which might be encountered in cigarette smoke. Predominant effect of inhaled acrolein at these doses was an increase in blood pressure and heart rate. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Acrolein can induce teratogenic and embryotoxic effects if administered directly into the amnion. Acrolein has been shown to interact with nucleic acids in vitro and to inhibit their synthesis both in vitro and in vivo. Without activation it induced gene mutations in bacteria and fungi and caused sister chromatid exchanges in mammalian cells. ECOTOXICITY STUDIES: Acrolein is very highly toxic (LD50 <10 mg/kg) to birds on an acute oral exposure basis. Acrolein is very toxic to aquatic organisms. Acute EC50 and LC50 values for bacteria, algae, crustacea, and fish are between 0.02 and 2.5 mg/liter, bacteria being the most sensitive species. A number of fish kills have been reported for acrolein.
Acrolein rapidly and irreversibly binds to lysine moieties and sulfhydryl groups found on many cellular molecules forming thiol ethers. By this mechanism acrolein can bind to messenger compounds to produce direct cytotoxic effects or secondary effects from interrupted cell signaling pathways. Perturbation of inflammatory responses in bronchial epithelial cells was demonstrated by direct action of acrolein on the inhibitor of nuclear factor kappa-B (IκB) kinase, which inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor and suppresses interleukin 8 (IL-8) production. Rapid binding of acrolein to neural receptors in the corneal and nasal mucosa results in rapid depolarization of the associated neurons to produce ocular and nasal irritation. Acrolein also binds rapidly to glutathione, which may be inhibitory to the enzyme glutathione peroxidase and result in a lower level of cellular protection against oxygen radical toxicity. Further, the adduction of glutathione generates GS-propionaldehyde, which produces oxygen and possibly hydroxy radicals via cytosolic aldehyde dehydrogenase. Acrolein inhibits thioredoxin and thioredoxin reductase, which disrupts the cellular thiol redox balance necessary for cell survival. It interferes with normal reverse cholesterol transport by high density lipoprotein (HDL) by modifying specific sites in apolipoprotein A-I. Acrolein also inhibits aldehyde dehydrogenases and activates the transient receptor potential cation channel. (L121, A84, A85, A86)
Under the Draft Revised Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999), the potential carcinogenicity of acrolein cannot be determined because the existing "data are inadequate for an assessment of human carcinogenic potential for either the oral or inhalation route of exposure." There are no adequate human studies of the carcinogenic potential of acrolein. Collectively, experimental studies provide inadequate evidence that acrolein causes cancer in laboratory animals. Specifically, two inhalation bioassays in laboratory animals are inadequate to make a determination because of protocol limitations. Two gavage bioassays failed to show an acrolein-induced tumor response in 2 species of laboratory animals. Suggestive evidence of an extra-thoracic tumorigenic response in a drinking water study in female rats was not supported in the reanalysis of data by an independently-convened pathology working group. Questions were also raised about the accuracy of the reported levels of acrolein in the drinking water from this study. A skin tumor initiation-promotion study was negative, and the findings from an intraperitoneal injection study were of uncertain significance. Although acrolein has been shown to be capable of inducing sister chromatid exchange, DNA cross-linking and mutations under certain conditions, its highly reactive nature and the lack of tumor induction at portals of entry make it unlikely that acrolein reaches systemic sites at biologically-significant exposure levels. The observations of positive mutagenic results in bacterial systems occurred at high concentrations near the lethal dose. This evaluation replaces the cancer assessment for acrolein added to the IRIS database in 1988. Under the Risk Assessment Guidelines of 1986 (EPA/600/8-87/045) applied at that time, acrolein was classified as a possible human carcinogen (Category C). The 1988 classification for acrolein was based on the increased incidence of adrenal cortical adenomas in female rats and carcinogenic potential of an acrolein metabolite, its mutagenicity in bacteria, and its structural relationship to probable or known human carcinogens. The updated cancer characterization considered new study results and reevaluated previous studies.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of acrolein. There is inadequate evidence in experimental animals for the carcinogenicity of acrolein. Overall evaluation: Acrolein is not classifiable as to its carcinogenicity to humans (Group 3).
Very little is known about the absorption and distribution of acrolein following exposure. Acrolein can be absorbed by inhalation, ingestion, or skin absorption. Eighty percent of inhaled acrolein is absorbed in the upper respiratory tract of dogs. Acrolein is metabolized in vitro to glycylaldehyde in animal liver and lung microsomes. It can also form conjugates with glutathione, cysteine, and/or N-acetylcysteine, which may be the most important detoxification mechanism.
... The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. ...
