Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 107-18-6 Toxicity Effects

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

Names (NTP)

  • Allyl alcohol
  • 2-PROPEN-1-OL (9CI)
  • ALLYLIC ALCOHOL
  • 3-HYDROXYPROPENE
  • 1-PROPENOL-3
  • 2-PROPENOL
  • 2-PROPENOL ALCOHOL
  • VINYL CARBINOL

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Absorption through the skin leads to deep muscle pain, presumably due to spasm. [Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., p. 299]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: ...Absorbed through intact skin in toxic and even lethal concentration. Dermatitis of variable types and degrees results, in addition to first and second-degree burns with vesiculation. [Arena, J.M. and Drew, R.H. (eds.) Poisoning-Toxicology, Symptoms, Treatments. 5th ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 275]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: ...Liquid may produce ...superficial necrosis. ...inhaled vapor may lead to pulmonary edema with slowly developing distress. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-98]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Severe eye irritation results from exposure to 25 ppm ...5 ppm is slightly irritating to some individuals. Corneal necrosis has been reported to result in temporary blindness. ...Skin penetration may lead to serious systemic injury (visceral congestion, periportal congestion of the liver, hematuria, and nephritis)... /allyl alcohol/ produces a syndrome of lacrimation, photophobia, blurred vision, and retrobulbar pain. Although these symptoms persist for some hours following exposure, neither increased sensitivity nor tolerance appear to develop. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 3]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Ethanol and certain short chain aryl (benzyl) and aliphatic (propyl, butyl) alcohols produced up to 10 fold increases in cyclic AMP concentration in purified human peripheral blood lymphocytes. Ethanol concentration as low as 80 mg/dl produced significant elevations in lymphocyte cyclic AMP. [Atkinson JP et al; J Clin Invest 60 (2): 284-94 (1977) ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Volunteers have complained that 12.5 ppm was moderately irritating to the nose; only slight nasal irritation was reported at 0.8 ppm, the lowest concentration tested. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 520]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Vapors are quite irritating to eyes, nose, and throat. Eye irritation may be accompanied by complaints of photophobia and pain in the eyeball; pain may not begin until 6 hr after exposure. [Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 55]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Potential symptoms of overexposure are eye irritation, tissue damage; irritation of upper respiratory system and skin; pulmonary edema. [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 54]**PEER REVIEWED**
  • CASE REPORTS: Oral ingestion of allyl alcohol by a 55-yr-old man resulted in death within 100 min. At autopsy, bloody, reddish fluid was found in mouth, larynx, esophagus, and trachea. The mucous membranes of the trachea, stomach, and duodenum were congested and inflamed. The stomach contained a pungent green-black fluid, and all internal organs exhibited a strong pungent odor. Toxicological analysis of blood identified allyl alcohol... . Total amounts of allyl alcohol in gastric contents, bile, and urine were 3.6 g, 15 mg, and 0.5 mg, respectively. The concentration in blood was 309 mg/L. Acrolein was not detected in gastric contents and only in small amounts in bile and urine. The concentration of acrolein in blood was 7.2 mg/L. Death was attributed to acrolein-induced acute cardiotoxicity, similar to that previously documented in animal experiments. [Toennes SW et al; J Anal Toxicol 26 (1): 55-7 (2002) ]**PEER REVIEWED**
  • EPIDEMIOLOGY STUDIES: In air moderately contaminated with allyl alcohol (concentration unspecified), men complained of excessive secretion of tears, pain behind the eyes, sensitivity to light, and some blurring of vision. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 520]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Three hr after oral administration to rats of 1 ml/100 g body weight of allyl alcohol, cytochrome p450 was increased by 33% in liver microsomes. Aminopyrine demethylase and dimethylaniline demethylase were stimulated. Activity of microsomal hydroxylation system gradually decreased. [Gorshtein ES et al; Eksp Med (Riga) 3: 15-20 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 0.05 ml/kg of allyl alcohol administered orally to mice caused depletion of hepatic glutathione activity. The extent of depletion was 44.5% of control values. [Siegers CP et al; Proc Eur Soc Toxicol 18 (Clin Toxicol): 160-2 (1977) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Cyclic(C)AMP was studied in male Sprague-Dawley rats administered a single dose of allyl alcohol. Adrenal (C)AMP concentration increased 10 hr after intoxication compared to controls. In final stage of experiment (30-39 hr after application) all intoxication was associated with significant increases in adrenal (C)AMP concentration. [Danz M, Kittlick P-D; Exp Pathol 13 (2-3): 139-44 (1977) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Allyl alcohol (20 mg/kg) enhanced mitotic activity of adrenocortical cells in rats after 24 hr but activity returned to normal values within following 12 hr. [Danz M et al; Exp Pathol 12: 301-8 (1976) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Single necrogenic doses of allyl alcohol admin to Fischer 344 rats were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Allyl alcohol administration increased serum alanine aminotransferase activity but had no effect on serum gamma-glutamyl transferase activity. [Leonard TB et al; Am J Pathol 116 (2): 262-9 (1984) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The effect of acute exposure of rats to allyl alcohol (0.05 ml/kg, ip) on the activity of enzymes of hepatic phase I (cytochrome p450-linked microsomal monooxygenases, epoxide hydrolase) and phase II (glucuronyl-, glutathione-, acetyl- and sulfotransferases) biotransformation were studied in rats. Allyl alcohol reduced hepatic cytochrome p450 in liver, and the activities of ethylmorphine demethylase, benzphetamine demethylase, benzo[a]pyrene hydroxylase, and ethoxyresorufin deethylase. No significant decrease in epoxide hydrolase or glucuronyltransferase activities were observed. The activities of cytosolic conjugating enzymes (glutathione-, sulfo- and acetyltransferases) also were minimally affected by toxic liver injury. [Gregus Z et al; J Pharmacol Exp Ther 222 (2): 471-9 (1982) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In rats a single dose of allyl alcohol (100 uL/kg) was given to produce periportal liver damage. The prothrombin index was reduced to a minimum after 12 hr and reestablished after 24 hr. The galactose elimination capacity was not changed. Hepatic glutathione content was unchanged for the first 24 hr but was then elevated two-fold. Microsomal D-nitroanisole demethylase showed a slight initial increase and a subsequent reduction. Thus, in chemical liver damage ribosomal function is more vulnerable than cytosolic phosphorylation of carbohydrate. [Poulsen HE, Korsholm B; Acta Pharmacol Toxicol 54 (2): 120-3 (1984) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Male NMRI mice were fed a sucrose diet for 48 hr in order to reduce the hepatic glutathione content and to level off its diurnal variation. After administration of allyl alcohol (AA: 1.1 mmol/kg), hepatic glutathione (24.3 +/- 7.0 nmol GSH/mg protein) was almost totally lost within the first 15 min (less than 0.5 nmol GSH/mg protein). Subsequently, a massive lipid peroxidation was observed, ie, the animals exhaled 414 +/- 186 nmol ethane/kg/hr compared to 0.9 +/- 0.8 of controls, and the hepatic TBA-reactive compounds had increased from 55 +/- 16 pmol/mg protein in controls to 317 +/- 163 after 1 hr. Concomitantly, a 40-45% loss of the polyunsaturated fatty acids (arachidonic and docosahexaenoic acid) in the liver lipids was observed. About 80% of the cytosolic alcohol dehydrogenase activity and about 50% of the microsomal p450-content were destroyed. In vivo-inhibition of alcohol dehydrogenase by pyrazole or induction of aldehyde dehydrogenase by phenobarbital abolished allyl alcohol-induced liver damage as well as glutathione depletion and lipid peroxidation, while inhibition of aldehyde dehydrogenase by cyanamide made a subtoxic dose of allyl alcohol (0.60 mmol/kg) highly toxic. In vitro, acrolein alone failed to initiate lipid peroxidation in soy bean phospholipid liposomes or in mouse liver microsomes. Thus, acrolein not only impairs the glutathione defense system but also directly destroys cellular proteins and evokes lipid peroxidation by an indirect iron-dependant mechanism. [Jaeschke H et al; Biochem Pharmacol 36 (1): 51-7 (1987) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The possible involvement of thiols and adenine nucleotides in the selective toxicity to periportal regions by allyl alcohol was evaluated in isolated perfused rat livers. Infusion of allyl alcohol (350 microM) for 20 min depleted hepatic glutathione content by 95% in both regions of the liver lobule yet damage was undetectable as indexed by release of lactate dehydrogenase or uptake of trypan blue. Perfusion for an additional 40 min in the absence of allyl alcohol resulted in lactate dehydrogenase release (2400 U/l) and uptake of trypan blue by 75% of hepatocytes in periportal regions of the liver lobule; however dye was not taken up by cells in pericentral areas. Because the content was depleted in the undamaged pericentral area, it was concluded that thiol depletion alone cannot explain local toxicity to periportal regions by allyl alcohol. [Belinsky SA et al; J Pharmacol Exp Ther 238 (3): 1132-7 (1986) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The toxicity of allyl alcohol was studied in freshly isolated renal epithelial cells prepared from male and female rats. Cells from female rats demonstrated a greater susceptibility to allyl alcohol toxicity as assessed by glutathione depletion and loss of cell viability. The sensitivity of female rat renal cells appears to relate to the higher activity of alcohol dehydrogenase found in the female rat kidney, which metabolizes allyl alcohol to the highly reactive aldehyde, acrolein. Pyrazole, an inhibitor of alcohol dehydrogenase, abolished the cytotoxic effects of allyl alcohol whereas inhibition of aldehyde dehydrogenase by disulfiram treatment was found to increase the sensitivity of renal cells to the effects of allyl alcohol. These results indicate that acrolein is the toxic metabolite responsible for the renal cell injury following exposure to allyl alcohol, and unless immediately inactivated acrolein interacts with critical nucleophilic sites of the cell and initiates cell injury. [Ohio Y et al; Chem Biol Interact 52 (3): 289-99 (1985) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Male CD-1 mice were tested with carbon tetrachloride (1ml/kg, ip), or allyl alcohol (0.05 ml/kg, ip) or both 24 hr prior to sacrifice. The livers were removed, homogenized and mitochondrial preparations were fractionated. The mitochondrial pellet from allyl alcohol-treated livers was characterized by a preponderance of condensed mitochondria whether carbon tetrachloride was given also or not. The mitochondrial fraction from carbon tetrachloride-treated mice failed to utilize oxygen whereas that fraction from mice given allyl alcohol did not differ from control in either its basal oxygen consumption (state 4) or oxygen utilization after the addition of adenosine diphosphate (state 3). State 4 respiration differed slightly but significantly from control in mitochondria from mice given both allyl alcohol and carbon tetrachloride whereas state 3 respiration was greatly and significantly decreased from that of control values. Electron micrographs of liver slices from mice given allyl alcohol or the combination of allyl alcohol and carbon tetrachloride showed normal mitochondrial morphology. [Rutkowski JV et al; Toxicology 40 (1): 25-30 (1986) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The influence of aging on the toxicity of allyl alcohol was studied in hepatocytes isolated from male Fischer 344 rats. Initial values for trypan blue uptake, lactate dehydrogenase (LDH) release, alanine aminotransferase release, and glutathione content were similar in cells isolated from rats aged 5, 15, or 26 months. Incubation with 0.1 to 0.8 mM allyl alcohol resulted in a dose- and time-dependent loss of viability. Inhibition by pyrazole of allyl alcohol-induced lactic dehydrogenase (LDH) release from hepatocytes also was affected by age. Total protection was observed for cells from young rats whereas no protection was found for those of old rats. Cells from middle-aged rats were between the extremes. [Rikans LE, Hornbrook KR; Toxicol Appl Pharmacol 84 (3): 634-9 (1986) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Male CD1 mice and male CD rats were administered allyl alcohol, 0.05 ml/kg in corn oil, ip, 24 hr prior to sacrifice. Pentobarbital sleeping time, serum glutamic pyruvic transaminase (SGPT), histologic evidence of liver necrosis, and respiratory activity of liver mitochondria were used as indices of hepatotoxicity. Allyl alcohol treatment resulted in a significant decrease in pentobarbital sleeping time in mice (p<0.05), but significantly prolonged the sleeping time in rats (p<0.005). SGPT was significantly elevated in treated mice (3-fold, p<0.05) and rats (20-fold). There was no visible liver necrosis in mice; livers from treated rats showed variable necrosis. Micrographs of mitochondria from treated rats showed flocculent densities in the matrix compartment. Mitochondria from control mice and rats and treated mice had normal state 3 respiratory activity and normal respiratory control. In treated rats state 3 respiratory activity was depressed relative to the control value and respiratory control was absent, indicating inability to carry out oxidative phosphorylation. [Jacobs JM et al; Toxicol Lett 38 (3): 257-64 (1987) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Two well known hepatotoxicants, allyl alcohol and bromobenzene, were studied using an in vitro system of cultured liver slices from control and phenobarbital-treated rats, respectively. Dose- and time-dependent increases in media lactate dehydrogenase (LDH), and decreases in slice K+ content and in protein synthesis were observed in rat liver slices incubated with either compound at concentrations between 0.1 and 1 mM over a period of 6 hr. Additionally, the toxicity of either bromobenzene or allyl alcohol, evaluated at 4 hr, was inhibited when slices were preincubated for 30 min with beta-ethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) (0.1 mM) or pyrazole (1.0 mM), respectively. [Smith PF et al; Toxicol Appl Pharmacol 87 (3): 509-22 (1987) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Allyl alcohol was slightly irritating to intact and abraded skin of rabbits. In rabbits, 0.02 mL of the undiluted material produced severe injury, including corneal necrosis. In another study, 0.05 mL was only a slight irritant and produced some conjunctivitis and corneal opacity that disappeared after 7 days. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 518]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Instillation of 0.05 ml allyl alcohol into rabbit eyes produced conjuntival erythema, swelling of the nicotinic membrane, and corneal sloughing. Corneal opacity developed in some of these rabbits but was said to resolve in one week. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 2]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Application to eyes causes erythema of conjunctiva and swelling of cornea, sometimes with opacity, but no permanent injury. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 380]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Rapid drop in carotid blood pressure, definite reduction in respiratory rate and amplitude, and increase in hemoconcentration (hematocrit), but no increase in concentration of histamine in plasma, followed iv injection of 40 mg/kg into a dog. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1487]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The livers of rats showed periportal necrosis and elevation of hepatic glutathione within 24 hr following the administration of allyl alcohol. [Atzori L et al; Boll Soc Ital Biol Sper 56 (21): 2218-22 (1980) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 0, 1, 3, 24, and 72 hr after oral administration to rats of 1 ml/100 g body weight of 1% allyl alcohol, livers contained 1.05, 1.088, 1.37, 1.21, and 1.51 (arbitrary) units of malonic aldehyde and 4.30, 5.68, 10.97, 6.67, and 7.13 (arbitrary) units of conjugated dienes. Alanine aminotransferase activity was very high during this period. Necrosis in the hepatocyte and Kupffer cell cytoplasm was observed from the 4th hr after administration which shows that the onset of lipid peroxidation precedes necrosis. [Kopylova TN, Vicupe Z; Eksp Med (Riga) 3: 58-61 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 30 mg/kg orally in rats cause marked periportal necrosis which was associated with losses of alcohol dehydrogenase and succinate dehydrogenase activities in liver. Benzo(a)pyrene hydroxylase and hepatic content of cytochrome p450 were decreased showing inhibition of xenobiotic metabolism. [Lake BG et al; Biochem Soc Trans 6 (1): 145-7 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 96 hr after single administration of allyl alcohol, acidophilia, necrosis and vacuolation of pancreatic acinar cells of rats were noted. Electron microscopy revealed cytoplasmic lipid droplets, mitochondrial degeneration and necrosis in acinar cells. [Nizze H et al; Digestion 19 (6): 359-69 (1979) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...5, 10 and 25 mg/kg doses of... allyl alcohol /was administered/ to obese Sprague-Dawley rats and age-matched non-obese controls. Alanine aminotransferase activity (ALT) in plasma was ten-fold more elevated in obese animals than in non-obese animals given the 25 mg/kg dose (P<0.05). ...The minimum dose required to produce elevated ALT (DMIN) was 50% lower for obese animals (DMIN 6.47 +/- 2.75 vs. 13.3 +/- 0.96 mg allyl alcohol; P<0.05). In a subsequent experiment, allyl alcohol was administered to obese rats based on ideal body weight, which is defined as the mean total body weight of an age-matched non-obese animal. With this dosing normalization, the 25 mg/kg ideal body weight doses translated to administration of a fixed dose of 13.5 mg allyl alcohol to obese rats. Obese rats treated in this fashion exhibited more severe necrosis in the periportal zone (median necrosis score 2 versus 0-1, P<0.05) and increased mortality over controls (44% versus 0%; P<0.05). [Salazar DE et al; Int J Obes Relat Metab Disord 18 (1): 25-33 (1994) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...Administration of allyl alcohol (30 or 40 mg/kg, ip) to rats caused extensive hepatic necrosis localized primarily to periportal regions. To test the involvement of Kupffer cells in the genesis of this injury, male rats (200-350 g) were treated with gadolinium chloride (GdCl3, 10 mg/kg, iv) which diminishes Kupffer cell function and number. The extent of hepatic damage assessed by light microscopy and serum enzymes, aspartate aminotransferase and alanine aminotransferase, was markedly attenuated by pretreatment of rats with GdCl3 24 hr prior to allyl alcohol injection. Thus, O2-dependent hepatic necrosis caused by allyl alcohol involves the presence of Kupffer cells. Since GdCl3 did not prevent toxicity in the perfused liver, circulating blood elements may also contribute to injury of the liver by allyl alcohol in vivo. [Przybocki JM et al; Toxicol Appl Pharmacol 115 (1): 57-63 (1992) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...The study comprised 130 male Wistar rats divided randomly into 2 groups: I (n=10) sham and II (n=120) /allyl alcohol/ (AA) injection (ip: 0.62 mmol/kg) and rhinogastric administration of /carbon tetrachloride/ (CCl4) (0.66 ml/kg, 1:1 volume dilution in corn oil). After injection was completed, animals of group II were assigned in 12 categories and sacrificed 2, 4, 6, 12, 18, 24, 33, 48, 57, 81, and 153 hr after. Tissue was obtained from the left anterior lobe and the hilum of the liver, and histological examination included H&E, silver methenamine and van Giesson stains. Liver sections from group II (AA+CCl4) demonstrated periportal together with pericentral necrosis; the peak was 57 hr after injection. In all 120 cases, H&E stain showed evidence of regeneration originated from zone 2, extending to zone 1 and occasionally to zone 3, and accomplished mainly by non-necrotic cell proliferation. Sections from the liver hilum showed thrombosis of the portal vein, whereas the hepatic artery and its branches developed a variety of changes. Initially (2, 4 hr), endothelial hypertrophy was observed which was followed by focal fibrinoid necrosis of the arterial wall (6 hr). Later on (9-153 hr) the following findings were present: hyperplasia and non-isometric cytoplasmic vacuolisation of media, disruption of the elastic lamina, aggregation of foam cells and macrophages in intima, media, and focally in adventitia of hepatic artery; and lymphocytic inflammation of intimal and periadventitial area. In 2 cases (153 hr) hepatic artery thrombosis was present. Additionally to liver parenchymal changes, simultaneous administration of allyl-alcohol and carbon tetrachloride in rats results /in/ vascular changes mainly in the hepatic artery and its branches. During liver parenchymal regeneration, the hepatic artery and its branches develop microscopic features that morphologically resemble those of atherosclerosis. These changes may result in hepatic artery thrombosis and or obstruction. [Papalambros E et al; Int Angiol 19 (2): 166-70 (2000) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Allyl alcohol was administered to rats in drinking water for 15 wk. Dose-related reductions in fluid intake was observed. Growth and food consumption decreased in both sexes given 800 ppm and in males administered 200 ppm. Less urine was produced in males administered 100 ppm or more and in females administered 200 or 800 ppm. Liver, spleen, and kidney weight increased. [Carpanini F MB et al; Toxicology 9 (1-2): 29-46 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ...Of 40 male adult rats, 30 were injected with 0.62 mmol/kg of allylalcohol ip twice a week, the remaining 10 with normal saline as controls. Ten rats were killed at each of 4, 8, and 16 weeks later. ...After 4 weeks, periportal fibrosis was produced in only 6 out of 10 rats, and was mild in extent. However, after 8 weeks, 8 out of 9 survivors showed moderate to severe fibrosis... . The extent of fibrosis correlated significantly with the amount of collagen and /transforming growth factor/ (TGF)beta1 mRNA expression in liver tissues. ... [Jung SA et al; Scand J Gastroenterol 35 (9): 969-75 (2000) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In repeated oral studies in rats, allyl alcohol produced principally kidney and liver injury. Multiple inhalation exposure caused liver, lung and kidney damage in a range of laboratory animals. [BIBRA working group; TA:Toxicity profile. BIBRA Toxicology International:5 (1995). ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: By inhalation, repeated exposure of rats to 40, 60 and 100 ppm caused gasping, severe depression and nasal discharge, and at highest levels some animals died by 10th exposure. ... /Rats, rabbits, guinea pigs and dogs were/ exposed to ...7 ppm 7 hr/day for 6 months. ...Liver showed cloudy swelling and focal necrosis, and kidney necrosis of convoluted tubules and proliferation of interstitial tissue; these changes were mild and reversible. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 379]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Male and female F344 rats (20/group) were given allyl alcohol in the drinking water at a concentration of 0 or 300 mg/L for 106 weeks. The incidence of tumors was similar to that in controls. Male and female hamsters (20/group) were dosed by oral gavage with 2 mg allyl alcohol/wk for 60 weeks. The incidence of tumors did not increase significantly compared to controls. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 520]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Litters sired by male rats treated with a dose of 0.86% allyl alcohol 7 days/wk to week 12 and 5 days/wk from week 13 to 33 did not develop any malformations. No adverse reproductive effects were observed. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 519]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Allyl alcohol was investigated for its property as sensory irritant in Ssc:CF-1 mice. The concentration of the chemical necessary to depress the respiratory rate by 50% (RD50) due to sensory irritation of the upper respiratory tract was 3.9 ppm. No pulmonary irritation was found at the concn causing a 50% decrease in respiratory rate. [Nielsen GD et al; Acta Pharmacol Toxicol 54 (4): 292-8 (1984) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: The role of calcium in allyl alcohol-induced hepatotoxicity was investigated in the isolated hemoglobin-free perfused rat liver. At a Ca2+ concentration of 2.5 mmol/l in the perfusate, allyl alcohol (initial concentration 1.17 mmol/l) produced an enhanced release of SGPT and sorbitol dehydrogenase (SDH) from the liver, an increase in the lactate/pyruvate ratio of the perfusate, a decrease in hepatic oxygen consumption and an increase of both hepatic calcium and malondialdehyde content. In the absence of Ca2+ in the perfusate, no hepatic calcium accumulation occurred with allyl alcohol, but all other signs of hepatic damage were as severe as with 2.5 mmol/l Ca2+. On the other hand, high extracellular Ca2+ (5 mmol/l) alone led to a threefold increase of liver calcium but produced only marginal hepatotoxicity and only slightly enhanced the hepatotoxic effects of allyl alcohol. The concentrations of allyl alcohol in the perfusate were not altered at different Ca2+ concentrations. [Strubelt O et al; Acta Pharmacol Toxicol 59 (1): 47-52 (1986) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: ...Inhibition or augmentation of cyclic AMP and/or protein kinase A (PKA) by Rp-Ado-3N,5N-cyclic monophosphorothioate triethylamine salt or 3-isobutyl-1-methylxanthine had no effect on allyl alcohol-induced cell death. H-7, an inhibitor of PKA, PKC, and PKG, partially inhibited cell killing by allyl alcohol, whereas chelerythrine chloride, a nonselective PKC inhibitor, almost completely abolished allyl alcohol cytotoxicity. Neither 2,2N,3,3N,4,4N-hexahydroxy-1,1N,-biphenyl-6,6N-dimethanol-dimethyl ether, a selective PKC alpha and beta inhibitor, nor bisindolylmaleimide I, an inhibitor of PKC alpha, beta, and epsilon, had any effect on allyl alcohol cytotoxicity. In contrast, rottlerin, a selective PKCdelta inhibitor, blocked hepatocellular killing by allyl alcohol. Cytoprotection by chelerythrine chloride and rottlerin was not the result of inhibition of bioactivation of allyl alcohol because each inhibitor also prevented cell death from acrolein. Western blotting and immunohistochemical techniques revealed that allyl alcohol stimulated phosphorylation and translocation of PKCdelta to hepatocyte membranes (i.e., activation), and this activity was inhibited by rottlerin. Cell death appeared to occur via oncotic necrosis rather than apoptosis based on single-stranded DNA ELISA and propidium iodide staining. Together, these results indicate that activation of PKCdelta is a critical, early event in initiating hepatocyte injury and death from allyl alcohol. [Maddox JF et al; Chem Res Toxicol 16 (5): 609-15 (2003) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: ...Liver slices were prepared from male Sprague-Dawley rats, male Dunkin-Hartley guinea-pigs and from samples of Cynomolgus monkey and human liver... /and/ were cultured with the test compounds for 24 hr... . ...At the concentrations examined, ...rat liver slices were less susceptible to allyl alcohol toxicity. ... [Price RJ et al; Arch Toxicol 71 (1-2): 107-11 (1996) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Allyl alcohol-induced LDH leakage from isolated rat hepatocytes was preceded by a ...a loss of mitochondrial membrane potential. Addition of dithiothreitol (DTT) prevented the drop in membrane potential and completely prevented cell killing by allyl alcohol. In contrast, cyclosporin A and trifluoperazine delayed the loss of membrane potential without affecting cytolethality. The results indicate that a drop in mitochondrial membrane potential is not essential for allyl alcohol lethality. The mitochondrial dysfunction produced by allyl alcohol appears to be the consequence of an earlier event in the toxicity that is reversible by DTT. [Rikans LE et al; Toxicol Lett 81 (2-3): 159-65 (1995) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Reversal by dithiothreitol (DTT) of allyl alcohol cytotoxicity was investigated in isolated rat hepatocytes. Allyl alcohol-induced protein sulfhydryl loss, bleb formation, and cell death were prevented by DTT, when it was added to hepatocytes 30 min after the toxicant. The protective effect of DTT also was demonstrated in cells that were washed after 30 min of exposure to allyl alcohol, indicating that protection was not related to inhibition of allyl alcohol metabolism or inactivation of acrolein. DTT reversed the cell surface protrusions that formed during exposure to allyl alcohol, but reversal of blebbing did not insure that the cells would remain viable. Glutathione disulfide was not formed in allyl alcohol-treated cells, and DTT reversal of cytotoxicity occurred without restoring glutathione levels. Moreover, protection against allyl alcohol toxicity required the continuous presence of DTT. The results suggest that initial events in the toxic process are reversible, and that DTT can prevent cytotoxicity if added to hepatocytes before irreversible damage occurs; however, the mechanism by which DTT exerts its protection is not clear. [Rikans LE, Cai Y; Toxicology 86 (1-2): 147-61 (1994) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: ...The action of allyl alcohol (100-500 microM) on isolated hepatocytes was studied using cells maintained at either 95 or 21% O2. Allyl alcohol toxicity, as indexed by trypan blue uptake, lactate dehydrogenase release, and ATP content, did not differ in the two groups of cells, suggesting that O2 dependency of allyl alcohol toxicity involves other cell types. [Przybocki JM et al; Toxicol Appl Pharmacol ]**PEER REVIEWED**
  • GENOTOXICITY: Allyl alcohol was ...mutagenic to V79 mammalian cells in vitro. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 520]**PEER REVIEWED**
  • GENOTOXICITY: Mutagenicity of vinyl compounds were tested in 5 strains of Salmonella typhimurium. Allyl alcohol was mutagenic in more than 1 strain. [Lijinsky W, Andrews AW; Teratog, Carcinog, Mutagen 1 (3): 259-67 (1980) ]**PEER REVIEWED**
  • GENOTOXICITY: Several alpha-, beta-unsaturated carbonylic cmpd and their corresponding allylic alcohols were tested in a modified Salmonella typhimurium assay with and without metabolic activation by S9 mix. Allyl alcohol exerted a significant direct mutagenic activity (750 revertants/umol). [Lutz D et al; Mutat Res 93 (2): 305-15 (1982) ]**PEER REVIEWED**
  • GENOTOXICITY: Five industrial and agricultural chemicals incl allyl alcohol were tested for their ability to induce reverse mutations in Salmonella typhimurium and forward mutations in Streptomyces coelicolor and Aspergillus nidulans. Allyl alcohol was completely negative in all test systems. [Principe P et al; J Sci Food Agric 32 (8): 826-32 (1981) ]**PEER REVIEWED**
  • GENOTOXICITY: Allyl alcohol was mutagenic in the Ames bacterial test and in mammalian cells in culture. There was no evidence of mutation in male rats treated orally. [BIBRA working group; TA:Toxicity profile. BIBRA Toxicology International:5 (1995). ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: The involvement of altered pyridine nucleotide concentrations in the cytolethality of allyl alcohol was studied in isolated rat hepatocytes. NAD+, NADH, NADP+, NADPH and viability loss (leakage of lactate dehydrogenase into the medium) were measured in cells incubated with 0.5 mM allyl alcohol with or without the addition of 2 mM dithiothreitol at 30 min. Exposure to allyl alcohol increased NADH levels in the first 15 min of incubation. A sharp drop in NADH and NADPH with an accumulation of NADP+ occurred between 30 and 60 min of incubation with allyl alcohol, indicating an oxidation and interconversion of pyridine nucleotides. Dithiothreitol prevented the oxidation of pyridine nucleotides, but not their reduction or interconversion, and protected against cell killing by allyl alcohol. ... [Rikans LE et al; Toxicology 106 (1-3): 85-92 (1996) ]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rabbit percutaneous 89 mg/kg [Farm Chemicals Handbook 1989. Willoughby, OH: Meister Publishing Co., 1989., p. C-16]**PEER REVIEWED**
  • LD50 Mouse oral 85 mg/kg [Worthing, C. R. (ed.). Pesticide Manual. 6th ed. Worcestershire, England: British Crop Protection Council, l979., p. 9]**PEER REVIEWED**
  • LD50 Rat oral 64 mg/kg [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 54]**PEER REVIEWED**
  • LC50 Rat inhalation 165 ppm/4 hr [USEPA; Health and Environmental Effects Profile for Allyl alcohol p.36 (1985) ECAO-CIN-P121]**PEER REVIEWED**
  • LC50 Rat inhalation 76 ppm/8 hr /from table/ [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 518]**PEER REVIEWED**
  • LC50 Rat inhalation 1060 ppm/1 hr /from table/ [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 518]**PEER REVIEWED**
  • LD50 Mouse ip 60 mg/kg [Dunlap MK et al; AMA Arch Ind Health 18: 303-11 (1958) as cited in USEPA; Health and Environmental Effects Profile for Allyl alcohol p.36 (1985) ECAO-CIN-P121 ]**PEER REVIEWED**
  • LD50 Mouse iv 78 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 92]**PEER REVIEWED**
  • LD50 Rabbit dermal 45 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 92]**PEER REVIEWED**
  • LD50 Rat ip 37 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 92]**PEER REVIEWED**
  • LC50 Mouse inhalation 500 mg/cu m/ 2hr [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 92]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Allyl alcohol is apparently oxidized readily since within few min after iv injection of rats with the dosage of 30 mg/kg, vena cava blood contained average concentration of about 24 ug/ml; within 15 min concentration was about 4 ug/ml and within 1 hr the alcohol had almost disappeared from the blood. During constant iv infusion the allyl alcohol disappeared at rate of about 23 mg/hr. During the period of 15-120 min after admin of single oral dose of allyl alcohol (120 mg/kg) to rats, mean concentration of this alcohol in the portal vein was between 9 and 15 ug/ml. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4668]**PEER REVIEWED**
  • ...Absorbed through intact skin in toxic and even lethal concentrations. [Arena, J.M. and Drew, R.H. (eds.) Poisoning-Toxicology, Symptoms, Treatments. 5th ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 275]**PEER REVIEWED**

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Metabolism/Metabolites

  • The biotransformation of allyl alcohol was studied in rat liver and lung preparation. Acrylic acid was formed from allyl alcohol. Lung and liver microsomal epoxidation products were also identified. [Patel JM et al; Drug Metab Dispos 8 (5): 305-8 (1980) ]**PEER REVIEWED**
  • Rats treated with single ip doses (0.05 ml/kg) of allyl alcohol showed significantly greater hepatic necrosis and elevation of plasma glutamic-pyruvic transaminase (GPT) levels 24 hr later than rats given the same dose of deuterium-labeled allyl alcohol (d2-allyl alcohol). The covalent binding of radiolabel to hepatic proteins of rats treated with (14)C allyl alcohol was three-fold greater than that in rats given the same dose of d2-(14)C allyl alcohol. The formation of acrolein and acrylic acid by hepatic 9000X g and cytosol fractions from d2-allyl alcohol was significantly less than that from allyl alcohol. The relationship of rate of formation of reactive metabolite (acrolein) to toxicity of allyl alcohol and d2-allyl alcohol is demonstrated. [Patel JM et al; Drug Metab Dispos 11 (2): 164-6 (1983)]**PEER REVIEWED**
  • Rates of allyl alcohol metabolism in periportal and pericentral regions of the liver lobule were measured to determine whether the zonal toxicity due to allyl alcohol results from its selective metabolism in periportal regions. Infusion of allyl alcohol into perfused livers from fed, phenobarbital-treated rats caused an increase in nicotinamide adenine dinucleotide, reduced form (NADH) fluorescence (366 leads to 450 nm) measured with a large-tipped (2 mm) light guide placed on the surface of the liver. A linear increase in NADH fluorescence was observed when 25-150 uM allyl alcohol was infused; however, when allyl alcohol exceeded 200 uM, oxygen uptake by the liver was inhibited 30-40%, and a large increase in NADH fluorescence occurred. /4-Methylpyrazole (80 umol), an inhibitor of alcohol dehydrogenase, prevented the fluorescence increased due to allyl alcohol in both regions, indicating that the changes were due entirely to NADH generated from alcohol dehydrogenase-dependent allyl alcohol metabolism./ Using the correlation (r= 0.91) between rates of allyl alcohol uptake and the increase in NADH fluorescence established for the whole organ, local rates of allyl alcohol metabolism were 23 and 31 mumoles/g/hr in periportal and pericentral regions, respectively. Since allyl alcohol is metabolized in both regions of the liver lobule, the hypothesis that the zone specific hepatotoxicity results from its exclusive metabolism to acrolein in periportal regions seems unlikely. [Belinsky SA et al; Mol Pharmacol 25 (1): 158-64 (1984) ]**PEER REVIEWED**
  • ...Allyl alcohol (CH2=CHCH2OH), ...is converted by /alcohol dehydrogenase/ to the highly hepatotoxic aldehyde acrolein (CH2=CHCHO). [Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 156]**PEER REVIEWED**
  • In rats, allyl alcohol is metabolized to acrolein by alcohol dehydrogenase. ...Acrolein can react with glutathione to form the corresponding thiol ether, which can be further metabolized to mercapturic acids and excreted in the urine. In the presence of NADPH and liver and lung microsomes, allyl alcohol and acrolein were oxidized to the corresponding epoxides, glycidol, and glycidaldehyde, respectively. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 519]**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.

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Web page last updated on May 14, 2008