Summary Of Exposure |
A) USES: Higher alcohols are alcohols that contain more than 2 carbons, including 1-pentanol (amyl alcohol), used as an industrial solvent and synthetic flavoring agent. N-butanol and 2-methyl-2-butanol (amylene hydrate) have been used as human sedatives. Other higher alcohols are major ingredients in lacquer thinners, paint strippers, and solvents. Other industrial uses for higher alcohols include the manufacture of lacquers, chemicals, plastics, rubber, fruit essences, explosives, hydraulic fluid, pharmaceuticals, ceramics, textiles, disinfectants, and cleaning products.
B) TOXICOLOGY: Butanols and amyl alcohols (pentanols) are irritants to the eyes, mucous membranes, lungs and GI. Severity of gastric irritation correlates with lipid solubility. Higher alcohols are of a low order of toxicity in an industrial setting. As the carbon chain lengthens, the toxicity decreases. They are not able to penetrate skin as readily as smaller molecular weight alcohols and are less likely to be absorbed by inhalation. The exact mechanism is unknown.
C) EPIDEMIOLOGY: Products containing higher alcohols are widely available but not many exposures are reported to poison centers with patients presenting with severe effects being very rare.
D) WITH POISONING/EXPOSURE
1) MILD TO MODERATE TOXICITY: Can cause gastrointestinal symptoms such as nausea, vomiting, abdominal cramps and diarrhea. Irritation of mucous membranes may also occur. Dermatitis of varying severity can happen with chronic exposure. Neurologic symptoms include headache, dizziness, giddiness, ataxia and sedation. Vapors from higher alcohols are irritating to the conjunctiva leading to burning, lacrimation, photophobia, corneal disturbances, and vision blurring.
2) SEVERE TOXICITY: Can cause hypotension and cardiac dysrhythmias, and if aspirated, a hemorrhagic pneumonitis. With severe respiratory exposures, pulmonary edema can occur. Severe ingestions can cause gastrointestinal hemorrhage and liver injury. Finally, hypoglycemia can occur after exposure. After exposure to n-butanol vapor in combination with other solvents, there have been reports of formation of vacuoles in the cornea.
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Heent |
3.4.3) EYES
A) WITH POISONING/EXPOSURE 1) EYE IRRITATION: Vapor of butanols and amyl alcohols are irritating to the conjunctiva leading to burning, lacrimation, photophobia, corneal disturbances and blurring of vision (HSDB , 2001; Harbison, 1998; Grant & Schuman, 1993; Clayton & Clayton, 1982). No permanent ocular damage has been reported. a) Irritation of the human eye has been reported at the following concentrations for the listed alcohols: Amyl alcohols (isoamyl alcohol): concentration 150 ppm: butyl alcohol: concentration 50 ppm (RTECS , 2001).
2) VACUOLAR KERATOPATHY: The formation of vacuoles in the cornea has been reported after exposure to n-butanol vapor in combination with other solvents (Cogan & Grant, 1945; Herman & Hickman, 1948; Jaeger, 1955). 3) IRITIS has been reported following severe exposures to 1-pentanol (amyl alcohol) (HSDB , 2001). |
Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) HYPOTENSIVE EPISODE 1) WITH POISONING/EXPOSURE a) Hypotension may occur following exposure (HSDB , 2001; Bunc et al, 2006).
B) TACHYCARDIA 1) WITH POISONING/EXPOSURE a) TERT-AMYL ALCOHOL: CASE REPORT: A 28-year-old man was found comatose after ingesting an unknown amount of tert-amyl alcohol. An empty 250-mL plastic bottle of tert-amyl alcohol 99% pure was found in his house. On presentation, he had clinical signs of respiratory failure, unresponsive narrow pupils, tachycardia (up to 150 beats/min), and hypertension (up to 175/95 mmHg). He was intubated and treated with supportive care for 24 hours, but later developed psychomotor agitation after extubation, requiring intensive pharmacological sedation and immobilization. Following the restoration of consciousness, he developed dizziness, headache, drowsiness, nausea, and ataxia, but all symptoms gradually resolved within the next 48 hours. Tert-amyl alcohol blood concentrations on day 1 and 2 of hospitalization were 83 mcg/mL and 19 mcg/mL, respectively. A urine tert-amyl alcohol concentration was 28 mcg/mL on day 2 (Anand et al, 2014).
C) HYPERTENSIVE DISORDER 1) WITH POISONING/EXPOSURE a) TERT-AMYL ALCOHOL: CASE REPORT: A 28-year-old man was found comatose after ingesting an unknown amount of tert-amyl alcohol. An empty 250-mL plastic bottle of tert-amyl alcohol 99% pure was found in his house. On presentation, he had clinical signs of respiratory failure, unresponsive narrow pupils, tachycardia (up to 150 beats/min), and hypertension (up to 175/95 mmHg). He was intubated and treated with supportive care for 24 hours, but later developed psychomotor agitation after extubation, requiring intensive pharmacological sedation and immobilization. Following the restoration of consciousness, he developed dizziness, headache, drowsiness, nausea, and ataxia, but all symptoms gradually resolved within the next 48 hours. Tert-amyl alcohol blood concentrations on day 1 and 2 of hospitalization were 83 mcg/mL and 19 mcg/mL, respectively. A urine tert-amyl alcohol concentration was 28 mcg/mL on day 2 (Anand et al, 2014).
D) CONDUCTION DISORDER OF THE HEART 1) WITH POISONING/EXPOSURE a) Cardiac dysrhythmias may occur, with potential cardiac failure, following significant exposure, although this is rare (HSDB , 2001; Gosselin et al, 1984).
3.5.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) HYPOTENSION a) RABBITS - Waugh (1992) reports some hypotension in rabbits treated with warm 7% butyl alcohol vapor for arterial hypoxemia in induced pulmonary edema (Waugh, 1992).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) IRRITATION SYMPTOM 1) WITH POISONING/EXPOSURE a) Inhalation of high concentrations may produce irritation of the respiratory tract. Cough and dyspnea may result from exposures (HSDB , 2001; Harbison, 1998; Clayton & Clayton, 1982).
B) ACUTE LUNG INJURY 1) WITH POISONING/EXPOSURE a) Pulmonary edema may occur as a result of the irritation or respiratory depression by inhalation (HSDB , 2001; Gosselin et al, 1984).
C) ACUTE RESPIRATORY INSUFFICIENCY 1) WITH POISONING/EXPOSURE a) 1-PROPANOL: Respiratory depression has been reported in patients with 1-propanol poisoning (Vujasinovic et al, 2007). 1) COMBINED INGESTION OF 1-PROPRANOL AND 2-PROPANOL: After ingesting an estimated 130 mL of 1-propanol and 300 mL of 2-propanol (Monopronto Extra solution 500 mL bottle; 27.6% of 1-propanol and 36.1% of 2-propanol) found in a hospital hand disinfectant, a 37-year-old man presented to the ED with a Glasgow coma scale of 3, temperature 36.4 degrees C, pulse 110 beats/min, blood pressure 130/80 mm Hg, and respiratory rate of 10/minute. Initial, pulse oximetry was 88% on room air. Physical examination revealed miosis, divergent ocular gaze, absent corneal reflex, hypotonic muscles, absent myotatic and plantar reflexes, and no focal neurological signs. Laboratory findings included metabolic acidosis (pH 7.29; bicarbonate 22.8 mmol/L, pCO2 6.1 kPa, and pO2 12 kPa while receiving 60% oxygen). He began to respond to painful stimuli 4 hours after admission and was fully conscious 2 hours later; he was extubated 12 hours after admission. At this time, the native urine examination revealed increased ketone levels (highest level occurred 14 hours after admission). With supportive therapy, he recovered completely and was discharged on the 3rd day after psychiatric evaluation (Vujasinovic et al, 2007).
b) TERT-AMYL ALCOHOL: CASE REPORT: A 28-year-old man was found comatose after ingesting an unknown amount of tert-amyl alcohol. An empty 250-mL plastic bottle of tert-amyl alcohol 99% pure was found in his house. On presentation, he had clinical signs of respiratory failure, unresponsive narrow pupils, tachycardia (up to 150 beats/min), and hypertension (up to 175/95 mmHg). He was intubated and treated with supportive care for 24 hours, but later developed psychomotor agitation after extubation, requiring intensive pharmacological sedation and immobilization. Following the restoration of consciousness, he developed dizziness, headache, drowsiness, nausea, and ataxia, but all symptoms gradually resolved within the next 48 hours. Tert-amyl alcohol blood concentrations on day 1 and 2 of hospitalization were 83 mcg/mL and 19 mcg/mL, respectively. A urine tert-amyl alcohol concentration was 28 mcg/mL on day 2 (Anand et al, 2014). c) Severe respiratory depression or death has not been reported with any of these compounds by inhalation. In very severe exposures, respiratory depression due to CNS depression could potentially result in death (HSDB , 2001), but this would be very rare. d) CASE REPORT: A 47-year-old man with no previous medical history was found comatose and soiled after having vomited while unconscious. He presented to the ED with a Glasgow Coma Scale score of 3, tachycardia (110 BPM), hypotension (systolic blood pressure 70 mmHg), shallow tachypneic breathing (36/min), hypotonic muscles, absent myotatic and plantar reflexes, and an aromatic odor. He was intubated and treated with dopamine, volume replacement, and oxygen. He was lavaged and given activated charcoal. Laboratory findings included acidosis with elevated lactate, renal insufficiency, hypokalemia, and hypercapnic respiratory insufficiency. He began to respond to painful stimuli 12 hours after admission, was fully conscious at 16 hours and was extubated 23 hours after admission. Toxicological examination of urine and gastric content by gas chromatography revealed 1-butanol. With supportive therapy, he had a complete recovery at 30 hours(Bunc et al, 2006). 3.6.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) HYPOVENTILATION a) MICE: Concentrations of n-butanol vapor above 3000 ppm by inhalation in mice produced a decrease in respiratory rate (Kristiansen et al, 1988). Inhalation of n-pentanol, n-heptanol, sec-butanol and tert-pentanol produced decreased respirations in mice (Hansen & Nielsen, 1994).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) CENTRAL NERVOUS SYSTEM DEFICIT 1) WITH POISONING/EXPOSURE a) CNS effects following oral ingestion or inhalation of high concentrations include headache, double vision, deafness, dizziness, giddiness, ataxia, delirium, sedation, respiratory depression, and coma (HSDB , 2001; Harbison, 1998; Arena & Drew, 1986). b) TERT-AMYL ALCOHOL: CASE REPORT: A 28-year-old man was found comatose after ingesting an unknown amount of tert-amyl alcohol. An empty 250-mL plastic bottle of tert-amyl alcohol 99% pure was found in his house. On presentation, he had clinical signs of respiratory failure, unresponsive narrow pupils, tachycardia (up to 150 beats/min), and hypertension (up to 175/95 mmHg). He was intubated and treated with supportive care for 24 hours, but later developed psychomotor agitation after extubation, requiring intensive pharmacological sedation and immobilization. Following the restoration of consciousness, he developed dizziness, headache, drowsiness, nausea, and ataxia, but all symptoms gradually resolved within the next 48 hours. Tert-amyl alcohol blood concentrations on day 1 and 2 of hospitalization were 83 mcg/mL and 19 mcg/mL, respectively. A urine tert-amyl alcohol concentration was 28 mcg/mL on day 2 (Anand et al, 2014). c) CASE REPORT: A 47-year-old man with no previous medical history was found comatose and soiled after having vomited while unconscious. He presented to the ED with a Glasgow Coma Scale score of 3, tachycardia (110 BPM), hypotension (systolic blood pressure 70 mmHg), shallow tachypneic breathing (36/min), hypotonic muscles, absent myotatic and plantar reflexes, and an aromatic odor. He was intubated and treated with dopamine, volume replacement, and oxygen. He was lavaged and given activated charcoal. Laboratory findings included acidosis with elevated lactate, renal insufficiency, hypokalemia, and hypercapnic respiratory insufficiency. He began to respond to painful stimuli 12 hours after admission, was fully conscious at 16 hours and was extubated 23 hours after admission. Toxicological examination of urine and gastric content by gas chromatography revealed 1-butanol. With supportive therapy, he had a complete recovery at 30 hours (Bunc et al, 2006). d) 1-PROPANOL: Somnolence and coma have been reported following an acute 1-propanol ingestion (Vujasinovic et al, 2007). 1) COMBINED INGESTION OF 1-PROPRANOL AND 2-PROPANOL: After ingesting an estimated 130 mL of 1-propanol and 300 mL of 2-propanol (Monopronto Extra solution 500 mL bottle; 27.6% of 1-propanol and 36.1% of 2-propanol) found in a hospital hand disinfectant, a 37-year-old man presented to the ED with a Glasgow coma scale of 3, temperature 36.4 degrees C, pulse 110 beat/min, blood pressure 130/80 mm Hg, and respiratory rate of 10/minute. Initial, pulse oximetry was 88% on room air. Physical examination revealed miosis, divergent ocular gaze, absent corneal reflex, hypotonic muscles, absent myotatic and plantar reflexes, and no focal neurological signs. Laboratory findings included metabolic acidosis. He began to respond to painful stimuli 4 hours after admission and was fully conscious 2 hours later; he was extubated 12 hours after admission. At this time, the native urine examination revealed increased ketone levels (highest level occurred 14 hours after admission). With supportive therapy, he recovered completely and was discharged on the 3rd day after psychiatric evaluation (Vujasinovic et al, 2007).
3.7.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) ATAXIA a) RATS/MICE: Rats and mice fed 0.25 to 4% w/v t-butyl alcohol experienced ataxia and hypoactivity, which were the earliest clinical signs of toxicity. A statistically significant depression in body weight was present, especially at the higher concentrations, in both mice and rats (Lindamood et al, 1992).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) GASTROINTESTINAL IRRITATION 1) WITH POISONING/EXPOSURE a) Gastrointestinal irritation with nausea, vomiting, and diarrhea are common with an odor of alcohol present in the vomitus and feces if orally ingested (HSDB , 2001; Gosselin et al, 1984).
b) 1-PROPANOL: Nausea, vomiting, abdominal cramps, diarrhea, and irritation of mucous membranes have been reported following an acute 1-propanol ingestion (Vujasinovic et al, 2007).
c) TERT-AMYL ALCOHOL: Nausea has been reported following the ingestion of tert-amyl alcohol (Anand et al, 2014).
B) GASTROENTERITIS 1) WITH POISONING/EXPOSURE a) Nausea, vomiting and diarrhea may occur (HSDB , 2001; Arena & Drew, 1986).
C) GASTROINTESTINAL HEMORRHAGE 1) WITH POISONING/EXPOSURE a) Gastrointestinal hemorrhage may rarely occur (HSDB , 2001; Weisbrodt et al, 1973).
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Hepatic |
3.9.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) HEPATOCELLULAR DAMAGE a) Damage to the liver is reported in animals but remains controversial after both acute and chronic toxicity (HSDB , 2001; Gosselin et al, 1984).
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) MYOGLOBINURIA 1) WITH POISONING/EXPOSURE a) Myoglobinuria has been reported, but is probably uncommon (Arena & Drew, 1986). Gosselin et al (1984) suggest that myoglobinuria does not usually occur (Gosselin et al, 1984).
B) GLYCOSURIA 1) WITH POISONING/EXPOSURE a) Glucosuria has been reported following exposure to 2-ethyl-1-hexanol (HSDB , 2001; Arena & Drew, 1986); there remains skepticism of the exact cause of this effect.
C) RENAL FAILURE SYNDROME 1) WITH POISONING/EXPOSURE a) Renal insufficiency has been reported in a case of 1-butanol poisoning (Bunc et al, 2006).
3.10.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) RENAL FUNCTION ABNORMAL a) RATS: Oral feedings in water, ranging from 0.25 to 4% w/v for 90 days, of t-butyl alcohol resulted in decreased urine volume with crystalluria, urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Renal changes were more notable in male rats, and toxicity results indicated the urinary tract as the target organ for t-butyl alcohol toxicity (Lindamood et al, 1992).
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Acid-Base |
3.11.2) CLINICAL EFFECTS
A) ACIDOSIS 1) WITH POISONING/EXPOSURE a) Primary alcohols are metabolized to corresponding aldehydes and acids. Accumulation of the acid metabolites is rare but may result in metabolic acidosis (Gosselin et al, 1984). b) Acidosis with elevated lactate has been reported in a case of 1-butanol poisoning (Bunc et al, 2006). c) 1-PROPANOL: Metabolic acidosis with elevated anion gap have been reported following 1-propanol poisoning. In contrast, patients with 2-propanol poisoning present with ketosis and ketonuria without acidosis 3 to 4 hours after ingestion. In one case report, a patient with a combined ingestion of 1-propranol and 2-propanol presented early with mixed acidosis and elevated anion gap and later with ketosis and ketonuria (12 hours after admission). Refer to "Isopropyl alcohol" management for more information on 2-propanol. 1) COMBINED INGESTION OF 1-PROPRANOL AND 2-PROPANOL: After ingesting an estimated 130 mL of 1-propanol and 300 mL of 2-propanol (Monopronto Extra solution 500 mL bottle; 27.6% of 1-propanol and 36.1% of 2-propanol) found in a hospital hand disinfectant, a 37-year-old man presented to the ED with a Glasgow coma scale of 3, temperature 36.4 degrees C, pulse 110 beats/min, blood pressure 130/80 mm Hg, and respiratory rate of 10/minute. Initial, pulse oximetry was 88% on room air. Laboratory findings included metabolic acidosis (pH 7.29; bicarbonate 22.8 mmol/L, pCO2 6.1 kPa, and pO2 12 kPa while receiving 60% oxygen). He began to respond to painful stimuli 4 hours after admission and was fully conscious 2 hours later; he was extubated 12 hours after admission. At this time, the native urine examination revealed increased ketone levels (highest level occurred 14 hours after admission). With supportive therapy, he recovered completely and was discharged on the 3rd day after psychiatric evaluation (Vujasinovic et al, 2007).
3.11.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) ACIDOSIS a) RABBITS - 7% warm n-butyl alcohol vapors, used to treat arterial hypoxemia in induced pulmonary edema in rabbits, caused a slight metabolic acidosis which developed slowly (Waugh, 1992; Waugh, 1993).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) METHEMOGLOBINEMIA 1) WITH POISONING/EXPOSURE a) Methemoglobinemia has rarely been reported from exposure to amyl alcohols (Clayton & Clayton, 1982; Arena & Drew, 1986). These reviews quote a 1903 article in which methemoglobinuria is reported. No evidence of methemoglobinemia is reported, nor is it likely that these alcohols could oxidize the iron of hemoglobin. Myoglobin may have been the compound found in the urine of the case in question, as may be seen after ethanol ingestion.
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) DERMATITIS 1) WITH POISONING/EXPOSURE a) Dermatitis of varying severity may occur (Gosselin et al, 1984), especially following chronic or repeated exposures (Harbison, 1998). Chronic dermal exposure can lead to drying and fissuring. 1) CASE REPORT: A 58-year-old man developed allergic contact dermatitis associated with use of a sunscreen. The patient was patch tested using the individual components supplied by the manufacturer. The test was positive at the site that corresponded to SD-40 alcohol. He was patch tested again using components of SD-40 alcohol, only the site of the tertiary butyl alcohol showed erythema at 72 hours (Edwards & Edwards, 1982).
B) ERUPTION 1) WITH POISONING/EXPOSURE a) Cutaneous erythema may occur in susceptible individuals following exposure to straight chain aliphatic alcohols (primary alcohols) (Wilkin & Stewart, 1987).
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Endocrine |
3.16.2) CLINICAL EFFECTS
A) HYPOGLYCEMIA 1) WITH POISONING/EXPOSURE a) Hypoglycemia may occur following exposure.
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Reproductive |
3.20.1) SUMMARY
A) Increased incidence of stillbirth and reduced weight gain in newborns were observed in experimental laboratory female mice given tert-butyl alcohol. Only slight teratogenicity in an inhalation teratology study of 3 butanol isomers.
3.20.2) TERATOGENICITY
A) CONGENITAL ANOMALY 1) tert-BUTYL ALCOHOL: Increased incidence of stillbirth and reduced weight gain in newborns were observed in experimental laboratory female mice given 103 g/kg orally on days 6 to 20 after conception (RTECS , 2001). a) Daniel & Evans (1982) concluded that t-butanol was approximately 5 times more potent than ethanol in producing a developmental delay in postnatal physiological and psychomotor performance in mice (Daniel & Evans, 1982).
b) Nelson et al (1989a) found only slight teratogenicity in an inhalation teratology study of 3 butanol isomers. Concentrations were such that there was evidence of both maternal toxicity (reduced food intake and weight gain) and fetotoxicity (increased variation in weights and reduced weights) (Nelson et al, 1989a).
c) NEGATIVE effect reported in neonatal rats following maternal inhalation exposure of 3000 and 6000 ppm administered 7 hours/day for 6 weeks throughout gestation and following paternal exposure for 7 hours/day for 6 weeks (Nelson et al, 1989b).
2) 3-METHYL-1-BUTANOL: Prenatal inhalation of 10 mg/L for 6 hr per day produced no embryo-fetotoxicity or teratogenicity in the fetuses of either rats or rabbits. The no-observable-adverse-effect level (NOAEL) for the dams of both species was determined to be 2.5 mg/L. At the higher concentrations of 10 mg/L a slight decrease in body weight gain in the dams of both species was observed (Klimisch & Hellwig, 1995). 3) 2-ETHYLHEXYL ALCOHOL: Musculoskeletal and urogenital abnormalities were noted in offspring of experimental laboratory female mice given 16 mg/kg orally for 12 days after conception (RTECS , 2001). 4) 1-PROPANOL: NEGATIVE effect reported in neonatal rats following maternal inhalation exposure of 3,500 and 7,000 ppm administered 7 hours/day for 6 weeks throughout gestation and following paternal exposure for 7 hours/day for 6 weeks (Nelson et al, 1989c). 5) 2-METHYL-1-PROPANOL: Prenatal inhalation of 10 mg/L for 6 hr per day produced no embryo-fetotoxicity or teratogenicity in the fetuses of either rats or rabbits (Klimisch & Hellwig, 1995). 3.20.4) EFFECTS DURING BREAST-FEEDING
A) BREAST MILK 1) BUTYL ALCOHOL: Grant & Samson (1982) noted that microcephaly was apparent in rats administered t-butanol in milk on postnatal days 4 to 7. Blood t-butanol concentration in the rats was approximately 250 mg/100 mL (Grant & Samson, 1982).
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Carcinogenicity |
3.21.4) ANIMAL STUDIES
A) CARCINOMA 1) ISOAMYL ALCOHOL - POSITIVE for liver tumors and leukemia in rats at 27 g/kg orally intermittently for 75 weeks (RTECS , 2001). a) POSITIVE for liver tumors and leukemia in rats at 3,800 mg/kg subcutaneously intermittently for 85 weeks (RTECS , 2001).
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