Toluene

CAS RN:108-88-3

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Toluene (toluol, methyl benzene) is an aromatic petroleum hydrocarbon that has many commercial and industrial applications. It is used as a solvent and starting material for organic synthesis and is found in paints, paint thinners, glues, and other products. Toluene products are abused via inhalation for their intoxicating effects.
    • B) TOXICOLOGY: It has long been held that toluene's effect on the central nervous system are via nonspecific lipophilic membrane interactions, which in turn modulates several neurotransmitter systems (ie, dopamine, acetylcholine, GABA, glycine, and serotonin).
    • C) EPIDEMIOLOGY: Exposures are common, but significant toxicity is generally only seen in the setting of deliberate inhalation abuse and deaths are rare.
    • D) WITH POISONING/EXPOSURE
      • 1) MILD TO MODERATE TOXICITY: Acute ingestion causes CNS depression, oropharyngeal and gastric pain and vomiting. Splash exposure to eyes may cause irritation, burning, blepharospasm, conjunctivitis, corneal edema, and corneal abrasions. Symptoms usually resolve within 48 hours. Prolonged or repeated dermal exposures may result in a defatting dermatitis. Occupational exposure has been linked to an increased risk of esophageal and rectal cancers as well as increased mortality from bone and connective tissue cancers.
      • 2) SEVERE TOXICITY: Acute inhalation produces a biphasic response with an initial CNS excitation followed by CNS depression, which is characterized by ataxia, fatigue, sedation, occasionally seizures, and at very high concentrations general anesthesia. Sudden death may occur from hypoxia or cardiac dysrhythmias. Chronic inhalational abuse is associated with muscular weakness, gastrointestinal symptoms (pain, nausea, vomiting), renal tubular acidosis (hypokalemia and metabolic acidosis), hepatic injury, and neuropsychiatric symptoms. Patients who chronically abuse toluene may exhibit hypokalemia, hematuria, proteinuria, oliguria, paresis, rhabdomyolysis, hallucinations, hyperactive reflexes, peripheral neuropathy, personality changes, tremors, headaches, emotional lability, and memory loss. Patients with long-term inhalational abuse may develop progressive irreversible encephalopathy with cognitive difficulty and cerebellar ataxia. Significant inhalational exposure causes an easily recognized odor to the breath that may persist for several days after exposure ceases. There are a small number of case reports of mothers who regularly abused toluene recreationally during pregnancy giving birth to children with microcephaly, CNS dysfunction, and minor head, face and limb anomalies. However, some of these mothers also abused ethanol as well.
0.2.3 VITAL SIGNS
  • 0.2.3.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Bradycardia, hypotension, and hypoventilation are rare effects.
0.2.4 HEENT
  • 0.2.4.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Splash exposure of the eye causes transient irritation and superficial injury. Chronic abuse is associated with decreased visual acuity, impaired color vision, optic atrophy and ototoxicity.
0.2.5 CARDIOVASCULAR
  • 0.2.5.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) ACUTE INHALATION may cause dysrhythmias (usually in chronic abusers). Bradycardia, ventricular fibrillation, and myocardial infarction have been reported.
      • 2) CHRONIC INHALATION: Chronic sniffers may develop dysrhythmias, including premature ventricular contractions and supraventricular tachycardia; dilated cardiomyopathy has been reported.
      • 3) ACUTE INGESTION may cause tachycardia and hypertension.
0.2.6 RESPIRATORY
  • 0.2.6.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Inhalation may cause irritation, acute bronchitis, bronchospasm, pulmonary edema, pneumonitis, and asphyxia. Chronic abusers may develop respiratory failure.
0.2.7 NEUROLOGIC
  • 0.2.7.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) ACUTE INGESTION: Toluene ingestion causes CNS depression.
      • 2) ACUTE INHALATION: 400 to 800 parts per million can produce euphoria, giddiness, tremors, nervousness, insomnia, headache, dizziness, fatigue, drowsiness, confusion, vertigo, increased reaction time; 800 ppm: ataxia, fatigue, and seizures; and 10,000 ppm: general anesthesia.
      • 3) CHRONIC INHALATION may cause hyperactive reflexes, peripheral neuropathy, ataxia, personality changes, tremors, headaches, emotional lability, cognitive dysfunction and memory loss.
0.2.8 GASTROINTESTINAL
  • 0.2.8.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Ingestion or inhalation may cause vomiting, abdominal cramps, and diarrhea.
0.2.9 HEPATIC
  • 0.2.9.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Rarely, hepatorenal failure has been attributed to toluene abuse or occupational exposure. Hepatomegaly and impaired liver function has also been reported.
0.2.10 GENITOURINARY
  • 0.2.10.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Transient distal renal tubular acidosis (RTA), with hyperchloremic metabolic acidosis, hypokalemia and urine pH greater than 5.5, is common in paint sniffers who have been hospitalized.
      • 2) Proximal renal tubular acidosis, or Fanconi syndrome, is less common (urine pH greater than 5.5, uricosuria, hypophosphatemia, hypocalcemia).
      • 3) Isolated cases of irreversible renal insufficiency, glomerulonephritis, focal segmental glomerulosclerosis, acute interstitial nephritis and renal failure secondary to myoglobinuria have been reported.
0.2.11 ACID-BASE
  • 0.2.11.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Hyperchloremic metabolic acidosis is common in hospitalized toluene abusers.
0.2.12 FLUID-ELECTROLYTE
  • 0.2.12.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Hypokalemia, metabolic acidosis, and hypophosphatemia are typical; hypercalcemia and hypouricemia less frequent. Hypocalcemia and precipitation of tetany has occurred during correction of acidemia.
      • 2) Patients with weakness may have severe fluid/electrolyte imbalance, most notably hypokalemia.
0.2.13 HEMATOLOGIC
  • 0.2.13.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Bone marrow dysplasia and anemia have occurred after exposure to toluene without benzene contamination. Decreased prothrombin has been reported after occupational toluene exposure.
      • 2) Granulocytopenia was found in rats injected with toluene.
0.2.14 DERMATOLOGIC
  • 0.2.14.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Prolonged contact may cause drying and defatting or superficial burns.
0.2.15 MUSCULOSKELETAL
  • 0.2.15.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Rhabdomyolysis is common in chronic toluene abusers; severe muscle weakness is a common presentation in chronic abuse.
0.2.18 PSYCHIATRIC
  • 0.2.18.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Psychiatric disorders are common in chronic toluene abusers, including bizarre behavior, acute paranoid psychosis, confusion, visual and auditory hallucinations, mood lability, and decreased IQ.
0.2.20 REPRODUCTIVE HAZARDS
  • A) Multiple physical deformities, with signs similar to fetal alcohol syndrome, microencephaly, CNS dysfunction, and variable growth deficiencies, have occurred in infants born to mothers who abused toluene during pregnancy.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS108-88-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) IARC Classification
        • a) Listed as: Toluene
        • b) Carcinogen Rating: 3
      • 1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) A link between toluene exposure and esophageal and rectal cancers, increased mortality from bone and connective tissue cancers, and one case of non-Hodgkin lymphoma has been suggested but not confirmed.
    • B) The International Agency for Research on Cancer (IARC) has described toluene as Group 3 (not classifiable as to its carcinogenicity in humans).
  • 0.2.21.3 ANIMAL OVERVIEW
    • A) Animal data have been limited and equivocal.
0.2.22 GENOTOXICITY
  • A) Chromosome damage has been linked to exposure to toluene. There is conflicting information regarding the potential of toluene to cause DNA strand breaks, and regarding its mutagenicity.
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