Agency for Toxic Substances and Disease Registry
Toluene Toxicity
Answers to Pretest and Challenge Questions

Pretest

1. The ingredients of the spray paint should be identified. Obtaining the original container and inspecting the label might be sufficient. If the ingredients are not listed on the label, the information can be obtained by contacting the distributor or manufacturer, or the information might be available from the regional poison control center.

   Further history should include questions regarding previous bouts of asthma, chronic bronchitis, allergic conditions, and prior episodes of chest complaints after chemical exposure.

2. Yes. The patient's transient nausea, headache, dizziness, and lightheadedness are consistent with exposure to toluene (but not with exposure to toluene diisocyanate). Although toluene can be irritating to the airways, the degree of wheezing and dyspnea experienced by this patient and the persistence for several hours after cessation of exposure both indicate that an intercurrent disorder might be present.

   The patient has no history of chronic respiratory disease, yet pulmonary function testing suggests airway obstruction. She has had a previous significant exposure to a strong respiratory-tract irritant (toluene diisocyanate), which caused severe respiratory symptoms within 24 hours; she reports that since this episode, exposure to irritating substances continues to provoke symptoms similar to asthma. This history suggests RADS. Criteria used to diagnose RADS are listed below. Using the spray paint in a poorly ventilated room could readily create a toluene concentration irritating enough to provoke bronchospasm in a patient with RADS.

   The diagnostic criteria for RADS include the following:

   • no history of respiratory system complaints prior to exposure;
   • a single, specific exposure involving high concentrations of an irritant fume, gas, or vapor that was associated with the initial symptoms;
   • onset of symptoms occurred within 24 hours of the initial exposure and persisted for at least 3 months;
   • pulmonary function tests usually indicate airflow obstruction;
   • methacholine challenge test is positive (e.g., <8 mg/mL); and
   • other types of pulmonary disease have been ruled out.
3. Toluene has caused fetal malformations in chronically exposed experimental animals. Cases have been reported of congenital malformations and severe neonatal acidosis in infants of women who chronically abused toluene throughout pregnancy. In most of those cases, the toluene doses were very high, but concomitant abuse of ethanol occurred, so fetal alcohol syndrome cannot be excluded. Given the mild, brief exposure that this patient incurred, it is unlikely that the fetus was harmed. Should the patient desire further counseling, you could refer her to a teratology consulting service such as the Motherisk Program at the Hospital for Sick Children in Toronto.
4. Treatment for RADS is essentially the same as treatment for asthma: beta-agonist inhalants (e.g., albuterol or terbutaline sulfate), cromolyn sodium, and corticosteroids should be administered. Of the various beta-agonist inhalants, terbutaline sulfate is nonteratogenic in experimental animals and might be the best choice for this patient. Consider cromolyn sodium if prophylactic treatment is deemed necessary. Cromolyn sodium prevents both antibody-mediated and nonantibody-mediated mast cell degranulation and mediator release. The usual precautions for use of corticosteroids apply. The patient should be advised to avoid exposure to all pulmonary irritants.

Challenge

1. You could explain to the patient that TDI is not the same chemical as the chemical in the spray paint. Both toluene and TDI are liquids, but their chemical structures are different, as are their toxicities. Toluene is a common solvent found in many household products; its toxicity is low, and at low doses (<100 ppm) it normally causes few symptoms. On the other hand, TDI is very irritating to the eyes and respiratory tract and can cause bronchospasm at levels <1 ppm. Furthermore, TDI can sensitize exposed individuals and cause coughing spasms at even lower levels than the original exposure, and this does not occur with toluene.
2. See answer (b) above.
3. There is little clinical benefit in measuring blood toluene levels or levels of toluene metabolites such as hippuric acid in the urine. Treatment would not be altered regardless of the results. The only available comparison data are from either deliberate toluene abusers or asymptomatic workers with chronic exposure, and it is unclear how such data would apply to this patient.
4. See answer (c) above.
5. There are few data to suggest that toluene is carcinogenic. Earlier reports of cancer occurring after chronic toluene exposure were probably caused by toluene's significant contamination with benzene, which is a known carcinogen. (Because of modern distillation methods, benzene is no longer a contaminant of toluene.) The patient can be reassured that a single exposure to toluene is unlikely to cause or contribute to the development of cancer.
6. See answer (d) above.

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