Initial Check

This initial check will help you assess your current knowledge about carbon tetrachloride toxicity. To take the initial check, read the case below and then answer the questions that follow.

A hazardous waste worker has delayed-onset abdominal pain, nausea, vomiting, and diarrhea.

As the physician on duty at a hospital emergency department (ED) in an urban community, you are notified that an ambulance is bringing three hazardous waste workers-two males (ages 40 and 25 years) and a female (age 30 years)-directly from their worksite to your emergency room. All three workers are complaining of

• headache,
• dizziness, and
• nausea.

You learn that the workers were handling several dozen barrels of a sweet-smelling hazardous waste liquid in a hot, unventilated room. Their work required taking samples from barrels obtained from a defunct chlorofluorocarbon manufacturing plant. All three workers were initially wearing full-face respirators and protective clothing. However, the younger of the two males removed his respirator early in the day. He said he had a hangover with nausea and felt it was easier to work without being hampered by the respirator. The other two workers continued in full protective gear.

After 3-4 hours, all three workers began to experience headache, dizziness, and nausea and notified their supervisor.

On clinical evaluation at the ED, initial routine laboratory results were within normal limits for all three workers. Two of the workers (the older male and female) had resolution of their symptoms within 2 hours, had no abnormal physical findings, and were discharged. The third worker (younger male) did not show significant symptom improvement at 2 hours and developed mild ataxia and concentration deficits on mental status exam. He was kept in the ED under close observation. You learn from this patient that he has been in good health with no history of similar problems. The previous evening, in celebration of his birthday, he drank 9-12 beers, which accounts for his hangover this morning. He also mentions that this morning, while cleaning several wounds sustained in a fight the previous evening, he spilled isopropyl alcohol on his hands and clothing, but did not bother to change his clothing.

Six hours later, while still in the ED, the younger male becomes acutely ill. He has

• abdominal pain,
• nausea,
• vomiting, and
• diarrhea.

His rectal temperature is now 101∘F, pulse 140/minute, and he has become disoriented and drowsy. Two days after hospital admission, he still has an elevated temperature and abnormal laboratory test results, as follows:

• Serum creatinine – 2.0 mg/dL (normal 0.7-1.5 mg/dL);
• AST (SGOT) – 80 U/L (normal 7-45 U/L);
• Total bilirubin – 2.4 mg/dL (normal 0.1-1.4 mg/dL);
• Prothrombin time (PT) – 15 seconds (normal 10-13 seconds).

Urinalysis reveals 2+ proteinuria, and urine output has decreased, despite intravenous hydration.

1. How will you identify the material to which the workers have been exposed?
2. You discuss the acute exposures with the workers’ company supervisor. He suspects that the waste barrels contain carbon tetrachloride (CCl₄) – a chemical with a sweet odor used as a starting material in the synthesis of chlorofluorocarbons. The 40-year-old (older) male worker in the case study has a full beard. He has a history of alcoholism, but he has been abstinent for several years. He also has a history of hepatitis B, the result of a blood transfusion more than 10 years ago. If the material in the barrels is CCl₄, is this worker at increased risk for CCl₄‘s adverse health effects?
3. The female co-worker later discovers she was almost 6 weeks pregnant at the time of this exposure episode. Her obstetrician calls you to discuss the implications of the exposure to the fetus. What is your recommendation? Explain.
4. Early that evening, the manager calls to inform you that the company has identified the hazardous waste as CCl₄. Now that you know the exposure is confirmed as CCl₄, do you consider the younger male worker to be at increased risk for acute health effects? Why?
5. What is the possible clinical course for the younger male?
6. What laboratory work-up is advised for patients exposed to CCl₄?
7. What initial action should be taken in the emergency department for patients exposed to CCl₄?
8. What treatment or antidote would you consider for the younger male worker?
9. What follow-up would you recommend for the younger male worker and his potentially exposed co-workers?
10. What specialized clinical resources are available for consultation or referral of patients exposed to hazardous substances, including CCl₄? What actions will the waste management company take to comply with the Occupational Safety and Health Administration (OSHA) Act and OSHA Hazard Communication Standard that protect workers from adverse health effects from exposure to hazardous substances in the workplace?

1. History of the source plant as a chlorofluorocarbon manufacturer is suggestive of CCl₄. You can request a CCl₄ safety data sheet (SDS) from the company while awaiting their barrel sample test results. You can also consider clinical consultation with a medical specialist with expertise and experience evaluating and treating patients exposed to hazardous substances, including CCl₄. Publicly available information on these types of clinical consultation and referral resources are provided under “Clinical Resources” in the “Sources of Additional Information” section of this course.

   More information for this answer can be found in the “What Is Carbon Tetrachloride?” and “Sources of Additional Information” sections.

2. The older male’s history of alcoholism and hepatitis B could put him at increased risk for CCl₄‘s adverse health effects. Underlying liver damage would increase the risk for acute effects and subsequent hepatocellular carcinoma. Although he was working in an appropriate protective suit and full-face respirator, he still could have been exposed. For example, his beard might have prevented proper fit of the respirator face piece. His symptoms could also be the result of working in a hot, enclosed space, or they could be psychophysiological.

   More information for this answer can be found in the “Who Is at Risk for Exposure to Carbon Tetrachloride?” section.

3. It is unclear if the female patient has been exposed to CCl₄. Her symptoms might be related to “morning sickness” associated with her pregnancy. Nevertheless, it is important that she discuss this possible exposure with her obstetrician.

   CCl₄ is lipophilic and can readily pass through the placenta to the fetus after maternal exposure. However, studies have not found sufficient evidence to associate CCl₄ exposure and adverse birth outcomes in humans. In animal studies, CCl₄ can induce embryotoxic and embryo lethal effects, but only at doses that are toxic to the mother.

   More information for this answer can be found in the “What Are the Toxicological Effects of Carbon Tetrachloride Exposure?” section.
4. Because the younger male removed his respirator and presumably breathed the solvent for a prolonged time, he is at higher risk for acute health effects from CCl₄ exposure. His previous ethanol intake and possibly his recent exposure to isopropyl alcohol increase his risk for CCl₄-induced adverse health effects. Alcohols can induce production of mixed function oxidase enzymes, thereby potentiating the formation of CCl₄ toxic intermediates and metabolites.

   More information for this answer can be found in the “Who Is at Risk for Exposure to Carbon Tetrachloride?” section.

5. Acute hepatic necrosis and renal impairment can occur up to 2 weeks after a CCl₄ exposure. Other secondary health effects can include coagulation disorders, cardiac dysrhythmias, and pulmonary edema. Without improvement in the kidney and liver disorders, these effects are not likely to resolve. Because of the patient’s multiple exposures to hepatotoxic agents (i.e., recent heavy consumption of ethanol and potential occupational exposure), acute care should begin as soon as possible as a preventive measure.

   Note: Whether or not the isopropyl alcohol spilled on the patient’s clothing will affect the patient’s medical condition is unclear. Reports of isopropyl alcohol’s ability to potentiate the harmful effects of CCl₄ are based on inhalation studies in experimental animals. Significant inhalation of isopropyl alcohol in this case is unlikely and intact skin does not readily absorb isopropyl alcohol.

   Most cases of fatal, CCl₄-induced hepatotoxicity involve persons with a history of heavy ethanol abuse. Although the patient consumed ethanol the night before the incident, he denies frequent alcohol use, which might make it more likely that his liver is healthy. Nevertheless, exposure to ethanol within 12 hours before CCl₄ exposure will potentiate CCl₄‘s toxicity. If the patient survives the first 2 weeks, the prognosis is good for complete recovery or for only mildly compromised liver and kidney function.

   More information for this answer can be found in the “What Are the Toxicological Effects of Carbon Tetrachloride Exposure?” section.
6. The following laboratory workup is recommended for patients exposed to any volatile solvent (including CCl₄): baseline hepatic and renal function tests (i.e., AST [SGOT], ALT [SGPT], bilirubin, alkaline phosphatase, BUN, creatinine, electrolytes, urinalysis, PT, PTT, and CBC.

   Some solvents might cause dysrhythmias and pulmonary edema (probably secondary to renal toxicity); therefore, you should obtain a baseline electrocardiogram and chest radiograph. To monitor the patient’s condition, you should repeat these tests periodically. Acutely ill patients should have their blood oxygen levels and cardiac rhythm monitored.

   You should also make sure appropriate public or occupational health reports are filed. Some states might require filing a doctor’s first report of illness with the state health department. ED physicians might overlook filing these reports.

   More information for this answer can be found in the “Clinical Assessment – Laboratory Tests” section.

7. Initial actions include removing all contaminated clothing (dermal absorption of some solvents is high) and cleansing the skin with mild soap and water. Care should be taken to prevent exposure of ED personnel to fumes from and skin contact with contaminated clothing. If possible, decontaminate the patient before he or she enters the ED.

   More information for this answer can be found in the “How Should Patients Exposed to Carbon Tetrachloride Be Treated and Managed?” section.

8. Treatment is generally supportive. Maintain an open airway and assist ventilation if necessary. Treat coma and arrhythmias. Avoid use of epinephrine and other sympathomimetic amines that might worsen any arrhythmias resulting from myocardial sympathomimetic sensitization caused by CCl₄. Treat tachyarrhythmias with propranolol or esmolol.

   Case reports from Europe, where antioxidants such as N-acetylcysteine (NAC) (Mucomyst, Acetadote) are used, suggest that when these free-radical scavengers are given intravenously within 12-16 hours after a high-level acute CCl₄ exposure, they might prevent or decrease hepatic and renal damage [De Ferreyra et al. 1974; De Ferreyra et al. 1977; Prescott et al. 1977; Kearney 2007]. No treatments (e.g., multi-dose activated charcoal, hemodialysis) are currently known to enhance CCl4 elimination. Consider consulting with a medical toxicologist (poison center) or other medical specialist with expertise and experience treating and managing patients exposed to CCl₄, and also consulting with a gastroenterologist/hepatologist.

   More information for this answer can be found in the “How Should Patients Exposed to Carbon Tetrachloride Be Treated and Managed?” section.

9. Immediate follow-up for the acutely ill patient includes monitoring liver and kidney function for up to 2 weeks. You should also periodically evaluate the patient’s cardiac and pulmonary systems and clotting ability; abnormalities can occur secondary to hepatic and renal damage.

   You should advise all three persons (the patient and his two coworkers) to avoid other hepatotoxic agents, such as ethanol, drugs, solvents, and chlorinated compounds. Both the 40-year-old male (with possible liver injury as a result of alcoholism and hepatitis B) who was discharged the morning after the incident and the acutely ill 25-year-old male patient might be at increased risk for hepatocellular carcinoma; they should be monitored periodically. If the 25-year-old patient’s vaccinations are not up-to-date, advise him to get the hepatitis B vaccine. The 30-year-old female, who used full protective gear and whose symptoms disappeared quickly, is probably at minimal risk.

   More information for this answer can be found in the “What Instructions Should Be Given to Patients Exposed to Carbon Tetrachloride?” section.

10. Typically, companies consult or hire health care providers with expertise in occupational health and safety to work with industrial hygienists and other worksite health personnel to provide care and assist with development of worker health and medical surveillance programs required by the Occupational Safety and Health Administration (OSHA). This includes protocols for periodic health examinations of all employees and confidential maintenance and storage of employee medical records (which should contain a complete exposure history). Under the OSHA Hazard Communication regulation (right-to-know provisions), safety data sheets (SDSs) for hazardous chemicals in the workplace must be made available to the workers, to their physician, and to a designated worker representative. All employees using a respirator should be fit-tested and properly trained before entering a hazardous environment. Proper supervision is necessary at all times. Employees who are ill should not be allowed to remain at work, nor should employees be permitted to work without the requisite protective gear.

    More information for this answer can be found in the “What Instructions Should Be Given to Patients Exposed to Carbon Tetrachloride?” section.