TOXICOLOGY DETECTIVE CASES
The following six cases raise important issues in toxicology and will be used for class discussions.
Case 1: THALIDOMIDE
The year is 1958, and you have just been selected to head the US Food and Drug Administration. On your desk are hundreds of letters from various health professionals suggesting the approval of a sedative drug called Thalidomide, which has low acute toxicity, and is negative in rat and rabbit organ, carcinogenic, and teratogenic assays. Thalidomide has been prescribed for 10,000 women over the last 8 years in Europe. Do you approve the use of this drug in the US? If so, why do you believe Thalidomide is safe? If not, how would you defend your decision, or what further tests would you require?
Case 2: ACETYLSALICYLIC ACID
As the new head of the FDA, you are presented with some conflicting evidence regarding a drug called acetylsalicylic acid. Apparently back in 1763, a Reverend Edmund Stone effectively treated fever with the bark from willow trees. The effective ingredient turned out to be salicylic acid. This drug has been used in different forms since then, and has shown good efficacy and low toxicity in treating fever, pain, and arthritis. However, acetylsalicylic acid is teratogenic in mice, rats, and hamsters. How do you approach this controversy in deciding whether or not to approve this drug for use?
Case 3: ASBESTOS
The year is 1967, and you have been hired by Johns/Manville as their chief health and safety officer, responsible for the health of thousands of workers on the job. A local health agency has just published a study where they found that the lung cancer rate amongst Johns/Manville blue collar workers (particularly those working in shipyards) is higher than white collar workers from another industry. The health agency claims that asbestos is to blame. Your boss has scheduled a meeting with workers, the health agency, and the public. How might you interpret and explain the results of the study? Does the study prove that asbestos caused the observed lung cancer?
Case 4: SICK BUILDING SYNDROME / CANCER STUDIES
You're a high school senior, about to enter biology lab, when you notice that the teacher is out with "sick building syndrome" ("What's that?").
You decide to run class yourself and begin a lecture on carcinogenicity. Your kind classmates decide to give you a test of fire and ask the following questions: 1)"I heard about one study where they used 23,000 mice to see if a chemical causes cancer. Why do they have to use so many animals, and give them such high doses?"
2) "When they did the saccharin study, they used such high doses. That would be like drinking 100 diet sodas a day. How can that study be relevant to my risk?"
3)"What's the shape of the dose (amount) vs. response (# animals with tumors) curve? Is it linear down to no dose, or is there a safe dose?"
Case 5: COMPARING RISKS
As a graduate student doing an internship with the Washington State Department of Labor and Industries, you have been asked to represent the City of Seattle in a debate over the health risks for a proposed waste incinerator. The company proposing to build the incinerator claims that people living nearby would be subject to an incremental risk of 1/1,000,000 of developing cancer. You strongly declare that this is too high a risk for the good citizens of Seattle! The company then produces the following statistics:
| ACTIVITY | RISK OF DEATH / YEAR |
| Smoking (10 cigarettes/day) | 1/400 |
| Driving a Car | 1/5,000 |
| Work in Industry | 1/30,000 |
| Being Struck by Lightning | 1/1,000,000 |
They suggest that the risk from the incinerator is insignificant compared to these common risks. What is your response? Are these risks comparable?
Case 6: CHEMICAL HALF-LIFE
The half-life (t 1/2) of a substance can be thought of as the time is takes to halve the amount in the body after stopping exposure. The half-life is also the time to reach 50% of the final amount in the body under constant exposure. As the new EPA Technical Director, you have been asked by your boss (who isn't versed in toxicology) to set 15-minute exposure limits for the following chemicals: Chemical A (t 1/2=5 min.), B (t 1/2=8 hr.), and C (t 1/2=20 min.). Is a 15-min. exposure limit appropriate for all of these chemicals? If so, why? If not, how long a limit should be used for each?
Having solved that problem, you are asked by the US Olympic Committee to calculate the percentage of an anabolic steroid (t 1/2=7 days) remaining in an athlete's body if she took a dose one month before competition.