ABSTRACT
A fundamental maxim of toxicology is “The dose makes the poison.”* Regulations must protect against exposure to toxic chemicals at doses large enough to result in toxic effects. Exposure prevention extends to multiple routes of exposure. For example, effective regulation will prevent the combination of ingesting contaminated drinking water and inhaling chemical vapors while showering with the same contaminated water. Unfortunately, the regulations promulgated by different agencies pursuing a wide range of protective oversight (such as food quality, air quality, water quality, and drinking water treatment) may not be holistically integrated to produce a framework that accounts for the additive effects of multiple routes of exposure to the same contaminant. For example, perchlorate, the oxidizing salt used in the production of solid rocket motors, fi rst emerged as a drinking water concern. We have subsequently learned that the relative source contribution (RSC) from ingestion of perchlorate in food is much larger than was originally understood; however, perchlorate in food is not regulated and remains the subject of ongoing investigation. Similarly, the concentration in water and air was the primary focus of regulations for trichloroethylene (TCE), whereas haloacetic acids-the breakdown products in the liver-were not. When accounting for total exposure to haloacetic acids from inhaling TCE vapors and ingesting haloacetic acids present in drinking water as disinfection by-products, it may be warranted to adjust the regulatory threshold for TCE downward to minimize the RSC to haloacetic acid exposure. These examples underscore the diffi cult challenge faced by government scientists who work to establish protective regulations. Their challenge is exacerbated by the large uncertainty associated with correlating laboratory animal data to estimation of toxic effects in humans.
