Chloroform: A Profile in Risk Management

In Scotland’s St. Giles Cathedral, there hangs a peculiar plaque praising the discovery of the anesthetic properties of the chemical compound chloroform. Scottish obstetrician Dr. James Simpson is widely credited with this 1847 medical milestone.

Chloroform, a simple compound consisting of carbon, chlorine and hydrogen, has more recently been in the news as a byproduct of water chlorination. These two dramatically different exposure scenarios, i.e., different levels and forms of exposure, present an example of a principle stated more than 500 years ago that “All things are poison, and nothing is without poison; only the dose permits something to not be poisonous.” Specifically, human exposure to the same compound under dramatically different scenarios results in dramatically different conclusions with regard to potential effects on human health.

Chloroform: Once a “go-to” anesthetic

When available (emphasis on when), chloroform was the “go-to” anesthetic during the American Civil War. To be effective, chloroform had to be inhaled at concentrations of 3,000 – 30,000 parts per million (1 ppm = 1 inch in 16 miles). Anesthesia was often unavailable, however, and many wounded soldiers endured unimaginable pain as limb amputations and other procedures were performed without the benefit of local numbing or general sedation. The “best surgeons” were the ones who could literally saw off a limb in the shortest possible time. (We are talking amputations measured in tens of seconds.) More often than not, these procedures resulted in patients dying from the shock of surgery, not from the wound itself.

Doctors eventually stopped relying on chloroform for surgery and childbirth after it was shown in some cases to cause adverse effects on the heart, liver and/or kidneys and safer anesthetics were developed, such as oxygen mixed with nitrous oxide. Surgery could be survived using a lower risk method of anesthetizing.

Chloroform: A byproduct of drinking water disinfection

The determination that (a) many human diseases, such as cholera and typhoid, are transmitted by drinking contaminated water, together with (b) the discovery that chlorine and related compounds are effective in disinfecting contaminated water led to one of the top 10 public health achievements of the 20th century—the control of infectious diseases. The ability to halt the spread of infectious diseases is one of the leading reasons for the recent and dramatic increase in human life spans.

In the early 1970s, sensitive laboratory methods revealed the presence in treated drinking water, at extremely low levels (e.g., 70 parts per billion; 1 ppb = 1 inch in 16,000 miles) of compounds, such as chloroform, that result from the reaction of chlorine disinfectants with natural organic matter in water. These substances are known as disinfection byproducts and they are an unintended consequence of water purification. The benefit versus risk issue facing the Environmental Protection Agency (EPA) and other national bodies in regulating disinfection byproducts is to protect the public from the proven risk of waterborne disease (see daily newspapers for occurrence during natural disasters and outbreaks in the developing world) while keeping the unproven risk (based on minute amounts consumed) of adverse health effects of chloroform low. The most common approach to further reducing disinfection byproducts like chloroform is to remove precursor organic matter from water prior to disinfection.

Risk vs. Benefit

The scientific principle illustrated above is the reduction of risk. Although risk can never be entirely eliminated, the goal is always to replace something of higher risk by something of lower risk. Thus, chloroform was used as an inhaled general anesthetic because the risk of dying in surgery was greater than the compound’s side effects under its condition of use. In simple terms, the benefit greatly outweighed the risk. As the health risks of high concentrations of inhaled chloroform became known, and with the advent of safer general anesthetics, chloroform’s use as an anesthetic was discontinued because its benefit–surviving amputation–could be achieved using lower risk methods.

We have come a long way from using chloroform as an anesthetic, and it may be surprising to some that chloroform may be present in chlorinated drinking water. However, the benefit versus risk calculation for its presence in drinking water is completely different than its use as an anesthetic. First, the levels of ingested chloroform in water are hundreds of thousands of times less than when it was inhaled as an anesthetic. In addition, the risk of illness and death from waterborne disease is significant and common for non-disinfected water. According to the EPA, at current regulated levels in drinking water, chloroform represents “no known or expected risk to health”. Finally, there are many circumstances under which there is no other method that provides the same advantages as chlorine disinfection, namely its ability to maintain “residual activity” over time, its use in the absence of machinery or source of power, its low cost and portability.

A Scientific Truth is one that is Reconfirmed through the Ages:

Over 500 years ago, Philippus Aureolus Theophrastus Bombastus Von Hohenheim (Paracelsus to his friends), the German-Swiss physician and Archbishop of Salzburg, established the role of chemistry in medicine and wrote Der grossen Wundartzney (Great Surgery Book). Paracelsus recognized that all compounds have levels at which they are harmful and levels at which they are safe, thus leading to his dictum, which is usually paraphrased as: ‘It’s the dose that makes the poison’. It is the role of science to determine these levels for each compound.

Recently the World Health Organization stated it more specifically for chloroform and other disinfection byproducts:

The health risks from these byproducts at the levels at which theyoccur in drinking water are extremely small in comparison with the risks associated with inadequate disinfection. Thus, it is important that disinfection not be compromised in attempting to control such byproducts.

Paracelsus would agree.

Bruce Bernard, PhD, is President of SRA International, Inc. and Associate Editor of the International Journal of Toxicology.