Tuesday, March 22, 2016

Parsley, prohibition, and machine gun oil: A sorrowful history of tricresyl phosphate poisoning

Some poisons are better known than others.

Arsenic, for example, is famous for its participation in many a murder and suicide from the Middle Ages through to the mid-19th century (after which it became easier to detect and more difficult to acquire). Even to this day, the malicious metalloid remains in the public eye as a contaminant of groundwater in parts of South Asia and of soil in old orchards.

A decidedly more obscure poison is a gooey industrial derivative of coal tar (leftovers from converting coal to coal gas) by the name of tricresyl phosphate (TCP). Over the course of the 20th century, up to 60,000 people across the globe ended up with nerve damage after ingesting foods, drinks, or medicines laced with this toxic substance. It's historically been added to plastics such as PVC to ensure their plasticity, to lubricants and hydraulic fluids to boost their effectiveness at high temperatures and pressures, and to gasoline to help ensure any engines it fuels will run smoothly.

Other things you can make with coal tar (Source)

While its name specifically refers to three similar compounds (isomers), which contain the same number of atoms but are arranged slightly differently, industrial preparations of TCP tend to be mixtures of many different aryl organophosphates. Some of these are toxic to our nervous system. Back in the day, the isomer tri-ortho-cresyl phosphate was thought to be the principal neurotoxic constituent, but it's now known other parts of the mixture are just as good at making people ill.

If it gets inside your body, TCP sets about inhibiting ester-breaking enzymes associated with your nerves, causing them to malfunction. Insecticide and nerve gas organophosphates (e.g. parathion and sarin) harm people by turning off the enzyme acetylcholinesterase, flooding nerve endings with overwhelming amounts of the neurotransmitter acetylcholine and thus disrupting our ability to control when our muscles contract and relax. Although constituents of TCP are known to inhibit acetylcholinesterase, their toxicity is primarily due to them inhibiting another esterase known as neuropathy or neurotoxic target esterase. By inactivating this enzyme, a bunch of biochemical changes take place over a week or two via which damage is inflicted on the brain, spinal cord, and peripheral nerves. This is known as organophosphorus-induced delayed neuropathy.

Ingesting a liquid contaminated with TCP initially results in an upset stomach (nausea, vomiting, diarrhea, and abdominal cramping). I'm guessing this is due to the inhibition of acetylcholinesterase and subsequent stimulation of acetylcholine receptors in the smooth muscle of the small intestine, causing it to ramp up peristalsis. After a delay of a week or two, a poisoned person's arms and legs start to ache and feel numb and weak (this usually starts in the feet, then moving up to the lower legs and forearms/hands). Within another week or so, this can progress to paralysis. Complete recovery is possible for mild cases, but usually takes several years. Some people end up with permanent nerve damage.

Our poisoning journey begins at the very end of the 19th century. French doctors, seeking an effective treatment for pulmonary tuberculosis (still one of the major causes of death in Europe at the time), decided to try giving their patients a substance called phospho-creosote. Instead of helping to fight the bacterial infection in their lungs, the liquid caused some of the patients to develop peripheral nerve inflammation (polyneuritis). It turns out phospho-creosote contains many of the same neurotoxic compounds found in TCP.

Moving forward a couple of decades, the largest ever outbreak of TCP poisoning bloomed across the Midwestern and Southwestern United States in the spring of 1930. This was well into the time of Prohibition (it ended in 1933), so black market alcoholic beverages were all the rage. One of the popular spirits was Jamaica ginger extract (also known as fluid extract of ginger or jake), a medicine that conveniently happened to be a >50% solution of ethanol. Tragically, a portion of the 1930 batches somehow became adulterated with TCP. Up until that time, jake had been prepared using, among other things, castor oil. It's thought a manufacturer out of Boston decided to swap the castor oil with TCP (specifically a preparation known as Lyndol), perhaps to save money. As the year drew to a close, some 15-20 thousand people had been affected by the bad booze (the vast majority survived), their illness having acquired the name 'Jamaica ginger paralysis'.

Only a year later, several dozen cases of paralysis were reported in the Netherlands among women who took a substance called apiol in an attempt to terminate their pregnancies. Apiol is an extract (essential oil) of parsley with a long history of use as an abortifacient and a treatment for menstrual cramps. Testing revealed the apiol taken by the women contained a substantial amount (28-50%) TCP. It's not known why it was there, but perhaps it was used to water down the apiol. Similar poisoning cases were also reported at the time (1931-32) in Germany, France, Switzerland, and Yugoslavia.

A pot of parsley (Source)

In 1937, TCP was responsible for an outbreak (68 people affected) of nerve damage in Durban, a port city in South Africa. This was traced back to a soybean cooking oil (Bestol superfine cooking oil, to be precise), which had been shipped from England in large drums previously used to store an industrial liquid containing TCP. The contaminated cooking oil also made its way on board a cargo ship, the Jean LD, which stopped in at Durban for a week. It caused three-quarters of the ship's crew to become ill. A second smaller outbreak affecting 11 people occurred in 1955. In this instance, poisoning resulted from the storage of drinking water in drums formerly filled with TCP. The drums had been obtained from a paint factory by some of the people employed there.

During WWII, a shortage of animal- or plant-derived edible fats and oils in Germany caused some of its citizens to make the unfortunate decision to cook their food using industrial oils derived from fossil fuels. These included torpedo oil and machine gun oil, both of which contained substantial amounts of TCP. As an example, factory workers in Münster became ill after bringing home oil from work and using it to fry up potato pancakes. It's not known just how many people were affected in Germany, but the Nazis did appear to be concerned about the problem, instructing factory medical officers to educate workers about the dangers of cooking with industrial oils. Similar poisonings also occurred in Switzerland and England during the war. The illness only went away once edible oils and fats again became widely available.

Fifty years after it transpired, a mysterious outbreak of paralysis in WWII-era Italy was attributed to TCP. In 1942, several dozen people living or working at a farm in Saval (on the outskirts of Verona) became ill. At the time, this illness was suspected to be the work of an infectious virus. Then, in 1994, a paper was published in which the authors reported they had examined still-paralyzed survivors of the outbreak and concluded it was likely the result of TCP poisoning. After talking to survivors and sifting through the literature, they proposed that exposure occurred via the consumption of vegetables grown in contaminated soil on the farm. At the time of the outbreak, farm workers collected old drums and tins for recycling. Some of these likely came from a nearby military truck depot, and so included residual amounts of TCP-containing engine oil. As part of the recycling process, the containers were emptied out onto the ground before being pressed into blocks, which contaminated the soil.

Olive oil adulterated with TCP struck down 10,000 people over three weeks in Morocco in the autumn of 1959. Most of those who were poisoned were in the city of Meknes. They inadvertently consumed the world's worst cooking oil: A mixture of olive oil and a jet engine lubricant containing TCP. Such a large number of people were exposed in part because the oil was sold in large containers, some of which had the lubricant added to them by dishonest, uncaring merchants seeking to stretch out their oil and increase profits.

Additional outbreaks of TCP poisoning occurred in Mumbai (India) in 1960 (contaminated mustard oil), Sri Lanka in 1977-78 (sesame oil contaminated via containers previously used to store mineral oils), and Xi'an (China) in 1995 (flour contaminated with lubricating oil via a flour processing machine).

Although TCP isn't a particularly famous poison, it's certainly harmed a lot of people. Many of those poisoned were just looking for affordable cooking oil or liquor, the means to end an unwanted pregnancy, or a reusable container to store food or water. While rarely fatal, TCP nevertheless can rob people of their mobility, sometimes for life. It should serve as a reminder of how important it is to ensure everyone has access to safe food, drinking water, and medicines.


References

Bowden DT, Turley LA, Shoemaker HA. 1930. The incidence of "Jake" paralysis in Oklahoma. American Journal of Public Health 20(11):1179-1186. [Full text]

Craig PH, Barth ML. 1999. Evaluation of the hazards of industrial exposure to tricresyl phosphate: A review and interpretation of the literature. Journal of Toxicology and Environmental Health, Part B: Critical Reviews 2(4):281-300.

Godfrey CM. 1961. An epidemic of triorthocresylphosphate poisoning. Canadian Medical Association Journal 85(12):689-691. [Full text]

Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ. 2011. Arsenic exposure and toxicology: A historical perspective. Toxicological Sciences 123(2):305-332. [Full text]

Hunter D, Perry KMA, Evans RB. 1944. Toxic polyneuritis arising during manufacture of tricresyl phosphate. British Journal of Industrial Medicine 1(4):227-231. [Full text]

Morgan JP, Penovich P. 1978. Jamaica ginger paralysis. Forty-seven-year follow-up. Archives of Neurology 35(8):530-532.

Sampson BF. 1942. The strange Durban epidemic of 1937. South African Medical Journal 16(1):1-9.

Spalding JM. 1969. Toxic chemicals and peripheral neuropathy. Proceedings of the Royal Society of Medicine 62(2):209-210. [Full text]

Tosi L, Righetti C, Adami L, Zanette G. 1994. October 1942: A strange epidemic paralysis in Saval, Verona, Italy. Revision and diagnosis 50 years later of tri-ortho-cresyl phosphate poisoning. Journal of Neurology, Neurosurgery, and Psychiatry 57(7):810-813. [Full text]

No comments:

Post a Comment