Chloropicrin: Everything old (in CBRN) is new again
Chloropicrin (NATO code PS) was first used as a chemical warfare agent by Russia in 1916 during WWI. It's relevant again today.
BLUF:
On a spectrum of severe effects, chloropicrin toxicity falls between chlorine and phosgene but also has GI symptoms. Ocular and direct skin exposure can resemble sulfur mustard contact.
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Later in WWI, allied forces also used Chloropicrin.1 More recently, Russia has likely been using it against Ukraine. See, the Wall Street Journal article from May 23, 2024: “Burning Skin, Teary Eyes: Ukraine’s Trops Say Russis is Using a Banned Toxic Gas. Ukrainian forces describe the physical effects of gas they say Moscow’s troops are using to oust them from their positions.”
Cloropicrin Background
Chloropicrin is a colorless-to-faint-yellow liquid with a highly irritating odor. Historically described as smelling like “fly paper,” it was first patented in 1908 as an insecticide.
In the 1950s, it was a common soil fumigant, able to kill fungus and other parasites. 2 It is currently a restricted-use pesticide in the US, but at one time, it was the 4th most common insecticide in the USA and was frequently used in Japan as well. 3 Despite its long history of use, little actual human clinical data exists. Most involve experimental animals or accidental human exposures as a fumigant.
Its high volatility causes it to dissipate rapidly in the environment. Low water solubility mainly results in central airway and mucus membrane effects.2
Chloropicrin Classification
Its use during WWI was often as a “vomiting agent” because it could penetrate through early protective masks and cause vomiting.* This resulted in soldiers removing their protective masks to vomit, thereby greatly increasing exposure to the agent. 2
Clinical Presentation
In a review of over 600 accidental exposures, 65 to 93% had ocular symptoms, 45 to 54% respiratory, and 19 to 47% systemic complaints. 5
Immediate low-level exposure results in watery eyes, runny nose, and cough from mucus membrane and upper respiratory tract irritation 5 This seems consistent with other traditional “riot control agents” like CS.
Ocular exposure can result in eyelid swelling and corneal ulceration by 24 hours, much slower than vesicants (i.e., sulfur mustard and lewisite). Unlike those later agents, recurrent corneal ulceration hasn’t been reported. Vesicants are known to cause corneal opacification, which can occur with chloropicrin as well, but generally takes 3 to 7 days, as opposed to hours with mustard and lewisite. 3
Oddly, hyphemia, blood pooling in the anterior chamber of the eye with gravity has been reported in mice exposed to chloropicrin, but it didn’t occur until day 25 post-exposure, which hasn’t been seen with the other agents. This can result in increased intraocular pressure and retinal damage. Currently, there is no specific ocular treatment for chloropicrin toxicity. 3
With increasing dose or prolonged exposure (likely because chloropicrin breakdown products include both chlorine and phosgene), death can occur from pulmonary edema. Methemoglobinemia can occur, but how it occurs is poorly understood. 2,5
Taken together, this is often called “PS syndrome”: eyes, nose, throat irritation, headache, nausea, vomiting, and shortness of breath both from lung irritation, subsequent decreased respiratory rate, and pulmonary edema. 2
Direct skin contact results in itching, irritation, rash, and blistering 2 which could be confused with sulfur mustard exposure.
*Current US DOD CBRN protective mask filters are able to filter out this agent.
Notes
1Henderson, Terry J., Chemistries of Chemical Warfare Agents. Chemical Warfare Agents, 3rd Ed, Editors, Brian J. Lukey, James A. Romano, Jr., Harry Salem. CRC Press, 2019.
2Salem, Harry, Riot Control Agents. Medical Aspects of Chemical Warfare, 2nd Ed, Editor Tuorinsky, Shirley. Borden Institute, 2008.
3Okoyeocha EOM, Tewari-Singh N. Chloropicrin induced ocular injury: Biomarkers, potential mechanisms, and treatments. Toxicol Lett. 2024 May 15;396:70-80. doi: 10.1016/j.toxlet.2024.04.006. Epub 2024 Apr 25. PMID: 38677567.
4Marzec J, Nadadur S. Countermeasures against Pulmonary Threat Agents. J Pharmacol Exp Ther. 2024 Jan 17;388(2):560-567. doi: 10.1124/jpet.123.001822. PMID: 37863486; PMCID: PMC10801713.
5Pesonen M, Vähäkangas K. Chloropicrin-induced toxicity in the respiratory system. Toxicol Lett. 2020 May 1;323:10-18. doi: 10.1016/j.toxlet.2020.01.022. Epub 2020 Jan 23. PMID: 31982502.
