Poisoning by an Illegally Imported Chinese Rodenticide Containing Tetramethylenedisulfotetramine --- New York City, 2002

Illegally imported foreign products can result in domestic exposures to unusual toxic chemicals, and health-care providers might not be able to provide appropriate therapy because the chemical ingredients might not be listed or recognized even after translation of the product label. This report describes the first known case in the United States of exposure to a Chinese rodenticide containing the toxin tetramethylenedisulfotetramine (TETS), a convulsant poison. The report of this investigation highlights the need to prevent such poisonings through increased public education, awareness, and enforcement of laws banning the importation of illegal toxic chemicals.

On May 15, 2002, a previously healthy female infant aged 15 months living with her family in New York City was found by her parents to be playing with a white rodenticide powder that they had brought from China and applied in the corner of their kitchen. After 15 minutes, the child had generalized seizures and was taken to an emergency department. Her initial blood glucose level was 108 mg/dL (normal range: 80--120 mg/dL). Despite aggressive therapy with lorazepam, phenobarbital, and pyridoxine, she had intermittent generalized seizure activity for 4 hours and required intubation.

After 3 days, the infant was extubated successfully but appeared to have multiple neurologic deficits, including absence seizures and possibly cortical blindness. Continuous electroencephalogram monitoring, performed during the initial hospitalization, revealed multiple epileptogenic foci. The infant was discharged in June; as of November 5, the infant remained severely developmentally delayed and was on valproic acid therapy for seizure control.

Translation of the rodenticide package labeling from Chinese to English did not clarify its contents (Figure). A search of the China National Poison Control Center's (NPCC) web-site for rodenticides suggested that the ingredients might have included sodium monofluoroacetate, fluoroacetamide, tetramethylenedinitrosotetramine, or strychnine. However, an initial laboratory analysis was negative for sodium fluoroacetate, fluoroacetamide, bromethalin, strychnine, 1,3-difluoro, 2-propanol, and carbamate insecticides.

On September 14, a snack shop owner in China poisoned food in a competitor's snack shop with a rodenticide identified as Dushuqiang, resulting in 38 deaths. Although Dushuqiang, which contains TETS, has been banned for sale since the mid-1980s, it is still widely available in China. Following news reports of this incident, the New York City Poison Control Center conducted additional laboratory testing of the product associated with the poisoning in New York City and confirmed TETS in the product by gas chromatography-mass spectrometry (GC-MS) (1). TETS concentration was 6.4% weight/weight [w/w] in one rodenticide packet and 13.8% w/w in another.

Reported by: F Barrueto Jr, MD, LS Nelson, MD, RS Hoffman, MD, New York City Poison Control Center; MB Heller, PhD, Public Health Laboratory, General Toxicology and Environmental Science Laboratory, New York City Dept of Health and Mental Hygiene; PM Furdyna, New York State Div of Environmental Conservation; RJ Hoffman, MD, Div of Toxicology, Maimonides Medical Center, New York, New York. KS Whitlow, DO, MG Belson, MD, AK Henderson, PhD, Div of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC.

Editorial Note:

TETS is a little-known, often unrecognized, and highly lethal neurotoxic rodenticide that once was used widely. An odorless, tasteless, and water-soluble white crystalline powder that acts as a -amino butyric acid (GABA) antagonist (China Center for Disease Control and Prevention [CDC], unpublished data, 2002), TETS, like picrotoxin, binds noncompetitively and irreversibly to the GABA receptor on the neuronal cell membrane and blocks chloride channels. The most common routes of exposures are through ingestion and inhalation (China CDC, unpublished data, 2002). TETS is not registered by the U.S. Environmental Protection Agency for use in the United States, and its importation, manufacture, and use in the United States are illegal.

TETS meets criteria for inclusion in the list of extremely hazardous pesticides maintained by the World Health Organization (WHO) and is more lethal than WHO's most toxic registered pesticide, sodium fluoroacetate (2). Multiple large intentional and unintentional exposures in China have demonstrated the human toxicity of TETS (1). The dose at which TETS kills 50% of mammals (LD50) is 0.1--0.3 mg/kg; a dose of 7.0--10.0 mg is considered lethal in humans. TETS is potentially 100 times more toxic to humans than potassium cyanide and might be a more powerful human convulsant than strychnine (3).

The most recognizable clinical signs after a TETS exposure are refractory seizures. Other potentially serious signs include coma and possible electrocardiogram evidence of ischemia (China CDC, unpublished data, 2002). Symptoms typically begin within 30 minutes after exposure and can begin as long as 13 hours after exposure. Severe poisonings are usually fatal within 3 hours (Sun C, China NPCC, personal communication, 2002). TETS intoxication is determined rapidly from history and clinical suspicion. Laboratory identification, although not clinically useful in an acute presentation, is accomplished by several methods, including gas chromatography (GC) with nitrogen-phosphorous detection, GC with flame photometric detection, and GC-MS (1,4,5). TETS is registered with the Chemical Abstract Service Division of the American Chemical Society as number 80-12-6, molecular weight 240, and chemical formula of C₄H₈N₄O₄ S₂. Every attempt should be made to identify this chemical if it is suspected.

No proven antidote exists for TETS poisoning. Treatment should follow accepted modalities for a poisoned, altered, or seizing patient (6). Universal precautions should be taken to prevent secondary exposure of health-care workers. If TETS is suspected, regional poison control centers can provide information and guidance. A small study of rodents conducted in China suggested that intravenous pyridoxine and dimercaptosuccinic acid might be effective treatments (7). In China, charcoal hemoperfusion and hemodialysis are used to provide extracorporeal removal in patients poisoned with TETS (1,3) (Sun C, China NPCC, personal communication, 2002).

This is the first known case of TETS poisoning in the United States. The chemical's morbidity and lethality and the lack of a known antidote present a danger to human health in areas where TETS might be imported illegally, especially large urban areas with substantial immigrant populations. The appearance of a banned or illegal substance presents challenges to regulatory and enforcement agencies because of the increased risk for unintentional and intentional exposures. Poisoning caused by TETS exposure can be prevented with heightened public health education, increased awareness, and adequate enforcement by customs, border, and regulatory agencies.

Acknowledgments

This report is based on data provided by N Besbelli, MD, World Health Organization, Geneva, Switzerland. J Blondell, PhD, U.S. Environmental Protection Agency, Washington, DC. A Buchwald, MD, D McNutt, MD, County of Santa Cruz Health Svcs Agency, Santa Cruz, California. M Mostin, MD, Centre Antipoisons-Antigifcentrum, Brussels, Belgium. D Rise, U.S. Environmental Protection Agency, Helena, Montana. D Sudakin, MD, National Pesticide Medical Monitoring Program, Oregon State Univ, Corvallis, Oregon. W Temple, MD, National Poisons Centre, New Zealand. R Imtiaz, MD, Div of International Health, Epidemiology Program Office, CDC.

References

1. Guan FY, Liu YT, Liu Y, et al. GC/MS identification of tetramine in samples from human alimentary intoxication and evaluation of artificial carbonic kidneys for the treatment of the victims. J Anal Toxicol 1993;17:199--201.
2. International Program on Chemical Safety. The WHO recommended classification of pesticides by hazard and guidelines to classification 2000--2002. Available at http://www.who.int/pcs/docs/Classification%20of%20Pesticides%202000-01.pdf.
3. National Poisons Centre. TOXINZ database. Dunedin, New Zealand: Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, 2002.
4. Sun J, Zhong-shan Y, Jing-zhen Z, Heng-zhi Z. Determination of tetramine in postmortem specimens by GC-NPD. J Anal Toxicol 1994;18:275--7.
5. Junting L, Chuichang F, Guohua W (letter). J Forensic Sci 1993;38:236--8.
6. Gallagher EJ. Neurologic principles. In: Goldfrank L, Flomenbaum N, Lewin N, et al., eds. Goldfrank's Toxicologic Emergencies, 7th ed. New York, New York: McGraw Hill, 2002.
7. Qiu Z, Lan H, Zhang S, Xia Y, Huang S. Antidotal effects of vitamin B(6) and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylenedisulfotetramine in animals. Zhonghua Nei Za Zhi 2002;41:186--8.

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