Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Currently viewing:

Administrative data

direct observations: clinical cases, poisoning incidents and other
Type of information:
other: poisoning incident
Adequacy of study:
supporting study
Study period:
no data
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Report on a poisoning incident with a herbicide containing amintrole and ammonium thiocyanate.

Data source

Reference Type:
Herbicide: fatal ammonium thiocyanate and aminotriazole poisoning.
Legras, A. Skrobala, D. Furet, Y. Kintz, P. Forveille, E. Dequin, P. F. Perrotin, D.
Bibliographic source:
Clinical Toxicology, 34(4), 441-446 (1996)

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
acute toxicity: oral
Test guideline
no guideline required
GLP compliance:

Test material

Details on test material:
Radoxone TL
Aminotriazole, whose chemical formula is C2H4N4, is the main active compound of Radoxone TL (240 g/L). Ammonium thiocyanate, which enhances the activity of aminotriazole is the second compound (215 g/L). The solvent is water. Radoxone TL is available in France through ICI/SOPRA (Zeneca).
It is a systemic nonselective herbicide, effective against a wide spectrum of weeds. It is not approved for use on food plants because of its
goitrogenic toxicity.


Type of population:
- Number of subjects exposed: 1
- Sex: male
- Age: 54
- Race: no data
- Demographic information: France, Tours Cedex region.
- Known diseases: chronic alcoholism, tabacco use
- Other:
Ethical approval:
not applicable
Route of exposure:
Reason of exposure:
other: unknown
Exposure assessment:
not specified
Details on exposure:
The amount of Radoxone TL ingested by our patient was unknown at the time of diagnosis. The distribution of thiocyanate in the body is predominantly extracellular. The apparent distribution volume (Vd) has a mean value of 0.25 L/kg in healthy subjects and 0.36 L/kg in subjects with renal failure. We used this Vd to estimate the amount of thiocyanate ingested by our patient: a blood level of 750 mg/L more than 12 h after ingestion corresponded to an amount ingested in excess of 12 to 17 g ammonium thiocyanate (190 to 270 mg/kg) and 13 to 19 g aminotriazole (200 to 300 mg/kg). These amounts are contained in 50 to 100 mL Radoxone TL.
- Urine analysis: no data
- Haematology: Blood chemistry values were measured
- Lung function parameters: No data
- Other: Electrocardiogram, Radiograph of the chest, Echocardiography, Electroencephalogram, Esogastroduodenal endoscopy.
Medical treatment:
Mechanical ventilation and vascular filling, continuous venovenous hemodiafiltration was performed in order to correct the electrolyte disorders
and to enhance elimination of the toxic substances.

Results and discussion

Clinical signs:
When the patient was hospitalized he had diffuse cyanosis, sweating, vomiting and diarrhea.Twelve hours after admission to the hospital, despite symptomatic treatment with mechanical ventilation and vascular filling, a life-threatening shock occurred with acute oliguric renal failure, hypoxemia, metabolic acidosis: pH 7.13, PaC02 32 mm Hg, PaOz (FiO, 1.0) 280 mm Hg, carbon dioxide 10 mmol/L, potassium 5.6 mmol/L, creatinine 106 mmol/L, urea nitrogen 12.1 mmol/L. Generalized convulsions occurred and were followed by complete atrioventricular heart block and cardiac arrest. Effective heart activity was restored after 15 min cardiopulmonary resuscitation, injection of 10 mg of epinephrine, 200 mmol of sodium bicarbonate and two external cardioversions. Although the patient had recovered from the state of shock, allowing withdrawal of dopamine and vascular replacement 24 h after beginning continuous venovenous hemodiafiltration, he died 48 h later as a result of postanoxic neurological complications due to the cardiac arrest.
Results of examinations:
- Urine analysis: no data
- Haematology: Blood chemistry values on admission were: Na 137 mmol/L, K 4.1 mmol/L, C1 141 mmol/L (normal 95-109), CO, 19 mmol/L, lactates 1.88 mmol/L, creatinine 61 pmol/L, glucose 5.8 mmol/L, creatine kinase 82 IU/L, ammonia 68 mmol/L (normal 14-38). The calculated anion gap was reversed at -19. The initial arterial blood gas indicated pH 7.35, PaCO, 27 mm Hg, Pa02 73 mm Hg (room air), carbon dioxide 15 mmol/L. Drug screening for barbiturates, benzo-diazepines, tricyclic antidepressants, salicylates, methanol and ethylene glycol was negative. Carboxyhemoglobinemia was 2% and methemoglo-binemia was 1.2%.
- Lung function parameters: no data
- Other: Electrocardiogram showed a sinus rhythm with premature atrial contractions, right bundle branch block and left anterior hemiblock. Radiograph of the chest showed bilateral alveolar opacities. Echocardiography showed nondilated ventricles, normal systolic function and concentric left ventricle hypertrophy. Electroencephalogram revealed a line without any paroxysmal element. Lumbar puncture yielded normal fluid. Esogastroduodenal
endoscopy revealed the presence of edematous esophagitis and congestive gastritis.
Effectivity of medical treatment:
Not effective the patient died.

Applicant's summary and conclusion

Experimental toxicity studies and previous human intoxications with these two substances suggest that the symptomatology of the patient was mainly due to the toxicity of thiocyanate. On admission he had gastrointestinal symptoms with vomiting and diarrhea. These were followed by neurologic signs with disorientation, confusion, myoclonic jerks, convulsions and coma. Initially blood pressure was high, but he developed intractable shock after several hours with profound metabolic acidosis and cardiac arrest.
Early diagnosis is important to eliminate the toxic substance from the stomach promptly and to utilize dialysis to enhance elimination of thiocyanate.
Executive summary:

Objective: To describe fatal herbicide poisoning with Radoxone IT composed of aminotriazole and ammonium thiocyanate. Case Report: A 54 -year-old man was hospitalized because of unexplained coma with myoclonic jerks and vascular collapse. Despite symptomatic treatment with mechanical ventilation and vascular filling, life-threatening shock occurred with oliguria, profound metabolic acidosis and cardiac arrest. Hyperchloremia (141 mmol/L) with reversed anion gap (-19) suggested inreference with chloride measurement caused by halogens (Br,F,l) or other anions such as thiocyanate. Eventually a weed killer, Radoxone TL containing ammonium thiocyanate was found at the patient's house. Thiocyanate and aminotriazole blood levels were 750 mg/L and 138 mgL respectively more than 12 hours after ingestion. Afier prolonged cardiopulmonary resuscitation, continuous venovenous hemodiafiltration was performed. Despite hemodyamic recovery the patient died 48 hours later of postanoxic coma. Conclusion: Aminotriazole, a systemic nonselective herbicide, is often associated with ammonium thiocyanate which enhances its activify. Experimental studies and previous fatal cases suggest a predominant toxicity of thiocyanate. Early diagnosis is important.