Substance-Specific Issues

Sodium chlorate; classification with respect to acute toxicity

Substance:

Sodium chlorate, CAS No. 7775-09-9: classification with respect to acute toxicity following ingestion.

Issue:

Does sodium chlorate fall within the Controlled Products Regulations (CPR) criteria of Division 1 of WHMIS Class D for acute toxicity based on human evidence?

Background:

Sodium chlorate is a powerful oxidizing agent used as a non-selective herbicide and as a chemical oxygen generator. When used as a pesticide, sodium chlorate may cause irritation of skin, eyes, or respiratory tract [1]. This odourless chemical reacts violently with combustible and reducing materials, causing fire, explosion hazard and toxic gases (chlorine).

Due to its oxidative nature, sodium chlorate can be toxic if ingested. Humans appear to be more susceptible to this effect than animals. Animal acute lethality values do not meet the criteria specified in the CPR. However, several human cases of death or serious injury have been reported following ingestion by adults.

Poisoning is characterized by the development of gastrointestinal symptoms within 2-24h including nausea, vomiting, and diarrhea and abdominal pain. After absorption, hemoglobin rapidly oxidizes to methemoglobin, leading to cyanosis, dyspnea, and coma in severe cases. Intravascular hemolysis also can occur [2]. Other symptoms include methemoglobinemia, possible liver injury, and nephritis (lumbar pain and oliguria). Nephritis presumably is the direct result of chlorate ion as well as secondary to the destruction of corpuscles. The blood pressure tends to fall and the heartbeat becomes irregular. The liver and spleen may be enlarged and tender. The urine, if any, is brown or black in color and contains casts, red cells, free hemoglobin, and methemoglobin. The blood is brownish in color, and the plasma contains free hemoglobin and free methemoglobin. The red cell count is very low and the white cell count high. Onset may be delayed by as much as 12 hr [3].

Death invariably follows a dose of 100g [4] but a dose of 5-10 g can prove to be fatal in adults, whereas a dose of 2g is sufficient for the same outcome in small children [5]. Death from sodium chlorate poisoning occurs within a few hours to a few days, due to severe methemoglobinemia, hyperkalemia from massive hemolysis or acute nephritis [6].

EU classifies sodium chlorate as: O; R9 - Oxidizing. Explosive when mixed with combustible material, Xn; R22 - Harmful. Harmful if swallowed, and N; R51-53 - Dangerous for the Environment. Toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment [7].

Considerations:

A 29 year old man ingested about 20 g of sodium chlorate (230 mg chlorate/kg body weight). He became cyanotic, and his hemoglobin dropped to 11 g/100 ml within 24 hr; methemoglobin and methemoalbumin were detected in his plasma. He was anuric for 14 days then gradually improved, and he was released from the hospital after 6 weeks [8].

A 42 year old male was admitted to hospital because of abdominal pain, diarrhea and arterial hypotension within 14hr of ingestion of an herbicide containing sodium chlorate corresponding to a total dose of 27g of sodium chlorate. The physical examination revealed cyanosed face and limbs, hypotension and oliguria [9].

A specific study has reported 14 cases of sodium chlorate poisoning. The patients' ages ranged from 3 to 55 years. Doses estimated to be in excess of 100g (or 79g as chlorate ion) were found to be uniformly fatal. One 46 year old woman given supportive therapy died 20 hours after a dose estimated to be 15g (218 mg chlorate/kg body wt). This was the lowest dose found to be fatal in these cases. Another female of unreported age died 5 days after ingesting 30g (436mg chlorate/kg body weight) despite treatment with methylene blue, peritoneal dialysis, and exchange transfusion. However, an 18 year old male survived a dose estimated at 100g (1.45g chlorate/kg body wt) after treatment with methylene blue, exchange transfusion, and hemodialysis. Cyanosis was seen in 50% of the patients, abdominal pain in 36%, diarrhea in 21%, dyspnea in 21%, anuria within 48 hours in 50%, coma in 12%, and methemoglobinemia in 93%. 64% of these cases resulted in death [3].

A 49-year-old, male, chemical worker developed respiratory distress, vomiting, headache and cyanosis. He was treated for methemoglobinemia, hemolysis and metabolic acidosis. Despite extensive treatment, he died within 36 hours. A forensic autopsy and analysis determined that the cause of his death was chlorate poisoning. The source and amount of exposure were not identified [10].

A 48-year-old, male gardener applied a very concentrated solution of sodium chlorate as a weed-killer in an atomizer. A strong wind was blowing the spray into his face. He was conscious of inhaling the spray and taking some into his mouth. That evening, he became unwell. The next day he was cyanotic, showed methemoglobin in his blood and eventually (by day 5) developed renal failure. He was seriously ill for more than 2 months. The amount of sodium chlorate in the solution was not reported [11].

A 28-year-old Korean physician accidentally ingested 40 grams sodium chlorate (570 mg/kg for a 70 kg man), mistaken for sodium chloride. He developed renal failure and was treated with blood transfusions and dialysis [12].

The criteria for acute toxicity set out in sections 46 and 49 of the CPR deal only with lethality in animals. However, specific chemicals may cause greater toxicity in humans than animals due to differences in the mechanism of toxicity between species. Although not explicit, subsection 33(2) indirectly supports the use of human data as evidence for classification in Class D - Poisonous and infectious material. The Reference Manual for the WHMIS Requirements of the Hazardous Products Act and Controlled Products Regulations states: In the case of a material (pure substance or tested mixture) which does not meet any of the criteria for Very Toxic Material or Toxic Material, but for which there is valid documented evidence based on established scientific principles that the material causes an adverse effect in humans following occupational exposure, this fact, by itself, is sufficient to include that material within Class D1. The WHMIS Information Bulletin Issue No. 8 indicates that suppliers may classify controlled products in Class D1 based on their professional judgement, if acute toxicity in humans is sufficiently documented.

Conclusion:

Sufficient cases of human poisoning have associated sodium chlorate with acute toxicity to conclude that this chemical falls within the CPR criteria for acute toxicity, i.e., Class D1B.

References:

1. Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 61.
2. Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1642.
3. Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 566.
4. Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1097.
5. Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A294/Aug 87.
6. Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972., p. 159.
7. Regulation (EC) No 1272/2008 of the European parliament and of the council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing, Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, Official Journal of the European Union.
8. National Research Council. Drinking Water and Health. Volume 7. Washington, DC: National Academy Press, 1987., p. 102.
9. Ranghino A, Constantini L, Deprado A, Filiberti O, Fontaneto C, Ottone S, Peron M, Ternavasio Cameroni G, Zamponi E, Guida G.: A case of acute sodium chlorate self poisoning successfully treated without conventional therapy. Nephrol Dial Tramsplant 2006; 21(10):2971-4.
10. Eysseric, H., et al. A fatal case of chlorate poisoning : confirmation by ion chromatography of body fluids. Journal of Forensic Sciences. Vol. 45, no. 2 (Mar. 2000). p. 474-477.
11. Jackson, R.C., et al. Sodium-chlorate poisoning. The Lancet. Vol. 2 (Dec. 23, 1961). p. 1381-1383.
12. Knight, R.K., et al. Suicidal chlorate poisoning treated with peritoneal dialysis. British Medical Journal (citing Klendshoj et al 1962). Vol. 3, no. 5565 (Sept. 2., 1967). p. 601-602.