1) OVERDOSE: Human overdose information is limited.
2) CASE REPORTS: FATALITIES: Ingestion of an herbicide containing atrazine, aminotriazole, ethylene glycol and formaldehyde has been associated with coma, circulatory collapse, hepatic necrosis, renal failure, and disseminated intravascular coagulation. The patient died several days after exposure of circulatory collapse. In another case, a death was reported following ingestion of a mixture of amitrole and ammonium thiocyanate, with cyanosis, sweating, seizures, vomiting, diarrhea, hypotension, heart block, chest X-ray abnormalities, esophageal and gastric injury, and renal failure. However, the reported thiocyanate concentration was sufficient to account for the observed findings and the role of amitrole, if any, was not known. SURVIVAL: Ingestion of a triazine herbicide and alcohol produced vomiting and metabolic acidosis in an adult; the patient recovered with supportive care.
3) INHALATION: A single case report suggests that lung injury may occur after inhalation of amitrole. It is not clear that there is a causal relationship in this isolated case report.
4) OTHER: Ocular and skin irritation may occur following atrazine and triazole exposure. DERMAL: Atrazine is a skin sensitizer.
5) ANIMAL DATA: When fed to sheep and cattle at high dosage, atrazine caused anorexia, salivation, depression of activity, muscle spasms and fasciculations, ataxia, increased body temperature and dyspnea. Hyperthyroidism and increased T3 levels with normal thyroxine and TSH levels were observed in animal studies. Atrazine appeared to interfere with hypothalamic control of pituitary-ovarian axis function in ovariectomized rats.

1) Limited overdose information. Product formulations of these herbicides can vary widely and a more toxic agent may be involved following an ingestion. Treatment is symptomatic and supportive. Vomiting may develop following ingestion. Monitor fluid status and electrolytes as indicated. Replace fluids (oral or IV) as necessary.

1) Treatment is symptomatic and supportive. Limited overdose information. Administer IV fluids for hypotension; add vasopressors if hypotension persists. Monitor mental status; drowsiness and CNS depression including coma may develop following a significant exposure. Assess airway and respiratory function frequently. Administer oxygen as needed; airway support and management as needed. A single case report exists of circulatory collapse including left ventricular failure, renal failure, hepatic necrosis, and disseminated intravascular coagulation following a mixed ingestion of atrazine, aminotriazole, ethylene glycol and formaldehyde. The patient died a few days later. In another case, a patient developed metabolic acidosis following the ingestion of prometryn and alcohol. Monitor ABGs as indicated following a significant ingestion.

1) PREHOSPITAL: INGESTION: A minor exposure to a triazine herbicide is generally NOT expected to result in significant toxicity. However, product formulations of these herbicides can vary widely and a more toxic agent may be involved. Do not induce emesis. Activated charcoal should only be considered if the patient is alert and not vomiting following a significant ingestion. Triazines can be moderately irritating to the skin, eyes, and respiratory tract. DERMAL: Remove contaminated clothing and wash exposed areas with soap and water. OCULAR: Irrigate exposed eyes thoroughly. INHALATION: Following an inhalational exposure, move patient to fresh air.
2) HOSPITAL: INGESTION: Gastrointestinal decontamination is not recommended after ingestion unless a more toxic agent is also involved. DERMAL: Remove contaminated clothing and wash exposed skin with soap and water. OCULAR: Irrigate exposed eyes with water or 0.9% saline.

1) Airway support is unlikely to be necessary after a minor or "taste" ingestion. Airway management may be necessary in patients who develop CNS depression or shock after a large ingestion.

1) None.

1) Enhanced elimination is unlikely to be necessary in most cases of exposure. There is one report of a patient developing significant metabolic acidosis following the ingestion of prometryn and alcohol and he received hemodialysis. His underlying metabolic derangements did improve but hemodialysis had no affect on serum prometryn concentrations.

1) HOME CRITERIA: Patients with no or minimal symptoms after inadvertent exposure may be observed at home.
2) OBSERVATION CRITERIA: Symptomatic patients and those with deliberate exposure should be referred to a healthcare facility. Observe symptomatic patients until symptoms are resolved.
3) ADMISSION CRITERIA: Patients with acidosis, coma, evidence of cardiovascular toxicity, or severe gastrointestinal symptoms should be admitted to the hospital.
4) CONSULT CRITERIA: Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.

1) Pitfalls include not evaluating for other coingestants such as solvents or surfactants, which may be ingredients included with the herbicide.

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

1) WITH POISONING/EXPOSURE

1) CARDIOMYOPATHY

1) WITH POISONING/EXPOSURE

1) DYSPNEA

1) CASE REPORT/FATALITY: A 38-year-old man who ingested 500 mL of a herbicide containing atrazine, aminotriazole, ethylene glycol and formaldehyde presented with coma (GCS 7), circulatory collapse, metabolic acidosis and gastric bleeding 7 hours after ingestion. The patient gradually deteriorated and died 3 days later due to intractable shock (Pommery et al, 1993).

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) TWITCHING

1) WITH POISONING/EXPOSURE

1) ANOREXIA

1) MIXED INGESTION: Hepatic necrosis was reported in a 38-year-old man several hours after intentional ingestion of 500 mL of a herbicide containing atrazine, aminotriazole, ethylene glycol and formaldehyde (Pommery et al, 1993).

1) LIVER FATTY

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) THYROID CARCINOMA
2) THYROID DISORDER
3) ESTROGEN INCREASED
4) PITUITARY INSUFFICIENCY
5) ALTERED HORMONE LEVEL

1) ATRAZINE: Dietary studies in rats receiving 100 ppm showed no teratogenicity. Embryotoxicity and fetotoxicity were absent at doses of less than 75 mg/kg/day in rats and 5 mg/kg in rabbits (Technical Information, 1987; Peters & Cook, 1973). Embryotoxic effects were seen at maternal doses of 800 to 2000 mg/kg (Peters & Cook, 1973).
2) Infurna et al (1988) reported atrazine was not teratogenic at maternally toxic dose levels in rats (70 mg/kg/day on gestational days 6 to 15) and rabbits (75 mg/kg/day on gestational days 7 to 19).
3) Full-litter resorption is seen following atrazine administration to rat dams during the LH-dependant luteal phase of pregnancy and seemed to be due to the loss of LH-dependent luteal function. Strain sensitivity varied considerably (Cummings et al, 2000; Narotsky et al, 2001).
4) Additional reproductive studies reported in secondary sources:

1) A study of 3510 births over a 1-year period found no clear association between maternal exposure to atrazine in drinking water and an increased risk of low birth weight or small-for-gestational-age infants. However, correlating with atrazine levels peaking from May to September, there was a slight increased risk of small-for-gestational-age status in those whose third trimester occurred partly or completely from May through September, compared with third trimesters that occurred at other times during the year. There was also a borderline significant increased risk of prematurity if the first trimester occurred from May to September (Villanueva et al, 2005).

1) ATRAZINE

1) ATRAZINE: ACGIH (2000) lists atrazine in Category A4, "not classifiable as a human carcinogen." IARC: Overall evaluation downgraded from 2B to 3 with supporting evidence from other data relevant to carcinogenicity and its mechanisms. The EPA listed atrazine as not likely to be carcinogenic in humans.
2) AMITROLE: ACGIH (2000) lists amitrole in Category A3, "confirmed animal carcinogen with unknown relevance to humans." IARC lists it in Group 2B, "possibly carcinogenic to humans."

1) Donna et al (1989) reported women previously exposed to triazines showed a significant relative risk of 2.7 for ovarian neoplasms in a population-based case-referent study.
2) Minder (1989) found the study flawed based on statistical aspects, possible confounders and biases, and the classification of the exposed women.
3) A population-based case-controlled study of 256 women with ovarian cancer and 1122 controls found that cases were slightly but not significantly more likely to have been occupationally exposed to triazines compared with controls (adjusted OR=1.34; 95% CI=0.77 to 2.33). No evidence of a dose-response relationship was observed (Young et al, 2005).

1) Loosli (1995) reviewed the available studies regarding atrazine, including the reports of ovarian cancer and associations with non-Hodgkin lymphoma and concluded that there was no convincing evidence of causation given the various flaws in these studies.
2) Based on a systematic review of epidemiologic studies of atrazine exposure and risk of cancer, it is unlikely to pose a cancer risk. The review included studies that analyzed the association of atrazine exposure and multiple cancer sites (ie, ovaries, thyroid, hairy-cell leukemia, non-Hodgkin lymphoma, prostate, breast, esophageal and liver, and childhood cancers) (Boffetta et al, 2013).
3) In a prospective study of 36,357 pesticide applicators that reported using atrazine, there was no increased overall cancer risk among workers applying atrazine (Freeman et al, 2011).
4) Sathiakumar and Delzell (1997) and MacLennan et al (2003) found that pooled epidemiological data were inadequate to associate atrazine or triazines with many cancer types.
5) In a nested case-control study, there was no association between atrazine exposure and prostate cancer (Hessel et al, 2004).

1) Atrazine, cyanazine and simazine seem to cause prolactin-dependent mammary tumors in selected rat strains. This mechanism is not believed to have relevance to human breast cancer (O'Connor et al, 2000; Eldridge et al, 1999; Stevens et al, 1999).

1) RATS - Daily oral administration of amitrole (up to 50 ppm) to rats for 2 years was associated with the development of enlarged thyroids. Carcinoma of the thyroid was noted in rats receiving 100 ppm amitrole in the diet for 2 years (Jukes & Schaffer, 1960).

1) Monitor CBC in symptomatic patients.

1) Monitor renal function and liver enzymes following a large ingestion or in a symptomatic patient.

1) Daily administration of amitrole was associated with thyroid enlargement (ACGIH, 1986). Thyroid size and function should be evaluated following large acute exposures or long-term occupational exposures to amitrole.

A) Patients with acidosis, coma, evidence of cardiovascular toxicity, or severe gastrointestinal symptoms should be admitted to the hospital.

A) Patients with no or minimal symptoms after inadvertent exposure may be observed at home.

A) Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.

A) Symptomatic patients and those with deliberate exposure should be referred to a healthcare facility. Observe symptomatic patients until symptoms are resolved.

1) INGESTION: A minor exposure to a triazine herbicide is generally NOT expected to result in significant toxicity. However, product formulations of these herbicides can vary widely and a more toxic agent may be involved. Do not induce emesis. Activated charcoal should only be considered if the patient is alert and not vomiting following a significant ingestion.
2) Triazines can be moderately irritating to the skin, eyes, and respiratory tract. DERMAL: Remove contaminated clothing and wash exposed areas with soap and water. OCULAR: Irrigate exposed eyes thoroughly with copious amounts of water.

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) If persons exposed to triazines exhibit symptoms of severe toxicosis, concurrent absorption of other or additional toxins should be considered.

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) ANIMAL DATA: Survival was enhanced in cattle receiving multiple-dose activated charcoal 4, 24, 48, and 72 hours after a lethal dose of atrazine (Kobel et al, 1985). There is no data regarding the use of multiple dose activated charcoal after human exposure to triazine herbicides and routine use is NOT recommended.

1) MANAGEMENT OF MILD TO MODERATE TOXICITY
2) MANAGEMENT OF SEVERE TOXICITY

1) Monitor vital signs and mental status.
2) Monitor serum electrolytes in patients with severe gastrointestinal symptoms after a large or deliberate ingestion.
3) Monitor CBC, renal function and liver enzymes following as necessary.
4) Obtain an ECG and institute continuous cardiac monitoring after a large or deliberate ingestion.
5) Monitor ABGs as indicated following a significant or mixed ingestion.
6) Plasma concentrations of these herbicides are not readily available or clinically useful in guiding therapy.
7) TRIAZOLE: Daily administration of amitrole was associated with thyroid enlargement (ACGIH, 1986). Thyroid size and function should be evaluated following large acute exposures or long-term occupational exposures to amitrole.

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE

1) Seizure activity has NOT been reported following ingestion of a triazine herbicide alone; however, a mixed ingestion or other agents contained in a herbicide product may result in seizures.
2) SUMMARY
3) DIAZEPAM
4) NO INTRAVENOUS ACCESS
5) LORAZEPAM
6) PHENOBARBITAL
7) OTHER AGENTS

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

a) A 39-year-old woman did not become ill following an ingestion of a mixture containing amitrole 20 mg/kg (Geldmacher-von Mallinckrodt & Schmidt, 1970).
b) Threshold Dose: Very slight inhibition of (131)-iodine uptake by the thyroid for 24 hours in healthy people and people with hyperthyroidism was reported with 10 mg of amitrole (Astwood, 1960).
c) ANIMAL DATA: The no-effect level (thyroid function) in RATS fed diets containing amitrole for 29 days is 0.5 part per million (ACGIH, 1986).

a) LACK OF EFFECT

a) CASE REPORT: A 62-year-old man intentionally ingested approximately 50 g (100 mL) of Prohelan T (TM) (suspension concentrate of prometryn, a triazine herbicide) and an unknown amount of wine. Upon arrival the patient was somnolent and had vomited. A few hours after presentation, the patient became uncooperative with Kussmaul pattern breathing. Metabolic acidosis was treated with bicarbonate hemodialysis. The patient also developed pneumonia during the course of his hospitalization. All laboratory and clinical findings improved and the patient was discharged on hospital day 6 with no permanent sequelae (Brvar et al, 2008).

1) SPECIFIC SUBSTANCE

1) Atrazine: 1780 mg/kg

1) Cyromazine: 3387 mg/kg

1) Hexazinone: 1690 mg/kg

1) Metribuzin: Greater than 2000 mg/kg

1) Prometon: 2980 mg/kg

1) Prometryn: 5235 mg/kg

1) Metribuzin: Greater than 2000 mg/kg

1) Simazine: Greater than 5000 mg/kg

1) 870 to 965 mg/kg

1) 1110 to 1405 mg/kg

1) 1465 to 2400 mg/kg

1) 1750 mg/kg

1) 1480 to 5100 mg/kg

1) 380 mg/kg

1) 149 to 334 mg/kg

1) 1200 mg/kg

1) 700 mg/kg

1) 1390 mg/kg

1) 1690 mg/kg

1) 5278 mg/kg

1) > 2500 mg/kg

1) > 10,000 mg/kg

1) > 1000 mg/kg

1) 1100 to 2300 mg/kg

1) 2160 mg/kg

1) 503 mg/kg
2) 2980 mg/kg

1) 1330 mg/kg

1) 3750 mg/kg

1) 5000 mg/kg

1) > 5000 mg/kg

1) > 5000 mg/kg

1) > 5000 mg/kg

1) 2000 to 2160 mg/kg

1) Begin treatment immediately.
2) Keep animal warm.
3) Sample vomitus, blood, urine, and feces for analysis.
4) If skin exposure has occurred, wash animal thoroughly with a mild detergent and flush with copious amounts of water.

1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

1) SMALL ANIMALS
2) LARGE ANIMALS

1) The lethal dose of atrazine in cattle has been reported to be 500 mg/kg within 24 hours. Single doses of 100 mg/kg have produced reversible intoxication (Palmer & Radeleff, 1964). Daily doses of 30 mg/kg for 25 days did not result in signs of toxicity (Johnson et al, 1972).

1) Daily oral doses of 75 mg/kg of atrazine given on gestational days 7 to 19 resulted in maternal toxicity (Infurna et al, 1988).

1) RAT - Maternal toxicity was observed at daily oral doses of at least 70 mg/kg atrazine given on gestational days 6 to 15 (Infurna et al, 1988).

A) GENERAL TREATMENT
B) ANIMAL POISON CONTROL CENTERS

A) GASTRIC DECONTAMINATION