DINOTERB

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1.2.1) MOLECULAR FORMULA
1) C10-H12-N2-O5

Available Forms Sources

1) Dinoterb is a dinitrophenolic compound. It occurs as a yellow crystalline solid with a phenolic odor (HSDB , 1993). It is soluble in aqueous alkalis, cyclohexanone, dimethylsulfoxide, ethyl acetate, glycols, alcohols, and aliphatic hydrocarbons, and is practically insoluble in water (HSDB , 1993).
2) The ACGIH has recommended a Biological Exposure Index (BEI) for methemoglobin inducers. Refer to the BIOMONITORING section for more information.
3) Symptoms caused by dinoterb are similar to those of other dinitrophenol or dinitro-o-cresol compounds, such as DINOSEB (EPA, 1985). This review is based on the properties of dinitrophenol and dinitro-o-cresol compounds in general, with effects attributed specifically to dinoterb noted.

1) Dinoterb was formerly used as a pre-emergence herbicide to control annual weeds in vegetable and cereal fields (HSDB , 1993). As dinoterb acetate, it was also used on grapevines and fruit trees as an insecticide and acaricide (HSDB , 1993). As a rodenticide, it was particularly effective against rats and mice (HSDB , 1993). All US EPA registrations for this agent were suspended in 1986 under emergency action to mitigate human exposures (EPA, 1988; Crawford, 1986) Fikes et al, 1986; (HSDB , 1993).
2) Dinitrophenols act by uncoupling oxidative phosphorylation at the cellular level, leading to increased oxygen uptake and diversion of available energy into production of heat, resulting in an increase in body temperature (EPA, 1988; Fikes et al, 1989; Finkel, 1983; Morgan, 1989).

Overview

Life Support

Clinical Effects

0.2.1)

A) Dinoterb is a dinitrophenolic compound formerly used as an herbicide and rodenticide. All EPA registrations for this agent were suspended under emergency action to mitigate human exposures in 1986.

1) Symptoms of dinoterb are similar to those of other dinitrophenol or dinitro-o-cresol compounds (such as dinoseb).

a) Systemic poisoning may be manifested by nausea, vomiting, abdominal pain, marked thirst, fatigue, diaphoresis, facial flushing, tachycardia, hyperthermia, respiratory distress, cyanosis, restlessness, anxiety, muscular cramping, excitement, coma, and convulsions. Some degree of renal and hepatic injury may result. Dinitrophenol poisoning may initially be confused clinically with organophosphate or carbamate poisoning.
b) Ataxia, weakness, difficulty with locomotion, polypnea, and death have been described in accidentally exposed pets.

B) When heated to decomposition, dinoterb releases toxic and irritating fumes of oxides of nitrogen. Inhalation exposure to these products of combustion would be expected to cause respiratory tract irritation, and could lead to bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
C) The mechanism of acute toxicity is uncoupling of oxidative phosphorylation by prevention of the conversion of ADP to ATP, resulting in cellular biochemical changes that lead to increased oxygen uptake, increased permeability of mitochondrial membranes to hydrogen ions, and diverting of energy available from metabolism into heat production which raises body temperature.
D) The similar compound, dinoseb, caused severe irritation when instilled into rabbit eyes. It may cause yellowish skin and nail staining and dermal irritation. Dust inhalation is irritating to the respiratory tract, and systemic absorption may occur by this route.
E) Developmental toxicity, embryotoxicity, male sterility, cataract formation, and immunotoxicity have been observed in laboratory animals or their offspring following exposure to the similar compound, dinoseb.

0.2.3)

A) An elevated respiratory rate and temperature with diaphoresis are commonly seen. Tachycardia frequently occurs in acute poisoning.

0.2.4)

A) The similar compound, dinoseb, caused severe irritation and permanent corneal injury when instilled into rabbit eyes. The sclera may be stained yellow

0.2.5)

A) Systemic dinoterb poisoning may be manifested by tachycardia.

0.2.6)

A) Intermittent chest pain has been described in a patient with dermal and inhalational exposure to the similar compound, dinoseb. Shortness of breath and hemoptysis were also described.
B) Decreased FEV1 and FVC were noted in one patient with acute dermal and inhalational exposure to the similar compound, dinoseb.
C) Inhalation of dinoterb dust or thermal decomposition products may be irritating to the respiratory tract and could lead to bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema. Tachypnea, labored breathing and cyanosis may develop in serious poisoning cases.

0.2.7)

A) Personality changes, toxic psychosis, night sweats, and lethargy have been described after acute dermal and inhalational exposure to the similar agent, dinoseb. Headache, lassitude, confusion, apprehension, and manic behavior may be seen. Coma and seizures may develop in serious poisonings.
B) Ataxia, weakness, difficulty with locomotion, polypnea, and death have been described in pets accidentally exposed to the similar agent, dinoseb

0.2.8)

A) Intermittent abdominal pain, nausea, vomiting, and excessive thirst have been described following exposure to the similar agent, dinoseb. The stools may be a bright yellow color.
B) Ingestion of the concentrated material may cause esophageal or gastrointestinal tract irritation or burns.

0.2.9)

A) Impairment of liver function has been noted following acute dermal and inhalational exposure to the similar agent, dinoseb.

0.2.10)

A) A yellowish discoloration of the urine and elevated BUN were reported following acute dermal and inhalational exposure to the similar agent, dinoseb. Renal tubular injury may occur in acute poisonings.

0.2.11)

A) Acidosis may be seen in acute poisonings.

0.2.13)

A) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans.

0.2.14)

A) Yellow staining of the skin, hair, and nails may be seen if direct contact occurs. Profuse sweating or shivering may be noted. Systemic dinoterb poisoning may be manifested by facial flushing.

0.2.15)

A) Systemic dinoterb poisoning may be manifested by muscular cramping.

0.2.16)

A) Glucose intolerance after exposure to dinitro-o-cresol compounds has been described.

0.2.17)

A) The mechanism of acute toxicity is uncoupling of oxidative phosphorylation by prevention of the conversion of ADP to ATP, resulting in cellular biochemical changes that lead to increased oxygen uptake, increased permeability of mitochondrial membranes to hydrogen ions, and diverting of energy available from metabolism into heat production which raises body temperature.
B) Basal metabolic rate is greatly increased after exposure secondary to uncoupling of oxidative phosphorylation.

0.2.19)

A) Immunotoxicity may occur in exposed laboratory animals exposed to the similar agent, dinoseb. This effect has not been reported in exposed humans.

0.2.20)

A) At the time of this review, no reproductive studies were found for dinoterb in humans or experimental animals. Dinoseb, a closely related compound, is embryotoxic, fetotoxic, and teratogenic in experimental animals, and has inhibited the development of sperm and male fertility in rats.

0.2.21)

A) The similar agent, dinoseb, is an equivocal tumorigenic agent by RTECS criteria in mice.
B) The similar agent, dinoseb, has been classified as a Category C Carcinogen by the EPA (Limited Evidence of Carcinogenicity in Animals) based on induction of hepatic adenomas. It may be oncogenic in mice. Several dinoseb formulations may also be contaminated with carcinogenic nitrosamines.

0.2.22)

A) Loss of 10 kg in one week has been described following acute dermal and inhalational exposure to the similar agent, dinoseb.

Laboratory Monitoring

1) In one acute poisoning case, dinoseb (a similar compound) plasma blood level was 0.3 micromoles per liter 59 days after exposure. Another patient who survived with supportive treatment after poisoning with dinitro-ortho- cresol had a blood level of 60 mcg/g (ppm). Serum levels of 10 mcg/mL or greater are usually seen when acute toxicity is present.

1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.

Treatment Overview

0.4.2)

A) Caution may be indicated in substantial recent ingestions because the patient may rapidly become obtunded, comatose, or convulsing, thereby at risk of aspiration of gastric contents into the lungs.
B) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.

1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.

E) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
F) MONITORING PARAMETERS

1) Monitor liver and renal function tests.
2) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated.

G) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism.
H) HYPERTHERMIA

1) Reduction of hyperthermia with tepid water baths is superior to alcohol sponging or ice packs which tend to constrict the peripheral circulation and could result in heat retention.
2) A rectal electrode thermometer, if available, should be used to monitor core temperature.
3) If tepid bathing is not sufficient, a cooling blanket or bath should be considered.
4) Administration of SALICYLATES to reduce hyperpyrexia is probably CONTRAINDICATED. Aspirin is also an oxidative phosphorylation uncoupler and may aggravate the hyperpyrexia.

I) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).

1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

J) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia.
K) Administration of oxygen may assist in minimizing tissue hypoxia.
L) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia.
M) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans.

1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.
2) SUMMARY

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

3) METHYLENE BLUE

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

4) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

N) Hemodialysis and forced diuresis have not been shown to be effective in poisoning with these agents. Hemoperfusion has not been sufficiently tested to state whether or not it could have any beneficial effect.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
C) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
D) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
E) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
F) MONITORING PARAMETERS

1) Monitor liver and renal function tests.
2) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated.

G) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism.
H) HYPERTHERMIA

1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.
2) SUMMARY

3) METHYLENE BLUE

4) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
B) No cases of systemic toxicity in humans following ocular exposure to this compound have been reported. Should systemic toxicity develop following eye exposure:

1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

0.4.5)

A) OVERVIEW

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).
2) Cutaneous exposure is usually accompanied by a yellowish discoloration which does not have to be removed entirely to prevent absorption.
3) Severe systemic dinitrophenol poisoning can occur from dermal exposure; hence aggressive and immediate skin decontamination must be undertaken and a physician consulted as soon as possible.
4) MONITORING PARAMETERS

a) Monitor liver and renal function tests.
b) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated.

5) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism.
6) HYPERTHERMIA

a) Reduction of hyperthermia with tepid water baths is superior to alcohol sponging or ice packs which tend to constrict the peripheral circulation and could result in heat retention.
b) A rectal electrode thermometer, if available, should be used to monitor core temperature.
c) If tepid bathing is not sufficient, a cooling blanket or bath should be considered.
d) Administration of SALICYLATES to reduce hyperpyrexia is probably CONTRAINDICATED. Aspirin is also an oxidative phosphorylation uncoupler and may aggravate the hyperpyrexia.

7) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).

a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

8) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia.
9) Administration of oxygen may assist in minimizing tissue hypoxia.
10) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia.
11) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans.

a) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.
b) SUMMARY

1) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

c) METHYLENE BLUE

1) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
2) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
3) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
4) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

d) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

1) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
2) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
3) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

12) Hemodialysis and forced diuresis have not been shown to be effective in poisoning with these agents. Hemoperfusion has not been sufficiently tested to state whether or not it could have any beneficial effect.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

1) Symptoms of dinoterb are similar to those of other dinitrophenol or dinitro-o-cresol compounds (such as dinoseb).

Vital Signs

3.3.1)

A) An elevated respiratory rate and temperature with diaphoresis are commonly seen. Tachycardia frequently occurs in acute poisoning.

3.3.2)

A) An elevated respiratory rate is commonly seen in acute poisoning (Morgan, 1989; HSDB , 1990).

3.3.3)

A) An elevated temperature may be seen following exposure (Smith, 1981). Fatal hyperpyrexia may occur (Finkel, 1983).

1) Elevated temperature with profuse diaphoresis is virtually always found after acute toxic exposure (Bidstrup & Payne, 1951; MacBryde & Taussig, 1935).

3.3.5)

A) A rapid pulse is frequently seen in acute poisoning (Morgan, 1989; HSDB , 1990).

Heent

3.4.1)

A) The similar compound, dinoseb, caused severe irritation and permanent corneal injury when instilled into rabbit eyes. The sclera may be stained yellow

3.4.3)

A) IRRITATION - The similar compound, dinoseb, caused severe irritation when instilled into rabbits eyes (RTECS , 1990).
B) CORNEAL INJURY - Permanent corneal damage was seen in the eyes of experimental animals following instillation of a drop of 10 or 20% concentration dinoseb, a similar compound (Grant, 1986).
C) SCLERAL STAINING - In acute poisoning, the sclera may be stained yellow (Morgan, 1989).
D) CATARACTS - Use of dinitrophenolic compounds as obesity control agents in the past resulted in development of cataracts following chronic ingestion (Finkel, 1983; Kurt et al, 1986). Cataracts have not been reported following occupational exposure.

Cardiovascular

3.5.1)

A) Systemic dinoterb poisoning may be manifested by tachycardia.

3.5.2)

A) TACHYARRHYTHMIA

1) Systemic poisoning may be manifested by tachycardia (EPA, 1985; Fikes et al, 1989; Smith, 1981).

Respiratory

3.6.1)

3.6.2)

A) CHEST PAIN

1) Intermittent chest pain has been described in a patient with dermal and inhalational exposure to the similar compound, dinoseb (Smith, 1981).

B) HEMOPTYSIS

1) Shortness of breath and hemoptysis have been described following acute dermal and inhalational exposure to the similar compound, dinoseb (Smith, 1981).

C) RESPIRATORY FAILURE

1) Decreased FEV1 and FVC were noted in one patient with acute dermal and inhalational exposure to the similar compound, dinoseb (Smith, 1981).

D) CYANOSIS

1) Tachypnea, labored breathing and cyanosis may develop in serious poisoning cases (Morgan, 1989).

E) HYPERVENTILATION

1) An elevated respiratory rate is commonly seen in acute poisoning (Morgan, 1989; HSDB , 1990).

F) IRRITATION SYMPTOM

1) Inhalation of dust may be irritating to the respiratory tract (Morgan, 1989).

G) RESPIRATORY CONDITION DUE TO CHEMICAL FUMES AND/OR VAPORS

1) Irritating and toxic oxides of nitrogen fumes may be released if dinoterb is heated to decomposition (Sax & Lewis, 1989). Inhalation exposure to such fumes would be expected to cause respiratory tract irritation and could lead to bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

Neurologic

3.7.1)

3.7.2)

A) PERSONALITY DISORDER

1) Personality changes, toxic psychosis, night sweats, and lethargy have been described after acute dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981; Morgan, 1989).

B) HEADACHE

1) Headache, lassitude, confusion, apprehension, and manic behavior may be seen in acute poisoning (Morgan, 1989).

C) ATAXIA

1) Ataxia, weakness, difficulty with locomotion, polypnea, and death have been described in accidentally exposed pets (Fikes et al, 1989).

D) COMA

1) Coma may develop in serious poisonings (Morgan, 1989).

E) SEIZURE

1) Convulsions may be noted in seriously poisoned patients (Morgan, 1989).

Gastrointestinal

3.8.1)

3.8.2)

A) ABDOMINAL PAIN

1) Intermittent abdominal pain has been described in a patient with dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981).

B) THIRST FINDING

1) Excessive thirst has been described following dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981).

C) CHEMICAL BURN

1) Ingestion of the concentrated material may cause esophageal or gastrointestinal tract irritation or burns (HSDB , 1990).

D) NAUSEA AND VOMITING

1) Systemic poisoning may be manifested by nausea, vomiting, abdominal pain, and marked thirst (EPA, 1985; Fikes et al, 1989; Smith, 1981).

E) STOOL FINDING

1) Stools may be a bright yellow color (Smith, 1981).

Hepatic

3.9.1)

A) Impairment of liver function has been noted following acute dermal and inhalational exposure to the similar agent, dinoseb.

3.9.2)

A) LIVER DAMAGE

1) Impairment of liver function has been noted following acute dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981; Morgan, 1989).

Genitourinary

3.10.1)

3.10.2)

A) ABNORMAL URINE

1) A yellowish discoloration of the urine has been reported following acute dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981; Morgan, 1989).

B) BLOOD UREA ABNORMAL

1) An elevated BUN was reported in one patient following acute dermal and inhalational exposure to the similar agent, dinoseb (Smith, 1981).

C) RENAL TUBULAR DISORDER

1) Renal tubular injury may occur in acute poisonings (Morgan, 1989).

Acid-Base

3.11.1)

A) Acidosis may be seen in acute poisonings.

3.11.2)

A) ACIDOSIS

1) Acidosis may be seen in acute poisonings (HSDB , 1990).

Hematologic

3.13.1)

A) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans.

3.13.2)

A) METHEMOGLOBINEMIA

1) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants (Froslie & Karlog, 1970; Froslie, 1973; Hayes, 1982). This effect has not been reported in exposed humans.

Dermatologic

3.14.1)

A) Yellow staining of the skin, hair, and nails may be seen if direct contact occurs. Profuse sweating or shivering may be noted. Systemic dinoterb poisoning may be manifested by facial flushing.

3.14.2)

A) DISCOLORATION OF SKIN

1) Yellow staining of the skin, hair, and nails may be seen if direct contact occurs (Smith, 1981; Morgan, 1989; Leftwich et al, 1982).

B) EXCESSIVE SWEATING

1) Profuse sweating may be noted (Smith, 1981).

C) CHILL

1) Shivering may be noted (Smith, 1981).

D) FLUSHING

1) Systemic poisoning may be manifested by facial flushing (EPA, 1985; Fikes et al, 1989; Smith, 1981).

Musculoskeletal

3.15.1)

A) Systemic dinoterb poisoning may be manifested by muscular cramping.

3.15.2)

A) INCREASED MUSCLE TONE

1) Systemic poisoning with the similar agent, dinoseb, may be manifested by muscular cramping (EPA, 1985; Fikes et al, 1989; Smith, 1981).

Endocrine

3.16.1)

A) Glucose intolerance after exposure to dinitro-o-cresol compounds has been described.

3.16.2)

A) ABNORMAL GLUCOSE TOLERANCE TEST

1) Glucose intolerance after exposure to dinitro-o-cresol compounds has been described (MacBryde & Taussig, 1935).

Immunologic

3.19.1)

A) Immunotoxicity may occur in exposed laboratory animals exposed to the similar agent, dinoseb. This effect has not been reported in exposed humans.

3.19.2)

A) DISORDER OF IMMUNE FUNCTION

1) Immunotoxicity may occur in exposed laboratory animals (EPA, 1988).

Reproductive

3.20.1)

3.20.2)

A) ANIMAL STUDIES

1) The similar agent, dinoseb, caused adverse developmental effects in rats and mice when administered to pregnant females (RTECS , 1990; Beaudoin & Fisher, 1981; Gibson, 1973).

3.20.3)

A) FETOTOXICITY

1) ANIMAL STUDIES

a) Fetotoxicity associated with maternal toxicity has been seen in rats and mice when the similar agent, dinoseb, was administered to pregnant females (RTECS , 1990; Giavini et al, 1986; Kavlock et al, 1985; McCormack et al, 1980).
b) Developmental toxicity and embryotoxicity has been observed in the offspring of laboratory animals exposed to the similar agent, dinoseb (EPA, 1988; Daston et al, 1988; Beaudoin & Fisher, 1981; Schardein, 1985; Preache & Gibson, 1975).
c) Administration of 7.5 mg/kg/day of the similar agent, dinoseb, intraperitoneally to pregnant mice resulted in an increased incidence of fetal resorption, low birth weight offspring, retardation, kinky tail, hydrocephalus, hydronephrosis, and delayed bone ossification in the fetuses (Preache & Gibson, 1975).
d) Pregnant rats fed the similar agent, dinoseb, at 200 ppm in their feed showed reductions in embryonic survival rates; surviving fetuses had lower birth weights than normal (Spencer & Tat Sing, 1982).
e) Initial morphologic abnormalities of the kidney have been described in the offspring of female rats given the similar agent, dinoseb, intraperitoneally; however, renal function and morphology subsequently returned to normal (McCormack et al, 1980).

3.20.4)

A) ANIMAL STUDIES

1) BREAST MILK

a) When cows were fed diets containing the similar agent, dinoseb, at 1 to 100 ppm for 21 days, no residues were found in the milk (McKellar, 1971).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS1420-07-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

3.21.3)

A) CARCINOMA

1) RELATED COMPOUNDS

a) The similar agent, dinoseb, is an equivocal tumorigenic agent by RTECS criteria in mice (RTECS , 1990).
b) The similar agent, dinoseb, has been classified as a Category C Carcinogen by the EPA (Limited Evidence of Carcinogenicity in Animals) based on induction of hepatic adenomas (EPA, 1988). It may be oncogenic in mice (Fikes et al, 1989).

1) Several dinoseb formulations may also be contaminated with carcinogenic nitrosamines (EPA, 1988).

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) The dinitro-o-cresol compounds can be identified in the serum or urine by a gas-liquid chromatographic method. Such analyses may be useful to confirm the etiology of the poisoning, but are not useful for patient management.

B) Glucose intolerance after exposure to dinitro-o-cresol compounds has been described. Monitor blood sugar in significantly exposed patients.
C) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans.

1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.

D) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
E) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
F) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
G) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.
H) If respiratory tract irritation is present, monitor chest x-ray.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Dinitro-o-cresol compounds can usually be detected in plasma and urine, but such levels are of little value in the management of an acutely poisoned patient (Baselt, 1988).
2) Serum levels of 10 mcg/mL or greater are usually seen when acute toxicity is present (NIOSH, 1978).
3) Blood levels of dinitro-ortho-cresol have not correlated with urine levels (Harvey, 1952).
4) Glucose intolerance after exposure to dinitro-o-cresol compounds has been described (MacBryde & Taussig, 1935). Monitor blood sugar in significantly exposed patients.
5) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.

B) HEMATOLOGIC

1) METHEMOGLOBINEMIA - Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants (Froslie & Karlog, 1970; Froslie, 1973; Hayes, 1982). This effect has not been reported in exposed humans.
2) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.

4.1.3)

A) URINALYSIS

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

4.1.4)

A) OTHER

1) MONITORING

a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

2) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

1) If respiratory tract irritation is present, monitor chest x-ray.

Treatment

Life Support

Monitoring

1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.

Oral Exposure

6.5.2)

A) SUMMARY

1) Caution may be indicated in substantial recent ingestions because the patient may rapidly become obtunded, comatose, or convulsing, thereby at risk of aspiration of gastric contents into the lungs.

B) GASTRIC LAVAGE/PRECAUTIONS

1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.

C) GASTRIC LAVAGE

1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).

a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2) PRECAUTIONS:

a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.

3) LAVAGE FLUID:

a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

4) COMPLICATIONS:

a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

5) CONTRAINDICATIONS:

a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

D) ACTIVATED CHARCOAL/CATHARTIC

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) DILUTION

1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).

B) MONITORING OF PATIENT

1) Monitor liver and renal function tests.
2) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated.
3) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism.

C) BODY TEMPERATURE ABOVE REFERENCE RANGE

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

E) ATROPINE

1) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia (Morgan, 1989).

F) OXYGEN

1) Administration of oxygen may assist in minimizing tissue hypoxia (Morgan, 1989).

G) PSYCHOMOTOR AGITATION

1) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia (Morgan, 1993).
2) INDICATION

a) If patient is severely agitated, sedate with IV benzodiazepines.

3) DIAZEPAM DOSE

a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

4) LORAZEPAM DOSE

a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

5) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.

H) METHEMOGLOBINEMIA

1) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants (Froslie & Karlog, 1970; Froslie, 1973; Hayes, 1982). This effect has not been reported in exposed humans.
2) If cyanosis is present, obtain methemoglobin level and monitor if abnormal.
3) SUMMARY

4) METHYLENE BLUE

5) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

I) IRRITATION SYMPTOM

1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.

J) ENDOSCOPIC PROCEDURE

1) There is little information regarding the use of endoscopy, corticosteroids or surgery in the setting of concentrated dinoterb ingestion. The following information is derived from experience with other corrosives.
2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
3) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

a) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)

5) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):

a) Advancing across the cricopharynx under direct vision
b) Gently advancing with minimal air insufflation
c) Never retroverting or retroflexing the endoscope
d) Using a pediatric flexible endoscope
e) Using extreme caution in advancing beyond burn lesion areas
f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).

6) GRADING

a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
b) Grade 0 - Normal examination
c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.

7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
8) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
9) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).

K) CORTICOSTEROID

1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
8) STUDIES

a) ANIMAL

1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).

b) HUMAN

1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
2) META ANALYSIS

a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).

3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).

a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).

6) ADVERSE EFFECTS

a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).

L) SURGICAL PROCEDURE

1) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
2) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
3) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).

a) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).

4) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
5) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
6) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).

a) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) IRRITATION SYMPTOM

1) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
2) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
3) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).

a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.

1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).

4) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
5) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.

B) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
8) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.

C) MONITORING OF PATIENT

D) BODY TEMPERATURE ABOVE REFERENCE RANGE

E) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

F) ATROPINE

1) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia (Morgan, 1989).

G) OXYGEN

1) Administration of oxygen may assist in minimizing tissue hypoxia (Morgan, 1989).

H) PSYCHOMOTOR AGITATION

1) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia (Morgan, 1993).
2) INDICATION

a) If patient is severely agitated, sedate with IV benzodiazepines.

3) DIAZEPAM DOSE

4) LORAZEPAM DOSE

I) METHEMOGLOBINEMIA

4) METHYLENE BLUE

5) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

J) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) SUPPORT

1) No cases of systemic toxicity in humans following ocular exposure to this compound have been reported. Should systemic toxicity develop following eye exposure:
2) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

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. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).

B) SKIN DISCOLORATION

1) Cutaneous exposure is usually accompanied by a yellowish discoloration which does not have to be removed entirely to prevent absorption.

C) DERMAL ABSORPTION

1) Severe systemic dinitrophenol poisoning can occur from dermal exposure; hence aggressive and immediate skin decontamination must be undertaken and a physician consulted as soon as possible.

D) OTHER

1) DINITROPHENOL COMPOUNDS: The survival doses and lethal doses from application of 3% solutions of various dinitrophenol compounds to guinea pig skin is shown below (Spencer et al, 1948):

COMPOUND	SURVIVAL DOSE (G/KG)	LETHAL DOSE (G/KG)
2-sec-Butyl-4,6-dinitrophenol	0.1	0.5
4,6-Dinitro-o-cresol	0.2	0.5
2,4-Dinitrophenol	0.2	0.7
2-Cyclohexyl-4,6-dinitrophenol	1.0 or more	>1.0
2-Cyclohexyl-4,6-dinitrophenol compound with dicyclohexylamine	1.0 or more	>1.0

6.9.2)

A) MONITORING OF PATIENT

B) BODY TEMPERATURE ABOVE REFERENCE RANGE

C) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

D) ATROPINE

1) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia (Morgan, 1989).

E) OXYGEN

1) Administration of oxygen may assist in minimizing tissue hypoxia (Morgan, 1989).

F) PSYCHOMOTOR AGITATION

1) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia (Morgan, 1993).
2) INDICATION

a) If patient is severely agitated, sedate with IV benzodiazepines.

3) DIAZEPAM DOSE

4) LORAZEPAM DOSE

G) METHEMOGLOBINEMIA

4) METHYLENE BLUE

5) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

H) IRRITATION SYMPTOM

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

I) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

1) HEMODIALYSIS

a) Hemodialysis has not been shown to be effective in poisoning with these agents (Morgan, 1989).

2) FORCED DIURESIS

a) Forced diuresis has not been shown to be of benefit in reducing the body burden of these agents (Morgan, 1989).

3) HEMOPERFUSION

a) Hemoperfusion has not been sufficiently tested in poisoning with these agents to state whether or not it could have any beneficial effect (Morgan, 1989).

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

1) The maximum tolerated human exposure to this agent has not been delineated.

Workplace Standards

1) Not Listed

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

1) Not Listed

Toxicity Information

7.7.1)

A) References: EPA, 1985 Sax & Lewis, 1989

1) LD50- (ORAL)MOUSE:

a) 25 mg/kg

2) LD50- (ORAL)RAT:

a) 62 mg/kg

Pharmacology Toxicology

Physicochemical

Physical Characteristics

Molecular Weight

Animal Toxicology

References

General Bibliography

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DINOTERB

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Endocrine

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Life Support

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Physical Characteristics

Molecular Weight

General Bibliography