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BORATES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The borate ion is a weak germicide when prepared in an aqueous solution and has limited bacteriostatic ability (Harvey, 1952; (Baselt, 2000).

Specific Substances

    A) Boric Acid
    1) Boracic Acid
    2) Orthoboric Acid
    3) CAS 10043-35-3
    4) References: RTECS, 1990
    Sodium Borate
    1) Antipyonin
    2) Borascu
    3) Borax
    4) Borax Decahydrate
    5) Boricin
    6) Gertley Borate
    7) Neobor
    8) Polybor
    9) Sodium Biborate
    10) Sodium Biborate Decahydrate
    11) Sodium Borate Decahydrate
    12) Sodium Metaborate
    13) Sodium Pyroborate
    14) Sodium Pyroborate Decahydrate
    15) Sodium Tetraborate
    16) Sodium Tetraborate Decahydrate
    17) Sodium Tetraborate Anhydrous
    18) Sodium Tetraborate Pentaborate
    19) CAS 1303-96-4
    20) References: RTECS, 1990; ACGIH, 1980
    Others
    1) Borate
    2) Boric Anhydride
    3) Boric Oxide
    4) Boron oxide
    5) Boron Sesquioxide
    6) Boron Trioxide
    7) Magnesium Perborate
    8) Sodium Borate Solution Compound (Dobell's Solution)
    9) Tincal
    10) Tinkal

Available Forms Sources

    A) FORMS
    1) The following compounds are grouped according to their similarities and equated to their nearest approximate boron content (Budavari, 1996): 
    A.  Sodium BORATE - sodium BIBORATE -
    sodium PYROBORATE - sodium TETRABORATE
    (found in borax cleansers)=Boron 21.50%
B.  Sodium BORATE SOLUTION COMPOUND (DOBELL'S
    SOLUTION - yellowish clear liquid)
    1.5 grams sodium borate, 1.5 grams sodium
    bicarbonate, 0.3 mL liquefied phenol,
    3.5 mL glycerol, water added to 100 mL
C.  BORIC ANHYDRIDE - BORON OXIDE - boron
    TRIOXIDE - boric OXIDE - boron SESQUIOXIDE -
    (improperly called anhydrous boric acid or
    fuse boric acid);  BORAX - TINCAL -
    TINKAL = boron 33%
D.  SODIUM PERBORATE (prepared from sodium
    metaborate & hydrogen peroxide - used as
    an oxidizer in dentrifices, soaps) = Boron 13.22%
E.  SODIUM METABORATE
    (obtained from fusing borax & sodium
    carbonate) = Boron 16.44%
F.  MAGNESIUM PERBORATE (an oxidizer often
    used with chalk in tooth powders) = Boron 15.23%
    SATURATED SOLUTIONS comparable to approximately
    5.55% boric acid
G.  Boric acid powder or crystals are commonly used
    to make extemporaneous eyewash or antiseptic
    solutions.  The usual method is to dissolve 1
    teaspoonful into 8 ounces of water.

    B) USES
    1) MEDICAL
    a) Borates have been used in a wide variety of pharmaceutical preparations (ITI, 1985) including medicated powders, skin lotions, mouthwash, toothpaste, topical astringents, and eyewash solutions. Boric acid and borax are used at concentrations of up to 5% in US cosmetics, up to 3% in cosmetics in Europe, and up to 0.5% in oral hygiene products in Europe and elsewhere (Hubbard, 1998). The effectiveness of borates of antiseptic agents has been questioned (Harvey, 1985).
    b) Boric acid has been used as a preservative for urine samples (S Sweetman , 2002).
    c) Boric acid possesses weak bacteriostatic and fungistatic properties, but it has generally been replaced by more effective and less toxic disinfectants Both boric acid and borax are NOT intended for internal use (S Sweetman , 2002).
    d) A preparation of borax is used in homeopathic medicine (S Sweetman , 2002).
    2) HOUSEHOLD
    a) Its use as a preservative in beverages and foods is prohibited by national and state legislation in the United States (HSDB , 2002). The use of boric acid in cosmetics and toiletries is also restricted in the UK (S Sweetman , 2002).
    b) Borates have been used as a home remedy for diaper rash and oral discomfort in infants. A mixture of boric acid and honey, in particular, has been applied to pacifiers of irritable infants. Severe toxicity and death have resulted from these practices (Goldbloom & Goldbloom, 1953; Baliah et al, 1969; Gordon et al, 1973; O'Sullivan & Taylor, 1983).
    c) Boric acid powder mixed with flour or sugar is used to kill ants and cockroaches in the home. Commercially available insecticides and herbicides used in the home may contain borates (S Sweetman , 2002).
    3) INDUSTRIAL
    a) Borates are boron-containing compounds used in making heat-resistant glass, glass fibers, glazes, enamels, fire-resistant materials and agents, pigments, paints, catalysts, gliding baths, photographic agents, and as insecticides and herbicides (ITI, 1985; ACGIH, 1980; Gosselin et al, 1984). Borates are used in the manufacture of paper and paperboard (HSDB , 2002).
    b) Borates are used to artificially age and preserve wood, as flame retardants in wood and textiles, in cleaning compounds, for soldering metals, and to cure and preserve skins (ACGIH, 1980; Gosselin et al, 1984).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Borates are used in medicated powders, lotions, soaps, mouthwash, toothpaste, astringents, eyewashes, and cosmetics. Also used as an antimicrobial to treat recurrent vulvovaginal candidiasis. Mixed with sugar, boric acid has been used as a cockroach killer.
    B) PHARMACOLOGY: Has some bacteriostatic activity.
    C) TOXICOLOGY: Boric acid is well absorbed through the gastrointestinal tract, open wounds, and serous cavities. Toxicity has been described following ingestion, parenteral injection, enemas, lavage of serous cavities, and dermal application to burned and abraded skin. Systemic toxicity is more likely to occur following chronic or multiple exposures. Local tissue injury is due to caustic effects. The mechanism of systemic toxicity is unknown.
    D) EPIDEMIOLOGY: Exposure is not common and severe toxicity is rare. Severe and fatal poisonings have rarely been reported following acute ingestion of boric acid/borates, usually following repeated dermal application to abraded or burned skin, or with chronic ingestion.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Nausea, vomiting, diarrhea, and skin erythema with subsequent desquamation are the most common effects from any route of exposure. Nausea and vomiting generally occur early, while dermatologic manifestations are delayed 3 to 5 days after exposure.
    2) SEVERE TOXICITY: Dehydration, hypotension, CNS excitation or depression, lethargy, seizures, coma, acute renal failure, dysrhythmias, and metabolic acidosis have been reported in patients with severe toxicity.
    0.2.3) VITAL SIGNS
    A) Significant ingestions or dermal exposures can be associated with weak, rapid pulse, cyanosis and hypotension. The patient may present with hypothermia, hyperthermia or normal body temperature.
    0.2.20) REPRODUCTIVE
    A) There is insufficient information concerning the reproductive effects of borates in humans. However, in 1 recent study of male workers exposed to boron, no unfavorable effects on reproductivity were observed. Adverse testicular effects and infertility have been reported in animals.
    B) There have been limited animal studies which suggest decreased ovulation, fetotoxicity and developmental defects may occur with very high exposure levels. Maternal toxicity was present in some studies.

Laboratory Monitoring

    A) Monitor renal function tests, cardiovascular status, and fluid and electrolyte balance in symptomatic patients.
    B) Blood borate concentrations may be useful to establish the diagnosis of borate intoxication, though they are not readily available and unlikely to be valuable for acute care.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is primarily supportive. Hydration, antiemetics, and electrolyte repletion are typically all that are required.
    2) MANAGEMENT OF SEVERE TOXICITY: Supportive care with consideration of dialysis. For hypotension, infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine or norepinephrine; titrate to desired response. For seizures, administer a benzodiazepine. Consider phenobarbital or propofol if seizures persist or recur.
    B) DECONTAMINATION
    1) PREHOSPITAL: Gastrointestinal decontamination is generally not recommended.
    2) HOSPITAL: There are no studies that have evaluated the adsorption of borates to activated charcoal. As there is substantial gastrointestinal irritation and most patients will have spontaneous emesis, routine use of activated charcoal is not recommended.
    C) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression.
    D) ANTIDOTE
    1) There is no specific antidote.
    E) ENHANCED ELIMINATION
    1) Boric acid is removed by hemodialysis, with an extraction ratio of approximately 70%. Hemodialysis should be considered in patients with severe toxicity who are not responding to conventional therapy, or for the management of severe fluid-electrolyte abnormalities refractory to conventional management.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with inadvertent exposures with minimal symptoms may be observed at home.
    2) OBSERVATION CRITERIA: Patients with deliberate exposure and those with more than mild symptoms (eg, persistent vomiting, CNS effects) should be referred to a healthcare facility for evaluation and treatment.
    3) ADMISSION CRITERIA: All symptomatic patients showing evidence of systemic toxicity (ie, cardiovascular effects, acidosis, CNS effects) should be admitted.
    4) CONSULT CRITERIA: Consult a medical toxicologist or local poison control center for patients with systemic toxicity or ongoing local tissue symptoms following borate exposure.
    G) PITFALLS
    1) Failing to recognize borate exposure as it is relatively rare, and failure to recognize that systemic poisoning may occur and produce delayed symptoms.
    H) PHARMACOKINETICS
    1) Boric acid is well absorbed through the gastrointestinal tract, open wounds, and serous cavities. After parenteral administration to animals, boric acid is distributed to all tissues, except the brain, within 30 minutes. Borates are primarily cleared unchanged by the kidney. The apparent elimination half-life is 5 to 10 hours.
    I) DIFFERENTIAL DIAGNOSIS
    1) Acutely, borate intoxication can appear similar to heavy metal ingestion.
    0.4.3) INHALATION EXPOSURE
    A) 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 inhaled beta-2 agonist. Observe for systemic effects and administer supportive treatment as necessary.
    0.4.4) EYE EXPOSURE
    A) Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. Observe for systemic effects which chiefly occur from chronic skin exposure, or application of borates to denuded skin.

Range Of Toxicity

    A) TOXICITY: The minimum lethal and maximum tolerated dose of ingested borates are not well established. There is wide variability in the response to borates. Fatalities occur more frequently in young children. Death has resulted from boric acid ingestions of 2 to 3 g in infants, 5 to 6 g in children, and 15 to 20 g in adults. There have also been reports of survival after an estimated 10 g ingested by a 2-year-old child, and an estimated 297 g ingested by an adult. There are 2.9 to 4.4 g of boric acid in 1 teaspoonful of 100% boric acid powder, crystals, or granules.

Clinical Effects

Summary Of Exposure

    A) USES: Borates are used in medicated powders, lotions, soaps, mouthwash, toothpaste, astringents, eyewashes, and cosmetics. Also used as an antimicrobial to treat recurrent vulvovaginal candidiasis. Mixed with sugar, boric acid has been used as a cockroach killer.
    B) PHARMACOLOGY: Has some bacteriostatic activity.
    C) TOXICOLOGY: Boric acid is well absorbed through the gastrointestinal tract, open wounds, and serous cavities. Toxicity has been described following ingestion, parenteral injection, enemas, lavage of serous cavities, and dermal application to burned and abraded skin. Systemic toxicity is more likely to occur following chronic or multiple exposures. Local tissue injury is due to caustic effects. The mechanism of systemic toxicity is unknown.
    D) EPIDEMIOLOGY: Exposure is not common and severe toxicity is rare. Severe and fatal poisonings have rarely been reported following acute ingestion of boric acid/borates, usually following repeated dermal application to abraded or burned skin, or with chronic ingestion.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Nausea, vomiting, diarrhea, and skin erythema with subsequent desquamation are the most common effects from any route of exposure. Nausea and vomiting generally occur early, while dermatologic manifestations are delayed 3 to 5 days after exposure.
    2) SEVERE TOXICITY: Dehydration, hypotension, CNS excitation or depression, lethargy, seizures, coma, acute renal failure, dysrhythmias, and metabolic acidosis have been reported in patients with severe toxicity.

Vital Signs

    3.3.1) SUMMARY
    A) Significant ingestions or dermal exposures can be associated with weak, rapid pulse, cyanosis and hypotension. The patient may present with hypothermia, hyperthermia or normal body temperature.
    3.3.3) TEMPERATURE
    A) HYPERTHERMIA, HYPOTHERMIA: Normal body temperature, fever (Webb et al, 2013; Gosselin et al, 1984; Linden et al, 1986; Baliah et al, 1969; Teshima et al, 2001) or hypothermia (Goldbloom & Goldbloom, 1953; Valdes-Dapena & Arey, 1962) can occur with borate ingestion or exposure to abraded skin. These effects may result from acute or chronic exposure.
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION: Severe hypotension and shock can occur following significant borate ingestion or exposure to abraded skin.

Heent

    3.4.5) NOSE
    A) IRRITATION: Nasal irritation, dryness and epistaxis have been reported among workers exposed to borax (Garabrant et al, 1985), boron oxide or boric acid dusts (Garabrant et al, 1984).
    3.4.6) THROAT
    A) IRRITATION: Throat irritation, soreness and dryness have been reported among workers exposed to borax (Garabrant et al, 1985), boron oxide or boric acid dusts (Garabrant et al, 1984).
    B) ERYTHEMA of the lips, tongue, palate and throat has been reported in infants following oral or dermal exposure to boric acid (Goldbloom & Goldbloom, 1953).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CYANOSIS
    1) WITH POISONING/EXPOSURE
    a) Cyanosis accompanied by weak, rapid pulse may be present in extreme exposures (Goldbloom & Goldbloom, 1953; Ishii et al, 1993).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Profound dehydration and circulatory collapse may occur in severe cases.
    b) CASE REPORTS
    1) ADULTS: Hypotension has been reported following acute ingestions of approximately 280 g (Restuccio et al, 1992) and 30 g of boric acid (Ishii et al, 1993).
    2) ADULT: A 26-year-old woman received emergent care 14 hours after ingesting 36 grams of boric acid, and developed hypotension (106/54 mmHg), an alteration in consciousness, erythema, and fever (37.3 degrees celsius). The patient gradually improved following gastric decontamination and forced diuresis (Teshima et al, 2001).
    3) ADULT: Persistent hypotension was reported in a 45-year-old man following ingestion of a large glassful containing boric acid pesticide that was mixed with water. His hypotension resolved following administration of vasopressors and continuous renal replacement therapy, initiated to enhance the elimination of the boric acid (Lung & Clancy, 2009).
    C) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: ATRIAL FIBRILLATION with a rapid ventricular response rate of 180/min was reported following an acute ingestion of approximately 280 g of boric acid. This rhythm deteriorated to electromechanical dissociation and death (Restuccio et al, 1992).
    b) CASE REPORTS: Two infants (a 3-month-old and a 40-day-old) developed tachycardia (heart rates 170 and 167 beats/min, respectively) after inadvertent ingestion of formula contaminated with boric acid (total boric acid ingestion of 655 mg/kg and 2570 mg/kg, respectively). The infants also developed other symptoms including dehydration, tachypnea, and oliguria. Both patients recovered without sequelae following continuous venovenous hemodialysis (Pedicelli et al, 2015).
    D) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Mild hypertension was reported in an 82-year-old man who unintentionally ingested 30 g of boric acid (Corradi et al, 2009).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) INJURY OF UPPER RESPIRATORY TRACT
    1) WITH POISONING/EXPOSURE
    a) IRRITATION: Reversible upper respiratory tract irritation has been reported with exposure to boron oxide or boric acid dust concentrations of < 10 mg/m(3) (Garabrant et al, 1984) and borax dust concentrations of 1.1 mg/m(3) to 14.6 mg/m(3) (Garabrant et al, 1985) and 10 to 14 mg/m(3) (Hu et al, 1992).
    1) Common symptoms included nasal irritation, mucous membrane dryness, dry or productive cough and nose bleeds. Shortness of breath, chest pain and/or chest tightness were reported less frequently (Garabrant et al, 1984; Garabrant et al, 1985; Hu et al, 1992).
    B) BRONCHITIS
    1) WITH POISONING/EXPOSURE
    a) A statistically significant increased risk of phlegm production and chronic bronchitis in non-smokers was associated with exposure to 14.6 mg/m(3) of borax dust (Garabrant et al, 1985).
    C) TACHYPNEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS: Two infants (a 3-month-old and a 40-day-old) developed tachypnea (respiratory rates 49 and 31 breaths/min, respectively) following inadvertent ingestion of formula contaminated with boric acid. Total amount of boric acid ingested was 655 mg/kg and 2570 mg/kg, respectively (Pedicelli et al, 2015)
    D) LACK OF EFFECT
    1) No changes in pulmonary function tests (PFTs), and no chest radiograph abnormalities were associated with borax exposure in non-smokers (Garabrant et al, 1985).
    2) Systemic effects following inhalation of borates have not been reported in humans (US DHHS, 1992).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Headache, weakness, lethargy, restlessness, tremors, seizures, altered reflexes, delirium and coma can occur but are less common than gastrointestinal effects (Webb et al, 2013; Goldbloom & Goldbloom, 1953; Gosselin et al, 1984; Litovitz et al, 1988; Ishii et al, 1993).
    b) Neurological effects are generally associated with chronic exposure (Linden et al, 1986).
    c) INCIDENCE OF NEUROLOGICAL EFFECTS: Neurological effects were not reported as key manifestations in a review of 354 acute poisoning cases of boric acid ingestion (Linden et al, 1986). Few details concerning the age distribution of the cases and clinical course were provided.
    1) CASE REPORT: A 26-year-old woman received emergent care 14 hours after ingesting 36 g of boric acid, and developed an alteration in consciousness (described as "clouded"), along with hypotension, erythema, and fever (37.3 degrees celsius) Following gastric decontamination and forced diuresis the patient gradually improved and made a complete recovery (Teshima et al, 2001).
    2) CASE REPORTS: No seizures or CNS effects were reported in 2 fatal adult cases of acute boric acid ingestion (Restuccio et al, 1992; Ishii et al, 1993).
    3) CASE SERIES: Among 109 cases of boric acid poisoning reviewed by Goldbloom & Goldbloom (1953), CNS effects including meningeal irritation, convulsions, delirium and coma occurred in 62% (n=39) of the patients over 2 years of age, and in 83% (n=41) of the patients under 2 years of age. The cases of poisoning resulted from various routes and durations of exposure (Goldbloom & Goldbloom, 1953).
    4) CASE SERIES: CNS effects occurred in 10 out of 11 neonates who had ingested boric acid containing formula (Wong et al, 1964). The estimated amount ingested ranged from 4 to 14.06 grams.
    B) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache and lightheadedness were infrequently reported in a retrospective chart review of 784 boric acid ingestions (Litovitz et al, 1988). Acute ingestions (782 out of 784) were the primary exposure, with 80.2% of the cases involving children less than 6 years of age.
    b) CASE REPORT: An 82-year-old man developed headache, agitation, mild hypertension, nausea, and vomiting after unintentionally ingesting 30 g of boric acid. His initial serum boric acid concentration was 1800 mcg/mL. Following hemodialysis and forced diuresis, the patient recovered. A repeat serum boric acid concentration, obtained approximately 132 hours postingestion (120 hours after initiating enhanced elimination procedures) was 30 mcg/mL (Corradi et al, 2009).
    c) CHRONIC: Chronic boric acid poisoning can cause lethargy, headache and weakness (Linden et al, 1986).
    C) FEELING NERVOUS
    1) WITH POISONING/EXPOSURE
    a) Extreme irritability was reported in neonates who ingested formula accidentally prepared with a 2.5% boric acid solution (Wong et al, 1964).
    b) Irritability was reported in 2 out of 784 cases of acute boric acid ingestion (Litovitz et al, 1988). It is not known if these were adult or pediatric cases.
    D) HYPERREFLEXIA
    1) WITH POISONING/EXPOSURE
    a) Exaggerated startle reflexes, brisk deep tendon reflexes and/or exaggerated Moro reflex have been reported in young infants who ingested boric acid (Gordon et al, 1973; Wong et al, 1964).
    b) Hypoactive tendon reflexes were reported in a 20-day-old infant who had boric acid applied to the buttocks several times per day, for several days (Goldbloom & Goldbloom, 1953).
    E) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Arching of the back (opisthotonus), convulsions and coma were reported in neonates who ingested boric acid-containing formula (Wong et al, 1964).
    b) O'Sullivan & Taylor (1983) reported seizures in 7 young infants, and Gordon et al (1973) reported seizures in 2 young infants who had chronic exposure to pacifiers coated with a honey and borax mixture. The estimated borax dose was 3 to 9 grams of borax per week for more than 4 weeks (O'Sullivan & Taylor, 1983).
    c) Periods of tremors, stiffening of the body and loss of consciousness were reported in a 20-day-old infant following application of boric acid to the buttocks several times per day, for 5 days (Goldbloom & Goldbloom, 1953).
    d) Convulsions, unconsciousness and coma have been reported in adults and infants exposed to boric acid by various routes and for various durations (Goldbloom & Goldbloom, 1953).
    e) Irritability, jerking tremors and hypotonia were reported in a 27-day-old infant following administration of boric acid powder to the buttocks 10 to 15 times during a 48 hr period (Baliah et al, 1969).
    F) CENTRAL NERVOUS SYSTEM DEFICIT
    1) CNS depression has been reported after acute and chronic poisoning, ranging from lethargy to coma in severe cases (Schillinger et al, 1982a; Litovitz et al, 1988; Wong et al, 1964; Valdes-Dapena & Arey, 1962).
    G) CRYING
    1) WITH POISONING/EXPOSURE
    a) MISCELLANEOUS PEDIATRIC EFFECTS: Staring, apprehensive facial expression and/or high-pitched cry have been reported in neonates following ingestion of boric acid containing formula (Wong et al, 1964) and application of boric acid to the buttocks of young infants (Goldbloom & Goldbloom, 1953).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Gastroenteritis (nausea, vomiting, diarrhea) is common (Lung & Clancy, 2009; Restuccio et al, 1992; Elmamlem et al, 1984; Linden et al, 1986) Litovitz et al, 1986). The vomitus and feces may be a blue-green color.
    b) CASE REPORT: An 82-year-old man developed headache, agitation, mild hypertension, nausea, and vomiting after unintentionally ingesting 30 g of boric acid. His initial serum boric acid concentration was 1800 mcg/mL. Following hemodialysis and forced diuresis, the patient recovered. A repeat serum boric acid concentration, obtained approximately 132 hours postingestion (120 hours after initiating enhanced elimination procedures) was 30 mcg/mL (Corradi et al, 2009).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) WITH POISONING/EXPOSURE
    a) Hepatomegaly and jaundice is rarely reported (Gosselin et al, 1984).
    b) CASE REPORT: Transient elevation of liver function tests were reported in a woman following ingestion of boric acid powder (Schillinger et al, 1982a).
    c) CASE REPORT: Jaundice in one infant who survived, and hepatic congestion, fatty changes and parenchymal cell degeneration in another infant who did not survive, were reported after ingesting approximately 14.06 grams and 9.25 grams of boric acid, respectively, over 3 to 5 days (Wong et al, 1964).
    1) The hepatic effects in these cases cannot be concluded as direct effects of boric acid. Jaundice is common among newborns. Renal and cardiovascular complications present in the infant who did not survive may have contributed to the hepatic effects.

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) OLIGURIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Oliguria and anuria occurred in 10 neonates who ingested an estimated 4 to 14.06 grams of boric acid (Wong et al, 1964). Oliguria and anuria did not occur in one infant who ingested approximately 2.0 grams of boric acid.
    b) CASE REPORT: A 44-year-old woman presented with oliguria and elevated BUN (62 mg/dl) and creatinine (11.1 mg/dl) 3 days after consuming half a container (size not provided) of boric acid powder (Schillinger et al, 1982).
    c) CASE REPORT: A 45-year-old man became oliguric shortly after ingesting approximately 2 cups of boric acid crystals (Restuccio et al, 1992). The patient was diagnosed with oliguric renal failure 2 days later.
    d) CASE REPORT: Oliguria was reported in a 3-month-old infant following inadvertent ingestion of water containing boric acid that was used to prepare milk formula. The total amount of boric acid ingested was 655 mg/kg (Pedicelli et al, 2015).
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS (ADULTS): Renal failure was reported following an acute ingestion of approximately 280 g (Restuccio et al, 1992), and 30 g of boric acid (Ishii et al, 1993).
    b) CASE REPORT: Acute renal failure (BUN 42 mg/dL [reference range 8.4 to 25.7 mg/dL]; creatinine 2.3 mg/dL [reference range 0.7 to 1.3 mg/dL]) occurred in a 56-year-old man who reportedly ingested 2 cups of an insecticide containing boric acid as its primary toxin (Webb et al, 2013).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Metabolic acidosis developed following an acute ingestion of approximately 280 g of boric acid (Restuccio et al, 1992).
    b) CASE REPORT: Metabolic acidosis (pH 7.36, PaCO2 26 mmHg, HCO3 17 mmol/L) was reported in a 56-year-old man following a reported ingestion of 2 cups of an insecticide containing boric acid as its primary toxin (Webb et al, 2013).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) Profound anemia developed in a 4.5-month-old infant following the use of borax and honey on the infant's pacifier for approximately 3.5 months (Gordon et al, 1973).
    2) Bone marrow suppression and anemia (hemoglobin 6.5 grams/deciliter, hematocrit 19%) developed 10 days after acute boric acid ingestion in a 45-year-old woman (Schillinger et al, 1982a).
    B) LEUKOPENIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Neutropenia (ANC of 0.7 k/mcL [reference range 1.80 to 8 k/mcL]) was reported in a 56-year-old man following a reported ingestion of 2 cups of an insecticide containing boric acid as its primary toxin. With supportive therapy, the patient's ANC normalized within 3 weeks post-ingestion (Webb et al, 2013).
    2) NEUTROPHIL COUNTS: Two cases of mild neutropenia and two cases of neutrophilia in young infants following repeated application of boric acid to the buttocks have been reported (Goldbloom & Goldbloom, 1953).
    3) These hematological effects may not have been directly related to boric acid exposure.
    C) THROMBOCYTOPENIC DISORDER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Thrombocytopenia (platelets 40,000/mcL [reference range 150,000 to 450,000/mcL]) was reported in a 56-year-old man following a reported ingestion of 2 cups of an insecticide containing boric acid as its primary toxin. With supportive therapy, his platelet count normalized within 3 weeks post-ingestion (Webb et al, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Boric acid poisoning presents with erythematous rash with desquamation (cooked lobster syndrome) (Restuccio et al, 1992; Schillinger et al, 1982; Wong et al, 1964) .
    b) FINDINGS: Erythema is usually present and prominent on the buttocks and scrotum. Desquamation occurs not only where the rash is present, but on the mucous membranes, perioral, and anal surfaces. The lips, oral mucosa and throat may be erythematous (Goldbloom & Goldbloom, 1953).
    c) Severe toxicity and death can occur in infants before the onset of dermal effects (Wong et al, 1964).
    d) CASE REPORT: A 45-year-old man presented to the emergency department with nausea and vomiting after ingesting a large glassful containing boric acid pesticide that was mixed with water. The patient had persistent hypotension and tachycardia, and on hospital day 2, developed a generalized red-orange rash with desquamation. A serum borate concentration, obtained on hospital day 3, was greater than 13,000 mcg/dL (normal is less than 100 mcg/dL). With supportive therapy, including continuous renal replacement therapy, the patient's condition improved and he was subsequently transferred to the psychiatry unit (Lung & Clancy, 2009).
    e) CASE REPORT: A 56-year-old man, with a history of diabetes, hypertension, depression, and suicide attempts, presented to the emergency department with altered mental status, hyperthermia, and diffuse erythematous dermal eruption. Physical examination revealed erythema and diffuse desquamation of his axilla, and inguinal, gluteal, and sacral areas, bullae of his upper extremities and neck, and hemorrhagic crusting of his lips with conjunctival edema. Laboratory analysis indicated acute renal failure, metabolic acidosis, hyperglycemia, and an elevated creatine kinase concentration. Further review of the patient's history revealed that he had ingested 2 cups of an insecticide containing boric acid as its primary toxin. Subsequently, his serum boron concentration was reported to be 34,000 mcg/L (normal is less than 100 mcg/L). The patient's condition continued to deteriorate with development of bilateral palmar erythema, alopecia, thrombocytopenia, and neutropenia. With supportive therapy, including topical wound care, the patient showed gradual improvement of his skin, with re-epithelialization beginning 7 days post-ingestion (Webb et al, 2013).
    B) ALOPECIA
    1) WITH POISONING/EXPOSURE
    a) Alopecia may also occur (Webb et al, 2013; Schillinger et al, 1982; Gordon et al, 1973).
    b) CASE REPORTS: Reversible alopecia occurred in three patients following occupational dermal exposure to solutions containing borax (decahydrate sodium tetraborate). The first patient experienced global alopecia within 7 days after his scalp was completely soaked with a solution containing 80% borax. Patients 2 and 3 developed patchy scalp hair loss over a 4-month period while working in the automotive industry and routinely removing antifreeze solution that contained 1% to 5% borax without wearing protective head gear. The alopecia in all 3 patients resolved following reduction or elimination of occupational exposure to the borax solutions (Beckett et al, 2001).

Reproductive

    3.20.1) SUMMARY
    A) There is insufficient information concerning the reproductive effects of borates in humans. However, in 1 recent study of male workers exposed to boron, no unfavorable effects on reproductivity were observed. Adverse testicular effects and infertility have been reported in animals.
    B) There have been limited animal studies which suggest decreased ovulation, fetotoxicity and developmental defects may occur with very high exposure levels. Maternal toxicity was present in some studies.
    3.20.2) TERATOGENICITY
    A) SKELETAL MALFORMATION
    1) ANIMALS - Developmental and skeletal malformations were reported in the fetuses of rats and mice fed boric acid as 0.2 to 0.8% of the diet during pregnancy (Heindel et al, 1992). Rats were more sensitive to the developmental effects of borates than mice. Maternal toxicity was present at all dose levels at which fetal defects occurred.
    a) RATS - Visceral and skeletal malformations, particularly short 13th rib, were most common at the 0.2% to 0.4% (163 to 330 mg/kg/d) dose levels administered during gestational days 0 to 20. External, visceral and skeletal malformations were present at the 0.8% (539 mg/kg/d) dose administered during gestational days 6 to 15.
    b) MICE - Fetal malformations were observed chiefly at the 0.4% (1003 mg/kg/d) dose level with exposure during gestational days 0 to 17. Short rib was the main dose-related effect. No adverse fetal effects were present at the 0.1% (248 mg/kg/day) boric acid dose level.
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) STILLBIRTH
    a) NEONATAL MORTALITY - No information was found regarding the effects of borates in humans during pregnancy.
    1) Animal studies have been reviewed by Barlow & Sullivan (1982) and the US DHHS (1992).
    2) Stillbirths and increased neonatal mortality occurred in offspring of female rats administered boric acid (up to 400 mg/kg boron) for 1 or 2 years prior to mating (Truhaut et al, 1964). Higher doses for 8 or 12 months prior to mating were also associated with decreased litter size and increased perinatal mortality.
    3) Embryo/fetotoxicity, reduced fetal body weight and/or increased prenatal mortality have been reported in rats and mice as a result of maternal consumption during gestation of boric acid as 0.1% to 0.8% of the diet (Heindel et al, 1992). Maternal toxicity occurred at all doses in the mice, and at greater than the 0.1% (78 mg/kg/day) dose in the rats.
    2) BIRTH PREMATURE
    a) REDUCED BODY WEIGHT - Reduced fetal or neonatal body weight have been reported in rats and mice exposed to boric acid orally during gestation (Heindel et al, 1992; Harris et al, 1992).
    3.20.5) FERTILITY
    A) TESTIS DISORDER
    1) In a review of borate toxicity, borates were observed to cause testicular toxicity in rats, mice, and dogs. Oral equivalent boron doses ranging from 26 mg/kg/day to 111 mg/kg/day resulted in effects such as reversible inhibition of spermiation, testicular atrophy, and reduced fertility (Hubbard, 1998).
    B) LACK OF EFFECT
    1) In a study of male workers in Turkey exposed to boron, no unfavorable effects on reproductivity were observed (Basaran et al, 2012).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) HUMANS - No information concerning carcinogenicity in humans due to boron, borates, borax or boric acid exposure was found in reports by the IARC (1987), the ASTDR (US DHHS, 1992), the NTP (US DHHS, 1994) and the ACGIH (1994). Carcinogenic potential of boron in humans currently cannot be conclusively determined (US DHHS, 1992).
    2) ANIMALS - No evidence of carcinogenicity was reported in a life-time bioassay involving mice exposed to boric acid in the diet (NTP, 1987). No information concerning carcinogenicity following other routes of exposure was found by the ATSDR (US DHHS, 1992).

Genotoxicity

    A) The ATSDR (US DHHS, 1992) has concluded from a review of available studies that genotoxicity as a result of boron exposure may not be a human health concern. There is insufficient information regarding genotoxic effects of borates in humans. Bacterial and limited mammalian assay results have been negative.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor renal function tests, cardiovascular status, and fluid and electrolyte balance in symptomatic patients.
    B) Blood borate concentrations may be useful to establish the diagnosis of borate intoxication, though they are not readily available and unlikely to be valuable for acute care.
    4.1.2) SERUM/BLOOD
    A) Monitor renal function tests and fluid and electrolyte balance in symptomatic patients.
    B) Blood borate concentrations may be useful to establish the diagnosis of borate intoxication, though they are not readily available and unlikely to be valuable for acute care.
    1) Serum boric acid levels do not appear to correlate adequately with the severity of symptoms.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Urinary boron concentrations can indicate total body burden of boron. The normal range of urinary boron has been reported as 0.004 to 0.66 mg/100mL (US DHHS, 1992).
    4.1.4) OTHER
    A) OTHER
    1) CARDIAC MONITORING
    a) Monitor cardiovascular status in symptomatic patients.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Boron levels can be determined in patient samples such as blood and urine, as well as in drinking water, soil, plants, and rock plants.
    a) Inductively coupled plasma atomic emission spectrometry with atomic emission spectrography is one type of high temperature atomic spectrometry that can be used. Other useful methods include colorimetry, prompt neutron activation analysis, and ion-exclusion chromatography (Mehra et al, 1990).
    b) Atomic absorption analysis is not the analytical method of choice. In addition, the tumeric acid test for the presence of borates in urine is neither quantitative nor reliable.
    c) A more sensitive colorimetric technique uses low temperature ashing of specimens and formation of a complex with curcumin (Baselt, 2000).
    2) Methods which are available for the determination of total boron and specific boron species are summarized by the ATSDR (US DHHS, 1992).
    3) Analyses of blood samples for boron is performed by National Medical Services:
    a) National Medical Services 3701 Welsh Road Willow Grove, PA 19090 (215) 657-4900 (215) 657-2972 FAX (800) LAB-NMS1 (800) 522-6671 nms@nmslab.com

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) All symptomatic patients showing evidence of systemic toxicity (ie, cardiovascular effects, acidosis, CNS effects) should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with inadvertent exposures with minimal symptoms may be observed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist or local poison control center for patients with systemic toxicity or ongoing local tissue symptoms following borate exposure.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate exposure and those with more than mild symptoms (eg, persistent vomiting, CNS effects) should be referred to a healthcare facility for evaluation and treatment.

Monitoring

    A) Monitor renal function tests, cardiovascular status, and fluid and electrolyte balance in symptomatic patients.
    B) Blood borate concentrations may be useful to establish the diagnosis of borate intoxication, though they are not readily available and unlikely to be valuable for acute care.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is generally not recommended.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) There are no studies that have evaluated the adsorption of borates to activated charcoal. As there is substantial gastrointestinal irritation and most patients will have spontaneous emesis, routine use of activated charcoal is not recommended.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is primarily supportive and includes monitoring for the development of hypotension, fluid and electrolyte imbalance, seizures, renal failure, cardiac arrhythmias and shock. Severe dehydration can occur and contribute to adverse renal and cardiovascular effects.
    a) Administer IV fluids to treat dehydration. Treatment of hypotension may include IV fluids, dopamine or norepinephrine.
    2) Hemodialysis, peritoneal dialysis and exchange transfusion may enhance elimination.
    B) MONITORING OF PATIENT
    1) Monitor renal function tests, cardiovascular status, and fluid and electrolyte balance in symptomatic patients.
    2) Blood borate concentrations may be useful to establish the diagnosis of borate intoxication, though they are not readily available and unlikely to be valuable for acute care.
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    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).
    7) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).
    E) DIURESIS
    1) CASE REPORT: A 26-year-old woman ingested 36 grams of boric acid, and developed hypotension (106/54 mmHg), an altered sensorium and fever. The patient was initially decontaminated, and then started on intravenous fluids (began with 3.25 liters) and 100 milligrams of furosemide given over a 4-hour period. Initial diuresis produced 3640 milliliters of urine. Boluses of fluid and an additional 20 milligrams of furosemide were given over the next 78 hours and the patient gradually improved with no residual effects. The serum boric acid also declined from 470 micrograms/milliliter to 169 micrograms/milliliter (Teshima et al, 2001).
    2) CASE REPORT: An 82-year-old man presented with headache, agitation, nausea and vomiting, without any signs of renal dysfunction, approximately 3 hours after unintentionally ingesting 30 grams of boric acid. The patient immediately underwent hemodialysis, which was interrupted 2 hours later due to increased irritability, agitation, and headache, but was completed the next day, approximately 12 hours later. The patient also underwent forced diuresis, with administration of intravenous fluids and furosemide, over the next 4 days. Following hemodialysis, the serum boric acid concentration decreased from 1800 to 530 mcg/mL. After the forced diuresis, the serum boric acid concentration continued to decrease from 530 mcg/mL to 30 mcg/mL (132 hours postingestion). The cumulative fluid volume and furosemide dose were 17.5 liters and 200 mg, respectively, and the total urine output was 17.4 liters (Corradi et al, 2009). Following these treatments, the patient recovered uneventfully and was discharged.
    F) EXPERIMENTAL THERAPY
    1) CHELATION THERAPY
    a) Animal studies suggested that the use of N-acetylcysteine chelation therapy may increase the excretion of boron and reverse boron induced oliguria (Banner et al, 1986).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    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.

Eye Exposure

    6.8.1) DECONTAMINATION
    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).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    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).

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) Hemodialysis, peritoneal dialysis, and exchange transfusion may enhance elimination.
    B) EXCHANGE TRANSFUSION
    1) Exchange transfusion has been advocated and successful in cases of chronic exposure (Boggs & Anrode, 1955; Segar, 1960).
    C) HEMODIALYSIS
    1) Hemodialysis and peritoneal dialysis have been advocated to increase excretion (Baliah et al, 1969). In comparison to renal elimination, the amount removed by peritoneal dialysis is small (Martin, 1971).
    2) INDICATIONS - Hemodialysis is probably indicated in severely symptomatic patients with oliguric renal failure (Stolpmann & Hopmann, 1975) and in patients with severe fluid-electrolyte abnormalities not correctable by conventional therapy.
    3) CASE REPORT: A 12-month-old girl with normal renal function who ingested 3 grams (300 mg/kg) of boric acid underwent hemodialysis on two occasions. The plasma boric acid half-life was 7 hours between dialysis and 3.6 and 4.4 hours during dialysis (Egfjord et al, 1988).
    4) CASE REPORT: Hemodialysis was successfully performed on a 45-year-old man who ingested an unknown amount of insecticide containing approximately 75 grams of boric acid. The patient's serum boric acid decreased from an initial level of 154.44 mcg/mL to 18.36 mcg/mL following a 2.5 hour hemodialysis session. Boric acid clearance was 268 to 289 ml/min and the extraction ratio was 67% to 70% during dialysis. The patient's recovery was uneventful and he was discharged one week postingestion (Naderi & Palmer, 2006).
    5) CASE SERIES: In 3 patients who were treated with hemodialysis for boric acid ingestion, the mean predialysis half-life was 20.4 hours (range 15.3 to 27.8 hours) compared to a mean of 3 hours during dialysis (Litovitz et al, 1988).
    6) CASE REPORT: An 82-year-old man presented with headache, agitation, nausea and vomiting, without any signs of renal dysfunction, approximately 3 hours after unintentionally ingesting 30 grams of boric acid instead of the intended magnesium sulfate in preparation for a colonoscopy. The patient immediately underwent hemodialysis, which was interrupted 2 hours later due to increased irritability, agitation, and headache, but was completed the next day, approximately 12 hours later. The patient also underwent forced diuresis over the next 4 days. Following hemodialysis, the serum boric acid concentration decreased from 1800 to 530 mcg/mL. After the forced diuresis, the serum boric acid concentration continued to decrease from 530 mcg/mL to 30 mcg/mL (132 hours postingestion). During dialysis, boric acid clearance was 235 mL/min with an extraction ratio of 70% (Corradi et al, 2009). Following these treatments, the patient recovered uneventfully and was discharged.
    D) CONTINUOUS VENOVENOUS HEMODIALYSIS
    1) CASE REPORTS: Two infants were treated with continuous venovenous hemodialysis (CVVHD) and recovered without sequelae following inadvertent ingestion of formula containing boric acid. The first patient was a 3-month-old infant who developed dehydration, tachypnea, tachycardia, and oliguria after ingesting 655 mg/kg boric acid that was in the water used to prepare milk formula. The second patient was a 40-day-old girl who developed vomiting, dehydration, tachycardia, and elevated blood pressure after ingesting 3 feedings containing a total of 2570 mg/kg of boric acid. Both patients underwent CVVHD for 36 to 38 hours, and were discharged from the pediatric intensive care unit 7 and 9 days, respectively, after admission (Pedicelli et al, 2015).

Abstracts

Case Reports

    A) INFANT
    1) A 24-day-old, 4.8 kg infant was given 4 ounces of baby formula containing approximately 2.6 grams of boric acid. Nine hours later, the infant presented to the emergency department with irritability, diarrhea, vomiting and marked perianal erythema. Gastric lavage was performed. Ten hours post-ingestion, the serum boric acid level was 147 mcg/mL. Peritoneal dialysis was started; 3,575 mL of dialysate was administered over 25 hours. Repeat serum borate levels decreased. The serum half-life both before and during dialysis was approximately 10 hours.
    a) The child was discharged after five days of hospitalization, having suffered no serious toxicity (Baker & Bogema, 1986).
    b) The 14-month-old, 11.2 kg sibling of the patient described above was given the same solution, receiving about 1.95 grams of boric acid. The serum borate level was 56 mcg/mL 3-1/2 hours post-ingestion. Serum half-life was determined to be eight hours. Except for a mild erythematous macular rash on the face and neck, the child remained asymptomatic and was discharged without incident (Baker & Bogema, 1986).
    2) A 12-month-old girl with normal renal function who ingested 3 grams (300 mg/kg) of boric acid underwent hemodialysis on two occasions. The plasma boric acid half-life was 7 hours between dialysis and 3.6 and 4.4 hours during dialysis (Egfjord et al, 1988).
    B) ADULT
    1) A 77-year-old man accidentally ingested approximately 30 g of boric acid (Ishii et al, 1993). He was initially asymptomatic, but developed vomiting, diarrhea and hiccups 23 hours post ingestion. He was hypotensive (blood pressure 70/0) upon hospital admission, with a low grade fever, marked erythema of the face and trunk, and cyanotic extremities. Laboratory results indicated acute renal failure.
    a) Approximately 30 hours post ingestion, serum concentration of boric acid was 37.7 mcg/mL. Hemodialysis and charcoal hemoperfusion were performed. Serum boric acid concentrations were 25.3 mcg/mL 55 hours post ingestion. Hypotension and shock were not reversed by intensive therapy. The patient died as a result of cardiac insufficiency 63 hours post ingestion.

Range Of Toxicity

Summary

    A) TOXICITY: The minimum lethal and maximum tolerated dose of ingested borates are not well established. There is wide variability in the response to borates. Fatalities occur more frequently in young children. Death has resulted from boric acid ingestions of 2 to 3 g in infants, 5 to 6 g in children, and 15 to 20 g in adults. There have also been reports of survival after an estimated 10 g ingested by a 2-year-old child, and an estimated 297 g ingested by an adult. There are 2.9 to 4.4 g of boric acid in 1 teaspoonful of 100% boric acid powder, crystals, or granules.

Minimum Lethal Exposure

    A) ROUTE OF EXPOSURE
    1) ORAL
    a) Adult fatalities due to single oral doses of boric acid are uncommon (Ishii et al, 1993). Fatalities occur more frequently in young children (Gosselin et al, 1984). The minimal lethal dose of boric acid for man is not entirely known. There is wide variability in the response to borates.
    b) Reports of the minimum oral lethal dose of boron, as boric acid, have been summarized by Locatelli et al (1987) and Wong et al (1964) (Locatelli et al, 1987; Wong et al, 1964):
    1) INFANTS: 2 to 3 g
    2) CHILDREN: 5 to 6 g
    3) ADULTS: 15 to 20 g
    2) DERMAL EXPOSURE
    a) Short-term or chronic exposure of denuded skin to borates can result in systemic toxicity and death. Concentrations of borates applied to abraded skin which will result in lethality or toxicity are not known.
    b) Application of boric acid to burns, wounds or skin eruptions in young infants has resulted in toxicity and death (Goldbloom & Goldbloom, 1953). Severe toxicity in 3 infants and death in one infant who had other perinatal problems, was reported following application of boric acid powder to the buttocks for 2 to 13 days.
    c) Three other cases of death in young infants following daily application of boric acid to diaper rash have been reported (Valdes-Dapena & Arey, 1962). The duration of exposure ranged from a few days to approximately one month.
    d) Two deaths resulted from the use of a 5% boric acid solution as a peritoneal cavity wash in a 25-year-old and as a wound irrigant in a 16-year-old (Valdes-Dapena & Arey, 1962).
    B) CASE REPORTS
    1) ADULTS
    a) In one fatality, a 66-year-old man ingested 1 to 1.5 ounces of sodium borate (borax) powder (Potter, 1921).
    b) In another case, a 53-year-old woman ingested 4 pancakes made with flour which contained 51% sodium borate (McNally & Rust, 1928).
    c) A 45-year-old man died about 63 hours after the acute ingestion of approximately 280 g (two "cupfuls") of boric acid. Renal insufficiency and dehydration may increase the risk of severe toxicity (Restuccio et al, 1992).
    d) A 77-year-old man died of refractory shock 63 hours after ingesting 30 g of boric acid (Ishii et al, 1993).
    2) PEDIATRICS
    a) Preparation of infant formula using a boric acid solution resulted in death in 5 out of 11 newborn infants (Wong et al, 1964). The estimated amounts of borate ingested in the fatalities ranged from 4.5 g to 14.06 g. Most fatal cases involved ingestions of greater than 6 g of borate.
    1) No fatalities were reported in the remaining infants who ingested estimated borate concentrations of less than 5 g. Four out of 6 of these survivors ingested less than or equal to 3 g of borate.
    b) Pediatric deaths have resulted from accidental ingestions and the use of boric acid to cleanse the nipples prior to nursing (Valdes-Dapena & Arey, 1962). The dose of boric acid ingested could not be determined in many of these cases.
    c) Many cases of pediatric ingestions have resulted in vomiting which may have decreased the absorbed dose and reduced the incidence of mortality. Medical treatment has also prevented mortality.

Maximum Tolerated Exposure

    A) CASE SERIES
    1) Litovitz et al (1988) reported that severe toxicity and fatalities did not occur with ingestions of up to 88.8 grams of boric acid, based on a retrospective chart review of 784 acute boric acid ingestions. Estimated doses of 3 g or more were tolerated by 21 children under 6 years of age. Eight adults tolerated ingestions equal to or exceeding an estimated 8 grams. Medical treatment was administered (Litovitz et al, 1988).
    2) Linden et al (1986) have reviewed 354 cases involving acute ingestion of boric acid or boric acid containing products, with doses ranging up to 297 g in an adult and 20 g in a child. No serious manifestations of toxicity resulted. Spontaneous vomiting occurred in most cases. Medical treatment was provided (Linden et al, 1986).
    3) In 10 adult brain tumor patients, borax (sodium and borate) was injected IV in a dose of about 20 g. No deaths resulted, but severe nausea, vomiting, hypotension, confusion, drowsiness, rash and intermittent retching for several days occurred. Renal insufficiency was not reported (Farr et al, 1954; Locksley & Farr, 1955).
    B) CASE REPORTS
    1) ADULT
    a) A 28-year-old woman survived an ingestion of approximately 297 g of a 99% boric acid formulation. Spontaneous vomiting occurred within one hour of ingestion. Gastric lavage and administration of activated charcoal and a cathartic were performed. The patient recovered without additional signs and symptoms (Baselt, 2000).
    b) A 35-year-old survived ingestion of 80 g of boric acid. Vomiting spontaneously occurred within 30 minutes of ingestion. Ipecac, activated charcoal and a cathartic were administered in a hospital. No additional adverse effects developed (Baselt, 2000).
    c) An 82-year-old man developed headache, agitation, mild hypertension, nausea, and vomiting after unintentionally ingesting 30 g of boric acid instead of the intended magnesium sulfate in preparation for a colonoscopy. His initial serum boric acid concentration was 1800 mcg/mL. Following hemodialysis and forced diuresis, the patient recovered. A repeat serum boric acid concentration, obtained approximately 132 hours postingestion (120 hours after initiating enhanced elimination procedures) was 30 mcg/mL (Corradi et al, 2009).
    2) PEDIATRIC
    a) A 2-year-old survived following ingestion of approximately 10 g of boric acid mixed with flour. Spontaneous vomiting had occurred within 3 hours post ingestion. The patient was asymptomatic during 72 hours of hospitalization (Linden et al, 1986).
    b) Two infants inadvertently ingested formula containing boric acid and recovered without sequelae following treatment with continuous venovenous hemodialysis (CVVHD). The first patient was a 3-month-old infant who developed dehydration, tachypnea, tachycardia, and oliguria after ingesting 655 mg/kg boric acid that was in the water used to prepare milk formula. The second patient was a 40-day-old girl who developed vomiting, dehydration, tachycardia, and elevated blood pressure after ingesting 3 feedings containing a total of 2570 mg/kg of boric acid. Both patients underwent CVVHD for 36 to 38 hours, and were discharged from the pediatric intensive care unit 7 and 9 days, respectively, after admission (Pedicelli et al, 2015).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) ADULT
    a) CASE SERIES - In a group of unexposed male workers (n=147) serum boron levels ranged from 3.90 to 36.5 micrograms per 100 gram; median 9.85 (Imbus et al, 1963).
    2) PEDIATRIC
    a) CASE SERIES - In a series of infants whose only exposure to boron was from dietary sources, serum boron levels ranged from 0.0 to 1.25 mcg/mL (average 0.25 mcg/mL) and those exposed to boron containing medications (i.e. bathed in boric acid, baby powder, ointments and laundry soaps) had similar serum levels (Fisher & Freimuth, 1958).
    b) NOTE: The relationship between serum boric acid and serum boron levels is: Serum boric acid in mg/dL = serum boron in mg/dL X 5.72 (Fisher & Freimuth, 1958).
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Serum boric acid levels do not appear to correlate adequately with the severity of symptoms.
    2) CONCENTRATION LEVEL
    a) LETHAL BLOOD CONCENTRATION - About 52 hours after the acute fatal ingestion of approximately 280 grams of boric acid in an adult, the blood boric acid concentration was 42 mg/dL, which is equivalent to a boron concentration of 7.3 milligrams/deciliter (Restuccio et al, 1992).
    b) Serum boric acid concentration was 37.7 mcg/mL 30 hours post ingestion in a 77-year-old man who died after ingesting 30 grams (Ishii et al, 1993).
    c) Post-mortem borate concentrations in heart blood and the gastric contents of an 18-month-old child were 8316 mcg/dL (reference range toxic greater than 2000 mcg/dL) and 6048 mcg/dL, respectively, following ingestion of an unknown amount of pesticide containing boric acid powder (Hamilton & Wolf, 2007).
    3) ACUTE
    a) Serum boric acid levels do not correlate well with the development or severity of symptoms in acute, single ingestions. In a review of case reports involving acute boric acid ingestion, 2 asymptomatic children had serum boric acid levels of 7.4 to 7.9 mg/dL (Linden et al, 1986).
    1) A child with only gastrointestinal symptoms had serum boric acid concentrations of 58 mg/dL, while another child developed systemic toxicity with a level of 12.6 mg/dL (Linden et al, 1986).
    2) Two adults had gastrointestinal symptoms with serum boric acid levels of 4.9 and 232.0 mg/dL, while a third adult developed systemic toxicity with a level of 2.1 mg/dL (Linden et al, 1986).
    b) In a series of 784 patients with boric acid exposure, 51 patients had boric acid blood levels ranging from 0 to 34 mg/dL and no severe toxicity (Litovitz et al, 1988).
    c) Brain and liver concentrations in children who have died from acute boric acid poisoning ranged from 126 to 540 mg/kg (Baselt, 2000).
    d) CASE REPORT - A 45-year-old man developed nausea, vomiting, hypotension, tachycardia, and a generalized erythroderma with desquamation ("boiled lobster" rash) after ingesting a large glassful containing boric acid pesticide that was mixed with water. His serum boric acid concentration, obtained approximately 3 days post-ingestion, was greater than 13,000 mcg/dL (normal is less than 100 mcg/dL) (Lung & Clancy, 2009).
    e) CASE REPORT - An 82-year-old man developed headache, agitation, mild hypertension, nausea, and vomiting after unintentionally ingesting 30 g of boric acid. His initial serum boric acid concentration was 1800 mcg/mL. Following hemodialysis and forced diuresis, the patient recovered. A repeat serum boric acid concentration, obtained approximately 132 hours postingestion (120 hours after initiating enhanced elimination procedures) was 30 mcg/mL (Corradi et al, 2009).
    4) CHRONIC
    a) A 2-year-old child died of chronic boric acid poisoning with a serum boron level of 0.38 mg/dL (equivalent to a serum boric acid level of 2.17 mg/dL) (Linden et al, 1986).
    b) Serum levels may also be of questionable prognostic value in chronic exposures.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) BORIC ACID
    1) LD50- (ORAL)MOUSE:
    a) 3450 mg/kg (RTECS , 2002)
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1740 mg/kg (RTECS , 2002)
    3) LD50- (ORAL)RAT:
    a) 2660 mg/kg (RTECS , 2002)

Pharmacology Toxicology

Toxicologic Mechanism

    A) MECHANISM - The mechanisms of the systemic effects of borates are not known (Gosselin et al, 1984; Wax, 1994). Circulatory collapse is a chief cause of death in the early stages of poisoning (Restuccio et al, 1992; Ishii et al, 1993). Dehydration and impaired renal function contribute to and increase the toxicity of boron (Restuccio et al, 1992).
    1) In animal studies, it was found that sodium tetraborate had a diuretic effect as observed by the increase in urine volume (Tagawa et al, 2000).
    B) IRRITANT EFFECTS - Borax is an alkaline salt and produces irritant effects upon contact with the mucous membranes. Boric acid is produced when boron oxide reacts with water. The irritant effects of boron oxide have been attributed to the exothermic (heat generating) nature of this reaction (Garabrant et al, 1984).

Physicochemical

Physical Characteristics

    A) Boric acid is a white powder or crystalline solid (Sax, 1984).
    B) Sodium Tetraborate Anhydrous is a light grey odorless solid (ACGIH, 1980).
    C) Sodium Tetraborate Decahydrate and Pentahydrate are white odorless, crystalline solids (ACGIH, 1980).

Molecular Weight

    A) Elemental boron: 10.81

Animal Toxicology

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) An 85-head herd of cattle was moved into a field in close proximity to a bag of sodium borate-containing fertilizer.
    1) During the ensuing week, weakness, ataxia, shivering-like fasciculations, stiffness, spasticity, seizures, greenish diarrhea, and vulvar discharge were observed in several of the cattle. A total of twenty-six cattle died.
    2) Borate poisoning was confirmed via post-mortem tissue analysis. The authors suggested that the animals may have been attracted to the fertilizer because of mineral depletion and due to the palatability of the product (Sisk et al, 1988).
    11.1.13) OTHER
    A) OTHER
    1) Clinical signs may include emesis, salivation, diarrhea, abdominal tenderness, tremors or seizures, muscle weakness, ataxia, hyperthermia, Cheyne-Stokes respiration, fluid-electrolyte imbalance, and shock. Metabolic acidosis may occur (Beasley et al, 1990).
    2) Renal failure may occur. Chronic intoxication may result in dry skin, alopecia, and conjunctivitis (Coppock et al, 1988).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Remove the patient and other animals from the source of contamination.
    3) Treatment should always be done on the advice and with the consultation of a veterinarian.
    a) Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
    4) ANIMAL POISON CONTROL CENTERS
    a) 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
    b) 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.
    c) 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.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) EMESIS AND LAVAGE - If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    1) Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    b) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    c) GASTRIC LAVAGE - Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) ACTIVATED CHARCOAL - Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    e) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) RUMINANTS/HORSES/SWINE
    a) EMESIS -
    1) Do not attempt to induce emesis in ruminants (cattle) or equids (horses).
    b) ACTIVATED CHARCOAL -
    1) Adult horses: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube.
    2) Neonates: Administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
    3) Adult cattle: Administer 2 to 9 grams/kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube.
    4) Sheep may be given 0.5 kilogram charcoal in slurry.
    c) CATHARTIC -
    1) Administer an oral cathartic:
    a) Mineral oil (small ruminants and swine, 60 to 200 milliliters; equids and cattle, 0.5 to 1 gallon) or
    b) Magnesium sulfate (ruminants and swine, 1 to 2 grams/kilogram; equine, 0.2 to 0.9 gram/kilogram) or
    c) Milk of Magnesia (small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os).
    2) Give these solutions via stomach tube and monitor for aspiration.
    11.2.5) TREATMENT
    A) DOGS/CATS
    1) MAINTAIN VITAL FUNCTIONS as necessary.
    2) SEIZURES -
    a) DIAZEPAM - Dose of diazepam for DOGS & CATS: 0.5 milligram/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes.
    b) PHENOBARBITAL - Phenobarbital may be used as adjunct treatment at 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously.
    c) REFRACTORY SEIZURES - Consider anesthesia or heavy sedation. Administer pentobarbital to DOGS & CATS at a dose of 3 to 15 milligrams/kilogram intravenously slowly to effect. May need to repeat in 4 to 8 hours. Be sure to protect the airway.
    3) FLUID THERAPY -
    a) Begin fluid diuresis at doses greater than maintenance (66 milliliters solution/kilogram body weight/day intravenously) or, in hypotensive patients, at very high doses (up to shock dose 60 milliliters/kilogram/hour). Monitor for urine production and pulmonary edema. Losses of fluid in diarrhea or vomition must be replaced, also.
    4) ELECTROLYTE BALANCE -
    a) Monitor the animal for metabolic acidosis and correct electrolyte abnormalities.
    5) SUPPORTIVE CARE -
    a) Supportive care includes proper padding for the recumbent animal; a clean, warm, dry environment; turning the recumbent animal regularly; assistance with eating, drinking, and elimination; and supportive alimentation (Beasley et al, 1990).
    B) RUMINANTS/HORSES/SWINE
    1) MAINTAIN VITAL FUNCTIONS -
    a) Secure airway, supply oxygen and begin supportive fluid therapy if necessary.
    2) SEIZURES -
    a) Seizures may be controlled with diazepam. Doses of diazepam, given slowly intravenously: HORSES: 1 milligram/kilogram; CATTLE, SHEEP AND SWINE: 0.5 to 1.5 milligrams/kilogram.
    3) FLUID THERAPY -
    a) Administer electrolyte and fluid therapy as needed. Maintenance dose of intravenous isotonic fluids for horses: 10 to 20 milliliters/ kilogram per day. High dose for shock: 20 to 45 milliliters/kilogram/hour.
    1) Monitor for packed cell volume, adequate urine output and pulmonary edema. Goal is to maintain a urinary flow of 0.1 milliliter/kilogram/minute (2.4 liters/ hour for an 880 pound horse).
    2) Maintenance dose of intravenous isotonic fluids for calves and debilitated adult cattle: 140 milliliters/kilogram/day. Dose for rehydration: 50 to 100 milliliters/kilogram given over 4 to 6 hours.
    4) ELECTROLYTE BALANCE -
    a) Monitor for metabolic acidosis and correct electrolyte abnormalities.
    5) SUPPORTIVE CARE -
    a) Supportive care includes proper padding for the recumbent animal; a clean, warm, dry environment; turning the recumbent animal regularly; assistance with eating, drinking, and elimination; and supportive alimentation (Beasley et al, 1990).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) SPECIFIC TOXIN
    1) LD50 (ORAL) RAT (BORIC ACID) - 2.68 g/kg to 4.08 g/kg (Beasley et al, 1990)
    2) LD50 (ORAL) RAT (BORATE) - 4.5 to 4.98 g/kg (Beasley et al, 1990)

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Remove the patient and other animals from the source of contamination.
    3) Treatment should always be done on the advice and with the consultation of a veterinarian.
    a) Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
    4) ANIMAL POISON CONTROL CENTERS
    a) 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
    b) 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.
    c) 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.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) EMESIS AND LAVAGE - If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    1) Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    b) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    c) GASTRIC LAVAGE - Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) ACTIVATED CHARCOAL - Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    e) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) RUMINANTS/HORSES/SWINE
    a) EMESIS -
    1) Do not attempt to induce emesis in ruminants (cattle) or equids (horses).
    b) ACTIVATED CHARCOAL -
    1) Adult horses: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube.
    2) Neonates: Administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
    3) Adult cattle: Administer 2 to 9 grams/kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube.
    4) Sheep may be given 0.5 kilogram charcoal in slurry.
    c) CATHARTIC -
    1) Administer an oral cathartic:
    a) Mineral oil (small ruminants and swine, 60 to 200 milliliters; equids and cattle, 0.5 to 1 gallon) or
    b) Magnesium sulfate (ruminants and swine, 1 to 2 grams/kilogram; equine, 0.2 to 0.9 gram/kilogram) or
    c) Milk of Magnesia (small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os).
    2) Give these solutions via stomach tube and monitor for aspiration.

Sources

    A) GENERAL
    1) Boric acid is most commonly accessible to pets as roach and ant poison. Large animals may be exposed to borate-containing fertilizers and other compounds (Beasley et al, 1990).

Other

    A) OTHER
    1) GENERAL
    a) CALCULATIONS -
    1) One gram boric acid = 1.55 grams Borax (Beasley et al, 1990)
    2) Sodium borate = 21.5 percent boron (Beasley et al, 1990)

References

General Bibliography

    1) ACGIH: Documentation of the Threshold Limit Values, 4th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1980, pp 46.
    2) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    3) Anon: Technical Data Sheet IP-14, Boric Acid. United States Borax & Chemical Co, Los Angeles, 1973.
    4) Baker MD & Bogema SC: Ingestion of boric acid by infants. Am J Emerg Med 1986; 4:358-351.
    5) Baliah T, MacLeish H, & Drummond KN: Acute boric acid poisoning: report of an infant successfully treated by peritoneal dialysis. Can Med Assoc J 1969; 101:166-168.
    6) Banner W, Koch M, & Capin DM: Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds. Toxicol Appl Pharmacol 1986; 83:142-147.
    7) Basaran N, Duydu Y, & Bolt HM: Reproductive toxicity in boron exposed workers in Bandirma, Turkey. J Trace Elem Med Biol 2012; 26(2-3):165-167.
    8) Baselt RC & Cravey RH: Disposition of Toxic Drugs and Chemicals in Man, 3rd ed, Year Book Medical Publishers, Chicago, IL, 1989.
    9) Baselt RC: Disposition of Toxic Drugs and Chemicals in Man, 2nd ed, Biomedical Publications, Davis, CA, 1982, pp 82.
    10) Baselt RC: Disposition of Toxic Drugs and Chemicals in Man, 5th ed, Chemical Toxicology Institute, Foster City, CA, 2000.
    11) Beasley VR, Dorman DC, & Fikes JD: A Systems Affected Approach to Veterinary Toxicology, University of Illinois, Urbana, IL, 1990.
    12) Beckett WS, Oskvig R, Gaynor ME, et al: Association of reversible alopecia with occupational topical exposure to common borax-containing solutions. J Am Acad Dermatol 2001; 44(4):599-602.
    13) Boggs TR & Anrode HG: Boric acid and exchange transfusion. Pediatrics 1955; 16:109-114.
    14) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    15) Budavari S: The Merck Index, 12th ed, Merck & Co., Inc, Whitehouse Station, NJ, 1996.
    16) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    17) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    18) Chao T, Maxwell SM, & Wong S: An outbreak of aflatoxicosis and boric acid poisoning in Malaysia: a clinicopathological study. J Pathol 1991; 164:225-233.
    19) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    20) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    21) Coppock RW, Mostrom MS, & Lillie LE: The toxicology of detergents, bleaches, antiseptics and disinfectants in small animals. Vet Hum Toxicol 1988; 30:463-473.
    22) Corradi F, Brusasco C, Palermo S, et al: A case report of massive acute boric acid poisoning. Eur J Emerg Med 2009; Epub:Epub.
    23) Egfjord M, Jansen JA, & Flachs H: Combined boric acid and cinchocaine chloride poisoning in a 12-month-old infant: evaluation of haemodialysis. Human Toxicol 1988; 7:175-178.
    24) Elmamlem J, Efthymiou M-L, & Fournier E: Reevaluation de la toxicite des borates: apropos de 134 intoxications au Centre Anti-Pousms de Paris. J Toxicol Med 1984; 4:317-325.
    25) Farr LE, Sweet JS, & Robertson CG: Neutron capture therapy with boron in the treatment of glioblastoma multiforme. Am J Roentgenol Radium Ther Nucl Med 1954; 71:279-293.
    26) Fisher RS & Freimuth HC: Blood boron levels in human infants. J Invest Dermatol 1958; 30:85-86.
    27) Friis-Hansen B, Aggerbeck B, & Jansen JA: Unaffected blood boron levels in newborn infants treated with a boric acid ointment. Food Chem Toxicol 1982; 20:451-454.
    28) Garabrant DH, Bernstein L, & Peters JM: Respiratory and eye irritation from boron oxide and boric acid dusts. 1984; 26:584-586.
    29) Garabrant DH, Bernstein L, & Peters JM: Respiratory effects of borax dust. Br J Ind Med 1985; 42:831-837.
    30) Goldbloom RB & Goldbloom A: Boric acid poisoning: report of 4 cases and a review of 109 cases from the world literature. J Pediatr 1953; 43:631-643.
    31) Gordon AS, Prichard JS, & Freedman MH: Seizure disorders and anemia associated with chronic borax intoxication. Can Med Assoc J 1973; 108:719-724.
    32) Gosselin RE, Smith RP, & Hodge HC: Clinical Toxicology of Commercial Products, 5th ed, Williams & Wilkins, Baltimore, MD, 1984.
    33) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    34) Hamilton RA & Wolf BC: Accidental boric acid poisoning following the ingestion of household pesticide. J Forensic Sci 2007; 52(3):706-708.
    35) Harris MW, Chapin RE, & Lockhart AC: Assessment of a short-term reproductive and developmental toxicity screen. Fundam Appl Toxicol 1992; 19:186-196.
    36) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    37) Heindel JJ, Price CJ, & Field EA: Developmental toxicity of boric acid in mice and rats. Fundam Appl Toxicol 1992; 18:266-277.
    38) Hu X, Wegman DH, & Eisen EA: Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts. British Journal of Industrial Medicine 1992; 49:706-713.
    39) Hubbard SA: Comparative toxicology of borates. Biol Trace Elem Research 1998; 66:343-357.
    40) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    41) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1985, pp 75-76.
    42) Imbus HR, Cholak J, & Miller LH: Boron, cadmium, chromium, and nickel in blood and urine. Arch Environ Health 1963; 6:286-295.
    43) Ishii Y, Fujizuka N, & Takahashi T: A fatal case of acute boric acid poisoning. Clinical Toxicology 1993; 31(2):345-352.
    44) Jansen JA, Schou JS, & Aggerbeck B: Gastro-intestinal absorption and in vitro release of boric acid from water-emulsifying ointments. Food Chem Toxicol 1984; 22:49-53.
    45) Kirk RW: Current Veterinary Therapy IX, Saunders, Philadelphia, PA, 1986.
    46) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    47) Kliegel W: Bor in Biologie, Medizin und Pharmazie, Springer-Verlag, Berlin, Germany, 1980, pp 266&710.
    48) Linden CH, Hall AH, & Kulig KW: Acute ingestions of boric acid. Clin Toxicol 1986; 24:269-279.
    49) Linder RE, Strader LF, & Rehnberg GL: Effect of acute exposure to boric acid on the male reproductive system of the rat. J Toxicol Environ Health 1990; 31:133-146.
    50) Litovitz TL, Klein-Schwartz W, & Oderda GM: Clinical manifestations of toxicity in a series of 784 boric acid ingestions. Am J Emerg Med 1988; 6:209-213.
    51) Locatelli C, Minoia C, & Tonini M: Human toxicology of boron with special reference to boric acid poisoning. G Ital Med Lav 1987; 9:141-146.
    52) Locksley HB & Farr LE: Tolerance of large doses of sodium borate intravenously by patients receiving neutron capture therapy. J Pharmacol Exp Ther 1955; 114:484-489.
    53) Locksley HB & Sweet WH: Tissue distribution of boron compounds in relation to neutron capture therapy of cancer. Proc Soc Exp Biol Med 1954; 86:56-63.
    54) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    55) Lung D & Clancy C: "Boiled lobster" rash of acute boric acid toxicity. Clin Toxicol (Phila) 2009; 47(5):432-432.
    56) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    57) Martin GI: Asymptomatic boric acid intoxication. State Med J 1971; 71:1842-1844.
    58) McNally WD & Rust CA: The distribution of boric acid in human organs in six deaths due to boric acid poisoning. JAMA 1928; 90:382-383.
    59) Mehra HC, Huysmans KD, & Frankenberger WT: Determination of borate at trace levels in environmental samples by ion-exclusion chromatography. J Chromatogr 1990; 508:265-270.
    60) NTP: National Toxicology Program Technical Report No 324: Toxicology and carcinogenesis studies of boric acid (CAS No 10043-35-3) in B6C3F1 mice (feed studies). NIH Publication No 88-2580, National Toxicology Program, US Department of Human Health Services, National Institutes of Health, Research Triangle Park, NC, 1987.
    61) Naderi AS & Palmer BF: Successful treatment of a rare case of boric acid overdose with hemodialysis. Am J Kidney Dis 2006; 48(6):e95-e97.
    62) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    63) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    64) O'Sullivan & Taylor M: Chronic boric acid poisoning in infants. Arch Dis Child 1983; 58:737-749.
    65) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    66) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    67) Pedicelli S, Picca S, Di Nardo M, et al: Treatment of boric acid overdose in two infants with Continuous Venovenous Hemodialysis. Clin Toxicol (Phila) 2015; 53(9):920-922.
    68) Pinto J, Ping Huang Y, & McConnell RJ: Increased urinary riboflavin excretion resulting from boric acid ingestion. J Lab Clin Med 1978; 92:126-134.
    69) Potter C: A case of borax poisoning. JAMA 1921; 76:378.
    70) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    71) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    72) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    73) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    74) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 8/31/2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    75) Restuccio A, Mortensen ME, & Kelley M: Fatal ingestion of boric acid in an adult. Am J Emerg Med 1992; 10:545-547.
    76) S Sweetman : Martindale: The Complete Drug Reference (electronic version). The Pharmaceutical Press. London,l, UK (Internet Version). Edition expires 2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    77) Schillinger BM, Berstein M, & Goldberg LA: Boric acid poisoning. J Am Acad Dermatol 1982; 7:667-673.
    78) Schillinger BM, Berstein M, Goldberg LA, et al: Boric acid poisoning. J Am Acad Dermatol 1982a; 7:667-673.
    79) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    80) Segar WE: N Engl J Med 1960; 262:798-800.
    81) Sisk DB, Colvin BM, & Bridges CR: Acute, fatal illness in cattle exposed to boron fertilizer. J Am Vet Med Assoc 1988; 193:943-945.
    82) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    83) Stolpmann R & Hopmann G: Hamodialyse behandling einer akuten borsaureuergiftung. Dtsch Med Wochenshr 1975; 100:899-901.
    84) Tagawa T, Kono K, & Dote T: Pharmacokinetics and effects after intravenous administration of high-dose boron to rat. Int arch Occup Environ Health 2000; 73(Suppl):S98-S100.
    85) Teshima D, Taniyama T, & Oishi R: Usefulness of forced diuresis for acute boric acid poisoning in an adult. J Clin Pharm Therapeutics 2001; 26:387-390.
    86) Truhaut R, Phu-Lich N, & Loisillier F: On the effects of repeated ingestion of small doses of boron compounds on the reproductive functions of the rat. Comptes Rendus Academie des Sciences 1964; 258:5099-5102.
    87) US DHHS: Seventh Annual Report on Carcinogens - Summary 1994, Technical Resources, Inc, Rockville, MD, 1994.
    88) US DHHS: Toxicological Profile for Boron and Compounds for the Agency for Toxic Substances and Disease Registry, US PHS. Life Systems, Inc, 1992.
    89) Valdes-Dapena & Arey: Boric acid poisoning. J Pediatr 1962; 61:531-46.
    90) Wax PM: Antiseptics, disinfectants, and sterilants, in Goldfrank LR, Flomenbaum NE, Lewin NA et al (eds): Goldfrank's Toxicologic Emergencies, 5th ed, Appleton & Lange, Norwalk, CT, 1994, pp 1089.
    91) Webb DV, Stowman AM, & Patterson JW: Boric acid ingestion clinically mimicking toxic epidermal necrolysis. J Cutan Pathol 2013; 40(11):962-965.
    92) Wiley HE: The excretion of boric acid from the human body. J Biol Chem 1907; 3:11-19.
    93) Wong LC, Heimbach MD, & Truscott DR: Boric acid poisoning. Canad Med Assoc J 1964; 90:1018-1023.