MOBILE VIEW  | 

ANTU

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Antu is a thiourea rodenticide specifically used against Norway rats.

Specific Substances

    1) Alpha naphthylthiourea
    2) Chemical-109
    3) U-5,227
    4) CAS 86-88-4
    5) ALPHA-NAPHTHYL THIOUREA
    6) ALPHANAPHTHYLTHIOCARBAMIDE
    1.2.1) MOLECULAR FORMULA
    1) C11-H10-N2-S

Available Forms Sources

    A) FORMS
    1) Trade names include: Bontu Prep Rat Baits, Bontu Rat Powder, College Brand Rodenticide, Dr. Hess Anturat, Nott's Rat-TU, Pied Piper for Rats and Mice (also contains warfarin).
    B) USES
    1) It is used as a rodenticide but some species of rats are not sensitive, while others develop resistance rapidly. It is used in baits in concentrations of 1 to 3%.

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Ingestion of ANTU is not expected to result in significant human toxicity; no human fatalities have been reported.
    0.2.3) VITAL SIGNS
    A) Hypothermia may develop.
    0.2.6) RESPIRATORY
    A) Inhalation of ANTU powder may result in dyspnea, rales, cyanosis, and pulmonary edema or effusion.
    0.2.10) GENITOURINARY
    A) Oliguria, anuria and hemorrhagic glomerular nephritis have been reported in test animals.
    0.2.14) DERMATOLOGIC
    A) Eczema has been attributed to occupational exposure to ANTU.
    0.2.16) ENDOCRINE
    A) Antithyroid activity and hyperglycemia may be noted following chronic sublethal exposure to ANTU.
    0.2.21) CARCINOGENICITY
    A) The carcinogenicity of ANTU is undetermined.

Laboratory Monitoring

    A) ANTU plasma levels are not clinically useful.
    B) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated. Blood sugar and pulmonary function evaluation should be considered in symptomatic patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Ingestion of ANTU is not expected to result in significant human toxicity; no human fatalities have been reported. Monitor patients for pulmonary edema and treat symptomatically.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) ANTU is "relatively" selective causing pulmonary edema in non-tolerant rats.
    B) In monkeys, the mean lethal dose by mouth is 4 grams/kg. This may be similar for man. The mean lethal dose (MLD) in man has been estimated to be 25 grams/70 kg.

Summary Of Exposure

    A) Ingestion of ANTU is not expected to result in significant human toxicity; no human fatalities have been reported.

Vital Signs

    3.3.1) SUMMARY
    A) Hypothermia may develop.

Respiratory

    3.6.1) SUMMARY
    A) Inhalation of ANTU powder may result in dyspnea, rales, cyanosis, and pulmonary edema or effusion.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) Symptoms, if they occur, would pertain to the respiratory tract. Dyspnea, rales, and cyanosis may occur if pulmonary edema or effusion develop (Cimbal, 1952). Pulmonary edema is rapid in onset and short in duration.

Genitourinary

    3.10.1) SUMMARY
    A) Oliguria, anuria and hemorrhagic glomerular nephritis have been reported in test animals.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) OLIGURIA
    a) In animals, oliguria or anuria may accompany the pleural effusion (Richter, 1952; Baker, 1954).
    2) GLOMERULONEPHRITIS
    a) Hemorrhagic glomerular nephritis has been reported 8 hours after acute exposure in rats (Patil & Radhakrishnamurty, 1978).

Dermatologic

    3.14.1) SUMMARY
    A) Eczema has been attributed to occupational exposure to ANTU.
    3.14.2) CLINICAL EFFECTS
    A) ECZEMA
    1) CASE REPORT - Laubstein (1962) reported a case of eczema that he attributed to occupational exposure to ANTU.

Endocrine

    3.16.1) SUMMARY
    A) Antithyroid activity and hyperglycemia may be noted following chronic sublethal exposure to ANTU.
    3.16.2) CLINICAL EFFECTS
    A) FINDING OF THYROID FUNCTION
    1) Chronic sublethal exposure may cause antithyroid activity (Fitzhugh & Nelson, 1947).
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERGLYCEMIA
    a) It has produced hyperglycemia in experimental animals of 3 times normal in 3 hours (DuBois, 1948; EPA, 1985).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS86-88-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: 1-Naphthylthiourea (ANTU)
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) The carcinogenicity of ANTU is undetermined.
    3.21.3) HUMAN STUDIES
    A) BLADDER CARCINOMA
    1) Exposure due to the alpha-naphthylamine impurity in ANTU led to investigation of 2 cases of bladder cancer in 2 rodent operators. It resulted in a recommendation that ANTU use be restricted to professional operators (Case, 1966). Since then no related cases have been reported.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) ANTU was found to be an equivocal tumorogenic agent by RTECS criteria, causing pulmonary, thoracic and blood tumors in mice (RTECS , 1991).

Genotoxicity

    A) Mutations were observed in S. Typhimurium, and oncogeric transformation was seen in hamster embryo cells.

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) ANTU plasma levels are not clinically useful.
    B) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated. Blood sugar and pulmonary function evaluation should be considered in symptomatic patients.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor blood sugar in symptomatic patients.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor pulmonary function in symptomatic patients.

Methods

    A) OTHER
    1) Antu can be precipitated by alkaloidal reagents to form typical crystals or colors, or dissolved in chloroform plus bromine water and give a blue violet color in the chloroform layer.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) ANTU plasma levels are not clinically useful.
    B) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated. Blood sugar and pulmonary function evaluation should be considered in symptomatic patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    B) EXPERIMENTAL THERAPY
    1) CYSTEINE - Because ANTU is a sulfhydryl blocking agent, cysteine has been tried in rats, and was effective in some cases (DuBois et al, 1946).
    2) There is no human experience with cysteine and its use is not recommended.

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).

Summary

    A) ANTU is "relatively" selective causing pulmonary edema in non-tolerant rats.
    B) In monkeys, the mean lethal dose by mouth is 4 grams/kg. This may be similar for man. The mean lethal dose (MLD) in man has been estimated to be 25 grams/70 kg.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) ANTU is probably not toxic to man except in large amounts; the mean lethal dose by mouth is 4 grams/kilogram in monkeys and presumably similar in man (Brewer & Haggerty, 1958). The estimated MLD in man is 25 grams/70 kilogram; the LDLo is 588 mg/kg.
    2) Probable oral lethal dose (human) 0.5 to 5 grams per kilogram, or between 1 ounce and 1 pint (or pound) for a 150 kilogram person (Gosselin et al, 1984).
    B) ACUTE
    1) LDLo - (UNREPORTED) HUMAN, Male: 588 mg/kg (RTECS , 1998).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The low toxicity is indicated by the results of a series of cases reported from France where chloralose was used alone or in combination with ANTU. Even where the dosage was large (in suicidal cases) all patients recovered. Classified as moderately toxic (LD50 = 50 to 500 mg/kg) (Goldfrank et al, 1981).
    2) Ingestion of 80 grams of a 30% bait in an adult, along with ethanol, resulted in prompt vomiting, dyspnea, and pulmonary rales, with complete recovery (Cimbal, 1952).

Workplace Standards

    A) ACGIH TLV Values for CAS86-88-4 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) ANTU
    a) TLV:
    1) TLV-TWA: 0.3 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Skin
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): Thyroid eff; nausea
    d) Molecular Weight: 202.27
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS86-88-4 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: ANTU
    2) REL:
    a) TWA: 0.3 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 100 mg/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS86-88-4 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: ANTU
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: 1-Naphthylthiourea (ANTU)
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: ANTU
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS86-88-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: ANTU (alpha Naphthylthiourea)
    2) Table Z-1 for ANTU (alpha Naphthylthiourea):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.3
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1990
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 10 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 5 mg/kg
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 2470 mcg/kg
    4) LD50- (ORAL)RAT:
    a) 6 mg/kg

Toxicologic Mechanism

    A) ANTU is a phenylthiourea compound. It is a single dose rodenticide used as a bait and tracking powder. Observation on experimental animals indicate that the principal organ affected is the lungs; pulmonary edema and pleural effusion develop due to the action of ANTU on pulmonary capillaries causing marked edema of the subepithelial spaces of the alveolar walls; pericardial effusion is less marked.
    B) ANTU toxicity in the rat is thought to depend on metabolic activation via the hepatic and lung microsomal enzymes to form a hydrodisulfide and alpha-naphthylurea. The metabolites are covalently bound to lung macromolecules. It is not known if these metabolites are produced in humans (Boyd & Neal, 1976; Lee et al, 1980).
    C) Production of oxygen free radicals via the cyclooxygenase pathway (Martin et al, 1986) has been implicated in mediating ANTU-induced lung damage.

Physical Characteristics

    A) This compound exists as colorless to white or grey crystalline or powder-like solid that is odorless and bitter tasting (Budavari, 1989; Sax & Lewis, 1989; EPA, 1985).

Molecular Weight

    A) 202.27 (Budavari, 1989)

Clinical Effects

    11.1.3) CANINE/DOG
    A) Dogs are one of few mammals that are extremely susceptible to ANTU poisoning. Prompt emesis may prevent toxicity. In fatal cases, pulmonary edema, usually hemorrhagic, was the predominant feature (Wanntorp, 1953).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Keep animal warm and do not handle unnecessarily.
    3) Sample vomitus, blood, urine, and feces for analysis.
    B) ANIMAL POISON CONTROL CENTERS
    1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    C) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.
    D) INHALATION - Move patient to fresh air. Monitor patient for respiratory distress. Emergency airway support and supplemental oxygen with assisted ventilation may be needed. If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.
    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) GENERAL TREATMENT
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. 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. 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. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    a) CAUTION - Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    b) ACTIVATED CHARCOAL -
    1) 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.
    c) CATHARTIC -
    1) 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.
    11.2.5) TREATMENT
    A) DOGS/CATS
    1) MAINTAIN VITAL FUNCTIONS - as necessary.
    2) VENTILATORY SUPPORT including oxygen, intubation, and artificial ventilation may be necessary.
    3) PULMONARY EDEMA -
    a) FLUIDS - Decrease rate of intravenous fluid administration to less than 66 milliliters/kilogram/day.
    b) BLOOD GASES - Monitor if possible. Maintain adequate ventilation and oxygenation via face mask or continuous-positive-airway pressure in awake patients or via positive-end-expiratory pressure in intubated patients. Maintain arterial PO2 above 50 millimeters mercury.
    4) FLUIDS - Begin intravenous administration of lactated ringers or other solution at a rate of up to 60 milliliters/kilograms/hour. If packed cell volume is less than 25 percent or total protein is less than 3.5 grams/deciliter, give 10 to 20 milliliters/kilogram of the appropriate solution (whole blood, plasma, packed cells or dextran).
    5) SUPPORTIVE CARE - Other supportive care may be necessary for several days.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Keep animal warm and do not handle unnecessarily.
    3) Sample vomitus, blood, urine, and feces for analysis.
    B) ANIMAL POISON CONTROL CENTERS
    1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    C) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.
    D) INHALATION - Move patient to fresh air. Monitor patient for respiratory distress. Emergency airway support and supplemental oxygen with assisted ventilation may be needed. If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. 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. 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. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    a) CAUTION - Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    b) ACTIVATED CHARCOAL -
    1) 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.
    c) CATHARTIC -
    1) 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.

Other

    A) OTHER
    1) GENERAL
    a) SUSCEPTIBILITY - Doses of less than 100 mg/kg can be lethal to Norway rats, dogs, and mice. Alexandrine rats, squirrels, and guinea pigs may die at 100 to 400 mg/kg, and monkeys, rabbits, and chickens were killed by doses of 5 g/kg (Richter, 1945).

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