Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

DOMOIC ACID

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Domoic acid is a neuroexcitatory tricarboxylic amino acid and is the causative agent in some shellfish (e.g. mussels, clams) poisoning outbreaks. It is structurally related to the excitatory neurotransmitter, glutamate. Symptoms are gastrointestinal and neurologic.

Specific Substances

    1) Amnesic shellfish poisoning
    2) L-Domoic acid
    3) (-)-Domoic acid
    4) Cancer magister
    5) Cerastoderma edule
    6) Chondria armata
    7) Cockles (Cerastoderma edule)
    8) Crabs (Cancer magister)
    9) Furrow shell (Scrobicularia plana)
    10) Macro red algae
    11) Mussels (Mytilus edulis)
    12) Mytilus edulis
    13) Nitzshia pungens
    14) P. australis
    15) P. nitzschia
    16) Pseudonitzschia multiseries
    17) P. pseudodelicatissima
    18) Pecten maximus
    19) P. Seriata
    20) Pseudo-nitzschia
    21) Razor clams (Siliqua patula)
    22) Scallops (Pecten maximus)
    23) Scrobicularia plana
    24) Siliqua patula
    25) Molecular Formula: C15-H21-N-O6
    26) CAS 14277-79-5

Available Forms Sources

    A) SOURCES
    1) The source of domoic acid-contaminated mussels responsible for human poisoning was the diatom, Nitzschia pungens, ingested by mussels during normal feeding (Bates et al, 1989; Subba Rao et al, 1988).
    2) Domoic acid, an amino acid produced by some species of phytoplankton, was originally discovered in macro red algae (seaweed), Chondria armata (known locally as Domoi) in Southern Japan. Following the outbreak of human poisoning in 1987 in Canada, it was found that domoic acid is also produced by marine diatoms of the genus Pseudo-nitzschia. These are found across the world in sea waters of both warm and cold climates (Jeffrey et al, 2004; Tryphonas et al, 1990).
    3) Domoic acid is produced by several strains of P. nitzschia such as Pseudonitzschia multiseries, P. pseudodelicatissima, and P. australis (Jeffrey et al, 2004).
    4) A wide variety of shellfish species can accumulate domoic acid, including: cockles (Cerastoderma edule), crabs (Cancer magister), furrow shells (Scrobicularia plana), mussels (Mytilus edulis), razor clams (Siliqua patula) and scallops (Pecten maximus) (Jeffrey et al, 2004).
    B) USES
    1) Seaweed extracts containing non-toxic amounts of domoic acid (20 mg) have been used in Japan as an ascaricidal agent (Daigo, 1959; Daigo, 1959a).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdc.gov.
    b) ACUTE SYMPTOMS (WITHIN 48 HOURS)
    1) HUMAN: Symptoms based on a small number of human exposures: GI: Initial symptoms include: nausea, vomiting, abdominal cramps, diarrhea, and anorexia are common. GI bleed and hiccups have occurred. NEURO: Headache, short-term memory loss, hemiparesis, visual abnormalities, ophthalmoplegia, seizures, myoclonus, confusion, lethargy, agitation, coma, mutism, areflexia, and loss of deep pain sensation. CV: Hypotension, peripheral vasodilation, tachycardia, and dysrhythmias. RESP: Pulmonary edema, excessive pulmonary secretions. DERM: Piloerection may occur during acute intoxication. SEVERE: Hypotension, dysrhythmias and bronchorrhea may develop. AGE: Patients under 40 are more likely to develop GI symptoms, while patients 50 years and older are likely to develop memory loss.
    2) ANIMAL: California sea lions have developed: ataxia, head bobbing, seizures, coma, and abortion.
    c) CHRONIC SYMPTOMS
    1) HUMAN: Symptoms may include: severe retrograde amnesia, motor or sensorimotor neuropathy, and possible seizure disorder.
    2) ANIMAL: Unusual behavior (ie, chew, circle), extreme aggression, epileptic seizures that progress to grand mal seizures.
    d) FATALITY RATE
    1) 3%
    e) TIME TO ONSET OF SYMPTOMS
    1) Usually less than 24 hours; initial symptoms can occur within 15 minutes to 38 hours after ingestion (mean 5.5 hours)
    f) DURATION
    1) HUMAN: May last days, possibly years.
    2) ANIMAL: Outbreaks in California sea lions indicate that neurologic lesions can be permanent.
    g) ROUTE OF EXPOSURE
    1) HUMAN: Eating contaminated shellfish.
    2) ANIMAL: Fetal exposure has occurred (via amniotic fluid) in California sea lions and rodent models.
    h) CAUSATIVE ORGANISM
    1) The following organisms may produce illness: diatom: pseudo-nitzschia spp., Nitzshia pungens.
    i) TOXIN
    1) The following toxins have been associated with domoic acid poisoning: domoic acid (5 congeners) - neuroexcitatory tricarboxylic amino acid (CAS 14277-79-5).
    j) VECTOR
    1) Contaminated bivalve shellfish including: scallops, mussels, clams (particularly razor clams, Siliqua patula), and oysters. Domoic acid has been found in Dungeness crab viscera. Of note, sardines and anchovies have been associated with sea lion intoxication events. Testing for domoic acid is not done in sardines or anchovies destined for human consumption.
    k) MECHANISM
    1) A glutamate receptor agonist.
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Organism found in temperate waters (eg, Florida).
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (eg, neurotoxic, paralytic or azaspiracid shellfish poisoning), ciguatera fish poisoning, scombroid fish poisoning, pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisonings, and food allergies may have potentially similar clinical findings.
    n) DIAGNOSIS
    1) Clinical presentation and shellfish test using mouse bioassay and HPLC.
    o) SUSPECT CASE
    1) Consumption of shellfish and development of gastrointestinal and neurologic symptoms.
    p) CONFIRMED CASE
    1) Suspect case and verification of domoic acid in urine OR verification of domoic acid in shellfish meal remnant OR in shellfish harvested from relevant geographic area.
    q) ANIMAL SENTINEL DATA
    1) California sea lions, common dolphins (west coast), pelicans and other shore birds.
    r) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential in humans. Based on limited animal data, mutagenicity potential was negative.

Laboratory Monitoring

    A) Monitor vital signs, mental status and neurologic exam. Monitor serum electrolytes in patients with significant gastrointestinal losses.
    B) Confirmatory testing may be performed to measure domoic acid in human urine if indicated. Bioassays, ELISA and chromatographic techniques have been used to detect domoic acid in research and food safety testing.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Exposure is generally not recognized until after symptoms have developed. In the rare case where exposure is recognized early, consider activated charcoal.
    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) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    D) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.

Range Of Toxicity

    A) Up to 20 mg has been ingested without serious effects; symptomatic patients have usually ingested approximately 60 to 295 mg domoic acid.
    B) An estimated dose of 295 mg of domoic acid ingested from contaminated mussels resulted in permanent neurological sequelae.
    C) Patients over 60 years of age who have ingested at least 60 mg (approximately 0.85 mg/kg) of domoic acid have developed the most severe symptoms.
    D) Diarrhea and vomiting have occurred following doses as small as 0.07 mg/kg, usually within 12 hours of ingestion and usually resolves within 72 hours.
    E) Following an outbreak of human poisoning with domoic acid in Washington State, only 1%-3% of patients exposed to 0.05 mg/kg of domoic acid experienced any symptoms.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdc.gov.
    b) ACUTE SYMPTOMS (WITHIN 48 HOURS)
    1) HUMAN: Symptoms based on a small number of human exposures: GI: Initial symptoms include: nausea, vomiting, abdominal cramps, diarrhea, and anorexia are common. GI bleed and hiccups have occurred. NEURO: Headache, short-term memory loss, hemiparesis, visual abnormalities, ophthalmoplegia, seizures, myoclonus, confusion, lethargy, agitation, coma, mutism, areflexia, and loss of deep pain sensation. CV: Hypotension, peripheral vasodilation, tachycardia, and dysrhythmias. RESP: Pulmonary edema, excessive pulmonary secretions. DERM: Piloerection may occur during acute intoxication. SEVERE: Hypotension, dysrhythmias and bronchorrhea may develop. AGE: Patients under 40 are more likely to develop GI symptoms, while patients 50 years and older are likely to develop memory loss.
    2) ANIMAL: California sea lions have developed: ataxia, head bobbing, seizures, coma, and abortion.
    c) CHRONIC SYMPTOMS
    1) HUMAN: Symptoms may include: severe retrograde amnesia, motor or sensorimotor neuropathy, and possible seizure disorder.
    2) ANIMAL: Unusual behavior (ie, chew, circle), extreme aggression, epileptic seizures that progress to grand mal seizures.
    d) FATALITY RATE
    1) 3%
    e) TIME TO ONSET OF SYMPTOMS
    1) Usually less than 24 hours; initial symptoms can occur within 15 minutes to 38 hours after ingestion (mean 5.5 hours)
    f) DURATION
    1) HUMAN: May last days, possibly years.
    2) ANIMAL: Outbreaks in California sea lions indicate that neurologic lesions can be permanent.
    g) ROUTE OF EXPOSURE
    1) HUMAN: Eating contaminated shellfish.
    2) ANIMAL: Fetal exposure has occurred (via amniotic fluid) in California sea lions and rodent models.
    h) CAUSATIVE ORGANISM
    1) The following organisms may produce illness: diatom: pseudo-nitzschia spp., Nitzshia pungens.
    i) TOXIN
    1) The following toxins have been associated with domoic acid poisoning: domoic acid (5 congeners) - neuroexcitatory tricarboxylic amino acid (CAS 14277-79-5).
    j) VECTOR
    1) Contaminated bivalve shellfish including: scallops, mussels, clams (particularly razor clams, Siliqua patula), and oysters. Domoic acid has been found in Dungeness crab viscera. Of note, sardines and anchovies have been associated with sea lion intoxication events. Testing for domoic acid is not done in sardines or anchovies destined for human consumption.
    k) MECHANISM
    1) A glutamate receptor agonist.
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Organism found in temperate waters (eg, Florida).
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (eg, neurotoxic, paralytic or azaspiracid shellfish poisoning), ciguatera fish poisoning, scombroid fish poisoning, pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisonings, and food allergies may have potentially similar clinical findings.
    n) DIAGNOSIS
    1) Clinical presentation and shellfish test using mouse bioassay and HPLC.
    o) SUSPECT CASE
    1) Consumption of shellfish and development of gastrointestinal and neurologic symptoms.
    p) CONFIRMED CASE
    1) Suspect case and verification of domoic acid in urine OR verification of domoic acid in shellfish meal remnant OR in shellfish harvested from relevant geographic area.
    q) ANIMAL SENTINEL DATA
    1) California sea lions, common dolphins (west coast), pelicans and other shore birds.
    r) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Vital Signs

    3.3.2) RESPIRATIONS
    A) WITH POISONING/EXPOSURE
    1) Respirations may be labored because of profuse bronchial secretions (Perl et al, 1990).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Hypotension (with peripheral vasodilatation) can occur (Perl et al, 1990). Severely poisoned patients may be hemodynamically unstable.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Miosis or mydriasis, disconjugate gaze, diplopia and ophthalmoplegia have occurred in severely poisoned patients (Perl et al, 1990; Teitelbaum et al, 1990).
    2) Complete external ophthalmoplegia developed acutely in some patients, and resolved over 10 days. This was often associated with hemiparesis (Teitelbaum et al, 1990).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A blood pressure of 70/0 mmHg occurred in a previously hypertensive patient. This patient was hemodynamically unstable and required vasopressors, antihypertensives, and antiarrhythmics (Perl et al, 1990). Patients were peripherally vasodilated.
    B) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia occurred in one severely intoxicated patient (Perl et al, 1990).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Pulmonary edema occurred in a patient who ingested approximately 225 grams of contaminated mussels (Perl et al, 1990).
    B) DISORDER OF RESPIRATORY SYSTEM
    1) WITH POISONING/EXPOSURE
    a) Increased pulmonary secretions requiring suctioning have occurred in severely poisoned patients (Perl et al, 1990; Teitelbaum et al, 1990).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) COMA
    1) WITH POISONING/EXPOSURE
    a) Coma can occur in severe cases (Perl et al, 1990). Seven of 14 cases reported by Teitelbaum et al (1990a) developed coma.
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures have occurred (Perl et al, 1990).
    b) Myoclonus may also develop (Teitelbaum et al, 1990).
    C) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache is often severe with an incidence of 43% of poisoned patients (Perl et al, 1990). In an amnesic shellfish poisoning outbreak in Canada, 64 of the 145 cases (34%) developed headache (Perl et al, 1990a).
    D) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) Confusion and disorientation are common (Perl et al, 1990).
    E) AMNESIA
    1) WITH POISONING/EXPOSURE
    a) Severe short-term memory loss has been reported up to 86 days postingestion (Perl et al, 1990).
    1) INCIDENCE - In an amnesic shellfish poisoning outbreak in Canada, 37 of the 145 cases (26%) developed memory loss (Perl et al, 1990a).
    F) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) In an amnesic shellfish poisoning outbreak in Canada, 48 of the 145 cases (33%) developed dizziness/loss of balance (Perl et al, 1990a).
    G) DISTURBANCE IN SPEECH
    1) WITH POISONING/EXPOSURE
    a) Mutism occurred in a number of poisoned patients (Perl et al, 1990).
    H) HICCOUGHS
    1) WITH POISONING/EXPOSURE
    a) Hiccups occurred in about 5% of poisoned patients (Perl et al, 1990).
    I) PSYCHOMOTOR AGITATION
    1) WITH POISONING/EXPOSURE
    a) Agitation occurred in a few poisoned patients (Teitelbaum et al, 1990).
    J) HYPOREFLEXIA
    1) WITH POISONING/EXPOSURE
    a) General weakness, unsteadiness, transient symmetric hyperreflexia, fasciculations, and Babinski signs occurred in some patients acutely. Four to six months later, distal atrophy, mild extremity weakness, hyporeflexia, and loss of distal sensitivity to pain were noted (Teitelbaum et al, 1990).
    K) HEMIPLEGIA
    1) WITH POISONING/EXPOSURE
    a) Spastic hemiparesis developed acutely and persisted for 24 to 36 hours. This was followed by transient hemiparesis on the opposite side (Teitelbaum et al, 1990).
    L) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Disconjugate gaze developed in one severe case (Perl et al, 1990).
    b) Complete external ophthalmoplegia developed acutely in some patients, and resolved over 10 days. This was often associated with hemiparesis (Teitelbaum et al, 1990).
    M) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Grimacing and purposeless chewing was noted in one case (Perl et al, 1990).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) RATS injected with 0.5 to 1 mg/kg IV developed seizure discharges in the hippocampus, tonic/clonic seizures, and death in a few days (Nakajima & Potvin, 1992).
    2) MENTAL DEFICIENCY
    a) RATS injected with domoic acid had severely impaired learning and relearning of tasks (Nakajima & Potvin, 1992).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, diarrhea, and abdominal pain occur in most human cases (Tryphonas et al, 1990). An experimental animal model demonstrates vomiting, diarrhea, and anorexia in monkeys. Symptoms may be mild or severe enough to require rehydration therapy (Perl et al, 1990).
    b) In an amnesic shellfish poisoning outbreak in Canada (n=145), nausea, vomiting, and abdominal cramps developed in 116 (80%), 94 (64%), and 59 (41%) cases, respectively; anorexia developed in 47 of 113 cases (42%) in which anorexia was assessed (Perl et al, 1990a).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea frequently occurs (Perl et al, 1990). In an amnesic shellfish poisoning outbreak in Canada, 59 of the 145 cases (41%) developed diarrhea (Perl et al, 1990a).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) PILOERECTION
    1) WITH POISONING/EXPOSURE
    a) Piloerection occurred in severely poisoned patients (Teitelbaum et al, 1990).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no human data were available to assess the teratogenic potential of domoic acid.
    B) ANIMAL STUDIES
    1) Specific concentrations of domoic acid injected into pregnant rats had an abortifacient effect and resulted in delayed ossification of the sternebrae (Khera et al, 1994). A dose-response relationship for these adverse effects; however, was not seen.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation in humans.
    2) ANIMAL DATA - Intrauterine exposure of mice to domoic acid resulted in progressive hippocampal degeneration and abnormal EEG activity during the neonatal period (Dakshinamurti et al, 1993). When exposed to an additional dose of domoic acid during the neonatal period, seizure threshold was decreased in these intrauterine-exposed mice.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS14277-97-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential in humans. Based on limited animal data, mutagenicity potential was negative.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent in humans. Based on experimental studies with hamster lung fibroblasts, no genotoxic effects are anticipated in humans (Rogers & Boyes, 1989).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs, mental status and neurologic exam. Monitor serum electrolytes in patients with significant gastrointestinal losses.
    B) Confirmatory testing may be performed to measure domoic acid in human urine if indicated. Bioassays, ELISA and chromatographic techniques have been used to detect domoic acid in research and food safety testing.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Seventeen patients were examined for domoic acid in blood serum or cerebrospinal fluid. None was identified, but all biologic samples were at last 2 days old (Perl et al, 1990).
    2) Some patients had elevated serum creatinine, but it was not possible to rule out causes other than the domoic acid (Teitelbaum et al, 1990).

Methods

    A) CHROMATOGRAPHY
    1) MUSSEL EXTRACTS - High performance liquid chromatography (HPLC) has been used to determine domoic acid in mussel extracts (Lawrence et al, 1989).
    2) CLINICAL SPECIMENS - Diluted specimens (1:25 to 1:100) were filtered through a sulfonic acid cation exchange column and then analyzed by HPLC (Perl et al, 1990).
    3) TISSUE EXTRACTS - Laboratory methods using methanol extraction with anion exchange purification and HPLC have been developed to determine domoic acid concentration in tissue extracts (None Listed, 1992).
    4) The following analytical methods have been used to detect and measure domoic acid in a range of matrices: HPLC-UV - mussels (Limit of detection (LOD), 1 mcg/g); HPLC-MS - anchovy (LOD, 0.1 mcg/g); HPLC-MS - razor clam, mussel, crab, serum, urine, feces; HPLC-fluorescence - mussels (LOD, 0.006 mcg/g), phytoplankton (LOD, 0.001 mcg/g); GC-MS - mussel (LOD, 1 mcg/g); TLC - mussel; Cation Exchange (CE) - mussel (LOD, 0.15 mcg/g), razor clam, anchovy (Jeffrey et al, 2004).
    B) BIOASSAY
    1) The following analytical methods have been used to detect and measure domoic acid in a range of matrices: Rodent bioassay - mussels; ELISA - urine (Limit of detection (LOD), 0.2 mcg/mL, 0.25 mcg/mL), serum (LOD, 10 mcg/mL), milk, mussels (LOD, 0.038 or 0.04 mcg/mg), scallops, oysters, phytoplankton, crab, oyster; Receptor binding assay - mussel extract (LOD, 0.002 mcg/mL) (Jeffrey et al, 2004).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor vital signs, mental status and neurologic exam. Monitor serum electrolytes in patients with significant gastrointestinal losses.
    B) Confirmatory testing may be performed to measure domoic acid in human urine if indicated. Bioassays, ELISA and chromatographic techniques have been used to detect domoic acid in research and food safety testing.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Exposure is generally not recognized until after symptoms have developed. In the rare case where exposure is recognized early, consider activated charcoal.
    B) 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) SUMMARY
    1) Exposure is generally not recognized until after symptoms have developed. In the rare case where exposure is recognized early, consider activated charcoal.
    B) 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) SUPPORT
    1) No specific antidote exists. Treatment is SYMPTOMATIC and SUPPORTIVE.
    B) ACUTE LUNG INJURY
    1) Pulmonary edema and excessive pulmonary secretions have occurred after severe poisoning.
    2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    3) 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)
    4) 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).
    5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    7) 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).
    8) 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).
    C) SEIZURE
    1) Experimentally induced seizures in rats could be prevented with diazepam (Nakajima & Potvin, 1992).
    2) 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).
    3) 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 .
    4) 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).
    5) 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).
    6) 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).
    7) 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).
    D) 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).
    E) NEUROLOGICAL FINDING
    1) No measures have been found to reverse the neurological damage or memory loss that may occur.
    F) EXPERIMENTAL THERAPY
    1) BENZODIAZEPINES - In one animal study, benzodiazepines selectively suppressed the neuronal activation induced by kainate. The authors suggested that a rapid treatment with high doses of benzodiazepines could possibly prevent the important and irreversible hippocampal damage (Debonnel et al, 1990).
    2) PROBENECID - In one animal study, probenecid, a blocker of organic acid transport, seemed to enhance protection against demoate toxicosis in a murine model (Bose et al, 1990).
    3) KNURENIC ACID, TRYPTOPHAN, HIGH-DOSE DEXTROMETHORPHAN - Knurenic acid, tryptophan (a knurenic acid precursor), and high-dose dextromethorphan can bind competitively to glutamate and may be examined as antidotes for demoate toxicosis (Bose et al, 1990).

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) 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) LACK OF INFORMATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Up to 20 mg has been ingested without serious effects; symptomatic patients have usually ingested approximately 60 to 295 mg domoic acid.
    B) An estimated dose of 295 mg of domoic acid ingested from contaminated mussels resulted in permanent neurological sequelae.
    C) Patients over 60 years of age who have ingested at least 60 mg (approximately 0.85 mg/kg) of domoic acid have developed the most severe symptoms.
    D) Diarrhea and vomiting have occurred following doses as small as 0.07 mg/kg, usually within 12 hours of ingestion and usually resolves within 72 hours.
    E) Following an outbreak of human poisoning with domoic acid in Washington State, only 1%-3% of patients exposed to 0.05 mg/kg of domoic acid experienced any symptoms.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Doses of 20 milligrams (in a seaweed extract) have been used as an ascaricidal (Daigo, 1959) 1959a).

Minimum Lethal Exposure

    A) The minimum lethal human dose to this agent has not been delineated.
    B) Of the 200 cases of illness seen in an outbreak in Canada, there were 3 deaths (Tryphonas et al, 1990).

Maximum Tolerated Exposure

    A) ACUTE
    1) Studies have indicated that up to 0.25 kg of seafood per day may be eaten by an adult without risk of poisoning (based on a level of 20 ppm of domoic acid) (None Listed, 1992).
    2) An estimated dose of 295 mg of domoic acid ingested from contaminated mussels resulted in nausea, vomiting, confusion and permanent neurological sequelae (Perl et al, 1990).
    3) Symptomatic patients were estimated to have ingested 60 to 295 milligrams of domoic acid (Perl et al, 1990). Based on this estimate, it has been suggested that an ingestion of as little as 60 mg domoic acid/person, approximately equivalent to 1 mg domoic acid/kilogram body weight/day, is enough to produce gastrointestinal illness. Neurological effects are anticipated with ingestions of 270 mg domoic acid/person, equivalent to 4.5 mg domoic acid/kilogram body weight/day (Jeffrey et al, 2004).
    4) Patients over 60 years of age who have ingested at least 60 mg (approximately 0.85 mg/kg) of domoic acid have developed the most severe symptoms. Diarrhea and vomiting have occurred following doses as small as 0.07 mg/kg, usually within 12 hours of ingestion and usually resolves within 72 hours. Following an outbreak of human poisoning with domoic acid in Washington State, only 1% to 3% of patients exposed to 0.05 mg/kg of domoic acid experienced any symptoms (None Listed, 1992).
    B) DOMOIC ACID CONCENTRATIONS IN SEAFOOD
    1) The level of domoic acid in mussel samples associated with illness ranged from 31 to 128 milligrams per 100 grams of mussel (Perl et al, 1990).
    2) In 1991, ingestion of razor clams contaminated with domoic acid may have been responsible for an outbreak of human illness in Washington state. Domoic acid concentrations in razor clams were as high as 154 ppm, with most of the highest levels found in the foot of the clams (None Listed, 1992).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) DOMOIC ACID CONCENTRATIONS IN ANIMALS
    a) The level of domoic acid in mussel samples ranged from 31 to 128 milligrams per 100 grams of mussel (Perl et al, 1990).
    b) In 1991, ingestion of razor clams contaminated with domoic acid may have been responsible for an outbreak of human illness in Washington state. Domoic acid concentrations in razor clams were as high as 154 ppm, with most of the highest levels found in the foot of the clams (None Listed, 1992).
    c) The following concentrations of domoic acid have been reported: California whole anchovies 184 ppm; anchovy gastrointestinal tract 2300 ppm; California dungeness crab, as high as 18 ppm in the hepatopancreas (often referred to as the "mustard" or "butter") (None Listed, 1992).

Workplace Standards

    A) ACGIH TLV Values for CAS14277-97-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS14277-97-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS14277-97-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS14277-97-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 3600 mcg/kg ((RTECS, 2000))

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Domoic acid is heat-stable and has physiologic properties similar to kainic acid and glutamic acid (Coyle, 1983; Biscoe et al, 1975; Ohfune & Tomita, 1982). Kainic acid is a compound known to bind in the brain to a group of the glutamate receptor family. Domoic acid was found to have a strong affinity for subclasses of the kainate receptor (Jeffrey et al, 2004).
    B) PET scans of patients poisoned by domoic acid-contaminated mussels revealed a severe reduction in glucose metabolism in the hippocampus which paralleled the degree of memory loss (Gjedde & Evans, 1990).

Toxicologic Mechanism

    A) Histological examination of brain tissue from those who died showed neuronal necrosis or cell loss and astrocytosis. This was most prominent in the amygdaloid nucleus and the hippocampus (Teitelbaum et al, 1990).
    B) It has been postulated that the neurotoxic effect is through kainate receptor activation in the dorsal hippocampus (Debonnel et al, 1989). Domoic acid is heat-stable and has physiologic properties similar to kainic acid and glutamic acid (Coyle, 1983; Biscoe et al, 1975; Ohfune & Tomita, 1982). Kainic acid is a compound known to bind in the brain to a group of the glutamate receptor family. Domoic acid was found to have a strong affinity for subclasses of the kainate receptor (Jeffrey et al, 2004).
    C) The high affinity of domoic acid to kainate receptors and the apparent co-localization of these receptors, and the sites of domoic acid-induced damage as observed in animal studies, strongly suggests that domoic acid-kainate receptor interactions mediate the toxic response. The apparent binding of domoic acid to glutamate receptor subtypes appears to stimulate neuronal firing. This binding also elicits an excitatory response in neuronal cells both in vitro and in vivo (Jeffrey et al, 2004).
    1) Although the precise mechanism is not known, the toxic effects of domoic acid in the rat brain appear to be mediated by calcium (Nijjar, 1993) Xi et al, 1996). Calcium uptake in rat brain cytoplasm increases with higher concentrations of domoic acid (Nijjar, 1993). Glucose depletion further increases calcium influx into the brain cytosol. Since calcium pumps are ATP-dependent, ATP depletion may be responsible for the influx and accumulation of intracellular calcium (Nijjar, 1993). This influx of calcium can lead to a failure to maintain intracellular ion homeostasis and neuronal cell death. Another study has suggested that nitric oxide synthesis in neurons may also contribute to the neurotoxicity observed with domoic acid exposure (Jeffrey et al, 2004).
    D) Teitelbaum et al (1990) suggested that the domoic acid in the mussels produced an acute, non-progressive neuronopathy involving anterior horn cells or a diffuse axonopathy primarily acting on motor axons (Teitelbaum et al, 1990).
    E) When tested on rat-spinal motor neurons and other animal models, domoic acid was found to have at least twice the magnitude of excitotoxic effect of L-glutamate and an effect at least equal to that of kainate (Biscoe et al, 1975).
    F) Experiments with a variety of excitatory neurotransmitter agonists and antagonists in mice have shown that domoic acid toxicity is mediated by non-MNDA (N-methyl-D-aspartate) receptors such as 2-aminoproprionic acid (AMPA) and kainate receptors (Tasker et al, 1995; (Larm et al, 1997).

Animal Toxicology

Clinical Effects

    11.1.12) RODENT
    A) When injected into mice, a characteristic hind-leg scratching syndrome was observed (starting in 7 to 21 minutes) which led to uncoordinated movements and death (Wright et al, 1989; (Tryphonas et al, 1990a).
    11.1.13) OTHER
    A) OTHER
    1) MONKEYS - Oral dosing of domoic acid in monkeys (dose range 0.521 to 10.0 mg/kg) resulted in anorexia, salivation, retching, diarrhea, and fatigue. Monkeys also developed licking, smacking, and mastication (Tryphonas et al, 1990).

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    14) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    15) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    16) Artigas A, Bernard GR, Carlet J, et al: The American-European consensus conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling.. Am J Respir Crit Care Med 1998; 157:1332-1347.
    17) Bates SS, Bird CJ, & de Freitas ASW: Pennate diatom Nitzschia pungens as the primary source of domoic acid: a toxin in shellfish from eastern Prince Edward Island, Canada. Can J Fish Aquat Sci 1989; 46:1203-1215.
    18) Biscoe TJ, Evans RH, & Headley PM: Domoic and quisqualic acids as potent amino acid excitants of frog and rat spinal neurones. Nature 1975; 255:166-167.
    19) Bose R, Pinsky C, & Glavin GB: Sensitive murine model and putative antidotes for behaviorial toxicosis from contaminated mussel extracts. Can Dis Wkly Rep 1990; 16 Suppl 1E:91-98.
    20) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    21) Brower RG, Matthay AM, & Morris A: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med 2000; 342:1301-1308.
    22) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    23) Cataletto M: Respiratory Distress Syndrome, Acute(ARDS). In: Domino FJ, ed. The 5-Minute Clinical Consult 2012, 20th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2012.
    24) 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.
    25) 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.
    26) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    27) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    28) Coyle JT: Neurotoxic action of kainic acid. J Neurochem 1983; 41:1-11.
    29) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    30) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    31) Daigo K: Studies on the constituents of Chondria armata. I. Detection of the anthelmintical constituents. Yakugaku Zasshi 1959; 79:350-353.
    32) Daigo K: Studies on the constituents of Chondria armata. II. Isolation of an anthelmintical constituent. Yakugaku Zasshi 1959a; 79:353-356.
    33) Debonnel G, Beauchesne L, & de Montigay C: Domoic acid, the alleged "mussel toxin", might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the dorsal hippocampus. Can J Physiol Pharmacol 1989; 67:29-33.
    34) Debonnel G, Weiss M, & deMontigny C: Neurotoxic effect of domoic acid: mediation by kainate receptor electrophysiological studies in the rat. Can Dis Wkly Rep 1990; 16 Suppl 1E:59-68.
    35) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    36) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    37) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    38) Gjedde A & Evans AC: PET studies of domoic acid poisoning in humans: excitotoxic destruction of brain glutamatergic pathways, revealed in measurements of glucose metabolism by positron emission tomography. Can Dis Wkly Rep 1990; 16(Suppl 1E):105-109.
    39) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    40) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    41) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    42) HABISS Work-Group & Backer, L: Harmful algal bloom-related illness surveillance system (HABISS) case definitions . Centers for Disease Control and Prevention, Health Studies Branch, National Center for Environmental Health , Jan 12, 2009.
    43) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    44) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    45) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    46) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    47) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    48) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    49) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    50) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    51) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    52) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    53) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    54) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    55) Jeffrey B, Barlow T, Moizer K, et al: Amnesic shellfish poison. Food Chem Toxicol 2004; 42:545-557.
    56) Khera KS, Whelan C, & Angers G: Domoic acid: A teratology and homeostatic study in rats. Bull Environ Contam Toxicol 1994; 53:18-24.
    57) 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.
    58) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    59) Larm JA, Beart PM, & Cheung NS: Neurotoxin domoic acid induces cytotoxicity via kainate- and AMPA-sensitive receptors in cultured cortical neurones. Neurochem Int 1997; 31:677-682.
    60) Lawrence JF, Charbonneau CF, & Menard C: Liquid chromatographic determination of domoic acid in shellfish products using the paralytic shellfish poison extraction procedure of the Association of Official Analytical Chemists. J Chromatogr 1989; 462:349-356.
    61) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    62) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    63) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    64) NHLBI ARDS Network: Mechanical ventilation protocol summary. Massachusetts General Hospital. Boston, MA. 2008. Available from URL: http://www.ardsnet.org/system/files/6mlcardsmall_2008update_final_JULY2008.pdf. As accessed 2013-08-07.
    65) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    66) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    67) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    68) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    69) Nakajima S & Potvin JL: Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat. Can J Psychol 1992; 46:569-581.
    70) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    71) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    72) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    73) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    74) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    75) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    76) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    77) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    78) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    79) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    80) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    81) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    82) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    83) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    84) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    85) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    86) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    87) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    88) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    89) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    90) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    91) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    92) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    111) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    112) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    113) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    114) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    115) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    116) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    117) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    118) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    119) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    120) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    121) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    122) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    123) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    124) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    125) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    126) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    127) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    128) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    129) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    130) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    131) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    132) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    133) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    140) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    141) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    142) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    143) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    144) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    145) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    146) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    147) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    148) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    149) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    150) Nijjar MS: Effects of domoate, glutamate and glucose deprivation on calcium uptake by rat brain tissue in rats. Biochem Pharmacol 1993; 46:131-138.
    151) None Listed: Domoic acid intoxication. Can Commun Dis Rep 1992; 18(15):118-120.
    152) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    153) Ohfune Y & Tomita M: Total synthesis of (-)-domoic acid: a revision of the original structure. J Am Chem Soc 1982; 104:3511-3513.
    154) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    155) 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.
    156) Perl T.M., Bedard L., Kosatsky T., et al: Amnesic shellfish poisoning: a new clinical syndrome due to domoic acid. Can Dis Wkly Rep 1990a; 16 Suppl 1E:7-8.
    157) Perl TM, Bedard L, & Kosatsky T: An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 1990; 322:1775-1780.
    158) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    159) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    160) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    161) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    162) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    163) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    164) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    165) Rogers CG & Boyes BG: Evaluation of the genotoxicity of domoic acid in a hepatocyte-mediated assay with V79 chinese hamster lung cells. Mutat Res 1989; 226:191-195.
    166) 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.
    167) Sierra-Beltran A, Palafox-Uribe M, & Grajales-Montiel J: Seabird mortality at Cabo San Lucas, Mexico: evidence of thattoxic diatom blooms are spreading. Toxicon 1997; 35:447-453.
    168) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    169) 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.
    170) Stolbach A & Hoffman RS: Respiratory Principles. In: Nelson LS, Hoffman RS, Lewin NA, et al, eds. Goldfrank's Toxicologic Emergencies, 9th ed. McGraw Hill Medical, New York, NY, 2011.
    171) Subba Rao DV, Quilliam MA, & Pocklington R: Domoic acid - a neurotoxic amino acid produced by the marine diatom Nitzschia pungens in culture. Can J Fish Aquat Sci 1988; 45:2076-2079.
    172) Suzuki CA & Hierlihy SL: Renal clearance of domoic acid in the rat. Food Chem Toxicol 1993; 31:701-706.
    173) Teitelbaum JS, Zatrorre RJ, & Carpenter S: Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 1990; 322:1781-1787.
    174) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    175) Tryphonas L, Truelone J, & Todd E: Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats: preliminary investigations. Fd Chem Toxicol 1990a; 28:707-715.
    176) Tryphonas L, Truelove J, & Nera E: Acute neurotoxicity of domoic acid in the rat. Toxicol Pathol 1990; 18:1-9.
    177) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    178) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    179) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    180) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    181) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    182) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    183) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    184) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    185) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    186) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    187) Wekell JC, Gauglitz EJ, & Barnett HJ: Occurrence of domoic acid in Washington state razor clams (Siliqua patula) during 1991-1993. Natural Toxins 1994; 2:197-205.
    188) Willson DF, Truwit JD, Conaway MR, et al: The adult calfactant in acute respiratory distress syndrome (CARDS) trial. Chest 2015; 148(2):356-364.
    189) Wilson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. JAMA 2005; 293:470-476.
    190) Work TM, Barr B, & Beale AM: Epidemiology of domoic acid poisoning in Brown pelicans (Pelecanus occidentalis) and Brandt's cormorants (Phalacrocorax penicillatus) in California. J Zoo Wildl Med 1993; 24:54-62.