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TETRAMETHYL LEAD

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Tetramethyl lead is an alkyl-lead compound in which a carbon atom of one or more organic molecules is bound to a metal atom. As with metallic lead, alkyl-lead compounds can occur naturally; however, most are man-made compounds used for various purposes (primarily as an "anti-knock" agent in gasoline).

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C4-H12-Pb

Available Forms Sources

    A) SOURCES
    1) Tetramethyl lead is produced by the alloy formation of methyl chloride with lead and sodium followed by dechlorination (Ashford, 1994).
    B) USES
    1) In the past, tetramethyl lead was used as a gasoline additive for automobiles to reduce the consumption of gasoline and to increase engine efficiency. However, given the present information regarding the toxic effects of lead on the environment, this compound is now rarely being used for this purpose (Clayton & Clayton; ILO, 1998).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Tetramethyl lead may be irritating to the eyes, skin, and mucous membranes. Signs and symptoms of exposure may include headache, anxiety, irritability, insomnia, disorientation, nightmares, hyperexcitability, delusions, muscle weakness, tremor, incoordination, seizures, cerebral edema, and coma. A metallic taste, sneezing, bronchitis, and pnuemonia may occur. Cardiovascular symptoms may include hypotension and bradycardia; hypothermia, pallor, vomiting, and diarrhea may also be noted.
    0.2.3) VITAL SIGNS
    A) Irregular respirations, hypotension, fever, or hypothermia have been reported.
    0.2.4) HEENT
    A) Slight eye irritation, rotary nystagmus, impaired vision, blepharospasm, or tinnitus may occur.
    0.2.5) CARDIOVASCULAR
    A) Hypotension or bradycardia may occur. Degeneration of the myocardium was seen in fatal exposure cases.
    0.2.6) RESPIRATORY
    A) Irregular respirations have been reported.
    0.2.7) NEUROLOGIC
    A) Clinical neurologic effects of organolead intoxication can be divided into MILD, MODERATE, and SEVERE.
    1) MILD - Anxiety, irritability, insomnia, lurid dreams, vomiting, metallic taste, pallor, cerebellar ataxia, and diarrhea.
    2) MODERATE - Disorientation, hyperexcitability, tremors, chorea, bradycardia, hypotension, and hypothermia.
    3) SEVERE - Delusions, hallucinations, mania, convulsions, cerebral edema, coma, and death.
    0.2.8) GASTROINTESTINAL
    A) Organolead intoxication usually lacks the common GI manifestations of inorganic lead intoxication. Nausea may occur.
    0.2.9) HEPATIC
    A) Tetraethyl lead may cause elevated liver enzymes.
    0.2.10) GENITOURINARY
    A) Urinary retention was reported in a patient with tetraethyl lead (TEL) intoxication.
    0.2.13) HEMATOLOGIC
    A) Anemia, neutrophilia, and basophilic stippling have been reported with exposure to organolead compounds.
    0.2.14) DERMATOLOGIC
    A) Irritation of the skin may occur from with prolonged skin contact.
    0.2.15) MUSCULOSKELETAL
    A) Elevated CPK may occur.
    0.2.18) PSYCHIATRIC
    A) Insomnia, excitability, strange dreams or delirium may occur.
    0.2.20) REPRODUCTIVE
    A) Tetramethyl lead is fetotoxic, but not teratogenic, in rats.
    B) The offspring of heavy gasoline sniffers have had severe mental retardation.
    C) Organolead has reduced libido, potency, and spermatogenesis in occupationally exposed men.
    D) At the time of this review, no reproductive studies were found for TML exposure in humans.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) Tetramethyl lead is hazardous by the inhalation, dermal, and oral exposure routes.

Laboratory Monitoring

    A) The blood lead level provides one measure of an individual's INORGANIC lead burden, but does not necessarily reflect the organic lead body burden. The normal upper limit is 30 mcg/dL. Inorganic lead levels correlate with CNS signs after chronic exposure.
    B) Urinary lead levels rarely exceeded 180 mcg/liter in workers with a mean exposure time of 18 years.
    C) Metabolic substrates of heme synthesis (delta-ALAD, EP or ZnPP, or coprophyrin) may or may not rise after prolonged exposure and are not reliable tests for diagnosis or assessment of the severity of organolead poisoning. Heme synthesis may not be affected.
    D) Monitor liver function tests, renal function tests, and hematologic parameters.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Vomiting is not recommended following ingestion of leaded gasoline or other products containing organolead compounds because of the potential for CNS depression, seizures, and aspiration of the hydrocarbon vehicle.
    B) If large amounts are ingested, consider placing a nasogastric tube to suction stomach contents. Endotracheal intubation should be strongly considered to prevent aspiration.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Organolead compounds can be absorbed via inhalation.
    C) Consider chelation therapy in patients with blood lead greater than 45 mcg/dL and where symptoms of lead encephalopathy are noted.
    1) BAL (dimercaprol) - 3 to 5 mg/kg/dose deep IM every 4 hours for 2 days; then every 4 to 6 hours for 2 more days; then every 4 to 12 hours up to an additional 7 days.
    2) CALCIUM EDTA - 50 to 75 mg/kg/day deep IM in 3 to 6 divided doses for up to 5 days. EDTA should only be administered after BAL in patients with encephalopathy or children with levels >69 mcg/dL.
    3) DMSA - Initial pediatric dose is 10 mg/kg or 350 mg/m(2) orally every 8 hours for 5 days; reduced to every 12 hours for an additional 2 weeks.
    4) D-PENICILLAMINE - 250 mg 4 times a day PO for up to 5 days. Do not exceed 40 mg/kg/day. OSHA prohibits prophylactic chelation therapy in workers occupationally exposed to lead.
    D) 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.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Routine occupational exposure to tetramethyl lead (TML) has not produced ill effects. The minimum lethal exposure is unknown.

Clinical Effects

Summary Of Exposure

    A) Tetramethyl lead may be irritating to the eyes, skin, and mucous membranes. Signs and symptoms of exposure may include headache, anxiety, irritability, insomnia, disorientation, nightmares, hyperexcitability, delusions, muscle weakness, tremor, incoordination, seizures, cerebral edema, and coma. A metallic taste, sneezing, bronchitis, and pnuemonia may occur. Cardiovascular symptoms may include hypotension and bradycardia; hypothermia, pallor, vomiting, and diarrhea may also be noted.

Vital Signs

    3.3.1) SUMMARY
    A) Irregular respirations, hypotension, fever, or hypothermia have been reported.
    3.3.2) RESPIRATIONS
    A) IRREGULAR RESPIRATIONS were reported as a nonspecific finding of tetraethyl lead (TEL) exposure (Ross, 1982).
    3.3.3) TEMPERATURE
    A) Fever was reported as a nonspecific finding in tetraethyl lead (TEL) poisoning (Ross, 1982).
    B) Hypothermia may occur (Proctor & Hughes, 1978; (Sittig, 1991).
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION may occur (EPA, 1985).

Heent

    3.4.1) SUMMARY
    A) Slight eye irritation, rotary nystagmus, impaired vision, blepharospasm, or tinnitus may occur.
    3.4.3) EYES
    A) IRRITATION - Tetramethyl lead vapors may be slightly irritating to the eyes at high concentrations (EPA, 1985; Sittig, 1991).
    B) ROTARY NYSTAGMUS and limited upward gaze were reported in a child fatally poisoned with tetraethyl lead (TEL) (Grant, 1986).
    C) IMPAIRED VISION was reported with tetraethyl lead (TEL) exposure and was thought to be associated with weakness of the extrinsic eye muscles (Grant, 1986).
    D) BLEPHAROSPASM - Gasoline containing tetraethyl lead (TEL) was applied to the eyes of rabbits, and resulted in pain and blepharospasm. With repeat application, no damage to the rabbit conjunctiva or cornea was reported (Grant, 1986).
    E) AMBLYOPIA was reported in one man who washed his upper body daily with gasoline containing organolead compounds (Grant, 1986).
    3.4.4) EARS
    A) TINNITUS was reported following inhalation of tetraethyl lead (TEL) fumes (Daniels & Latcham, 1984).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension or bradycardia may occur. Degeneration of the myocardium was seen in fatal exposure cases.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Hypotension may occur (EPA, 1985).
    B) BRADYCARDIA
    1) Bradycardia was reported as a nonspecific finding from exposure to tetraethyl lead (TEL) (Ross, 1982).
    C) HEART FAILURE
    1) Seven cases of fatal tetramethyl lead exposure had degenerative alterations in the myocardium, myocardial fragmentation, and swelling and lipofuscin deposits in cardiac muscle fibers (HSDB , 1996).

Respiratory

    3.6.1) SUMMARY
    A) Irregular respirations have been reported.
    3.6.2) CLINICAL EFFECTS
    A) DISORDER OF RESPIRATORY SYSTEM
    1) IRREGULAR RESPIRATIONS were reported as a nonspecific finding of exposure to tetraethyl lead (TEL) (Ross, 1982).

Neurologic

    3.7.1) SUMMARY
    A) Clinical neurologic effects of organolead intoxication can be divided into MILD, MODERATE, and SEVERE.
    1) MILD - Anxiety, irritability, insomnia, lurid dreams, vomiting, metallic taste, pallor, cerebellar ataxia, and diarrhea.
    2) MODERATE - Disorientation, hyperexcitability, tremors, chorea, bradycardia, hypotension, and hypothermia.
    3) SEVERE - Delusions, hallucinations, mania, convulsions, cerebral edema, coma, and death.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) The BRAIN is the critical target organ for tetraalkyl lead toxicity (Nielsen et al, 1978). Clinical effects of organolead intoxication can be divided into MILD, MODERATE, and SEVERE exposure.
    a) MILD - Anxiety, irritability, insomnia, lurid dreams, anorexia (especially at breakfast), nausea, vomiting (especially following ingestion of food), dysgusia, pallor, mild diarrhea, dizziness, tremulousness, lack of coordination, and truncal ataxia (Proctor & Hughes, 1978; (Sittig, 1991).
    b) MODERATE - Disorientation, hyperexcitability, tremors, twitching, chorea, hyperactive reflexes, bradycardia, hypotension, hypothermia, limited upward gaze, and rotary or horizontal nystagmus.
    c) SEVERE - Delusions, hallucinations, mania, decreased peripheral nerve conduction velocity, convulsions, cerebral edema, coma, and death (Proctor & Hughes, 1978; (HSDB , 1991; Sittig, 1991).
    B) SEIZURE
    1) Coulehan et al (1983) reported that 4/23 patients had seizures related to (?leaded?) gasoline sniffing.
    C) TOXIC ENCEPHALOPATHY
    1) Boeckx et al (1977) reported anorexia, delirium, nausea, nervous irritability, pallor, tremor, and vomiting in acutely poisoned (?leaded?) gasoline sniffers.
    D) CHOREOATHETOSIS
    1) CHOREOATHETOID MOVEMENTS have been reported in acute tetraethyl lead poisonings, with involvement of the arms, extensor tendons of the feet, facial muscles, and hands (Ross, 1982).
    E) LACK OF EFFECT
    1) SENSATION - No defects in sensation were reported in 50 patients who had been sniffing leaded gasoline (Seshia et al, 1978).

Gastrointestinal

    3.8.1) SUMMARY
    A) Organolead intoxication usually lacks the common GI manifestations of inorganic lead intoxication. Nausea may occur.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) Vomiting, nausea, and diarrhea may occur (Sittig, 1991; HSDB , 1996).

Hepatic

    3.9.1) SUMMARY
    A) Tetraethyl lead may cause elevated liver enzymes.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) Elevated serum levels of liver enzymes have been seen in severe tetraethyl lead poisoning cases (Robinson, 1978).

Genitourinary

    3.10.1) SUMMARY
    A) Urinary retention was reported in a patient with tetraethyl lead (TEL) intoxication.
    3.10.2) CLINICAL EFFECTS
    A) RETENTION OF URINE
    1) Urinary retention was reported in a single patient with tetraethyl lead intoxication (Ross, 1982).

Hematologic

    3.13.1) SUMMARY
    A) Anemia, neutrophilia, and basophilic stippling have been reported with exposure to organolead compounds.
    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) On hospital admission, 14 of 23 patients with tetraethyl lead intoxication were anemic with a hematocrit less than 35%; 3 of 14 had basophilic RBC's stippling (Coulehan, 1983).
    B) WHITE BLOOD CELL ABNORMALITY
    1) NEUTROPHILIA - Transient neutrophilia was reported as a nonspecific finding (Ross, 1982).
    2) BASOPHILIC STIPPLING may be noted (Hansen & Sharp, 1978).

Dermatologic

    3.14.1) SUMMARY
    A) Irritation of the skin may occur from with prolonged skin contact.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) Tetramethyl lead is a skin irritant and may cause second degree burns with prolonged dermal exposure (EPA, 1985).

Musculoskeletal

    3.15.1) SUMMARY
    A) Elevated CPK may occur.
    3.15.2) CLINICAL EFFECTS
    A) ENZYMES/SPECIFIC PROTEIN LEVELS - FINDING
    1) Elevated serum levels of CPK have been reported in severe cases of tetraethyl lead poisoning (Robinson, 1978).

Reproductive

    3.20.1) SUMMARY
    A) Tetramethyl lead is fetotoxic, but not teratogenic, in rats.
    B) The offspring of heavy gasoline sniffers have had severe mental retardation.
    C) Organolead has reduced libido, potency, and spermatogenesis in occupationally exposed men.
    D) At the time of this review, no reproductive studies were found for TML exposure in humans.
    3.20.2) TERATOGENICITY
    A) MENTAL DEFICIENCY
    1) A syndrome with severe mental retardation has been seen among children of heavy gasoline sniffers (Hunter et al, 1979).
    B) ANIMAL STUDIES
    1) FETOTOXICITY
    a) In rat studies, post-implantation mortality, fetotoxicity, and developmental abnormalities in the musculoskeletal system were noted (RTECS , 1996).
    b) Increased resorptions, embryotoxicity, and fetotoxicity occurred in rats, including delayed ossification of bones, but these effects may have been secondary to maternal toxicity as some of the dams were paralyzed and unable to eat (Barlow & Sullivan, 1982).
    2) GROWTH RETARDED
    a) Tetramethyl lead (TML) was reported not to be teratogenic in rats (Schardein, 1985). When given at a dose of 5 mg/kg to pregnant rats on days 9 to 11 or 12 to 14 of gestation, no gross malformations were seen in the absence of maternal toxicity; increased resorptions and growth retardation were seen, however (McLain & Becker, 1972).
    b) Tetramethyl lead (TML) given in an oily vehicle once a week during gestation produced lower brain:body weight ratios in rats (Cragg & Rees, 1984).
    3) CNS EFFECTS
    a) Tetraethyl lead (TML) is converted to the more stable and more toxic triethyl lead by the liver, kidney, and brain. Triethyl lead is the primary nervous system toxicant.
    4) LACK OF EFFECT
    a) It has generally not caused birth defects in laboratory animals at doses which were not toxic to the mothers (Barlow & Sullivan, 1982).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS75-74-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Tetramethyllead
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    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.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) The blood lead level provides one measure of an individual's INORGANIC lead burden, but does not necessarily reflect the organic lead body burden. The normal upper limit is 30 mcg/dL. Inorganic lead levels correlate with CNS signs after chronic exposure.
    B) Urinary lead levels rarely exceeded 180 mcg/liter in workers with a mean exposure time of 18 years.
    C) Metabolic substrates of heme synthesis (delta-ALAD, EP or ZnPP, or coprophyrin) may or may not rise after prolonged exposure and are not reliable tests for diagnosis or assessment of the severity of organolead poisoning. Heme synthesis may not be affected.
    D) Monitor liver function tests, renal function tests, and hematologic parameters.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Obtain a blood lead level (BLL). The BLL correlates less well with organolead intoxication than with inorganic lead intoxication. Blood lead probably represents the treatable body lead fraction and appears to be a better predictor of clinical poisoning (Beattie et al, 1972). Patients with blood lead levels in excess of 50 mcg/dL should be chelated; those with blood levels in excess of 80 mcg/dL require immediate hospitalization and chelation therapy.
    2) Lead in the lipid fraction of the blood was elevated three-fold more than total blood lead following TEL exposure (Beattie et al, 1972).
    3) An elevated EP (ZnPP) (in the absence of other causes, such as iron deficiency anemia, sickle cell anemia, certain hemoglobinopathies, etc) indicates excess absorption of TEL or lead (the test is not specific for TEL). Because of the slow conversion of TEL to the inorganic (ionic) form, finding a normal EP level does not rule possible excess TEL absorption.
    4) Abnormal liver function tests, renal function tests, and hematologic parameters are seen in severe organolead poisoning cases (Robinson, 1978).
    B) HEMATOLOGIC
    1) Abnormal hematologic parameters are seen in severe organolead poisonings (Robinson, 1978).
    2) Monitor WBC with differential counts on a frequent basis in persons receiving chronic oral penicillamine chelation therapy.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Urinary lead levels might represent a better predictor of clinical poisoning (Proctor & Hughes, 1978).
    a) Urinary lead levels rarely exceeded 180 mcg/L in 592 TEL-exposed workers with a mean exposure time of 18 years (Robinson, 1974).
    b) Levels greater than 350 mcg/L may be indicative of severe intoxication (Proctor & Hughes, 1978).
    c) Fleming reported urinary lead levels of 0 to 140 mcg/L among 60 "normal salesmen" compared to 200 to 1200 mcg/L in 11 TEL-workmen with clinical evidence of lead poisoning (Fleming, 1964).
    2) Monitor urinary levels in persons receiving chronic oral penicillamine chelation therapy.
    4.1.4) OTHER
    A) OTHER
    1) TISSUE
    a) Lead levels found in the tissues of men fatally poisoned by tetramethyl lead (TML) were 0.7 to 13 mg/100 g in brain, liver, and kidneys (HSDB , 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) The blood lead level provides one measure of an individual's INORGANIC lead burden, but does not necessarily reflect the organic lead body burden. The normal upper limit is 30 mcg/dL. Inorganic lead levels correlate with CNS signs after chronic exposure.
    B) Urinary lead levels rarely exceeded 180 mcg/liter in workers with a mean exposure time of 18 years.
    C) Metabolic substrates of heme synthesis (delta-ALAD, EP or ZnPP, or coprophyrin) may or may not rise after prolonged exposure and are not reliable tests for diagnosis or assessment of the severity of organolead poisoning. Heme synthesis may not be affected.
    D) Monitor liver function tests, renal function tests, and hematologic parameters.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) NASOGASTRIC SUCTION
    1) If large amounts are ingested, consider placing a nasogastric tube to suction stomach contents. This should be preceded by endotracheal intubation in cases of ingestion of large amounts of leaded gasoline or other similar products when CNS depression is present.
    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) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATIONAL EXPOSURE section where appropriate.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) DISORDER OF BRAIN
    1) Lead encephalopathy is a medical emergency. Patient should be hospitalized in an intensive care setting. Prompt neurosurgical and toxicological consultation should be obtained to assist in management. Withhold spinal tap until status of intracranial pressure has been fully considered. Place intracranial pressure probe.
    B) CEREBRAL EDEMA
    1) CLINICAL IMPLICATIONS
    a) Cerebral edema and elevated intracranial pressure (ICP) may occur. Emergent management includes head elevation and administration of mannitol; hyperventilation should be performed if there is evidence of impending herniation.
    2) MONITORING
    a) Patients will usually require endotracheal intubation and mechanical ventilation. Monitor intracranial pressure, cerebral perfusion pressure and cerebral blood flow.
    3) TREATMENT
    a) Most information on the treatment of cerebral edema is derived from studies of traumatic brain injury.
    4) MANNITOL
    a) ADULT/PEDIATRIC DOSE: 0.25 to 1 gram/kilogram intravenously over 10 to 15 minutes (None Listed, 2000).
    b) AVAILABLE FORMS: Mannitol injection (5%, 10%, 15%, 20%, 25%).
    c) MAJOR ADVERSE REACTIONS: Congestive heart failure, hypernatremia, hyponatremia, hyperkalemia, renal failure, pulmonary edema, and allergic reactions.
    d) PRECAUTIONS: Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia. Do not add to whole blood for transfusions; enhanced neuromuscular blockade has occurred with tubocurarine. Keep serum osmolarity below 320 mOsm.
    e) MONITORING PARAMETERS: Renal function, urine output, fluid balance, serum potassium levels, serum osmolarity, and CVP.
    5) HYPERTONIC SALINE
    a) Preliminary studies suggest that hypertonic saline (7.5% saline/6% dextran) 100 ml reduced ICP more effectively than 200 mL of 20% mannitol in adults with elevated ICP after traumatic brain injury(Battison et al, 2005).
    6) ELEVATION
    a) Elevation of the head of the bed to approximately 30 degrees decreases ICP and improves cerebral perfusion pressure (Meixensberger et al, 1997; Schneider et al, 1993; Feldman et al, 1992).
    7) MECHANICAL DECOMPRESSION
    a) Early surgical decompression, ventriculostomy with CSF drainage, or craniectomy may be useful in patients with persistent elevation of ICP (Sahuquillo & Arikan, 2006; Sakai et al, 1998; Polin et al, 1997; Taylor et al, 2001). Most experience with these modalities has been in patients with traumatic brain injury.
    8) HYPERVENTILATION
    a) SUMMARY: Hyperventilation has been associated with adverse outcomes and should not be performed routinely (Muizelaar et al, 1991). It is indicated in patients who have clinical evidence of herniation or if there is intracranial hypertension refractory to sedation, paralysis, CSF drainage and osmotic diuretics (None Listed, 2000a).
    b) RECOMMENDATION:
    1) The PCO2 must be controlled in the range of 25 torr; further lowering of PCO2 may create undesirable effects secondary to local tissue hypoxia.
    2) End-tidal CO2 tension, correlated with an initial ABG measurement, provides a noninvasive means of monitoring PCO2 (Mackersie & Karagianes, 1990).
    3) Most authorities advise that hyperventilation should be considered a temporizing measure only; SUSTAINED hyperventilation should be avoided (Am Acad Neurol, 1997; Bullock et al, 1996; Kirkpatrick, 1997).
    9) DEXAMETHASONE - There is controversy in the literature as to whether dexamethasone is an effective treatment for cerebral edema that is induced by other mechanisms than malignancy and as to the appropriate dose.
    a) LOW DOSE - 16 mg/day in divided doses (De Los Reyes et al, 1981).
    b) HIGH DOSES - 1 to 2 mg/kg/day in divided doses (Heinemeyer, 1987).
    c) Or by other appropriate methods.
    C) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    D) CHELATION THERAPY
    1) CONTROVERSY - Strong differences of opinion exist as to the appropriateness of chelation therapy in exposure to organolead compounds, especially in a symptomatic patient.
    2) RECOMMENDATIONS -
    a) Chelation therapy is not indicated in patients with acute toxicity only because chelators cannot chelate organic lead because potential ligands are covalently bound by the ethyl groups (Pers Comm, 1991).
    b) An elevated blood lead probably reflects largely inorganic lead and the presence of lead encephalopathy indicates chelation. Chelation should also be considered in children with blood lead level above 45 mcg/dL and symptomatic adults.
    3) CASE REPORTS -
    a) Although generally discouraged in several handbooks and textbooks, experience with industrial exposure (Beattie et al, 1972), a severely poisoned 15-year-old (Robinson, 1978), and a 27-year-old heavy gasoline sniffer (Hansen & Sharp, 1978), demonstrate increased lead excretion with chelation.
    b) Several other case reports and two large case series have demonstrated increased urinary lead excretion and declining blood lead levels with clinical improvement associated with chelation therapy (Edminster & Bayer, 1985; McCracken, 1987; Moss & Cooper, 1986; Goodheart & Dunne, 1994)( McGrath, 1986; Currie et al, 1994).
    E) PROCEDURE EDUCATION
    1) CHILDREN - Chelation therapy is indicated in children with blood lead levels greater than 45 mcg/dL or if signs and symptoms of lead encephalopathy are noted (CDC, 1991).
    2) ADULTS - Chelation should also be considered in symptomatic adults.
    F) DIMERCAPROL
    1) SUMMARY - British-Anti-Lewisite (BAL) or dimercaprol is a small-molecule drug which will cross into cells and prevent the worsening of clinical and biochemical status on the first day of EDTA therapy (Chisolm, 1971).
    2) INDICATIONS - BAL in conjunction with Calcium EDTA is recommended if evidence of encephalopathy exists, if blood lead levels are >69 mcg/dL in children, or if protracted vomiting necessitates parenteral therapy.
    a) CONTRAINDICATIONS - BAL should not be used in children who have an allergy to peanuts or peanut products (CDC, 1991).
    3) DOSE - 3 to 5 mg/kg/dose by deep intramuscular injection every 4 hours for 2 days; then every 4 to 6 hours for an additional 2 days; then every 4 to 12 hours for up to an additional 7 days.
    4) ADVERSE EFFECTS - Include urticaria, pyrexia, and hypertension. Treat side effects with antihistamines or cessation of drug.
    G) EDETATE CALCIUM DISODIUM
    1) SUMMARY - The most efficient parenteral chelating agent is calcium disodium ethylene diamine tetraacetic acid (edathamil, EDTA, or CaVersinate).
    2) INDICATIONS - CaNa2EDTA is recommended in conjunction with BAL if evidence of encephalopathy exists, if blood lead levels are >69 mcg/dL in children, or if protracted vomiting necessitates parenteral therapy.
    a) CHILDREN - Only calcium disodium EDTA, not disodium edetate, may be used in children. Disodium edetate may induce tetany and possibly fatal hypocalcemia (CDC, 1991).
    3) PREPARATION - Dilute to less than 0.5% solution in dextrose or normal saline. Infuse intravenously slowly over 15 to 20 minutes or by continuous infusion over 6 hours.
    4) DOSE - Calculate dosage on weight or body surface area. In encephalopathy the dose is larger than for all other therapy. There is no proven difference between intramuscular administration, and intravenous therapy given in 4 to 24 hours. In all cases the total daily dose is the same. 50 to 75 mg/kg/day (or 500 to 1000 mg/square meter/day) by deep intramuscular injection or slow intravenous infusion given in 3 to 6 divided doses for up to 5 days; may be repeated for 2nd course after a minimum of 2 days; each course should not exceed a total of 500 mg/kg of body weight. Some authors recommend a maximum of 1 gram/day for children and 4 grams/day for adults. The larger dose (75 mg/kg/day) (1500 mg/square meter/day) is generally reserved for encephalopathy.
    5) ADVERSE EFFECTS - Toxicity of EDTA is due to 1) renal tubular injury and 2) chelation of other metals. Acute tubular necrosis may occur with a frequency as high as 3/100 cases. It is not directly related to the concentration of lead, nor to the route of administration.
    a) It is dose related and recommended doses should not be exceeded. Cessation of therapy will usually lead to recovery. EDTA chelates zinc.
    b) While serum zinc returns rapidly to normal, some administer zinc after therapy. EDTA removes iron. If iron stores are marginal or questionable, or ferritin is low, administer iron after therapy.
    6) REBOUND - If the blood lead level rebounds to its pretreatment level or is greater than 50 mcg/dL a repeat course of chelation should be considered.
    7) PRECAUTIONS - Calcium EDTA should only be administered after adequate urine flow is established (Chisolm, 1971). If urine flow has NOT been established in a symptomatic child after 3 hours of fluids, administer the EDTA and initiate simultaneous hemodialysis to remove the EDTA-Pb complex which is nephrotoxic.
    a) Up to 16% of children receiving calcium EDTA and BAL for lead poisoning may develop a nephrotoxic reaction (Moel & Kumar, 1982). At least every other day urinalysis and serum creatinine are recommended.
    8) INTERNAL REDISTRIBUTION - In a rat model of chronic low-level lead exposure, single dose calcium disodium edetate increased urine, brain, and hepatic lead levels and decreased blood and renal lead levels (Cory-Slechta, 1988).
    a) Brain lead level increased by 100% over control suggesting concerns about the safety of calcium disodium edetate mobilization test (Chisolm, 1987).
    b) Five daily injections of calcium disodium edetate in rats showed no net loss in brain, hepatic, and bone lead compared with controls (Cory-Slechta, 1988).
    H) SUCCIMER
    1) EFFICACY
    a) SUMMARY - It has been shown to be an effective chelator of lead in rats (Graziano et al, 1978; Kapoor et al, 1989), lead-poisoned workers (Friedheim et al, 1978; Graziano et al, 1985), a patient poisoned with lead contaminated bread (Bentur et al, 1987), children (Graziano et al, 1986; Graziano et al, 1988), and 9 adult lead-poisoned patients (Fournier et al, 1988).
    b) Succimer decreased blood lead concentrations by 35 to 81% and induced a 4.5- to 16.9-fold increase in mean daily urinary excretion of lead in a study of 9 adult lead-poisoned patients treated with a dose of 30 milligrams/kilogram/day of DMSA for 5 days (Fournier et al, 1988).
    c) DMSA was reported to be equally efficacious as Calcium EDTA in a 45-year-old man with lead toxicity (Thomas & Ashton, 1991).
    2) SUCCIMER/DOSE/ADMINISTRATION
    a) PEDIATRIC: Initial dose is 10 mg/kg or 350 mg/m(2) orally every 8 hours for 5 days (Prod Info CHEMET(R) oral capsules, 2011).
    1) The dosing interval is then increased to every 12 hours for the next 14 days. A repeat course may be given if indicated by elevated blood levels. A minimum of 2 weeks between courses is recommended, unless blood lead concentrations indicate the need for prompt retreatment.
    2) Succimer capsule contents may be administered mixed in a small amount of food (Prod Info CHEMET(R) oral capsules, 2011).
    b) ADULT: Succimer is not FDA approved for use in adults, however it has been shown to be safe and effective when used to treat adults with poisoning from a variety of heavy metals (Fournier et al, 1988a). Initial dose is 10 mg/kg or 350 mg/m(2) orally every 8 hours for 5 days (Prod Info CHEMET(R) oral capsules, 2011).
    1) The dosing interval then is increased to every 12 hours for the next 14 days. A repeat course may be given if indicated by elevated blood levels. A minimum of 2 weeks between courses is recommended, unless the patient's symptoms or blood concentrations indicate a need for more prompt treatment (Prod Info CHEMET(R) oral capsules, 2011).
    3) MONITORING PARAMETERS
    a) The manufacturer recommends monitoring liver enzymes and complete blood count with differential and platelet count prior to the start of therapy and at least weekly during therapy (Prod Info CHEMET(R) oral capsules, 2011).
    b) Succimer therapy did not worsen preexisting borderline abnormal liver enzyme levels in a prospective evaluation of 15 children with lead poisoning (Kuntzelman & Angle, 1992).
    4) ADVERSE EFFECTS
    a) SUCCIMER/ADVERSE EFFECTS: The following adverse events have occurred in children and adults during clinical trials: nausea, vomiting and diarrhea; transient liver enzyme elevations; rash, pruritus; drowsiness and paresthesia. Events reported infrequently include: sore throat, rhinorrhea, mucosal vesicular eruption, thrombocytosis, eosinophilia, and mild to moderate neutropenia (Prod Info CHEMET(R) oral capsules, 2011).
    b) ODOR: Succimer has a sulfurous odor that may be evident in the patient's breath or urine (Prod Info CHEMET(R) oral capsules, 2005).
    c) HYPERTHERMIA: One adult developed acute severe hyperthermia associated with hypotension; rechallenge resulted in hyperthermia with shaking chills and hypertension (Marcus et al, 1991).
    d) AVAILABLE FORMS: Succimer (Chemet (R)), 100 mg capsules (Prod Info CHEMET(R) oral capsules, 2011).
    I) PENICILLAMINE
    1) SUMMARY - Can be used orally as outpatient chelation therapy when the exposure has ceased. Due to lesser efficacy and increased adverse reactions and precautions, succimer is the drug of choice when oral therapy is indicated.
    a) DOSE - ADULTS: 250 mg four times a day orally for up to 5 days for long-term therapy; do not exceed 40 mg/kg/24 hours. CHILD: 20 to 30 mg/kg/day orally. Administer on an empty stomach with orange juice or applesauce. For treatment in children with blood lead levels of 30 mcg/dL or less, 15 to 30 mg/kg were administered daily (Shannon et al, 1989a).
    2) ADVERSE EFFECTS
    a) Adverse effects in children receiving D-penicillamine include eosionphila, leukopenia, thrombocytopenia, elevations of blood urea nitrogen, proteinuria, microscopic hematuria, incontinence, abdominal pain and upset, urticarial eruptions, and erythema multiforme (Marcus, 1982) Shannon et al, 1989; (Sue et al, 1991).
    b) Rashes: Urticaria, toxic erythema, erythema multiforme, and a "ampicillin" type rash. All but the last require cessation of therapy.
    c) Neutropenia: Requires a neutrophil count on a biweekly basis as continued therapy with a neutropenic response may result in aplastic anemia.
    d) Eosinophilia commonly occurs in the first to third week of therapy though usually of little consequence.
    e) CHRONIC - Chronic administration (weeks to months) of penicillamine is associated with a high incidence of adverse reactions including proteinuria, thrombocytopenia, leukopenia, pruritic mucocutaneous rash and gastrointestinal intolerance (Halverson et al, 1978).
    f) PREGNANCY - Penicillamine can cause congenital tissue defects when used throughout pregnancy (Linares et al, 1979; Solomon et al, 1977; Anon, 1981). However, the teratogenic effect when used in low doses or for short periods of time such as in metal chelation has yet to be determined.
    J) UNITHIOL
    1) 2,3-Dimercaptopropane-1-sulfonate (DMPS) is a promising experimental drug (Chisolm & Thomas, 1985). CaNa2EDTA and dimercaprol are becoming outmoded and can be expected to be replaced by DMSA and DMPS for the treatment of lead intoxication (Aposhian et al, 1995).
    2) Adverse effects in a series of 23 cases included 2 cases of erythema multiforme requiring steroids and a severe maculopapular rash developing after completion of therapy (Hla et al, 1992).
    K) AIRWAY MANAGEMENT
    1) Because of the high incidence of aspiration pneumonia in patients who chronically abuse leaded gasoline, early aggressive airway management and careful pulmonary toilet are recommended (Currie et al, 1994).
    L) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

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).
    6.8.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATIONAL EXPOSURE section where appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATIONAL EXPOSURE section where appropriate.
    B) SKIN ABSORPTION
    1) There are no published cases where chelation has been required after dermal exposure.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) Routine occupational exposure to tetramethyl lead (TML) has not produced ill effects. The minimum lethal exposure is unknown.

Minimum Lethal Exposure

    A) ACUTE
    1) In humans, tetraethyl lead (TEL) is approximately 3 times more toxic than tetramethyl lead (TML) (HSDB , 2000).
    B) CARCINOGENICITY: Tetramethyl lead's carcinogenic risk to humans is not classifiable (Group 3); carcinogenic evidence for this compound is inadequate in both animals and humans (HSDB , 2000).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The half-life of lead in human blood is 36 days (HSDB , 2000).
    2) Fish and higher animals can accumulate lead and pass it up the food chain(OHM/TADS, 2000).
    B) CASE REPORTS
    1) Several cases of acute toxicity, usually in the form of degenerative brain disease, have been described following occupational TML exposure (EPA, 1985).

Workplace Standards

    A) ACGIH TLV Values for CAS75-74-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Tetramethyl lead, as Pb
    a) TLV:
    1) TLV-TWA: 0.15 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Skin
    3) Definitions:
    a) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): CNS impair
    d) Molecular Weight: 267.33
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS75-74-1 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Tetramethyl lead (as Pb)
    2) REL:
    a) TWA: 0.075 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: [skin]
    1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.
    f) Note(s):
    3) IDLH:
    a) IDLH: 40 mg Pb/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS75-74-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Tetramethyl lead, as Pb
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Tetramethyllead
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Tetramethyl lead (as Pb)
    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 CAS75-74-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Tetramethyl lead (as Pb)
    2) Table Z-1 for Tetramethyl lead (as Pb):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.075
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: Yes
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)RAT:
    1) 90 mg/kg (RTECS , 2000a; HSDB , 2000a; OHM/TADS, 2000; Lewis, 1996b; Hathaway et al, 1996)
    B) LD50- (ORAL)RAT:
    1) 108 mg/kg (RTECS , 2000a; HSDB , 2000a; OHM/TADS, 2000; Lewis, 1996b; Hathaway et al, 1996)
    2) 105 mg/kg (RTECS , 2000a; HSDB , 2000a; OHM/TADS, 2000; Lewis, 1996b; Hathaway et al, 1996)
    C) TCLo- (INHALATION)RAT:
    1) 900 mg/m(3) for 1H for 5D, intermittent (RTECS , 2000a; HSDB , 2000a; OHM/TADS, 2000; Lewis, 1996b; Hathaway et al, 1996)

Physicochemical

Physical Characteristics

    A) Tetramethyl lead is an oily liquid that carries a slightly musty or fruity odor. Although it is colorless in its natural state, it is generally dyed red, blue, or orange in commerce. This compound shows signs of toxicity and flammability (Ashford, 1994; CHRIS , 2000; HSDB , 2000; Lewis, 1996; Lewis, 1998; Sittig, 1991)

Molecular Weight

    A) 267.34

References

General Bibliography

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    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) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 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.
    6) 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.
    7) 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.
    8) 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.
    9) 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.
    10) 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.
    11) 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.
    12) 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.
    13) ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indicies, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986, pp 565.
    14) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
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