Substances Included Synonyms

Therapeutic Toxic Class

A)

B)

Specific Substances

1) Acetylene Trichloride
2) Ethinyl Trichloride
3) TCE
4) Trichloroethene
5) Trichloroethylene
6) Trichlorethylenum
7) Trichloroethylenum
8) CAS 79-01-6
9) TRICHLOROETILENE (ITALIAN)

1.2.1) MOLECULAR FORMULA
1) C2-H-Cl3 Cl2C=CHCl Cl-CH=C-Cl2

Available Forms Sources

A)

1) Trichloroethylene is a stable, photoreactive liquid with a low boiling point. It is colorless or dyed blue, and has a sweet, chloroform-like odor (Lewis, 1997; Harbison, 1998).
2) It is available in the following grades: USP, technical, high-purity, electronic, metal-degreasing and extraction (Lewis, 1997).
3) Trichloroethylene may contain thymol as preservative (medicinal form) or stabilizers such as triethylamine (industrial grade) (Budavari, 2000).

a) "Stabilised grades are produced for vapor cleaning applications" (Ashford, 1994).

B)

1) Trichloroethylene is prepared from sym-tetrachloroethane. This is done by eliminating hydrogen chloride (by boiling with lime) (Budavari, 2000).

a) It can be prepared by passing tetrachloroethane vapor over calcium chloride catalyst at 300 degrees C. In the absence of the catalyst, the required temperature is 450-470 degrees C (Budavari, 2000)

2) It also can be produced using the following methods (Ashford, 1994):

a) Ethylene dichloride + chlorine (chlorination; coproduced with perchlorethylene)
b) Ethylene dichloride + chlorine + oxygen (oxychlorination/dehydrochlorination; coproduced with perchlorethylene)
c) Acetylene + chlorine (addition/dehydrochlorination)

3) It can be manufactured by treating tetrachloroethane with alkali or lime in the presence of water; or via thermal decomposition and subsequent steam distillation (Lewis, 1997).
4) It can be manufactured through chlorination or oxychlorination of C2-chlorinated halocarbons such as 1,2-dichloroethane. Prior to 1978, it was mainly generated through chlorination of acetylene with subsequent dechlorination (HSDB , 2001).

C)

1) Trichloroethylene is used as an industrial degreaser, extraction medium and household cleaning solvent (Ashford, 1994; Ellenhorn & Barceloux, 1988; ILO , 1998; Sittig, 1991). It is used in the preparation of insecticidal fumigants and in both extraction and degreasing processes (Hayes & Laws, 1991). It is used for olive oil extraction, to remove basting threads in textile industry and as swelling agent for dyeing polyester (ILO , 1998).
2) It is used as a solvent for fats, waxes, resins, oils, rubber, paints and varnishes, as well as cellulose esters and ethers; for solvent extraction in many industries; in degreasing; in dry cleaning; and in organic chemicals, pharmaceuticals, and chloroacetic acid manufacturing (Budavari, 2000; Sittig, 1991).
3) It is also used in solvent dyeing; as a refrigerant and heat-exchange liquid; as a fumigant; for cleaning and drying electronic parts; as a diluent in paints and adhesives; in textile processing; and in aerospace operations (flushing liquid oxygen) (Lewis, 1997).
4) Trichloroethylene has been used as a surgical inhalation anesthetic and analgesic (ACGIH, 1996a; Hathaway et al, 1996). It is a potent analgesic with poor muscle-relaxant properties (ACGIH, 1996a; JEF Reynolds , 2000).
5) The use of trichloroethylene as an extractant in food processing was discontinued in 1975. The National Cancer Institute issued an alert warning that trichloroethylene may be a carcinogen on the basis of liver tumors in mice (ACGIH, 1996a).
6) Prior to trichloroethylene's removal in 1977, it was an ingredient in grain fumigants, disinfectants and pet food, and was an extractant of caffeine in coffee (Barceloux & Rosenberg, 1990). However, the FDA has prohibited the use of this compound in foods, drugs and cosmetics (Lewis, 1997). In caffeine extraction from coffee, most trichloroethylene has been replaced with methylene chloride (Lewis, 1998).
7) Consumer products containing trichloroethylene include typewriter correction fluids, paint removers and strippers, cosmetics, adhesives, rug-cleaning fluids and spot removers (Barceloux & Rosenberg, 1990).
8) Trichloroethylene is used in gas purification, as a solvent for sulfur and phosphorus (HSDB , 2001). It is also used as chain-transfer agent in polyvinyl chloride production and as heat-transfer fluid (Ashford, 1994). Other uses include: solvent in characterization tests for asphalt and in metal phosphatizing systems; entrainer for recovery of formic acid; extractant for spice olefins (HSDB , 2001).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) GENERAL - Trichloroethylene (TCE) is toxic by ingestion, inhalation or dermal exposure. Inhalation of TCE can cause euphoria, hallucinations and distorted perceptions; inhalational abuse, with addiction, has been reported. TCE vapor may be irritating to the nose and throat.
B) INHALATION - Narcosis and anesthesia occur after inhalation. Adverse effects from inhalation exposure include bronchial irritation, dyspnea, pulmonary edema, respiratory depression, euphoria, dizziness, restlessness, irritability, incoordination, central nervous system depression, impaired concentration, confusion, drowsiness, loss of consciousness, seizures, renal and hepatic damage, as well as fatal cardiac dysrhythmias.
C) INGESTION - Effects from ingestion include nausea, vomiting, diarrhea, abdominal pain, dysphagia, jaundice, somnolence, headache, dizziness, incoordination, elevated creatine kinase, hallucinations or distorted perceptions, paresthesia, partial paralysis, dysrhythmias and circulatory collapse. The main systemic response is CNS depression.
D) OCULAR - Direct contact with the eye may result in pain and injury to the corneal epithelium; recovery usually occurs within a few days. Double vision, blurred vision, optic neuritis and blindness can occur after exposure.
E) DERMAL - TCE is a skin irritant and may cause defatting dermatitis of the skin. Scleroderma has been linked with TCE exposure. Dermal absorption is not likely to be significant if dermatitis is prevented. Vasodilation and malaise ('degreasers flush') recur in workers who drink ethanol after exposure to TCE. Chemical burns have been reported with concentrated exposure to TCE vapors.
F) CHRONIC - Long-term occupational exposure may result in hearing loss, memory loss, fatigue, flushing, ECG changes, vomiting, renal and hepatic damage, CNS depression, irritability, encephalopathy, dementia, neuropathy, paresthesias and possibly systemic sclerosis. Visual disturbances, oculomotor paralysis and trigeminal palsies have been reported after occupational exposure.

0.2.4)

A) WITH POISONING/EXPOSURE

1) Optic neuritis and blindness has been reported after exposure. Direct contact with the eye may result in injury to the corneal epithelium; recovery usually occurs within a few days and permanent injury is unlikely.
2) Hearing deficiency and bilateral, symmetrical sixth cranial nerve deafness have been reported.
3) Cranial nerve palsies have developed as a result of TCE exposure.

0.2.5)

A) WITH POISONING/EXPOSURE

1) Cardiac dysrhythmias (ventricular and atrial fibrillation), hypotension, conduction defects and myocardial injury have been noted.

0.2.6)

A) WITH POISONING/EXPOSURE

1) Respiratory depression, cyanosis, pulmonary hemorrhages and edema have been reported after exposure to TCE.

0.2.7)

A) WITH POISONING/EXPOSURE

1) CNS depression, lightheadedness, dizziness and euphoria, particularly after inhalation, have been noted. Trigeminal nerve impairment has been reported in individuals chronically and acutely poisoned by TCE.
2) CNS depression, tremor and motor restless may occur after ingestion.
3) Multiple nerve palsies and peripheral neuropathy have been reported after intoxication.

0.2.8)

A) WITH POISONING/EXPOSURE

1) Nausea, vomiting, salivation, loss of taste, anorexia, abdominal pain, diarrhea and dysphagia have all been linked with exposure to TCE. Fatal abdominal compartment syndrome was reported in one adult.

0.2.9)

A) Liver injury has been reported.

0.2.10)

A) WITH POISONING/EXPOSURE

1) Renal failure may occur after oral or inhalation exposure to TCE.

0.2.14)

A) WITH POISONING/EXPOSURE

1) TCE is mildly irritating to the skin. Defatting dermatitis can occur after contact with the liquid. Higher concentrations, including vapor exposure, may result in chemical burns. Chronic exposure may produce rash, dry skin, and scleroderma. Chemical burns have been reported with concentrated exposure to TCE vapors. Stevens-Johnson syndrome has been described following TCE exposure.

0.2.15)

A) WITH POISONING/EXPOSURE

1) Diffuse fasciitis with eosinophilia has been reported after chronic ingestion.
2) Systemic sclerosis has been described after occupational exposures.

0.2.16)

A) WITH POISONING/EXPOSURE

1) Menstrual irregularities and possible anovulation were reported after occupational exposure to TCE vapor.

0.2.18)

A) Organic dementia has been reported after occupational exposure to TCE.

0.2.19)

A) WITH POISONING/EXPOSURE

1) Symptoms of systemic lupus erythematosus have been reported after chronic exposures.
2) Eosinophilia has been reported after acute exposures.

0.2.20)

A) Although some studies have found birth defects and spontaneous abortions related to exposure to TCE, most involved concomitant confounding exposure to other chemicals. It does cross the placenta. Abnormal sperm morphology has occurred after exposure.
B) Many laboratory animal studies have shown that TCE does not adversely affect fertility or embryo implantation and survival, and does not cause teratogenic effects. TCE has, however, been shown to produce some developmental abnormalities. Reversible suppression of male copulation was shown in a few studies.

0.2.21)

A) Conflicting results have been obtained regarding the carcinogenicity of trichloroethylene in humans. As of 2014, IARC has classified trichlorethylene as Group 1 - carcinogenic to humans.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) Because of the potential for CNS depression and seizures, DO NOT induce emesis.
B) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.

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

C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
D) Monitor ECG and vital signs frequently in symptomatic patients.
E) AVOID EPINEPHRINE - and other catecholamines (especially beta agonists) which may increase the risk of dysrhythmias.
F) Pulmonary edema, renal failure and liver injury should be managed symptomatically.
G) DEGREASERS FLUSH - May respond to propranolol (40 to 80 mg PO).
H) VENTRICULAR DYSRHYTHMIAS/SUMMARY: Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
I) Ventricular dysrhythmias may also respond to beta blockers. A short acting titratable agent such as esmolol is preferred.
J) 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.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
B) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

A)

B)

C)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

F)

Vital Signs

3.3.3)

A) WITH POISONING/EXPOSURE

1) CASE REPORT - Hypothermia was reported in an 83-year-old female after she ingested benzodiazepines and a spot remover containing TCE (Lumpe, 1993).
2) CASE REPORT - Fever was reported in a 17-year-old male after he ingested approximately 70 mL TCE (Bruning et al, 1998).

Heent

3.4.1)

A) WITH POISONING/EXPOSURE

1) Optic neuritis and blindness has been reported after exposure. Direct contact with the eye may result in injury to the corneal epithelium; recovery usually occurs within a few days and permanent injury is unlikely.
2) Hearing deficiency and bilateral, symmetrical sixth cranial nerve deafness have been reported.
3) Cranial nerve palsies have developed as a result of TCE exposure.

3.4.2)

A) Weakness and numbness of the face, as well as trigeminal neuralgias may occur (NIOSH, 1973).

3.4.3)

A) Direct contact with the eye causes eye pain without permanent injury (ACGIH, 1996).
B) OPTIC NEURITIS and blindness have been reported after inhalation, as have double vision and blurred vision (Mitchell & Parsons-Smith, 1969; Buxton & Hayward, 1967; NIOSH, 1973; Grant & Schuman, 1993).
C) CONJUNCTIVITIS - Direct contact with the eye produces irritation and injury to the corneal epithelium (Hathaway et al, 1996), but permanent injury is unlikely. However, first- and second-degree burns have been attributed to the vapors (NIOSH, 1973; Browning, 1965; Grant & Schuman, 1993).
D) CASE REPORT - A 48-year-old woman developed uveitis, along with pain and blurred vision, after chronic (several years) occupational exposure to TCE vapor (550 ppm). The patient was treated successfully with topical corticosteroids and mydriatics (Schattner & Malnick, 1990).
E) MYDRIASIS has been reported after ingestion of an unknown amount of TCE (Perbellini et al, 1991).
F) CASE REPORT - A 35-year-old man developed diplopia in all fields and palsies of the left third cranial nerve and bilateral sixth cranial nerves after inhaling TCE for 3 days (Szlatenyi & Wang, 1994).
G) Some evidence indicates that it is TCE decomposition products or impurities that may be responsible for cranial nerve injuries, producing palsies of the oculomotor and trigeminal nerves, optic or retrobulbar neuritis, and optic neuropathy/atrophy (Grant & Schuman, 1993) Cavanaugh & Buxton, 1989; (Feldman et al, 1988).

3.4.4)

A) Occupational exposure for 1 to 23 years has resulted in hearing deficiency (Bingham et al, 2001).
B) DEAFNESS - Bilateral, symmetrical sixth cranial nerve deafness, slight for low frequencies but complete for tones over 1,000 cycles/second, has been reported with TCE exposure (NIOSH, 1973).

1) RATS - Mid-frequency hearing loss at 20 kHz with reduced acoustic startle response was reported in rats exposed by inhalation to 3,000 ppm TCE (Jaspers et al, 1993). Mid-frequency hearing loss only, as opposed to low- or high-frequency loss, was reported in rats exposed to 3,500 to 4,000 ppm TCE over a 5-day period (Crofton et al, 1994; Crofton & Zhao, 1993).

Cardiovascular

3.5.1)

A) WITH POISONING/EXPOSURE

1) Cardiac dysrhythmias (ventricular and atrial fibrillation), hypotension, conduction defects and myocardial injury have been noted.

3.5.2)

A) VENTRICULAR FIBRILLATION

1) WITH POISONING/EXPOSURE

a) Ventricular fibrillation may occur as a result of cardiac sensitization to endogenous catecholamines and is thought to be the cause of death in fatal exposure (Anon, 1974; Lewis, 2000).
b) CASE REPORT - Ventricular fibrillation and cardiac arrest were reported in a 15-year-old male who inhaled typewriter correction fluid. Serial electrocardiograms and subsequent stress echocardiogram findings were consistent with recent antero-apical subendocardial infarction. The patient was discharged 4 days after admission (Wodka & Jeong, 1991).

B) ATRIAL FIBRILLATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Atrial fibrillation, beginning within 12 hours of admission to the emergency department and resolving over 2 days, occurred in a 35-year-old male after intentional TCE inhalation (Szlatenyi & Wang, 1994).
b) CASE REPORT - A 17-year-old male developed sinus tachycardia with intermittent atrial flutter after ingesting 70 mL of TCE. Dysrhythmia developed approximately 20 hours after ingestion and persisted for 5 days (Bruning et al, 1998).

C) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension and first-degree heart block have been reported after ingestion of TCE (Wells, 1982; Perbellini et al, 1991).
b) CASE REPORT - Hypotension with sinus rhythm and hydrocarbon pneumonitis were reported in an 83-year-old woman after an intentional ingestion of spot remover containing TCE (Lumpe, 1993).
c) CASE REPORT - Hypotension and sinus tachycardia occurred in a man after ingesting an unknown amount of trichloroethylene in a suicide attempt (Vattemi et al, 2005).

D) ELECTROCARDIOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) Bradycardia, occasional premature contractions and, in a few cases, a rapid irregular pulse have been reported as ECG changes during TCE anesthesia (Barnes & Ives, 1944; Gutch et al, 1965).

1) CASE REPORT - Prolongation of PR interval (0.26 seconds) occurred after an ingestion of nearly 5 ounces of TCE in a 22-year-old (Stentiford & Logan, 1956).

b) CASE REPORT - Hypotension and sinus tachycardia occurred in a man after ingesting an unknown amount of trichloroethylene in a suicide attempt. He developed ventricular bigeminy after 4 days of hospitalization. He died of complete heart block 24 days post-ingestion (Vattemi et al, 2005).

E) ECTOPIC BEATS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Atrioventricular extrasystoles have been reported after ingestion of an unknown amount of TCE (Perbellini et al, 1991).
b) CASE REPORT - After ingesting a liter of 90 percent TCE, a 70-year-old female was admitted to the ED with several extrasystolic beats and normal ECG. By the second day, the patient developed bigeminy followed by junctional rhythm. Treatment with esmolol resolved the abnormal dysrhythmia without recurrence of ESV (Moritz et al, 2000).

F) HEART FAILURE

1) CASE REPORT - Severe heart failure was reported in a 16-year-old male who died after inhalational exposure to plastic cement containing TCE (Gosselin et al, 1984).

G) SINUS TACHYCARDIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Sinus tachycardia and hypotension occurred in a man after ingesting an unknown amount of trichloroethylene in a suicide attempt (Vattemi et al, 2005).

3.5.3)

A) ANIMAL STUDIES

1) BRADYCARDIA

a) RATS exposed to high vapor concentrations of TCE experienced bradycardia and bradyarrhythmias during the recovery period. It is suggested that hypoxia triggers increased cardiac vagal efferent tone, which in turn stimulates the arrhythmias accompanying apnea during paradoxical sleep (Arito et al, 1993).

Respiratory

3.6.1)

A) WITH POISONING/EXPOSURE

1) Respiratory depression, cyanosis, pulmonary hemorrhages and edema have been reported after exposure to TCE.

3.6.2)

A) ACUTE RESPIRATORY INSUFFICIENCY

1) WITH POISONING/EXPOSURE

a) Respiratory depression resulting in cyanosis is common (Derobert, 1952).

B) PULMONARY HEMORRHAGE

1) WITH POISONING/EXPOSURE

a) Pulmonary hemorrhage and edema have been reported (Koch, 1931; Patel, 1973).

C) DYSPNEA

1) WITH POISONING/EXPOSURE

a) Bronchial irritation and shortness of breath from TCE inhalation exposure have been reported (Anderssen, 1957; McCarthy & Jones, 1983).

D) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary edema and severe dyspnea were reportedly caused by the decomposition products phosgene and dichloroacetyl chloride, created by welding in the presence of TCE (Sjogren et al, 1991; Selden & Sundell, 1991).
b) CASE REPORT - Mild pulmonary edema was found at autopsy in a 24-year-old male occupationally exposed to high concentrations of TCE over several hours (Ford et al, 1995).
c) CASE REPORT - A 24-year-old male developed hypoxia after inhalational exposure to TCE at greater than 3000 ppm for one hour. Chest x-ray and CT demonstrated a left upper lobe infiltrate. Biopsy of this area noted bronchial mucosal edema, intra-alveolar RBC's and vacuolation of type II pneumocytes (Morimatsu et al, 2006).

E) PNEUMONIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Accidental occupational inhalation exposure to TCE resulted in mild respiratory acidosis (pH, 7.3; PCO2, 53.1 mm Hg) and pneumonia of the lower lobes in a 36-year-old male (Kostrzewski et al, 1993).

F) ACUTE RESPIRATORY FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A man presented with a Glasgow Coma Scale rating of 3, hypotension, sinus tachycardia, severe diarrhea, and acute respiratory failure after ingesting an unknown amount of trichloroethylene in a suicide attempt. He developed ventricular bigeminy after 4 days of hospitalization. He died of complete heart block 24 days post-ingestion (Vattemi et al, 2005).

3.6.3)

A) ANIMAL STUDIES

1) PULMONARY FIBROSIS

a) MICE - Pulmonary fibrosis was detected initially 15 days after acute exposure and progressing for the 3 months of study, in mice treated with a single dose of 2,000 mg/kg IP (Forkert & Forkert, 1994).

Neurologic

3.7.1)

A) WITH POISONING/EXPOSURE

1) CNS depression, lightheadedness, dizziness and euphoria, particularly after inhalation, have been noted. Trigeminal nerve impairment has been reported in individuals chronically and acutely poisoned by TCE.
2) CNS depression, tremor and motor restless may occur after ingestion.
3) Multiple nerve palsies and peripheral neuropathy have been reported after intoxication.

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) Ingestion and inhalation will produce central nervous system depression, coma, visual disturbances, mental confusion, ataxia, dizziness, loss of coordination and fatigue (McCunney, 1988; Stentiford & Logan, 1956; McCarthy & Jones, 1983; Szlatenyi & Wang, 1994; Moritz et al, 2000; Bruning et al, 1998).

1) Exposure levels above 100 ppm are associated with adverse effects that include restlessness, impaired concentration, irritability and euphoria (Feldman, 1979).
2) CASE REPORT - After 20 years of occupational dermal and inhalation exposure, a 62-year-old male experienced residual effects of peripheral paresthesias, headaches, vertigo, lassitude and forgetfulness (Kohlmuller & Kochen, 1994).
3) Kilburn (2002) reported subtle deficits on neuropsychiatric testing in individuals exposed to TCE in drinking water. Water concentrations of TCE varied from less than 0.2 ppb to greater than 10,000 ppb. This study did not attempt to determine a dose-response relationship between degree of exposure and neuropsychiatric testing results. No biomarkers of exposure were obtained. Results were further confounded by the fact that many of the subjects were concurrently involved in litigation concerning TCE water contamination (Kilburn, 2002).

B) TOXIC ENCEPHALOPATHY

1) WITH POISONING/EXPOSURE

a) CASE SERIES/CHRONIC - As a result of a cohort study of 99 metal degreasing workers, it was determined that chronic toxic encephalopathy after long-term occupational exposure to TCE was present in a significant number of subjects (Rasmussen et al, 1993) Rasmussen et al, 1993a).

C) NEUROPATHY

1) WITH POISONING/EXPOSURE

a) GENERAL - Multiple nerve palsies and peripheral neuropathy have been noted after TCE intoxication (NIOSH, 1973; Joron et al, 1955).
b) INTENTIONAL

1) CASE REPORT - A patient developed palsies of the third, fifth and sixth cranial nerves after intentional exposure to TCE (Szlatenyi & Wang, 1996).
2) CASE REPORT - A 35-year-old man developed palsies of the left third cranial nerve and bilateral sixth cranial nerves, as well as substantial ataxia, after inhaling TCE for 3 days (Szlatenyi & Wang, 1994).

c) OCCUPATIONAL

1) CASE REPORT - Industrial exposure to TCE presenting as MULTIPLE SCLEROSIS has been reported. Symptoms included vertigo, left facial numbness, nausea, fatigue, tinnitus, hearing loss, nystagmus and ataxia (Noseworthy & Rice, 1988).
2) Peripheral myelinopathy, sensory and motor, is linked with TCE exposure (Goldfrank, 1998).
3) Occupational exposure to TCE results in a cranial nerve syndrome, especially trigeminal, with loss of facial sensation and difficulty chewing (Goldfrank, 1998).
4) DEAFNESS - Bilateral, symmetrical sixth cranial nerve deafness has been reported with TCE exposure (NIOSH, 1973).
5) Some evidence indicates that TCE decomposition products or impurities may be responsible for cranial nerve injuries, producing palsies of the oculomotor and trigeminal nerves and optic neuropathy (Grant & Schuman, 1993) Cavanaugh & Buxton, 1989; (Feldman et al, 1988).

D) DRUG DEPENDENCE

1) WITH POISONING/EXPOSURE

a) Inhalation may result in euphoria and addiction (JEF Reynolds , 2000).

E) NEURALGIA

1) WITH POISONING/EXPOSURE

a) INTENTIONAL

1) CASE REPORT - Damage to the trigeminal nerve was diagnosed with trigeminal potentials evoked by infraorbital nerve stimulation in a patient exposed to 15 minutes of TCE-contaminated air (Leandri et al, 1995).

b) OCCUPATIONAL

1) TRIGEMINAL NERVE IMPAIRMENT - Clinical hypesthesia of the trigeminal nerve has been noted in some individuals suffering from chronic poisoning (Mitchell & Parsons-Smith, 1969; Buxton & Hayward, 1967); tests of somatosensory evoked potential seem to be useful in assessing chronic intoxication caused by TCE (Barret et al, 1982; Arezzo, 1985).

F) MULTIPLE SCLEROSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Progressive systemic sclerosis was associated with dermal exposure to TCE of 2.5 hours' duration in a 47-year-old previously healthy woman (Lockey et al, 1987).

G) HEADACHE

1) WITH POISONING/EXPOSURE

a) Headache has been reported (Derobert, 1952).

H) TREMOR

1) WITH POISONING/EXPOSURE

a) Resting tremor may occur (McCunney, 1988). Bruning et al (1998) reported tremors and motor restlessness, lasting about 18 hours, in a 17-year-old male after he ingested approximately 70 mL TCE.

I) SPASM

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 46-year-old worker developed carpal spasm of 6 weeks' duration after cleaning a vapor degreaser. He wore an air-purifying respirator during the cleaning procedure, which took about 1 hour to complete (McCunney, 1988).

J) COMA

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 70-year-old female was admitted to the emergency department in a coma (Glasgow coma scale of 7) after she ingested 1 liter of 90% TCE (Moritz et al, 2000).
b) CASE REPORT - Deep coma lasting 3 days was reported after ingestion of an unknown quantity of TCE (Perbellini et al, 1991).
c) CASE REPORT - A man presented with a Glasgow Coma Scale rating of 3 after ingesting an unknown amount of trichloroethylene in a suicide attempt (Vattemi et al, 2005).

K) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) CNS depression is common after acute TCE exposure (Barceloux & Rosenberg, 1990; Clayton & Clayton, 1981; Moritz et al, 2000).
b) INTENTIONAL - Inhalation of high concentrations causes narcosis and anesthesia. A form of addiction has been observed in exposed workers. Prolonged inhalation of moderate concentrations causes headache and drowsiness (Lewis, 2000).
c) CASE REPORT - Unconsciousness resulted from an accidental occupational acute overexposure (Kohlmuller & Kochen, 1994).
d) CASE REPORT - Ingestion of an unknown quantity of TCE produced lethargy and incoherence in a 52-year-old female (Sottili et al, 1993).

L) CEREBRAL EDEMA

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Edema of the brain was noted at autopsy in a 24-year-old male exposed to high concentrations (7500 to 10,000 ppm) of TCE over several hours (Ford et al, 1995).

M) NEUROLOGICAL DEFICIT

1) WITH POISONING/EXPOSURE

a) Long-term exposure to low levels of TCE (equal or less than 5 ppb) has been associated with neurobehavioral deficits. A strong interaction between exposure to TCE and alcohol consumption in the induction of neurobehavioral deficits has also been found (Reif et al, 2003).
b) Results of neuropsychological tests of groups of people exposed to TCE have indicated that whose who were younger at the time of exposure demonstrated deficits in a larger variety of subjects than those who were older; language deficits in particular were found in younger rather than older subjects (White et al, 1997).

3.7.3)

A) ANIMAL STUDIES

1) VESTIBULAR DISORDER

a) RATS - TCE caused a dose-related decrease in ability of visual suppression. During exposure of rats to TCE, the duration of post-stimulatory nystagmus was prolonged. TCE lessened the ability to cancel nystagmus with vestibular stimulation. The effects on eye movements indicate a site of toxicity within the cerebellar-vestibular system (Niklasson et al, 1993).

2) RETINAL DISORDER

a) RABBITS - Chronic exposure of rabbits to TCE evoked significant increases in the amplitudes of a- and b-waves on electroretinogram readings with corresponding decreases in the amplitude of oscillatory potentials. These changes reversed to baseline 6 weeks after discontinuation of exposure (Blain et al, 1994).

3) EEG ABNORMAL

a) RATS exposed to high vapor concentrations (3,000 and 6,000 ppm) had abnormal EEG activity and inability to maintain posture during exposure (Arito et al, 1993).

Gastrointestinal

3.8.1)

A) WITH POISONING/EXPOSURE

1) Nausea, vomiting, salivation, loss of taste, anorexia, abdominal pain, diarrhea and dysphagia have all been linked with exposure to TCE. Fatal abdominal compartment syndrome was reported in one adult.

3.8.2)

A) VOMITING

1) WITH POISONING/EXPOSURE

a) Gastric pain and vomiting were reported after inhalation exposure to TCE (Derobert, 1952; (McCarthy & Jones, 1983; Kohlmuller & Kochen, 1994). Nausea, vomiting, abdominal pain and diarrhea may occur after ingestion (Hayes & Laws, 1991; Moritz et al, 2000).

B) DYSPHAGIA

1) WITH POISONING/EXPOSURE

a) Dysphagia has been reported in workers exposed to TCE (Lawrence & Partyka, 1981; Grant & Schuman, 1993).
b) CASE REPORT - Difficulty in swallowing and hypersalivation occurred in three coal miners accidentally poisoned by TCE subjected to decomposition in closed circuit oxygen respirators (Grant & Schuman, 1993).

C) TASTE SENSE ALTERED

1) WITH POISONING/EXPOSURE

a) Loss of taste and anorexia have been noted (Mitchell & Parsons-Smith, 1969) McCunny, 1988).

D) PNEUMATOSIS CYSTOIDES INTESTINALIS

1) WITH POISONING/EXPOSURE

a) There are reports associating primary pneumatosis cystoides intestinalis with exposure to TCE before the onset of the disease. No cause-and-effect relationship could be established (Yamaguchi et al, 1985; Sato et al, 1987).

E) ABDOMINAL COMPARTMENT SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 47-year-old woman with a history of severe anorexia nervosa (weight 33 kg; height 149 cm) intentionally ingested benzodiazepines and 500 mL of trichloroethylene and developed respiratory failure, coma and abdominal compartment syndrome (ACS). She rapidly developed shock and multiple organ failure as noted by an increase in abdominal perfusion pressure of 20 mmHg (ACS is defined as intra-abdominal pressures of greater than 20 mmHg with at least one organ failure). The patient developed abdominal distension leading to worsening multiple organ failure and surgical decompression was attempted. A CT scan indicated abdominal perforation. Life sustaining treatments were withdrawn after a laparotomy indicated small bowel and right colon diffuse ischemia. The patient died approximately 12 hours after ingestion (Liotier et al, 2008). The authors concluded that the persistent increase in intra-abdominal pressure impaired splanchnic blood flow and capillary perfusion and induced multiorgan failure dysfunction.

Hepatic

3.9.1)

A) Liver injury has been reported.

3.9.2)

A) LIVER DAMAGE

1) WITH POISONING/EXPOSURE

a) GENERAL - Acute hepatic damage has been reported infrequently and usually only after massive exposure (AMA, 1985; Joron et al, 1955; James, 1963).
b) CASE REPORT - Increased liver enzymes, transaminases and alkaline phosphatase, with normal bilirubin, were reported after an acute exposure to TCE fumes. Levels returned to normal in 6 weeks (Balakrishnan et al, 1993).
c) CASE REPORT - Increased liver enzyme levels, with no cholestasis, was reported in a metal degreaser one month after beginning his job, which involved dermal contact with TCE. Hepatitis tests were all negative (Bond, 1995).
d) CASE REPORT - A 27-year-old man with a history of volatile substance abuse was diagnosed with acute liver failure (liver enzymes peaked at: AST 11475 International Units/L and ALT 4938 International Units/L) after inhaling tubes of glue containing trichlorethylene. Gas chromatography analysis of urine was positive for trichloroacetate, a metabolite of trichloroethylene. His hospital course was complicated by severe coagulopathy and DIC. Although plasma exchange, continuous hemodiafiltration and blood products improved liver and hematologic function, progressive brain edema and acute renal failure occurred. Six days after admission, an EEG showed flat waves, as well as the absence of light reflexes; treatment was withdrawn and the patient died the following day (Takaki et al, 2008). Although viral hepatitis was excluded in this patient, the possibility of other toxins was not adequately evaluated.

B) TOXIC HEPATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A female patient developed hepatitis after exposure to TCE; her symptoms improved and liver function tests returned to baseline within 3 months of removal from exposure (Chittasobhaktra et al, 1997).
b) CASE REPORT - A 28-year-old man developed hepatitis that was associated with the use of TCE in a small, unventilated, basement room. Other causes of hepatitis were ruled out. A urinary trichloroacetic acid level, at 6 months after the hepatitis, by 24 hour collection, was 9 mg/L (McCunney, 1988).
c) Hepatitis has also been reported after TCE anesthesia (Herdman, 1945).
d) CASE REPORT - A 48-year-old woman developed anicteric hepatitis after chronic (several years) occupational exposure to TCE vapor (550 ppm). The patient slowly recovered over a 6-week TCE-free period (Schattner & Malnick, 1990).
e) CASE REPORT - A 55-year-old male presented with anorexia, fatigue, upper abdominal discomfort, and markedly elevated liver enzymes. He was working as a shoemaker during the last 6 years using a glue containing 1,1,1-trichloroethylene (TCE) in a small unventilated basement room. Liver biopsy revealed centrilobular necrosis with portal inflammation and moderate portal fibrosis. The patient was removed from the TCE exposure source and 3 months later he was feeling well and liver enzymes were within normal limits. At 6 months, a second liver biopsy was performed and hepatic histology was markedly improved (Anagnostopoulos et al, 2004).
f) Hepatitis, jaundice, hepatomegaly or hepatosplenomegaly have been reported in patients with generalized exfoliative dermatitis similar to Stevens-Johnson syndrome after exposure to trichloroethylene. Patients with the slow acetylator genotype for N-acetyltransferase may be at increased risk for this type of reaction (Nakajima et al, 2003).

C) FULMINANT HEPATIC FAILURE

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE - A 24-year-old woman developed hepatomegaly and Stevens-Johnson syndrome following 5 weeks of occupational exposure to TCE. She died of fulminant hepatic failure approximately one month later (Pantucharoensri et al, 2004).

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) INCREASED BILE ACIDS - Hamdan & Stacey (1993) have demonstrated a correlation of increasing bile acids with increasing TCE serum levels, both peaking at 4 hours in rats given 1 mmol/kg TCE intraperitoneally. By 16 hours, bile acid levels had returned to normal and TCE levels were no longer detectable. TCE possibly interferes with the transport mechanisms and uptake of bile acids by isolated hepatocytes (Bai & Stacey, 1993).
b) HEPATIC OXIDATIVE STRESS - TCE-induced hepatotoxicity in mice may be related to increased liver microsome oxygen consumption, b-nicotinamide adenine dinucleotide reduced form (NADPH) oxidation and production of malondialdehyde in liver microsomes (Atkinson et al, 1993).

Genitourinary

3.10.1)

A) WITH POISONING/EXPOSURE

1) Renal failure may occur after oral or inhalation exposure to TCE.

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) GENERAL:Acute tubular necrosis and renal failure may follow oral or respiratory exposure (Gutch et al, 1965; JEF Reynolds , 2000; David et al, 1989). An acute single ingestion resulted in selective renal tubular damage (increased urinary excretion of alpha-1- and beta-2-microglobulin and beta-N-acetyl-glucosaminidase) (Bruning et al, 1998). A case of acute renal tubular degeneration after intentional inhalation of spot remover was reported (Gosselin et al, 1984).

B) RENAL TUBULAR DISORDER

1) WITH POISONING/EXPOSURE

a) Persistent changes to the proximal tubules can result from chronic exposure to high doses of TCE (Bruning et al, 1999).

C) TOXIC NEPHROPATHY

1) WITH POISONING/EXPOSURE

a) In one study, the nephrotoxic potential of trichloroethylene was investigated among occupationally exposed workers, using sensitive urinary markers (eg; N-acetylglucosaminidase (NAG), albumin, formic acid) of kidney damage. In workers exposed to trichloroethylene 250 ppm or lower, no evidence of kidney damage was found. However, dose dependent increases in urinary formate, methyl-malonate, and glutathione transferase alpha suggested that trichloroethylene can impair folate metabolism, causing a urinary acidosis which could result in kidney damage at high exposure levels (greater than 250 ppm) (Green et al, 2004).
b) CASE REPORT - Urine collected 36 to 40 hours after ingestion of 70 mL TCE in a 17-year-old male contained elevated levels albumin, microglobulins and beta-NAG; these findings indicated renal tubule damage. However, the patient had normal urine output and serum creatinine and BUN levels following ingestion (Bruning et al, 1999).

D) NEOPLASM OF KIDNEY

1) WITH POISONING/EXPOSURE

a) A retrospective study of 169 workers in a cardboard factory found a statistically significant increased incidence of renal cell tumors in workers exposed to TCE (Henschler et al, 1995). Subsequent studies have shown mixed results. Long term follow-up of workers exposed to TCE found no overall increased rates of renal cancer (Hansen et al, 2001; Blair et al, 1998). A large epidemiologic study of TCE exposed workers found no statistically-significant increase in renal cancer. However, a slight increase was observed in a more highly exposed subcohort (Raaschou-Nielsen et al, 2003). Similarly, another study found no statistically significant increases in renal cancer in TCE exposed workers, but an increased risk was found in the subpopulation with the highest exposure level (Charbotel et al, 2006).

E) IMPOTENCE

1) CASE REPORT - A 42-year-old man developed gynecomastia and impotence after prolonged exposure to TCE (Barlow & Sullivan, 1982).

F) LACK OF EFFECT

1) CASE SERIES - 31 healthy metal workers were tested for urinary levels of the tubular enzyme N-acetyl-B-D-glucosaminidase after low level occupational exposure to TCE. No significant increases of this enzyme were found. The authors concluded that TCE does not seem to be nephrotoxic at low-level exposures (Selden et al, 1993).

3.10.3)

A) ANIMAL STUDIES

1) TOXIC NEPHROPATHY

a) In one animal study, it was reported that trichloroethanol, the major metabolite of trichloroethylene, can impair folate metabolism, causing urinary acidosis and kidney damage (Green et al, 2003).

Hematologic

3.13.3)

A) ANIMAL STUDIES

1) ANEMIA APLASTIC

a) Aplastic anemia and hemorrhaging was reported in cattle after ingestion of TCE-extracted soybean oil meal (Goeptar et al, 1995).

Dermatologic

3.14.1)

A) WITH POISONING/EXPOSURE

1) TCE is mildly irritating to the skin. Defatting dermatitis can occur after contact with the liquid. Higher concentrations, including vapor exposure, may result in chemical burns. Chronic exposure may produce rash, dry skin, and scleroderma. Chemical burns have been reported with concentrated exposure to TCE vapors. Stevens-Johnson syndrome has been described following TCE exposure.

3.14.2)

A) DERMATITIS

1) WITH POISONING/EXPOSURE

a) TCE is mildly irritating to the skin and prolonged contact may give rise to eczema and dermatitis (Anon, 1974).
b) Direct dermal contact results in a burning sensation within 3 to 18 minutes; this becomes more severe immediately after removal from exposure, with tingling persisting for as much as 30 minutes. Erythema persists for 2 hours (Hayes & Laws, 1991).
c) Contact with the liquid defats the skin causing dermatitis. Although it is absorbed through the skin, dermal absorption is not likely to be significant if dermatitis is prevented (ACGIH, 1986).
d) CASE REPORT - A female patient developed generalized dermatitis after exposure to TCE; her symptoms improved within 3 months of removal from exposure. A TCE-induced immunologic reaction was believed to be the pathological process responsible (Chittasobhaktra et al, 1997).
e) Chronic use may produce rough, chapped skin (Clayton & Clayton, 1981).

B) FLUSHING

1) WITH POISONING/EXPOSURE

a) 'Degreaser's flush', a transient face and neck erythema (vasodilation), is accompanied by a feeling of fullness in the chest, with dyspnea and a feeling of malaise; although transient, it may recur when alcohol is consumed (Baxter et al, 2000; Waters et al, 1977; Stewart et al, 1974).

C) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 44-year-old male experienced second-degree partial-thickness burns on 25 percent of his body surface after acute exposure to TCE fumes. These areas proved to be acidic when tested for pH. Satisfactory healing occurred after hydrotherapy, fluids, and dressings (Balakrishnan et al, 1993).
b) CASE REPORT - Second-degree chemical burns were reported on the cheeks, shoulder, neck and back of a 70-year-old woman after intentional ingestion of and splash injuries from a 90 percent TCE solution (Moritz et al, 2000).
c) CASE REPORT - A 36-year-old woman lost consciousness and collapsed over the grill of a degreasing apparatus containing TCE. She was exposed to an unknown concentration of TCE vapor for 5 minutes. She sustained full thickness burns involving 22% BSA and died 13 days later. The report notes that initial burn assessment was difficult since no skin discoloration was present, only changes in texture (Thorburn et al, 2004).

D) GENERALIZED EXFOLIATIVE DERMATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Exfoliative dermatitis occurred on two separate occasions after inhalational exposure to TCE in a 29-year-old male (Goh & Ng, 1988).
b) CASE REPORT - A 21-year-old male developed exfoliative dermatitis with mucous membrane involvement, fever and liver dysfunction associated with occupational exposure to TCE. A positive patch-test reaction to TCE and trichloroethanol was obtained (Nakayama et al, 1988).
c) CASE REPORT - A 30-year-old metal degreaser experienced a sensitization to TCE, evidenced as an exfoliative dermatitis, a diffuse, blanching rash and 27 percent eosinophilia (Bond, 1995).
d) CASE REPORT - A 24 -year-old woman developed hepatomegaly and Stevens-Johnson syndrome following 5 weeks of occupational exposure to TCE. The patient died of fulminant hepatic failure approximately one month later (Pantucharoensri et al, 2004).
e) In a review of published cases of generalized skin reactions to trichloroethylene, many cases were accompanied by hepatitis, jaundice, hepatomegaly or hepatosplenomegaly and appeared to be clinically similar to Stevens-Johnson syndrome. Many of these patients were found to have the slow acetylator genotype of N-acetyltransferase (NAT) 2, suggesting that this genotype may increase susceptibility to trichloroethylene-induced generalized skin reactions (Nakajima et al, 2003).

E) SYSTEMIC SCLEROSIS

1) WITH POISONING/EXPOSURE

a) Occupational exposure to TCE is reportedly a possible cause of scleroderma-like disorder (Zenz, 1994).
b) CASE REPORT - A case of scleroderma was reported after a 2-year history of occupational inhalation exposure to TCE in a 26-year-old female. Morphea-like plaques developed on her arms and ankles. Scleroderma was confirmed from a skin biopsy (Czirjak et al, 1994).

F) ERUPTION

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A worker exposed to TCE during degreasing developed, along with flu-like symptoms, dry skin, a red rash with bumps, peeling face and itching, over the month following the exposure. He subsequently developed a red diffuse rash upon returning to work weeks later, and during the following few days away from work the rash continued and peeled. Sensitization to TCE or one of its metabolites was believed to be responsible (Bond, 1996).

Musculoskeletal

3.15.1)

A) WITH POISONING/EXPOSURE

1) Diffuse fasciitis with eosinophilia has been reported after chronic ingestion.
2) Systemic sclerosis has been described after occupational exposures.

3.15.2)

A) DISORDER OF TENDON

1) WITH POISONING/EXPOSURE

a) CASE REPORT/CHRONIC - Diffuse fasciitis with eosinophilia (Shulman syndrome) was reported in a 63-year-old female after 6 years of drinking TCE-contaminated water. The main signs and symptoms included skin thickening, synovitis and increased eosinophils. Improvement of all symptoms occurred within several weeks of discontinuation of exposure. A second case of eosinophilic fasciitis was reported resulting from occupational exposure to TCE (Waller et al, 1994).

B) MUSCULOSKELETAL FINDING

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Skeletal muscle damage occurred in a man after ingesting an unknown amount of trichloroethylene in a suicide attempt. He presented 3 hours after the ingestion to the hospital with a Glasgow Coma Scale rating of 3, hypotension, sinus tachycardia, severe diarrhea, and acute respiratory failure. He developed ventricular bigeminy after 4 days of hospitalization. In addition, serum creatine kinase (peak level greater than 10,000 IU/L) and lactate dehydrogenase levels were elevated. On the 17th day, a muscle biopsy revealed abnormalities of lipid storage and mitochondrial degeneration. He died of complete heart block 24 days post-ingestion (Vattemi et al, 2005).
b) CASE REPORT/CHRONIC - Systemic sclerosis was identified at autopsy in a 62-year-old female after a 2-year occupational exposure to TCE. A speckled antinuclear antibody staining pattern on HEp-2 cell monolayers was present. Symptoms before death included Raynaud's phenomenon, acrosclerosis, joint symptoms, esophageal involvement, renal dysfunction, congestive heart failure and thrombocytopenia (Czirjak et al, 1993).

C) PARALYSIS

1) Extraocular muscle palsies have been reported historically. Oculomotor paralysis sometimes accompanies trigeminal palsies (Grant & Schuman, 1993).

Endocrine

3.16.1)

A) WITH POISONING/EXPOSURE

1) Menstrual irregularities and possible anovulation were reported after occupational exposure to TCE vapor.

3.16.2)

A) DISORDER OF MENSTRUATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Menstrual irregularities occurred in a 20-year-old woman after an exposure in the workplace to a high concentration of TCE vapor. Basal body temperature indicated lack of ovulation (Barlow & Sullivan, 1982).

Immunologic

3.19.1)

A) WITH POISONING/EXPOSURE

1) Symptoms of systemic lupus erythematosus have been reported after chronic exposures.
2) Eosinophilia has been reported after acute exposures.

3.19.2)

A) DRUG-INDUCED LUPUS ERYTHEMATOSUS

1) WITH POISONING/EXPOSURE

a) Chronic exposure to TCE from contaminated well water has resulted in symptoms of systemic lupus erythematosus and the presence of positive ANA (Kilburn & Warshaw, 1992).

B) EOSINOPHIL COUNT RAISED

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Eosinophilia and increased platelets occurred in a 44-year-old male after acute exposure to TCE vapors. He also sustained second-degree burns over 25 percent of his body surface (Balakrishnan et al, 1993).
b) CASE REPORT - A metal degreaser experienced a sensitization to TCE with 27 percent eosinophilia and a diffuse, blanching rash (Bond, 1995).
c) CASE REPORT - Diffuse fasciitis with eosinophilia (Shulman syndrome) is reported in a 63-year-old female after 6 years of drinking TCE-contaminated water (Waller et al, 1994).

C) IMMUNE SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) One study evaluated possible quantitative changes of two type-1 cytokines (IL-2, INF-gamma) and one type-2 cytokine (IL-4) in workers occupationally exposed to TCE. The occupational exposure of 3 groups of workers [workers exposed in the degreasing process (group A; n=35), workers doing other work in the same factory (group B; n=30), and non-exposed office workers (group C; n=40)] was evaluated by measuring TCE in the breathing zone and urinary trichloroacetic acid (TCA). Group A workers had a mean urinary TCA concentration of 13.3 +/- 5.9 mg/g creatinine and were exposed to a mean environmental TCE level of 35 +/- 14 mg/m(3); group B workers had urinary TCA levels of 0.2 +/- 0.02 mg/g creatinine. A significant increase in type-1 cytokines (IL-2 and INF-gamma) levels and a reduction in type-2 cytokine (IL-4) levels were observed in group A subjects compared with those in groups B and C (Iavicoli et al, 2005).

3.19.3)

A) ANIMAL STUDIES

1) IMMUNE SYSTEM DISORDER

a) MICE - TCE-induced autoimmunity was demonstrated in female mice administered IP injections of TCE. Both TCE and its metabolite, dichloroacetyl chloride (DCAC), were capable of inducing or accelerating autoimmune responses as shown by measurement of autoimmune antibodies (anti-nuclear, anti-ssDNA, and anti-cardiolipin) (Khan et al, 1995).

Reproductive

3.20.1)

A) Although some studies have found birth defects and spontaneous abortions related to exposure to TCE, most involved concomitant confounding exposure to other chemicals. It does cross the placenta. Abnormal sperm morphology has occurred after exposure.
B) Many laboratory animal studies have shown that TCE does not adversely affect fertility or embryo implantation and survival, and does not cause teratogenic effects. TCE has, however, been shown to produce some developmental abnormalities. Reversible suppression of male copulation was shown in a few studies.

3.20.2)

A) CONGENITAL ANOMALY

1) There is one unconfirmed report of five cases of sacral agenesis in offspring of mothers exposed to mixed industrial solvents, including TCE; two other cases of multiple malformations have also been linked to TCE exposure (Schardein, 2000).
2) Many case reports have associated birth defects with maternal exposure to mixtures containing TCE, toluene, 1,1-dichloroethane, methyl chloride, acetone and other chemicals. Exposure levels and other details are lacking in many of these reports. The specific contribution of TCE to observed birth defects cannot be determined (Barlow & Sullivan, 1982; Schardein, 2000).
3) A study reviewed by the ATSDR (1992) evaluated reproductive outcomes in workers exposed to TCE. The actual TCE concentrations were not determined, and there were co-exposures to other reproductively toxic chemicals. This study involving 2,000 individuals exposed to TCE in the workplace found no increased risk of birth defects among the offspring.
4) Another study reported developmental defects (nervous system, oral cleft anomalies) and an increased likelihood of developing childhood leukemia in infants born to parents exposed to water contaminated with 267 ppb TCE and other solvents (Lagakos et al, 1986). The overall conduct of the study and data interpretation have been questioned (ATSDR, 1992). As a result, no definitive conclusion regarding the contribution of TCE to adverse reproductive effects can be made.

B) HEART MALFORMATION

1) Goldberg et al (1990) reported an association between parental exposure to drinking water contaminated with TCE (concentration range, 6 to 239 ppb) and congenital heart disease. Mothers exposed to the contaminated water during the first trimester were three times more likely to have children with congenital heart disease than were non-exposed mothers.

a) However, a direct cause and effect relationship could not be established, as the drinking water contained other potentially toxic chemicals in addition to TCE, and the study had additional methodological problems. Thus, the birth defects could not be conclusively attributed to TCE exposure.

2) A review of epidemiologic and laboratory studies in the published literature reported that the evidence in these studies does not support the hypothesis that trichloroethylene or dichloroethylene are selective developmental toxins in general or cardiac teratogens, specifically (Hardin et al, 2005).

a) Another review of epidemiologic data also concluded that there was no conclusive link between maternal TCE exposure and congenital heart defects (Watson et al, 2006).

C) ANIMAL STUDIES

1) CONGENITAL ANOMALY

a) Exposure of female rats to TCE by inhalation during pregnancy resulted in musculoskeletal system, urogenital system, and other developmental abnormalities; oral exposure led to developmental abnormalities of the central nervous system and behavioral effects in the newborn (RTECS , 2002).
b) Significant increases (compared with untreated controls) of incomplete sternum ossification and displacement of the ovary were found in the offspring of rats exposed only during pregnancy; these were considered developmental delays in maturation rather than teratogenicity, however (Dorfmueller et al, 1979).

1) The biological significance of these developmental defects has been questioned, as untreated control animals had higher rates of these defects than offspring of animals treated with TCE before pregnancy (Barlow & Sullivan, 1982).

c) A similar study was reported by Healy et al (1982). Delays in fetal maturation (impaired skeletal ossification, reduced fetal weight), but no teratogenic effects, were noted in the offspring of rats exposed to TCE.
d) Five aliphatic chlorinated hydrocarbons were tested for teratogenic potential in fertilized chicken eggs. The following decreasing order of potential was found (Elovaara et al, 1979).

1) 1,1,1-Trichloroethane
2) Trichloroethylene
3) Methylene chloride
4) Tetrachloroethylene
5) 1,1,2-Trichloroethane
6) Olive oil (control)

2) HEART MALFORMATION

a) Cardiac malformations were seen in rat fetuses when the maternal rat was given the TCE metabolite trichloroacetic acid at a dose of 2,730 ppm in drinking water (Johnson et al, 1998).
b) Dawson et al (1993) found a significant increase in congenital cardiac abnormalities (10.5 percent) in fetuses of rats exposed during pregnancy to a high concentration of TCE in drinking water (1,100 ppm) compared with controls. Rats exposed to 1.5 ppm or 1,100 ppm for 61 to 76 days before pregnancy and during pregnancy had 8.2 and 9.2 percent, respectively, of fetal cardiac abnormalities. No noncardiac congenital abnormalities were detected in controls or TCE-treated rats.

3) LACK OF EFFECT

a) Animal studies have not found TCE to be particularly teratogenic or fetotoxic; it was not found to be teratogenic in mice, rats and rabbits (Dorfmueller et al, 1979; Land et al, 1981; Schardein, 2000; Schwetz et al, 1975).
b) No maternal toxicity or adverse effects on embryonic and fetal development were identified in a study in which female mice were given TCE during pregnancy. Up to 10 percent of the oral LD50 of TCE given by oral gavage on days 1 to 5, 6 to 10 or 11 to 15 of pregnancy failed to produce a maternal or reproductive adverse effect in female mice or their offspring (Cosby & Dukelow, 1992).
c) No significant abnormalities in the offspring were identified in a continuous breeding study involving mice and rats (George et al, 1990).
d) Exposure of female rats to TCE vapor before mating and/or during the first 20 days of pregnancy failed to produce embryotoxicity, fetotoxicity, teratogenicity or behavioral effects in the offspring (Dorfmueller et al, 1979).

3.20.3)

A) HYPOXIA

1) TCE has been used as an anesthetic in obstetrics. It may aggravate the normal acidosis and hypoxia of second stage of labor (Phillips & Macdonald, 1971).

B) PLACENTAL BARRIER

1) TCE rapidly crosses the placenta, with subsequent exposure of the fetus. In three of ten pregnancies, concentrations of TCE in umbilical venous blood (reflecting fetal blood concentrations) exceeded those in the maternal venous blood after 10 to 15 minutes of exposure to TCE (Trilene(R)) and nitrous oxide anesthesia (Laham, 1970; JEF Reynolds , 2000).

C) ABORTION

1) A case-control study (n=1926) examined the occurrence of spontaneous abortion in relation to self-reported exposure to solvents. Increased risk (greater than twofold) of spontaneous abortion was reportedly associated with exposure to TCE (Windham et al, 1991). Interpretation and application of the data from this study are limited due to methodological problems (poor recall, no actual exposure data, bias from telephone interview, limited control of other variables) and the absence of a dose-response relationship.
2) Another study examined the occurrence of medically diagnosed spontaneous abortion in relation to solvent exposure among female workers (Lindbohm et al, 1990). The risk of spontaneous abortion from exposure to TCE was low (odds ratio, 0.6). Poor recall of exposure and limited control of other variables limit the applicability of this study.
3) An increased number of miscarriages was reported in operating room nurses exposed to TCE and other chemicals (Corbett et al, 1974). These adverse effects cannot be definitively attributed to TCE, due to the known reproductive hazards of other agents present in operating rooms (such as nitrous oxide, ethylene oxide, other waste anesthetic gases and so on).

D) BIRTH WEIGHT SUBNORMAL

1) An association was found between maternal exposure to TCE in drinking water and very low birth weight (less than 1,501 grams); no association was found for low birth weight. However, this association was not statistically significant (OR 3.3, 95% CI 0.5, 20.6). No association was found for low birth weight (Rodenbeck et al, 2000).

E) ANIMAL STUDIES

1) FETOTOXICITY

a) Exposure of female rats to TCE by inhalation during pregnancy resulted in post-implantation mortality and fetotoxicity (RTECS , 2002).
b) Dose-related decreases in live litters per mating pair, and in live pups per litter, were identified in some groups in a continuous breeding study involving mice and rats (George et al, 1990).

2) LACK OF EFFECT

a) A test of dominant lethality in the mouse was negative. Male mice were exposed to TCE vapor for 24 hours before mating. Males were then mated with a different untreated female every 4 days for a total of 12 mating periods. No significant effects on pregnancy rate, or pre- or post-implantation losses were identified (Slacik-Erben et al, 1980).
b) There was no decrease in the number of embryos retrieved from the oviducts of female mice with TCE exposure during the early stages of embryonic development (Coberly et al, 1992). No significant defects in embryonic cell proliferation were observed in cells from treated female mice, compared with cells from untreated animals. An in vitro study showed that addition of TCE to rodent embryo cultures resulted in a dose-dependent decrease of embryonic growth (Irvin, 1989).
c) No significant effects on implantation sites, resorptions, litter size, fetal weight or development were observed in rats exposed to TCE during pregnancy. The period of TCE exposure was 7 hours/day, 7 days/week, from day 6 to day 20 of pregnancy (Barlow & Sullivan, 1982).

3.20.4)

A) ANIMAL STUDIES

1) Oral exposure of female rats to TCE during pregnancy produced effects on weaning or on the lactation index (RTECS , 2002).

3.20.5)

A) ANIMAL STUDIES

1) No decrease in fertility was identified in a continuous breeding study involving mice and rats (George et al, 1990).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS79-01-6 (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: Trichloroethylene
b) Carcinogen Rating: 1

1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

3.21.2)

A) Conflicting results have been obtained regarding the carcinogenicity of trichloroethylene in humans. As of 2014, IARC has classified trichlorethylene as Group 1 - carcinogenic to humans.

3.21.3)

A) SUMMARY

1) As of 2014, IARC has classified trichlorethylene as Group 1 - carcinogenic to humans (International Agency for Research on Cancer, 2015).

B) CARCINOMA

1) A case-control study conducted in Montreal, Canada of occupational exposures to any of 6 chlorinated solvents (carbon tetrachloride, methylene chloride, 1,1,1-trichloroethane, chloroform, trichloroethylene, and tetrachloroethylene) and association with cancer found an increased risk of prostate cancer with tetrachloroethylene exposure and an increased risk of melanoma with trichloroethylene exposure. The analysis that included 3730 cancer cases (occurring from 1979 to 1985) and 533 population controls focused on the following 11 cancer types: esophagus, stomach, colon, rectum, liver, pancreas, prostate, bladder, kidney, melanoma, and non-Hodgkin lymphoma. An association was observed between tetrachloroethylene exposure and risk of prostate cancer (odds ratio [OR], 2.2; 95% CI, 0.8 to 5.7 for any exposure and OR, 4.3; 95% CI, 1.4 to 13 for substantial exposure), as well as between trichloroethylene exposure and melanoma risk (OR, 3; 95% CI, 1.2 to 7.2 for any exposure and OR, 3.2; 95% CI, 1 to 9.9 for substantial exposure). There was also an association between substantial exposure to chlorinated alkenes (ie, trichloroethylene and tetrachloroethylene) in general and melanoma risk (OR, 2.6; 95% CI, 1 to 7.1). Substantial exposure was defined as a degree of confidence that the exposure actually occurred of probable or definite, a medium or high solvent concentration and frequency of exposure, and a duration of exposure that was greater than 5 years. While an association between substantial exposure to chloroform and risk of pancreatic cancer exists (OR, 10.6; 95% CI, 1.2 to 93), this was based on only 2 exposed workers. The majority of ORs were close to null or like the chloroform and pancreatic association, were based on very small numbers, thereby providing limited power to detect real risk (Christensen et al, 2013).
2) One cohort study (n=40,049) revealed an association between TCE exposure and non-Hodgkin's lymphoma. For the overall population, the incidence ratio was 1.2 (95% CI; 1.0, 1.5). For a subcohort with higher exposure, the incidence ratio was slightly elevated at 1.5 (95% CI; 1.2, 2.0). Although associations between TCE exposure and other cancers (eg, renal cell carcinoma, esophageal adenocarcinoma, liver and biliary tract cancer) were found, they were less consistent (Raaschou-Nielsen et al, 2003).

C) HEPATIC CARCINOMA

1) Historically, studies reviewed by the IARC (1997) failed to provide sufficient evidence of carcinogenicity with human trichloroethylene exposure; three cohort studies indicated a link with excess relative risk for cancer of the liver and biliary tract. No significant increases in cancer risk were found in seven reports reviewed by the ATSDR (1992). In several of these studies, small sample sizes and short follow-up periods limited the likelihood of successfully detecting cancer.
2) A cohort of 14,457 people who had worked in an aircraft maintenance facility for at least 1 year was followed for a 26-year period to assess mortality risk and causes of death. Increased biliary and liver cancer in white men who lived through 1980 was reported. Measures of trichloroethylene exposure, however, did not correlate with increased risk of cancer. Exposure to other chemicals was also possible (Spirtas et al, 1991).

D) PANCREATIC CARCINOMA

1) A meta-analysis of pancreatic cancer risk related to chlorinated hydrocarbon exposure noted a weak link for trichloroethylene. Relative risk was reported at 1.24, but with a 95% CI of 0.79 to 1.97 (Ojajarvi et al, 2001).

E) RENAL CARCINOMA

1) High and prolonged occupational exposure has been linked to renal cell carcinoma (Baxter et al, 2000).
2) CASE SERIES: In a retrospective cohort study of 169 males exposed to trichloroethylene for at least 1 year, a statistically significant higher incidence in renal cell tumors in cardboard-factory workers exposed to trichloroethylene than in a control group (Henschler et al, 1995). This study has been criticized, however, because it seems to be based on initial finding of a cancer cluster, and retrospective construction of groups to demonstrate this cluster (Swaen, 1995).
3) Subsequent studies have shown mixed results. Long term follow-up of workers exposed to trichloroethylene found no overall increased rates of renal cancer (Hansen et al, 2001; Blair et al, 1998). A large epidemiologic study of trichloroethylene exposed workers found no statistically significant increase in renal cancer. However, a slight increase was observed in a more highly exposed subcohort (Raaschou-Nielsen et al, 2003). Similarly, no statistically significant increases in renal cancer was observed in trichloroethylene exposed workers, but an increase risk in the subpopulation with the highest exposure levels was noted (Charbotel et al, 2006).
4) Nevertheless, higher levels of tubular damage have been seen in renal cell carcinoma patients who have been exposed to trichloroethylene than in patients who have not (Bruning et al, 1996).

F) BRAIN CARCINOMA

1) CASE SERIES: Association between "likely" occupational exposure to trichloroethylene and astrocytic brain cancer was seen in a case-control study in white men (Heineman et al, 1994).

G) ESOPHAGEAL CARCINOMA

1) Data updated through 1990 in a cohort of male and female dry-cleaning workers exposed only to trichloroethylene has shown significant excess deaths from esophageal cancer. Other sub-groups with multiple chemical exposures had excess deaths from bladder, intestinal, and pancreatic, as well as esophageal cancer (Ruder et al, 1994).
2) A large cohort study of workers to trichloroethylene noted an increased incidence for esophageal cancer (incidence ratio 1.8, 95% CI; 1.2 to 2.7) (Raaschou-Nielsen et al, 2003).

H) LYMPHOMA-LIKE DISORDER

1) Studies reviewed by the IARC (1997) failed to provide sufficient evidence of carcinogenicity with human trichloroethylene exposure; three cohort studies indicated a link with a slight excess relative risk for non-Hodgkin lymphoma.
2) A cohort of 14,457 people who had worked in an aircraft maintenance facility for at least 1 year was followed for a 26-year period to assess mortality risk and causes of death. Among white women, increased mortality for multiple myeloma and non-Hodgkin lymphoma was reported. Measures of trichloroethylene exposure, however, did not correlate with increased risk of cancer. Exposure to other chemicals was also possible (Spirtas et al, 1991).
3) Another cohort study (n=40,049) revealed an association between trichloroethylene exposure and non-Hodgkin's lymphoma. Although associations between trichloroethylene exposure and other cancers (eg, renal cell carcinoma, esophageal adenocarcinoma, liver and biliary tract cancer) were found, they were less consistent (Raaschou-Nielsen et al, 2003).
4) A meta-analysis and review of 4 case-control studies and 14 occupational cohort studies reported a modest positive association between trichloroethylene exposure and non-Hodgkin's lymphoma in a trichloroethylene sub-cohort analysis. However, they reported that there was insufficient evidence to suggest a causal link between trichloroethylene exposure and non-Hodgkin's lymphoma (Mandel et al, 2006).

I) OTHER

1) Two other studies identified an excessive number of lymphomas, bladder, skin, respiratory tract and/or cervical cancers (ATSDR, 1992). These studies were flawed, however, due to additional exposures to tetrachloroethylene, carbon tetrachloride, petroleum solvents and other chemicals, as well as inadequate reporting of the levels of trichloroethylene exposure.
2) A case control study of trichloroethylene exposed workers noted a statistically significant increased risk of prostate cancer (OR 2.1, 95% CI; 1.2, 3.9). This relationship was only noted in workers with relatively higher exposure levels. Data are possibly confounded by the high degree of coexposure to other substances such as polycyclic aromatic hydrocarbons (PAHs) (Krishnadasan et al, 2007).

J) LACK OF EFFECT

1) In earlier work, trichloroethylene was considered by some sources to NOT be a carcinogen in man (Chang et al, 2003; AMA, 1985; Kimbrough et al, 1985).
2) However, trichloroethylene was earlier classified as Group 2A (probably carcinogenic to humans) by IARC (IARC, 1997). In 2014, IARC reclassified trichlorethylene as Group 1 (carcinogenic to humans) (International Agency for Research on Cancer, 2015). Moreover, the US Environmental Protection Agency (EPA) has concluded that trichloroethylene is carcinogenic in laboratory animals and is a probable human carcinogen (ATSDR, 1992a).
3) The laboratory animal studies do not meet the National Toxicology Program (NTP) guidelines, which require positive carcinogenicity in multiple species of both sexes (ATSDR, 1992a). Therefore, trichloroethylene is not listed as a carcinogen by the NTP.
4) CASE SERIES: In a cohort study of 1,670 employees of a manufacturing plant using trichloroethylene, there was no evidence that trichloroethylene is a human carcinogen (Axelson et al, 1994).

3.21.4)

A) HEPATIC CARCINOMA

1) MICE: Trichloroethylene is an hepatocarcinogen in mice, but not in other species, including rats and dogs. The production of the metabolite dichloroacetate from trichloroethylene in significant quantities is specific for mice and may account for the increased liver cancers in this species (Templin et al, 1995).
2) Exposure to epoxide-free trichloroethylene produced liver tumors in mice. The trichloroethylene may have contained minute quantities of the carcinogenic stabilizer epichlorohydrin (ATSDR, 1992). Trichloroethylene produced liver tumors in mice and hamsters, and is considered a carcinogen by RTECS criteria (RTECS , 2002).
3) An NTP carcinogenesis study found that epichlorohydrin-free trichloroethylene was carcinogenic for B6C3F1 mice, causing significantly increased incidences of hepatocellular carcinomas in males and females and of hepatocellular adenomas in females (US Dept Health & Human Services, 1990).
4) In another report, hepatocellular carcinoma was reported in B6C3F1 mice only after chronic administration of high, cytotoxic dose levels (AMA, 1985).

B) RENAL CARCINOMA

1) A slight increase in kidney tumors (tubular renal adenocarcinoma) was found in male rats (Maltoni et al, 1988). Other animal studies have failed to show convincing carcinogenic effects (ATSDR, 1992).
2) An NTP carcinogenesis study found that in the conditions of their study, epichlorohydrin-free trichloroethylene caused renal tubular-cell neoplasms in male F344/N rats, produced toxic nephrosis in both sexes and shortened the survival time of males. For female F344/N rats receiving trichloroethylene containing no epichlorohydrin, there was no evidence of carcinogenicity (US Dept Health & Human Services, 1990).
3) The experiment in male F344/N rats was considered to be inadequate to evaluate the presence or absence of a carcinogenic response to trichloroethylene, due to the high mortality in the treatment groups relative to controls (US Dept Health & Human Services, 1990).

C) PULMONARY CARCINOMA

1) Exposure to epoxide-free trichloroethylene produced pulmonary tumors in mice. Other pulmonary tumors (adenocarcinomas) were increased in female mice treated with TCE. The TCE may have contained minute quantities of the carcinogenic stabilizer epichlorohydrin (ATSDR, 1992).
2) Inhalational exposure to TCE resulted in 'respiratory' tumors in rats and mice; trichloroethylene is considered carcinogenic by RTECS criteria (RTECS , 2002).
3) However, the development of lung tumors in mice after exposure to trichloroethylene may be related to the failure of mouse Clara cells to conjugate trichloroethylene, resulting in an accumulation of chloral, and cytotoxicity (Odum et al, 1992).

D) LYMPHOMA-LIKE DISORDER

1) Lymphomas and unspecified 'blood' or 'vascular' tumors were produced in mice and hamsters exposed to trichloroethylene (RTECS , 2002).

E) TESTICULAR DISORDER

1) A slight increase in testicular tumors was found in male rats (Maltoni et al, 1988). This result may not be significant, as these animals commonly develop such tumors. Other animal studies have failed to show convincing carcinogenic effects (ATSDR, 1992).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Trichloroethylene plasma levels after overdose are not clinically useful.
B) Monitor renal and liver function tests if kidney or liver injury is suspected.
C) Monitor ECG after substantial exposures.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Anesthesia achieved with an induction level of 1 percent trichloroethylene for 30 minutes represented an average blood level of 64 mg/L (range, 33 to 90 mg/L) in 22 patients (Baselt, 2000). The blood concentration of trichloroethylene associated with anesthesia was reported to be 5 to 10 mg/dL (Polson & Tattersall, 1969).
2) Exposure to 211 ppm for 2 hours resulted in an average blood level of 6 mg/L (range, 4.5 to 7 mg/L) in seven subjects (Baselt, 2000). A 17-year-old male ingesting 70 mL of TCE had a peak serum blood level of 4.05 mg/L (Bruning et al, 1998).
3) In an experimental model, 6 adults breathing TCE at 100 ppm for four hours achieved an average peak blood concentration of 1.49 mg/L (Pleil et al, 1998).
4) Monitor serum electrolytes and BUN and creatinine levels when renal damage is suspected or after substantial exposure.
5) Monitor serum liver enzyme levels if liver damage is suspected or after substantial exposure.

B) ACID/BASE

1) Monitor blood gases in patients with pulmonary symptoms or substantial exposure.

4.1.3)

A) URINARY LEVELS

1) A urine concentration of trichloroacetic acid of 100 mg/L is consistent with exposure to an 8-hour TWA exposure to trichloroethylene levels of 300 ppm. However, some other chlorinated hydrocarbons are also metabolized to trichloroacetic acid (ACGIH, 1996).
2) Both trichloroacetic acid and trichloroethylene can be measured in the urine as indicators of exposure. Trichloroethylene is the main metabolite (as a glucuronide conjugate) that appears in the urine shortly after exposure, and is an indicator of recent exposure (the current or previous day) (Zenz, 1994). Trichloroacetic acid excretion is delayed, thus it reflects the mean exposure during the previous week, and may remain increased up to 3 weeks after exposure ceases (ATSDR, 1992a; Zenz, 1994).
3) Trichloroethanol (TCOH), or its glucuronide conjugate (TCOG), has also been measured in urine as a marker of TCE exposure, with possibly a more delayed excretion than trichloroacetic acid (Chiu et al, 2007; Lock & Reed, 2006; Lash et al, 2000; Bruning et al, 1998). In a controlled study of inhalation exposure, urinary recovery of TCE was primarily in the form of TCOG with little free TCOH. TCOG levels were almost ten-fold higher than trichloroacetic acid on a molar basis (Chiu et al, 2007).
4) Urinary excretion of glutathione S transferase alpha is considered a good marker for quantifying the extent of renal damage resulting from chronic exposure to high doses of TCE (Bruning et al, 1999).

4.1.4)

A) OTHER

1) ECG

a) Monitor ECG for cardiac dysrhythmias after substantial exposure.

2) BREATH ANALYSIS

a) Analysis of TCE in the breath is a better measure of exposure than determination of metabolites in the urine (Baselt, 1997; Hathaway et al, 1996). At inhalational equilibrium conditions, breath TCE levels correlated well with blood levels (Pleil et al, 1998).
b) Alveolar air concentrations of TCE correlate well with ambient air levels of TCE. Alveolar air samples should be taken at least 6 hours before the end of the exposure period, and just before starting work on the following day (Baselt, 1997).
c) Measurement of TCE in end-exhaled air may be used if the results of TCAA and/or TCOH monitoring are in question. TCE concentrations in the blood can also be used to confirm the degree of exposure (ACGIH, 1992).
d) Breath analysis for trichloroethylene analyzed by gas chromatography appeared to be an accurate indicator of the time-weighted vapor exposure to a worker (Stewart et al, 1974a).

Radiographic Studies

A)

1) Obtain a chest X-ray in patients with pulmonary symptoms.

a) Trichloroethylene was radio-opaque in vitro (Dally et al, 1987).

B)

1) X-ray examination of chest and abdomen revealed a radio-opaque material later identified as trichloroethylene. The level of radio-opacity was shown to be only slightly less than that of Gastrographin(R) (Sottili et al, 1993).

Methods

A)

1) Gas chromatography with solvent extraction and headspace sampling methods are used to measure trichloroethylene in body fluids and tissues; colorimetric and gas chromatographic methods are used to measure the metabolites trichloroacetic acid and trichloroethanol (Baselt, 2000).
2) Trichloroethylene concentrations may be measured in venous blood by gas chromatography with head space analysis (Kostrzewski et al, 1993).
3) Exposure to trichloroethylene may be confirmed by detection of trichloroacetic acid and trichloroethanol in the urine and blood by gas chromatography/mass spectrometry (GC/MS) (Koppel et al, 1988; Inoue et al, 1989; O'Donnell et al, 1995; Bruning et al, 1998).

a) Kostrzewski et al (1993) found serum trichloroethylene levels to be more clinically significant than urinary measurements of trichloroacetic acid in determining total inhalation exposures.
b) O'Donnell et al (1995) describe a capillary gas chromatography method for analysis of trichloroacetic acid in the urine with a relative recovery of 99.6 percent. The authors suggest this method for monitoring occupational trichloroethylene exposures.

4) Measurement of changes in visual fields and trigeminal nerve potentials have also been proposed, due to the effects of trichloroethylene or dichloroacetylene (a decomposition product of trichloroethylene) on the cranial nerves. An abnormal trigeminal somatosensory evoked potential, in the absence of clinical signs, may provide objective determination of risk assessment (ATSDR, 1992a; Barret et al, 1988).
5) Trichloroethylene can be detected in the breath and urine up to 16 hours after exposure, metabolites for a week or more (Barceloux & Rosenberg, 1990).
6) Skender et al (1991) suggest that the most accurate indicator of trichloroethylene exposure is the presence of trichloroethanol in the blood.

Treatment

Life Support

A)

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) EMESIS/NOT RECOMMENDED

1) Because of the potential for CNS depression and seizures, DO NOT induce emesis.

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)

A) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

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

2) CHARCOAL DOSE

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

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

b) ADVERSE EFFECTS/CONTRAINDICATIONS

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

B) GASTRIC LAVAGE

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

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

2) PRECAUTIONS:

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

3) LAVAGE FLUID:

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

4) COMPLICATIONS:

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

5) CONTRAINDICATIONS:

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

6.5.3)

A) MONITORING OF PATIENT

1) Monitor cardiac function and vital signs frequently.
2) As hepatic and renal injury are possible, liver and renal function should be monitored.

B) SUPPORT

1) Pulmonary edema, renal failure and liver damage should be treated symptomatically.

C) BRADYCARDIA

1) ATROPINE

a) ATROPINE/DOSE

1) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
2) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

a) There is no minimum dose (de Caen et al, 2015).
b) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

2) Epinephrine or other stimulants should be avoided when possible because of the danger of inducing cardiac dysrhythmias. This agent lowers the myocardial threshold to the arrhythmogenic effects of beta-adrenergic agonists.

D) VENTRICULAR ARRHYTHMIA

1) VENTRICULAR DYSRHYTHMIAS SUMMARY

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

2) LIDOCAINE

a) LIDOCAINE/INDICATIONS

1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).

b) LIDOCAINE/DOSE

1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.

a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

c) LIDOCAINE/MAJOR ADVERSE REACTIONS

1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

d) LIDOCAINE/MONITORING PARAMETERS

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

3) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

4) PROCAINAMIDE

a) PROCAINAMIDE/INDICATIONS

1) An alternative drug in the treatment of PVCs or recurrent ventricular tachycardia when lidocaine is contraindicated or not effective. It should be avoided when the ingestion involves agents with quinidine-like effects (e.g. tricyclic antidepressants, phenothiazines, chloroquine, antidysrhythmics) and when the ECG reveals QRS widening or QT prolongation suspected to be secondary to overdose(Neumar et al, 2010; Vanden Hoek,TLet al,null).

b) Patients allergic to penicillin products may have cross-sensitivity to penicillamine (Prod Info DEPEN(R) titratable oral tablets, 2009).
c) Monitor for proteinuria and hematuria; heavy metals may also cause renal toxicity (Prod Info DEPEN(R) titratable oral tablets, 2009).
d) Monitor CBC with differential, platelet count, and hepatic enzymes (Prod Info DEPEN(R) titratable oral tablets, 2009).

5) ESMOLOL

a) Moritz et al (2000) reported the use of an esmolol 20 mg intravenous bolus in a 70-year-old who developed bigeminy followed by junctional rhythm. This resulted in sinus rhythm without recurrence of ESV. A 2 mg/minute esmolol infusion was also used. This drug was chosen for its rapid onset of action and short elimination half-life of 9 minutes.
b) TACHYCARDIA SUMMARY

1) Evaluate patient to be sure that tachycardia is not a physiologic response to dehydration, anemia, hypotension, fever, sepsis, or hypoxia. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
2) If therapy is required, a short acting, cardioselective agent such as esmolol is generally preferred (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
3) ESMOLOL/ADULT LOADING DOSE

a) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010).

4) ESMOLOL/ADULT MAINTENANCE DOSE

a) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010).
b) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010).
c) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
d) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).

5) CAUTION

a) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010).

E) HYPOTENSIVE EPISODE

1) Epinephrine or other stimulants should be avoided when possible because of the danger of inducing cardiac dysrhythmias. This agent lowers the myocardial threshold to the arrhythmogenic effects of beta-adrenergic agonists.
2) 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.

3) 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).

4) 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).

F) ACUTE LUNG INJURY

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

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

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

G) PROPRANOLOL

1) Propranolol 40 to 80 milligrams orally in adults MAY be useful to reverse "degreaser's flush."

H) EXPERIMENTAL THERAPY

1) ANIMAL STUDIES - In rats, cimetidine had a tendency to decrease the metabolism of trichloroethylene and may exert a protective effect against some of the hepatotoxicity (Landriault et al, 1989).

Inhalation Exposure

6.7.1)

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

6.7.2)

A) ACUTE LUNG INJURY

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

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

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

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

Eye Exposure

6.8.1)

A) OTHER

1) 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)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

A)

1) No data are available on the effectiveness of hemodialysis or hemoperfusion to increase the elimination of trichloroethylene.

B)

1) Koppel et al (1988) estimated 70 percent of the absorbed dose was eliminated in expired air when hyperventilation therapy was used in a 32-year-old male after a suicidal ingestion of 150 grams of trichloroethylene and ethanol.
2) Previous reports indicated 75 percent of the absorbed dose is metabolized in the liver when hyperventilation treatment was not used (Baselt, 1982). No liver or renal dysfunction were noted and level of consciousness improved with hyperventilation therapy.

Abstracts

Case Reports

A)

1) Troutman (1988) reported 3 deaths from the intentional inhalation abuse of a typewriter correction fluid containing both 1,1,1-trichloroethane and trichloroethylene. One patient was found collapsed in a field with a bottle of this material in his hand, one was found locked in a bathroom with a bag containing the material over his head, and the third collapsed during an altercation after abusing the material throughout the day. None of the three patients could be resuscitated. Although mustard oil has been added to this product to discourage abuse, it did not deter these three victims.

Range Of Toxicity

Minimum Lethal Exposure

A)

1) The estimated human lethal dose is between 3 and 5 mg/kg (HSDB , 2002).
2) Inhalation of between 5000 and 20,000 ppm of trichloroethylene has produced light anesthesia, followed by death from cardiac arrest in rare cases (Hathaway et al, 1996).
3) After administration of trichloroethylene as an anesthetic, fatal hepatic failure has occurred in patients with conditions such as toxemia, malnutrition or burns (HSDB , 2002).
4) A 24-year-old male died after ingesting 200 to 300 milliliters (3 to 5 milliliters/kilogram) of pure trichloroethylene (Froboese, 1943).
5) A 24-year-old deceased male reportedly had been exposed to TCE concentrations between 7,500 and 10,000 ppm in an industrial accident (Ford et al, 1995).
6) Exposure to 8,000 ppm can lead to death (Sittig, 1991).

B)

1) The lowest dose that has produced death in cats, dogs and rabbits is reported to be 6,000 to 7,000 mg/kg (ACGIH, 1996a).
2) Animal deaths are mainly due to anesthesia, which results from trichloroethylene exposure. Full anesthesia occurs at airborne concentrations of 4,800 ppm or more (Clayton & Clayton, 1994).
3) Dogs died after exposure to 150 mg/kg, administered intravenously (Hayes & Laws, 1991).
4) Rats died after inhalation exposure to 17,000 ppm for 7 hours (Hayes & Laws, 1991).

Maximum Tolerated Exposure

A)

1) ACUTE

a) GENERAL

1) The central nervous system depressant effects of trichloroethylene may be potentiated by ethanol (Barceloux & Rosenberg, 1990; Hayes & Laws, 1991).
2) Exposure to concentrations above 1,500 mg/m(3) may first lead to an excitatory or euphoric stage, which is followed by dizziness, confusion, drowsiness, nausea, vomiting, and possibly loss of consciousness (Baselt, 2000).
3) Volunteers who had placed their thumbs in trichloroethylene for 30 minutes experienced a burning sensation on the dorsum of their thumbs within 3 to 18 minutes. Within 5 minutes after the onset of the sensation, burning became severe in two of the three volunteers. After removal of their thumbs from the solution, pain became more intense and tingling persisted for 30 minutes. Erythema subsided within 2 hours (Hayes & Laws, 1991).
4) Volunteers exposed to 500 to 1,000 ppm showed symptoms of CNS disturbance (dizziness, light-headedness, lethargy, impairment in visual-motor response tests) (Hathaway et al, 1996).

b) ORAL EXPOSURE

1) Ingestion of a glassful of trichloroethylene (25%) and water produced coma with cardiovascular collapse, renal injury, and blood streaked liquid diarrhea (Calvet et al, 1959).
2) After swallowing 70 mL of trichloroethylene, a 17-year-old male developed prolonged coma and renal tubular damage. He survived with treatment (Baselt, 2000).

c) INHALATION EXPOSURE

1) An estimated 0.5% to 2% trichloroethylene vapor produces analgesia and light anesthesia within 3 to 5 minutes (JEF Reynolds , 1988).
2) Hepatotoxicity has been reported after exposure to airborne concentrations greater than 15,000 ppm (ACGIH, 1996a).
3) Inhalation exposure of 8 volunteers to concentrations of 100, 200 and 1,000 ppm for two hours showed significantly impaired performance of visual-motor tasks only at the 1,000-ppm level. Tasks were performed within the 2 hour exposure period, and consisted of tests in depth perception, steadiness and manual skills (Hayes & Laws, 1991).
4) Short-term inhalation of 100 ppm caused headache, sleepiness, nausea, vomiting, dizziness and coughing. Long-term exposure to the same concentration caused giddiness, nervous exhaustion and increased sensitivity to alcohol (leading to facial trichloroethylene blush). Addiction to the vapors may also occur at this concentration (Sittig, 1991).

d) OCCUPATIONAL EXPOSURE

1) Industrial experience and human studies (Clayton & Clayton, 1994) -

Concentration	Response
100	Odor threshold
200	Mild eye irritation
400	Slight eye irritation, minimal light-headedness after 3 hours
1000 to 1200	Unpleasant odor, eye and nasal irritation, light-headedness, dizziness after 6 min
2000	Strong odor (not tolerated), irritating to eyes and respiratory tract, drowsiness, dizziness, nausea in 5 minutes

2) Pre-narcotic symptoms were seen in workers exposed to 200 to 300 ppm (Hathaway et al, 1996).
3) Workers exposed to 100 to 200 ppm have reported fatigue, vertigo, dizziness, headache, memory loss and impaired ability to concentrate (Hathaway et al, 1996).
4) After a 5-minute exposure to trichloroethylene, a worker developed nausea, lethargy, confusion, blurred vision and numbness of face and mouth within 10 hours. All symptoms except for some hypoalgesia in the face subsided within 18 months (Baselt, 1997).
5) An update to a Swedish study evaluated the effects of low-level occupational exposure (<20 ppm) to trichloroethylene. The results showed that within the parameters of this study, there was no evidence for carcinogenic effects at this level (Hathaway et al, 1996).

B)

1) Chronic occupational exposure to concentrations between 40 and 270 ppm often results in symptoms of fatigue, headache, irritability, vomiting, flushing of the skin, intolerance to alcohol and electrocardiographic changes (Baselt, 2000).

C)

1) Rats experienced hepatic injury after a 2-hour exposure to 10,000 ppm of the compound, following pretreatment with phenobarbital, Aroclor 1254, hexachlorobenzene, and 3-methyl cholanthrene or pregneolone-16-alpha- carbonitrile (ACGIH, 1996a).
2) For single exposures survived by all rats, the maximum time-concentrations were the following: 18 min at 20,000 ppm; 1.5 hr at 6400 ppm; 8 hr at 3000 (Clayton & Clayton, 1994).
3) Dogs survived exposure to oral doses of 6000 mg/kg and intravenous doses of 125 mg/kg (Hayes & Laws, 1991).
4) Rats survived inhalation exposure to 3,000 ppm for 7 hours (Hayes & Laws, 1991).
5) Animals tolerated without adverse effects the following inhalation exposures (Hayes & Laws, 1991):

1) Rats - 151 exposures at 200 ppm for 7H/D,5D/W
2) Monkeys - 400 ppm for 6 months
3) Rabbits - 200 ppm for 6 months
4) Guinea Pig - 100 ppm for 6 months

6) Following intragastric administration of trichloroethylene at the indicated levels five times per week for 78 weeks showed the effects listed below. Trichloroethylene was technical grade but later found to be contaminated with other chemicals (Hathaway et al, 1996):

1) 2.4 g/kg - male B6C3F1 mice: hepatocellular carcinomas in 31 of 48 animals;
2) 1.2 g/kg - male B6C3F1 mice: hepatocellular carcinoma in 26 of 50 animals (control group 5% incidence rat);
3) 1.2 g/kg - female B6C3F1 mice: hepatocellular carcinoma in 11 of 47 animals (control group 1 of 80 animals).

7) Intragastric administration of epichlorohydrin-free trichloroethylene at 1.0 g/kg for 2 years resulted in increased incidences for hepatocellular adenomas and carcinomas in mice, and an increase in renal adenocarcinomas in rats (Hathaway et al, 1996).
8) Inhalation exposure to 500 ppm of trichloroethylene for 6 hours/day, 5 days/week for 18 months resulted in an increased incidence of malignant lymphomas in female MRI mice. No change in incidence rate for tumor formation was found for rats and hamsters exposed to the same levels (Hathaway et al, 1996).
9) ICR mice, exposed for 107 weeks to trichloroethylene vapor showed the following effects (Hathaway et al, 1996):

1) 150 ppm - 16% incidence for lung carcinoma (control group 2%);
2) 450 ppm - 15% incidence for lung carcinoma (control group 2%);
3) No change in incidence rate was found for rats exposed to the same levels.

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) GENERAL

a) Deep coma and dysrhythmia have been associated with trichloroethylene blood concentrations greater than 1,500 micrograms/liter (Perbellini et al, 1991; Moritz et al, 2000).
b) Exposure to trichloroethylene airborne levels of 27 ppm for 4 hours resulted in mucous membrane irritation and drowsiness; airborne levels of 81 parts per million resulted in headaches (Barceloux & Rosenberg, 1990).
c) Toxic trichloroethylene serum level of 0.7 milligrams/liter was reported in a patient with clinical signs including pneumonia, respiratory acidosis, tachycardia and blurred consciousness (Kostrzewski et al, 1993).
d) A maximum blood trichloroethylene (TCE) concentration of 4.1 milligrams/liter was attained 13 hours after ingestion of 70 milliliters of TCE in a 17-year-old male. The patient developed prolonged coma and renal tubular damage (Bruning et al, 1998).
e) Blood concentration of TCE and trichloroethanol were reported to be 67 and 36 milligrams/liter, respectively, several hours after ingestion of 1 liter of 90% TCE in a 70-year-old female. This patient developed coma and life-threatening dysrhythmias (Moritz et al, 2000).
f) CASE REPORT - A 42-year-old male died of asphyxia from TCE fumes. Exposure was for less than 5 hours at an unknown concentration. Blood concentrations were 40 mg/L in femoral blood and 84 mg/L in subclavian blood (Coopman et al, 2003).
g) Skeletal muscle damage occurred in a man after ingesting an unknown amount of trichloroethylene in a suicide attempt. He presented 3 hours after the ingestion to the hospital with a Glasgow Coma Scale rating of 3, hypotension, sinus tachycardia, severe diarrhea, and acute respiratory failure. He developed ventricular bigeminy after 4 days of hospitalization. On the 17th day, a muscle biopsy revealed abnormalities of lipid storage and mitochondrial degeneration. The muscle trichloroacetic acid (TCA, a metabolite) and the urine TCA concentrations were 28.7 mcg/g and 15.8 mg/L (normal less than 60 mcg/L), respectively, were also measured on day 17. He died of complete heart block 24 days post-ingestion (Vattemi et al, 2005).

Workplace Standards

A)

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) Trichloroethylene

a) TLV:

1) TLV-TWA: 10 ppm
2) TLV-STEL: 25 ppm
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A2
2) Codes: Not Listed
3) Definitions:

a) A2: Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s), or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans.

c) TLV Basis - Critical Effect(s): CNS impair; cognitive decrements; renal toxicity
d) Molecular Weight: 131.4

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 CAS79-01-6 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Trichloroethylene
2) REL:

a) TWA:
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A; See Appendix C

3) IDLH:

a) IDLH: 1000 ppm
b) Note(s): Ca

1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

C) Carcinogenicity Ratings for CAS79-01-6 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A2 ; Listed as: Trichloroethylene

a) A2 :Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s), or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans.

2) EPA (U.S. Environmental Protection Agency, 2011): Information reviewed but value not estimated. Refer to Full IRIS Summary. ; Listed as: Trichloroethylene
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): 1 ; Listed as: Trichloroethylene

a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Trichloroethylene

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

5) MAK (DFG, 2002): Category 1 ; Listed as: Trichloroethylene

a) Category 1 : Substances that cause cancer in man and can be assumed to make a significant contribution to cancer risk. Epidemiological studies provide adequate evidence of a positive correlation between the exposure of humans and the occurence of cancer. Limited epidemiological data can be substantiated by evidence that the substance causes cancer by a mode of action that is relevant to man.

6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS79-01-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Trichloroethylene
2) Table Z-1 for Trichloroethylene:

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:

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

3) Table Z-2 for Trichloroethylene (Z37.19-1967):

a) 8-hour TWA:100 ppm
b) Acceptable Ceiling Concentration: 200 ppm
c) Acceptable Maximum Peak above the Ceiling Concentration for an 8-hour Shift:

1) Concentration: 300 ppm
2) Maximum Duration: 5 min. in any 2 hrs

d) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: ATSDR, 2001 ATSDR, 1997; Budavari, 2000 Clayton & Clayton, 1994 ITI, 1995 HSDB, 2002 Lewis, 2000 OHM/TADS, 2002 RTECS, 2002

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 3222 mg/kg (Hayes & Laws, 1991; HSDB, 2002)

2) LD50- (ORAL)MOUSE:

a) Male, 2402 mg/kg - change in sleep time; change in righting reflex; ataxia; hair changes
b) 2850 mg/kg (Clayton & Clayton, 1994)
c) Female, 2443 mg/kg (Clayton & Clayton, 1994; Hayes & Laws, 1991)

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 16 mg/kg - sleep changes; ataxia

4) LD50- (INTRAPERITONEAL)RAT:

a) 3300 mg/kg (OHM/TADS, 2002)
b) 1282 mg/kg (Lewis, 2000)

5) LD50- (ORAL)RAT:

a) 5650 mg/kg (Lewis, 2000)
b) 4.92 mL/kg (Budavari, 2000)
c) 4920 mg/kg (Clayton & Clayton, 1994; Hayes & Laws, 1991; ITI, 1995)
d) 7180 mg/kg for 14D (OHM/TADS, 2002)

6) TCLo- (INHALATION)HUMAN:

a) 6900 mg/m(3) for 10M -- somnolence, hallucinations
b) 160 ppm for 83M -- hallucinations, distorted perceptions
c) 812 mg/kg -- somnolence; changes in gastro-intestinal tract; jaundice and other liver changes
d) 500 ppm for 16.1Y-intermittent -- changes in kidney tubuli and glomeruli; proteinuria; effects on transferases
e) 110 ppm for 8H -- hallucinations, distorted perceptions

7) TCLo- (INHALATION)MOUSE:

a) 150 ppm for 24H, 30D- continuous -- liver weight changes; weight loss or decreased weight gain; effects on phosphatases
b) 10,000 ppm for 1H, 12D-intermittent -- respiratory depression and other changes; death
c) Female, 100 ppm for 7H, 5D before mating -- effects on spermatogenesis

8) TCLo- (INHALATION)RAT:

a) Female, 100 ppm for 4H, 6-22D post -- teratogenic effects; postimplantation mortality; fetotoxicity (Lewis, 2000)
b) 150 ppm for 7H, 2Y-intermittent -- carcinogenic effects (Lewis, 2000)
c) 150 ppm for 24H, 3D-continuous -- liver weight changes
d) 300 ppm for 24H, 12W-continuous -- changes in serum; change in liver weight; effect on lipids
e) 2400 for 6H, 13W-intermittent -- change in acuity of sense organs
f) 3200 ppm for 12H, 12W- intermittent -- CNS changes; changes in urine composition
g) 4330 ppm for 4H, 2W-intermittent -- ataxia; changes in psychophysiological tests
h) 50 mg/m(3) for 5H, 26W- intermittent -- CNS changes; changes in urine composition
i) Female, 100 ppm for 4H, 8-21D preg -- musculoskeletal system developmental abnormalities
j) Female, 1800 ppm for 6H, 1-20D preg -- urogenital system developmental abnormalities
k) Female, 1800 ppm for 24H, 1-20D preg -- musculoskeletal system developmental abnormalities

7.7.2)

A) References: ATSDR, 2001 ATSDR, 1997; Budavari, 2000 Clayton & Clayton, 1994 ITI, 1995 HSDB, 2002 Lewis, 2000 OHM/TADS, 2002 RTECS, 2002

1) NOEL- (INHALATION)GUINEA_PIG:

a) 730 ppm for 6W, 8H/D (HSDB, 2002)

2) NOEL- (INHALATION)PRIMATE:

a) 730 ppm for 6W, 8H/D (HSDB, 2002)

3) NOEL- (INHALATION)RABBIT:

a) 1,200 ppm for 473H (HSDB, 2002)
b) 730 ppm for 6W, 8H/D (HSDB, 2002)

4) NOEL- (INHALATION)RAT:

a) 100 ppm for 8H (HSDB, 2002)
b) 730 ppm for 6W, 8H/D (HSDB, 2002)

Summary

A)

B)

C)

Therapeutic Dose

7.2.1)

A) ROUTE OF ADMINISTRATION

1) LIGHT ANESTHESIA - 0.5 to 2 percent of the trichloroethylene vapor (JEF Reynolds , 1991)
2) ANALGESIA DURING CHILDBIRTH - 0.35 to 0.5 percent of trichloroethylene vapor (JEF Reynolds , 1991)
3) TRIGEMINAL NEURALGIA - 1 milliliter is inhaled from a crushable glass ampule while the patient is in a reclining position (JEF Reynolds , 1988).

Pharmacology Toxicology

Pharmacologic Mechanism

A)

Toxicologic Mechanism

A)

1) Bruning et al (1998) reported the excretion of several low-molecular-mass proteins between 10,000 and 55,000 Da, which indicates renal tubular damage, following the acute ingestion of trichloroethylene. Excretion of alpha1 and beta2-microglobulin, as well as B-NAG was significantly increased, a typical marker of selective tubule damage (Bruning et al, 1998).

B)

C)

D)

Physicochemical

Physical Characteristics

A)

B)

C)

Molecular Weight

A)

Other

A)

1) 50 ppm (CHRIS , 2002)

Animal Toxicology

References

General Bibliography

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TRICHLOROETHYLENE

Classification | Detailed evidence-based information

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General Bibliography