Introduction

Ingestion of ethylene glycol has significant toxicologic implications if undetected or left untreated. The preceding section described the clinical features of ethylene glycol poisoning in three stages that are based on the time after ingestion. This section depicts the systemic effects associated with significant ethylene glycol exposure.

Neurologic Effects

The initial phase of ethylene glycol poisoning is characterized by inebriation caused by unmetabolized ethylene glycol. In acute poisoning cases, the following symptoms are common (Parry and Wallach 1974; Buell, Sterling et al. 1998)

• ataxia
• slurred speech
• drowsiness
• irritation
• restlessness
• disorientation

Possible Sequelae

Possible sequelae of severe poisonings (Walder and Tyler 1994; Hantson, Vanbinst et al. 2002) include

• myoclonic jerks
• convulsions
• coma
• death

Cerebral edema and deposition of calcium oxalate crystals in the walls of small blood vessels in the brain contribute to this CNS toxicity (Jobard, Harry et al. 1996; Bey, Walter et al. 2002; Tobe, Braam et al. 2002). Some studies also documented brain dysfunction with corresponding cranial computed tomography findings after ethylene glycol ingestion (Chung and Tuso 1989; Zeiss, Velasco et al. 1989; Morgan, Ford et al. 2000).

Cranial Nerve Damage

Recovery in survivors is usually rapid and complete. However, the following cranial nerve palsies have been reported one or more weeks after acute exposure

• facial palsy
• hearing loss
• dysphagia
• opthalmoplegia
• visual disturbances

Such adverse effects are not seen often, but delayed treatment may contribute to their development (Momont and Dahlberg 1989; Broadley, Ferguson et al. 1997; Lewis, Smith et al. 1997; Tobe, Braam et al. 2002).

Respiratory Effects

Inhaled ethylene glycol can irritate the respiratory tract.

• Throat and upper respiratory irritation were the most common complaints following prolonged experimental exposures in humans (4 weeks at concentrations of 1-25 ppm).
• Exposure to 60 ppm aerosolized ethylene glycol caused very noticeable irritation.
• Exposure to 80 ppm aerosolized ethylene glycol was judged “intolerable” because respiratory discomfort developed rapidly (Wills, Coulston et al. 1974).

Pulmonary effects typically occur 12 to 72 hours after ingestion of ethylene glycol. Pulmonary edema and adult respiratory distress syndrome (ARDS) have been reported in ethylene glycol victims (Haupt, Zull et al. 1988; Piagnerelli, Carlier et al. 1999).

The following respiratory effects often occur 12 hours or more after exposure in victims of severe ethylene glycol poisoning.

• tachypnea,
• hyperventilation,
• Kussmaul respirations.

Such effects most often reflect physiological compensation for severe metabolic acidosis rather than primary lung disease (Friedman, Greenberg et al. 1962; Parry and Wallach 1974; Godolphin, Meagher et al. 1980). Autopsies of ethylene glycol victims revealed the following

• pulmonary edema with diffuse hemorrhagic exudates,
• bronchopneumonia (probably caused by aspiration), and
• deposits of calcium oxalate crystals in lung parenchyma (Vale 1979).

Cardiovascular Effects

The following severe cardiovascular effects have been reported in ingestion victims, during stage 2 (Friedman, Greenberg et al. 1962; Parry and Wallach 1974; Vale 1979):

• Congestive heart failure with cardiogenic pulmonary edema
• Circulatory collapse

Severe metabolic and fluid electrolyte abnormalities (Friedman, Greenberg et al. 1962; Parry and Wallach 1974) may cause

• cardiac dysrhythmias
• cardiac arrest

Ingestion of antifreeze (Walder and Tyler 1994), (Jobard, Harry et al. 1996; Rasic, Cengic et al. 1999) may affect blood pressure, causing either

• hypertension or
• hypotension, which may progress to cardiogenic shock.

Metabolic Effects

Severe ethylene glycol poisoning is characterized by metabolic acidosis.

• Onset occurs within 24 hours after ingestion.
• Acidosis is caused primarily by the accumulation of glycolic and glyoxylic acid. Oxalic and excess lactic acid also contribute.

The metabolic acidosis of ethylene glycol poisoning is characterized as normochloremic (Berman, Schreiner et al. 1957; Curtin, Kraner et al. 1992; Hantson, Hassoun et al. 1998; Bey, Walter et al. 2002)with

• low serum bicarbonate level and pH and
• elevated acidemia and anion gap.

Ethylene glycol is a small, osmotically active molecule that

• markedly increases plasma osmolality and
• causes a large osmolal gap.

Osmolality reflects the number of solute particles in a solution. Numerical measures of osmolality express the number of particles present in a given weight of solvent.

Tetany can sometimes occur due to hypocalcemia that results from precipitation of calcium by the oxalate formed during ethylene glycol metabolism (Parry and Wallach 1974).

Renal Effects

Kidney damage typically occurs during stage 3 of ethylene glycol intoxication.

• Kidney damage manifests as acute oliguric renal failure.
• Costovertebral angle tenderness is the most common physical finding (Friedman, Greenberg et al. 1962).
• The most characteristic abnormality is the presence of large numbers of “tent-shaped” (octahedral) or needle-shaped oxalate crystals in the urine (Olivero 1993; Huhn and Rosenberg 1995).
• Absence of oxalate crystals does not rule out the diagnosis of ethylene glycol poisoning (Haupt, Zull et al. 1988; Curtin, Kraner et al. 1992; Baum, Langman et al. 2000; Boyer, Mejia et al. 2001; Hantson, Vanbinst et al. 2002).

Other typical urinalysis abnormalities are

• low specific gravity
• proteinuria
• microhematuria
• pyuria
• elevated serum BUN and creatinine

Disturbed renal function may be mild and short-lived or severe and persistent for several months. Permanent renal insufficiency is uncommon but does occur (Berman, Schreiner et al. 1957; Friedman, Greenberg et al. 1962; Parry and Wallach 1974; Buell, Sterling et al. 1998; Hantson, Hassoun et al. 1998).

The toxicity of ethylene glycol is linked with two metabolites.

• Glycolic acid, which causes the acidosis.
• Oxalic acid.
  • Oxalic acid is poorly soluble in the presence of calcium.
  • Calcium oxalate crystals in the urine are diagnostic.
  • The precipitation of oxalate crystals in the tubular lumen leads to luminal blockage and compression-induced loss of glomerular filtration (renal failure).

In transformed kidney cells, the oxalate ion induces cytotoxic damage (McMartin and Cenac 2000). Another study, however, stated that glycoaldehyde and glyoxylate are the principal metabolites responsible for ethylene glycol nephrotoxicity (Poldelski, Johnson et al. 2001).

Carcinogenicity and Teratogenicity

Data are insufficient to determine whether ethylene glycol causes cancer or developmental defects.

• Human studies have shown no link between ethylene glycol exposure and cancer or reproductive or developmental hazards.
• Animal studies have not found an association between ethylene glycol exposure and cancer.
• Ethylene glycol exposure was teratogenic to mice and rats, resulting in craniofacial and neural tube closure defects and skeletal dysplasia (Lamb, Maronpot et al. 1985; Price, Kimmel et al. 1985; Marr, Price et al. 1992; Tyl, Ballantyne et al. 1995). Ethylene glycol itself is used to cryopreserve embryos of many mammal and is thus an unlikely cause of these abnormalities.

Other Effects

Nausea, vomiting (with or without blood), and abdominal pain are frequent early findings following ethylene glycol ingestion (Meditext 2004). Ethylene glycol is only a minor skin and mucous membrane irritant, although a few cases of allergic contact dermatitis have been documented (Clayton GD & Clayton FE 1994). Reported effects on the blood have included leukocytosis, occasional methemoglobinemia, and bone marrow arrest (Verrilli, Deyling et al. 1987; Hantson, Hassoun et al. 1998; Rasic, Cengic et al. 1999). Reported musculoskeletal effects have included muscle tenderness and elevation of creatine kinase (Friedman, Greenberg et al. 1962; Parry and Wallach 1974; Verrilli, Deyling et al. 1987).

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