SOURCES

Metaldehyde is primarily used to kill slugs and snails to protect horticultural crops and household gardens. Baits are commonly available in the form of granules (often dyed), but can also be obtained as liquid, powder, or pellets that can release metaldehyde for approximately 10 days under moderately moist conditions. Baits are sometimes mixed with other herbicides and pesticides, most commonly with carbamate insecticides. Bran or molasses is commonly added to the bait to increase its attractiveness to snails and slugs, causing this form of bait to be attractive and palatable to dogs as well. Regulatory action requiring that snail baits be unattractive to dogs exists in some countries and states.^1,2

The concentration of metaldehyde in baits sold for domestic use in the United States is generally between 1.5% and 5%. Some trade names of metaldehyde bait available in the United States include Ortho Bug-Geta Snail & Slug Killer, Slug Pellets, Metason, Ortho Metaldehyde 4% Bait, Antimitace, Antimilace, Cekumeta, Deadline, Slugit Pellets, and Slug-Tox. In Europe baits can contain up to 50% metaldehyde, and metaldehyde is also used as a fuel in small heating systems, such as camping stoves and lamps.³ Trade names for metaldehyde fuel are Meta-fuel and Meta-Brennstoff, which are available in the form of tablets, solid blocks, or powder. In Japan metaldehyde is an ingredient in color flame tablets that are ignited for entertainment.³

TOXIC DOSE

Metaldehyde is moderately toxic when ingested. Acute oral median lethal dose (LD₅₀) values range from 210 to 600 mg/kg of body weight for dogs and 207 mg/kg of body weight for cats.^5–7 For example, if a 20-kg dog ingests 1 lb of a 4-lb box of 3.25% metaldehyde, the animal is exposed to 738 mg of metaldehyde/kg of body weight, which is a dose that is potentially lethal. Inhalation exposure is unlikely, but can occur with exposure to dusts of commercial pesticide products. Inhalation LD₅₀ values (4 hours) of 203 mg/m³, 203 mg/m³, and 175 to 700 mg/m³ are reported for rats, mice, and guinea pigs, respectively.⁸

TOXICOKINETICS

The solubility of metaldehyde in water is poor, which may limit the rate of absorption; however, metaldehyde is absorbed intact from the gastrointestinal tract.⁹ In the stomach, metaldehyde may undergo some acid hydrolysis to acetaldehyde. The half-life of metaldehyde at 24° C is 0.75 and 4 hours, in 0.1 and 0.01 mol/L aqueous hydrochloric acid, respectively.¹⁰ In 0.18 mol/L physiological gastric hydrochloric acid, metaldehyde is unlikely to hydrolyze extensively in the stomach before absorption. Once absorbed, the metabolic fate of metaldehyde is largely unknown, although a rapid metabolism is suspected. The involvement of cytochrome P450 enzymes has been suggested because P450 inducers protect against metaldehyde toxicity.¹¹ In mice it was reported that only 8% of an oral dose was excreted unmetabolized in urine and feces.¹¹ Urinary excretion in dogs dosed with metaldehyde was less than 1%.⁵ The apparent elimination half-life derived from a human metaldehyde poisoning case was approximately 27 hours.¹² Although data on elimination kinetics in animals is not available, it is presumed that the hydrolysis product acetaldehyde is rapidly converted to carbon dioxide and eliminated via expiration.

MECHANISM OF TOXICITY

Recent studies have suggested that acetaldehyde is unlikely to be the toxicant in metaldehyde poisoning since acetaldehyde is extremely unstable and is rapidly oxidized to carbon dioxide.¹³ This finding is supported by several studies in which acetaldehyde was not detected in the plasma or urine of metaldehyde-treated dogs⁶ or in the brains of mice poisoned with metaldehyde.¹⁰ Thus the toxicity of metaldehyde is not mediated by or perhaps is only partly mediated by the degradation product acetaldehyde. Instead metaldehyde itself may be the actual toxicant that acts on the γ-aminobutyric acid (GABA)-ergic system.

Metaldehyde readily crosses the blood-brain barrier. Metaldehyde was detected in the brain, blood, and liver of mice given metaldehyde orally at toxic and nontoxic doses.¹⁰ It was also found in the serum and urine of a human for up to 3 to 4 days following exposure.¹² Decreased brain concentrations of GABA, norepinephrine (NA), and 5-hydroxytryptamine (5-HT) and increased monoamine oxidase (MAO) activity were seen in mice dosed with metaldehyde.^14,15 GABA has an inhibitory role in neuronal excitation, and a decrease in GABA levels may lead to convulsions. The mechanism of disruption of the GABAergic system by metaldehyde is still unknown, but inhibition of glutamic acid decarboxylase (GAD) as the cause of reduction of GABA concentrations is unlikely.¹⁰ Depletion of central stores of NA and 5-HT is correlated with a decreased threshold of convulsions.¹⁶ Because MAO is an important enzyme in the metabolism of NA and 5-HT, these may interact to contribute to the mode of action, in addition to GABA.

Hyperthermia can play a major role in the pathophysiology of metaldehyde toxicosis, and it is assumed that the muscle tremors often seen in metaldehyde-poisoned animals are the primary cause of body temperatures in excess of 42° C. At body temperatures of 42° C to 43° C (107° F-109° F), cellular necrosis may begin to occur within a few minutes in all organ systems.¹⁷ Hyperthermia may alter electrolyte balances, and metaldehyde is reported to cause severe acid-base derangements. The resulting metabolic acidosis is associated with hyperpnea and central nervous system (CNS) depression.