The first indication of the extreme toxicity of dimethylmercury (DMM) was documented in 1863 when two laboratory assistants died of DMM poisoning while synthesizing DMM in the laboratory of Frankland and Duppa. There are numerous reports of people dying from alkyl mercury compounds including a chemist who was preparing several thousand grams of DMM in his laboratory in 1974. The extreme toxicity was revisited in 1997, when Karen Wetterhahn, an internationally renowned researcher of the carcinogenic effects of heavy metals on DNA repair proteins, died within a few months after a single exposure of less than a milliliter of DMM on her latex-covered hand. DMM is extremely toxic and lethal at a dose of approximately 400 mg of mercury (equivalent to a few drops) or about 5mgkg-1 of body weight or as little as 0.1 ml.

DMM has limited use because of its toxicity but can be used to calibrate research equipment, as in its application as a standard reference material for 199Hg NMR measurements.

Environmental Fate

DMM is a colorless liquid that is volatile at room temperature (vapor pressure 62.3 mmHg) and is slightly soluble in water (water solubility 8860 mg l-1). There are no reports on the partition behavior of DMM but it is known to readily evaporate and is thus rarely found in sediment or soil. No reports were found on the environmental persistence of DMM. While DMM vaporizes, no studies were found on long range transport. The lipophilicity of DMM results in its accumulation inadipose tissue, plasma proteins, and brain. DMM has not been found in fish.

Mechanism of Toxicity 

In contrast to the white crystalline solids of the pure forms of methylmercury (MMM) and phenylmercury, DMM exists as a colorless liquid at room temperature with high volatility. These physical qualities enable high concentrations of the substance to be absorbed by exposure pathways of the skin and lungs that circumvent first-pass elimination. Effectively, this prolongs the systemic circulation of DMM, and extends its residence time in the body.

The additional alkyl group flanking the mercury imparts DMM with lipophilicity that exceeds its monoalkylated counterpart, and allows DMM to be sequestered in lipid-rich depots. The metabolic delay allows the neurotoxicity of DMM to remain latent for months.

The gradual conversion into MMM results in the release of DMM from depots such as lipid-rich tissues and plasma proteins, and permits its movement through barriers such as the blood–brain and placenta. A cysteine complex of the monomethylated metabolite penetrates the endothelial cells of the blood–brain barrier by mimicking methionine and using the large neutral amino acid transporter.

Thus, the toxicity of DMM is mediated by its dealkylation. Cleavage of the carbon–mercury bond generates MMM metabolites, which can form covalent bonds with cellular ligands with amphiphilic properties. The mercury center reacts with sulfur and sulfur-containing thiol groups of enzymes and thereby inhibits them, resulting in cellular dysfunction.

The metal center of DMM acts as a soft acid, and binds tightly to polarizable donor atoms in soft bases. An additional mechanism of adverse effect is the disruption of the prooxidant– antioxidant balance, causing oxidative damage to biomolecules resulting cellular damage. Within cells, mercury may interact with a variety of proteins, particularly microsomal and mitochondrial enzymes. Recent studies demonstrated that the combined administration of the antioxidants N-acetyl cysteine, zinc, and selenium mitigated DMM acute and chronic toxicity by reducing enzymatic and cellular dysfunction.