Pharmacokinetics Of Nickel

The major routes of nickel intake are dietary ingestion and inhalation. In most individuals, diet constitutes the main source of nickel intake. Recent studies indicate that average dietary intake is approximately 0.16 mg Ni/day. Nickel in drinking water (averages ranging from <0.001 to 0.01 mg Ni/L) and ambient air (averages ranging from 1 to 60 ng Ni/m3) is generally quite low. Other sources of nickel exposure include contact with nickel-containing articles such as jewelry, medical applications, and tobacco smoke.

For individuals occupationally exposed, total nickel intake is likely to be higher than that of the general populace. Whether diet or workplace exposures constitute the main source of nickel in workers depends upon a number of factors. These factors include the aerodynamic size of the particles and whether the particles are inhalable, the concentration of the nickel that is inhaled, the minute ventilation rate of a worker, whether breathing is nasal or oronasal, the use of respiratory protection equipment, personal hygiene practices, and general work patterns.

Toxicologically speaking, inhalation is the most important route of nickel exposure in the workplace, followed by dermal exposure. Deposition, absorption, and retention of nickel particles in the respiratory tract will depend on many of the factors noted above for intake. Not all particles are inhalable. Humans inhale only about half of the particles with aerodynamic diameters >30 µm, and it is believed that this efficiency may decline rapidly for particles with aerodynamic diameters between 100 and 200 µm. Of the particles inhaled, only a small portion with aerodynamic diameters larger than 10 µm are deposited in the lower regions of the lung, with deposition in this region predominantly limited to particles =4 µm.

Factors such as the amount deposited, solubility, and surface area of the particle will influence the behavior of particles once they are deposited in the lung. The smaller and more soluble the particle, the more rapidly it will be absorbed into the bloodstream and excreted. The residence time of nickel-containing particles in the lung is believed to be an important component of toxicity.

With respect to skin absorption, divalent nickel has been shown to penetrate the skin fastest at sweat ducts and hair follicles; however, the surface area of these ducts and follicles is small. Hence, penetration through the skin is primarily determined by the rate at which nickel is able to diffuse through the horny layer of the epidermis. Although the actual amount of nickel permeating the skin from nickel-containing materials is unknown, in studies using excised human skin, the percent permeation was small, ranging from 0.23 (non-occluded skin) to 3.5 percent (occluded skin) of an administered dose of nickel chloride. Marked differences in the rate of nickel permeation have been reported for nickel solutions, with nickel sulfate solutions permeating the skin at a rate 50 times slower than nickel chloride solutions.

Analyses of human tissues from autopsy studies have shown highest concentrations of nickel in the lungs, thyroid gland, and adrenal gland, followed by lesser concentrations in kidney, liver, heart, spleen, and other tissues. Excretion of absorbed nickel is mainly through urine, whereas unabsorbed nickel is excreted mainly in feces. Nickel also may be excreted in sweat, hair, and human breast milk.