have signed informed consent documents regarding possible toxicity and as long as these trials employ appropriate safety monitoring of trial subjects. In addition, the UL is not meant to apply to individuals who are receiving nickel under medical supervision.

There is no evidence in humans of adverse effects associated with exposure to nickel through consumption of a normal diet. The UL derived here applies to excess nickel intake as soluble nickel salts.

Human Data. A few case reports have documented the acute effects of the ingestion of high doses of soluble nickel salts. Twenty workers who accidentally ingested 0.5 to 2.5 g of nickel as nickel sulfate and chloride hexahydrate in contaminated water developed nausea, abdominal pain, diarrhea, vomiting, and shortness of breath among other symptoms (Sunderman et al., 1988). Ten of these subjects were found to have altered hematological parameters. In one other case report, one subject who ingested approximately 50 μg/kg of nickel as nickel sulfate in water was reported to have developed transient hemianopsia at the time of peak serum concentrations (Sunderman et al., 1989). In persons with hypersensitivity to nickel, oral exposure has been reported to result in contact dermatitis-like symptoms (Gawkrodger et al., 1986).

Animal Data. In oral subchronic (ABC, 1988) and chronic (Ambrose et al., 1976) studies with rats, exposure to soluble nickel compounds has been associated with increased mortality, clinical signs of general systemic toxicity (e.g., lethargy, ataxia, irregular breathing, hypothermia, and salivation), decreased body weight gains, and changes in absolute and relative organ weights (kidney, liver, spleen, and heart). Fetotoxicity associated with oral exposure to nickel chloride and nickel sulfate has been reported in two separate two-generation studies (RTI, 1988; Smith et al., 1993) and in one three-generation study (Schroeder and Mitchner, 1971). Nickel salts also have been shown to interfere with the reproductive capacity of male rats (Hoey, 1966; Laskey and Phelps, 1991; Waltschewa et al., 1972).

On the basis of considerations of data quality, sensitivity of the