Hazard Identification and Dose Response of Ingested Nickel-Soluble Salts

Abstract

People can ingest soluble nickel compounds as a normal constituent of food or as a contaminant in drinking water. This paper presents an assessment of the noncancer and cancer human health risks from ingestion of soluble nickel compounds. A reference dose (RfD) of 8 x 10(-3) mg Ni/kg/day in addition to the amount in food was calculated, based on albuminuria in female rats exposed to nickel sulfate in drinking water for 6 months (A. Vyskocil et al., 1994, Hum. Exp. Toxicol. 13, 689-693). This RfD is comparable to the current RfD based on decreased body weight in a chronic feeding study in rats (A. M. Ambrose et al., 1976, J. Food Sci. Technol. 13, 181-187). The potential for nickel-induced reproductive toxicity was also taken into account in the derivation of the RfD. There are a number of negative animal bioassays with soluble nickel salts, but all of them have deficiencies that preclude a definitive conclusion. According to EPA's 1996 draft cancer guidelines, the carcinogenic potential of oral exposure to soluble nickel "cannot be determined because there are inadequate data to perform an assessment."

Soluble and insoluble nickel compounds exert a differential inhibitory effect on cell growth through IKKα‐dependent cyclin D1 down‐regulation

“…These lines of evidence clearly indicate that insoluble nickel compounds are potent carcinogens, while soluble nickel compounds are less potent. Accordingly, the insoluble nickel compounds are classified as a human carcinogen, while soluble nickel compounds are considered as “not classifiable as a human carcinogen” (ACGIH, 1998) or “the carcinogenicity of soluble nickel compounds cannot be determined” (Haber et al, 2000a,b).…”

Respiratory carcinogenicity assessment of soluble nickel compounds.

“…Similar contrasting assessments were made the following year. In 1999, Beraterkreis Toxikologie in Germany recommended a category C1 classification (substances known to be carcinogenic to man) for water-soluble nickel compounds (6), whereas the Toxicological Excellence in Risk Assessment group conducting a risk assessment for Health Canada, U.S. Environmental Protection Agency, and the Metal Finishers Association of Southern California concluded that the "carcinogenicity of soluble nickel compounds cannot be determined" (7,8).…”

Toleranzinduktion gegen Nickel

“…Diese Referenzdosis basiert auf Toxizitätsstudien bei Ratten, denen Ni in hohen Dosen (80 mg Ni 2+ /kg KG/Tag bzw. 7,6 mg Ni 2+ /kg KG/Tag) im Trinkwasser über einen Zeitraum von 2 Jahren oder 6 Monaten verabreicht wurde und als Nebenwirkung eine Gewichtsabnahme [30] bzw. eine verminderte glomeruläre Funktion mit Albuminurie [93] auftraten.…”

“…Das Schwermetall Ni sollte jedoch nicht nur mit der Auslösung einer Allergie assoziiert werden: Außer über die Haut besteht ein täglicher Ni-Kontakt durch Aufnahme von Ni über die Luft, Nahrung und das Trinkwasser, wobei die tägliche Ni-Zufuhr durchschnittlich 70 µg mit der Nahrung und 2 µg mit dem Trinkwasser beträgt [30]. Eine erhöhte orale Ni-Exposition, z.…”