The Production of Malignant Tumours by Nickel in the Rat

Abstract

In May 1932 a Parliamentary question drew attention to a number of cases of nasal cancer which had occurred among workers in a nickel refinery at Clydach, South Wales. The report of the Chief Inspector of Factories for 1931 (published in July 1932) listed several cases, and Stephens (1933), in discussing cases of industrial epitheliomata, suggested that nickel was one of the agents responsible. It was already known that nickel compounds, including gaseous nickel carbonyl, were toxic, but they were not suspected of being carcinogens. Subsequent statistical investigations by Doll (1958) and Gwynne Morgan (1958), and pathological studies by L0ken (1950) and Jones Williams (1958) have confirmed the relatively high incidence of respiratory cancer in nickel workers.Animal experiments by Hueper (1958) on the effect of inhalation of metallic nickel powder by rats and guinea-pigs, and by Sunderman, Donnelly, West and Kincaid (1959) on the effect of inhalation of nickel carbonyl by rats, confirmed that nickel could produce neoplastic changes in the respiratory tract, leading sometimes to frankly malignant tumours (Sunderman et al., 1959). Hueper (1952) had previously shown that powdered nickel, injected into rats by various routes, produced malignant tumours in at least 8 out of 70 animals. He also showed (Hueper, 1955) that the same agent, introduced by five different routes into rats, mice, and rabbits, produced malignant tumours of various types in 27 out of 100 rats, one out of six rabbits, and none of 125 mice. It is of interest that he draws attention to a possible species-specificity.Recently, Gilman (1962) has shown that nickel sulphide and nickel oxide, injected intramuscularly into rats and mice, produce tumours at the injection site. The tumours he obtained in the rats were mainly rhabdomyosarcomata; in the mice, although many of the tumours had the characteristics of fibrosarcomata, their cellularity, numerous oval nuclei and lack of collagen suggested to him that they contained myomatous elements. He has observed (personal communication) a strain-specificity of the carcinogenic action of nickel in rats.We are investigating the mechanisms of metal carcinogenesis, and thought it necessary to look for the possible carcinogenic effects of pure nickel powder under the same conditions as those in which cobalt (Heath, 1954 and) and cadmium (Heath, Daniel, Dingle and Webb, 1962; Heath and Daniel, 1964) are carcinogenic. MATERIALS AND METHODSTen female rats of the hooded strain, aged 2-3 months, were used. 0-0283 g. of spectrographically pure nickel metal powder (Johnson Matthey) was shaken into suspension with 0 4 ml. of fowl serum and injected into the muscle of the right thigh of each animal from the medial aspect, approximately parallel with the

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

“…The tumors were aggressive and fast growing, necessitating euthanasia of the animals several weeks later. On the basis of previously published literature (Heath and Daniel 1964), we expected the Ni-implanted positive control rats to develop tumors at the implantation site, but the speed at which the tumors developed was surprising: approximately 5 months after implantation. Figure 1 shows the percentage of surviving animals as a function of time after pellet implantation.…”

“…Intramuscular injections (28 mg) of soluble metallic Ni or Co result in formation of rhabdomyosarcomas at the injection site. With Ni, 100% of injected rats develop a tumor within 41 weeks (Heath and Daniel 1964), whereas administration of Co results in tumor formation in 40% of the rats with a latency period of 71 weeks (Heath 1954, 1956). However, intramuscular implantation of rods or pellets composed of various Ni or Co alloys used in orthopedic prosthetics results in no excessive tumor formation (Gaechter et al 1977; Sunderman 1989).…”

ATSDR evaluation of health effects of tungsten and relevance to public health

“…and Daniel, 1964). All of the nickel-embedded rats developed tumors similar to those observed in the tungsten alloy-embedded rats (Kalinich et al, 2005).…”

Experimental Chemotherapy of Nickel-Induced Fibrosarcomas

“…When nickel pow der suspended in tallow is introduced intrafemorally [12] or when the powder is suspended in trioctanoin [10] or fowl serum [11] is injected i.m., fibrosarco mas appear at the site of injection. These tumors metastasize to the lungs and are readily transplantable.…”