Carcinogenesis Tests of Nickel Arsenides, Nickel Antimonide, and Nickel Telluride in Rats

Abstract

Carcinogenicity of nickel arsenides (NiAs, Ni11As8, Ni5As2, NiAsS), nickel antimonide (NiSb), and nickel telluride (NiTe) was tested by IM administration to male Fischer rats (14 mg Ni/rat). Three negative control groups received similar IM injections of glycerol vehicle, ferronickel alloy (NiFe), or nickel titanate (NiTiO3); two positive control groups received nickel oxide (NiO) or ferronickel sulfide (Ni4FeS4) at equivalent dosages (14 mg Ni/rat). Within 2 years, the incidences of sarcomas at the injection site were: 0/20 (0%) in NiAs-treated rats, 8/16 (50%) in Ni11As8-treated rats; 17/20 (85%) in Ni5As2-treated rats; 14/16 (85%) in NiAsS-treated rats; 17/29 (59%) in NiSb-treated rats; and 14/26 (54%) in NiTe-treated rats. No local sarcomas occurred in the negative control groups, including 40 glycerol-treated rats, 16 NiFe-treated rats, and 20 NiTiO3-treated rats; in the positive control groups, local sarcomas occurred in 14/15 (93%) of NiO-treated rats and 15/15 (100%) of Ni4FeS4-treated rats. The 99 sarcomas that were induced by the various nickel compounds included 67 rhabdomyosarcomas, 11 fibrosarcomas, 15 osteosarcomas, 1 fibrous histiocytic sarcoma, and 5 undifferentiated sarcomas; metastases were found in 57 sarcoma-bearing rats. This study demonstrates that Ni11As8, Ni5As2, NiAsS, NiSb, and NiTe are carcinogenic for rats. Since Ni11As8, Ni5As2, and NiAsS are likely to be formed during oil shale retorting, environmental contamination by nickel arsenides in spent shale products could conceivably pose a carcinogenic hazard if large-scale production of petroleum from oil share is established.

Mechanisms of nickel carcinogenesis.

“…+ , a portion o f which binds to nuc!eoproteins (20)(21)(22). The pronounced di fferen ces in the carcinogen ic activities of nickel compounds tha t have been observed in carcinog enes is bioassa ys (23)(24)(25) hypotheticall y refl ect va ria tio ns in the rates of (i) di ssolution of the co mpounds in extr acellular fluid s, (ii) uptake o f the compounds by tar get cells a nd subseq uent intracellular re-lease of Ni 2+ , and (iii) cellular efflux of NiH versus translocation of Ni 2+ to nuclear binding sites.…”

Risk of Cancer for Workers Exposed to Antimony Compounds: A Systematic Review

“…Regarding PubMed articles, there was a discussion about 4 more articles (Zhang 2018 [26], Kotsopoulos 2012 [27], Rossi 1987 [28], and Sunderman 1983 [29]). All 4 were eventually excluded based on the exclusion criteria: Zhang 2018 [26] was no pure animal study because it studied human prostate cancer cells (LnCaP) implanted in mice, Kotsopoulos 2012 [27] was no animal study, Rossi 1987 [28] had uncertain relevance to health endpoint, and Sunderman 1983 [29] met exclusion criterion intramuscular administration. Regarding ToxLine articles, 3 more articles were discussed (Zhang 2018 [26], Rossi 1987 [28], and Sunderman 1983 [29]), which had been excluded before.…”

CHAPTER 17. Arsenic, Antimony and Bismuth

“…230 A second study claimed that 17 of 29 male rats exposed to nickel antimonide (NiSb) by intramuscular injection developed subcutaneous sarcoma within two years, but in view of the 93% incidence of tumours in nickel oxide-treated animals (positive control), the risk apportioned to antimony per se must be low. 231 Antimony has been listed by the NTP, US DHHS and IARC for investigation as a putative human carcinogen, but expert evaluation of data up to 2011 has failed to identify a carcinogenic risk following occupational exposures to elemental antimony, antimony trioxide as a by-product from stibnite ores, antimony trisulfide, or antimony contamination in lead smelting. 232 The carcinogenicity of antimony in mining and associated industrial processes is difficult to establish in view of the frequent exposure to other environmental contaminants, notably arsenic, lead, nickel, silica and zirconium.…”

“…239 The limited studies in rodents suggesting a greater a female sensitivity to antimony-induced lung tumours are inadequate. 230,231 …”