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Toxicological information

Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The follwoing is cited from ATSDR (2003):

"In 1975, the International Agency for Research on Cancer (IARC) evaluated the literature relating selenium to carcinogenesis in both humans and animals. The Agency stated that the available data provided no suggestion that selenium is carcinogenic in humans (IARC 1975a), and IARC subsequently assigned selenium to Group 3: not classifiable as to its carcinogenicity to humans (IARC 1987). The forms of selenium considered included sodium selenate, sodium selenite, and the organic forms of selenium contained in plant materials. Separate evaluations of ethyl selenac and methyl selenac assigned them to Group 3, also (IARC 1975a, 1987). According to EPA, selenium is not classifiable as to its carcinogenicity in humans and is rated as Group D (IRIS 2003)."

Additional information

An independent, publicly available review of the carcinogenicity of selenium and selenium substances is available from ATSDR (2003). The key conclusions from this ATSDR summary on long-term carcinogen effects are cited below:

Data evaluation by ATSDR

The following general statement was made by ATSDR related to the cancer risk of selenium substances: "Studies of laboratory animals and people show that most selenium compounds probably do not cause cancer. In fact, some studies of cancer in humans suggest that lower-than-normal selenium levels in the diet might increase the risk of cancer. Other studies suggest that dietary levels of selenium that are higher than normal might reduce the risk of cancer in humans. However, taking selenium so that your daily amount is greater than that required might just increase your risk of selenium poisoning. Based on studies done until 1987, the International Agency for Research on Cancer (IARC) determined that selenium and selenium compounds could not be classified as to their ability to cause cancer in humans. However, since then, the EPA has determined that one specific form of selenium, called selenium sulfide, is a probable human carcinogen.Selenium sulfide is the only selenium compound shown to cause cancer in animals. "

Selenium sulfide is definitely outside the scope of this hazard assessment, because it is very different from the other inorganic selenium substances, so that the following statement can be regarded as appropriate for metallic Selenium and inorganic tetravalent (e.g. sodium selenite or selenium dioxide) and hexavalent (e.g. sodium selenate) selenium substances: “There is no evidence to support a causal association between selenium compounds and cancer in humans. In fact, some epidemiological and experimental evidence suggests that selenium exposure under certain conditions may contribute to a reduction in cancer risk. The chemopreventive potential of supplemental selenium is currently under research. "

The mechanism of selenium acting against cancer formation is described in ATSDR as follows: "Hypotheses for the protective role of selenium against cancer development include the inhibition of carcinogen-induced covalent DNA adduct formation, retardation of oxidative damage to DNA, lipids, and proteins, and modulation of cellular and molecular events that are critical in cell growth inhibition and in the multi-step carcinogenesis process.”

It is also worth mentioning that:“The possible inverse relationship between dietary selenium intake and the risk of various types of cancer has been examined in numerous epidemiological studies in the United States and other countries. [... ] In recent years, much of the research in laboratory animals using the oral route of administration of selenium compounds has been directed toward the anticarcinogenic properties of selenium compounds. “

 

The following is summarised in the ATSDR related to the different routes of exposure and carcinogenicity.

Oral exposure:

“Human dietary studies generally do not identify the selenium form specifically; both organic (from grains and other plant and animal products) and inorganic (from drinking water) forms are ingested. Animal bioassays in which selenium was administered as sodium selenate, sodium selenite, or organic forms of selenium have all shown similar negative results.”

In general it is stated by ATSDR that “The majority of oral studies have provided information on the absence of carcinogenic effects in humans and animals (Beems 1986; Clark et al. 1996a, 1999; Coates et al. 1988; Duffield-Lillico et al. 2002; Harr et al. 1967; Menkes et al. 1986; Thompson and Becci 1979; Virtamo et al. 1987). ”

It is also noted that in „Early studies reporting that selenium was carcinogenic in mammals after being provided as seleniferous corn or wheat in the diet, as sodium selenite or sodium selenate in drinking water, or as sodium selenate in the diet were flawed. “

Two studies(Schroeder and Mitchener 1971a; Vinceti et al. 1998), which showed incidences of melanoma or tumours possibly correlated with administration of selenites were discussed by ATSDR and it was concluded that "There were several inadequacies in the early studies that reported carcinogenic effects in animals following oral administration of selenium-containing compounds.”

 

Overall, it was concluded by the ATSDR expert review that "The majority of subsequent studies of humans and animals have revealed no association between selenium intake and the incidence of cancer (e. g. Azin et al. 1998; Beems 1986; Coates et al. 1988; Harr et al. 1967; Ma et al. 1995; Menkes et al. 1986; Ratnasinghe et al. 2000; Thompson and Becci 1979; Vinceti et al. 1995; Virtamo et al. 1987) or a clear chemopreventive association (Birt et al. 1982; Clark et al. 1996a, 1999; Finley et al. 2000; Ip 1981, 1983; Ip and Lisk 1995; Ip et al. 1996, 1997, 1998, 2000a, 2000b; Jiang et al. 1999; Ma et al. 1995; Medina and Shepherd 1981; Overvad et al. 1985; Schrauzer et al. 1976, 1977; Shamberger et al. 1976; Soullier et al. 1981; Thompson and Becci 1980; Woutersen et al. 1999; Yoshizawa et al. 1998).Some epidemiological and experimental evidence suggests that selenium exposure, under certain conditions, may contribute to a reduction in cancer risk(Clark et al. 1996a, 1999; El-Bayoumy 2001; Ganther 1999; Moyad 2002; Spallholz 2001; Yoshizawa et al. 1998) ", and that“... selenium supplementation has generally been shown to significantly inhibit tumours induced by chemicals, viruses, or ultraviolet light(e. g. Birt et al. 1982; Finley et al. 2000; Ip 1981, 1983; Jabobs 1983; Jacobs et al. 1977a, 1977b, 1979, 1981; Jiang et al. 1999; Medina and Shepherd 1981; Overvad et al. 1985; Schrauzer et al. 1976; Soullier et al. 1981; Thompson and Becci 1980; Woutersen et al. 1999). Results following administration of selenium as sodium selenate, sodium selenite, and organic forms of selenium are similar.”

 

Inhalation exposure

According to ATSDR,"no studies were located regarding carcinogenic effects in laboratory animals after inhalation exposure to selenium or selenium compounds. No further investigation is needed since humans have not been shown to have an increased risk of malignancy from selenium exposure [...] There are no epidemiologic data that support a causal association between the inhalation of elemental selenium dusts or selenium compounds and the induction of cancer in humans (Gerhardsson et al. 1986; Wester et al. 1981). In one study, postmortem samples were collected from copper smelter workers who were exposed to several different airborne compounds, including selenium compounds. Samples from lung cancer cases had lower concentrations of selenium in lung tissue than samples from controls or from workers who had died from other causes (Gerhardsson et al. 1986). In another autopsy study of smelter workers,Wester et al. (1981)found that the selenium concentrations in kidney tissues from workers who had died of malignancies were lower than the selenium concentrations in kidney tissues from workers who died of other causes."

 

Dermal exposure

No study reports on dermal exposure are described in ATSDR (2003). According to ATSDR, "no studies were located regarding carcinogenic effects in humans after dermal exposure to selenium or selenium compounds. The results of most animal studies have not indicated that elemental selenium or selenium compounds are carcinogenic when topically applied to the skin of experimental animals... ”