Registration Dossier

Administrative data

Description of key information

There is no evidence for carcinogenic activity of zinc compounds in humans.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Species:
other: human
Quality of whole database:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Species:
other: human
Quality of whole database:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Species:
other: human
Quality of whole database:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Additional information

Zinc bis[12-hydroxyoctadecanoate]

Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as it is assumed that during exposure or after intake and absorption zinc bis[12-hydroxyoctadecanoate] is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The carcinogenic potential of the fatty acid chain, i.e. 12-hydroxystearate, is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). A full read-across of data based on the solubility and a zinc content correction is considered for zinc bis[12-hydroxyoctadecanoate].

There are a range of epidemiological studies that investigated the association between zinc exposure either through occupational activities or food supplementation and increased cancer risks. While no associations were found between occupational zinc exposure and excess cancer risk, the main association that has been made in this context is related to dietary/supplemental zinc and prostate cancer risk. On the basis of the existing information it can be concluded that there is no conclusive evidence for carcinogenic activity of any of the zinc compounds considered in this chemical safety report.

For comprehensive assessment of the carcinogenicity of “Zinc”, see the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1 of the CSR and cited in excerpts below.

 

Read-across approach and conclusion are in accordance to conclusion on carcinogenicity of a structural analogue in EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1):

“The available data are limited. Zinc deficiency or supplementation may influence carcinogenesis, since promoting and inhibiting actions have been reported. However, there is no clear experimental or epidemiological evidence for a direct carcinogenic action of zinc or its compounds.”

ZINC:

There are a range of epidemiological studies that investigated the association between zinc exposure either through occupational activities or food supplementation and increased cancer risks. While no associations were found between occupational zinc exposure and excess cancer risk, the main association that has been made in this context is related to dietary/supplemental zinc and prostate cancer risk.

In contrast to established clinical and experimental evidence that prostate cancer is associated with a decrease in the zinc uptake, numerous epidemiology studies and reports of the effect of dietary and supplemental zinc on the incidence of prostated cancer have provided divergent, inconsistent and inconclusive results which range from adverse effects of zinc, protective effects of zinc and no effect of zinc on the risk of prostate cancer. Clinical and experimental studies have established that zinc levels are decreased in prostate cancer and support a role of zinc as a tumor suppressor agent. Malignant prostate cells in situ are incapable of accumulating high zinc levels from circulation (Franklin R.B.et al.,2005; Costello L.C, and Franklin R.B., 2006; Franklin R.B. and Costello L.C,, 2007).

In a recent critical assessment of epidemiology studies regarding dietary/supplemental zinc and prostate cancer risk, Costello et al., concluded that epidemiological studies have not provided an established relationship for any effect or lack thereof of dietary/supplemental zinc on the risk of prostate cancer. Proclamations of an association of dietary/supplemental zinc and increased prostate cancer are based on inconclusive and uncorroborated reports (Costello L.C.et al.,2007).

References:

Franklin RB, Milon B, Feng P and Costello LC.(2005) Zinc and zinc transporters in normal prostate and the pathogenesis of prostate cancer.Front Biosci. 1;10:2230-9. Review.

Costello LC andFranklin RB.(2006) The clinical relevance of the metabolism of prostate cancer: zinc and tumor suppression: connecting the dotsMol Cancer.15;5:17. Review.

Franklin RB and Costello LC. (2007) Zinc as an anti-tumor agent in prostate cancer and in other cancers.Arch Biochem Biophys. 15;463(2):211-7. Review.

Costello LC and Franklin RB. (2007) Re: Silvano Gallus, Roberto Foschi, Eva Negri et al. Dietary zinc and prostate cancer risk: a case-control study from Italy Eur Urol 52: 1052-7;Eur Urol. 52(4):1262-3; author reply 1263-4.


Justification for selection of carcinogenicity via oral route endpoint:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Justification for selection of carcinogenicity via inhalation route endpoint:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Justification for selection of carcinogenicity via dermal route endpoint:
Data on the carcinogenicity of zinc bis[12-hydroxyoctadecanoate] are not available. Data on other zinc compounds have been used, as the basic assumption is made that after intake all zinc compounds (including zinc bis[12-hydroxyoctadecanoate]) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds. This approach is in accordance to the European RAs on zinc and zinc compounds. As part of the RAs, available toxicological data was extensively discussed and scrutinised by the experts from Member States and other stakeholders during the meetings of the “Technical committee on new and existing substances” (TCNES), during which the relevant data sets were approved. Data used in the RARs on zinc metal and zinc compounds are the main data source for this chapter. Decisions on data quality and relevancy approved by TCNES are used as in the EU risk assessment process. Consequently, the current analysis will focus on the data considered relevant, adequate and reliable, and hence of high quality, for the assessment within the framework of Regulation (EC) No 1907/2006. The toxic potential of the fatty acid chain, i.e. bis[12-hydroxyoctadecanoate], is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The most relevant dose descriptor has been derived from epidemiological studies that investigated the association though occupational activities and increased cancer risks. This approach is in accordance to the European RAs on zinc and zinc compounds.

Justification for classification or non-classification

There is not any evidence for an intrinsic carcinogenicity of zinc compounds relevant to humans. Therefore, a classification is not required for carcinogenicity according to CLP Regulation (EC) No 1272/2008 and Directive 67/548 EEC.