Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No data identified.

Endpoint conclusion
Endpoint conclusion:
no study available

Genetic toxicity in vivo

Description of key information

No reliable genotoxicity data for platinum dioxide were identified. Platinum oxide [oxidation state not clear] displayed no evidence of genotoxicity in a limited dominant lethal mutation assay in mice (Arnold et al., 1975).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

Additional information from genetic toxicity in vivo:

No reliable genotoxicity data for platinum dioxide were identified.

In a limited dominant lethal mutation assay, no evidence of genotoxicity was seen following a single subcutaneous injection of powdered platinum oxide [oxidation state not clear] to male mice prior to mating with untreated females (Arnold et al., 1975). It is worth noting, that the study has several deviations (e.g. inappropriate route, single dose, no positive control) and does not meet the acceptance criteria listed in the current OECD Test Guideline (478).

 

Several Expert Groups have assessed the toxicity profile of platinum, and various platinum compounds, including CMR properties in their assessment. All reviews have indicated that platinum compounds have been reported to be mutagenic in a range of in vitro studies (DECOS, 2008; EMA, 2008; SCOEL, 2011; WHO, 1991). Cisplatin and related compounds are known DNA-reactive carcinogens and, as these compounds are better investigated due to their pharmaceutical properties, this has been confirmed in vivo. As cisplatin-type substances differ in chemical reactivity (liability of ligands, number of active sites etc.) it is reasonable to expect that not all forms of platinum are carcinogenic (DECOS, 2008). Limited experimental data on reproductive toxicity and carcinogenicity for other platinum compounds give no evidence of activity that would meet classification criteria (DECOS, 2008; SCOEL, 2011).

 

Despite the generally positive in vitro results identified for the platinum compounds in various bacterial/mammalian cell mutagenicity assays (supported by some mammalian cell cytogenicity tests), the in vivo relevance of these in vitro findings remains unclear. Indeed, the available in vivo data returned mostly negative results. However, some of the identified studies might not be considered sufficiently robust (according to ECHA standards) to override the in vitro mutagenicity findings (e.g. a sex-linked recessive lethal test in Drosophila melanogaster (OECD TG 477, performed with dipotassium tetrachloroplatinate) and a liver unscheduled DNA synthesis assay (OECD TG 486, performed with tetraammineplatinum hydrogen carbonate)). Indeed, further in vivo testing of certain platinum compounds has been proposed to further elucidate the in vivo relevance of the in vitro findings.

 

References

DECOS (2008). Dutch Expert Committee on Occupational Standards. Platinum and Platinum Compounds. Health-based recommended occupational exposure limit. Gezondheidsraad, 2008/12OSH. https://www.gezondheidsraad.nl/en/publications/gezonde-arbeidsomstandigheden/platinum-and-platinum-compounds-health-based-recommended

 

EMA (2008). European Medicines Agency. Guideline on the specification limits for residues of metal catalysts or metal reagents. Committee for Medicinal Products for Human Use (CHMP). EMEA/CHMP/SWP/4446/2000. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003586.pdf

 

SCOEL (2011). Recommendation from the Scientific Committee on Occupational Exposure Limits for platinum and platinum compounds. SCOEL/SUM/150. http://ec.europa.eu/social/BlobServlet?docId=7303&langId=en

 

WHO (1991). World Health Organization. Platinum. International Programme on Chemical Safety. Environmental Health Criteria 125. http://www.inchem.org/documents/ehc/ehc/ehc125.htm#SectionNumber:7.4


Justification for selection of genetic toxicity endpoint
The only genetic toxicity study available.

Justification for classification or non-classification

Based on the existing data set, platinum dioxide does not currently meet the criteria for classification as a germ cell mutagen (category 1A or 1B). However, this conclusion should be revisited when the results of the planned in vivo studies are available.