Platinum

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No reliable in vitro genotoxicity data were identified.

Endpoint conclusion

Endpoint conclusion:

no study available

Genetic toxicity in vivo

Description of key information

No reliable in vivo genotoxicity data for platinum metal were identified.

 

However, in a limited dominant lethal mutation assay, no evidence of genotoxicity was seen following a single subcutaneous injection of powdered elemental platinum to male mice prior to mating with untreated females (Arnold et al., 1975).

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

Not reported

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Brief abstract, basic data only reported, does not meet current guideline methodology

Qualifier:

no guideline followed

Principles of method if other than guideline:

Dominant lethal study in mice to detect mutagenic potential (usually as a result of chromosome aberrations). Treated males were housed with 3 untreated, virgin females/week for 6 consecutive weeks. Mating ability, impregnating ability, viable embryos and percent early deaths (i.e. resorptions) were assessed.

GLP compliance:

not specified

Type of assay:

rodent dominant lethal assay

Species:

mouse

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

No details reported in brief abstract.

Route of administration:

subcutaneous

Vehicle:

Saline (suspension)

Details on exposure:

Single subcutaneous injection of 100 mg powdered material as a suspension in saline (1 ml)

Duration of treatment / exposure:

n/a

Frequency of treatment:

Single dose administered

Post exposure period:

[Presumably] 6 weeks

Remarks:

Doses / Concentrations:
100 mg
Basis:
other: nominal in saline

No. of animals per sex per dose:

10 males

Control animals:

yes, concurrent vehicle

Positive control(s):

no data

Tissues and cell types examined:

Dominant lethal mutations were measured as the percentage of all implants that resulted in early death in utero (i.e. percentage resorptions).

Evaluation criteria:

Early (in utero) deaths as a percentage of all implants were compared in treated and control animals

Statistics:

None reported

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

Mortality and behavioural assessment only

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Additional information on results:

Numbers of viable embryos: 10.4-11.7 and 10.2-11.5 in control groups; 10.5-11.4 in treated animals.
Percentage early deaths: 3.0-6.7 and 4.8-8.1 in control groups; 5.0-7.6 in treated group

Observations, viable embryo numbers, percentage of early deaths as a proportion of implantations did not differ between treated and control animals.

Conclusions:

Interpretation of results (migrated information): negative

In a limited dominant lethal mutation assay, no evidence of genotoxicity was seen following a single subcutaneous injection of powdered elemental platinum to male mice prior to mating with untreated females.

Executive summary:

In a limited non-guideline pre-GLP study, elemental platinum was tested for its ability to induce heritable genetic damage (usually indicative of chromosome aberrations) in a dominant lethal mutation assay in albino mice. Single subcutaneous injections of 100 mg powdered platinum in saline (1 ml) were given to 10 males before housing with 3 untreated, virgin females/week for 6 consecutive weeks. The percentage of implants that resulted in early foetal deaths (in utero) did not differ from those measured in saline-treated controls.

 

In conclusion, a mutagenic effect (indicative of chromosome aberrations) was not indicated for elemental platinum under the conditions of this limited dominant lethal mutation assay in mice.

 

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).

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

No reliable genotoxicity data for platinum metal were identified.

 

However, ina limited non-guideline pre-GLP study, elemental platinum was tested for its ability to induce heritable genetic damage (usually indicative of chromosome aberrations) in a dominant lethal mutation assay in albino mice. Single subcutaneous injections of 100 mg powdered platinum in saline (1 ml) were administered to 10 males before housing with 3 untreated, virgin females/week for 6 consecutive weeks. The percentage of implants that resulted in early foetal deaths (in utero) did not differ from those measured in saline-treated controls. In conclusion, a mutagenic effect (indicative of chromosome aberrations) was not indicated for elemental platinum under the conditions of this limited dominant lethal mutation assay in mice (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).

 

Further, availability considerations provide good support for the conclusion that genotoxicity testing can be waived.

 

Platinum is considered to be non-bioavailable following oral and dermal exposure, as evidenced by transformation/dissolution and bio-elution test data.

 

It is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure. Further, bio-elution test data indicates lack of bioavailability in lung fluid.

 

Since a chemical is required to be bioavailable in order to induce genotoxicity, platinum is not considered to pose a toxicity hazard for this endpoint. Consequently, no testing for genotoxicity of platinum is considered justified.

Justification for classification or non-classification

No reliable genotoxicity data are available for platinum. However, such effects are not expected, based on a lack of bioavailability following exposure via the oral, dermal and inhalation routes, with support from the limited dominant lethal study in mice. As such, there is no evidence to classify it for germ cell mutagenicity according to EU CLP criteria (EC 1272/2008).