Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1975

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
NOTE: The brief abstract provided few details; it is not clear whether the monoxide or dioxide form was tested.

Test animals

Species:
mouse
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
No details reported in brief abstract.

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
Saline (suspension)
Details on exposure:
Single subcutaneous injection of powdered material (100 mg, as the metal) 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
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg
Basis:
other: nominal quantity of elemental metal in saline
No. of animals per sex per dose:
10 males
Control animals:
yes, concurrent vehicle
Positive control(s):
no data

Examinations

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

Results and discussion

Test results
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; 10.6-12.0 in treated animals.
Percentage early deaths: 3.0-6.7 and 4.8-8.1 in control groups; 5.8-9.3 in treated group

Any other information on results incl. tables

Observations, viable embryo numbers, percentage of early deaths as a proportion of implantations were comparable in treated and control groups.

Applicant's summary and conclusion

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 platinum oxide [oxidation state not clear] to male mice prior to mating with untreated females.
Executive summary:

In a limited non-guideline pre-GLP study, platinum oxide [oxidation state not clear] 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 powdered material (100 mg as the metal) 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 platinum oxide under the conditions of this limited dominant lethal mutation assay in mice.

Its 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).